Federal Practitioner

The Food and Drug Administration has granted accelerated approval to the off-the-shelf biologic agent elranatamab (Elrexfio) for the treatment of relapsed or refractory multiple myeloma.

The B-cell maturation antigen (BCMA) CD3-targeted bispecific antibody (BsAb) was given Priority Review in February and had previously received Breakthrough Therapy Designation for relapsed or refractory multiple myeloma (RRMM), according to Pfizer.

Olivier Le Moal/Getty Images

FDA approval was based on favorable response and duration of response rates in the single-arm, phase 2 MagnetisMM-3 trial. The trial showed meaningful responses in heavily pretreated patients with RRMM who received elranatamab as their first BCMA-directed therapy.

The overall response rate in 97 BCMA-naive patients (cohort A) who previously received at least four lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, was 58%, with an estimated 82% maintaining the response for 9 months or longer. Median time to first response was 1.2 months.

In 63 patients who received at least four prior lines of therapy, which also included a BCMA-directed therapy, the overall response rate was 33% after median follow-up of 10.2 months. An estimated 84% maintained a response for at least 9 months.

Elranatamab was given subcutaneously at a dose of 76 mg weekly on a 28-day cycle with a step-up priming dose regimen. The priming regimen included 12 mg and 32 mg doses on days 1 and 4, respectively, during cycle 1. Patients who received at least six cycles and showed at least a partial response for 2 or more months had a biweekly dosing interval.

Elranatamab carries a boxed warning for cytokine release syndrome (CRS) and neurologic toxicity, as well as warnings and precautions for infections, neutropenia, hepatotoxicity, and embryo–fetal toxicity. Therefore, the agent is available only through a restricted Risk Evaluation and Mitigation Strategy (REMS).

The boxed warning is included in the full prescribing information.

A confirmatory trial to gather additional safety and efficacy data was launched in 2022. Continued FDA approval is contingent on confirmed safety and efficacy data.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has granted accelerated approval to the off-the-shelf biologic agent elranatamab (Elrexfio) for the treatment of relapsed or refractory multiple myeloma.

The B-cell maturation antigen (BCMA) CD3-targeted bispecific antibody (BsAb) was given Priority Review in February and had previously received Breakthrough Therapy Designation for relapsed or refractory multiple myeloma (RRMM), according to Pfizer.

Olivier Le Moal/Getty Images

FDA approval was based on favorable response and duration of response rates in the single-arm, phase 2 MagnetisMM-3 trial. The trial showed meaningful responses in heavily pretreated patients with RRMM who received elranatamab as their first BCMA-directed therapy.

The overall response rate in 97 BCMA-naive patients (cohort A) who previously received at least four lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, was 58%, with an estimated 82% maintaining the response for 9 months or longer. Median time to first response was 1.2 months.

In 63 patients who received at least four prior lines of therapy, which also included a BCMA-directed therapy, the overall response rate was 33% after median follow-up of 10.2 months. An estimated 84% maintained a response for at least 9 months.

Elranatamab was given subcutaneously at a dose of 76 mg weekly on a 28-day cycle with a step-up priming dose regimen. The priming regimen included 12 mg and 32 mg doses on days 1 and 4, respectively, during cycle 1. Patients who received at least six cycles and showed at least a partial response for 2 or more months had a biweekly dosing interval.

Elranatamab carries a boxed warning for cytokine release syndrome (CRS) and neurologic toxicity, as well as warnings and precautions for infections, neutropenia, hepatotoxicity, and embryo–fetal toxicity. Therefore, the agent is available only through a restricted Risk Evaluation and Mitigation Strategy (REMS).

The boxed warning is included in the full prescribing information.

A confirmatory trial to gather additional safety and efficacy data was launched in 2022. Continued FDA approval is contingent on confirmed safety and efficacy data.

A version of this article first appeared on Medscape.com.

The Food and Drug Administration has granted accelerated approval to the off-the-shelf biologic agent elranatamab (Elrexfio) for the treatment of relapsed or refractory multiple myeloma.

The B-cell maturation antigen (BCMA) CD3-targeted bispecific antibody (BsAb) was given Priority Review in February and had previously received Breakthrough Therapy Designation for relapsed or refractory multiple myeloma (RRMM), according to Pfizer.

Olivier Le Moal/Getty Images

FDA approval was based on favorable response and duration of response rates in the single-arm, phase 2 MagnetisMM-3 trial. The trial showed meaningful responses in heavily pretreated patients with RRMM who received elranatamab as their first BCMA-directed therapy.

The overall response rate in 97 BCMA-naive patients (cohort A) who previously received at least four lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, was 58%, with an estimated 82% maintaining the response for 9 months or longer. Median time to first response was 1.2 months.

In 63 patients who received at least four prior lines of therapy, which also included a BCMA-directed therapy, the overall response rate was 33% after median follow-up of 10.2 months. An estimated 84% maintained a response for at least 9 months.

Elranatamab was given subcutaneously at a dose of 76 mg weekly on a 28-day cycle with a step-up priming dose regimen. The priming regimen included 12 mg and 32 mg doses on days 1 and 4, respectively, during cycle 1. Patients who received at least six cycles and showed at least a partial response for 2 or more months had a biweekly dosing interval.

Elranatamab carries a boxed warning for cytokine release syndrome (CRS) and neurologic toxicity, as well as warnings and precautions for infections, neutropenia, hepatotoxicity, and embryo–fetal toxicity. Therefore, the agent is available only through a restricted Risk Evaluation and Mitigation Strategy (REMS).

The boxed warning is included in the full prescribing information.

A confirmatory trial to gather additional safety and efficacy data was launched in 2022. Continued FDA approval is contingent on confirmed safety and efficacy data.

A version of this article first appeared on Medscape.com.

Gastrointestinal (GI) bleeding is a common cause of hospital admissions. The yearly incidence of upper GI bleeding is 80 to 150/100,000 people and lower GI bleeding is 87/100,000 people.^1,2 The differential tends to initially be broad but narrows with good history followed by endoscopic findings. Getting an appropriate history can be difficult at times, which leads health care practitioners to rely more on interventional results.

Amyloidosis is a rare disorder of abnormal protein folding, leading to the deposition of insoluble fibrils that disrupt normal tissues and cause disease.³ There are 2 main types of amyloidosis, systemic and transthyretin, and 4 subtypes. Systemic amyloidosis includes amyloid light-chain (AL) deposition, caused by plasma cell dyscrasia, and amyloid A (AA) protein deposition, caused by systemic autoimmune illness or infections. Transthyretin amyloidosis is caused by changes and deposition of the transthyretin protein consisting of either unstable, mutant protein or wild type protein. Biopsy-proven amyloidosis of the GI tract is rare.⁴ About 60% of patients with AA amyloidosis and 8% with AL amyloidosis have GI involvement.⁵

We present a case of nonspecific symptoms that ultimately lined up perfectly with the official histologic confirmation of intestinal amyloidosis.

Case Presentation

A 79-year-old man with a history of type 2 diabetes mellitus, congestive heart failure, hyperlipidemia, obstructive sleep apnea, hypothyroidism, hypertension, coronary artery disease status postcoronary artery bypass grafting, and stent placements presented for 3 episodes of large, bright red bowel movements. He reported past bleeding and straining with stools, but bleeding of this amount had not been noted prior. He also reported dry heaves, lower abdominal pain, constipation with straining, early satiety with dysphagia, weakness, and decreased appetite. Lastly, he mentioned intentionally losing about 35 to 40 pounds in the past 3 to 4 months and over the past several months increased abdominal distention. However, he stated he had no history of alcohol misuse, liver or intestinal disease, cirrhosis, or other autoimmune diseases. His most recent colonoscopy was more than a decade prior and showed no acute process. The patient never had an esophagogastroduodenoscopy (EGD).

On initial presentation, the patient’s vital signs showed no acute findings. His physical examination noted a chronically ill–appearing male with decreased breath sounds to the bases bilaterally and noted abdominal distention with mild generalized tenderness. Laboratory findings were significant for a hemoglobin level, 9.4 g/dL (reference range, 11.6-15.3); iron, 23 ug/dL (reference range, 45-160); transferrin saturation, 8% (reference range, 15-50); ferritin level, 80 ng/mL (reference range, 30-300); and carcinoembryonic antigen level, 1.5 ng/mL (reference range, 0-2.9). Aspartate aminotransferase level was 54 IU/L (reference range, 0-40); alanine transaminase, 24 IU/L (reference range, 7-52); albumin, 2.7 g/dL (reference range, 3.4-5.7); international normalized ratio, 1.3 (reference range, 0-1.1); creatinine, 1.74 mg/dL (reference range, 0.44-1.27); alkaline phosphatase, 369 IU/L (reference range, 39-117). White blood cell count was 15.5 × 10⁹/L (reference range, 3.5-10.3), and lactic acid was 2.5 mmol/L (reference range, 0.5-2.2). He was started on piperacillin/tazobactam in the emergency department and transitioned to ciprofloxacin and metronidazole for presumed intra-abdominal infection. Paracentesis showed a serum ascites albumin gradient of > 1.1 g/dL with no signs of spontaneous bacterial peritonitis. Computed tomography of the abdomen and pelvis with contrast was suspicious for colitis involving the proximal colon, and colonic mass could not be excluded. Also noted was hepatosplenomegaly with abdominopelvic ascites.

Based on these findings, an EGD and colonoscopy were done. The EGD showed mild portal hypertensive gastropathy.

Discussion

Amyloidosis is a rare disorder of abnormal protein folding, leading to the deposition of insoluble fibrils that disrupt normal tissues and cause disease.³ There are several variations of amyloid, but the most common type is AL amyloidosis, which affects several organs, including the heart, kidney, liver, nervous system, and GI tract. When AL amyloidosis involves the liver, the median survival time is about 8.5 months.⁶ There are different ways to diagnose the disease, but a tissue biopsy and Congo Red staining can confirm specific organ involvement as seen in our case.

This case adds another layer to our constantly expanding differential as health care practitioners and proves that atypical patient presentations may not be atypical after all. GI amyloidosis tends to present similarly to our patient with bleeding, malabsorption, dysmotility, and protein-losing gastroenteropathy as ascites, edema, pericardial effusions, and laboratory evidence of hypoalbuminemia.⁷ Because amyloidosis is a systemic illness, early recognition is important as intestinal complications tend to present as symptoms, but mortality is more often caused by renal failure, cardiomyopathy, or ischemic heart disease, making early multispecialty involvement very important.⁸

Conclusions

Health care practitioners in all specialties should be aware of and include intestinal amyloidosis in their differential diagnosis when working up GI bleeds with the hope of identifying the disease early. With early recognition, rapid biopsy identification, and early specialist involvement, patients will get the opportunity for expedited multidisciplinary treatment and potentially delay rapid decompensation as shown by the evidence in this case.

Gastrointestinal (GI) bleeding is a common cause of hospital admissions. The yearly incidence of upper GI bleeding is 80 to 150/100,000 people and lower GI bleeding is 87/100,000 people.^1,2 The differential tends to initially be broad but narrows with good history followed by endoscopic findings. Getting an appropriate history can be difficult at times, which leads health care practitioners to rely more on interventional results.

Amyloidosis is a rare disorder of abnormal protein folding, leading to the deposition of insoluble fibrils that disrupt normal tissues and cause disease.³ There are 2 main types of amyloidosis, systemic and transthyretin, and 4 subtypes. Systemic amyloidosis includes amyloid light-chain (AL) deposition, caused by plasma cell dyscrasia, and amyloid A (AA) protein deposition, caused by systemic autoimmune illness or infections. Transthyretin amyloidosis is caused by changes and deposition of the transthyretin protein consisting of either unstable, mutant protein or wild type protein. Biopsy-proven amyloidosis of the GI tract is rare.⁴ About 60% of patients with AA amyloidosis and 8% with AL amyloidosis have GI involvement.⁵

We present a case of nonspecific symptoms that ultimately lined up perfectly with the official histologic confirmation of intestinal amyloidosis.

Case Presentation

A 79-year-old man with a history of type 2 diabetes mellitus, congestive heart failure, hyperlipidemia, obstructive sleep apnea, hypothyroidism, hypertension, coronary artery disease status postcoronary artery bypass grafting, and stent placements presented for 3 episodes of large, bright red bowel movements. He reported past bleeding and straining with stools, but bleeding of this amount had not been noted prior. He also reported dry heaves, lower abdominal pain, constipation with straining, early satiety with dysphagia, weakness, and decreased appetite. Lastly, he mentioned intentionally losing about 35 to 40 pounds in the past 3 to 4 months and over the past several months increased abdominal distention. However, he stated he had no history of alcohol misuse, liver or intestinal disease, cirrhosis, or other autoimmune diseases. His most recent colonoscopy was more than a decade prior and showed no acute process. The patient never had an esophagogastroduodenoscopy (EGD).

On initial presentation, the patient’s vital signs showed no acute findings. His physical examination noted a chronically ill–appearing male with decreased breath sounds to the bases bilaterally and noted abdominal distention with mild generalized tenderness. Laboratory findings were significant for a hemoglobin level, 9.4 g/dL (reference range, 11.6-15.3); iron, 23 ug/dL (reference range, 45-160); transferrin saturation, 8% (reference range, 15-50); ferritin level, 80 ng/mL (reference range, 30-300); and carcinoembryonic antigen level, 1.5 ng/mL (reference range, 0-2.9). Aspartate aminotransferase level was 54 IU/L (reference range, 0-40); alanine transaminase, 24 IU/L (reference range, 7-52); albumin, 2.7 g/dL (reference range, 3.4-5.7); international normalized ratio, 1.3 (reference range, 0-1.1); creatinine, 1.74 mg/dL (reference range, 0.44-1.27); alkaline phosphatase, 369 IU/L (reference range, 39-117). White blood cell count was 15.5 × 10⁹/L (reference range, 3.5-10.3), and lactic acid was 2.5 mmol/L (reference range, 0.5-2.2). He was started on piperacillin/tazobactam in the emergency department and transitioned to ciprofloxacin and metronidazole for presumed intra-abdominal infection. Paracentesis showed a serum ascites albumin gradient of > 1.1 g/dL with no signs of spontaneous bacterial peritonitis. Computed tomography of the abdomen and pelvis with contrast was suspicious for colitis involving the proximal colon, and colonic mass could not be excluded. Also noted was hepatosplenomegaly with abdominopelvic ascites.

Based on these findings, an EGD and colonoscopy were done. The EGD showed mild portal hypertensive gastropathy.

Discussion

Amyloidosis is a rare disorder of abnormal protein folding, leading to the deposition of insoluble fibrils that disrupt normal tissues and cause disease.³ There are several variations of amyloid, but the most common type is AL amyloidosis, which affects several organs, including the heart, kidney, liver, nervous system, and GI tract. When AL amyloidosis involves the liver, the median survival time is about 8.5 months.⁶ There are different ways to diagnose the disease, but a tissue biopsy and Congo Red staining can confirm specific organ involvement as seen in our case.

This case adds another layer to our constantly expanding differential as health care practitioners and proves that atypical patient presentations may not be atypical after all. GI amyloidosis tends to present similarly to our patient with bleeding, malabsorption, dysmotility, and protein-losing gastroenteropathy as ascites, edema, pericardial effusions, and laboratory evidence of hypoalbuminemia.⁷ Because amyloidosis is a systemic illness, early recognition is important as intestinal complications tend to present as symptoms, but mortality is more often caused by renal failure, cardiomyopathy, or ischemic heart disease, making early multispecialty involvement very important.⁸

Conclusions

Health care practitioners in all specialties should be aware of and include intestinal amyloidosis in their differential diagnosis when working up GI bleeds with the hope of identifying the disease early. With early recognition, rapid biopsy identification, and early specialist involvement, patients will get the opportunity for expedited multidisciplinary treatment and potentially delay rapid decompensation as shown by the evidence in this case.

Gastrointestinal (GI) bleeding is a common cause of hospital admissions. The yearly incidence of upper GI bleeding is 80 to 150/100,000 people and lower GI bleeding is 87/100,000 people.^1,2 The differential tends to initially be broad but narrows with good history followed by endoscopic findings. Getting an appropriate history can be difficult at times, which leads health care practitioners to rely more on interventional results.

Amyloidosis is a rare disorder of abnormal protein folding, leading to the deposition of insoluble fibrils that disrupt normal tissues and cause disease.³ There are 2 main types of amyloidosis, systemic and transthyretin, and 4 subtypes. Systemic amyloidosis includes amyloid light-chain (AL) deposition, caused by plasma cell dyscrasia, and amyloid A (AA) protein deposition, caused by systemic autoimmune illness or infections. Transthyretin amyloidosis is caused by changes and deposition of the transthyretin protein consisting of either unstable, mutant protein or wild type protein. Biopsy-proven amyloidosis of the GI tract is rare.⁴ About 60% of patients with AA amyloidosis and 8% with AL amyloidosis have GI involvement.⁵

We present a case of nonspecific symptoms that ultimately lined up perfectly with the official histologic confirmation of intestinal amyloidosis.

Case Presentation

A 79-year-old man with a history of type 2 diabetes mellitus, congestive heart failure, hyperlipidemia, obstructive sleep apnea, hypothyroidism, hypertension, coronary artery disease status postcoronary artery bypass grafting, and stent placements presented for 3 episodes of large, bright red bowel movements. He reported past bleeding and straining with stools, but bleeding of this amount had not been noted prior. He also reported dry heaves, lower abdominal pain, constipation with straining, early satiety with dysphagia, weakness, and decreased appetite. Lastly, he mentioned intentionally losing about 35 to 40 pounds in the past 3 to 4 months and over the past several months increased abdominal distention. However, he stated he had no history of alcohol misuse, liver or intestinal disease, cirrhosis, or other autoimmune diseases. His most recent colonoscopy was more than a decade prior and showed no acute process. The patient never had an esophagogastroduodenoscopy (EGD).

On initial presentation, the patient’s vital signs showed no acute findings. His physical examination noted a chronically ill–appearing male with decreased breath sounds to the bases bilaterally and noted abdominal distention with mild generalized tenderness. Laboratory findings were significant for a hemoglobin level, 9.4 g/dL (reference range, 11.6-15.3); iron, 23 ug/dL (reference range, 45-160); transferrin saturation, 8% (reference range, 15-50); ferritin level, 80 ng/mL (reference range, 30-300); and carcinoembryonic antigen level, 1.5 ng/mL (reference range, 0-2.9). Aspartate aminotransferase level was 54 IU/L (reference range, 0-40); alanine transaminase, 24 IU/L (reference range, 7-52); albumin, 2.7 g/dL (reference range, 3.4-5.7); international normalized ratio, 1.3 (reference range, 0-1.1); creatinine, 1.74 mg/dL (reference range, 0.44-1.27); alkaline phosphatase, 369 IU/L (reference range, 39-117). White blood cell count was 15.5 × 10⁹/L (reference range, 3.5-10.3), and lactic acid was 2.5 mmol/L (reference range, 0.5-2.2). He was started on piperacillin/tazobactam in the emergency department and transitioned to ciprofloxacin and metronidazole for presumed intra-abdominal infection. Paracentesis showed a serum ascites albumin gradient of > 1.1 g/dL with no signs of spontaneous bacterial peritonitis. Computed tomography of the abdomen and pelvis with contrast was suspicious for colitis involving the proximal colon, and colonic mass could not be excluded. Also noted was hepatosplenomegaly with abdominopelvic ascites.

Based on these findings, an EGD and colonoscopy were done. The EGD showed mild portal hypertensive gastropathy.

Discussion

Amyloidosis is a rare disorder of abnormal protein folding, leading to the deposition of insoluble fibrils that disrupt normal tissues and cause disease.³ There are several variations of amyloid, but the most common type is AL amyloidosis, which affects several organs, including the heart, kidney, liver, nervous system, and GI tract. When AL amyloidosis involves the liver, the median survival time is about 8.5 months.⁶ There are different ways to diagnose the disease, but a tissue biopsy and Congo Red staining can confirm specific organ involvement as seen in our case.

This case adds another layer to our constantly expanding differential as health care practitioners and proves that atypical patient presentations may not be atypical after all. GI amyloidosis tends to present similarly to our patient with bleeding, malabsorption, dysmotility, and protein-losing gastroenteropathy as ascites, edema, pericardial effusions, and laboratory evidence of hypoalbuminemia.⁷ Because amyloidosis is a systemic illness, early recognition is important as intestinal complications tend to present as symptoms, but mortality is more often caused by renal failure, cardiomyopathy, or ischemic heart disease, making early multispecialty involvement very important.⁸

Conclusions

Health care practitioners in all specialties should be aware of and include intestinal amyloidosis in their differential diagnosis when working up GI bleeds with the hope of identifying the disease early. With early recognition, rapid biopsy identification, and early specialist involvement, patients will get the opportunity for expedited multidisciplinary treatment and potentially delay rapid decompensation as shown by the evidence in this case.

Health care systems need practical, scalable methods to reach patients and connect them to available, evidence-based resources. Ideally, these systems need to be resource nonintensive to deploy, maintain, and use. They should also be low cost, have a relative advantage to the organization, be sensitive to patient needs, use available resources, and have rigorous evidence regarding their effect on patient-centered outcomes.^1,2 Phone service is one way to reach people that remains viable. More than 97% of Americans own a cellphone of some kind, and 40% still have a landline.^3,4 One intervention that has been increasingly used in routine care settings is an interactive voice response (IVR) system that uses phones for connecting to patients.

IVR systems are a type of telehealth that provides information or adjunct health services through use of a telecommunication platform and information technologies.⁵ These systems are automated telephone systems that use prerecorded or text-to-speech–generated messages that allow respondents to provide and access information without a live agent.⁶ Text messaging (SMS) is another modality that can be used to asynchronously engage with participants. IVR systems have been used successfully for many health conditions and services, such as improving veterans’ adherence to continuous positive airway pressure, colorectal cancer screening, and cognitive behavioral therapy.^7-10 By building on existing technology and infrastructure, IVR systems can be a cost-effective option for health care system services.

A 2016 Cochrane review of IVR systems for smoking cessation identified 7 studies.¹¹ Although none used opt-out mechanisms (where individuals are automatically enrolled in programs until they decide not to participate) to engage people without an expressed motivation to quit, these interventions seemed safe and were promisingly effective. Among patients enrolled in primary care, a trial of an IVR system led to a higher quit rate: 18% vs 8%.¹²

In one study, patients in the emergency department, particularly older ones, preferred phone-based interventions over SMS.¹³ IVR-based proactive tobacco cessation systems are cost-effective and have been successfully used in the US Department of Veterans Affairs (VA).^14,15 IVR systems using opt-out approaches are being studied, though their effectiveness in this setting has not been proven. The pros and cons of different interventions need to be explored since there is likely a tradeoff between feasibility and effectiveness. For example, intensive smoking cessation interventions are more effective but often require more resources to implement and sustain.¹⁶ Basing interventions that are not resource intensive within a reputable organizational system may amplify the effectiveness.¹⁷

This endeavor to establish an IVR system was initiated as part of our research study, a randomized trial of the Teachable Moment to Opt-Out of Tobacco (TeaM OUT) intervention at the VA Portland Health Care System in Oregon. We measured the reach and effectiveness of a novel, proactive, resource nonintensive, and pragmatic intervention to engage veterans with a recently diagnosed lung nodule who smoke cigarettes.¹⁸ Our research team extracted the contact information for patients currently smoking and found to a have a pulmonary nodule from the VA Corporate Data Warehouse.¹⁹ We then manually uploaded those data to an IVR website where the system contacted patients to connect them to smoking cessation resources on an opt-out basis. In the research study, we measured the acceptability and effectiveness of the TeaM OUT intervention using quantitative and qualitative methods.

We developed and implemented an IVR system for use at 4 facilities: VA Portland Health Care System, Minneapolis VA Health Care System, Ralph H. Johnson VA Medical Center (Charleston, NC), and the Baltimore VA Medical Center. Setting up any type of wide-scale technology within the VA can be challenging. Due to our experience in developing and implementing the IVR system in the VA, we share what we have learned about the process of finding, contracting, developing, and implementing an IVR system. We share our experiences with developing and implementing this system to provide guidance for those who may want to establish an IVR system (or similar technologies) within the VA.

Lessons Learned

During our development and implementation process, we learned several lessons about setting up an IVR system in the VA. It is important to note that VA facilities may have differing processes, and policies frequently change; thus coordination with departments (eg, contracting, finance, Office of Information and Technology [OIT], etc) to verify the following strategies is essential (Figure).

Vendor Selection

Check with the local OIT and contracting offices to see if the facility has previously used any vendors for these services and for advice on selection. We compiled a list of questions that may be helpful based on our discussions with 4 vendors, prior to selection of a vendor already VA-approved (Appendix). There are also questions to think about in parallel with choosing a vendor. Contact your OIT, contracting, and privacy (if necessary) offices before choosing a vendor.

Online Security

After selecting a vendor, if you want an online portal to view, upload, or downloaddata, then you will need to initiate the single sign-on internal (SSOI) process (www.data.va.gov/dataset/Single-Sign-On-Internal-SSOi-/cber-kxf9). Other benefits of a website are to identify call patterns (eg, no one picks up after the 10th call) and track respondents’ selections. The SSOI process can take up to 1 year. Notably, the website login at minimum needs to be created by the IVR vendor to start the process. After the SSOI is approved you can add more to the website beyond just the login capability. Note that the script needs to be finalized prior to SSOI initiation. You will need to initiate with the SSOI team, then the vendor will need to complete the process.

Contracting

Concurrent with the above steps, contact the contracting office to get a sense of the paperwork and timeline. Make sure you are comfortable with the vendor’s responses to the questions in the Appendix, and view their written proposal or scope of work (SOW) to ensure they can do what the project protocol demands.

If the vendor has previously worked with the VA, contact your local contract office (usually part of the Finance Office) for updated forms. We needed the 6500.6 Checklist, Document Checklist for Service Requests, Single Source Justification, Research & Development Order (if research-related), and Vendor File Request forms. The vendor can help complete these forms. Review the proposal/SOW and budget first, knowing that budgets have a wide range and depend on the length and complexity of the script, number of calls, number of respondents, etc. For example, our quote was $110,000 over 4 years, including development, training, hosting on a secure server, and maintenance. Our IVR system will call about 5000 patients across 4 sites. Each patient will receive up to 15 calls over 2 weeks if they do not answer. We created 2 IVR lines (1 inbound and 1 outbound). Next, contact the lead of the local OIT and contracting departments by email to justify sharing veteran information with a contracted entity via approved methods. Finally, contact the privacy officer and information security officer. Discuss where software would be installed, whether cloud storage would be used, and what information can be shared/stored. Remember that the rules may differ for research vs nonresearch projects. Also, determine whether a data-use agreement between the VA and the vendor is needed and how the institutional review board (if research) gets integrated.

If using an outside vendor who has never worked with the VA, submit form 6550.6. Note that contracting requires several months. First, contact OIT and contracting departments. Again, you will need to justify sharing veteran information with a contracted entity. Next, complete the Project Special Forces Software and Privacy Threshold Analysis process to purchase the system. Set up a meeting with OIT to determine other forms and next steps. Business need/case use form and data security categorization may be needed. If the software needs to be installed on a VA computer, you will need to submit a Technical Reference Model request if it does not have an entry.

Vendors can answer technical questions from the contracting office, especially about the SOW, but the VA team needs to write the contract and manage all documentation and communication. You will also need sole source documentation (receive from contracting office) with justification for why you want to use a specific vendor. If you do not have that justification, in cooperation with the contracts office, you must solicit bids from other companies. Importantly, understand the staff support needed for contracting and build into your timeline and budget. Not surprisingly, we found that in-person or phone meetings were invaluable compared with email correspondence. Meet with all parties involved early and often. Once the contract is clear, this begins the build process where the vendor can program and record the script. This process usually takes 1 to 2 months.

Patient Engagement, Tracking, and Long-term Support

The new Patient Engagement, Tracking, and Long-term Support (PETALS) initiative is an excellent place to start with any VA IVR-related questions. PETALS is used for research.²⁰ We hoped to use this system for our study, but its implementation was delayed until 2022. The PETALS system is designed for VA investigators who conduct research studies and need a secure platform that is compliant with VA policies for deploying SMS and IVR systems for research.²⁰ At this time, PETALS is for use only with veterans, so if research will occur outside the VA, you must use an outside vendor. Users who want to set up a new IVR system can ask their local contracting office whether any contracts have already been established for IVR development and support.

From our perspective as researchers who are not telehealth savvy, we encountered several delays from failing to ask the appropriate questions or inability to navigate complicated systems. For instance, there were several tasks that needed to be completed and were not included in the original timeline developed by the vendor and researcher. Therefore, it is important to have clear communication on both sides about who is doing what, when, and how. We tried to detail these unexpected steps to help researchers, administrators, or other VA employees in the future.

Conclusions

IVR systems, once they are developed and implemented, can be efficient, low-cost, resource-nonintensive solutions in a health care setting that can effectively connect patients with needed health care services. Our experience developing an IVR system within the VA was challenging and was a huge learning curve for our research team. We hope that our experience and lessons will help VA personnel in the future.

Acknowledgments

Thank you to everyone involved in this project and who answered questions about the process, especially Nicolle Marinec, MPH; Toan Tran, and Molly Delorit, BA. This study and Christopher Slatore, MD, are supported by an award from the US Department of Veterans Affairs (HSR&D IIR 19-425). It was also supported by resources from the Center to Improve Veteran Involvement in Care, VA Portland Health Care System, Portland, Oregon (VAPORHCS).

Health care systems need practical, scalable methods to reach patients and connect them to available, evidence-based resources. Ideally, these systems need to be resource nonintensive to deploy, maintain, and use. They should also be low cost, have a relative advantage to the organization, be sensitive to patient needs, use available resources, and have rigorous evidence regarding their effect on patient-centered outcomes.^1,2 Phone service is one way to reach people that remains viable. More than 97% of Americans own a cellphone of some kind, and 40% still have a landline.^3,4 One intervention that has been increasingly used in routine care settings is an interactive voice response (IVR) system that uses phones for connecting to patients.

IVR systems are a type of telehealth that provides information or adjunct health services through use of a telecommunication platform and information technologies.⁵ These systems are automated telephone systems that use prerecorded or text-to-speech–generated messages that allow respondents to provide and access information without a live agent.⁶ Text messaging (SMS) is another modality that can be used to asynchronously engage with participants. IVR systems have been used successfully for many health conditions and services, such as improving veterans’ adherence to continuous positive airway pressure, colorectal cancer screening, and cognitive behavioral therapy.^7-10 By building on existing technology and infrastructure, IVR systems can be a cost-effective option for health care system services.

A 2016 Cochrane review of IVR systems for smoking cessation identified 7 studies.¹¹ Although none used opt-out mechanisms (where individuals are automatically enrolled in programs until they decide not to participate) to engage people without an expressed motivation to quit, these interventions seemed safe and were promisingly effective. Among patients enrolled in primary care, a trial of an IVR system led to a higher quit rate: 18% vs 8%.¹²

In one study, patients in the emergency department, particularly older ones, preferred phone-based interventions over SMS.¹³ IVR-based proactive tobacco cessation systems are cost-effective and have been successfully used in the US Department of Veterans Affairs (VA).^14,15 IVR systems using opt-out approaches are being studied, though their effectiveness in this setting has not been proven. The pros and cons of different interventions need to be explored since there is likely a tradeoff between feasibility and effectiveness. For example, intensive smoking cessation interventions are more effective but often require more resources to implement and sustain.¹⁶ Basing interventions that are not resource intensive within a reputable organizational system may amplify the effectiveness.¹⁷

This endeavor to establish an IVR system was initiated as part of our research study, a randomized trial of the Teachable Moment to Opt-Out of Tobacco (TeaM OUT) intervention at the VA Portland Health Care System in Oregon. We measured the reach and effectiveness of a novel, proactive, resource nonintensive, and pragmatic intervention to engage veterans with a recently diagnosed lung nodule who smoke cigarettes.¹⁸ Our research team extracted the contact information for patients currently smoking and found to a have a pulmonary nodule from the VA Corporate Data Warehouse.¹⁹ We then manually uploaded those data to an IVR website where the system contacted patients to connect them to smoking cessation resources on an opt-out basis. In the research study, we measured the acceptability and effectiveness of the TeaM OUT intervention using quantitative and qualitative methods.

We developed and implemented an IVR system for use at 4 facilities: VA Portland Health Care System, Minneapolis VA Health Care System, Ralph H. Johnson VA Medical Center (Charleston, NC), and the Baltimore VA Medical Center. Setting up any type of wide-scale technology within the VA can be challenging. Due to our experience in developing and implementing the IVR system in the VA, we share what we have learned about the process of finding, contracting, developing, and implementing an IVR system. We share our experiences with developing and implementing this system to provide guidance for those who may want to establish an IVR system (or similar technologies) within the VA.

Lessons Learned

During our development and implementation process, we learned several lessons about setting up an IVR system in the VA. It is important to note that VA facilities may have differing processes, and policies frequently change; thus coordination with departments (eg, contracting, finance, Office of Information and Technology [OIT], etc) to verify the following strategies is essential (Figure).

Vendor Selection

Check with the local OIT and contracting offices to see if the facility has previously used any vendors for these services and for advice on selection. We compiled a list of questions that may be helpful based on our discussions with 4 vendors, prior to selection of a vendor already VA-approved (Appendix). There are also questions to think about in parallel with choosing a vendor. Contact your OIT, contracting, and privacy (if necessary) offices before choosing a vendor.

Online Security

After selecting a vendor, if you want an online portal to view, upload, or downloaddata, then you will need to initiate the single sign-on internal (SSOI) process (www.data.va.gov/dataset/Single-Sign-On-Internal-SSOi-/cber-kxf9). Other benefits of a website are to identify call patterns (eg, no one picks up after the 10th call) and track respondents’ selections. The SSOI process can take up to 1 year. Notably, the website login at minimum needs to be created by the IVR vendor to start the process. After the SSOI is approved you can add more to the website beyond just the login capability. Note that the script needs to be finalized prior to SSOI initiation. You will need to initiate with the SSOI team, then the vendor will need to complete the process.

Contracting

Concurrent with the above steps, contact the contracting office to get a sense of the paperwork and timeline. Make sure you are comfortable with the vendor’s responses to the questions in the Appendix, and view their written proposal or scope of work (SOW) to ensure they can do what the project protocol demands.

If the vendor has previously worked with the VA, contact your local contract office (usually part of the Finance Office) for updated forms. We needed the 6500.6 Checklist, Document Checklist for Service Requests, Single Source Justification, Research & Development Order (if research-related), and Vendor File Request forms. The vendor can help complete these forms. Review the proposal/SOW and budget first, knowing that budgets have a wide range and depend on the length and complexity of the script, number of calls, number of respondents, etc. For example, our quote was $110,000 over 4 years, including development, training, hosting on a secure server, and maintenance. Our IVR system will call about 5000 patients across 4 sites. Each patient will receive up to 15 calls over 2 weeks if they do not answer. We created 2 IVR lines (1 inbound and 1 outbound). Next, contact the lead of the local OIT and contracting departments by email to justify sharing veteran information with a contracted entity via approved methods. Finally, contact the privacy officer and information security officer. Discuss where software would be installed, whether cloud storage would be used, and what information can be shared/stored. Remember that the rules may differ for research vs nonresearch projects. Also, determine whether a data-use agreement between the VA and the vendor is needed and how the institutional review board (if research) gets integrated.

If using an outside vendor who has never worked with the VA, submit form 6550.6. Note that contracting requires several months. First, contact OIT and contracting departments. Again, you will need to justify sharing veteran information with a contracted entity. Next, complete the Project Special Forces Software and Privacy Threshold Analysis process to purchase the system. Set up a meeting with OIT to determine other forms and next steps. Business need/case use form and data security categorization may be needed. If the software needs to be installed on a VA computer, you will need to submit a Technical Reference Model request if it does not have an entry.

Vendors can answer technical questions from the contracting office, especially about the SOW, but the VA team needs to write the contract and manage all documentation and communication. You will also need sole source documentation (receive from contracting office) with justification for why you want to use a specific vendor. If you do not have that justification, in cooperation with the contracts office, you must solicit bids from other companies. Importantly, understand the staff support needed for contracting and build into your timeline and budget. Not surprisingly, we found that in-person or phone meetings were invaluable compared with email correspondence. Meet with all parties involved early and often. Once the contract is clear, this begins the build process where the vendor can program and record the script. This process usually takes 1 to 2 months.

Patient Engagement, Tracking, and Long-term Support

The new Patient Engagement, Tracking, and Long-term Support (PETALS) initiative is an excellent place to start with any VA IVR-related questions. PETALS is used for research.²⁰ We hoped to use this system for our study, but its implementation was delayed until 2022. The PETALS system is designed for VA investigators who conduct research studies and need a secure platform that is compliant with VA policies for deploying SMS and IVR systems for research.²⁰ At this time, PETALS is for use only with veterans, so if research will occur outside the VA, you must use an outside vendor. Users who want to set up a new IVR system can ask their local contracting office whether any contracts have already been established for IVR development and support.

From our perspective as researchers who are not telehealth savvy, we encountered several delays from failing to ask the appropriate questions or inability to navigate complicated systems. For instance, there were several tasks that needed to be completed and were not included in the original timeline developed by the vendor and researcher. Therefore, it is important to have clear communication on both sides about who is doing what, when, and how. We tried to detail these unexpected steps to help researchers, administrators, or other VA employees in the future.

Conclusions

IVR systems, once they are developed and implemented, can be efficient, low-cost, resource-nonintensive solutions in a health care setting that can effectively connect patients with needed health care services. Our experience developing an IVR system within the VA was challenging and was a huge learning curve for our research team. We hope that our experience and lessons will help VA personnel in the future.

Acknowledgments

Thank you to everyone involved in this project and who answered questions about the process, especially Nicolle Marinec, MPH; Toan Tran, and Molly Delorit, BA. This study and Christopher Slatore, MD, are supported by an award from the US Department of Veterans Affairs (HSR&D IIR 19-425). It was also supported by resources from the Center to Improve Veteran Involvement in Care, VA Portland Health Care System, Portland, Oregon (VAPORHCS).

Health care systems need practical, scalable methods to reach patients and connect them to available, evidence-based resources. Ideally, these systems need to be resource nonintensive to deploy, maintain, and use. They should also be low cost, have a relative advantage to the organization, be sensitive to patient needs, use available resources, and have rigorous evidence regarding their effect on patient-centered outcomes.^1,2 Phone service is one way to reach people that remains viable. More than 97% of Americans own a cellphone of some kind, and 40% still have a landline.^3,4 One intervention that has been increasingly used in routine care settings is an interactive voice response (IVR) system that uses phones for connecting to patients.

IVR systems are a type of telehealth that provides information or adjunct health services through use of a telecommunication platform and information technologies.⁵ These systems are automated telephone systems that use prerecorded or text-to-speech–generated messages that allow respondents to provide and access information without a live agent.⁶ Text messaging (SMS) is another modality that can be used to asynchronously engage with participants. IVR systems have been used successfully for many health conditions and services, such as improving veterans’ adherence to continuous positive airway pressure, colorectal cancer screening, and cognitive behavioral therapy.^7-10 By building on existing technology and infrastructure, IVR systems can be a cost-effective option for health care system services.

A 2016 Cochrane review of IVR systems for smoking cessation identified 7 studies.¹¹ Although none used opt-out mechanisms (where individuals are automatically enrolled in programs until they decide not to participate) to engage people without an expressed motivation to quit, these interventions seemed safe and were promisingly effective. Among patients enrolled in primary care, a trial of an IVR system led to a higher quit rate: 18% vs 8%.¹²

In one study, patients in the emergency department, particularly older ones, preferred phone-based interventions over SMS.¹³ IVR-based proactive tobacco cessation systems are cost-effective and have been successfully used in the US Department of Veterans Affairs (VA).^14,15 IVR systems using opt-out approaches are being studied, though their effectiveness in this setting has not been proven. The pros and cons of different interventions need to be explored since there is likely a tradeoff between feasibility and effectiveness. For example, intensive smoking cessation interventions are more effective but often require more resources to implement and sustain.¹⁶ Basing interventions that are not resource intensive within a reputable organizational system may amplify the effectiveness.¹⁷

This endeavor to establish an IVR system was initiated as part of our research study, a randomized trial of the Teachable Moment to Opt-Out of Tobacco (TeaM OUT) intervention at the VA Portland Health Care System in Oregon. We measured the reach and effectiveness of a novel, proactive, resource nonintensive, and pragmatic intervention to engage veterans with a recently diagnosed lung nodule who smoke cigarettes.¹⁸ Our research team extracted the contact information for patients currently smoking and found to a have a pulmonary nodule from the VA Corporate Data Warehouse.¹⁹ We then manually uploaded those data to an IVR website where the system contacted patients to connect them to smoking cessation resources on an opt-out basis. In the research study, we measured the acceptability and effectiveness of the TeaM OUT intervention using quantitative and qualitative methods.

We developed and implemented an IVR system for use at 4 facilities: VA Portland Health Care System, Minneapolis VA Health Care System, Ralph H. Johnson VA Medical Center (Charleston, NC), and the Baltimore VA Medical Center. Setting up any type of wide-scale technology within the VA can be challenging. Due to our experience in developing and implementing the IVR system in the VA, we share what we have learned about the process of finding, contracting, developing, and implementing an IVR system. We share our experiences with developing and implementing this system to provide guidance for those who may want to establish an IVR system (or similar technologies) within the VA.

Lessons Learned

During our development and implementation process, we learned several lessons about setting up an IVR system in the VA. It is important to note that VA facilities may have differing processes, and policies frequently change; thus coordination with departments (eg, contracting, finance, Office of Information and Technology [OIT], etc) to verify the following strategies is essential (Figure).

Vendor Selection

Check with the local OIT and contracting offices to see if the facility has previously used any vendors for these services and for advice on selection. We compiled a list of questions that may be helpful based on our discussions with 4 vendors, prior to selection of a vendor already VA-approved (Appendix). There are also questions to think about in parallel with choosing a vendor. Contact your OIT, contracting, and privacy (if necessary) offices before choosing a vendor.

Online Security

After selecting a vendor, if you want an online portal to view, upload, or downloaddata, then you will need to initiate the single sign-on internal (SSOI) process (www.data.va.gov/dataset/Single-Sign-On-Internal-SSOi-/cber-kxf9). Other benefits of a website are to identify call patterns (eg, no one picks up after the 10th call) and track respondents’ selections. The SSOI process can take up to 1 year. Notably, the website login at minimum needs to be created by the IVR vendor to start the process. After the SSOI is approved you can add more to the website beyond just the login capability. Note that the script needs to be finalized prior to SSOI initiation. You will need to initiate with the SSOI team, then the vendor will need to complete the process.

Contracting

Concurrent with the above steps, contact the contracting office to get a sense of the paperwork and timeline. Make sure you are comfortable with the vendor’s responses to the questions in the Appendix, and view their written proposal or scope of work (SOW) to ensure they can do what the project protocol demands.

If the vendor has previously worked with the VA, contact your local contract office (usually part of the Finance Office) for updated forms. We needed the 6500.6 Checklist, Document Checklist for Service Requests, Single Source Justification, Research & Development Order (if research-related), and Vendor File Request forms. The vendor can help complete these forms. Review the proposal/SOW and budget first, knowing that budgets have a wide range and depend on the length and complexity of the script, number of calls, number of respondents, etc. For example, our quote was $110,000 over 4 years, including development, training, hosting on a secure server, and maintenance. Our IVR system will call about 5000 patients across 4 sites. Each patient will receive up to 15 calls over 2 weeks if they do not answer. We created 2 IVR lines (1 inbound and 1 outbound). Next, contact the lead of the local OIT and contracting departments by email to justify sharing veteran information with a contracted entity via approved methods. Finally, contact the privacy officer and information security officer. Discuss where software would be installed, whether cloud storage would be used, and what information can be shared/stored. Remember that the rules may differ for research vs nonresearch projects. Also, determine whether a data-use agreement between the VA and the vendor is needed and how the institutional review board (if research) gets integrated.

If using an outside vendor who has never worked with the VA, submit form 6550.6. Note that contracting requires several months. First, contact OIT and contracting departments. Again, you will need to justify sharing veteran information with a contracted entity. Next, complete the Project Special Forces Software and Privacy Threshold Analysis process to purchase the system. Set up a meeting with OIT to determine other forms and next steps. Business need/case use form and data security categorization may be needed. If the software needs to be installed on a VA computer, you will need to submit a Technical Reference Model request if it does not have an entry.

Vendors can answer technical questions from the contracting office, especially about the SOW, but the VA team needs to write the contract and manage all documentation and communication. You will also need sole source documentation (receive from contracting office) with justification for why you want to use a specific vendor. If you do not have that justification, in cooperation with the contracts office, you must solicit bids from other companies. Importantly, understand the staff support needed for contracting and build into your timeline and budget. Not surprisingly, we found that in-person or phone meetings were invaluable compared with email correspondence. Meet with all parties involved early and often. Once the contract is clear, this begins the build process where the vendor can program and record the script. This process usually takes 1 to 2 months.

Patient Engagement, Tracking, and Long-term Support

The new Patient Engagement, Tracking, and Long-term Support (PETALS) initiative is an excellent place to start with any VA IVR-related questions. PETALS is used for research.²⁰ We hoped to use this system for our study, but its implementation was delayed until 2022. The PETALS system is designed for VA investigators who conduct research studies and need a secure platform that is compliant with VA policies for deploying SMS and IVR systems for research.²⁰ At this time, PETALS is for use only with veterans, so if research will occur outside the VA, you must use an outside vendor. Users who want to set up a new IVR system can ask their local contracting office whether any contracts have already been established for IVR development and support.

From our perspective as researchers who are not telehealth savvy, we encountered several delays from failing to ask the appropriate questions or inability to navigate complicated systems. For instance, there were several tasks that needed to be completed and were not included in the original timeline developed by the vendor and researcher. Therefore, it is important to have clear communication on both sides about who is doing what, when, and how. We tried to detail these unexpected steps to help researchers, administrators, or other VA employees in the future.

Conclusions

IVR systems, once they are developed and implemented, can be efficient, low-cost, resource-nonintensive solutions in a health care setting that can effectively connect patients with needed health care services. Our experience developing an IVR system within the VA was challenging and was a huge learning curve for our research team. We hope that our experience and lessons will help VA personnel in the future.

Acknowledgments

Thank you to everyone involved in this project and who answered questions about the process, especially Nicolle Marinec, MPH; Toan Tran, and Molly Delorit, BA. This study and Christopher Slatore, MD, are supported by an award from the US Department of Veterans Affairs (HSR&D IIR 19-425). It was also supported by resources from the Center to Improve Veteran Involvement in Care, VA Portland Health Care System, Portland, Oregon (VAPORHCS).

The costs for wound care play a significant role in total health care costs and are expected to rise dramatically. A 2018 Medicare analysis estimated chronic wound care cost $28.1 to $96.8 billion in supplies, hospitalization, and nursing care: Most costs were accrued in outpatient wound care.¹ The global market for advanced wound care supplies is projected to reach $13.7 billion by 2027, and negative wound pressure therapy alone is projected to grow at a compound annual growth rate of 5% over the analysis period 2020 to 2027.² Chronic wound care also impacts the patient physiologically, socially, and psychologically. One study compared the 5-year mortality of a patient with a diabetic foot ulcer (30.5%) as similar to those patients with cancer (31%).³ Yet the investment in cancer research far outstrips wound care research.

There is no perfect wound dressing for all chronic wounds, but there is expert consensus on interventions that facilitate wound healing. In 2021, Nuutila and Eriksson stated that wound dressings should fulfill the following criteria: protection against trauma, esthetically acceptable, painless to remove, easy to apply, protection for the wound from contamination and further trauma, a moist environment, and an optimal water vapor transmission rate.⁴ Balanced moisture control is considered essential for healing chronic wounds. Indeed, moisture control within the wound bed may be the most important factor in chronic wound management and healing. The body communicates through a liquid medium, and if that medium is compromised, communication and marshaling of the immune and healing responses may become inefficient.⁴ Too much moisture, exudate, or fluid in the wound, and the healing is slowed; too little moisture in the wound results in a compromised responses from the body’s immune system, thus delaying healing. In 1988, Dyson and colleagues demonstrated that moist wound care was superior for the inflammatory and proliferative phases of dermal repair compared with dry wound care. The results showed that 5 days after injury, 66% of the cells in the moist wound were fibroblasts and endothelial cells vs 48% of those in the dry wounds.⁵

The question of dry vs moist wound care has resulted in various wound dressings that produce favorable moisture balance. Moisture balance in a wound creates the ideal environment for wound healing. Sound wound care practices promote the following physiologic responses: increased probability of autolytic debridement; increased collagen synthesis; keratinocyte migration and reepithelization; decreased pain, inflammation, scarring, and necrosis;enhancement of cell-to-cell signaling; and increase in growth factors.^5,6 All these processes are mediated through proper wound moisture control. In addition to proper moisture control, antibiotics added to the wound care milieu (either directly to the wound or systemically) may have a place in chronic wound care. In 2013, Junker and colleagues reported that low-dose antibiotics combined with appropriate moisture balance in wounds demonstrated less scar tissue compared with dry wound care.⁶

Approaches to chronic wound care are worlds apart: In developing nations the care of chronic wounds often involves traditional management with local products (eg, honey, boiled potato peels, aloe vera gel, banana leaves), whereas in developed nations, more expensive and technologically advanced products are available (eg, wound vacuum, saline wound chamber, hyperbaric oxygen therapy, antibacterial foam). Developing countries often do not have access to technologically advanced wound care products. Local products are often used by local healers, priests, and shamans. The use of these wound interventions in developing countries has produced satisfactory results. In contrast, developed countries have multiple chronic wound care products available (Table).

CASE Presentation

An athletic, healthy 60-year-old Utah National Guard member presented to the George E. Wahlen Department of Veterans Affairs Medical Center in Salt Lake City, Utah, 6 days after experiencing a spider bite. For the first 6 days, the patient applied bacitracin at home. On day 7, the patient noticed that the wound was enlarging and appeared to be fluctuant. The patient was prescribed clindamycin 300 mg 4 times daily on an outpatient basis, which was taken on days 7 to 14.

The wound’s total surface area continued to expand, and the patient returned to the Salt Lake City Veterans Hospital wound care clinic on day 17 stating that the wound was very painful and more fluctuant. The wound care nursing staff were consulted, the wound was debrided, and attempts to drain the wound resulted in minimal exudate expressed from the wound. Clindamycin was increased to 450 mg 4 times daily. However, the wound continued to enlarge and become more painful.

On day 20, the patient reported to nursing services and was admitted to the Salt Lake City Veterans Hospital general surgery department with mental status changes and symptoms of septicemia (Figure 1).

Discussion

Traditional Wound Care

Honey. Honey has been used as a treatment for wounds for almost 3000 years. It has antiseptic and antibacterial properties and contributes to a moist wound care environment. In 2011, Gupta and colleagues reported on the use of honey in 108 patients with burns of < 50% of the total body surface area.⁷ This report stated that delay in seeking medical care increased wound infection rates, contamination, time to sterilization, and healing. Compared with silver sulfadiazine cream, honey dressings improved the time to wound healing (33 days vs 18 days, respectively), decreased the time to wound sterilization (1 day vs no sterilization), and had better outcomes (37% vs 81%, respectively) with fewer hypertrophic scars and postburn contractures.⁷

Separate studies in 2011 and 2010 from Fukuda and colleagues and Majtan and colleagues, respectively, reported that honey eliminates pathogens from wounds, augments correct moisture balance, and elevates cytokine activity.^8,9 Additional studies in 2006, 2008, and 2014 by Henriques and colleagues, Van den Berg and colleagues, and Majtan suggested that honey reduces reactive oxygen species, is responsible for direct antimicrobial effects in a healing wound, inhibits free radical production, and promotes antitumor activity, respectively.^10-12 Van den Berg and colleagues suggested that buckwheat honey is the most effective honey in reducing reactive oxygen species.¹¹

Sterile banana leaves. In medically underserved and rural areas, boiled banana leaves are used to treat burns and nonhealing wounds. In a 2015 study, Waffa and Hayah compared gauze dressings with sterile banana leaves wound dressing in patients with partial thickness burns. Topical antibiotics were added to each type of dressing. The results suggested that the banana leaf dressings were easier to remove, patients reported less pain overall, less pain with dressing changes, and demonstrated a decreased time to healing when contrasted with gauze.¹³ In 2003, Gore and Akolekar compared autoclaved banana leaves with boiled potato peels in the treatment of patients with partial thickness burns. The time to epithelialization, eschar formation, and skin graft healing were equal in both groups. However, banana leaves were 11 times cheaper and rated easier to prepare than boiled potato peels.¹⁴ In a study comparing petroleum gauze with sterile banana leaves, Chendake and colleagues reported that in measures of overall pain and trauma during dressing changes, patients with contused and sutured wounds on the face and neck achieved better outcomes with boiled banana leaves compared with petroleum gauze.¹⁵

Boiled potato peels. This treatment is used in rural areas of the world as an adjunct for wound care. In 2015, Manjunath and colleagues theorized that the use of boiled potato peels in patients with necrotizing fasciitis decreased the acidic environment created by the bacteria. Additionally, the study asserted that the toxic wound environment created by the bacteria was neutralized by the potassium content in the peel, and the flavonoids in the peel acted as a free radical scavenger.¹⁶ In 2011, Panda and colleagues, using povidone-iodine as a baseline control, reported that peel extract and a peel bandage of sweet potato showed an increased wound closure percentage measured by enhanced epithelialization.¹⁷ This increased epithelialization was attributed to the antioxidant effect of the peels enhancing collagen synthesis.¹⁷

In contrast, in 1996, a study by Subrahmanyam compared autoclaved potato peel bandages with honey dressings as adjuncts in burn patients with < 40% of the total body surface area affected. The author reported that 90% of the wounds treated with honey were sterile in 7 days, while infection persisted in the potato peel group after 7 days. In the same study, 100% of the wounds treated with honey were healed in 15 days vs 50% in the potato peel group.¹⁸ In 1990, Keswani and colleagues compared boiled potato peels with plain gauze as adjuncts in the treatment of burn patients and concluded that although the potato peels had no antibacterial effect, the wounds in both groups had identical bacterial species. But the wounds treated with the potato peels showed reduced desiccation, permitting the survival of skin cells, and enhanced epithelial regeneration.¹⁹

Aloe vera. First recorded by the Egyptians and Greeks, aloe vera gel has been used for centuries in many cultures for a variety of ailments, particularly burns and chronic wounds. In a 2016 wound healing study performed on rats, Oryan and colleagues demonstrated that aloe vera gel was superior to saline used as the baseline control. Aloe vera gel used in a dose-dependent fashion demonstrated increased tissue levels of collagen and glycosaminoglycans compared with controls. Aloe vera gel modulated wound inflammation, increased wound contraction, wound epithelialization, decreased scar tissue size, and increased alignment and organization of the scar tissue.²⁰

Gauze. Iodoform gauze is a highly absorbent wound product. Sterile gauze promotes granulation and wound healing. It is well suited for wounds with minimal drainage. However, although gauze is inexpensive, it is easily overwhelmed by the moisture content in the wound, requiring frequent dressing changes (up to 3 times a day), ideally by nursing staff. The resulting increase in nursing care may actually increase the cost of wound care compared with other care modalities.

Petroleum gauze is often used in the care of acute and chronic wounds. However, petroleum-impregnated gauze has a water vapor transmission rate that needs to be remoistened every 4 hours. If the affected area is not remoistened during the exudative phase of wound healing, it may precipitate a delay in healing and increase pain and the prevalence of clinical infections compared with hydrocolloid, film, or foam dressings. Bolton suggested stopping the use of petroleum gauze as the control in studies because it does not provide a balanced and moist wound healing environment.²¹

Advanced Wound Treatments

Film products. Film products, including plastic food wrap, can be used as wound dressings and meet many of the necessary criteria for enhancing wound healing. These include moisture permeability, carbon dioxide, oxygen transfer, and wound protection. Transmission of moisture varies among products known as the moisture vapor transpiration rate. Film dressings have no absorptive qualities and are unsuited for highly exudative wounds.^22,23 Adding polymers, antibacterial, and bioactive agents may increase the wound care properties of film dressings.²² Film dressings excel in protecting shallow nonexudative wounds, are waterproof, and help protect the wound. These products are transparent, allowing clinicians to monitor the progress of the wound without removing the covering, and allowing the dressing to remain in place longer, which decreases the repeated trauma that can occur with dressing changes. Film dressings for wounds differ from those used for IV dressings and should not be used interchangeably.²³

Bioactive wound care. These solutions contribute to a moist wound-healing environment. Found naturally in brown seaweed, alginate-containing compounds were used by sailors for centuries to heal wounds. This was known in traditional medicine as the mariner’s cure. Alginate dressings are highly absorbent and can absorb up to 20 times their weight, which makes them desirable for use in highly exudative wounds. First synthesized more than 50 years ago, newer products contain bioactive compounds that prevent tissue damage, stimulate wound healing, improve cell proliferation and migration, and enhance metabolite formation.^24-26

In 2018, Aderibigbe and Buyana reported that polymers in the form of hydrogels were able to absorb fluid, making them a suitable choice for minimally exudative wounds. However, in their distended state, the hydrogel subgroup of these products became unstable (perhaps making them a poor choice for extensively exudative wounds), tended to dehydrate, and often needed a secondary dressing, which could lead to wound maceration.²² Most commonly used for wounds with minimal exudate, these dressings shine when used in nominally exudative dry wounds to promote autolytic debridement and hydrate the wound that has formed an eschar.

Hydrocolloid dressings are another type of bioactive wound dressing. These dressings are composed of 2 layers: an inner hydrophilic layer and an outer vapor-permeable layer that promote a moist wound environment. Hydrocolloid dressings assist in hydrating dry eschar wounds and have slight absorbency for exudative wounds. These dressings are not designed to be changed daily and can remain in place for 3 to 6 days. In a 2008 extensive review article, Thomas compared the utility of these dressings in patients with superficial or partial thickness burns, donor sites, surgical wounds, and minor traumatic wounds with basic wound dressings. The results of the review suggested that hydrocolloid dressings conferred statistically significant advantages in measures of decreased pain, healing times (decreased in donor sites by 40%), mobility restriction, and number of dressing changes.²⁷ Although more expensive than basic dressings, the longevity of the hydrocolloid dressing helps defray the original cost. Unfortunately, as these dressings remain in place and continue absorbing exudate, they can take on a very unpleasant odor.

A 2013 Cochrane database review comparing hydrocolloids with foams, alginate, basic wound dressing, and topical treatment found no statistical difference between hydrocolloids and basic wound dressings in patients with diabetes who have noncomplex foot ulcers.²⁸ In 2014, Pott and colleagues suggested a slight superiority in the performance of polyurethane foam dressings over hydrocolloid dressings used in pressure ulcers in older adults.²⁹ In a large pooled analysis in 2010, Davies compared foam to hydrocolloid dressings used in exudative wounds and reported that in 11 of 12 studies, foam dressings were superior to hydrocolloid in terms of exudate management, conformity to the wound, ease of use, decreased trauma and pain at dressing changes, and reduced odor of the wound.³⁰

Foam dressings. These products are typically composed of silicone or polyurethane. Consisting of 2 to 3 layers with a hydrophilic surface, foams are cut to approximate the wound size and serve to wick the macerated wound products to a secondary dressing above the foam. The micropores in the foam matrix absorb exudate from the wound bed while maintaining moisture equilibrium in the wound by donating back moisture to the wound, creating an environment conducive to wound healing. Foam dressings can be combined with various antiseptics (silver, GV/MB, etc) and serve as a delivery vehicle of those products directly to the wound surface.

A 2011 review comparing 8 studies found no difference among foam products available at that time in the use for chronic wounds.³¹ However, newer products on the market today have produced intriguing results with chronic wounds.

In 2017, Woo and Heil observed that chronic wounds treated with foam products containing GV/MB produced significant improvement when measured at week 4 in the areas of mean wound surface area (42.5%), decrease in baseline Pressure Ulcer Scale for Healing scores (from 13.3 to 10.7), wound coverage by devitalized tissue reduced (from 52.6% to 11.4%), and mean upper and lower wound infection scores were reduced by 75%.³² Further, the researchers reported a moist wound bed was achieved at dressing changes with polyvinyl alcohol (PVA) foam dressing. This led to the presumption that adequate moisture balance and autolytic debridement were facilitated using GV/MB antibacterial PVA foam dressings.

Many foam products on the market today exert an antibacterial effect on the wound bed. Antibiotic properties of various foam dressings create a microenvironment hostile to bacterial growth.³² In addition, the antibacterial properties combined with foam products contribute to the following: autolytic debridement, absorptive qualities (which reduce the bioburden of the wound), and maintenance of moisture in the wound bed. These qualities contribute significantly to the effectiveness of foam products with antibacterial properties.³² The correct balance of moisture in the wound has been identified as a superior environment and perhaps the most important component in chronic wounds.⁴ Foam dressings are less painful to change, easier to change, and in this case report, contributed to faster wound healing than gauze alone. In 2016, a study by Lee and colleagues suggested that the makeup of the foam product, defined as smaller pore and uniform cell size (foam density), resulted in greater permeability and better moisture absorption and retention capacity, contributing to improved wound healing.³³

In 2004, Sibbald and colleagues reported that in a 4-week study of nonhealing chronic wounds, foam wound dressing impregnated with sustained-release silver compared with foam dressing without silver resulted in a reduction in wound size (50% vs 30%, respectively), decreased fluid leakage (27% vs 44% respectively), and reduction in ulcer size measured from baseline (45% vs 25%, respectively).³⁴

In a 2006 study, Varma and colleagues compared sterilized, saline-soaked, nonmedicated polyurethane industrial upholstery foam in nonhealing wounds used in patients with diabetes with conventional techniques using topical antibiotics, hydrocolloid or hydrogel dressings as necessary, and desloughing agents as controls. At the end of a 3-month follow-up period, 100% of the wounds of the foam group had healed compared with 29.2% of the control group. Additionally, the time to wound healing was less than half for the foam group (22.5 days) compared with the control group (52 days), and the time to granulation and epithelialization was faster in the foam group.³⁵

In a 2012 meta-analysis, Aziz and colleagues reported that silver-impregnated dressings and topical silver were no better or worse than controls in preventing wound infection and promoting the healing of burn wounds.³⁶ The authors also noted that the nonsilver dressing groups continuing povidone-iodine, ionic hydrogel, or silicone-coated dressing showed reduced healing time compared with the silver-containing group.³⁶ This is intriguing because silver has long been used as a standard for the treatment of burn wounds.

Wound vacuum dressings. These dressings are very effective on highly exudative wounds involving a large surface area. However, wound vacuum dressing changes are time intensive and often painful to change. This is a foam dressing placed in the wound and attached to a vacuum device. The wound and foam are then covered with an impermeable membrane and attached to a negative pressure device that exerts a small negative pressure within the wound bed. This negative pressure increases the flow of blood to the less oxygenated areas in the center of the wound, promoting an increased concentration gradient of blood and nutrients and enhancing the evacuation of exudative material from the wound. Thus, a wound vacuum assists in forming an excellent moist wound-healing environment. Reporting in a review article in 2019, Agarwal and colleagues suggested that intermittent negative pressure was superior to constant negative pressure in wound healing due to the increased blood flow in the off phase, and 125 mm Hg negative pressure was optimal for wound healing.³⁷ This type of wound care has been touted as superior in wound care circles, and it may be; however, its cost, time commitment, and painful dressing changes along with cumbersome equipment make the choice difficult for some patients.

Conclusions

Although there is no perfect wound dressing, some wound care products seem to perform better due to fewer adverse effects and a much lesser cost. Important aspects of wound care appear to be time from injury to wound care, cleanliness of the wound, moist wound environment, cost, ease of use, and pain of dressing changes.

Primitive wound care products perform admirably in many situations. Modern medicated foam dressings containing antibacterial properties may have beneficial properties compared with other wound care products; however, comparison studies are lacking and need broad-based, randomized, controlled trials to confirm utility. Finally, any choice of wound care product must be tailored to the particular wound and individual patient needs. More large, robust, randomized controlled trials are needed.

Acknowledgments

The authors thank Sarah Maria Paulsen and Rosemary Ellen Brown Smith for their editing, proofreading, and preparation of the manuscript.

The costs for wound care play a significant role in total health care costs and are expected to rise dramatically. A 2018 Medicare analysis estimated chronic wound care cost $28.1 to $96.8 billion in supplies, hospitalization, and nursing care: Most costs were accrued in outpatient wound care.¹ The global market for advanced wound care supplies is projected to reach $13.7 billion by 2027, and negative wound pressure therapy alone is projected to grow at a compound annual growth rate of 5% over the analysis period 2020 to 2027.² Chronic wound care also impacts the patient physiologically, socially, and psychologically. One study compared the 5-year mortality of a patient with a diabetic foot ulcer (30.5%) as similar to those patients with cancer (31%).³ Yet the investment in cancer research far outstrips wound care research.

There is no perfect wound dressing for all chronic wounds, but there is expert consensus on interventions that facilitate wound healing. In 2021, Nuutila and Eriksson stated that wound dressings should fulfill the following criteria: protection against trauma, esthetically acceptable, painless to remove, easy to apply, protection for the wound from contamination and further trauma, a moist environment, and an optimal water vapor transmission rate.⁴ Balanced moisture control is considered essential for healing chronic wounds. Indeed, moisture control within the wound bed may be the most important factor in chronic wound management and healing. The body communicates through a liquid medium, and if that medium is compromised, communication and marshaling of the immune and healing responses may become inefficient.⁴ Too much moisture, exudate, or fluid in the wound, and the healing is slowed; too little moisture in the wound results in a compromised responses from the body’s immune system, thus delaying healing. In 1988, Dyson and colleagues demonstrated that moist wound care was superior for the inflammatory and proliferative phases of dermal repair compared with dry wound care. The results showed that 5 days after injury, 66% of the cells in the moist wound were fibroblasts and endothelial cells vs 48% of those in the dry wounds.⁵

The question of dry vs moist wound care has resulted in various wound dressings that produce favorable moisture balance. Moisture balance in a wound creates the ideal environment for wound healing. Sound wound care practices promote the following physiologic responses: increased probability of autolytic debridement; increased collagen synthesis; keratinocyte migration and reepithelization; decreased pain, inflammation, scarring, and necrosis;enhancement of cell-to-cell signaling; and increase in growth factors.^5,6 All these processes are mediated through proper wound moisture control. In addition to proper moisture control, antibiotics added to the wound care milieu (either directly to the wound or systemically) may have a place in chronic wound care. In 2013, Junker and colleagues reported that low-dose antibiotics combined with appropriate moisture balance in wounds demonstrated less scar tissue compared with dry wound care.⁶

Approaches to chronic wound care are worlds apart: In developing nations the care of chronic wounds often involves traditional management with local products (eg, honey, boiled potato peels, aloe vera gel, banana leaves), whereas in developed nations, more expensive and technologically advanced products are available (eg, wound vacuum, saline wound chamber, hyperbaric oxygen therapy, antibacterial foam). Developing countries often do not have access to technologically advanced wound care products. Local products are often used by local healers, priests, and shamans. The use of these wound interventions in developing countries has produced satisfactory results. In contrast, developed countries have multiple chronic wound care products available (Table).

CASE Presentation

An athletic, healthy 60-year-old Utah National Guard member presented to the George E. Wahlen Department of Veterans Affairs Medical Center in Salt Lake City, Utah, 6 days after experiencing a spider bite. For the first 6 days, the patient applied bacitracin at home. On day 7, the patient noticed that the wound was enlarging and appeared to be fluctuant. The patient was prescribed clindamycin 300 mg 4 times daily on an outpatient basis, which was taken on days 7 to 14.

The wound’s total surface area continued to expand, and the patient returned to the Salt Lake City Veterans Hospital wound care clinic on day 17 stating that the wound was very painful and more fluctuant. The wound care nursing staff were consulted, the wound was debrided, and attempts to drain the wound resulted in minimal exudate expressed from the wound. Clindamycin was increased to 450 mg 4 times daily. However, the wound continued to enlarge and become more painful.

On day 20, the patient reported to nursing services and was admitted to the Salt Lake City Veterans Hospital general surgery department with mental status changes and symptoms of septicemia (Figure 1).

Discussion

Traditional Wound Care

Honey. Honey has been used as a treatment for wounds for almost 3000 years. It has antiseptic and antibacterial properties and contributes to a moist wound care environment. In 2011, Gupta and colleagues reported on the use of honey in 108 patients with burns of < 50% of the total body surface area.⁷ This report stated that delay in seeking medical care increased wound infection rates, contamination, time to sterilization, and healing. Compared with silver sulfadiazine cream, honey dressings improved the time to wound healing (33 days vs 18 days, respectively), decreased the time to wound sterilization (1 day vs no sterilization), and had better outcomes (37% vs 81%, respectively) with fewer hypertrophic scars and postburn contractures.⁷

Separate studies in 2011 and 2010 from Fukuda and colleagues and Majtan and colleagues, respectively, reported that honey eliminates pathogens from wounds, augments correct moisture balance, and elevates cytokine activity.^8,9 Additional studies in 2006, 2008, and 2014 by Henriques and colleagues, Van den Berg and colleagues, and Majtan suggested that honey reduces reactive oxygen species, is responsible for direct antimicrobial effects in a healing wound, inhibits free radical production, and promotes antitumor activity, respectively.^10-12 Van den Berg and colleagues suggested that buckwheat honey is the most effective honey in reducing reactive oxygen species.¹¹

Sterile banana leaves. In medically underserved and rural areas, boiled banana leaves are used to treat burns and nonhealing wounds. In a 2015 study, Waffa and Hayah compared gauze dressings with sterile banana leaves wound dressing in patients with partial thickness burns. Topical antibiotics were added to each type of dressing. The results suggested that the banana leaf dressings were easier to remove, patients reported less pain overall, less pain with dressing changes, and demonstrated a decreased time to healing when contrasted with gauze.¹³ In 2003, Gore and Akolekar compared autoclaved banana leaves with boiled potato peels in the treatment of patients with partial thickness burns. The time to epithelialization, eschar formation, and skin graft healing were equal in both groups. However, banana leaves were 11 times cheaper and rated easier to prepare than boiled potato peels.¹⁴ In a study comparing petroleum gauze with sterile banana leaves, Chendake and colleagues reported that in measures of overall pain and trauma during dressing changes, patients with contused and sutured wounds on the face and neck achieved better outcomes with boiled banana leaves compared with petroleum gauze.¹⁵

Boiled potato peels. This treatment is used in rural areas of the world as an adjunct for wound care. In 2015, Manjunath and colleagues theorized that the use of boiled potato peels in patients with necrotizing fasciitis decreased the acidic environment created by the bacteria. Additionally, the study asserted that the toxic wound environment created by the bacteria was neutralized by the potassium content in the peel, and the flavonoids in the peel acted as a free radical scavenger.¹⁶ In 2011, Panda and colleagues, using povidone-iodine as a baseline control, reported that peel extract and a peel bandage of sweet potato showed an increased wound closure percentage measured by enhanced epithelialization.¹⁷ This increased epithelialization was attributed to the antioxidant effect of the peels enhancing collagen synthesis.¹⁷

In contrast, in 1996, a study by Subrahmanyam compared autoclaved potato peel bandages with honey dressings as adjuncts in burn patients with < 40% of the total body surface area affected. The author reported that 90% of the wounds treated with honey were sterile in 7 days, while infection persisted in the potato peel group after 7 days. In the same study, 100% of the wounds treated with honey were healed in 15 days vs 50% in the potato peel group.¹⁸ In 1990, Keswani and colleagues compared boiled potato peels with plain gauze as adjuncts in the treatment of burn patients and concluded that although the potato peels had no antibacterial effect, the wounds in both groups had identical bacterial species. But the wounds treated with the potato peels showed reduced desiccation, permitting the survival of skin cells, and enhanced epithelial regeneration.¹⁹

Aloe vera. First recorded by the Egyptians and Greeks, aloe vera gel has been used for centuries in many cultures for a variety of ailments, particularly burns and chronic wounds. In a 2016 wound healing study performed on rats, Oryan and colleagues demonstrated that aloe vera gel was superior to saline used as the baseline control. Aloe vera gel used in a dose-dependent fashion demonstrated increased tissue levels of collagen and glycosaminoglycans compared with controls. Aloe vera gel modulated wound inflammation, increased wound contraction, wound epithelialization, decreased scar tissue size, and increased alignment and organization of the scar tissue.²⁰

Gauze. Iodoform gauze is a highly absorbent wound product. Sterile gauze promotes granulation and wound healing. It is well suited for wounds with minimal drainage. However, although gauze is inexpensive, it is easily overwhelmed by the moisture content in the wound, requiring frequent dressing changes (up to 3 times a day), ideally by nursing staff. The resulting increase in nursing care may actually increase the cost of wound care compared with other care modalities.

Petroleum gauze is often used in the care of acute and chronic wounds. However, petroleum-impregnated gauze has a water vapor transmission rate that needs to be remoistened every 4 hours. If the affected area is not remoistened during the exudative phase of wound healing, it may precipitate a delay in healing and increase pain and the prevalence of clinical infections compared with hydrocolloid, film, or foam dressings. Bolton suggested stopping the use of petroleum gauze as the control in studies because it does not provide a balanced and moist wound healing environment.²¹

Advanced Wound Treatments

Film products. Film products, including plastic food wrap, can be used as wound dressings and meet many of the necessary criteria for enhancing wound healing. These include moisture permeability, carbon dioxide, oxygen transfer, and wound protection. Transmission of moisture varies among products known as the moisture vapor transpiration rate. Film dressings have no absorptive qualities and are unsuited for highly exudative wounds.^22,23 Adding polymers, antibacterial, and bioactive agents may increase the wound care properties of film dressings.²² Film dressings excel in protecting shallow nonexudative wounds, are waterproof, and help protect the wound. These products are transparent, allowing clinicians to monitor the progress of the wound without removing the covering, and allowing the dressing to remain in place longer, which decreases the repeated trauma that can occur with dressing changes. Film dressings for wounds differ from those used for IV dressings and should not be used interchangeably.²³

Bioactive wound care. These solutions contribute to a moist wound-healing environment. Found naturally in brown seaweed, alginate-containing compounds were used by sailors for centuries to heal wounds. This was known in traditional medicine as the mariner’s cure. Alginate dressings are highly absorbent and can absorb up to 20 times their weight, which makes them desirable for use in highly exudative wounds. First synthesized more than 50 years ago, newer products contain bioactive compounds that prevent tissue damage, stimulate wound healing, improve cell proliferation and migration, and enhance metabolite formation.^24-26

In 2018, Aderibigbe and Buyana reported that polymers in the form of hydrogels were able to absorb fluid, making them a suitable choice for minimally exudative wounds. However, in their distended state, the hydrogel subgroup of these products became unstable (perhaps making them a poor choice for extensively exudative wounds), tended to dehydrate, and often needed a secondary dressing, which could lead to wound maceration.²² Most commonly used for wounds with minimal exudate, these dressings shine when used in nominally exudative dry wounds to promote autolytic debridement and hydrate the wound that has formed an eschar.

Hydrocolloid dressings are another type of bioactive wound dressing. These dressings are composed of 2 layers: an inner hydrophilic layer and an outer vapor-permeable layer that promote a moist wound environment. Hydrocolloid dressings assist in hydrating dry eschar wounds and have slight absorbency for exudative wounds. These dressings are not designed to be changed daily and can remain in place for 3 to 6 days. In a 2008 extensive review article, Thomas compared the utility of these dressings in patients with superficial or partial thickness burns, donor sites, surgical wounds, and minor traumatic wounds with basic wound dressings. The results of the review suggested that hydrocolloid dressings conferred statistically significant advantages in measures of decreased pain, healing times (decreased in donor sites by 40%), mobility restriction, and number of dressing changes.²⁷ Although more expensive than basic dressings, the longevity of the hydrocolloid dressing helps defray the original cost. Unfortunately, as these dressings remain in place and continue absorbing exudate, they can take on a very unpleasant odor.

A 2013 Cochrane database review comparing hydrocolloids with foams, alginate, basic wound dressing, and topical treatment found no statistical difference between hydrocolloids and basic wound dressings in patients with diabetes who have noncomplex foot ulcers.²⁸ In 2014, Pott and colleagues suggested a slight superiority in the performance of polyurethane foam dressings over hydrocolloid dressings used in pressure ulcers in older adults.²⁹ In a large pooled analysis in 2010, Davies compared foam to hydrocolloid dressings used in exudative wounds and reported that in 11 of 12 studies, foam dressings were superior to hydrocolloid in terms of exudate management, conformity to the wound, ease of use, decreased trauma and pain at dressing changes, and reduced odor of the wound.³⁰

Foam dressings. These products are typically composed of silicone or polyurethane. Consisting of 2 to 3 layers with a hydrophilic surface, foams are cut to approximate the wound size and serve to wick the macerated wound products to a secondary dressing above the foam. The micropores in the foam matrix absorb exudate from the wound bed while maintaining moisture equilibrium in the wound by donating back moisture to the wound, creating an environment conducive to wound healing. Foam dressings can be combined with various antiseptics (silver, GV/MB, etc) and serve as a delivery vehicle of those products directly to the wound surface.

A 2011 review comparing 8 studies found no difference among foam products available at that time in the use for chronic wounds.³¹ However, newer products on the market today have produced intriguing results with chronic wounds.

In 2017, Woo and Heil observed that chronic wounds treated with foam products containing GV/MB produced significant improvement when measured at week 4 in the areas of mean wound surface area (42.5%), decrease in baseline Pressure Ulcer Scale for Healing scores (from 13.3 to 10.7), wound coverage by devitalized tissue reduced (from 52.6% to 11.4%), and mean upper and lower wound infection scores were reduced by 75%.³² Further, the researchers reported a moist wound bed was achieved at dressing changes with polyvinyl alcohol (PVA) foam dressing. This led to the presumption that adequate moisture balance and autolytic debridement were facilitated using GV/MB antibacterial PVA foam dressings.

Many foam products on the market today exert an antibacterial effect on the wound bed. Antibiotic properties of various foam dressings create a microenvironment hostile to bacterial growth.³² In addition, the antibacterial properties combined with foam products contribute to the following: autolytic debridement, absorptive qualities (which reduce the bioburden of the wound), and maintenance of moisture in the wound bed. These qualities contribute significantly to the effectiveness of foam products with antibacterial properties.³² The correct balance of moisture in the wound has been identified as a superior environment and perhaps the most important component in chronic wounds.⁴ Foam dressings are less painful to change, easier to change, and in this case report, contributed to faster wound healing than gauze alone. In 2016, a study by Lee and colleagues suggested that the makeup of the foam product, defined as smaller pore and uniform cell size (foam density), resulted in greater permeability and better moisture absorption and retention capacity, contributing to improved wound healing.³³

In 2004, Sibbald and colleagues reported that in a 4-week study of nonhealing chronic wounds, foam wound dressing impregnated with sustained-release silver compared with foam dressing without silver resulted in a reduction in wound size (50% vs 30%, respectively), decreased fluid leakage (27% vs 44% respectively), and reduction in ulcer size measured from baseline (45% vs 25%, respectively).³⁴

In a 2006 study, Varma and colleagues compared sterilized, saline-soaked, nonmedicated polyurethane industrial upholstery foam in nonhealing wounds used in patients with diabetes with conventional techniques using topical antibiotics, hydrocolloid or hydrogel dressings as necessary, and desloughing agents as controls. At the end of a 3-month follow-up period, 100% of the wounds of the foam group had healed compared with 29.2% of the control group. Additionally, the time to wound healing was less than half for the foam group (22.5 days) compared with the control group (52 days), and the time to granulation and epithelialization was faster in the foam group.³⁵

In a 2012 meta-analysis, Aziz and colleagues reported that silver-impregnated dressings and topical silver were no better or worse than controls in preventing wound infection and promoting the healing of burn wounds.³⁶ The authors also noted that the nonsilver dressing groups continuing povidone-iodine, ionic hydrogel, or silicone-coated dressing showed reduced healing time compared with the silver-containing group.³⁶ This is intriguing because silver has long been used as a standard for the treatment of burn wounds.

Wound vacuum dressings. These dressings are very effective on highly exudative wounds involving a large surface area. However, wound vacuum dressing changes are time intensive and often painful to change. This is a foam dressing placed in the wound and attached to a vacuum device. The wound and foam are then covered with an impermeable membrane and attached to a negative pressure device that exerts a small negative pressure within the wound bed. This negative pressure increases the flow of blood to the less oxygenated areas in the center of the wound, promoting an increased concentration gradient of blood and nutrients and enhancing the evacuation of exudative material from the wound. Thus, a wound vacuum assists in forming an excellent moist wound-healing environment. Reporting in a review article in 2019, Agarwal and colleagues suggested that intermittent negative pressure was superior to constant negative pressure in wound healing due to the increased blood flow in the off phase, and 125 mm Hg negative pressure was optimal for wound healing.³⁷ This type of wound care has been touted as superior in wound care circles, and it may be; however, its cost, time commitment, and painful dressing changes along with cumbersome equipment make the choice difficult for some patients.

Conclusions

Although there is no perfect wound dressing, some wound care products seem to perform better due to fewer adverse effects and a much lesser cost. Important aspects of wound care appear to be time from injury to wound care, cleanliness of the wound, moist wound environment, cost, ease of use, and pain of dressing changes.

Primitive wound care products perform admirably in many situations. Modern medicated foam dressings containing antibacterial properties may have beneficial properties compared with other wound care products; however, comparison studies are lacking and need broad-based, randomized, controlled trials to confirm utility. Finally, any choice of wound care product must be tailored to the particular wound and individual patient needs. More large, robust, randomized controlled trials are needed.

Acknowledgments

The authors thank Sarah Maria Paulsen and Rosemary Ellen Brown Smith for their editing, proofreading, and preparation of the manuscript.

The costs for wound care play a significant role in total health care costs and are expected to rise dramatically. A 2018 Medicare analysis estimated chronic wound care cost $28.1 to $96.8 billion in supplies, hospitalization, and nursing care: Most costs were accrued in outpatient wound care.¹ The global market for advanced wound care supplies is projected to reach $13.7 billion by 2027, and negative wound pressure therapy alone is projected to grow at a compound annual growth rate of 5% over the analysis period 2020 to 2027.² Chronic wound care also impacts the patient physiologically, socially, and psychologically. One study compared the 5-year mortality of a patient with a diabetic foot ulcer (30.5%) as similar to those patients with cancer (31%).³ Yet the investment in cancer research far outstrips wound care research.

There is no perfect wound dressing for all chronic wounds, but there is expert consensus on interventions that facilitate wound healing. In 2021, Nuutila and Eriksson stated that wound dressings should fulfill the following criteria: protection against trauma, esthetically acceptable, painless to remove, easy to apply, protection for the wound from contamination and further trauma, a moist environment, and an optimal water vapor transmission rate.⁴ Balanced moisture control is considered essential for healing chronic wounds. Indeed, moisture control within the wound bed may be the most important factor in chronic wound management and healing. The body communicates through a liquid medium, and if that medium is compromised, communication and marshaling of the immune and healing responses may become inefficient.⁴ Too much moisture, exudate, or fluid in the wound, and the healing is slowed; too little moisture in the wound results in a compromised responses from the body’s immune system, thus delaying healing. In 1988, Dyson and colleagues demonstrated that moist wound care was superior for the inflammatory and proliferative phases of dermal repair compared with dry wound care. The results showed that 5 days after injury, 66% of the cells in the moist wound were fibroblasts and endothelial cells vs 48% of those in the dry wounds.⁵

The question of dry vs moist wound care has resulted in various wound dressings that produce favorable moisture balance. Moisture balance in a wound creates the ideal environment for wound healing. Sound wound care practices promote the following physiologic responses: increased probability of autolytic debridement; increased collagen synthesis; keratinocyte migration and reepithelization; decreased pain, inflammation, scarring, and necrosis;enhancement of cell-to-cell signaling; and increase in growth factors.^5,6 All these processes are mediated through proper wound moisture control. In addition to proper moisture control, antibiotics added to the wound care milieu (either directly to the wound or systemically) may have a place in chronic wound care. In 2013, Junker and colleagues reported that low-dose antibiotics combined with appropriate moisture balance in wounds demonstrated less scar tissue compared with dry wound care.⁶

Approaches to chronic wound care are worlds apart: In developing nations the care of chronic wounds often involves traditional management with local products (eg, honey, boiled potato peels, aloe vera gel, banana leaves), whereas in developed nations, more expensive and technologically advanced products are available (eg, wound vacuum, saline wound chamber, hyperbaric oxygen therapy, antibacterial foam). Developing countries often do not have access to technologically advanced wound care products. Local products are often used by local healers, priests, and shamans. The use of these wound interventions in developing countries has produced satisfactory results. In contrast, developed countries have multiple chronic wound care products available (Table).

CASE Presentation

An athletic, healthy 60-year-old Utah National Guard member presented to the George E. Wahlen Department of Veterans Affairs Medical Center in Salt Lake City, Utah, 6 days after experiencing a spider bite. For the first 6 days, the patient applied bacitracin at home. On day 7, the patient noticed that the wound was enlarging and appeared to be fluctuant. The patient was prescribed clindamycin 300 mg 4 times daily on an outpatient basis, which was taken on days 7 to 14.

The wound’s total surface area continued to expand, and the patient returned to the Salt Lake City Veterans Hospital wound care clinic on day 17 stating that the wound was very painful and more fluctuant. The wound care nursing staff were consulted, the wound was debrided, and attempts to drain the wound resulted in minimal exudate expressed from the wound. Clindamycin was increased to 450 mg 4 times daily. However, the wound continued to enlarge and become more painful.

On day 20, the patient reported to nursing services and was admitted to the Salt Lake City Veterans Hospital general surgery department with mental status changes and symptoms of septicemia (Figure 1).

Discussion

Traditional Wound Care

Honey. Honey has been used as a treatment for wounds for almost 3000 years. It has antiseptic and antibacterial properties and contributes to a moist wound care environment. In 2011, Gupta and colleagues reported on the use of honey in 108 patients with burns of < 50% of the total body surface area.⁷ This report stated that delay in seeking medical care increased wound infection rates, contamination, time to sterilization, and healing. Compared with silver sulfadiazine cream, honey dressings improved the time to wound healing (33 days vs 18 days, respectively), decreased the time to wound sterilization (1 day vs no sterilization), and had better outcomes (37% vs 81%, respectively) with fewer hypertrophic scars and postburn contractures.⁷

Separate studies in 2011 and 2010 from Fukuda and colleagues and Majtan and colleagues, respectively, reported that honey eliminates pathogens from wounds, augments correct moisture balance, and elevates cytokine activity.^8,9 Additional studies in 2006, 2008, and 2014 by Henriques and colleagues, Van den Berg and colleagues, and Majtan suggested that honey reduces reactive oxygen species, is responsible for direct antimicrobial effects in a healing wound, inhibits free radical production, and promotes antitumor activity, respectively.^10-12 Van den Berg and colleagues suggested that buckwheat honey is the most effective honey in reducing reactive oxygen species.¹¹

Sterile banana leaves. In medically underserved and rural areas, boiled banana leaves are used to treat burns and nonhealing wounds. In a 2015 study, Waffa and Hayah compared gauze dressings with sterile banana leaves wound dressing in patients with partial thickness burns. Topical antibiotics were added to each type of dressing. The results suggested that the banana leaf dressings were easier to remove, patients reported less pain overall, less pain with dressing changes, and demonstrated a decreased time to healing when contrasted with gauze.¹³ In 2003, Gore and Akolekar compared autoclaved banana leaves with boiled potato peels in the treatment of patients with partial thickness burns. The time to epithelialization, eschar formation, and skin graft healing were equal in both groups. However, banana leaves were 11 times cheaper and rated easier to prepare than boiled potato peels.¹⁴ In a study comparing petroleum gauze with sterile banana leaves, Chendake and colleagues reported that in measures of overall pain and trauma during dressing changes, patients with contused and sutured wounds on the face and neck achieved better outcomes with boiled banana leaves compared with petroleum gauze.¹⁵

Boiled potato peels. This treatment is used in rural areas of the world as an adjunct for wound care. In 2015, Manjunath and colleagues theorized that the use of boiled potato peels in patients with necrotizing fasciitis decreased the acidic environment created by the bacteria. Additionally, the study asserted that the toxic wound environment created by the bacteria was neutralized by the potassium content in the peel, and the flavonoids in the peel acted as a free radical scavenger.¹⁶ In 2011, Panda and colleagues, using povidone-iodine as a baseline control, reported that peel extract and a peel bandage of sweet potato showed an increased wound closure percentage measured by enhanced epithelialization.¹⁷ This increased epithelialization was attributed to the antioxidant effect of the peels enhancing collagen synthesis.¹⁷

In contrast, in 1996, a study by Subrahmanyam compared autoclaved potato peel bandages with honey dressings as adjuncts in burn patients with < 40% of the total body surface area affected. The author reported that 90% of the wounds treated with honey were sterile in 7 days, while infection persisted in the potato peel group after 7 days. In the same study, 100% of the wounds treated with honey were healed in 15 days vs 50% in the potato peel group.¹⁸ In 1990, Keswani and colleagues compared boiled potato peels with plain gauze as adjuncts in the treatment of burn patients and concluded that although the potato peels had no antibacterial effect, the wounds in both groups had identical bacterial species. But the wounds treated with the potato peels showed reduced desiccation, permitting the survival of skin cells, and enhanced epithelial regeneration.¹⁹

Aloe vera. First recorded by the Egyptians and Greeks, aloe vera gel has been used for centuries in many cultures for a variety of ailments, particularly burns and chronic wounds. In a 2016 wound healing study performed on rats, Oryan and colleagues demonstrated that aloe vera gel was superior to saline used as the baseline control. Aloe vera gel used in a dose-dependent fashion demonstrated increased tissue levels of collagen and glycosaminoglycans compared with controls. Aloe vera gel modulated wound inflammation, increased wound contraction, wound epithelialization, decreased scar tissue size, and increased alignment and organization of the scar tissue.²⁰

Gauze. Iodoform gauze is a highly absorbent wound product. Sterile gauze promotes granulation and wound healing. It is well suited for wounds with minimal drainage. However, although gauze is inexpensive, it is easily overwhelmed by the moisture content in the wound, requiring frequent dressing changes (up to 3 times a day), ideally by nursing staff. The resulting increase in nursing care may actually increase the cost of wound care compared with other care modalities.

Petroleum gauze is often used in the care of acute and chronic wounds. However, petroleum-impregnated gauze has a water vapor transmission rate that needs to be remoistened every 4 hours. If the affected area is not remoistened during the exudative phase of wound healing, it may precipitate a delay in healing and increase pain and the prevalence of clinical infections compared with hydrocolloid, film, or foam dressings. Bolton suggested stopping the use of petroleum gauze as the control in studies because it does not provide a balanced and moist wound healing environment.²¹

Advanced Wound Treatments

Film products. Film products, including plastic food wrap, can be used as wound dressings and meet many of the necessary criteria for enhancing wound healing. These include moisture permeability, carbon dioxide, oxygen transfer, and wound protection. Transmission of moisture varies among products known as the moisture vapor transpiration rate. Film dressings have no absorptive qualities and are unsuited for highly exudative wounds.^22,23 Adding polymers, antibacterial, and bioactive agents may increase the wound care properties of film dressings.²² Film dressings excel in protecting shallow nonexudative wounds, are waterproof, and help protect the wound. These products are transparent, allowing clinicians to monitor the progress of the wound without removing the covering, and allowing the dressing to remain in place longer, which decreases the repeated trauma that can occur with dressing changes. Film dressings for wounds differ from those used for IV dressings and should not be used interchangeably.²³

Bioactive wound care. These solutions contribute to a moist wound-healing environment. Found naturally in brown seaweed, alginate-containing compounds were used by sailors for centuries to heal wounds. This was known in traditional medicine as the mariner’s cure. Alginate dressings are highly absorbent and can absorb up to 20 times their weight, which makes them desirable for use in highly exudative wounds. First synthesized more than 50 years ago, newer products contain bioactive compounds that prevent tissue damage, stimulate wound healing, improve cell proliferation and migration, and enhance metabolite formation.^24-26

In 2018, Aderibigbe and Buyana reported that polymers in the form of hydrogels were able to absorb fluid, making them a suitable choice for minimally exudative wounds. However, in their distended state, the hydrogel subgroup of these products became unstable (perhaps making them a poor choice for extensively exudative wounds), tended to dehydrate, and often needed a secondary dressing, which could lead to wound maceration.²² Most commonly used for wounds with minimal exudate, these dressings shine when used in nominally exudative dry wounds to promote autolytic debridement and hydrate the wound that has formed an eschar.

Hydrocolloid dressings are another type of bioactive wound dressing. These dressings are composed of 2 layers: an inner hydrophilic layer and an outer vapor-permeable layer that promote a moist wound environment. Hydrocolloid dressings assist in hydrating dry eschar wounds and have slight absorbency for exudative wounds. These dressings are not designed to be changed daily and can remain in place for 3 to 6 days. In a 2008 extensive review article, Thomas compared the utility of these dressings in patients with superficial or partial thickness burns, donor sites, surgical wounds, and minor traumatic wounds with basic wound dressings. The results of the review suggested that hydrocolloid dressings conferred statistically significant advantages in measures of decreased pain, healing times (decreased in donor sites by 40%), mobility restriction, and number of dressing changes.²⁷ Although more expensive than basic dressings, the longevity of the hydrocolloid dressing helps defray the original cost. Unfortunately, as these dressings remain in place and continue absorbing exudate, they can take on a very unpleasant odor.

A 2013 Cochrane database review comparing hydrocolloids with foams, alginate, basic wound dressing, and topical treatment found no statistical difference between hydrocolloids and basic wound dressings in patients with diabetes who have noncomplex foot ulcers.²⁸ In 2014, Pott and colleagues suggested a slight superiority in the performance of polyurethane foam dressings over hydrocolloid dressings used in pressure ulcers in older adults.²⁹ In a large pooled analysis in 2010, Davies compared foam to hydrocolloid dressings used in exudative wounds and reported that in 11 of 12 studies, foam dressings were superior to hydrocolloid in terms of exudate management, conformity to the wound, ease of use, decreased trauma and pain at dressing changes, and reduced odor of the wound.³⁰

Foam dressings. These products are typically composed of silicone or polyurethane. Consisting of 2 to 3 layers with a hydrophilic surface, foams are cut to approximate the wound size and serve to wick the macerated wound products to a secondary dressing above the foam. The micropores in the foam matrix absorb exudate from the wound bed while maintaining moisture equilibrium in the wound by donating back moisture to the wound, creating an environment conducive to wound healing. Foam dressings can be combined with various antiseptics (silver, GV/MB, etc) and serve as a delivery vehicle of those products directly to the wound surface.

A 2011 review comparing 8 studies found no difference among foam products available at that time in the use for chronic wounds.³¹ However, newer products on the market today have produced intriguing results with chronic wounds.

In 2017, Woo and Heil observed that chronic wounds treated with foam products containing GV/MB produced significant improvement when measured at week 4 in the areas of mean wound surface area (42.5%), decrease in baseline Pressure Ulcer Scale for Healing scores (from 13.3 to 10.7), wound coverage by devitalized tissue reduced (from 52.6% to 11.4%), and mean upper and lower wound infection scores were reduced by 75%.³² Further, the researchers reported a moist wound bed was achieved at dressing changes with polyvinyl alcohol (PVA) foam dressing. This led to the presumption that adequate moisture balance and autolytic debridement were facilitated using GV/MB antibacterial PVA foam dressings.

Many foam products on the market today exert an antibacterial effect on the wound bed. Antibiotic properties of various foam dressings create a microenvironment hostile to bacterial growth.³² In addition, the antibacterial properties combined with foam products contribute to the following: autolytic debridement, absorptive qualities (which reduce the bioburden of the wound), and maintenance of moisture in the wound bed. These qualities contribute significantly to the effectiveness of foam products with antibacterial properties.³² The correct balance of moisture in the wound has been identified as a superior environment and perhaps the most important component in chronic wounds.⁴ Foam dressings are less painful to change, easier to change, and in this case report, contributed to faster wound healing than gauze alone. In 2016, a study by Lee and colleagues suggested that the makeup of the foam product, defined as smaller pore and uniform cell size (foam density), resulted in greater permeability and better moisture absorption and retention capacity, contributing to improved wound healing.³³

In 2004, Sibbald and colleagues reported that in a 4-week study of nonhealing chronic wounds, foam wound dressing impregnated with sustained-release silver compared with foam dressing without silver resulted in a reduction in wound size (50% vs 30%, respectively), decreased fluid leakage (27% vs 44% respectively), and reduction in ulcer size measured from baseline (45% vs 25%, respectively).³⁴

In a 2006 study, Varma and colleagues compared sterilized, saline-soaked, nonmedicated polyurethane industrial upholstery foam in nonhealing wounds used in patients with diabetes with conventional techniques using topical antibiotics, hydrocolloid or hydrogel dressings as necessary, and desloughing agents as controls. At the end of a 3-month follow-up period, 100% of the wounds of the foam group had healed compared with 29.2% of the control group. Additionally, the time to wound healing was less than half for the foam group (22.5 days) compared with the control group (52 days), and the time to granulation and epithelialization was faster in the foam group.³⁵

In a 2012 meta-analysis, Aziz and colleagues reported that silver-impregnated dressings and topical silver were no better or worse than controls in preventing wound infection and promoting the healing of burn wounds.³⁶ The authors also noted that the nonsilver dressing groups continuing povidone-iodine, ionic hydrogel, or silicone-coated dressing showed reduced healing time compared with the silver-containing group.³⁶ This is intriguing because silver has long been used as a standard for the treatment of burn wounds.

Wound vacuum dressings. These dressings are very effective on highly exudative wounds involving a large surface area. However, wound vacuum dressing changes are time intensive and often painful to change. This is a foam dressing placed in the wound and attached to a vacuum device. The wound and foam are then covered with an impermeable membrane and attached to a negative pressure device that exerts a small negative pressure within the wound bed. This negative pressure increases the flow of blood to the less oxygenated areas in the center of the wound, promoting an increased concentration gradient of blood and nutrients and enhancing the evacuation of exudative material from the wound. Thus, a wound vacuum assists in forming an excellent moist wound-healing environment. Reporting in a review article in 2019, Agarwal and colleagues suggested that intermittent negative pressure was superior to constant negative pressure in wound healing due to the increased blood flow in the off phase, and 125 mm Hg negative pressure was optimal for wound healing.³⁷ This type of wound care has been touted as superior in wound care circles, and it may be; however, its cost, time commitment, and painful dressing changes along with cumbersome equipment make the choice difficult for some patients.

Conclusions

Although there is no perfect wound dressing, some wound care products seem to perform better due to fewer adverse effects and a much lesser cost. Important aspects of wound care appear to be time from injury to wound care, cleanliness of the wound, moist wound environment, cost, ease of use, and pain of dressing changes.

Primitive wound care products perform admirably in many situations. Modern medicated foam dressings containing antibacterial properties may have beneficial properties compared with other wound care products; however, comparison studies are lacking and need broad-based, randomized, controlled trials to confirm utility. Finally, any choice of wound care product must be tailored to the particular wound and individual patient needs. More large, robust, randomized controlled trials are needed.

Acknowledgments

The authors thank Sarah Maria Paulsen and Rosemary Ellen Brown Smith for their editing, proofreading, and preparation of the manuscript.

The United States’ initial public health response to the COVID-19 pandemic included containment measures that varied by state but generally required closing or suspending schools, nonessential businesses, and travel (commonly called lockdown).¹ During these periods, hospitalizations for serious and common conditions declined.^2,3 In Massachusetts, a state of emergency was declared on March 10, 2020, which remained in place until May 18, 2020, when a phased reopening of businesses began.

Although the evidence on the mental health impact of containment periods has been mixed, it has been suggested that these measures could lead to increases in alcohol-related hospitalizations.⁴ Social isolation and increased psychosocial and financial stressors raise the risk of relapse among patients with substance use disorders.^5-7 Marketing and survey data from the US and United Kingdom from the early months of the pandemic suggest that in-home alcohol consumption and sales of alcoholic beverages increased, while consumption of alcohol outside the home decreased.^8-10 Other research has shown an increase in the percentage—but not necessarily the absolute number—of emergency department (ED) visits and hospitalizations for alcohol-related diagnoses during periods of containment.^11,12 At least 1 study suggests that alcohol-related deaths increased beginning in the lockdown period and persisting into mid-2021.¹³

Because earlier studies suggest that lockdown periods are associated with increased alcohol consumption and relapse of alcohol use disorder, we hypothesized that the spring 2020 lockdown period in Massachusetts would be associated temporally with an increase in alcohol-related hospitalizations. To evaluate this hypothesis, we examined all hospitalizations in the US Department of Veterans Affairs (VA) Boston Healthcare System (VABHS) before, during, and after this lockdown period. VABHS includes a 160-bed acute care hospital and a 50-bed inpatient psychiatric facility.

Methods

We conducted an interrupted time-series analysis including all inpatient hospitalizations at VABHS from January 1, 2017, to December 31, 2020, to compare the daily number of alcohol-related hospitalizations across 3 exposure groups: prelockdown (the reference group, 1/1/2017-3/9/2020); lockdown (3/10/2020-5/18/2020); and postlockdown (5/19/2020-12/31/2020).

The VA Corporate Data Warehouse at VABHS was queried to identify all hospitalizations on the medical, psychiatry, and neurology services during the study period. Hospitalizations were considered alcohol-related if the International Statistical Classification of Diseases, Tenth Revision (ICD-10) primary diagnosis code (the main reason for hospitalization) was defined as an alcohol-related diagnosis by the VA Centralized Interactive Phenomics Resource (eAppendix 1, available online at doi:10.1278/fp.0404). This database, which has been previously used for COVID-19 research, is a catalog and knowledge-sharing platform of VA electronic health record–based phenotype algorithms, definitions, and metadata that builds on the Million Veteran Program and Cooperative Studies Program.^14,15 Hospitalizations under observation status were excluded.

To examine whether alcohol-related hospitalizations could have been categorized as COVID-19 when the conditions were co-occurring, we identified 244 hospitalizations coded with a primary ICD-10 code for COVID-19 during the lockdown and postlockdown periods. At the time of admission, each hospitalization carries an initial (free text) diagnosis, of which 3 had an initial diagnosis related to alcohol use. The population at risk for alcohol-related hospitalizations was estimated as the number of patients actively engaged in care at the VABHS. This was defined as the number of patients enrolled in VA care who have previously received any VA care; patients who are enrolled but have never received VA care were excluded from the population-at-risk denominator. Population-at-risk data were available for each fiscal year (FY) of the study period (9/30-10/1); the following population-at-risk sizes were used: 38,057 for FY 2017, 38,527 for FY 2018, 39,472 for FY 2019, and 37,893 for FY 2020.

The primary outcome was the daily number of alcohol-related hospitalizations in the prelockdown, lockdown, and postlockdown periods. A sensitivity analysis was performed using an alternate definition of the primary outcome using a broader set of alcohol-related ICD-10 codes (eAppendix 2, available online at doi:10.1278/fp.0404).

Statistical Analysis

To visually examine hospitalization trends during the study period, we generated a smoothed time-series plot of the 7-day moving average of the daily number of all-cause hospitalizations and the daily number of alcohol-related hospitalizations from January 1, 2017, to December 31, 2020. We used multivariable regression to model the daily number of alcohol-related hospitalizations over prelockdown (the reference group), lockdown, and postlockdown. In addition to the exposure, we included the following covariates in our model: day of the week, calendar date (to account for secular trends), and harmonic polynomials of the day of the year (to account for seasonal variation).¹⁶

We also examined models that included the daily total number of hospitalizations to account for the reduced likelihood of hospital admission for any reason during the pandemic. We used generalized linear models with a Poisson link to generate rate ratios and corresponding 95% CIs for estimates of the daily number of alcohol-related hospitalizations. We estimated the population incidence of alcohol-related hospitalizations per 100,000 patient-months for the exposure periods using the population denominators previously described. All analyses were performed in Stata 16.1.

Results

During the study period, 27,508 hospitalizations were available for analysis. The 7-day moving average of total daily hospitalizations and total daily alcohol-related hospitalizations over time for the period January 1, 2017, to December 31, 2020, are shown in the Figure.

The incidence of alcohol-related hospitalizations in the population dropped from 72 per 100,000 patient-months to 10 per 100,000 patient-months during the lockdown period and increased to 46 per 100,000 patient-months during the postlockdown period (Table).

Discussion

During the spring 2020 COVID-19 lockdown period in Massachusetts, the daily number of VABHS alcohol-related hospitalizations decreased by nearly 80% compared with the prelockdown period. During the postlockdown period, the daily number of alcohol-related hospitalizations increased but only to 72% of the prelockdown baseline by the end of December 2020. A similar trend was observed for all-cause hospitalizations for the same exposure periods.

These results differ from 2 related studies on the effect of the COVID-19 pandemic on alcohol-related hospitalizations.^10,11 In a retrospective study of ED visits to 4 hospitals in New York City, Schimmel and colleagues reported that from March 1 to 31, 2020 (the initial COVID-19 peak), hospital visits for alcohol withdrawal increased while those for alcohol use decreased.¹⁰ However, these results are reported as a percentage of total ED visits rather than the total number of visits, which are vulnerable to spurious correlation because of concomitant changes in the total number of ED visits. In their study, the absolute number of alcohol-related ED visits did not increase during the initial 2020 COVID-19 peak, and the number of visits for alcohol withdrawal syndrome declined slightly (195 in 2019 and 180 in 2020). However, the percentage of visits increased from 7% to 10% because of a greater decline in total ED visits. This pattern of decline in the number of alcohol-related ED visits, accompanied by an increase in the percentage of alcohol-related ED visits, has been observed in at least 1 nationwide surveillance study.¹⁷ This apparent increase does not reflect an absolute increase in ED visits for alcohol withdrawal syndrome and represents a greater relative decline in visits for other causes during the study period.

Sharma and colleagues reported an increase in the percentage of patients who developed alcohol withdrawal syndrome while hospitalized in Delaware per 1000 hospitalizations during consecutive 2-week periods during the pandemic in 2020 compared with corresponding weeks in 2019.¹¹ The greatest increase occurred during the last 2 weeks of the Delaware stay-at-home order. The Clinical Institute Withdrawal Assessment of Alcohol Scale, revised (CIWA-Ar) score of > 8 was used to define alcohol withdrawal syndrome. The American Society of Addiction Medicine does not recommend using CIWA-Ar to diagnose alcohol withdrawal syndrome because the scale was developed to monitor response to treatment, not to establish a diagnosis.¹⁸

Although the true population incidence of alcohol-related hospitalizations is difficult to estimate because the size of the population at risk (ie, the denominator) often is not known, the total number of hospitalizations is not a reliable surrogate.¹⁹ Individuals hospitalized for nonalcohol causes are no longer at risk for alcohol-related hospitalization.

In our study, we assume the population at risk during the study period is constant and model changes in the absolute number—rather than percentage—of alcohol-related ED visits. These absolute estimates of alcohol-related hospitalizations better reflect the true burden on the health care system and avoid the confounding effect of declining total ED visits and hospitalizations that could lead to artificially increased percentages and spurious correlation.²⁰ The absolute percentage of alcohol-related hospitalizations also decreased during this period; therefore, our results are not sensitive to this approach.

Several factors could have contributed to the decrease in alcohol-related hospitalizations. Our findings suggest that patient likelihood to seek care and clinician threshold to admit patients for alcohol-related conditions are influenced by external factors, in this case, a public health lockdown. Although our data do not inform why hospitalizations did not return to prelockdown levels, our experience suggests that limited bed capacity and longer length of stay might have contributed. Other hypotheses include a shift to outpatient care, increased use of telehealth (a significant focus early in the pandemic), and avoiding care for less severe alcohol-related complications because of lingering concerns about exposure to COVID-19 in health care settings reported early in the pandemic. Massachusetts experienced a particularly deadly outbreak of COVID-19 in the Soldiers’ Home, a long-term care facility for veterans in Holyoke.²¹

Evidence suggests that in-home consumption of alcohol increased during lockdowns.^8-10 Our results show that during this period hospitalizations for alcohol-related conditions decreased at VABHS, a large urban VA medical system, while alcohol-related deaths increased nationally.¹³ Although this observation is not evidence of causality, these outcomes could be related.

In the 2 decades before the pandemic, alcohol-related deaths increased by about 2% per year.²² From 2019 to 2020, there was a 25% increase that continued through 2021.¹³ Death certificate data often are inaccurate, and it is difficult to determine whether COVID-19 had a substantial contributing role to these deaths, particularly during the initial period when testing was limited or unavailable. Nonetheless, deaths due to alcohol-associated liver disease, overdoses involving alcohol, and alcohol-related traffic fatalities increased by > 10%.^13,23 These trends, along with a decrease in hospitalization for alcohol-related conditions, suggest missed opportunities for intervention with patients experiencing alcohol use disorder.

Limitations

In this study, hospitalizations under observation status were excluded, which could underestimate the total number of hospitalizations related to alcohol. We reasoned that this effect was likely to be small and not substantially different by year. ICD-10 codes were used to identify alcohol-related hospitalizations as any hospitalization with an included ICD-10 code listed as the primary discharge diagnosis code. This also likely underestimated the total number of alcohol-related hospitalizations. An ICD-10 code for COVID-19 was not in widespread use during our study period, which prohibited controlling explicitly for the volume of admissions due to COVID-19. The prelockdown period only contains data from the preceding 3 years, which might not be long enough for secular trends to become apparent. We assumed the population at risk remained constant when in reality, the net movement of patients into and out of VA care during the pandemic likely was more complex but not readily quantifiable. Nonetheless, the large drop in absolute number of alcohol-related hospitalizations is not likely to be sensitive to this change. In the absence of an objective measure of care-seeking behavior, we used the total daily number of hospitalizations as a surrogate for patient propensity to seek care. The total daily number of hospitalizations also reflects changes in physician admitting behavior over time. This allowed explicit modeling of care-seeking behavior as a covariate but does not capture other important determinants such as hospital capacity.

Conclusions

In this interrupted time-series analysis, the daily number of alcohol-related hospitalizations during the initial COVID-19 pandemic–associated lockdown period at VABHS decreased by 80% and remained 28% lower in the postlockdown period compared with the prepandemic baseline. In the context of evidence suggesting that alcohol-related mortality increased during the COVID-19 pandemic, alternate strategies to reach vulnerable individuals are needed. Because of high rates of relapse, hospitalization is an important opportunity to engage patients experiencing alcohol use disorder in treatment through referral to substance use treatment programs and medication-assisted therapy. Considering the reduction in alcohol-related hospitalizations during lockdown, other strategies are needed to ensure comprehensive and longitudinal care for this vulnerable population.

The United States’ initial public health response to the COVID-19 pandemic included containment measures that varied by state but generally required closing or suspending schools, nonessential businesses, and travel (commonly called lockdown).¹ During these periods, hospitalizations for serious and common conditions declined.^2,3 In Massachusetts, a state of emergency was declared on March 10, 2020, which remained in place until May 18, 2020, when a phased reopening of businesses began.

Although the evidence on the mental health impact of containment periods has been mixed, it has been suggested that these measures could lead to increases in alcohol-related hospitalizations.⁴ Social isolation and increased psychosocial and financial stressors raise the risk of relapse among patients with substance use disorders.^5-7 Marketing and survey data from the US and United Kingdom from the early months of the pandemic suggest that in-home alcohol consumption and sales of alcoholic beverages increased, while consumption of alcohol outside the home decreased.^8-10 Other research has shown an increase in the percentage—but not necessarily the absolute number—of emergency department (ED) visits and hospitalizations for alcohol-related diagnoses during periods of containment.^11,12 At least 1 study suggests that alcohol-related deaths increased beginning in the lockdown period and persisting into mid-2021.¹³

Because earlier studies suggest that lockdown periods are associated with increased alcohol consumption and relapse of alcohol use disorder, we hypothesized that the spring 2020 lockdown period in Massachusetts would be associated temporally with an increase in alcohol-related hospitalizations. To evaluate this hypothesis, we examined all hospitalizations in the US Department of Veterans Affairs (VA) Boston Healthcare System (VABHS) before, during, and after this lockdown period. VABHS includes a 160-bed acute care hospital and a 50-bed inpatient psychiatric facility.

Methods

We conducted an interrupted time-series analysis including all inpatient hospitalizations at VABHS from January 1, 2017, to December 31, 2020, to compare the daily number of alcohol-related hospitalizations across 3 exposure groups: prelockdown (the reference group, 1/1/2017-3/9/2020); lockdown (3/10/2020-5/18/2020); and postlockdown (5/19/2020-12/31/2020).

The VA Corporate Data Warehouse at VABHS was queried to identify all hospitalizations on the medical, psychiatry, and neurology services during the study period. Hospitalizations were considered alcohol-related if the International Statistical Classification of Diseases, Tenth Revision (ICD-10) primary diagnosis code (the main reason for hospitalization) was defined as an alcohol-related diagnosis by the VA Centralized Interactive Phenomics Resource (eAppendix 1, available online at doi:10.1278/fp.0404). This database, which has been previously used for COVID-19 research, is a catalog and knowledge-sharing platform of VA electronic health record–based phenotype algorithms, definitions, and metadata that builds on the Million Veteran Program and Cooperative Studies Program.^14,15 Hospitalizations under observation status were excluded.

To examine whether alcohol-related hospitalizations could have been categorized as COVID-19 when the conditions were co-occurring, we identified 244 hospitalizations coded with a primary ICD-10 code for COVID-19 during the lockdown and postlockdown periods. At the time of admission, each hospitalization carries an initial (free text) diagnosis, of which 3 had an initial diagnosis related to alcohol use. The population at risk for alcohol-related hospitalizations was estimated as the number of patients actively engaged in care at the VABHS. This was defined as the number of patients enrolled in VA care who have previously received any VA care; patients who are enrolled but have never received VA care were excluded from the population-at-risk denominator. Population-at-risk data were available for each fiscal year (FY) of the study period (9/30-10/1); the following population-at-risk sizes were used: 38,057 for FY 2017, 38,527 for FY 2018, 39,472 for FY 2019, and 37,893 for FY 2020.

The primary outcome was the daily number of alcohol-related hospitalizations in the prelockdown, lockdown, and postlockdown periods. A sensitivity analysis was performed using an alternate definition of the primary outcome using a broader set of alcohol-related ICD-10 codes (eAppendix 2, available online at doi:10.1278/fp.0404).

Statistical Analysis

To visually examine hospitalization trends during the study period, we generated a smoothed time-series plot of the 7-day moving average of the daily number of all-cause hospitalizations and the daily number of alcohol-related hospitalizations from January 1, 2017, to December 31, 2020. We used multivariable regression to model the daily number of alcohol-related hospitalizations over prelockdown (the reference group), lockdown, and postlockdown. In addition to the exposure, we included the following covariates in our model: day of the week, calendar date (to account for secular trends), and harmonic polynomials of the day of the year (to account for seasonal variation).¹⁶

We also examined models that included the daily total number of hospitalizations to account for the reduced likelihood of hospital admission for any reason during the pandemic. We used generalized linear models with a Poisson link to generate rate ratios and corresponding 95% CIs for estimates of the daily number of alcohol-related hospitalizations. We estimated the population incidence of alcohol-related hospitalizations per 100,000 patient-months for the exposure periods using the population denominators previously described. All analyses were performed in Stata 16.1.

Results

During the study period, 27,508 hospitalizations were available for analysis. The 7-day moving average of total daily hospitalizations and total daily alcohol-related hospitalizations over time for the period January 1, 2017, to December 31, 2020, are shown in the Figure.

The incidence of alcohol-related hospitalizations in the population dropped from 72 per 100,000 patient-months to 10 per 100,000 patient-months during the lockdown period and increased to 46 per 100,000 patient-months during the postlockdown period (Table).

Discussion

During the spring 2020 COVID-19 lockdown period in Massachusetts, the daily number of VABHS alcohol-related hospitalizations decreased by nearly 80% compared with the prelockdown period. During the postlockdown period, the daily number of alcohol-related hospitalizations increased but only to 72% of the prelockdown baseline by the end of December 2020. A similar trend was observed for all-cause hospitalizations for the same exposure periods.

These results differ from 2 related studies on the effect of the COVID-19 pandemic on alcohol-related hospitalizations.^10,11 In a retrospective study of ED visits to 4 hospitals in New York City, Schimmel and colleagues reported that from March 1 to 31, 2020 (the initial COVID-19 peak), hospital visits for alcohol withdrawal increased while those for alcohol use decreased.¹⁰ However, these results are reported as a percentage of total ED visits rather than the total number of visits, which are vulnerable to spurious correlation because of concomitant changes in the total number of ED visits. In their study, the absolute number of alcohol-related ED visits did not increase during the initial 2020 COVID-19 peak, and the number of visits for alcohol withdrawal syndrome declined slightly (195 in 2019 and 180 in 2020). However, the percentage of visits increased from 7% to 10% because of a greater decline in total ED visits. This pattern of decline in the number of alcohol-related ED visits, accompanied by an increase in the percentage of alcohol-related ED visits, has been observed in at least 1 nationwide surveillance study.¹⁷ This apparent increase does not reflect an absolute increase in ED visits for alcohol withdrawal syndrome and represents a greater relative decline in visits for other causes during the study period.

Sharma and colleagues reported an increase in the percentage of patients who developed alcohol withdrawal syndrome while hospitalized in Delaware per 1000 hospitalizations during consecutive 2-week periods during the pandemic in 2020 compared with corresponding weeks in 2019.¹¹ The greatest increase occurred during the last 2 weeks of the Delaware stay-at-home order. The Clinical Institute Withdrawal Assessment of Alcohol Scale, revised (CIWA-Ar) score of > 8 was used to define alcohol withdrawal syndrome. The American Society of Addiction Medicine does not recommend using CIWA-Ar to diagnose alcohol withdrawal syndrome because the scale was developed to monitor response to treatment, not to establish a diagnosis.¹⁸

Although the true population incidence of alcohol-related hospitalizations is difficult to estimate because the size of the population at risk (ie, the denominator) often is not known, the total number of hospitalizations is not a reliable surrogate.¹⁹ Individuals hospitalized for nonalcohol causes are no longer at risk for alcohol-related hospitalization.

In our study, we assume the population at risk during the study period is constant and model changes in the absolute number—rather than percentage—of alcohol-related ED visits. These absolute estimates of alcohol-related hospitalizations better reflect the true burden on the health care system and avoid the confounding effect of declining total ED visits and hospitalizations that could lead to artificially increased percentages and spurious correlation.²⁰ The absolute percentage of alcohol-related hospitalizations also decreased during this period; therefore, our results are not sensitive to this approach.

Several factors could have contributed to the decrease in alcohol-related hospitalizations. Our findings suggest that patient likelihood to seek care and clinician threshold to admit patients for alcohol-related conditions are influenced by external factors, in this case, a public health lockdown. Although our data do not inform why hospitalizations did not return to prelockdown levels, our experience suggests that limited bed capacity and longer length of stay might have contributed. Other hypotheses include a shift to outpatient care, increased use of telehealth (a significant focus early in the pandemic), and avoiding care for less severe alcohol-related complications because of lingering concerns about exposure to COVID-19 in health care settings reported early in the pandemic. Massachusetts experienced a particularly deadly outbreak of COVID-19 in the Soldiers’ Home, a long-term care facility for veterans in Holyoke.²¹

Evidence suggests that in-home consumption of alcohol increased during lockdowns.^8-10 Our results show that during this period hospitalizations for alcohol-related conditions decreased at VABHS, a large urban VA medical system, while alcohol-related deaths increased nationally.¹³ Although this observation is not evidence of causality, these outcomes could be related.

In the 2 decades before the pandemic, alcohol-related deaths increased by about 2% per year.²² From 2019 to 2020, there was a 25% increase that continued through 2021.¹³ Death certificate data often are inaccurate, and it is difficult to determine whether COVID-19 had a substantial contributing role to these deaths, particularly during the initial period when testing was limited or unavailable. Nonetheless, deaths due to alcohol-associated liver disease, overdoses involving alcohol, and alcohol-related traffic fatalities increased by > 10%.^13,23 These trends, along with a decrease in hospitalization for alcohol-related conditions, suggest missed opportunities for intervention with patients experiencing alcohol use disorder.

Limitations

In this study, hospitalizations under observation status were excluded, which could underestimate the total number of hospitalizations related to alcohol. We reasoned that this effect was likely to be small and not substantially different by year. ICD-10 codes were used to identify alcohol-related hospitalizations as any hospitalization with an included ICD-10 code listed as the primary discharge diagnosis code. This also likely underestimated the total number of alcohol-related hospitalizations. An ICD-10 code for COVID-19 was not in widespread use during our study period, which prohibited controlling explicitly for the volume of admissions due to COVID-19. The prelockdown period only contains data from the preceding 3 years, which might not be long enough for secular trends to become apparent. We assumed the population at risk remained constant when in reality, the net movement of patients into and out of VA care during the pandemic likely was more complex but not readily quantifiable. Nonetheless, the large drop in absolute number of alcohol-related hospitalizations is not likely to be sensitive to this change. In the absence of an objective measure of care-seeking behavior, we used the total daily number of hospitalizations as a surrogate for patient propensity to seek care. The total daily number of hospitalizations also reflects changes in physician admitting behavior over time. This allowed explicit modeling of care-seeking behavior as a covariate but does not capture other important determinants such as hospital capacity.

Conclusions

In this interrupted time-series analysis, the daily number of alcohol-related hospitalizations during the initial COVID-19 pandemic–associated lockdown period at VABHS decreased by 80% and remained 28% lower in the postlockdown period compared with the prepandemic baseline. In the context of evidence suggesting that alcohol-related mortality increased during the COVID-19 pandemic, alternate strategies to reach vulnerable individuals are needed. Because of high rates of relapse, hospitalization is an important opportunity to engage patients experiencing alcohol use disorder in treatment through referral to substance use treatment programs and medication-assisted therapy. Considering the reduction in alcohol-related hospitalizations during lockdown, other strategies are needed to ensure comprehensive and longitudinal care for this vulnerable population.

The United States’ initial public health response to the COVID-19 pandemic included containment measures that varied by state but generally required closing or suspending schools, nonessential businesses, and travel (commonly called lockdown).¹ During these periods, hospitalizations for serious and common conditions declined.^2,3 In Massachusetts, a state of emergency was declared on March 10, 2020, which remained in place until May 18, 2020, when a phased reopening of businesses began.

Although the evidence on the mental health impact of containment periods has been mixed, it has been suggested that these measures could lead to increases in alcohol-related hospitalizations.⁴ Social isolation and increased psychosocial and financial stressors raise the risk of relapse among patients with substance use disorders.^5-7 Marketing and survey data from the US and United Kingdom from the early months of the pandemic suggest that in-home alcohol consumption and sales of alcoholic beverages increased, while consumption of alcohol outside the home decreased.^8-10 Other research has shown an increase in the percentage—but not necessarily the absolute number—of emergency department (ED) visits and hospitalizations for alcohol-related diagnoses during periods of containment.^11,12 At least 1 study suggests that alcohol-related deaths increased beginning in the lockdown period and persisting into mid-2021.¹³

Because earlier studies suggest that lockdown periods are associated with increased alcohol consumption and relapse of alcohol use disorder, we hypothesized that the spring 2020 lockdown period in Massachusetts would be associated temporally with an increase in alcohol-related hospitalizations. To evaluate this hypothesis, we examined all hospitalizations in the US Department of Veterans Affairs (VA) Boston Healthcare System (VABHS) before, during, and after this lockdown period. VABHS includes a 160-bed acute care hospital and a 50-bed inpatient psychiatric facility.

Methods

We conducted an interrupted time-series analysis including all inpatient hospitalizations at VABHS from January 1, 2017, to December 31, 2020, to compare the daily number of alcohol-related hospitalizations across 3 exposure groups: prelockdown (the reference group, 1/1/2017-3/9/2020); lockdown (3/10/2020-5/18/2020); and postlockdown (5/19/2020-12/31/2020).

The VA Corporate Data Warehouse at VABHS was queried to identify all hospitalizations on the medical, psychiatry, and neurology services during the study period. Hospitalizations were considered alcohol-related if the International Statistical Classification of Diseases, Tenth Revision (ICD-10) primary diagnosis code (the main reason for hospitalization) was defined as an alcohol-related diagnosis by the VA Centralized Interactive Phenomics Resource (eAppendix 1, available online at doi:10.1278/fp.0404). This database, which has been previously used for COVID-19 research, is a catalog and knowledge-sharing platform of VA electronic health record–based phenotype algorithms, definitions, and metadata that builds on the Million Veteran Program and Cooperative Studies Program.^14,15 Hospitalizations under observation status were excluded.

To examine whether alcohol-related hospitalizations could have been categorized as COVID-19 when the conditions were co-occurring, we identified 244 hospitalizations coded with a primary ICD-10 code for COVID-19 during the lockdown and postlockdown periods. At the time of admission, each hospitalization carries an initial (free text) diagnosis, of which 3 had an initial diagnosis related to alcohol use. The population at risk for alcohol-related hospitalizations was estimated as the number of patients actively engaged in care at the VABHS. This was defined as the number of patients enrolled in VA care who have previously received any VA care; patients who are enrolled but have never received VA care were excluded from the population-at-risk denominator. Population-at-risk data were available for each fiscal year (FY) of the study period (9/30-10/1); the following population-at-risk sizes were used: 38,057 for FY 2017, 38,527 for FY 2018, 39,472 for FY 2019, and 37,893 for FY 2020.

The primary outcome was the daily number of alcohol-related hospitalizations in the prelockdown, lockdown, and postlockdown periods. A sensitivity analysis was performed using an alternate definition of the primary outcome using a broader set of alcohol-related ICD-10 codes (eAppendix 2, available online at doi:10.1278/fp.0404).

Statistical Analysis

To visually examine hospitalization trends during the study period, we generated a smoothed time-series plot of the 7-day moving average of the daily number of all-cause hospitalizations and the daily number of alcohol-related hospitalizations from January 1, 2017, to December 31, 2020. We used multivariable regression to model the daily number of alcohol-related hospitalizations over prelockdown (the reference group), lockdown, and postlockdown. In addition to the exposure, we included the following covariates in our model: day of the week, calendar date (to account for secular trends), and harmonic polynomials of the day of the year (to account for seasonal variation).¹⁶

We also examined models that included the daily total number of hospitalizations to account for the reduced likelihood of hospital admission for any reason during the pandemic. We used generalized linear models with a Poisson link to generate rate ratios and corresponding 95% CIs for estimates of the daily number of alcohol-related hospitalizations. We estimated the population incidence of alcohol-related hospitalizations per 100,000 patient-months for the exposure periods using the population denominators previously described. All analyses were performed in Stata 16.1.

Results

During the study period, 27,508 hospitalizations were available for analysis. The 7-day moving average of total daily hospitalizations and total daily alcohol-related hospitalizations over time for the period January 1, 2017, to December 31, 2020, are shown in the Figure.

The incidence of alcohol-related hospitalizations in the population dropped from 72 per 100,000 patient-months to 10 per 100,000 patient-months during the lockdown period and increased to 46 per 100,000 patient-months during the postlockdown period (Table).

Discussion

During the spring 2020 COVID-19 lockdown period in Massachusetts, the daily number of VABHS alcohol-related hospitalizations decreased by nearly 80% compared with the prelockdown period. During the postlockdown period, the daily number of alcohol-related hospitalizations increased but only to 72% of the prelockdown baseline by the end of December 2020. A similar trend was observed for all-cause hospitalizations for the same exposure periods.

These results differ from 2 related studies on the effect of the COVID-19 pandemic on alcohol-related hospitalizations.^10,11 In a retrospective study of ED visits to 4 hospitals in New York City, Schimmel and colleagues reported that from March 1 to 31, 2020 (the initial COVID-19 peak), hospital visits for alcohol withdrawal increased while those for alcohol use decreased.¹⁰ However, these results are reported as a percentage of total ED visits rather than the total number of visits, which are vulnerable to spurious correlation because of concomitant changes in the total number of ED visits. In their study, the absolute number of alcohol-related ED visits did not increase during the initial 2020 COVID-19 peak, and the number of visits for alcohol withdrawal syndrome declined slightly (195 in 2019 and 180 in 2020). However, the percentage of visits increased from 7% to 10% because of a greater decline in total ED visits. This pattern of decline in the number of alcohol-related ED visits, accompanied by an increase in the percentage of alcohol-related ED visits, has been observed in at least 1 nationwide surveillance study.¹⁷ This apparent increase does not reflect an absolute increase in ED visits for alcohol withdrawal syndrome and represents a greater relative decline in visits for other causes during the study period.

Sharma and colleagues reported an increase in the percentage of patients who developed alcohol withdrawal syndrome while hospitalized in Delaware per 1000 hospitalizations during consecutive 2-week periods during the pandemic in 2020 compared with corresponding weeks in 2019.¹¹ The greatest increase occurred during the last 2 weeks of the Delaware stay-at-home order. The Clinical Institute Withdrawal Assessment of Alcohol Scale, revised (CIWA-Ar) score of > 8 was used to define alcohol withdrawal syndrome. The American Society of Addiction Medicine does not recommend using CIWA-Ar to diagnose alcohol withdrawal syndrome because the scale was developed to monitor response to treatment, not to establish a diagnosis.¹⁸

Although the true population incidence of alcohol-related hospitalizations is difficult to estimate because the size of the population at risk (ie, the denominator) often is not known, the total number of hospitalizations is not a reliable surrogate.¹⁹ Individuals hospitalized for nonalcohol causes are no longer at risk for alcohol-related hospitalization.

In our study, we assume the population at risk during the study period is constant and model changes in the absolute number—rather than percentage—of alcohol-related ED visits. These absolute estimates of alcohol-related hospitalizations better reflect the true burden on the health care system and avoid the confounding effect of declining total ED visits and hospitalizations that could lead to artificially increased percentages and spurious correlation.²⁰ The absolute percentage of alcohol-related hospitalizations also decreased during this period; therefore, our results are not sensitive to this approach.

Several factors could have contributed to the decrease in alcohol-related hospitalizations. Our findings suggest that patient likelihood to seek care and clinician threshold to admit patients for alcohol-related conditions are influenced by external factors, in this case, a public health lockdown. Although our data do not inform why hospitalizations did not return to prelockdown levels, our experience suggests that limited bed capacity and longer length of stay might have contributed. Other hypotheses include a shift to outpatient care, increased use of telehealth (a significant focus early in the pandemic), and avoiding care for less severe alcohol-related complications because of lingering concerns about exposure to COVID-19 in health care settings reported early in the pandemic. Massachusetts experienced a particularly deadly outbreak of COVID-19 in the Soldiers’ Home, a long-term care facility for veterans in Holyoke.²¹

Evidence suggests that in-home consumption of alcohol increased during lockdowns.^8-10 Our results show that during this period hospitalizations for alcohol-related conditions decreased at VABHS, a large urban VA medical system, while alcohol-related deaths increased nationally.¹³ Although this observation is not evidence of causality, these outcomes could be related.

In the 2 decades before the pandemic, alcohol-related deaths increased by about 2% per year.²² From 2019 to 2020, there was a 25% increase that continued through 2021.¹³ Death certificate data often are inaccurate, and it is difficult to determine whether COVID-19 had a substantial contributing role to these deaths, particularly during the initial period when testing was limited or unavailable. Nonetheless, deaths due to alcohol-associated liver disease, overdoses involving alcohol, and alcohol-related traffic fatalities increased by > 10%.^13,23 These trends, along with a decrease in hospitalization for alcohol-related conditions, suggest missed opportunities for intervention with patients experiencing alcohol use disorder.

Limitations

In this study, hospitalizations under observation status were excluded, which could underestimate the total number of hospitalizations related to alcohol. We reasoned that this effect was likely to be small and not substantially different by year. ICD-10 codes were used to identify alcohol-related hospitalizations as any hospitalization with an included ICD-10 code listed as the primary discharge diagnosis code. This also likely underestimated the total number of alcohol-related hospitalizations. An ICD-10 code for COVID-19 was not in widespread use during our study period, which prohibited controlling explicitly for the volume of admissions due to COVID-19. The prelockdown period only contains data from the preceding 3 years, which might not be long enough for secular trends to become apparent. We assumed the population at risk remained constant when in reality, the net movement of patients into and out of VA care during the pandemic likely was more complex but not readily quantifiable. Nonetheless, the large drop in absolute number of alcohol-related hospitalizations is not likely to be sensitive to this change. In the absence of an objective measure of care-seeking behavior, we used the total daily number of hospitalizations as a surrogate for patient propensity to seek care. The total daily number of hospitalizations also reflects changes in physician admitting behavior over time. This allowed explicit modeling of care-seeking behavior as a covariate but does not capture other important determinants such as hospital capacity.

Conclusions

In this interrupted time-series analysis, the daily number of alcohol-related hospitalizations during the initial COVID-19 pandemic–associated lockdown period at VABHS decreased by 80% and remained 28% lower in the postlockdown period compared with the prepandemic baseline. In the context of evidence suggesting that alcohol-related mortality increased during the COVID-19 pandemic, alternate strategies to reach vulnerable individuals are needed. Because of high rates of relapse, hospitalization is an important opportunity to engage patients experiencing alcohol use disorder in treatment through referral to substance use treatment programs and medication-assisted therapy. Considering the reduction in alcohol-related hospitalizations during lockdown, other strategies are needed to ensure comprehensive and longitudinal care for this vulnerable population.

Veterans speak of losing their innocence and longing to regain it. They ask: “Why can’t I just go back to the way I was?”

Jonathan Shay, Achilles in Vietnam ¹

On July 17, 2023, several media outlets covering military and federal news carried a story about the US Department of Veterans Affairs (VA) plan to conduct a major survey of moral injury in veterans.² This is not the first such survey: There have been numerous previous studies conducted by both VA and non-VA investigators.³ Moral injury has been increasingly recognized as the signature wound of service members, especially those who fought in Operation Enduring Freedom and Operation Iraqi Freedom.⁴ This new VA survey can provide crucial information because we know so little about moral injury or how to help those with the condition.

At the time of this writing, there has been no official VA public statement about the study. At face value, this seemed to be strange, given that the groundbreaking research could improve the diagnosis and therapy of moral injury. According to a June 2023 VA Office of Research and Development internal announcement, the primary goal of the study is to determine the prevalence of moral injury among US veterans. The secondary goals of the study are to (1) compare those who develop moral injury and those who do not after exposure to similar traumas; and (2) conduct interviews about thoughts and experiences from 20 veterans who identify as having moral injury and 20 who do not but who have similar exposure to morally injurious events.

Data for the study will be collected through an extensive online survey from a nationally representative sample of 3000 post-9/11 war veterans. The sample will include at least 950 who served in a war zone and at least 400 who are aged 18 to 54 years. The respondents will be paid $20 for the 30 to 45 minutes survey. The collection and analysis of data are expected to take 3 or more years.

The modern version of moral injury is often associated with Jonathan Shay, MD, a VA psychiatrist.⁵ Shay wrote about the origin of moral injury found in Homer’s The Iliad and The Odyssey and how the poems offer ancient echoes of his therapy with modern-day combat veterans.¹

There is no universal agreement on the definition of moral injury. A working definition of moral injury used in the VA suggests that it describes the difficulties that people face after doing high-stakes actions that violate a sense of what is right and just or after being forced to experience others’ immoral actions.⁶

Two conditions are necessary for moral injury to occur. First, an individual acts or witnesses an action that contravenes their core ethical principles. Secondly, that occurrence is experienced as a breach of the person’s moral barrier. Military personnel killing civilians to protect their lives and those of their fellow troops is a tragic example of moral injury. The translation of this for health care professionals may be the inability to save severely wounded service members in the combat theater due to the exigencies of war.⁷

Experts in moral injury emphasize the importance of distinguishing the phenomenon from posttraumatic stress disorder (PTSD). Unlike many psychiatric disorders, both moral injury and PTSD have known etiologies: traumatic events. An individual may have 1 or both conditions, and each can manifest anger, guilt, shame, and loss of trust in others. One way that moral injury can be distinguished from PTSD is that it goes beyond the psychological to compromise the moral and often spiritual beliefs and values of the individual. One of the characteristics that makes us human is that we have a conscience to guide us in navigating the moral field of human life, but moral injury scrambles the internal compass that discerns right and wrong, good and bad. When an individual commits an action or witnesses the perpetration of an action that crosses their personal moral boundary, their integrity is shattered, and they may lose faith in their intrinsic worth. These beliefs prevent many service members from disclosing their distress, leading some commentators to refer to moral injury as a silent or invisible wound.⁸

The timing of the VA’s launching of a study of moral injury of this size and scope may reflect 3 recent developments: Not unexpected in VA matters, one is political, another is benefits, and the last pertains to health care.

First, August marks the second anniversary of the withdrawal of American troops from Afghanistan. Many Afghans who assisted US forces during the war were not evacuated. For some of the troops who served in the country, these events as well as the chaotic end to the long war were experienced as a contravening of an ethical code, resulting in moral injury.⁹

Second, many of those service members are now calling on the federal government to recognize and respond to the detrimental impact of the withdrawal, including the high prevalence of moral injury in troops who served in Afghanistan.¹⁰ Moral injury at this time is not considered a psychiatric diagnosis; hence, not eligible for VA benefits. However, many of the psychological manifestations of moral injury, such as depression and anxiety, are established service-connected disorders.

Third, several VA studies have demonstrated that moral injury either alone or combined with PTSD substantially elevates the risk of suicide.¹¹ Since preventing suicide is a major strategic priority for the VA, the importance of learning more about the epidemiology of moral injury is the necessary first step to developing therapeutic approaches. At a time when organized medicine is becoming increasingly technological and fragmented, launching this unprecedented survey demonstrates the VA’s commitment to delivering holistic and humanistic care of the service member: body, mind, and spirit.

This project also sends a strong message to those who lobby for shifting funding from the VA to community care or call for privatization. Veterans are different: They experience unique disorders borne of the battles they fought for our freedom. The VA has the specialized knowledge and skills in research and health care to develop the knowledge to ground innovative treatments for conditions like moral injury, PTSD, and traumatic brain injuries. VA chaplains and mental health professionals have pioneered assessment instruments and promising therapies for moral injury. Their distinctive expertise unrivaled in the civilian sector benefits not only veterans but also the wider community where there is a growing awareness of the devastating impact of moral injury, particularly on health care professionals.¹² And there may have been no other time in history when this broken, violent world was more in need of moral healing and peace.