Patrice Wendling

MADRID – Use of practice-based asthma navigators significantly reduced symptoms and emergency room and inpatient visits among inner-city children with moderate to severe asthma in a prospective, case-matched study.

"We’ve seen with our home-visit studies that we’re able to reduce asthma morbidity, but what we hear from the parents all the time is that they feel their communication with providers is lacking, and that they really needed someone to help them navigate the clinical system," Dr. Tyra Bryant-Stephens, founder and director of the Community Asthma Prevention Program at Children’s Hospital of Philadelphia (CHOP), said in an interview.

To overcome this hurdle, CHOP began integrating community health workers as asthma navigators into the clinical team at its inner-city asthma clinics. Key tasks are to teach caregivers about the Asthma Care Plan and proper use of controller medications, facilitate appointment scheduling and set up reminders, contact and share asthma care plans with school nurses, work with social workers to identify appropriate resources for families, and set care coordination goals.

Patrice Wendling/Frontline Medical News

The study enrolled children, aged 2-17 years, on at least two asthma control medications. The participants had been hospitalized or had at least two emergency department (ED) visits in the past year. Their average age was 4.6 years.

After 12 months in the navigator program, preliminary data on 99 children revealed a clear 2- to 3-day reduction over the past 14 days in days using rescue asthma medications (5.28 vs. 3.07; P less than .01), days with symptoms (6.93 to 3.8; P less than .01), and nights with symptoms (6.11 to 3.34; P less than .01), Dr. Bryant-Stephens reported at the world congress of the American College of Chest Physicians.

Compared with baseline, the number of days not taking asthma medications at 12 months was not significantly different (1.48 vs. 1.22) nor was the number of days during which activities had to be slowed (4.41 vs. 3.73).

Enrollment in the navigator program, however, lowered the number of school days missed (16 vs. 2; P less than .05), workdays missed (9.11 vs. 1.13; P less than .01), unscheduled visits to the doctor (2.5 vs. 0.5; P less than .05), ED visits (3.65 vs. 1.31; P less than .01), and hospitalizations (1.73 vs. 0.4; P less than .01).

Although the final analysis comparing participants with matched controls receiving usual care is not yet complete, the data so far show a definite reduction in health care utilization by participants, despite controls being less sick at baseline, Dr. Bryant-Stephens said. This is particularly encouraging because earlier studies at CHOP showed that roughly 50% of asthmatic children never made it back to their primary care physician for follow-up between ED visits.

Making appointments for and keeping follow-up visits were listed by 146 of 157 (93%) caregivers as one of the most important care coordination goals, and were achieved by 80% at 12 months with the assistance of phone calls from the asthma navigator, transportation tokens, and insurance cotransportation, according to the poster presentation.

Success among the other top five caregiver goals was 92% for learning how to properly use asthma medications (126/136 caregivers), 98% for reducing asthma triggers (154/157), 54% for stopping smoking in the house and car (23/42), and 94% for the surprising goal of losing weight in hopes it would reduce asthma symptoms (34/36).

There is no "magic bullet," or single component of the navigator program responsible for the results, but "I think what the navigators have been most effective at is bringing them back to the office. It’s unbelievable compared with the control group," Dr. Bryant-Stephens said at the meeting.

Ultimately, the goal is to make the program self-sufficient, with a pilot program currently underway in which Pennsylvania’s largest Medicaid provider, Keystone First, will pay CHOP to have their clients assigned an asthma navigator when they enroll at an asthma clinic.

Dr. Bryant-Stephens reported funding from the Merck Childhood Asthma Network.

pwendling@frontlinemedcom.com

MADRID – Use of practice-based asthma navigators significantly reduced symptoms and emergency room and inpatient visits among inner-city children with moderate to severe asthma in a prospective, case-matched study.

"We’ve seen with our home-visit studies that we’re able to reduce asthma morbidity, but what we hear from the parents all the time is that they feel their communication with providers is lacking, and that they really needed someone to help them navigate the clinical system," Dr. Tyra Bryant-Stephens, founder and director of the Community Asthma Prevention Program at Children’s Hospital of Philadelphia (CHOP), said in an interview.

To overcome this hurdle, CHOP began integrating community health workers as asthma navigators into the clinical team at its inner-city asthma clinics. Key tasks are to teach caregivers about the Asthma Care Plan and proper use of controller medications, facilitate appointment scheduling and set up reminders, contact and share asthma care plans with school nurses, work with social workers to identify appropriate resources for families, and set care coordination goals.

Patrice Wendling/Frontline Medical News

The study enrolled children, aged 2-17 years, on at least two asthma control medications. The participants had been hospitalized or had at least two emergency department (ED) visits in the past year. Their average age was 4.6 years.

After 12 months in the navigator program, preliminary data on 99 children revealed a clear 2- to 3-day reduction over the past 14 days in days using rescue asthma medications (5.28 vs. 3.07; P less than .01), days with symptoms (6.93 to 3.8; P less than .01), and nights with symptoms (6.11 to 3.34; P less than .01), Dr. Bryant-Stephens reported at the world congress of the American College of Chest Physicians.

Compared with baseline, the number of days not taking asthma medications at 12 months was not significantly different (1.48 vs. 1.22) nor was the number of days during which activities had to be slowed (4.41 vs. 3.73).

Enrollment in the navigator program, however, lowered the number of school days missed (16 vs. 2; P less than .05), workdays missed (9.11 vs. 1.13; P less than .01), unscheduled visits to the doctor (2.5 vs. 0.5; P less than .05), ED visits (3.65 vs. 1.31; P less than .01), and hospitalizations (1.73 vs. 0.4; P less than .01).

Although the final analysis comparing participants with matched controls receiving usual care is not yet complete, the data so far show a definite reduction in health care utilization by participants, despite controls being less sick at baseline, Dr. Bryant-Stephens said. This is particularly encouraging because earlier studies at CHOP showed that roughly 50% of asthmatic children never made it back to their primary care physician for follow-up between ED visits.

Making appointments for and keeping follow-up visits were listed by 146 of 157 (93%) caregivers as one of the most important care coordination goals, and were achieved by 80% at 12 months with the assistance of phone calls from the asthma navigator, transportation tokens, and insurance cotransportation, according to the poster presentation.

Success among the other top five caregiver goals was 92% for learning how to properly use asthma medications (126/136 caregivers), 98% for reducing asthma triggers (154/157), 54% for stopping smoking in the house and car (23/42), and 94% for the surprising goal of losing weight in hopes it would reduce asthma symptoms (34/36).

There is no "magic bullet," or single component of the navigator program responsible for the results, but "I think what the navigators have been most effective at is bringing them back to the office. It’s unbelievable compared with the control group," Dr. Bryant-Stephens said at the meeting.

Ultimately, the goal is to make the program self-sufficient, with a pilot program currently underway in which Pennsylvania’s largest Medicaid provider, Keystone First, will pay CHOP to have their clients assigned an asthma navigator when they enroll at an asthma clinic.

Dr. Bryant-Stephens reported funding from the Merck Childhood Asthma Network.

pwendling@frontlinemedcom.com

MADRID – Use of practice-based asthma navigators significantly reduced symptoms and emergency room and inpatient visits among inner-city children with moderate to severe asthma in a prospective, case-matched study.

"We’ve seen with our home-visit studies that we’re able to reduce asthma morbidity, but what we hear from the parents all the time is that they feel their communication with providers is lacking, and that they really needed someone to help them navigate the clinical system," Dr. Tyra Bryant-Stephens, founder and director of the Community Asthma Prevention Program at Children’s Hospital of Philadelphia (CHOP), said in an interview.

To overcome this hurdle, CHOP began integrating community health workers as asthma navigators into the clinical team at its inner-city asthma clinics. Key tasks are to teach caregivers about the Asthma Care Plan and proper use of controller medications, facilitate appointment scheduling and set up reminders, contact and share asthma care plans with school nurses, work with social workers to identify appropriate resources for families, and set care coordination goals.

Patrice Wendling/Frontline Medical News

The study enrolled children, aged 2-17 years, on at least two asthma control medications. The participants had been hospitalized or had at least two emergency department (ED) visits in the past year. Their average age was 4.6 years.

After 12 months in the navigator program, preliminary data on 99 children revealed a clear 2- to 3-day reduction over the past 14 days in days using rescue asthma medications (5.28 vs. 3.07; P less than .01), days with symptoms (6.93 to 3.8; P less than .01), and nights with symptoms (6.11 to 3.34; P less than .01), Dr. Bryant-Stephens reported at the world congress of the American College of Chest Physicians.

Compared with baseline, the number of days not taking asthma medications at 12 months was not significantly different (1.48 vs. 1.22) nor was the number of days during which activities had to be slowed (4.41 vs. 3.73).

Enrollment in the navigator program, however, lowered the number of school days missed (16 vs. 2; P less than .05), workdays missed (9.11 vs. 1.13; P less than .01), unscheduled visits to the doctor (2.5 vs. 0.5; P less than .05), ED visits (3.65 vs. 1.31; P less than .01), and hospitalizations (1.73 vs. 0.4; P less than .01).

Although the final analysis comparing participants with matched controls receiving usual care is not yet complete, the data so far show a definite reduction in health care utilization by participants, despite controls being less sick at baseline, Dr. Bryant-Stephens said. This is particularly encouraging because earlier studies at CHOP showed that roughly 50% of asthmatic children never made it back to their primary care physician for follow-up between ED visits.

Making appointments for and keeping follow-up visits were listed by 146 of 157 (93%) caregivers as one of the most important care coordination goals, and were achieved by 80% at 12 months with the assistance of phone calls from the asthma navigator, transportation tokens, and insurance cotransportation, according to the poster presentation.

Success among the other top five caregiver goals was 92% for learning how to properly use asthma medications (126/136 caregivers), 98% for reducing asthma triggers (154/157), 54% for stopping smoking in the house and car (23/42), and 94% for the surprising goal of losing weight in hopes it would reduce asthma symptoms (34/36).

There is no "magic bullet," or single component of the navigator program responsible for the results, but "I think what the navigators have been most effective at is bringing them back to the office. It’s unbelievable compared with the control group," Dr. Bryant-Stephens said at the meeting.

Ultimately, the goal is to make the program self-sufficient, with a pilot program currently underway in which Pennsylvania’s largest Medicaid provider, Keystone First, will pay CHOP to have their clients assigned an asthma navigator when they enroll at an asthma clinic.

Dr. Bryant-Stephens reported funding from the Merck Childhood Asthma Network.

pwendling@frontlinemedcom.com

Protocol-based resuscitation did not reduce sepsis deaths or morbidity, compared with usual care, in the Protocolized Care for Early Septic Shock study conducted at 31 U.S. academic hospitals.

Among 1,341 evaluable patients, the primary endpoint of 60-day in-hospital mortality was 21% with protocol-based early goal-directed therapy (EGDT), 18.2% with protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions, and 18.9% with usual care according to the treating physician’s judgment.

The difference was not statistically significant between the protocol-based interventions and usual care (relative risk, 1.04; P = .83) or between protocol-based EGDT and protocol-based standard therapy (RR, 1.15; P = .31), according to data presented at the International Symposium on Intensive Care and Emergency Medicine and simultaneously published in the New England Journal of Medicine (N. Engl. J. Med. 2014 March 18 [doi:10.1056/NEJMoa1401602]).

The three groups also did not differ significantly with regard to 90-day mortality, incidence of cardiovascular or respiratory failure, length of hospital stay, or discharge disposition.

The results from ProCESS differ from those reported more than a decade ago in the pivotal, single-center Rivers et al. study, in which mortality was significantly reduced for patients with severe sepsis or septic shock treated with 6 hours of EGDT therapy versus standard therapy (N. Engl. J. Med. 2001;345:1368-77).

Though both trials used the same EGDT protocol delivered by a trained, dedicated team at each site, possible reasons for the discordance are that the Rivers study showed nearly perfect adherence to protocol and that its cohort was slightly older, had higher rates of preexisting heart and liver disease, and had a higher initial serum lactate level, noted Dr. Derek Angus, ProCESS principal investigator and chair of critical care medicine at the University of Pittsburgh.

In addition, changes in the management of critically ill patient in the ensuing decade, including use of lower hemoglobin levels as a threshold for transfusion, use of lung-protection strategies, and tighter blood sugar control, "may have helped lower the overall mortality and may have reduced the marginal benefit of alternative resuscitation strategies," he observed.

Dr. Angus received grant support from the National Institutes of General Medical Sciences and nonfinancial support from Edwards Inc. during the trial, grant support to his university from Eisai, and personal fees from Pfizer and MedImmune outside this trial.

pwendling@frontlinemedcom.com

Protocol-based resuscitation did not reduce sepsis deaths or morbidity, compared with usual care, in the Protocolized Care for Early Septic Shock study conducted at 31 U.S. academic hospitals.

Among 1,341 evaluable patients, the primary endpoint of 60-day in-hospital mortality was 21% with protocol-based early goal-directed therapy (EGDT), 18.2% with protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions, and 18.9% with usual care according to the treating physician’s judgment.

The difference was not statistically significant between the protocol-based interventions and usual care (relative risk, 1.04; P = .83) or between protocol-based EGDT and protocol-based standard therapy (RR, 1.15; P = .31), according to data presented at the International Symposium on Intensive Care and Emergency Medicine and simultaneously published in the New England Journal of Medicine (N. Engl. J. Med. 2014 March 18 [doi:10.1056/NEJMoa1401602]).

The three groups also did not differ significantly with regard to 90-day mortality, incidence of cardiovascular or respiratory failure, length of hospital stay, or discharge disposition.

The results from ProCESS differ from those reported more than a decade ago in the pivotal, single-center Rivers et al. study, in which mortality was significantly reduced for patients with severe sepsis or septic shock treated with 6 hours of EGDT therapy versus standard therapy (N. Engl. J. Med. 2001;345:1368-77).

Though both trials used the same EGDT protocol delivered by a trained, dedicated team at each site, possible reasons for the discordance are that the Rivers study showed nearly perfect adherence to protocol and that its cohort was slightly older, had higher rates of preexisting heart and liver disease, and had a higher initial serum lactate level, noted Dr. Derek Angus, ProCESS principal investigator and chair of critical care medicine at the University of Pittsburgh.

In addition, changes in the management of critically ill patient in the ensuing decade, including use of lower hemoglobin levels as a threshold for transfusion, use of lung-protection strategies, and tighter blood sugar control, "may have helped lower the overall mortality and may have reduced the marginal benefit of alternative resuscitation strategies," he observed.

Dr. Angus received grant support from the National Institutes of General Medical Sciences and nonfinancial support from Edwards Inc. during the trial, grant support to his university from Eisai, and personal fees from Pfizer and MedImmune outside this trial.

pwendling@frontlinemedcom.com

Protocol-based resuscitation did not reduce sepsis deaths or morbidity, compared with usual care, in the Protocolized Care for Early Septic Shock study conducted at 31 U.S. academic hospitals.

Among 1,341 evaluable patients, the primary endpoint of 60-day in-hospital mortality was 21% with protocol-based early goal-directed therapy (EGDT), 18.2% with protocol-based standard therapy that did not require the placement of a central venous catheter, administration of inotropes, or blood transfusions, and 18.9% with usual care according to the treating physician’s judgment.

The difference was not statistically significant between the protocol-based interventions and usual care (relative risk, 1.04; P = .83) or between protocol-based EGDT and protocol-based standard therapy (RR, 1.15; P = .31), according to data presented at the International Symposium on Intensive Care and Emergency Medicine and simultaneously published in the New England Journal of Medicine (N. Engl. J. Med. 2014 March 18 [doi:10.1056/NEJMoa1401602]).

The three groups also did not differ significantly with regard to 90-day mortality, incidence of cardiovascular or respiratory failure, length of hospital stay, or discharge disposition.

The results from ProCESS differ from those reported more than a decade ago in the pivotal, single-center Rivers et al. study, in which mortality was significantly reduced for patients with severe sepsis or septic shock treated with 6 hours of EGDT therapy versus standard therapy (N. Engl. J. Med. 2001;345:1368-77).

Though both trials used the same EGDT protocol delivered by a trained, dedicated team at each site, possible reasons for the discordance are that the Rivers study showed nearly perfect adherence to protocol and that its cohort was slightly older, had higher rates of preexisting heart and liver disease, and had a higher initial serum lactate level, noted Dr. Derek Angus, ProCESS principal investigator and chair of critical care medicine at the University of Pittsburgh.

In addition, changes in the management of critically ill patient in the ensuing decade, including use of lower hemoglobin levels as a threshold for transfusion, use of lung-protection strategies, and tighter blood sugar control, "may have helped lower the overall mortality and may have reduced the marginal benefit of alternative resuscitation strategies," he observed.

Dr. Angus received grant support from the National Institutes of General Medical Sciences and nonfinancial support from Edwards Inc. during the trial, grant support to his university from Eisai, and personal fees from Pfizer and MedImmune outside this trial.

pwendling@frontlinemedcom.com

Use of a high mean arterial pressure during initial resuscitation in patients with septic shock did not improve mortality at 28 or 90 days in the multicenter, open-label SEPSISPAM trial.

The Surviving Sepsis Campaign guidelines recommend targeting a mean arterial pressure (MAP) of at least 65 mm Hg, but suggest a higher target may be better for patients with atherosclerosis or previous hypertension. Retrospective data also suggest a MAP of more than 75 mm Hg may be needed to maintain kidney function during early sepsis.

For the current trial, investigators at 29 centers in France evenly randomized 776 patients to vasopressor treatment adjusted to maintain a MAP of 80-85 mm Hg (high-target group) or 65-70 mm Hg (low-target group).

The study’s primary endpoint of all-cause mortality at 28 days was 36.5% in the high-target group and 34% in the low-target group (nonsignificant hazard ratio in the high-target group, 1.07), according to data presented at the International Symposium on Intensive Care and Emergency Medicine and simultaneously published online (N. Engl. J. Med. 2014 March 18 [doi:10.1056/NEJMoa1312173]).

In addition, there were no significant differences between the high- and low-target groups in the secondary outcomes of 90-day mortality (43.7% vs. 42.3%; HR, 1.04), need for mechanical ventilation, ICU length of stay, or Sequential Organ Failure Assessment score at day 7.

Atrial fibrillation, however, was significantly more common in the high-target group than in the low-target group, at 6.7%, compared with 2.8%. This could be related to the high-target group receiving significantly higher doses of vasopressor catecholamines over a significantly longer time period, although other confounding factors cannot be ruled out, lead author Dr. Pierre Asfar of University Hospital of Angers (France), reported on behalf of SEPSISPAM investigators.

Among patients with chronic arterial hypertension, who comprised more than 40% of the study population, use of the high MAP target significantly reduced both the incidence of doubling of plasma creatinine (39% vs. 52%) and the rate of renal-replacement therapy (31.7% vs. 42.2%).

The authors noted that, although investigators were asked to treat patients to a MAP of 65-70 mm Hg in the low-target group, the observed pressures were for the most part between 70 and 75 mm Hg. The high-target group was likewise off goal, at a mean of 70 mm Hg. They also acknowledged that the lower-than-expected death rate, albeit in line with more recent trials, led to an underpowered study.

The French Ministry of Health funded the trial. Dr. Asfar reported lecture fees from LFB Biomedicaments.

pwendling@frontlinemedcom.com

Use of a high mean arterial pressure during initial resuscitation in patients with septic shock did not improve mortality at 28 or 90 days in the multicenter, open-label SEPSISPAM trial.

The Surviving Sepsis Campaign guidelines recommend targeting a mean arterial pressure (MAP) of at least 65 mm Hg, but suggest a higher target may be better for patients with atherosclerosis or previous hypertension. Retrospective data also suggest a MAP of more than 75 mm Hg may be needed to maintain kidney function during early sepsis.

For the current trial, investigators at 29 centers in France evenly randomized 776 patients to vasopressor treatment adjusted to maintain a MAP of 80-85 mm Hg (high-target group) or 65-70 mm Hg (low-target group).

The study’s primary endpoint of all-cause mortality at 28 days was 36.5% in the high-target group and 34% in the low-target group (nonsignificant hazard ratio in the high-target group, 1.07), according to data presented at the International Symposium on Intensive Care and Emergency Medicine and simultaneously published online (N. Engl. J. Med. 2014 March 18 [doi:10.1056/NEJMoa1312173]).

In addition, there were no significant differences between the high- and low-target groups in the secondary outcomes of 90-day mortality (43.7% vs. 42.3%; HR, 1.04), need for mechanical ventilation, ICU length of stay, or Sequential Organ Failure Assessment score at day 7.

Atrial fibrillation, however, was significantly more common in the high-target group than in the low-target group, at 6.7%, compared with 2.8%. This could be related to the high-target group receiving significantly higher doses of vasopressor catecholamines over a significantly longer time period, although other confounding factors cannot be ruled out, lead author Dr. Pierre Asfar of University Hospital of Angers (France), reported on behalf of SEPSISPAM investigators.

Among patients with chronic arterial hypertension, who comprised more than 40% of the study population, use of the high MAP target significantly reduced both the incidence of doubling of plasma creatinine (39% vs. 52%) and the rate of renal-replacement therapy (31.7% vs. 42.2%).

The authors noted that, although investigators were asked to treat patients to a MAP of 65-70 mm Hg in the low-target group, the observed pressures were for the most part between 70 and 75 mm Hg. The high-target group was likewise off goal, at a mean of 70 mm Hg. They also acknowledged that the lower-than-expected death rate, albeit in line with more recent trials, led to an underpowered study.

The French Ministry of Health funded the trial. Dr. Asfar reported lecture fees from LFB Biomedicaments.

pwendling@frontlinemedcom.com

Use of a high mean arterial pressure during initial resuscitation in patients with septic shock did not improve mortality at 28 or 90 days in the multicenter, open-label SEPSISPAM trial.

The Surviving Sepsis Campaign guidelines recommend targeting a mean arterial pressure (MAP) of at least 65 mm Hg, but suggest a higher target may be better for patients with atherosclerosis or previous hypertension. Retrospective data also suggest a MAP of more than 75 mm Hg may be needed to maintain kidney function during early sepsis.

For the current trial, investigators at 29 centers in France evenly randomized 776 patients to vasopressor treatment adjusted to maintain a MAP of 80-85 mm Hg (high-target group) or 65-70 mm Hg (low-target group).

The study’s primary endpoint of all-cause mortality at 28 days was 36.5% in the high-target group and 34% in the low-target group (nonsignificant hazard ratio in the high-target group, 1.07), according to data presented at the International Symposium on Intensive Care and Emergency Medicine and simultaneously published online (N. Engl. J. Med. 2014 March 18 [doi:10.1056/NEJMoa1312173]).

In addition, there were no significant differences between the high- and low-target groups in the secondary outcomes of 90-day mortality (43.7% vs. 42.3%; HR, 1.04), need for mechanical ventilation, ICU length of stay, or Sequential Organ Failure Assessment score at day 7.

Atrial fibrillation, however, was significantly more common in the high-target group than in the low-target group, at 6.7%, compared with 2.8%. This could be related to the high-target group receiving significantly higher doses of vasopressor catecholamines over a significantly longer time period, although other confounding factors cannot be ruled out, lead author Dr. Pierre Asfar of University Hospital of Angers (France), reported on behalf of SEPSISPAM investigators.

Among patients with chronic arterial hypertension, who comprised more than 40% of the study population, use of the high MAP target significantly reduced both the incidence of doubling of plasma creatinine (39% vs. 52%) and the rate of renal-replacement therapy (31.7% vs. 42.2%).

The authors noted that, although investigators were asked to treat patients to a MAP of 65-70 mm Hg in the low-target group, the observed pressures were for the most part between 70 and 75 mm Hg. The high-target group was likewise off goal, at a mean of 70 mm Hg. They also acknowledged that the lower-than-expected death rate, albeit in line with more recent trials, led to an underpowered study.

The French Ministry of Health funded the trial. Dr. Asfar reported lecture fees from LFB Biomedicaments.

pwendling@frontlinemedcom.com

SAN FRANCISCO – Cultivating mindfulness in patients with diabetes is a useful self-help strategy to combat depression and foster healthy habits.

"How can you effectively manage yourself if you’re not aware of your self?" posited Dr. Laura Young at the annual advanced postgraduate course held by the American Diabetes Association.

One in four patients living with diabetes will develop depression in their lifetime, with 80% relapsing within 5 years of their depression going into remission, she said. Comorbid diabetes and depression increase mortality 2.5-fold, as well as raising the risk of all diabetes complications.

Mindfulness-based interventions teach individuals to be in the present moment, without judgment or emotional reactivity. The benefits are thought to be improved clarity, awareness, and acceptance.

Mindfulness also helps to weaken old, unhelpful, and automatic thinking habits that can potentially prevent positive action. This is critical for patients with diabetes, particularly those with type 1, who tend to go into autopilot when managing their disease, said Dr. Young, with the University of North Carolina in Durham.

"So many of our patients just get into a pattern of ‘It’s just what I’ve always done,’ " she said. "Mindfulness can help patients take a step back, evaluate those habits, and decide which are helping and which are not so great, and potentially change those habits."

Dr. Young recalled a recent patient who each evening had a bedtime snack that was sometimes healthful, but more often, not. The patient could offer no concrete reason for this snacking habit and admitted that 75% of the time he wasn’t even hungry.

"It hadn’t even occurred to him that it was something he shouldn’t be doing because it was something he’d always done," she said.

Mindfulness-based interventions have been studied for decades and have some of the best, most robust evidence behind them among self-help strategies, Dr. Young observed. In the Heidelberger Diabetes and Stress Study, patients with type 2 diabetes randomized to a mindfulness-based intervention had lower levels of depression, psychosocial distress, and improved health status over 5 years of follow-up compared with treatment-as-usual controls (Diabetes Care 2012;35:945-7).

A recent study found a mindful-eating intervention was as effective as a diabetes education self-management "Smart Choices" intervention in significantly improving depressive symptoms, cognitive control, and disinhibition of control regarding eating habits in adults, aged 35-65 years, with type 2 diabetes not on insulin therapy. Weight control at 3 months was also similar with either group-based intervention (Health Educ. Behav. 2014 April;41:145-54)

Mindfulness interventions have been readily adopted in some areas, often combined with yoga or cognitive-behavioral therapy, but these could be a hard sell for those who envision sitting cross-legged on yoga mats in the lotus position.

"I have a lot of patients from rural North Carolina, and they aren’t going to buy into that," Dr. Young said.

For these patients, her university offers a 2.5-hour class in which patients simply sit in a circle on chairs while being guided through mindfulness exercises. An ongoing study at the university is comparing this approach with a health education control group on physiological and psychological outcomes in patients with type 2 diabetes and high levels of diabetes-related distress, she said.

A show of hands at the meeting revealed that about a third of the audience is already using mindfulness training in their patients with diabetes. Dr. Young pointed out that the meeting host city of San Francisco had 386 therapists who use a combination of cognitive-behavioral therapy and mindfulness, whereas 40 therapists are available in Mississippi, as are a handful in rural North Carolina.

"So your patients can do this," she added.

Dr. Young reported research support paid to her university from numerous pharmaceutical firms and the National Institutes of Health.

pwendling@frontlinemedcom.com

SAN FRANCISCO – Cultivating mindfulness in patients with diabetes is a useful self-help strategy to combat depression and foster healthy habits.

"How can you effectively manage yourself if you’re not aware of your self?" posited Dr. Laura Young at the annual advanced postgraduate course held by the American Diabetes Association.

One in four patients living with diabetes will develop depression in their lifetime, with 80% relapsing within 5 years of their depression going into remission, she said. Comorbid diabetes and depression increase mortality 2.5-fold, as well as raising the risk of all diabetes complications.

Mindfulness-based interventions teach individuals to be in the present moment, without judgment or emotional reactivity. The benefits are thought to be improved clarity, awareness, and acceptance.

Mindfulness also helps to weaken old, unhelpful, and automatic thinking habits that can potentially prevent positive action. This is critical for patients with diabetes, particularly those with type 1, who tend to go into autopilot when managing their disease, said Dr. Young, with the University of North Carolina in Durham.

"So many of our patients just get into a pattern of ‘It’s just what I’ve always done,’ " she said. "Mindfulness can help patients take a step back, evaluate those habits, and decide which are helping and which are not so great, and potentially change those habits."

Dr. Young recalled a recent patient who each evening had a bedtime snack that was sometimes healthful, but more often, not. The patient could offer no concrete reason for this snacking habit and admitted that 75% of the time he wasn’t even hungry.

"It hadn’t even occurred to him that it was something he shouldn’t be doing because it was something he’d always done," she said.

Mindfulness-based interventions have been studied for decades and have some of the best, most robust evidence behind them among self-help strategies, Dr. Young observed. In the Heidelberger Diabetes and Stress Study, patients with type 2 diabetes randomized to a mindfulness-based intervention had lower levels of depression, psychosocial distress, and improved health status over 5 years of follow-up compared with treatment-as-usual controls (Diabetes Care 2012;35:945-7).

A recent study found a mindful-eating intervention was as effective as a diabetes education self-management "Smart Choices" intervention in significantly improving depressive symptoms, cognitive control, and disinhibition of control regarding eating habits in adults, aged 35-65 years, with type 2 diabetes not on insulin therapy. Weight control at 3 months was also similar with either group-based intervention (Health Educ. Behav. 2014 April;41:145-54)

Mindfulness interventions have been readily adopted in some areas, often combined with yoga or cognitive-behavioral therapy, but these could be a hard sell for those who envision sitting cross-legged on yoga mats in the lotus position.

"I have a lot of patients from rural North Carolina, and they aren’t going to buy into that," Dr. Young said.

For these patients, her university offers a 2.5-hour class in which patients simply sit in a circle on chairs while being guided through mindfulness exercises. An ongoing study at the university is comparing this approach with a health education control group on physiological and psychological outcomes in patients with type 2 diabetes and high levels of diabetes-related distress, she said.

A show of hands at the meeting revealed that about a third of the audience is already using mindfulness training in their patients with diabetes. Dr. Young pointed out that the meeting host city of San Francisco had 386 therapists who use a combination of cognitive-behavioral therapy and mindfulness, whereas 40 therapists are available in Mississippi, as are a handful in rural North Carolina.

"So your patients can do this," she added.

Dr. Young reported research support paid to her university from numerous pharmaceutical firms and the National Institutes of Health.

pwendling@frontlinemedcom.com

SAN FRANCISCO – Cultivating mindfulness in patients with diabetes is a useful self-help strategy to combat depression and foster healthy habits.

"How can you effectively manage yourself if you’re not aware of your self?" posited Dr. Laura Young at the annual advanced postgraduate course held by the American Diabetes Association.

One in four patients living with diabetes will develop depression in their lifetime, with 80% relapsing within 5 years of their depression going into remission, she said. Comorbid diabetes and depression increase mortality 2.5-fold, as well as raising the risk of all diabetes complications.

Mindfulness-based interventions teach individuals to be in the present moment, without judgment or emotional reactivity. The benefits are thought to be improved clarity, awareness, and acceptance.

Mindfulness also helps to weaken old, unhelpful, and automatic thinking habits that can potentially prevent positive action. This is critical for patients with diabetes, particularly those with type 1, who tend to go into autopilot when managing their disease, said Dr. Young, with the University of North Carolina in Durham.

"So many of our patients just get into a pattern of ‘It’s just what I’ve always done,’ " she said. "Mindfulness can help patients take a step back, evaluate those habits, and decide which are helping and which are not so great, and potentially change those habits."

Dr. Young recalled a recent patient who each evening had a bedtime snack that was sometimes healthful, but more often, not. The patient could offer no concrete reason for this snacking habit and admitted that 75% of the time he wasn’t even hungry.

"It hadn’t even occurred to him that it was something he shouldn’t be doing because it was something he’d always done," she said.

Mindfulness-based interventions have been studied for decades and have some of the best, most robust evidence behind them among self-help strategies, Dr. Young observed. In the Heidelberger Diabetes and Stress Study, patients with type 2 diabetes randomized to a mindfulness-based intervention had lower levels of depression, psychosocial distress, and improved health status over 5 years of follow-up compared with treatment-as-usual controls (Diabetes Care 2012;35:945-7).

A recent study found a mindful-eating intervention was as effective as a diabetes education self-management "Smart Choices" intervention in significantly improving depressive symptoms, cognitive control, and disinhibition of control regarding eating habits in adults, aged 35-65 years, with type 2 diabetes not on insulin therapy. Weight control at 3 months was also similar with either group-based intervention (Health Educ. Behav. 2014 April;41:145-54)

Mindfulness interventions have been readily adopted in some areas, often combined with yoga or cognitive-behavioral therapy, but these could be a hard sell for those who envision sitting cross-legged on yoga mats in the lotus position.

"I have a lot of patients from rural North Carolina, and they aren’t going to buy into that," Dr. Young said.

For these patients, her university offers a 2.5-hour class in which patients simply sit in a circle on chairs while being guided through mindfulness exercises. An ongoing study at the university is comparing this approach with a health education control group on physiological and psychological outcomes in patients with type 2 diabetes and high levels of diabetes-related distress, she said.

A show of hands at the meeting revealed that about a third of the audience is already using mindfulness training in their patients with diabetes. Dr. Young pointed out that the meeting host city of San Francisco had 386 therapists who use a combination of cognitive-behavioral therapy and mindfulness, whereas 40 therapists are available in Mississippi, as are a handful in rural North Carolina.

"So your patients can do this," she added.

Dr. Young reported research support paid to her university from numerous pharmaceutical firms and the National Institutes of Health.

pwendling@frontlinemedcom.com

SAN FRANCISCO – Cultivating mindfulness in patients with diabetes is a useful self-help strategy to combat depression and foster healthy habits.

"How can you effectively manage yourself if you’re not aware of your self?" posited Dr. Laura Young at the annual advanced postgraduate course held by the American Diabetes Association.

One in four patients living with diabetes will develop depression in their lifetime, with 80% relapsing within 5 years of their depression going into remission, she said. Comorbid diabetes and depression increase mortality 2.5-fold, as well as raising the risk of all diabetes complications.

Mindfulness-based interventions teach individuals to be in the present moment, without judgment or emotional reactivity. The benefits are thought to be improved clarity, awareness, and acceptance.

Mindfulness also helps to weaken old, unhelpful, and automatic thinking habits that can potentially prevent positive action. This is critical for patients with diabetes, particularly those with type 1, who tend to go into autopilot when managing their disease, said Dr. Young, with the University of North Carolina in Durham.

"So many of our patients just get into a pattern of ‘It’s just what I’ve always done,’ " she said. "Mindfulness can help patients take a step back, evaluate those habits, and decide which are helping and which are not so great, and potentially change those habits."

Dr. Young recalled a recent patient who each evening had a bedtime snack that was sometimes healthful, but more often, not. The patient could offer no concrete reason for this snacking habit and admitted that 75% of the time he wasn’t even hungry.

"It hadn’t even occurred to him that it was something he shouldn’t be doing because it was something he’d always done," she said.

Mindfulness-based interventions have been studied for decades and have some of the best, most robust evidence behind them among self-help strategies, Dr. Young observed. In the Heidelberger Diabetes and Stress Study, patients with type 2 diabetes randomized to a mindfulness-based intervention had lower levels of depression, psychosocial distress, and improved health status over 5 years of follow-up compared with treatment-as-usual controls (Diabetes Care 2012;35:945-7).

A recent study found a mindful-eating intervention was as effective as a diabetes education self-management "Smart Choices" intervention in significantly improving depressive symptoms, cognitive control, and disinhibition of control regarding eating habits in adults, aged 35-65 years, with type 2 diabetes not on insulin therapy. Weight control at 3 months was also similar with either group-based intervention (Health Educ. Behav. 2014 April;41:145-54)

Mindfulness interventions have been readily adopted in some areas, often combined with yoga or cognitive-behavioral therapy, but these could be a hard sell for those who envision sitting cross-legged on yoga mats in the lotus position.

"I have a lot of patients from rural North Carolina, and they aren’t going to buy into that," Dr. Young said.

For these patients, her university offers a 2.5-hour class in which patients simply sit in a circle on chairs while being guided through mindfulness exercises. An ongoing study at the university is comparing this approach with a health education control group on physiological and psychological outcomes in patients with type 2 diabetes and high levels of diabetes-related distress, she said.

A show of hands at the meeting revealed that about a third of the audience is already using mindfulness training in their patients with diabetes. Dr. Young pointed out that the meeting host city of San Francisco had 386 therapists who use a combination of cognitive-behavioral therapy and mindfulness, whereas 40 therapists are available in Mississippi, as are a handful in rural North Carolina.

"So your patients can do this," she added.

Dr. Young reported research support paid to her university from numerous pharmaceutical firms and the National Institutes of Health.

pwendling@frontlinemedcom.com

SAN FRANCISCO – Cultivating mindfulness in patients with diabetes is a useful self-help strategy to combat depression and foster healthy habits.

"How can you effectively manage yourself if you’re not aware of your self?" posited Dr. Laura Young at the annual advanced postgraduate course held by the American Diabetes Association.

One in four patients living with diabetes will develop depression in their lifetime, with 80% relapsing within 5 years of their depression going into remission, she said. Comorbid diabetes and depression increase mortality 2.5-fold, as well as raising the risk of all diabetes complications.

Mindfulness-based interventions teach individuals to be in the present moment, without judgment or emotional reactivity. The benefits are thought to be improved clarity, awareness, and acceptance.

Mindfulness also helps to weaken old, unhelpful, and automatic thinking habits that can potentially prevent positive action. This is critical for patients with diabetes, particularly those with type 1, who tend to go into autopilot when managing their disease, said Dr. Young, with the University of North Carolina in Durham.

"So many of our patients just get into a pattern of ‘It’s just what I’ve always done,’ " she said. "Mindfulness can help patients take a step back, evaluate those habits, and decide which are helping and which are not so great, and potentially change those habits."

Dr. Young recalled a recent patient who each evening had a bedtime snack that was sometimes healthful, but more often, not. The patient could offer no concrete reason for this snacking habit and admitted that 75% of the time he wasn’t even hungry.

"It hadn’t even occurred to him that it was something he shouldn’t be doing because it was something he’d always done," she said.

Mindfulness-based interventions have been studied for decades and have some of the best, most robust evidence behind them among self-help strategies, Dr. Young observed. In the Heidelberger Diabetes and Stress Study, patients with type 2 diabetes randomized to a mindfulness-based intervention had lower levels of depression, psychosocial distress, and improved health status over 5 years of follow-up compared with treatment-as-usual controls (Diabetes Care 2012;35:945-7).

A recent study found a mindful-eating intervention was as effective as a diabetes education self-management "Smart Choices" intervention in significantly improving depressive symptoms, cognitive control, and disinhibition of control regarding eating habits in adults, aged 35-65 years, with type 2 diabetes not on insulin therapy. Weight control at 3 months was also similar with either group-based intervention (Health Educ. Behav. 2014 April;41:145-54)

Mindfulness interventions have been readily adopted in some areas, often combined with yoga or cognitive-behavioral therapy, but these could be a hard sell for those who envision sitting cross-legged on yoga mats in the lotus position.

"I have a lot of patients from rural North Carolina, and they aren’t going to buy into that," Dr. Young said.

For these patients, her university offers a 2.5-hour class in which patients simply sit in a circle on chairs while being guided through mindfulness exercises. An ongoing study at the university is comparing this approach with a health education control group on physiological and psychological outcomes in patients with type 2 diabetes and high levels of diabetes-related distress, she said.

A show of hands at the meeting revealed that about a third of the audience is already using mindfulness training in their patients with diabetes. Dr. Young pointed out that the meeting host city of San Francisco had 386 therapists who use a combination of cognitive-behavioral therapy and mindfulness, whereas 40 therapists are available in Mississippi, as are a handful in rural North Carolina.

"So your patients can do this," she added.

Dr. Young reported research support paid to her university from numerous pharmaceutical firms and the National Institutes of Health.

pwendling@frontlinemedcom.com

SAN FRANCISCO – Cultivating mindfulness in patients with diabetes is a useful self-help strategy to combat depression and foster healthy habits.

"How can you effectively manage yourself if you’re not aware of your self?" posited Dr. Laura Young at the annual advanced postgraduate course held by the American Diabetes Association.

One in four patients living with diabetes will develop depression in their lifetime, with 80% relapsing within 5 years of their depression going into remission, she said. Comorbid diabetes and depression increase mortality 2.5-fold, as well as raising the risk of all diabetes complications.

Mindfulness-based interventions teach individuals to be in the present moment, without judgment or emotional reactivity. The benefits are thought to be improved clarity, awareness, and acceptance.

Mindfulness also helps to weaken old, unhelpful, and automatic thinking habits that can potentially prevent positive action. This is critical for patients with diabetes, particularly those with type 1, who tend to go into autopilot when managing their disease, said Dr. Young, with the University of North Carolina in Durham.

"So many of our patients just get into a pattern of ‘It’s just what I’ve always done,’ " she said. "Mindfulness can help patients take a step back, evaluate those habits, and decide which are helping and which are not so great, and potentially change those habits."

Dr. Young recalled a recent patient who each evening had a bedtime snack that was sometimes healthful, but more often, not. The patient could offer no concrete reason for this snacking habit and admitted that 75% of the time he wasn’t even hungry.

"It hadn’t even occurred to him that it was something he shouldn’t be doing because it was something he’d always done," she said.

Mindfulness-based interventions have been studied for decades and have some of the best, most robust evidence behind them among self-help strategies, Dr. Young observed. In the Heidelberger Diabetes and Stress Study, patients with type 2 diabetes randomized to a mindfulness-based intervention had lower levels of depression, psychosocial distress, and improved health status over 5 years of follow-up compared with treatment-as-usual controls (Diabetes Care 2012;35:945-7).

A recent study found a mindful-eating intervention was as effective as a diabetes education self-management "Smart Choices" intervention in significantly improving depressive symptoms, cognitive control, and disinhibition of control regarding eating habits in adults, aged 35-65 years, with type 2 diabetes not on insulin therapy. Weight control at 3 months was also similar with either group-based intervention (Health Educ. Behav. 2014 April;41:145-54)

Mindfulness interventions have been readily adopted in some areas, often combined with yoga or cognitive-behavioral therapy, but these could be a hard sell for those who envision sitting cross-legged on yoga mats in the lotus position.

"I have a lot of patients from rural North Carolina, and they aren’t going to buy into that," Dr. Young said.

For these patients, her university offers a 2.5-hour class in which patients simply sit in a circle on chairs while being guided through mindfulness exercises. An ongoing study at the university is comparing this approach with a health education control group on physiological and psychological outcomes in patients with type 2 diabetes and high levels of diabetes-related distress, she said.

A show of hands at the meeting revealed that about a third of the audience is already using mindfulness training in their patients with diabetes. Dr. Young pointed out that the meeting host city of San Francisco had 386 therapists who use a combination of cognitive-behavioral therapy and mindfulness, whereas 40 therapists are available in Mississippi, as are a handful in rural North Carolina.

"So your patients can do this," she added.

Dr. Young reported research support paid to her university from numerous pharmaceutical firms and the National Institutes of Health.

pwendling@frontlinemedcom.com

U.S. surveillance data show that half of high-grade cervical lesions are caused by human papillomavirus 16 and 18.

Another 25% are attributable to the five additional HPV types 31/33/45/52/58 included in the investigational 9-valent vaccine.

National Cancer Institute

The analysis fills in some knowledge gaps regarding U.S. women and was based on 5,189 specimens drawn from women, aged 21-39 years, diagnosed with cervical intraepithelial neoplasia (CIN) 2 and 3 and adenocarcinoma in situ (AIS) (CIN2+) from 2008 through 2011 at five U.S. sites in the HPV-IMPACT sentinel surveillance project.

HPV 16 was the most commonly detected type among all lesions, while type 18 was relatively uncommon, accounting for only about 5% of lesions, Dr. Susan Hariri said at a meeting of the Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on Immunization Practices (ACIP).

HPV 16 and 18 increased with lesion severity from 40% in CIN2 to 66% in CIN3/AIS.

Type 31 was the most common of the five additional HPV types in the 9-valent vaccine, followed by types 52 and 58, both of which are more frequent in CIN2 than CIN3. Types 33 and 45 were detected in less than 5% of specimens across all histologic types.

The most common other high-risk, oncogenic types not found in any vaccine were 35 and 51, identified in 7% and 9% of CIN2 lesions, said Dr. Hariri of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention.

American Nurses Association representative Carol Hayes, M.P.H., a certified nurse-midwife, questioned this finding and asked why types 33 and 45 were included in the 9-valent vaccine, but 35 and 51 were not.

A representative from Merck responded that the five additional types in the 9-valent vaccine were selected based on their attribution to cervical cancer lesions, not precancers.

Proportional type attribution data analyses by race and age revealed HPV 16 and 18 were most common across all age and racial/ethnic groups, although some differences were identified. Types 16 and 18 declined from 50% for all groups to about 44% among the oldest age group (55-99 years), where the five additional HPV vaccine types were on the rise.

Types 31/33/45/52/58 were more common in racial and ethnic groups (28%-32%) than in whites (22%), while other high-risk HPV types were more common in blacks (20%) than other racial groups (14%-16%).

"The reasons for these differences are not clear and are probably multifactorial, but may be due to differences in the underlying prevalence of HPV in the subpopulations or to differences in screening and treatment," Dr. Hariri said.

Dr. Alain Luxembourg of Merck, the vaccine developer, said the 9-valent vaccine has the potential not only to prevent cancer, but to prevent a lot of "precancerous lesions, which in countries with cervical cancer screening programs, means a lower need for invasive procedures."

He presented a summary of 9-valent clinical data including the pivotal efficacy trial among females, aged 16-26 years, which showed noninferior immunogenicity for HPV 16 and 18 compared with the quadrivalent vaccine, and about 97% protection against disease related to the five additional strains. An immunobridging study also showed noninferior immunogenicity in adolescents compared with adults.

Regulatory action is expected by the Food and Drug Administration on the 9-valent vaccine within the next 3 months, he said.

ACIP is not expected to vote on whether to recommend the 9-valent vaccine until February 2015 at the earliest, following further review of clinical and health economics data and regulatory approval, said Dr. Lauri Markowitz of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention.

Considerations for the candidate vaccine include routine vaccination at age 11 or 12 years, vaccination of older females and males who were not vaccinated at the recommended age, vaccination of persons fully or partially vaccinated with quadrivalent vaccine, and the timing for consideration of males, aged 16-26 years, because it’s anticipated that the vaccine will not be licensed in this age group at the time of first licensure.

ACIP’s HPV work group also plans to review reduced-dose vaccination schedules in more detail. Some jurisdictions are already using two-dose schedules in their national or provincial immunization programs, and GlaxoSmithKline’s Cervarix received European marketing approval in December 2013 as a two-dose schedule (0, 6 months) for girls aged 9-14 years, Dr. Markowitz said.

As ACIP members met, Sanofi Pasteur announced that its quadrivalent HPV vaccine, Gardasil, was one step closer to receiving European approval for a two-dose schedule (0, 6 months) in girls and boys aged 9-13 years.

Finally, ACIP’s members unanimously affirmed efforts to update its 2007 HPV vaccine statement. The new statement, which still needs to go through editing before a final vote, consolidates and clarifies existing recommendations and updates background and clinical trial data. It also adds a variety of new sections including postlicensure safety data, areas of ongoing research, and future priorities, including the 9-valent vaccine and reduced-dose schedules, she said.

Dr. Hariri and Dr. Markowitz reported having no financial disclosures. Dr. Luxembourg is an employee of Merck.

pwendling@frontlinemedcom.com

U.S. surveillance data show that half of high-grade cervical lesions are caused by human papillomavirus 16 and 18.

Another 25% are attributable to the five additional HPV types 31/33/45/52/58 included in the investigational 9-valent vaccine.

National Cancer Institute

The analysis fills in some knowledge gaps regarding U.S. women and was based on 5,189 specimens drawn from women, aged 21-39 years, diagnosed with cervical intraepithelial neoplasia (CIN) 2 and 3 and adenocarcinoma in situ (AIS) (CIN2+) from 2008 through 2011 at five U.S. sites in the HPV-IMPACT sentinel surveillance project.

HPV 16 was the most commonly detected type among all lesions, while type 18 was relatively uncommon, accounting for only about 5% of lesions, Dr. Susan Hariri said at a meeting of the Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on Immunization Practices (ACIP).

HPV 16 and 18 increased with lesion severity from 40% in CIN2 to 66% in CIN3/AIS.

Type 31 was the most common of the five additional HPV types in the 9-valent vaccine, followed by types 52 and 58, both of which are more frequent in CIN2 than CIN3. Types 33 and 45 were detected in less than 5% of specimens across all histologic types.

The most common other high-risk, oncogenic types not found in any vaccine were 35 and 51, identified in 7% and 9% of CIN2 lesions, said Dr. Hariri of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention.

American Nurses Association representative Carol Hayes, M.P.H., a certified nurse-midwife, questioned this finding and asked why types 33 and 45 were included in the 9-valent vaccine, but 35 and 51 were not.

A representative from Merck responded that the five additional types in the 9-valent vaccine were selected based on their attribution to cervical cancer lesions, not precancers.

Proportional type attribution data analyses by race and age revealed HPV 16 and 18 were most common across all age and racial/ethnic groups, although some differences were identified. Types 16 and 18 declined from 50% for all groups to about 44% among the oldest age group (55-99 years), where the five additional HPV vaccine types were on the rise.

Types 31/33/45/52/58 were more common in racial and ethnic groups (28%-32%) than in whites (22%), while other high-risk HPV types were more common in blacks (20%) than other racial groups (14%-16%).

"The reasons for these differences are not clear and are probably multifactorial, but may be due to differences in the underlying prevalence of HPV in the subpopulations or to differences in screening and treatment," Dr. Hariri said.

Dr. Alain Luxembourg of Merck, the vaccine developer, said the 9-valent vaccine has the potential not only to prevent cancer, but to prevent a lot of "precancerous lesions, which in countries with cervical cancer screening programs, means a lower need for invasive procedures."

He presented a summary of 9-valent clinical data including the pivotal efficacy trial among females, aged 16-26 years, which showed noninferior immunogenicity for HPV 16 and 18 compared with the quadrivalent vaccine, and about 97% protection against disease related to the five additional strains. An immunobridging study also showed noninferior immunogenicity in adolescents compared with adults.

Regulatory action is expected by the Food and Drug Administration on the 9-valent vaccine within the next 3 months, he said.

ACIP is not expected to vote on whether to recommend the 9-valent vaccine until February 2015 at the earliest, following further review of clinical and health economics data and regulatory approval, said Dr. Lauri Markowitz of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention.

Considerations for the candidate vaccine include routine vaccination at age 11 or 12 years, vaccination of older females and males who were not vaccinated at the recommended age, vaccination of persons fully or partially vaccinated with quadrivalent vaccine, and the timing for consideration of males, aged 16-26 years, because it’s anticipated that the vaccine will not be licensed in this age group at the time of first licensure.

ACIP’s HPV work group also plans to review reduced-dose vaccination schedules in more detail. Some jurisdictions are already using two-dose schedules in their national or provincial immunization programs, and GlaxoSmithKline’s Cervarix received European marketing approval in December 2013 as a two-dose schedule (0, 6 months) for girls aged 9-14 years, Dr. Markowitz said.

As ACIP members met, Sanofi Pasteur announced that its quadrivalent HPV vaccine, Gardasil, was one step closer to receiving European approval for a two-dose schedule (0, 6 months) in girls and boys aged 9-13 years.

Finally, ACIP’s members unanimously affirmed efforts to update its 2007 HPV vaccine statement. The new statement, which still needs to go through editing before a final vote, consolidates and clarifies existing recommendations and updates background and clinical trial data. It also adds a variety of new sections including postlicensure safety data, areas of ongoing research, and future priorities, including the 9-valent vaccine and reduced-dose schedules, she said.

Dr. Hariri and Dr. Markowitz reported having no financial disclosures. Dr. Luxembourg is an employee of Merck.

pwendling@frontlinemedcom.com

U.S. surveillance data show that half of high-grade cervical lesions are caused by human papillomavirus 16 and 18.

Another 25% are attributable to the five additional HPV types 31/33/45/52/58 included in the investigational 9-valent vaccine.

National Cancer Institute

The analysis fills in some knowledge gaps regarding U.S. women and was based on 5,189 specimens drawn from women, aged 21-39 years, diagnosed with cervical intraepithelial neoplasia (CIN) 2 and 3 and adenocarcinoma in situ (AIS) (CIN2+) from 2008 through 2011 at five U.S. sites in the HPV-IMPACT sentinel surveillance project.

HPV 16 was the most commonly detected type among all lesions, while type 18 was relatively uncommon, accounting for only about 5% of lesions, Dr. Susan Hariri said at a meeting of the Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on Immunization Practices (ACIP).

HPV 16 and 18 increased with lesion severity from 40% in CIN2 to 66% in CIN3/AIS.

Type 31 was the most common of the five additional HPV types in the 9-valent vaccine, followed by types 52 and 58, both of which are more frequent in CIN2 than CIN3. Types 33 and 45 were detected in less than 5% of specimens across all histologic types.

The most common other high-risk, oncogenic types not found in any vaccine were 35 and 51, identified in 7% and 9% of CIN2 lesions, said Dr. Hariri of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention.

American Nurses Association representative Carol Hayes, M.P.H., a certified nurse-midwife, questioned this finding and asked why types 33 and 45 were included in the 9-valent vaccine, but 35 and 51 were not.

A representative from Merck responded that the five additional types in the 9-valent vaccine were selected based on their attribution to cervical cancer lesions, not precancers.

Proportional type attribution data analyses by race and age revealed HPV 16 and 18 were most common across all age and racial/ethnic groups, although some differences were identified. Types 16 and 18 declined from 50% for all groups to about 44% among the oldest age group (55-99 years), where the five additional HPV vaccine types were on the rise.

Types 31/33/45/52/58 were more common in racial and ethnic groups (28%-32%) than in whites (22%), while other high-risk HPV types were more common in blacks (20%) than other racial groups (14%-16%).

"The reasons for these differences are not clear and are probably multifactorial, but may be due to differences in the underlying prevalence of HPV in the subpopulations or to differences in screening and treatment," Dr. Hariri said.

Dr. Alain Luxembourg of Merck, the vaccine developer, said the 9-valent vaccine has the potential not only to prevent cancer, but to prevent a lot of "precancerous lesions, which in countries with cervical cancer screening programs, means a lower need for invasive procedures."

He presented a summary of 9-valent clinical data including the pivotal efficacy trial among females, aged 16-26 years, which showed noninferior immunogenicity for HPV 16 and 18 compared with the quadrivalent vaccine, and about 97% protection against disease related to the five additional strains. An immunobridging study also showed noninferior immunogenicity in adolescents compared with adults.

Regulatory action is expected by the Food and Drug Administration on the 9-valent vaccine within the next 3 months, he said.

ACIP is not expected to vote on whether to recommend the 9-valent vaccine until February 2015 at the earliest, following further review of clinical and health economics data and regulatory approval, said Dr. Lauri Markowitz of the CDC’s National Center for HIV, Viral Hepatitis, STD, and TB Prevention.

Considerations for the candidate vaccine include routine vaccination at age 11 or 12 years, vaccination of older females and males who were not vaccinated at the recommended age, vaccination of persons fully or partially vaccinated with quadrivalent vaccine, and the timing for consideration of males, aged 16-26 years, because it’s anticipated that the vaccine will not be licensed in this age group at the time of first licensure.

ACIP’s HPV work group also plans to review reduced-dose vaccination schedules in more detail. Some jurisdictions are already using two-dose schedules in their national or provincial immunization programs, and GlaxoSmithKline’s Cervarix received European marketing approval in December 2013 as a two-dose schedule (0, 6 months) for girls aged 9-14 years, Dr. Markowitz said.

As ACIP members met, Sanofi Pasteur announced that its quadrivalent HPV vaccine, Gardasil, was one step closer to receiving European approval for a two-dose schedule (0, 6 months) in girls and boys aged 9-13 years.

Finally, ACIP’s members unanimously affirmed efforts to update its 2007 HPV vaccine statement. The new statement, which still needs to go through editing before a final vote, consolidates and clarifies existing recommendations and updates background and clinical trial data. It also adds a variety of new sections including postlicensure safety data, areas of ongoing research, and future priorities, including the 9-valent vaccine and reduced-dose schedules, she said.

Dr. Hariri and Dr. Markowitz reported having no financial disclosures. Dr. Luxembourg is an employee of Merck.

pwendling@frontlinemedcom.com

C-reactive protein levels can serve as a reliable indicator for severe cytokine release syndrome in patients receiving chimeric antigen receptor T-cell therapy, according to additional analyses from a phase I trial.

"We have found that daily monitoring of CRP [C-reactive protein] in combination with simple clinical parameters allows us to identify patients in need of intensive medical monitoring and potentially pharmacologic management," reported Dr. Marco Davila in Science Translational Medicine.

The observations were based on analysis of clinical data and serum cytokine levels over the first 21 days after infusing CD19-targeted 19-28z chimeric antigen receptor (CAR) T cells into 16 patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) (Sci. Transl. Med. 2014;6:1-9).

CAR therapy has demonstrated activity against several treatment-refractory leukemias, but in some patients has induced cytokine release syndrome (CRS), a clinical syndrome of fevers, hypotension, hypoxia, and neurologic changes including seizures.

Patients with CRS typically have fevers that start about 24 hours after infusion with 19-28z CAR T cells and can persist for several days. These fevers, however, aren’t always the harbinger for more clinically relevant toxicities, and premature intervention to curb the CRS can diminish T-cell persistence or efficacy, explained Dr. Davila of Memorial Sloan-Kettering Cancer Center in New York.

In an effort to distinguish between patients whose fevers would spontaneously resolve and those with clinically meaningful or severe CRS, the investigators retrospectively analyzed cytokine increases in serum samples from all 16 patients on the phase I trial. Of the 39 cytokines screened, 7 inflammatory cytokines correlated with pretreatment tumor burden and severe CRS. They are interferon-gamma, interleukin-5, IL-6, IL-10, Flt-3L, granulocyte-macrophage colony-stimulating factor, and fractalkine.

In addition, patients requiring intensive medical intervention had a 75-fold increase over pretreatment baseline levels in two of the seven cytokines, and universally exhibited at least one clinical sign of toxicity such as hypotension, hypoxia, or neurologic disorders.

"Thus, on the basis of the combined clinical and cytokine data, we could accurately define a severe CRS in those patients with the triad of persistent fevers (38° C) for more than 3 days, selected cytokine elevations, and additional clinical evidence of toxicity," Dr. Davila reported.

CRP as a surrogate

Cytokine monitoring, however, is unlikely to be performed daily because of cost and time constraints. CRP was selected as a surrogate for cytokine elevation based on the well-known association between CRP levels and IL-6 and the clinical amelioration of severe CRS afforded by IL-6 receptor blockade.

"We observed a clear difference between the CRP levels of patients with a severe CRS vs. patients classified as having either mild or no CRS," he noted.

Only those patients who met the criteria for severe CRS had a CRP level of 20 mg/dL or more. Patients whose CRP exceeded this threshold were at particularly high risk for CRS (sensitivity, 86%; specificity, 100%).

"CRP, a routinely available lab test, can serve as a surrogate for predicting development of the CRS," coauthor and colleague Dr. Renier J. Brentjens said in an interview. "This allows for sensitive day-to-day assessment of cytokine release in treated patients, which will allow for better management of CRS in CAR T-cell-treated patients," said Dr. Brentjens, director of cellular therapeutics at Memorial Sloan-Kettering Cancer Center.

Dr. David L. Porter, director of blood and marrow transplantation at the University of Pennsylvania Hospital, Philadelphia, said they too have found that CRP tracks with severity of CRS. However, at least at this point, while it may help predict which patients have a more severe reaction, it does not allow for early or different intervention.

"It remains completely unknown whether early intervention for CRS will inhibit the T-cell activity," he said in an interview. "We have developed a grading system for CRS that was designed to help determine when patients require intervention for CRS based on clinical criteria rather than laboratory values. But ultimately, if CRP or other measurements predict when intervention is appropriate, this will be a very useful assay."

CRS intervention

Treating severe CRS with high-dose steroids resulted in rapid reversal of fevers, cytokines, and other clinical symptoms, but abrogated T-cell expansion and persistence, whereas IL-6 receptor blockade with tocilizumab (Actemra) did not, Dr. Avila reported. Indeed, two patients demonstrated an almost 7,000-fold expansion after first-line tocilizumab.

In addition, the manner of treating severe CRS may affect clinical outcomes. All three patients treated with high-dose steroids relapsed despite previously achieving a complete molecular remission whereas untreated patients or those treated with tocilizumab alone had no evidence of recurrent disease after achieving a complete molecular remission.

Efficacy

The complete response rate in the study was 88%, with 12 of these 14 patients further classified as having minimal residual disease. Seven (44%) patients were successfully bridged to allogeneic stem cell transplantation. This is "especially meaningful" when compared with the historic low of just 5% of relapsed/refractory adult B-ALL patients transitioning to transplant after salvage chemotherapy, Dr. Davila noted.

Still, the persistence of the 19-28z CAR T cells was about 3 months, compared with several months to even more than one year in at least one B-ALL patient and several CLL patients reported by the University of Pennsylvania researchers. Dr. Davila and his colleagues hypothesize that the longer persistence of CD19-targeted CARs incorporating a 4-1BB moiety, rather than CD28, may be due, in part, to antigen-independent signaling through the 4-1BB CAR, as previously shown in preclinical studies. They are also currently developing a human anti-mouse antibody assay to determine whether immune-mediated rejection might be a contributing factor to the limited persistence of the 19-28z CAR T cells.

Dr. Porter said it’s not known why their T cells persist longer, but agreed it may have to do with the novel signal domain of their CAR (4-1BB). "This may be important for high levels of expansion, but may also provide a survival signal to the T cells allowing for longer persistence," he said.

The study was supported by MSKCC. Dr. Davila reported having no financial disclosures. Dr. Brentjens holds a patent that covers the 19-28z receptor and is a cofounder of Juno Therapeutics, which holds the license.

pwendling@frontlinemedcom.com

C-reactive protein levels can serve as a reliable indicator for severe cytokine release syndrome in patients receiving chimeric antigen receptor T-cell therapy, according to additional analyses from a phase I trial.

"We have found that daily monitoring of CRP [C-reactive protein] in combination with simple clinical parameters allows us to identify patients in need of intensive medical monitoring and potentially pharmacologic management," reported Dr. Marco Davila in Science Translational Medicine.

The observations were based on analysis of clinical data and serum cytokine levels over the first 21 days after infusing CD19-targeted 19-28z chimeric antigen receptor (CAR) T cells into 16 patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) (Sci. Transl. Med. 2014;6:1-9).

CAR therapy has demonstrated activity against several treatment-refractory leukemias, but in some patients has induced cytokine release syndrome (CRS), a clinical syndrome of fevers, hypotension, hypoxia, and neurologic changes including seizures.

Patients with CRS typically have fevers that start about 24 hours after infusion with 19-28z CAR T cells and can persist for several days. These fevers, however, aren’t always the harbinger for more clinically relevant toxicities, and premature intervention to curb the CRS can diminish T-cell persistence or efficacy, explained Dr. Davila of Memorial Sloan-Kettering Cancer Center in New York.

In an effort to distinguish between patients whose fevers would spontaneously resolve and those with clinically meaningful or severe CRS, the investigators retrospectively analyzed cytokine increases in serum samples from all 16 patients on the phase I trial. Of the 39 cytokines screened, 7 inflammatory cytokines correlated with pretreatment tumor burden and severe CRS. They are interferon-gamma, interleukin-5, IL-6, IL-10, Flt-3L, granulocyte-macrophage colony-stimulating factor, and fractalkine.

In addition, patients requiring intensive medical intervention had a 75-fold increase over pretreatment baseline levels in two of the seven cytokines, and universally exhibited at least one clinical sign of toxicity such as hypotension, hypoxia, or neurologic disorders.

"Thus, on the basis of the combined clinical and cytokine data, we could accurately define a severe CRS in those patients with the triad of persistent fevers (38° C) for more than 3 days, selected cytokine elevations, and additional clinical evidence of toxicity," Dr. Davila reported.

CRP as a surrogate

Cytokine monitoring, however, is unlikely to be performed daily because of cost and time constraints. CRP was selected as a surrogate for cytokine elevation based on the well-known association between CRP levels and IL-6 and the clinical amelioration of severe CRS afforded by IL-6 receptor blockade.

"We observed a clear difference between the CRP levels of patients with a severe CRS vs. patients classified as having either mild or no CRS," he noted.

Only those patients who met the criteria for severe CRS had a CRP level of 20 mg/dL or more. Patients whose CRP exceeded this threshold were at particularly high risk for CRS (sensitivity, 86%; specificity, 100%).

"CRP, a routinely available lab test, can serve as a surrogate for predicting development of the CRS," coauthor and colleague Dr. Renier J. Brentjens said in an interview. "This allows for sensitive day-to-day assessment of cytokine release in treated patients, which will allow for better management of CRS in CAR T-cell-treated patients," said Dr. Brentjens, director of cellular therapeutics at Memorial Sloan-Kettering Cancer Center.

Dr. David L. Porter, director of blood and marrow transplantation at the University of Pennsylvania Hospital, Philadelphia, said they too have found that CRP tracks with severity of CRS. However, at least at this point, while it may help predict which patients have a more severe reaction, it does not allow for early or different intervention.

"It remains completely unknown whether early intervention for CRS will inhibit the T-cell activity," he said in an interview. "We have developed a grading system for CRS that was designed to help determine when patients require intervention for CRS based on clinical criteria rather than laboratory values. But ultimately, if CRP or other measurements predict when intervention is appropriate, this will be a very useful assay."

CRS intervention

Treating severe CRS with high-dose steroids resulted in rapid reversal of fevers, cytokines, and other clinical symptoms, but abrogated T-cell expansion and persistence, whereas IL-6 receptor blockade with tocilizumab (Actemra) did not, Dr. Avila reported. Indeed, two patients demonstrated an almost 7,000-fold expansion after first-line tocilizumab.

In addition, the manner of treating severe CRS may affect clinical outcomes. All three patients treated with high-dose steroids relapsed despite previously achieving a complete molecular remission whereas untreated patients or those treated with tocilizumab alone had no evidence of recurrent disease after achieving a complete molecular remission.

Efficacy

The complete response rate in the study was 88%, with 12 of these 14 patients further classified as having minimal residual disease. Seven (44%) patients were successfully bridged to allogeneic stem cell transplantation. This is "especially meaningful" when compared with the historic low of just 5% of relapsed/refractory adult B-ALL patients transitioning to transplant after salvage chemotherapy, Dr. Davila noted.

Still, the persistence of the 19-28z CAR T cells was about 3 months, compared with several months to even more than one year in at least one B-ALL patient and several CLL patients reported by the University of Pennsylvania researchers. Dr. Davila and his colleagues hypothesize that the longer persistence of CD19-targeted CARs incorporating a 4-1BB moiety, rather than CD28, may be due, in part, to antigen-independent signaling through the 4-1BB CAR, as previously shown in preclinical studies. They are also currently developing a human anti-mouse antibody assay to determine whether immune-mediated rejection might be a contributing factor to the limited persistence of the 19-28z CAR T cells.

Dr. Porter said it’s not known why their T cells persist longer, but agreed it may have to do with the novel signal domain of their CAR (4-1BB). "This may be important for high levels of expansion, but may also provide a survival signal to the T cells allowing for longer persistence," he said.

The study was supported by MSKCC. Dr. Davila reported having no financial disclosures. Dr. Brentjens holds a patent that covers the 19-28z receptor and is a cofounder of Juno Therapeutics, which holds the license.

pwendling@frontlinemedcom.com

C-reactive protein levels can serve as a reliable indicator for severe cytokine release syndrome in patients receiving chimeric antigen receptor T-cell therapy, according to additional analyses from a phase I trial.

"We have found that daily monitoring of CRP [C-reactive protein] in combination with simple clinical parameters allows us to identify patients in need of intensive medical monitoring and potentially pharmacologic management," reported Dr. Marco Davila in Science Translational Medicine.

The observations were based on analysis of clinical data and serum cytokine levels over the first 21 days after infusing CD19-targeted 19-28z chimeric antigen receptor (CAR) T cells into 16 patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) (Sci. Transl. Med. 2014;6:1-9).

CAR therapy has demonstrated activity against several treatment-refractory leukemias, but in some patients has induced cytokine release syndrome (CRS), a clinical syndrome of fevers, hypotension, hypoxia, and neurologic changes including seizures.

Patients with CRS typically have fevers that start about 24 hours after infusion with 19-28z CAR T cells and can persist for several days. These fevers, however, aren’t always the harbinger for more clinically relevant toxicities, and premature intervention to curb the CRS can diminish T-cell persistence or efficacy, explained Dr. Davila of Memorial Sloan-Kettering Cancer Center in New York.

In an effort to distinguish between patients whose fevers would spontaneously resolve and those with clinically meaningful or severe CRS, the investigators retrospectively analyzed cytokine increases in serum samples from all 16 patients on the phase I trial. Of the 39 cytokines screened, 7 inflammatory cytokines correlated with pretreatment tumor burden and severe CRS. They are interferon-gamma, interleukin-5, IL-6, IL-10, Flt-3L, granulocyte-macrophage colony-stimulating factor, and fractalkine.

In addition, patients requiring intensive medical intervention had a 75-fold increase over pretreatment baseline levels in two of the seven cytokines, and universally exhibited at least one clinical sign of toxicity such as hypotension, hypoxia, or neurologic disorders.

"Thus, on the basis of the combined clinical and cytokine data, we could accurately define a severe CRS in those patients with the triad of persistent fevers (38° C) for more than 3 days, selected cytokine elevations, and additional clinical evidence of toxicity," Dr. Davila reported.

CRP as a surrogate

Cytokine monitoring, however, is unlikely to be performed daily because of cost and time constraints. CRP was selected as a surrogate for cytokine elevation based on the well-known association between CRP levels and IL-6 and the clinical amelioration of severe CRS afforded by IL-6 receptor blockade.

"We observed a clear difference between the CRP levels of patients with a severe CRS vs. patients classified as having either mild or no CRS," he noted.

Only those patients who met the criteria for severe CRS had a CRP level of 20 mg/dL or more. Patients whose CRP exceeded this threshold were at particularly high risk for CRS (sensitivity, 86%; specificity, 100%).

"CRP, a routinely available lab test, can serve as a surrogate for predicting development of the CRS," coauthor and colleague Dr. Renier J. Brentjens said in an interview. "This allows for sensitive day-to-day assessment of cytokine release in treated patients, which will allow for better management of CRS in CAR T-cell-treated patients," said Dr. Brentjens, director of cellular therapeutics at Memorial Sloan-Kettering Cancer Center.

Dr. David L. Porter, director of blood and marrow transplantation at the University of Pennsylvania Hospital, Philadelphia, said they too have found that CRP tracks with severity of CRS. However, at least at this point, while it may help predict which patients have a more severe reaction, it does not allow for early or different intervention.

"It remains completely unknown whether early intervention for CRS will inhibit the T-cell activity," he said in an interview. "We have developed a grading system for CRS that was designed to help determine when patients require intervention for CRS based on clinical criteria rather than laboratory values. But ultimately, if CRP or other measurements predict when intervention is appropriate, this will be a very useful assay."

CRS intervention

Treating severe CRS with high-dose steroids resulted in rapid reversal of fevers, cytokines, and other clinical symptoms, but abrogated T-cell expansion and persistence, whereas IL-6 receptor blockade with tocilizumab (Actemra) did not, Dr. Avila reported. Indeed, two patients demonstrated an almost 7,000-fold expansion after first-line tocilizumab.

In addition, the manner of treating severe CRS may affect clinical outcomes. All three patients treated with high-dose steroids relapsed despite previously achieving a complete molecular remission whereas untreated patients or those treated with tocilizumab alone had no evidence of recurrent disease after achieving a complete molecular remission.

Efficacy

The complete response rate in the study was 88%, with 12 of these 14 patients further classified as having minimal residual disease. Seven (44%) patients were successfully bridged to allogeneic stem cell transplantation. This is "especially meaningful" when compared with the historic low of just 5% of relapsed/refractory adult B-ALL patients transitioning to transplant after salvage chemotherapy, Dr. Davila noted.

Still, the persistence of the 19-28z CAR T cells was about 3 months, compared with several months to even more than one year in at least one B-ALL patient and several CLL patients reported by the University of Pennsylvania researchers. Dr. Davila and his colleagues hypothesize that the longer persistence of CD19-targeted CARs incorporating a 4-1BB moiety, rather than CD28, may be due, in part, to antigen-independent signaling through the 4-1BB CAR, as previously shown in preclinical studies. They are also currently developing a human anti-mouse antibody assay to determine whether immune-mediated rejection might be a contributing factor to the limited persistence of the 19-28z CAR T cells.

Dr. Porter said it’s not known why their T cells persist longer, but agreed it may have to do with the novel signal domain of their CAR (4-1BB). "This may be important for high levels of expansion, but may also provide a survival signal to the T cells allowing for longer persistence," he said.

The study was supported by MSKCC. Dr. Davila reported having no financial disclosures. Dr. Brentjens holds a patent that covers the 19-28z receptor and is a cofounder of Juno Therapeutics, which holds the license.

pwendling@frontlinemedcom.com