Geriatrics

In Aleyadeh W, Hutt-Centeno E, Ahmed HM, Shah NP. Hypertension guidelines: treat patients, not numbers. Cleve Clin J Med 2019; 86(1):47–56. doi:10.3949/ccjm.86a.18027, on page 50, the following statement was incorrect: “In 2017, the American College of Physicians (ACP) and the American Academy of Family Physicians (AAFP) recommended a relaxed systolic blood pressure target, ie, below 150 mm Hg, for adults over age 60, but a tighter goal of less than 130 mm Hg for the same age group if they have transient ischemic attack, stroke, or high cardiovascular risk.9” In fact, the ACP and AAFP recommended a tighter goal of less than 140 mm Hg for this higher-risk group. This has been corrected online.

In Aleyadeh W, Hutt-Centeno E, Ahmed HM, Shah NP. Hypertension guidelines: treat patients, not numbers. Cleve Clin J Med 2019; 86(1):47–56. doi:10.3949/ccjm.86a.18027, on page 50, the following statement was incorrect: “In 2017, the American College of Physicians (ACP) and the American Academy of Family Physicians (AAFP) recommended a relaxed systolic blood pressure target, ie, below 150 mm Hg, for adults over age 60, but a tighter goal of less than 130 mm Hg for the same age group if they have transient ischemic attack, stroke, or high cardiovascular risk.9” In fact, the ACP and AAFP recommended a tighter goal of less than 140 mm Hg for this higher-risk group. This has been corrected online.

In Aleyadeh W, Hutt-Centeno E, Ahmed HM, Shah NP. Hypertension guidelines: treat patients, not numbers. Cleve Clin J Med 2019; 86(1):47–56. doi:10.3949/ccjm.86a.18027, on page 50, the following statement was incorrect: “In 2017, the American College of Physicians (ACP) and the American Academy of Family Physicians (AAFP) recommended a relaxed systolic blood pressure target, ie, below 150 mm Hg, for adults over age 60, but a tighter goal of less than 130 mm Hg for the same age group if they have transient ischemic attack, stroke, or high cardiovascular risk.9” In fact, the ACP and AAFP recommended a tighter goal of less than 140 mm Hg for this higher-risk group. This has been corrected online.

Delaying or withholding antibiotics in elderly patients with a urinary tract infection (UTI) increases the risk of sepsis and death, results of a large, population-based study suggest.

andresr/Getty Images

The risk of bloodstream infection was more than seven times greater in patients who did not receive antibiotics immediately after seeing a general practitioner for a UTI versus those who did, according to results of the study based on primary care records and other data for nearly 160,000 U.K. patients aged 65 years or older. Death rates and hospital admissions were significantly higher for these patients, according to the study published in The BMJ by Myriam Gharbi, PharmD, Phd, Imperial College London, and her colleagues.

The publication of these findings coincides with an increase in Escherichia coli bloodstream infections in England.

“Our study suggests the early initiation of antibiotics for UTI in older high risk adult populations (especially men aged [older than] 85 years) should be recommended to prevent serious complications,” Dr. Gharbi and her coauthors said in their report.

The population-based cohort study comprised 157,264 adult primary care patients at least 65 years of age who had one or more suspected or confirmed lower UTIs from November 2007 to May 2015. The researchers found that health care providers had diagnosed a total of 312,896 UTI episodes in these patients during the period they studied. In 7.2% (22,534) of the UTI episodes, the researchers were unable to find records of the patients having been prescribed antibiotics by a general practitioner within 7 days of the UTI diagnosis. These 22,534 episodes included those that occurred in patients who had a complication before an antibiotic was prescribed. An additional 6.2% (19,292) of the episodes occurred in patients who were prescribed antibiotics, but not during their first UTI-related visit to a general practitioner or on the same day of such a visit. The researchers classified this group of patients as having been prescribed antibiotics on a deferred or delayed basis, as they were not prescribed such drugs within 7 days of their visit.

Overall, there were 1,539 cases (0.5% of the total number of UTIs) of bloodstream infection within 60 days of the initial urinary tract infection diagnosis, the researchers reported.

The bloodstream infection rate was 2.9% for patients who were not prescribed antibiotics ever or prior to an infection occurring, 2.2% in those who were prescribed antibiotics on a deferred basis, and 0.2% in those who were prescribed antibiotics immediately, meaning during their first visit to a general practitioner for a UTI or on the same day of such a visit (P less than .001). After adjustment for potential confounding variables such as age, sex, and region, the patients classified as having not been prescribed antibiotics or having been prescribed antibiotics on a deferred basis were significantly more likely to have a bloodstream infection within 60 days of their visit to a health care provider, compared with those who received antibiotics immediately, with odds ratios of 8.08 (95% confidence interval, 7.12-9.16) and 7.12 (95% CI, 6.22-8.14), respectively.

Hospital admissions after a UTI episode were nearly twice as high in the no- or deferred-antibiotics groups (27.0% and 26.8%, respectively), compared with the group that received antibiotics right away (14.8%), the investigators reported. The lengths of hospital stays were 12.1 days for the group classified as having not been prescribed antibiotics, 7.7 days for the group subject to delayed antibiotic prescribing, and 6.3 days for the group who received antibiotics immediately.

Deaths within 60 days of experiencing a urinary tract infection occurred in 5.4% of patients in the no-antibiotics group, 2.8% of the deferred-antibiotics group, and 1.6% of the immediate-antibiotics group. After adjustment for covariates, a regression analysis showed the risks for all-cause mortality were 1.16 and 2.18 times higher in the deferred-antibiotics group and the no-antibiotics group, respectively, according to the paper.

In the immediate-antibiotics group, those patients who received nitrofurantoin had a “small but significant increase” in 60-day survival versus those who received trimethoprim, the investigators noted in the discussion section of their report.

“This increase could reflect either higher levels of resistance to trimethoprim or a healthier population treated with nitrofurantoin, the latest being not recommended for patients with poor kidney function,” the researchers wrote.

This study was supported by the National Institute for Health Research and other U.K. sources. One study coauthor reported working as an epidemiologist with GSK in areas not related to the study.

SOURCE: Gharbi M et al. BMJ. 2019 Feb 27. doi: 10.1136/bmj.l525.

Delaying or withholding antibiotics in elderly patients with a urinary tract infection (UTI) increases the risk of sepsis and death, results of a large, population-based study suggest.

andresr/Getty Images

The risk of bloodstream infection was more than seven times greater in patients who did not receive antibiotics immediately after seeing a general practitioner for a UTI versus those who did, according to results of the study based on primary care records and other data for nearly 160,000 U.K. patients aged 65 years or older. Death rates and hospital admissions were significantly higher for these patients, according to the study published in The BMJ by Myriam Gharbi, PharmD, Phd, Imperial College London, and her colleagues.

The publication of these findings coincides with an increase in Escherichia coli bloodstream infections in England.

“Our study suggests the early initiation of antibiotics for UTI in older high risk adult populations (especially men aged [older than] 85 years) should be recommended to prevent serious complications,” Dr. Gharbi and her coauthors said in their report.

The population-based cohort study comprised 157,264 adult primary care patients at least 65 years of age who had one or more suspected or confirmed lower UTIs from November 2007 to May 2015. The researchers found that health care providers had diagnosed a total of 312,896 UTI episodes in these patients during the period they studied. In 7.2% (22,534) of the UTI episodes, the researchers were unable to find records of the patients having been prescribed antibiotics by a general practitioner within 7 days of the UTI diagnosis. These 22,534 episodes included those that occurred in patients who had a complication before an antibiotic was prescribed. An additional 6.2% (19,292) of the episodes occurred in patients who were prescribed antibiotics, but not during their first UTI-related visit to a general practitioner or on the same day of such a visit. The researchers classified this group of patients as having been prescribed antibiotics on a deferred or delayed basis, as they were not prescribed such drugs within 7 days of their visit.

Overall, there were 1,539 cases (0.5% of the total number of UTIs) of bloodstream infection within 60 days of the initial urinary tract infection diagnosis, the researchers reported.

The bloodstream infection rate was 2.9% for patients who were not prescribed antibiotics ever or prior to an infection occurring, 2.2% in those who were prescribed antibiotics on a deferred basis, and 0.2% in those who were prescribed antibiotics immediately, meaning during their first visit to a general practitioner for a UTI or on the same day of such a visit (P less than .001). After adjustment for potential confounding variables such as age, sex, and region, the patients classified as having not been prescribed antibiotics or having been prescribed antibiotics on a deferred basis were significantly more likely to have a bloodstream infection within 60 days of their visit to a health care provider, compared with those who received antibiotics immediately, with odds ratios of 8.08 (95% confidence interval, 7.12-9.16) and 7.12 (95% CI, 6.22-8.14), respectively.

Hospital admissions after a UTI episode were nearly twice as high in the no- or deferred-antibiotics groups (27.0% and 26.8%, respectively), compared with the group that received antibiotics right away (14.8%), the investigators reported. The lengths of hospital stays were 12.1 days for the group classified as having not been prescribed antibiotics, 7.7 days for the group subject to delayed antibiotic prescribing, and 6.3 days for the group who received antibiotics immediately.

Deaths within 60 days of experiencing a urinary tract infection occurred in 5.4% of patients in the no-antibiotics group, 2.8% of the deferred-antibiotics group, and 1.6% of the immediate-antibiotics group. After adjustment for covariates, a regression analysis showed the risks for all-cause mortality were 1.16 and 2.18 times higher in the deferred-antibiotics group and the no-antibiotics group, respectively, according to the paper.

In the immediate-antibiotics group, those patients who received nitrofurantoin had a “small but significant increase” in 60-day survival versus those who received trimethoprim, the investigators noted in the discussion section of their report.

“This increase could reflect either higher levels of resistance to trimethoprim or a healthier population treated with nitrofurantoin, the latest being not recommended for patients with poor kidney function,” the researchers wrote.

This study was supported by the National Institute for Health Research and other U.K. sources. One study coauthor reported working as an epidemiologist with GSK in areas not related to the study.

SOURCE: Gharbi M et al. BMJ. 2019 Feb 27. doi: 10.1136/bmj.l525.

Delaying or withholding antibiotics in elderly patients with a urinary tract infection (UTI) increases the risk of sepsis and death, results of a large, population-based study suggest.

andresr/Getty Images

The risk of bloodstream infection was more than seven times greater in patients who did not receive antibiotics immediately after seeing a general practitioner for a UTI versus those who did, according to results of the study based on primary care records and other data for nearly 160,000 U.K. patients aged 65 years or older. Death rates and hospital admissions were significantly higher for these patients, according to the study published in The BMJ by Myriam Gharbi, PharmD, Phd, Imperial College London, and her colleagues.

The publication of these findings coincides with an increase in Escherichia coli bloodstream infections in England.

“Our study suggests the early initiation of antibiotics for UTI in older high risk adult populations (especially men aged [older than] 85 years) should be recommended to prevent serious complications,” Dr. Gharbi and her coauthors said in their report.

The population-based cohort study comprised 157,264 adult primary care patients at least 65 years of age who had one or more suspected or confirmed lower UTIs from November 2007 to May 2015. The researchers found that health care providers had diagnosed a total of 312,896 UTI episodes in these patients during the period they studied. In 7.2% (22,534) of the UTI episodes, the researchers were unable to find records of the patients having been prescribed antibiotics by a general practitioner within 7 days of the UTI diagnosis. These 22,534 episodes included those that occurred in patients who had a complication before an antibiotic was prescribed. An additional 6.2% (19,292) of the episodes occurred in patients who were prescribed antibiotics, but not during their first UTI-related visit to a general practitioner or on the same day of such a visit. The researchers classified this group of patients as having been prescribed antibiotics on a deferred or delayed basis, as they were not prescribed such drugs within 7 days of their visit.

Overall, there were 1,539 cases (0.5% of the total number of UTIs) of bloodstream infection within 60 days of the initial urinary tract infection diagnosis, the researchers reported.

The bloodstream infection rate was 2.9% for patients who were not prescribed antibiotics ever or prior to an infection occurring, 2.2% in those who were prescribed antibiotics on a deferred basis, and 0.2% in those who were prescribed antibiotics immediately, meaning during their first visit to a general practitioner for a UTI or on the same day of such a visit (P less than .001). After adjustment for potential confounding variables such as age, sex, and region, the patients classified as having not been prescribed antibiotics or having been prescribed antibiotics on a deferred basis were significantly more likely to have a bloodstream infection within 60 days of their visit to a health care provider, compared with those who received antibiotics immediately, with odds ratios of 8.08 (95% confidence interval, 7.12-9.16) and 7.12 (95% CI, 6.22-8.14), respectively.

Hospital admissions after a UTI episode were nearly twice as high in the no- or deferred-antibiotics groups (27.0% and 26.8%, respectively), compared with the group that received antibiotics right away (14.8%), the investigators reported. The lengths of hospital stays were 12.1 days for the group classified as having not been prescribed antibiotics, 7.7 days for the group subject to delayed antibiotic prescribing, and 6.3 days for the group who received antibiotics immediately.

Deaths within 60 days of experiencing a urinary tract infection occurred in 5.4% of patients in the no-antibiotics group, 2.8% of the deferred-antibiotics group, and 1.6% of the immediate-antibiotics group. After adjustment for covariates, a regression analysis showed the risks for all-cause mortality were 1.16 and 2.18 times higher in the deferred-antibiotics group and the no-antibiotics group, respectively, according to the paper.

In the immediate-antibiotics group, those patients who received nitrofurantoin had a “small but significant increase” in 60-day survival versus those who received trimethoprim, the investigators noted in the discussion section of their report.

“This increase could reflect either higher levels of resistance to trimethoprim or a healthier population treated with nitrofurantoin, the latest being not recommended for patients with poor kidney function,” the researchers wrote.

This study was supported by the National Institute for Health Research and other U.K. sources. One study coauthor reported working as an epidemiologist with GSK in areas not related to the study.

SOURCE: Gharbi M et al. BMJ. 2019 Feb 27. doi: 10.1136/bmj.l525.

In May 2014, a 70-year-old retiree underwent repair of a fracture of her left ankle. The procedure was performed at a local hospital. A splint was applied to the ankle, and a nurse provided crutches.

Following discharge from the hospital, the patient hailed a taxi to take her home. As she was exiting the taxi at her residence, the patient fell and sustained comminuted fractures to the distal radius and distal ulna of her right (dominant) wrist and a trimalleolar fracture to her repaired left ankle.

The plaintiff was transported back to the hospital via ambulance. She underwent closed reduction of her wrist fractures and 11 days later was transferred to another facility for open reduction and internal fixation of her left ankle fracture. Her hospitalizations totaled 13 days and were followed by a course of inpatient rehabilitative therapy; the latter lasted until late August 2014, with a brief interruption in June when she underwent open reduction and internal fixation of her wrist fractures. When she returned home in August, the patient required the assistance of visiting aides and 3 additional months of rehabilitative therapy.

At trial, the plaintiff claimed that her left ankle and her right wrist remained painful, that she sustained a mild residual diminution of each area’s range of motion, and that these residual effects hindered her performance of basic physical activities (eg, cleaning and cooking).

The plaintiff alleged that her fall while exiting the taxi resulted from unsteadiness, which was a lingering effect of morphine that was administered during the repair of her fracture. She sought recovery of damages for past and future pain and suffering from the hospital’s operator. The lawsuit alleged that the nurse had failed to provide instructions on the proper use of crutches, that the nurse had failed to undertake measures that would have diminished the plaintiff’s likelihood of falling, that the nurse’s failures constituted malpractice and negligence, and that the hospital operator was vicariously liable for the nurse’s actions.

The plaintiff claimed that she repeatedly warned that she did not believe that she could safely use the crutches provided by the nurse. She claimed that she was unsteady and lightheaded, and that when she requested a wheelchair, an escort, or an ambulance, the nurse rejected the request. The nursing standards expert for the plaintiff opined that the request should have been satisfied or alternatively, that the nurse should have explained the manner in which a crutch-dependent person could safely enter and exit a vehicle.

Defense counsel claimed that the nurse explained proper use of the crutches, the plaintiff indicated that she understood the explanation, and the plaintiff demonstrated proper use and did not express concern. The defense’s expert contended that the nurse did not have to explain how a crutch-dependent person could safely enter and exit a vehicle and that the plaintiff’s fall resulted from her own failure to exercise appropriate caution. The defense further contended that the plaintiff achieved an excellent recovery.

Continue to: After a 7-day trial...

After a 7-day trial and 3 hours and 45 minutes’ deliberation, the jury found in favor of the plaintiff. It found that the nurse was negligent in her provision of crutches and that the act was a substantial cause of the plaintiff’s injuries. The jury also found that the nurse did not properly explain the use of crutches but determined that the error was not a substantial cause of the plaintiff’s injuries.

VERDICT

The jury awarded the plaintiff a total of $850,000 in damages. The plaintiff also recovered stipulated medical expenses.

COMMENTARY

Medical malpractice litigation involves recovery for acts or omissions that constitute a departure from the standard of care. We all recognize injurious acts—improper esophageal intubation in the emergency department, transection of a nerve in the operating room, or prescription of a contraindicated medication to an allergic patient—and acknowledge damaging omissions, such as failure to screen for colon cancer or recognize treatable diabetes.

However, some cases are disposition related; they arise from how patients are discharged, what instructions they are given, where they go, and what they do after discharge. These cases involve the patient’s medical issues engrafted on his or her transportation, job, and more generally, living environment.

The lay public expects patients to have a right of self-determination, to control the nature and course of their medical care. Yet, the modern lay public also expects the medical profession to act as an authority figure—exercising a degree of paternalism to safeguard patients from harm. This expectation is commonly articulated in retrospect, after something has gone wrong. Consequently, clinicians must be aware of what will happen to the patient after discharge.

Continue to: With all interventions...

With all interventions, weigh the post-discharge consequences. If you give an injection of hydromorphone, you cannot discharge the patient to drive home 45 minutes later. If you have diagnosed vertigo in a patient, you cannot prescribe meclizine and return that patient to her job working on scaffolding 50 ft above ground. If a frail patient lives alone and cannot safely walk, and you’ve started him on furosemide, you cannot discharge him without considering how he will get to the bathroom. Other concerns are even more difficult—for example, the homeless patient who does not have the environment or resources to follow your instructions.

It is tempting to view these concerns as not our responsibility or dismiss them as “not medicine.” Clinicians can feel frustrated at being pulled into the realm of social work, where we are ill equipped to deal with and sort out the patient’s “life problems.” For one thing, we don’t often have the resources to deal with these issues. And for another, addressing the patient’s postdischarge living situation takes time—something in short supply and intangible to the other patients in the waiting room, who are expecting your attention and wondering, “What’s the holdup?”

In the case presented, the plaintiff was a 70-year-old retiree. She was discharged from the hospital with crutches. Crutches are age-old and familiar devices. Nevertheless, crutches are for people who are able to use their arms for weight bearing and propulsion and require a fair amount of physical strength, timing, and dexterity. While a potentially debatable point, an assumption that a 70-year-old patient has the arm strength and dexterity to properly propel herself with crutches may be faulty. There was disagreement between the patient, who claimed she could not safely use the crutches, and the nurse, who said the patient accepted the crutches without concern. The safest course of action would be for discharge personnel to demonstrate the use of crutches, observe the patient using the crutches, and document that in the record.

In this case, it is unclear if the nurse demonstrated how to use the crutches or witnessed the plaintiff demonstrating she could safely use them. The jury found the nurse was negligent “in her provision” of crutches—an act they deemed a substantial cause of the plaintiff’s injuries. Interestingly, the jury did not consider the lack of explanation on the crutches’ use to be a substantial cause of injury. But the bottom line is, they faulted the nurse for the act of giving this patient crutches and awarded $850,000 in damages.

Society is changing. Fifty years ago, jurors would expect people to be familiar with crutches, and if you fell while using them, that was your own fault. Modern jurors expect hospitals and providers to get more involved in what happens to a patient after discharge. The news media has heavily publicized cases of alleged “patient dumping.”

Continue to: As a result...

As a result, we see legislative changes, such as the recently passed California Senate Bill 1152, which requires that homeless patients be fed; provided weather-appropriate clothing, filled prescriptions, and vaccinations; given medical screening, examination, and evaluation that requires the “treating physician” to arrange behavioral health care; and enrolled in “any affordable health insurance coverage for which he or she is eligible.”

Whether it is appropriate to ask hospitals and clinicians to get this involved is beyond the scope of this column. What is clear is that society increasingly expects clinicians and hospitals to take responsibility for patients. This societal change has an impact on the lay public’s perception of what is expected of health care providers. Tomorrow’s juror comes to court with a belief that hospitals and clinicians owe a duty of care that extends beyond the walls of the exam room.

IN SUMMARY

Reality test your post-treatment instructions to be sure they will work for the patient and are not grossly incompatible with his or her known postdischarge environment. To the extent possible, involve discharge planning personnel in your practice. Let your record reflect that you are acting in the patient’s best interest, and evade the temptation to squint narrowly to avoid seeing circumstances in the patient’s life that prevent safe implementation of your plan.

In May 2014, a 70-year-old retiree underwent repair of a fracture of her left ankle. The procedure was performed at a local hospital. A splint was applied to the ankle, and a nurse provided crutches.

Following discharge from the hospital, the patient hailed a taxi to take her home. As she was exiting the taxi at her residence, the patient fell and sustained comminuted fractures to the distal radius and distal ulna of her right (dominant) wrist and a trimalleolar fracture to her repaired left ankle.

The plaintiff was transported back to the hospital via ambulance. She underwent closed reduction of her wrist fractures and 11 days later was transferred to another facility for open reduction and internal fixation of her left ankle fracture. Her hospitalizations totaled 13 days and were followed by a course of inpatient rehabilitative therapy; the latter lasted until late August 2014, with a brief interruption in June when she underwent open reduction and internal fixation of her wrist fractures. When she returned home in August, the patient required the assistance of visiting aides and 3 additional months of rehabilitative therapy.

At trial, the plaintiff claimed that her left ankle and her right wrist remained painful, that she sustained a mild residual diminution of each area’s range of motion, and that these residual effects hindered her performance of basic physical activities (eg, cleaning and cooking).

The plaintiff alleged that her fall while exiting the taxi resulted from unsteadiness, which was a lingering effect of morphine that was administered during the repair of her fracture. She sought recovery of damages for past and future pain and suffering from the hospital’s operator. The lawsuit alleged that the nurse had failed to provide instructions on the proper use of crutches, that the nurse had failed to undertake measures that would have diminished the plaintiff’s likelihood of falling, that the nurse’s failures constituted malpractice and negligence, and that the hospital operator was vicariously liable for the nurse’s actions.

The plaintiff claimed that she repeatedly warned that she did not believe that she could safely use the crutches provided by the nurse. She claimed that she was unsteady and lightheaded, and that when she requested a wheelchair, an escort, or an ambulance, the nurse rejected the request. The nursing standards expert for the plaintiff opined that the request should have been satisfied or alternatively, that the nurse should have explained the manner in which a crutch-dependent person could safely enter and exit a vehicle.

Defense counsel claimed that the nurse explained proper use of the crutches, the plaintiff indicated that she understood the explanation, and the plaintiff demonstrated proper use and did not express concern. The defense’s expert contended that the nurse did not have to explain how a crutch-dependent person could safely enter and exit a vehicle and that the plaintiff’s fall resulted from her own failure to exercise appropriate caution. The defense further contended that the plaintiff achieved an excellent recovery.

Continue to: After a 7-day trial...

After a 7-day trial and 3 hours and 45 minutes’ deliberation, the jury found in favor of the plaintiff. It found that the nurse was negligent in her provision of crutches and that the act was a substantial cause of the plaintiff’s injuries. The jury also found that the nurse did not properly explain the use of crutches but determined that the error was not a substantial cause of the plaintiff’s injuries.

VERDICT

The jury awarded the plaintiff a total of $850,000 in damages. The plaintiff also recovered stipulated medical expenses.

COMMENTARY

Medical malpractice litigation involves recovery for acts or omissions that constitute a departure from the standard of care. We all recognize injurious acts—improper esophageal intubation in the emergency department, transection of a nerve in the operating room, or prescription of a contraindicated medication to an allergic patient—and acknowledge damaging omissions, such as failure to screen for colon cancer or recognize treatable diabetes.

However, some cases are disposition related; they arise from how patients are discharged, what instructions they are given, where they go, and what they do after discharge. These cases involve the patient’s medical issues engrafted on his or her transportation, job, and more generally, living environment.

The lay public expects patients to have a right of self-determination, to control the nature and course of their medical care. Yet, the modern lay public also expects the medical profession to act as an authority figure—exercising a degree of paternalism to safeguard patients from harm. This expectation is commonly articulated in retrospect, after something has gone wrong. Consequently, clinicians must be aware of what will happen to the patient after discharge.

Continue to: With all interventions...

With all interventions, weigh the post-discharge consequences. If you give an injection of hydromorphone, you cannot discharge the patient to drive home 45 minutes later. If you have diagnosed vertigo in a patient, you cannot prescribe meclizine and return that patient to her job working on scaffolding 50 ft above ground. If a frail patient lives alone and cannot safely walk, and you’ve started him on furosemide, you cannot discharge him without considering how he will get to the bathroom. Other concerns are even more difficult—for example, the homeless patient who does not have the environment or resources to follow your instructions.

It is tempting to view these concerns as not our responsibility or dismiss them as “not medicine.” Clinicians can feel frustrated at being pulled into the realm of social work, where we are ill equipped to deal with and sort out the patient’s “life problems.” For one thing, we don’t often have the resources to deal with these issues. And for another, addressing the patient’s postdischarge living situation takes time—something in short supply and intangible to the other patients in the waiting room, who are expecting your attention and wondering, “What’s the holdup?”

In the case presented, the plaintiff was a 70-year-old retiree. She was discharged from the hospital with crutches. Crutches are age-old and familiar devices. Nevertheless, crutches are for people who are able to use their arms for weight bearing and propulsion and require a fair amount of physical strength, timing, and dexterity. While a potentially debatable point, an assumption that a 70-year-old patient has the arm strength and dexterity to properly propel herself with crutches may be faulty. There was disagreement between the patient, who claimed she could not safely use the crutches, and the nurse, who said the patient accepted the crutches without concern. The safest course of action would be for discharge personnel to demonstrate the use of crutches, observe the patient using the crutches, and document that in the record.

In this case, it is unclear if the nurse demonstrated how to use the crutches or witnessed the plaintiff demonstrating she could safely use them. The jury found the nurse was negligent “in her provision” of crutches—an act they deemed a substantial cause of the plaintiff’s injuries. Interestingly, the jury did not consider the lack of explanation on the crutches’ use to be a substantial cause of injury. But the bottom line is, they faulted the nurse for the act of giving this patient crutches and awarded $850,000 in damages.

Society is changing. Fifty years ago, jurors would expect people to be familiar with crutches, and if you fell while using them, that was your own fault. Modern jurors expect hospitals and providers to get more involved in what happens to a patient after discharge. The news media has heavily publicized cases of alleged “patient dumping.”

Continue to: As a result...

As a result, we see legislative changes, such as the recently passed California Senate Bill 1152, which requires that homeless patients be fed; provided weather-appropriate clothing, filled prescriptions, and vaccinations; given medical screening, examination, and evaluation that requires the “treating physician” to arrange behavioral health care; and enrolled in “any affordable health insurance coverage for which he or she is eligible.”

Whether it is appropriate to ask hospitals and clinicians to get this involved is beyond the scope of this column. What is clear is that society increasingly expects clinicians and hospitals to take responsibility for patients. This societal change has an impact on the lay public’s perception of what is expected of health care providers. Tomorrow’s juror comes to court with a belief that hospitals and clinicians owe a duty of care that extends beyond the walls of the exam room.

IN SUMMARY

Reality test your post-treatment instructions to be sure they will work for the patient and are not grossly incompatible with his or her known postdischarge environment. To the extent possible, involve discharge planning personnel in your practice. Let your record reflect that you are acting in the patient’s best interest, and evade the temptation to squint narrowly to avoid seeing circumstances in the patient’s life that prevent safe implementation of your plan.

In May 2014, a 70-year-old retiree underwent repair of a fracture of her left ankle. The procedure was performed at a local hospital. A splint was applied to the ankle, and a nurse provided crutches.

Following discharge from the hospital, the patient hailed a taxi to take her home. As she was exiting the taxi at her residence, the patient fell and sustained comminuted fractures to the distal radius and distal ulna of her right (dominant) wrist and a trimalleolar fracture to her repaired left ankle.

The plaintiff was transported back to the hospital via ambulance. She underwent closed reduction of her wrist fractures and 11 days later was transferred to another facility for open reduction and internal fixation of her left ankle fracture. Her hospitalizations totaled 13 days and were followed by a course of inpatient rehabilitative therapy; the latter lasted until late August 2014, with a brief interruption in June when she underwent open reduction and internal fixation of her wrist fractures. When she returned home in August, the patient required the assistance of visiting aides and 3 additional months of rehabilitative therapy.

At trial, the plaintiff claimed that her left ankle and her right wrist remained painful, that she sustained a mild residual diminution of each area’s range of motion, and that these residual effects hindered her performance of basic physical activities (eg, cleaning and cooking).

The plaintiff alleged that her fall while exiting the taxi resulted from unsteadiness, which was a lingering effect of morphine that was administered during the repair of her fracture. She sought recovery of damages for past and future pain and suffering from the hospital’s operator. The lawsuit alleged that the nurse had failed to provide instructions on the proper use of crutches, that the nurse had failed to undertake measures that would have diminished the plaintiff’s likelihood of falling, that the nurse’s failures constituted malpractice and negligence, and that the hospital operator was vicariously liable for the nurse’s actions.

The plaintiff claimed that she repeatedly warned that she did not believe that she could safely use the crutches provided by the nurse. She claimed that she was unsteady and lightheaded, and that when she requested a wheelchair, an escort, or an ambulance, the nurse rejected the request. The nursing standards expert for the plaintiff opined that the request should have been satisfied or alternatively, that the nurse should have explained the manner in which a crutch-dependent person could safely enter and exit a vehicle.

Defense counsel claimed that the nurse explained proper use of the crutches, the plaintiff indicated that she understood the explanation, and the plaintiff demonstrated proper use and did not express concern. The defense’s expert contended that the nurse did not have to explain how a crutch-dependent person could safely enter and exit a vehicle and that the plaintiff’s fall resulted from her own failure to exercise appropriate caution. The defense further contended that the plaintiff achieved an excellent recovery.

Continue to: After a 7-day trial...

After a 7-day trial and 3 hours and 45 minutes’ deliberation, the jury found in favor of the plaintiff. It found that the nurse was negligent in her provision of crutches and that the act was a substantial cause of the plaintiff’s injuries. The jury also found that the nurse did not properly explain the use of crutches but determined that the error was not a substantial cause of the plaintiff’s injuries.

VERDICT

The jury awarded the plaintiff a total of $850,000 in damages. The plaintiff also recovered stipulated medical expenses.

COMMENTARY

Medical malpractice litigation involves recovery for acts or omissions that constitute a departure from the standard of care. We all recognize injurious acts—improper esophageal intubation in the emergency department, transection of a nerve in the operating room, or prescription of a contraindicated medication to an allergic patient—and acknowledge damaging omissions, such as failure to screen for colon cancer or recognize treatable diabetes.

However, some cases are disposition related; they arise from how patients are discharged, what instructions they are given, where they go, and what they do after discharge. These cases involve the patient’s medical issues engrafted on his or her transportation, job, and more generally, living environment.

The lay public expects patients to have a right of self-determination, to control the nature and course of their medical care. Yet, the modern lay public also expects the medical profession to act as an authority figure—exercising a degree of paternalism to safeguard patients from harm. This expectation is commonly articulated in retrospect, after something has gone wrong. Consequently, clinicians must be aware of what will happen to the patient after discharge.

Continue to: With all interventions...

With all interventions, weigh the post-discharge consequences. If you give an injection of hydromorphone, you cannot discharge the patient to drive home 45 minutes later. If you have diagnosed vertigo in a patient, you cannot prescribe meclizine and return that patient to her job working on scaffolding 50 ft above ground. If a frail patient lives alone and cannot safely walk, and you’ve started him on furosemide, you cannot discharge him without considering how he will get to the bathroom. Other concerns are even more difficult—for example, the homeless patient who does not have the environment or resources to follow your instructions.

It is tempting to view these concerns as not our responsibility or dismiss them as “not medicine.” Clinicians can feel frustrated at being pulled into the realm of social work, where we are ill equipped to deal with and sort out the patient’s “life problems.” For one thing, we don’t often have the resources to deal with these issues. And for another, addressing the patient’s postdischarge living situation takes time—something in short supply and intangible to the other patients in the waiting room, who are expecting your attention and wondering, “What’s the holdup?”

In the case presented, the plaintiff was a 70-year-old retiree. She was discharged from the hospital with crutches. Crutches are age-old and familiar devices. Nevertheless, crutches are for people who are able to use their arms for weight bearing and propulsion and require a fair amount of physical strength, timing, and dexterity. While a potentially debatable point, an assumption that a 70-year-old patient has the arm strength and dexterity to properly propel herself with crutches may be faulty. There was disagreement between the patient, who claimed she could not safely use the crutches, and the nurse, who said the patient accepted the crutches without concern. The safest course of action would be for discharge personnel to demonstrate the use of crutches, observe the patient using the crutches, and document that in the record.

In this case, it is unclear if the nurse demonstrated how to use the crutches or witnessed the plaintiff demonstrating she could safely use them. The jury found the nurse was negligent “in her provision” of crutches—an act they deemed a substantial cause of the plaintiff’s injuries. Interestingly, the jury did not consider the lack of explanation on the crutches’ use to be a substantial cause of injury. But the bottom line is, they faulted the nurse for the act of giving this patient crutches and awarded $850,000 in damages.

Society is changing. Fifty years ago, jurors would expect people to be familiar with crutches, and if you fell while using them, that was your own fault. Modern jurors expect hospitals and providers to get more involved in what happens to a patient after discharge. The news media has heavily publicized cases of alleged “patient dumping.”

Continue to: As a result...

As a result, we see legislative changes, such as the recently passed California Senate Bill 1152, which requires that homeless patients be fed; provided weather-appropriate clothing, filled prescriptions, and vaccinations; given medical screening, examination, and evaluation that requires the “treating physician” to arrange behavioral health care; and enrolled in “any affordable health insurance coverage for which he or she is eligible.”

Whether it is appropriate to ask hospitals and clinicians to get this involved is beyond the scope of this column. What is clear is that society increasingly expects clinicians and hospitals to take responsibility for patients. This societal change has an impact on the lay public’s perception of what is expected of health care providers. Tomorrow’s juror comes to court with a belief that hospitals and clinicians owe a duty of care that extends beyond the walls of the exam room.

IN SUMMARY

Reality test your post-treatment instructions to be sure they will work for the patient and are not grossly incompatible with his or her known postdischarge environment. To the extent possible, involve discharge planning personnel in your practice. Let your record reflect that you are acting in the patient’s best interest, and evade the temptation to squint narrowly to avoid seeing circumstances in the patient’s life that prevent safe implementation of your plan.

SAN DIEGO – A nationally representative survey of ICU patients older than age 65 years shows an improvement over time in the frequency of advance care planning (ACP), but one in four have no ACP; the problem is more pronounced among some blacks and Hispanics and those with lower net worth. The study also found that these patients see physicians an average of 20 times in the year preceding the ICU visit, which suggests that there are plenty of opportunities to put ACP in place.

marcosmartinezromero/iStockphoto

“Over two-thirds were seen by a doctor in the last 2 weeks. So they’re seeing doctors, but they’re still not doing advance care planning,” said Brian Block, MD, during a presentation of the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine. Dr. Block is with the University of California, San Francisco.

Lack of advance planning can put major road blocks in front of patient care in the ICU, as well as complicate communication between physicians and family members. The findings underscore the need to encourage conversations about end-of-life care between physicians and their patients – before the patients wind up in intensive care.

One audience member believes these conversations are already happening. Paul Yodice, MD, chairman of medicine at Saint Barnabas Medical Center in Livingston, N.J., suggested that physicians are attempting to engage older patients and family members in ACP, but many are unready to make decisions. “In my experience, it is happening much more frequently than is captured either in the medical record or in the research that we’ve been publishing. I’ve been a part of those conversations. Those individuals who are faced with those toughest of choices choose to delay making the decision or speaking about it further because it’s just too painful to consider, and they hold out hope of being the one to beat the odds, to have one more day,” said Dr. Yodice.

He called for further research to document whether ACP conversations are happening and to identify barriers to decisions and the means to overcome them. “A next good study would be to send out a respectful survey to the families of those who have lost people they love and ask: Has someone in the past year spoken with you or offered to have a discussion about end-of-life issues? We could get a better handle on [how often] the discussion is being had, and then find a solution,” said Dr. Yodice.

ACP can also be difficult for the provider, he added. Family members and patients, desperate for another treatment option, will often ask if there’s anything else that can be done. “In medicine, the answer almost always is ‘Well, we can try something else even though I know it’s not going to work.’ And people hold on to that, including us,” said Dr. Yodice.

The study analyzed data from a Medicare cohort of 1,109 patients who died during 2000-2013 and had an ICU admission within the last 30 days of their life. Ages were fairly evenly distributed, with 29% aged 65-74 years, 39% aged 75-84, and 32% aged 85 and over. Fifty-four percent were women, 26% were nonwhite, 42% had not completed high school, and 11% were in skilled nursing facilities.

About 35% had no ACP in 2000-2001, and that percentage gradually declined, to about 20% in 2012-2013 (slope, –1.6%/year; P = .009).

Seventeen percent of white participants had no ACP, compared with 51% of blacks and 49% of Hispanics. Net worth was also strongly associated with having ACP: The top quartile had 13% lacking ACP, compared with 43% of the bottom quartile.

The study found that 94% of patients who had no ACP had visited a health care provider in the past year. The average number of visits in the past year was 20, and 83% had seen a provider within the past 30 days.

Dr. Block did not declare a source of funding or potential conflicts. Dr. Yodice had no disclosures.
 

chestphysiciannews@chestnet.org

SOURCE: Block B et al. CCC48, Abstract 401.

SAN DIEGO – A nationally representative survey of ICU patients older than age 65 years shows an improvement over time in the frequency of advance care planning (ACP), but one in four have no ACP; the problem is more pronounced among some blacks and Hispanics and those with lower net worth. The study also found that these patients see physicians an average of 20 times in the year preceding the ICU visit, which suggests that there are plenty of opportunities to put ACP in place.

marcosmartinezromero/iStockphoto

“Over two-thirds were seen by a doctor in the last 2 weeks. So they’re seeing doctors, but they’re still not doing advance care planning,” said Brian Block, MD, during a presentation of the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine. Dr. Block is with the University of California, San Francisco.

Lack of advance planning can put major road blocks in front of patient care in the ICU, as well as complicate communication between physicians and family members. The findings underscore the need to encourage conversations about end-of-life care between physicians and their patients – before the patients wind up in intensive care.

One audience member believes these conversations are already happening. Paul Yodice, MD, chairman of medicine at Saint Barnabas Medical Center in Livingston, N.J., suggested that physicians are attempting to engage older patients and family members in ACP, but many are unready to make decisions. “In my experience, it is happening much more frequently than is captured either in the medical record or in the research that we’ve been publishing. I’ve been a part of those conversations. Those individuals who are faced with those toughest of choices choose to delay making the decision or speaking about it further because it’s just too painful to consider, and they hold out hope of being the one to beat the odds, to have one more day,” said Dr. Yodice.

He called for further research to document whether ACP conversations are happening and to identify barriers to decisions and the means to overcome them. “A next good study would be to send out a respectful survey to the families of those who have lost people they love and ask: Has someone in the past year spoken with you or offered to have a discussion about end-of-life issues? We could get a better handle on [how often] the discussion is being had, and then find a solution,” said Dr. Yodice.

ACP can also be difficult for the provider, he added. Family members and patients, desperate for another treatment option, will often ask if there’s anything else that can be done. “In medicine, the answer almost always is ‘Well, we can try something else even though I know it’s not going to work.’ And people hold on to that, including us,” said Dr. Yodice.

The study analyzed data from a Medicare cohort of 1,109 patients who died during 2000-2013 and had an ICU admission within the last 30 days of their life. Ages were fairly evenly distributed, with 29% aged 65-74 years, 39% aged 75-84, and 32% aged 85 and over. Fifty-four percent were women, 26% were nonwhite, 42% had not completed high school, and 11% were in skilled nursing facilities.

About 35% had no ACP in 2000-2001, and that percentage gradually declined, to about 20% in 2012-2013 (slope, –1.6%/year; P = .009).

Seventeen percent of white participants had no ACP, compared with 51% of blacks and 49% of Hispanics. Net worth was also strongly associated with having ACP: The top quartile had 13% lacking ACP, compared with 43% of the bottom quartile.

The study found that 94% of patients who had no ACP had visited a health care provider in the past year. The average number of visits in the past year was 20, and 83% had seen a provider within the past 30 days.

Dr. Block did not declare a source of funding or potential conflicts. Dr. Yodice had no disclosures.
 

chestphysiciannews@chestnet.org

SOURCE: Block B et al. CCC48, Abstract 401.

SAN DIEGO – A nationally representative survey of ICU patients older than age 65 years shows an improvement over time in the frequency of advance care planning (ACP), but one in four have no ACP; the problem is more pronounced among some blacks and Hispanics and those with lower net worth. The study also found that these patients see physicians an average of 20 times in the year preceding the ICU visit, which suggests that there are plenty of opportunities to put ACP in place.

marcosmartinezromero/iStockphoto

“Over two-thirds were seen by a doctor in the last 2 weeks. So they’re seeing doctors, but they’re still not doing advance care planning,” said Brian Block, MD, during a presentation of the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine. Dr. Block is with the University of California, San Francisco.

Lack of advance planning can put major road blocks in front of patient care in the ICU, as well as complicate communication between physicians and family members. The findings underscore the need to encourage conversations about end-of-life care between physicians and their patients – before the patients wind up in intensive care.

One audience member believes these conversations are already happening. Paul Yodice, MD, chairman of medicine at Saint Barnabas Medical Center in Livingston, N.J., suggested that physicians are attempting to engage older patients and family members in ACP, but many are unready to make decisions. “In my experience, it is happening much more frequently than is captured either in the medical record or in the research that we’ve been publishing. I’ve been a part of those conversations. Those individuals who are faced with those toughest of choices choose to delay making the decision or speaking about it further because it’s just too painful to consider, and they hold out hope of being the one to beat the odds, to have one more day,” said Dr. Yodice.

He called for further research to document whether ACP conversations are happening and to identify barriers to decisions and the means to overcome them. “A next good study would be to send out a respectful survey to the families of those who have lost people they love and ask: Has someone in the past year spoken with you or offered to have a discussion about end-of-life issues? We could get a better handle on [how often] the discussion is being had, and then find a solution,” said Dr. Yodice.

ACP can also be difficult for the provider, he added. Family members and patients, desperate for another treatment option, will often ask if there’s anything else that can be done. “In medicine, the answer almost always is ‘Well, we can try something else even though I know it’s not going to work.’ And people hold on to that, including us,” said Dr. Yodice.

The study analyzed data from a Medicare cohort of 1,109 patients who died during 2000-2013 and had an ICU admission within the last 30 days of their life. Ages were fairly evenly distributed, with 29% aged 65-74 years, 39% aged 75-84, and 32% aged 85 and over. Fifty-four percent were women, 26% were nonwhite, 42% had not completed high school, and 11% were in skilled nursing facilities.

About 35% had no ACP in 2000-2001, and that percentage gradually declined, to about 20% in 2012-2013 (slope, –1.6%/year; P = .009).

Seventeen percent of white participants had no ACP, compared with 51% of blacks and 49% of Hispanics. Net worth was also strongly associated with having ACP: The top quartile had 13% lacking ACP, compared with 43% of the bottom quartile.

The study found that 94% of patients who had no ACP had visited a health care provider in the past year. The average number of visits in the past year was 20, and 83% had seen a provider within the past 30 days.

Dr. Block did not declare a source of funding or potential conflicts. Dr. Yodice had no disclosures.
 

chestphysiciannews@chestnet.org

SOURCE: Block B et al. CCC48, Abstract 401.

HONOLULU – Covert strokes are relatively common in elderly patients who undergo noncardiac surgery, with a 7% incidence among a group of prospectively followed but generally unselected patients in a multicenter, international study.

By definition, these covert strokes were acutely asymptomatic, but showed evidence of clinical effects during the subsequent year. Twelve months after surgery, patients with acute, perioperative covert strokes found by systematic collection of postoperative MRI brain scans had a twofold increased rate of cognitive decline and a greater than twofold increased rate of delirium, compared with the patients who did not have evidence of a covert stroke, Marko Mrkobrada, MD, said at the International Stroke Conference sponsored by the American Heart Association.

The message from these findings is that, when elderly patients exhibit confusion or delirium after noncardiac surgery, their physicians should have a high index of suspicion that a covert stroke may have occurred, Dr. Mrkobrada said in a video interview. It’s possible that typical stroke symptoms do not appear in many of the covert stroke patients because they are masked in the immediate postoperative period, he added.

Right now, the only way to screen for a covert stroke is with a brain MR, a test that generally costs several hundred dollars, which is too expensive for routine screening. Dr. Mrkobrada said that his team hopes further study will identify a biomarker that can flag patients with a covert stroke at a lower cost. For example, colleagues of Dr. Mrkobrada have successfully used high-sensitivity troponin T, a biomarker of myocardial injury, to identify patients who have myocardial injury after noncardiac surgery (MINS; JAMA. 2017 April 25;371[16]:1642-51). Study results also established that treating MINS patients with dabigatran improved their long-term clinical outcomes (Lancet. 2018 June 9;391[10137]:2325-34).

Covert stroke after noncardiac surgery “is the same concept” as MINS, said Dr. Mrkobrada, a researcher at the London Health Sciences Centre in Canada. “We find strokes that do not get picked up after noncardiac surgery just like MIs that are not picked up,” he said. It’s also possible that certain interventions may improve outcomes in patients with covert strokes, just as they have helped MINS patients, he suggested. Potentially helpful interventions could include aspirin, a statin, and improved blood pressure control. A major goal for his research group is finding a biomarker that makes diagnosing covert stroke as easy as using high sensitivity troponin T to diagnose MINS.

The NeuroVISION (Detection and Neurological Impact of Cerebrovascular Events In Noncardiac Surgery Patients: A Cohort EvaluatioN) study enrolled and tested 1,114 people aged 65 years or older scheduled for elective noncardiac surgery anticipated to keep them hospitalized for at least 2 days at any of 12 participating centers in nine countries. Patients underwent cognitive function testing before surgery and had a brain MR scan 2-9 days after surgery, and they were excluded if they developed an overt stroke prior to the scan. Patients underwent a second round of cognitive testing a year after surgery. Patients averaged 73 years old.

The screening MR scans identified covert strokes in 78 of the study subjects (7%). The 1-year cognitive tests showed measurable drops in cognitive function in 42% of those who had experience covert strokes and in 29% of everyone else. Those rates translated to a doubled odds ratio for cognitive decline after covert stroke, compared with people without covert stroke after adjustment for baseline between-group differences, a highly statistically significant between-group difference for the study’s primary endpoint. Delirium occurred 2.2-fold more often in the covert stroke patients after adjustment, and overt strokes during 1-year follow-up were 4.1-fold more common patients who’d experienced a covert stroke, compared with everyone else, after adjustment, Dr. Mrkobrada reported. NeuroVISION is the first large-scale study to assess the incidence and associations of covert strokes after noncardiac surgery, he noted.

mzoler@mdedge.com

SOURCE: Mrkobrada M. ISC 2019, Late-Breaking Abstract LB18.

HONOLULU – Covert strokes are relatively common in elderly patients who undergo noncardiac surgery, with a 7% incidence among a group of prospectively followed but generally unselected patients in a multicenter, international study.

By definition, these covert strokes were acutely asymptomatic, but showed evidence of clinical effects during the subsequent year. Twelve months after surgery, patients with acute, perioperative covert strokes found by systematic collection of postoperative MRI brain scans had a twofold increased rate of cognitive decline and a greater than twofold increased rate of delirium, compared with the patients who did not have evidence of a covert stroke, Marko Mrkobrada, MD, said at the International Stroke Conference sponsored by the American Heart Association.

The message from these findings is that, when elderly patients exhibit confusion or delirium after noncardiac surgery, their physicians should have a high index of suspicion that a covert stroke may have occurred, Dr. Mrkobrada said in a video interview. It’s possible that typical stroke symptoms do not appear in many of the covert stroke patients because they are masked in the immediate postoperative period, he added.

Right now, the only way to screen for a covert stroke is with a brain MR, a test that generally costs several hundred dollars, which is too expensive for routine screening. Dr. Mrkobrada said that his team hopes further study will identify a biomarker that can flag patients with a covert stroke at a lower cost. For example, colleagues of Dr. Mrkobrada have successfully used high-sensitivity troponin T, a biomarker of myocardial injury, to identify patients who have myocardial injury after noncardiac surgery (MINS; JAMA. 2017 April 25;371[16]:1642-51). Study results also established that treating MINS patients with dabigatran improved their long-term clinical outcomes (Lancet. 2018 June 9;391[10137]:2325-34).

Covert stroke after noncardiac surgery “is the same concept” as MINS, said Dr. Mrkobrada, a researcher at the London Health Sciences Centre in Canada. “We find strokes that do not get picked up after noncardiac surgery just like MIs that are not picked up,” he said. It’s also possible that certain interventions may improve outcomes in patients with covert strokes, just as they have helped MINS patients, he suggested. Potentially helpful interventions could include aspirin, a statin, and improved blood pressure control. A major goal for his research group is finding a biomarker that makes diagnosing covert stroke as easy as using high sensitivity troponin T to diagnose MINS.

The NeuroVISION (Detection and Neurological Impact of Cerebrovascular Events In Noncardiac Surgery Patients: A Cohort EvaluatioN) study enrolled and tested 1,114 people aged 65 years or older scheduled for elective noncardiac surgery anticipated to keep them hospitalized for at least 2 days at any of 12 participating centers in nine countries. Patients underwent cognitive function testing before surgery and had a brain MR scan 2-9 days after surgery, and they were excluded if they developed an overt stroke prior to the scan. Patients underwent a second round of cognitive testing a year after surgery. Patients averaged 73 years old.

The screening MR scans identified covert strokes in 78 of the study subjects (7%). The 1-year cognitive tests showed measurable drops in cognitive function in 42% of those who had experience covert strokes and in 29% of everyone else. Those rates translated to a doubled odds ratio for cognitive decline after covert stroke, compared with people without covert stroke after adjustment for baseline between-group differences, a highly statistically significant between-group difference for the study’s primary endpoint. Delirium occurred 2.2-fold more often in the covert stroke patients after adjustment, and overt strokes during 1-year follow-up were 4.1-fold more common patients who’d experienced a covert stroke, compared with everyone else, after adjustment, Dr. Mrkobrada reported. NeuroVISION is the first large-scale study to assess the incidence and associations of covert strokes after noncardiac surgery, he noted.

mzoler@mdedge.com

SOURCE: Mrkobrada M. ISC 2019, Late-Breaking Abstract LB18.

HONOLULU – Covert strokes are relatively common in elderly patients who undergo noncardiac surgery, with a 7% incidence among a group of prospectively followed but generally unselected patients in a multicenter, international study.

By definition, these covert strokes were acutely asymptomatic, but showed evidence of clinical effects during the subsequent year. Twelve months after surgery, patients with acute, perioperative covert strokes found by systematic collection of postoperative MRI brain scans had a twofold increased rate of cognitive decline and a greater than twofold increased rate of delirium, compared with the patients who did not have evidence of a covert stroke, Marko Mrkobrada, MD, said at the International Stroke Conference sponsored by the American Heart Association.

The message from these findings is that, when elderly patients exhibit confusion or delirium after noncardiac surgery, their physicians should have a high index of suspicion that a covert stroke may have occurred, Dr. Mrkobrada said in a video interview. It’s possible that typical stroke symptoms do not appear in many of the covert stroke patients because they are masked in the immediate postoperative period, he added.

Right now, the only way to screen for a covert stroke is with a brain MR, a test that generally costs several hundred dollars, which is too expensive for routine screening. Dr. Mrkobrada said that his team hopes further study will identify a biomarker that can flag patients with a covert stroke at a lower cost. For example, colleagues of Dr. Mrkobrada have successfully used high-sensitivity troponin T, a biomarker of myocardial injury, to identify patients who have myocardial injury after noncardiac surgery (MINS; JAMA. 2017 April 25;371[16]:1642-51). Study results also established that treating MINS patients with dabigatran improved their long-term clinical outcomes (Lancet. 2018 June 9;391[10137]:2325-34).

Covert stroke after noncardiac surgery “is the same concept” as MINS, said Dr. Mrkobrada, a researcher at the London Health Sciences Centre in Canada. “We find strokes that do not get picked up after noncardiac surgery just like MIs that are not picked up,” he said. It’s also possible that certain interventions may improve outcomes in patients with covert strokes, just as they have helped MINS patients, he suggested. Potentially helpful interventions could include aspirin, a statin, and improved blood pressure control. A major goal for his research group is finding a biomarker that makes diagnosing covert stroke as easy as using high sensitivity troponin T to diagnose MINS.

The NeuroVISION (Detection and Neurological Impact of Cerebrovascular Events In Noncardiac Surgery Patients: A Cohort EvaluatioN) study enrolled and tested 1,114 people aged 65 years or older scheduled for elective noncardiac surgery anticipated to keep them hospitalized for at least 2 days at any of 12 participating centers in nine countries. Patients underwent cognitive function testing before surgery and had a brain MR scan 2-9 days after surgery, and they were excluded if they developed an overt stroke prior to the scan. Patients underwent a second round of cognitive testing a year after surgery. Patients averaged 73 years old.

The screening MR scans identified covert strokes in 78 of the study subjects (7%). The 1-year cognitive tests showed measurable drops in cognitive function in 42% of those who had experience covert strokes and in 29% of everyone else. Those rates translated to a doubled odds ratio for cognitive decline after covert stroke, compared with people without covert stroke after adjustment for baseline between-group differences, a highly statistically significant between-group difference for the study’s primary endpoint. Delirium occurred 2.2-fold more often in the covert stroke patients after adjustment, and overt strokes during 1-year follow-up were 4.1-fold more common patients who’d experienced a covert stroke, compared with everyone else, after adjustment, Dr. Mrkobrada reported. NeuroVISION is the first large-scale study to assess the incidence and associations of covert strokes after noncardiac surgery, he noted.

mzoler@mdedge.com

SOURCE: Mrkobrada M. ISC 2019, Late-Breaking Abstract LB18.

The Food and Drug Administration has issued warning letters to 12 companies and advisory letters to 5 companies illegally selling more than 58 products claiming to treat Alzheimer’s disease.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The products, many of which are marketed as dietary supplements, are being sold in a variety of forms, including tablets, capsules, and oils. These drugs are either unapproved or mislabeled and claim to prevent, treat, or cure Alzheimer’s disease, as well as a number of other serious diseases and health conditions, in violation of the Federal Food, Drug, and Cosmetic Act.

“Alzheimer’s is a challenging disease that, unfortunately, has no cure. Any products making unproven drug claims could mislead consumers to believe that such therapies exist and keep them from accessing therapies that are known to help support the symptoms of the disease, or worse, as some fraudulent treatments can cause serious or even fatal injuries,” FDA Commissioner Scott Gottlieb, MD, said in a press release.

In an additional statement, Dr. Gottlieb detailed several new strategies for improving the safety and accuracy of dietary supplements, including efforts to more rapidly communicate to the public potential safety issues with dietary supplement products and to establish a flexible regulatory framework that promotes innovation and upholds product safety.

lfranki@mdedge.com

The Food and Drug Administration has issued warning letters to 12 companies and advisory letters to 5 companies illegally selling more than 58 products claiming to treat Alzheimer’s disease.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The products, many of which are marketed as dietary supplements, are being sold in a variety of forms, including tablets, capsules, and oils. These drugs are either unapproved or mislabeled and claim to prevent, treat, or cure Alzheimer’s disease, as well as a number of other serious diseases and health conditions, in violation of the Federal Food, Drug, and Cosmetic Act.

“Alzheimer’s is a challenging disease that, unfortunately, has no cure. Any products making unproven drug claims could mislead consumers to believe that such therapies exist and keep them from accessing therapies that are known to help support the symptoms of the disease, or worse, as some fraudulent treatments can cause serious or even fatal injuries,” FDA Commissioner Scott Gottlieb, MD, said in a press release.

In an additional statement, Dr. Gottlieb detailed several new strategies for improving the safety and accuracy of dietary supplements, including efforts to more rapidly communicate to the public potential safety issues with dietary supplement products and to establish a flexible regulatory framework that promotes innovation and upholds product safety.

lfranki@mdedge.com

The Food and Drug Administration has issued warning letters to 12 companies and advisory letters to 5 companies illegally selling more than 58 products claiming to treat Alzheimer’s disease.

Wikimedia Commons/FitzColinGerald/Creative Commons License

The products, many of which are marketed as dietary supplements, are being sold in a variety of forms, including tablets, capsules, and oils. These drugs are either unapproved or mislabeled and claim to prevent, treat, or cure Alzheimer’s disease, as well as a number of other serious diseases and health conditions, in violation of the Federal Food, Drug, and Cosmetic Act.

“Alzheimer’s is a challenging disease that, unfortunately, has no cure. Any products making unproven drug claims could mislead consumers to believe that such therapies exist and keep them from accessing therapies that are known to help support the symptoms of the disease, or worse, as some fraudulent treatments can cause serious or even fatal injuries,” FDA Commissioner Scott Gottlieb, MD, said in a press release.

In an additional statement, Dr. Gottlieb detailed several new strategies for improving the safety and accuracy of dietary supplements, including efforts to more rapidly communicate to the public potential safety issues with dietary supplement products and to establish a flexible regulatory framework that promotes innovation and upholds product safety.

lfranki@mdedge.com

Exercise prevents falls in people older than 60 years, especially if it focuses on balance and mimics daily activities, according to a Cochrane Review meta-analysis of 108 randomized controlled trials.

kali9/Getty Images

Exercise has been shown to prevent falls in older people, but given the potential consequences, the investigators thought an up-to-date synthesis of the evidence was in order. The analysis focused on people living independently who had not recently been discharged from a hospital. The trials involved 23,407 subjects from 25 countries. The review was exhaustive; the final report is almost 600 pages long (Cochrane Database Syst Rev. 2019 Jan 31;1:CD012424. doi: 10.1002/14651858.CD012424.pub2).

The type of exercise matters. The researchers cited “high-certainty evidence” that exercise involving balance and functional training reduces falls. “Tai chi may also prevent falls,” they noted, adding that they were uncertain of the effect of dance, walking, and resistance training by itself. There was no evidence to determine the effects of flexibility or endurance exercises, added the researchers, led by Cathie Sherrington, PhD, of the University of Sydney Institute for Musculoskeletal Health.

Functional exercise mimics everyday movement, with the goal of improving performance. Multidirectional lunges are an example, helping the body prepare for vacuuming, yard work, and other common activities.

“Exercise [programs] carried out in group classes or done at home prescribed by a health professional ... or a trained exercise leader were effective. Exercises were mostly done while standing as this better enhances balance and the ability to do daily activities such as standing up from a low chair or climbing stairs,” according to a Cochrane press release regarding the study.

Overall, exercise reduced the number of falls by 23%, and the number of fallers by 15%, with high-certainty evidence.

Exercise also brought down the number of people facing fall fractures by over 27%, the number of people requiring medical attention for a fall by 39%, and the number ending up in the hospital for a fall by 22%.

Balance and functional exercises reduced the rate of falls by 24%, and the number of fallers by 13%. The effects were even greater when resistance exercises were added to the mix; drops in fall rates and the number of people experiencing falls were 34% and 22%, respectively. There was low-certainty evidence that tai chi reduces the rate of falls by 19% and the number of people experiencing falls by 20%.

Despite fall prevention, “exercise may make little important difference to health-related quality of life;” when results were converted to EQ-5D and 36-Item Short Form Survey scores, “the respective 95% [confidence intervals] were much smaller than minimally important differences,” the investigators said.

Serious adverse events occurred in participants in one of the 27 trials that reported adverse events. These two serious adverse events were a pelvic stress fracture and an inguinal hernia surgery. Most of the other adverse events reported, all non-serious, were musculoskeletal.

On average, participants were 76 years old, and 77% were women. Disease specific trials – such as exercise for stroke rehabilitation – were excluded.

The work was supported primarily by the Cochrane Bone, Joint and Muscle Trauma Group, based at the University of Manchester, England, and Cochrane’s Acute and Emergency Care Network. There were no industry disclosures.
 

aotto@mdedge.com

SOURCE: Sherrington C et al. Cochrane Database Syst Rev. 2019 Jan 31;1:CD012424. doi: 10.1002/14651858.CD012424.pub2.

Exercise prevents falls in people older than 60 years, especially if it focuses on balance and mimics daily activities, according to a Cochrane Review meta-analysis of 108 randomized controlled trials.

kali9/Getty Images

Exercise has been shown to prevent falls in older people, but given the potential consequences, the investigators thought an up-to-date synthesis of the evidence was in order. The analysis focused on people living independently who had not recently been discharged from a hospital. The trials involved 23,407 subjects from 25 countries. The review was exhaustive; the final report is almost 600 pages long (Cochrane Database Syst Rev. 2019 Jan 31;1:CD012424. doi: 10.1002/14651858.CD012424.pub2).

The type of exercise matters. The researchers cited “high-certainty evidence” that exercise involving balance and functional training reduces falls. “Tai chi may also prevent falls,” they noted, adding that they were uncertain of the effect of dance, walking, and resistance training by itself. There was no evidence to determine the effects of flexibility or endurance exercises, added the researchers, led by Cathie Sherrington, PhD, of the University of Sydney Institute for Musculoskeletal Health.

Functional exercise mimics everyday movement, with the goal of improving performance. Multidirectional lunges are an example, helping the body prepare for vacuuming, yard work, and other common activities.

“Exercise [programs] carried out in group classes or done at home prescribed by a health professional ... or a trained exercise leader were effective. Exercises were mostly done while standing as this better enhances balance and the ability to do daily activities such as standing up from a low chair or climbing stairs,” according to a Cochrane press release regarding the study.

Overall, exercise reduced the number of falls by 23%, and the number of fallers by 15%, with high-certainty evidence.

Exercise also brought down the number of people facing fall fractures by over 27%, the number of people requiring medical attention for a fall by 39%, and the number ending up in the hospital for a fall by 22%.

Balance and functional exercises reduced the rate of falls by 24%, and the number of fallers by 13%. The effects were even greater when resistance exercises were added to the mix; drops in fall rates and the number of people experiencing falls were 34% and 22%, respectively. There was low-certainty evidence that tai chi reduces the rate of falls by 19% and the number of people experiencing falls by 20%.

Despite fall prevention, “exercise may make little important difference to health-related quality of life;” when results were converted to EQ-5D and 36-Item Short Form Survey scores, “the respective 95% [confidence intervals] were much smaller than minimally important differences,” the investigators said.

Serious adverse events occurred in participants in one of the 27 trials that reported adverse events. These two serious adverse events were a pelvic stress fracture and an inguinal hernia surgery. Most of the other adverse events reported, all non-serious, were musculoskeletal.

On average, participants were 76 years old, and 77% were women. Disease specific trials – such as exercise for stroke rehabilitation – were excluded.

The work was supported primarily by the Cochrane Bone, Joint and Muscle Trauma Group, based at the University of Manchester, England, and Cochrane’s Acute and Emergency Care Network. There were no industry disclosures.
 

aotto@mdedge.com

SOURCE: Sherrington C et al. Cochrane Database Syst Rev. 2019 Jan 31;1:CD012424. doi: 10.1002/14651858.CD012424.pub2.

Exercise prevents falls in people older than 60 years, especially if it focuses on balance and mimics daily activities, according to a Cochrane Review meta-analysis of 108 randomized controlled trials.

kali9/Getty Images

Exercise has been shown to prevent falls in older people, but given the potential consequences, the investigators thought an up-to-date synthesis of the evidence was in order. The analysis focused on people living independently who had not recently been discharged from a hospital. The trials involved 23,407 subjects from 25 countries. The review was exhaustive; the final report is almost 600 pages long (Cochrane Database Syst Rev. 2019 Jan 31;1:CD012424. doi: 10.1002/14651858.CD012424.pub2).

The type of exercise matters. The researchers cited “high-certainty evidence” that exercise involving balance and functional training reduces falls. “Tai chi may also prevent falls,” they noted, adding that they were uncertain of the effect of dance, walking, and resistance training by itself. There was no evidence to determine the effects of flexibility or endurance exercises, added the researchers, led by Cathie Sherrington, PhD, of the University of Sydney Institute for Musculoskeletal Health.

Functional exercise mimics everyday movement, with the goal of improving performance. Multidirectional lunges are an example, helping the body prepare for vacuuming, yard work, and other common activities.

“Exercise [programs] carried out in group classes or done at home prescribed by a health professional ... or a trained exercise leader were effective. Exercises were mostly done while standing as this better enhances balance and the ability to do daily activities such as standing up from a low chair or climbing stairs,” according to a Cochrane press release regarding the study.

Overall, exercise reduced the number of falls by 23%, and the number of fallers by 15%, with high-certainty evidence.

Exercise also brought down the number of people facing fall fractures by over 27%, the number of people requiring medical attention for a fall by 39%, and the number ending up in the hospital for a fall by 22%.

Balance and functional exercises reduced the rate of falls by 24%, and the number of fallers by 13%. The effects were even greater when resistance exercises were added to the mix; drops in fall rates and the number of people experiencing falls were 34% and 22%, respectively. There was low-certainty evidence that tai chi reduces the rate of falls by 19% and the number of people experiencing falls by 20%.

Despite fall prevention, “exercise may make little important difference to health-related quality of life;” when results were converted to EQ-5D and 36-Item Short Form Survey scores, “the respective 95% [confidence intervals] were much smaller than minimally important differences,” the investigators said.

Serious adverse events occurred in participants in one of the 27 trials that reported adverse events. These two serious adverse events were a pelvic stress fracture and an inguinal hernia surgery. Most of the other adverse events reported, all non-serious, were musculoskeletal.

On average, participants were 76 years old, and 77% were women. Disease specific trials – such as exercise for stroke rehabilitation – were excluded.

The work was supported primarily by the Cochrane Bone, Joint and Muscle Trauma Group, based at the University of Manchester, England, and Cochrane’s Acute and Emergency Care Network. There were no industry disclosures.
 

aotto@mdedge.com

SOURCE: Sherrington C et al. Cochrane Database Syst Rev. 2019 Jan 31;1:CD012424. doi: 10.1002/14651858.CD012424.pub2.

A plasma proteomic study has identified new biomarkers of Alzheimer’s disease pathology in cognitively unimpaired individuals, researchers reported in Science Advances.

Kheng guan Toh/Thinkstock

“To our knowledge, this is the first time that a multianalyte plasma biomarker panel for an Alzheimer’s disease–related phenotype has been found and independently replicated by a nontargeted mass spectrometry approach,” said Nicholas J. Ashton, PhD, of King’s College London and the University of Gothenburg in Sweden, and his research colleagues.

Blood-based measures that predict amyloid-beta burden in preclinical Alzheimer’s disease have the potential to help investigators conduct clinical trials and aid in diagnostic management. However, this novel approach needs to be validated and translated “to a simpler automated platform suitable for wider utility,” the investigators noted. In addition, it is unclear whether their classifier can track changes in amyloid-beta or differentiate between other diseases with amyloid-beta pathology.

Advances in mass spectrometry technology have renewed interest in the analysis of plasma proteins in patients with various diseases. To assess whether proteomic discovery in plasma can help predict amyloid-beta burden in preclinical Alzheimer’s disease, Dr. Ashton and his colleagues studied 238 cognitively unimpaired individuals from the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) and the Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH). The participants had undergone PET to determine their amyloid-beta status. In the AIBL cohort (n = 144), 100 participants were amyloid-beta negative, and 44 were amyloid-beta positive. In the KARVIAH cohort (n = 94), 59 participants were amyloid-beta negative, and 35 were amyloid-beta positive. There were significantly more APOE4 carriers in the amyloid-beta–positive groups than in the amyloid-beta–negative groups. In addition, the amyloid-beta–positive groups tended to be older.

A support vector machine analysis created classifiers predicting amyloid-beta positivity in the AIBL cohort using demographics, proteins, or both. The researchers then tested each classifier in the KARVIAH dataset to identify which model best predicted amyloid-beta positivity. The optimal model included 10 protein features (prothrombin, adhesion G protein–coupled receptor, amyloid-beta A4 protein, NGN2, DNAH10, REST, NfL, RPS6KA3, GPSM2, FHAD1) and two demographic features (APOE4 count and age).

The classifier achieved a testing area under the receiver operator characteristic curve of 0.891 in the KARVIAH cohort to predict amyloid-beta positivity in cognitively unimpaired individuals with a sensitivity of 0.78 and specificity of 0.77.

The 10 protein features “represent a diverse array of pathways,” and the highest ranked feature was the serine protease prothrombin, which is a precursor to thrombin, the authors noted. “Multiple lines of evidence support that cerebrovascular disease may play a role in AD and that amyloid-beta may be involved in thrombosis, fibrinolysis, and inflammation via its interaction with the coagulation cascade,” the researchers wrote.

Two of the biomarkers – amyloid-beta A4 protein and NfL – have been examined in prior research and had a greater effect size in a secondary analysis that included participants with mild cognitive impairment and Alzheimer’s disease. This finding confirms “their connection with the more established disease state,” Dr. Ashton and colleagues said. In the secondary analysis, the optimal classifier included one demographic factor (APOE4 count) and nine protein features, eight of which also were used in the cognitively unimpaired classifier.

The study was funded in part by the National Institute for Health Research Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, and many authors reported additional research support from various institutions. One author is an employee of Johnson & Johnson and a named inventor on unrelated biomarker intellectual property owned by Proteome Science and King’s College London.

jremaly@mdedge.com

SOURCE: Ashton NJ et al. Sci Adv. 2019 Feb 6. doi: 10.1126/sciadv.aau7220.

A plasma proteomic study has identified new biomarkers of Alzheimer’s disease pathology in cognitively unimpaired individuals, researchers reported in Science Advances.

Kheng guan Toh/Thinkstock

“To our knowledge, this is the first time that a multianalyte plasma biomarker panel for an Alzheimer’s disease–related phenotype has been found and independently replicated by a nontargeted mass spectrometry approach,” said Nicholas J. Ashton, PhD, of King’s College London and the University of Gothenburg in Sweden, and his research colleagues.

Blood-based measures that predict amyloid-beta burden in preclinical Alzheimer’s disease have the potential to help investigators conduct clinical trials and aid in diagnostic management. However, this novel approach needs to be validated and translated “to a simpler automated platform suitable for wider utility,” the investigators noted. In addition, it is unclear whether their classifier can track changes in amyloid-beta or differentiate between other diseases with amyloid-beta pathology.

Advances in mass spectrometry technology have renewed interest in the analysis of plasma proteins in patients with various diseases. To assess whether proteomic discovery in plasma can help predict amyloid-beta burden in preclinical Alzheimer’s disease, Dr. Ashton and his colleagues studied 238 cognitively unimpaired individuals from the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) and the Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH). The participants had undergone PET to determine their amyloid-beta status. In the AIBL cohort (n = 144), 100 participants were amyloid-beta negative, and 44 were amyloid-beta positive. In the KARVIAH cohort (n = 94), 59 participants were amyloid-beta negative, and 35 were amyloid-beta positive. There were significantly more APOE4 carriers in the amyloid-beta–positive groups than in the amyloid-beta–negative groups. In addition, the amyloid-beta–positive groups tended to be older.

A support vector machine analysis created classifiers predicting amyloid-beta positivity in the AIBL cohort using demographics, proteins, or both. The researchers then tested each classifier in the KARVIAH dataset to identify which model best predicted amyloid-beta positivity. The optimal model included 10 protein features (prothrombin, adhesion G protein–coupled receptor, amyloid-beta A4 protein, NGN2, DNAH10, REST, NfL, RPS6KA3, GPSM2, FHAD1) and two demographic features (APOE4 count and age).

The classifier achieved a testing area under the receiver operator characteristic curve of 0.891 in the KARVIAH cohort to predict amyloid-beta positivity in cognitively unimpaired individuals with a sensitivity of 0.78 and specificity of 0.77.

The 10 protein features “represent a diverse array of pathways,” and the highest ranked feature was the serine protease prothrombin, which is a precursor to thrombin, the authors noted. “Multiple lines of evidence support that cerebrovascular disease may play a role in AD and that amyloid-beta may be involved in thrombosis, fibrinolysis, and inflammation via its interaction with the coagulation cascade,” the researchers wrote.

Two of the biomarkers – amyloid-beta A4 protein and NfL – have been examined in prior research and had a greater effect size in a secondary analysis that included participants with mild cognitive impairment and Alzheimer’s disease. This finding confirms “their connection with the more established disease state,” Dr. Ashton and colleagues said. In the secondary analysis, the optimal classifier included one demographic factor (APOE4 count) and nine protein features, eight of which also were used in the cognitively unimpaired classifier.

The study was funded in part by the National Institute for Health Research Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, and many authors reported additional research support from various institutions. One author is an employee of Johnson & Johnson and a named inventor on unrelated biomarker intellectual property owned by Proteome Science and King’s College London.

jremaly@mdedge.com

SOURCE: Ashton NJ et al. Sci Adv. 2019 Feb 6. doi: 10.1126/sciadv.aau7220.

A plasma proteomic study has identified new biomarkers of Alzheimer’s disease pathology in cognitively unimpaired individuals, researchers reported in Science Advances.

Kheng guan Toh/Thinkstock

“To our knowledge, this is the first time that a multianalyte plasma biomarker panel for an Alzheimer’s disease–related phenotype has been found and independently replicated by a nontargeted mass spectrometry approach,” said Nicholas J. Ashton, PhD, of King’s College London and the University of Gothenburg in Sweden, and his research colleagues.

Blood-based measures that predict amyloid-beta burden in preclinical Alzheimer’s disease have the potential to help investigators conduct clinical trials and aid in diagnostic management. However, this novel approach needs to be validated and translated “to a simpler automated platform suitable for wider utility,” the investigators noted. In addition, it is unclear whether their classifier can track changes in amyloid-beta or differentiate between other diseases with amyloid-beta pathology.

Advances in mass spectrometry technology have renewed interest in the analysis of plasma proteins in patients with various diseases. To assess whether proteomic discovery in plasma can help predict amyloid-beta burden in preclinical Alzheimer’s disease, Dr. Ashton and his colleagues studied 238 cognitively unimpaired individuals from the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) and the Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH). The participants had undergone PET to determine their amyloid-beta status. In the AIBL cohort (n = 144), 100 participants were amyloid-beta negative, and 44 were amyloid-beta positive. In the KARVIAH cohort (n = 94), 59 participants were amyloid-beta negative, and 35 were amyloid-beta positive. There were significantly more APOE4 carriers in the amyloid-beta–positive groups than in the amyloid-beta–negative groups. In addition, the amyloid-beta–positive groups tended to be older.

A support vector machine analysis created classifiers predicting amyloid-beta positivity in the AIBL cohort using demographics, proteins, or both. The researchers then tested each classifier in the KARVIAH dataset to identify which model best predicted amyloid-beta positivity. The optimal model included 10 protein features (prothrombin, adhesion G protein–coupled receptor, amyloid-beta A4 protein, NGN2, DNAH10, REST, NfL, RPS6KA3, GPSM2, FHAD1) and two demographic features (APOE4 count and age).

The classifier achieved a testing area under the receiver operator characteristic curve of 0.891 in the KARVIAH cohort to predict amyloid-beta positivity in cognitively unimpaired individuals with a sensitivity of 0.78 and specificity of 0.77.

The 10 protein features “represent a diverse array of pathways,” and the highest ranked feature was the serine protease prothrombin, which is a precursor to thrombin, the authors noted. “Multiple lines of evidence support that cerebrovascular disease may play a role in AD and that amyloid-beta may be involved in thrombosis, fibrinolysis, and inflammation via its interaction with the coagulation cascade,” the researchers wrote.

Two of the biomarkers – amyloid-beta A4 protein and NfL – have been examined in prior research and had a greater effect size in a secondary analysis that included participants with mild cognitive impairment and Alzheimer’s disease. This finding confirms “their connection with the more established disease state,” Dr. Ashton and colleagues said. In the secondary analysis, the optimal classifier included one demographic factor (APOE4 count) and nine protein features, eight of which also were used in the cognitively unimpaired classifier.

The study was funded in part by the National Institute for Health Research Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, and many authors reported additional research support from various institutions. One author is an employee of Johnson & Johnson and a named inventor on unrelated biomarker intellectual property owned by Proteome Science and King’s College London.

jremaly@mdedge.com

SOURCE: Ashton NJ et al. Sci Adv. 2019 Feb 6. doi: 10.1126/sciadv.aau7220.

Statin therapy appears to reduce the risk of major vascular events for patients of all age groups, but there is less evidence that older patients with evidence of occlusive vascular disease benefit from the treatment, according to a recent meta-analysis of 28 trials from the Cholesterol Treatment Trialists’ Collaboration published in The Lancet.

Louise Koenig/MDedge News

Statins are “useful and affordable drug[s] that reduce heart attacks and strokes in older patients. Until now there has been an evidence gap and we wanted to look at their efficacy and safety in older people,” Jordan Fulcher, BSc (Med), MBBS, from the Cholesterol Treatment Trialists’ (CTT) Collaboration and the University of Sydney stated in a press release. “Our analysis indicates that major cardiovascular events were reduced by about a fifth, per mmol/L lower LDL cholesterol, by statin therapy across all age groups. Despite previous concerns, we found no adverse effect on cancer or nonvascular mortality in any age group.”

The researchers examined 186,854 participants from 28 CTT trials undergoing statin therapy, of whom 14,483 (8%) were older than 75 years. Patients were divided into six groups based on age and examined the risk of major cardiovascular events such as stroke, coronary revascularization and major coronary events, as well as the incidence of cancer and vascular mortality.

Among all age groups, there was a significant reduction in major vascular events, with a 21% proportional per 1.0-mmol/L reduction in LDL cholesterol (risk ratio, 0.79; 95% confidence interval, 0.77-0.81) among patients receiving statin therapy or a more intensive statin regimen, and there was a 24% proportional reduction (RR, 0.76; 95% CI, 0.73-0.79) of major coronary events per 1.0-mmol/L reduction in LDL cholesterol, with older age resulting in a lower proportional reduction of major coronary events (P = .009). The researchers also found a proportional reduction of coronary revascularization procedures by 25% (RR, 0.75; 95% CI, 0.73-0.78) and stroke by 16% (RR, 0.84; 95% CI, 0.80-0.89) among patients of any age group receiving statin therapy or more intensive statin regimen, with no significant differences between age groups.

There was a 12% proportional reduction in vascular mortality per 1.0-mmol/L reduction in LDL cholesterol (RR, 0.88; 95% CI, 0.85-0.91), but this statistic did not remain significant after the researchers excluded four trials that included patients with heart failure or who were receiving renal dialysis. After excluding these trials from the overall analysis, the researchers found the smaller proportional reductions persisted for older patients for major coronary events (P = .01) but was no longer significant for major vascular events.

The researchers noted their study was limited by the highly selected patient population, low percentage of patients older than 75 years, including trials with efficacy endpoints where some nonserious adverse events may not have been recorded, and not including some trials in the meta-analysis if they were not part of the CTT.

This study was funded by Australian National Health and Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, and British Heart Foundation. The authors have reported personal fees, grants, and consulting fees from Abbott, Aegerion, Amgen, Arisaph, AstraZeneca, Bayer, Beckmann, Berlin-Chemie, Boehringer Ingelheim, Daiichi Sankyo, Dalcor, DuPont, Esperion, GlaxoSmithKline, ISIS Pharmaceuticals, Kowa, Mylan, Pfizer, Roche, Sanofi, Singulex, The Medicines Company, and Vatera Capital, as well as the British Heart Foundation, Cancer Research UK, National Institute for Health Research Oxford Biomedical Research Centre, Medical Research Council, Nuffield Department of Population Health, Weill Cornell Medicine, and UK Biobank.

SOURCE: Fulcher J et al. Lancet. 2019;393:407-15.

Statin therapy appears to reduce the risk of major vascular events for patients of all age groups, but there is less evidence that older patients with evidence of occlusive vascular disease benefit from the treatment, according to a recent meta-analysis of 28 trials from the Cholesterol Treatment Trialists’ Collaboration published in The Lancet.

Louise Koenig/MDedge News

Statins are “useful and affordable drug[s] that reduce heart attacks and strokes in older patients. Until now there has been an evidence gap and we wanted to look at their efficacy and safety in older people,” Jordan Fulcher, BSc (Med), MBBS, from the Cholesterol Treatment Trialists’ (CTT) Collaboration and the University of Sydney stated in a press release. “Our analysis indicates that major cardiovascular events were reduced by about a fifth, per mmol/L lower LDL cholesterol, by statin therapy across all age groups. Despite previous concerns, we found no adverse effect on cancer or nonvascular mortality in any age group.”

The researchers examined 186,854 participants from 28 CTT trials undergoing statin therapy, of whom 14,483 (8%) were older than 75 years. Patients were divided into six groups based on age and examined the risk of major cardiovascular events such as stroke, coronary revascularization and major coronary events, as well as the incidence of cancer and vascular mortality.

Among all age groups, there was a significant reduction in major vascular events, with a 21% proportional per 1.0-mmol/L reduction in LDL cholesterol (risk ratio, 0.79; 95% confidence interval, 0.77-0.81) among patients receiving statin therapy or a more intensive statin regimen, and there was a 24% proportional reduction (RR, 0.76; 95% CI, 0.73-0.79) of major coronary events per 1.0-mmol/L reduction in LDL cholesterol, with older age resulting in a lower proportional reduction of major coronary events (P = .009). The researchers also found a proportional reduction of coronary revascularization procedures by 25% (RR, 0.75; 95% CI, 0.73-0.78) and stroke by 16% (RR, 0.84; 95% CI, 0.80-0.89) among patients of any age group receiving statin therapy or more intensive statin regimen, with no significant differences between age groups.

There was a 12% proportional reduction in vascular mortality per 1.0-mmol/L reduction in LDL cholesterol (RR, 0.88; 95% CI, 0.85-0.91), but this statistic did not remain significant after the researchers excluded four trials that included patients with heart failure or who were receiving renal dialysis. After excluding these trials from the overall analysis, the researchers found the smaller proportional reductions persisted for older patients for major coronary events (P = .01) but was no longer significant for major vascular events.

The researchers noted their study was limited by the highly selected patient population, low percentage of patients older than 75 years, including trials with efficacy endpoints where some nonserious adverse events may not have been recorded, and not including some trials in the meta-analysis if they were not part of the CTT.

This study was funded by Australian National Health and Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, and British Heart Foundation. The authors have reported personal fees, grants, and consulting fees from Abbott, Aegerion, Amgen, Arisaph, AstraZeneca, Bayer, Beckmann, Berlin-Chemie, Boehringer Ingelheim, Daiichi Sankyo, Dalcor, DuPont, Esperion, GlaxoSmithKline, ISIS Pharmaceuticals, Kowa, Mylan, Pfizer, Roche, Sanofi, Singulex, The Medicines Company, and Vatera Capital, as well as the British Heart Foundation, Cancer Research UK, National Institute for Health Research Oxford Biomedical Research Centre, Medical Research Council, Nuffield Department of Population Health, Weill Cornell Medicine, and UK Biobank.

SOURCE: Fulcher J et al. Lancet. 2019;393:407-15.

Statin therapy appears to reduce the risk of major vascular events for patients of all age groups, but there is less evidence that older patients with evidence of occlusive vascular disease benefit from the treatment, according to a recent meta-analysis of 28 trials from the Cholesterol Treatment Trialists’ Collaboration published in The Lancet.

Louise Koenig/MDedge News

Statins are “useful and affordable drug[s] that reduce heart attacks and strokes in older patients. Until now there has been an evidence gap and we wanted to look at their efficacy and safety in older people,” Jordan Fulcher, BSc (Med), MBBS, from the Cholesterol Treatment Trialists’ (CTT) Collaboration and the University of Sydney stated in a press release. “Our analysis indicates that major cardiovascular events were reduced by about a fifth, per mmol/L lower LDL cholesterol, by statin therapy across all age groups. Despite previous concerns, we found no adverse effect on cancer or nonvascular mortality in any age group.”

The researchers examined 186,854 participants from 28 CTT trials undergoing statin therapy, of whom 14,483 (8%) were older than 75 years. Patients were divided into six groups based on age and examined the risk of major cardiovascular events such as stroke, coronary revascularization and major coronary events, as well as the incidence of cancer and vascular mortality.

Among all age groups, there was a significant reduction in major vascular events, with a 21% proportional per 1.0-mmol/L reduction in LDL cholesterol (risk ratio, 0.79; 95% confidence interval, 0.77-0.81) among patients receiving statin therapy or a more intensive statin regimen, and there was a 24% proportional reduction (RR, 0.76; 95% CI, 0.73-0.79) of major coronary events per 1.0-mmol/L reduction in LDL cholesterol, with older age resulting in a lower proportional reduction of major coronary events (P = .009). The researchers also found a proportional reduction of coronary revascularization procedures by 25% (RR, 0.75; 95% CI, 0.73-0.78) and stroke by 16% (RR, 0.84; 95% CI, 0.80-0.89) among patients of any age group receiving statin therapy or more intensive statin regimen, with no significant differences between age groups.

There was a 12% proportional reduction in vascular mortality per 1.0-mmol/L reduction in LDL cholesterol (RR, 0.88; 95% CI, 0.85-0.91), but this statistic did not remain significant after the researchers excluded four trials that included patients with heart failure or who were receiving renal dialysis. After excluding these trials from the overall analysis, the researchers found the smaller proportional reductions persisted for older patients for major coronary events (P = .01) but was no longer significant for major vascular events.

The researchers noted their study was limited by the highly selected patient population, low percentage of patients older than 75 years, including trials with efficacy endpoints where some nonserious adverse events may not have been recorded, and not including some trials in the meta-analysis if they were not part of the CTT.

This study was funded by Australian National Health and Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, UK Medical Research Council, and British Heart Foundation. The authors have reported personal fees, grants, and consulting fees from Abbott, Aegerion, Amgen, Arisaph, AstraZeneca, Bayer, Beckmann, Berlin-Chemie, Boehringer Ingelheim, Daiichi Sankyo, Dalcor, DuPont, Esperion, GlaxoSmithKline, ISIS Pharmaceuticals, Kowa, Mylan, Pfizer, Roche, Sanofi, Singulex, The Medicines Company, and Vatera Capital, as well as the British Heart Foundation, Cancer Research UK, National Institute for Health Research Oxford Biomedical Research Centre, Medical Research Council, Nuffield Department of Population Health, Weill Cornell Medicine, and UK Biobank.

SOURCE: Fulcher J et al. Lancet. 2019;393:407-15.

Here are 5 articles from the February issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Short-term lung function better predicts mortality risk in SSc

To take the posttest, go to: https://bit.ly/2RrRuIY
Expires November 26, 2019

2. Healthier lifestyle in midlife women reduces subclinical carotid atherosclerosis

To take the posttest, go to: https://bit.ly/2TvDH5G
Expires November 28, 2019

3. Three commonly used quick cognitive assessments often yield flawed results

To take the posttest, go to: https://bit.ly/2G1qkHn
Expires November 28, 2019

4. Missed HIV screening opportunities found among subsequently infected youth

To take the posttest, go to: https://bit.ly/2HGa8Nm
Expires November 29, 2019

5. Aspirin appears underused to prevent preeclampsia in SLE patients

To take the posttest, go to: https://bit.ly/2G0dU2v
Expires January 2, 2019

Here are 5 articles from the February issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Short-term lung function better predicts mortality risk in SSc

To take the posttest, go to: https://bit.ly/2RrRuIY
Expires November 26, 2019

2. Healthier lifestyle in midlife women reduces subclinical carotid atherosclerosis

To take the posttest, go to: https://bit.ly/2TvDH5G
Expires November 28, 2019

3. Three commonly used quick cognitive assessments often yield flawed results

To take the posttest, go to: https://bit.ly/2G1qkHn
Expires November 28, 2019

4. Missed HIV screening opportunities found among subsequently infected youth

To take the posttest, go to: https://bit.ly/2HGa8Nm
Expires November 29, 2019

5. Aspirin appears underused to prevent preeclampsia in SLE patients

To take the posttest, go to: https://bit.ly/2G0dU2v
Expires January 2, 2019

Here are 5 articles from the February issue of Clinician Reviews (individual articles are valid for one year from date of publication—expiration dates below):

1. Short-term lung function better predicts mortality risk in SSc

To take the posttest, go to: https://bit.ly/2RrRuIY
Expires November 26, 2019

2. Healthier lifestyle in midlife women reduces subclinical carotid atherosclerosis

To take the posttest, go to: https://bit.ly/2TvDH5G
Expires November 28, 2019

3. Three commonly used quick cognitive assessments often yield flawed results

To take the posttest, go to: https://bit.ly/2G1qkHn
Expires November 28, 2019

4. Missed HIV screening opportunities found among subsequently infected youth

To take the posttest, go to: https://bit.ly/2HGa8Nm
Expires November 29, 2019

5. Aspirin appears underused to prevent preeclampsia in SLE patients

To take the posttest, go to: https://bit.ly/2G0dU2v
Expires January 2, 2019