Geriatrics

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.
 

[email protected]

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.
 

[email protected]

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.
 

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.
 

[email protected]

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.
 

[email protected]

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.
 

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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

Whether subclinical hypothyroidism is clinically important and should be treated remains controversial. Studies have differed in their findings, and although most have found this condition to be associated with a variety of adverse outcomes, large randomized controlled trials are needed to clearly demonstrate its clinical impact in various age groups and the benefit of levothyroxine therapy.

Currently, the best practical approach is to base treatment decisions on the magnitude of elevation of thyroid-stimulating hormone (TSH) and whether the patient has thyroid autoantibodies and associated comorbid conditions.

HIGH TSH, NORMAL FREE T₄ LEVELS

Subclinical hypothyroidism is defined by elevated TSH along with a normal free thyroxine (T₄).¹

The hypothalamic-pituitary-thyroid axis is a balanced homeostatic system, and TSH and thyroid hormone levels have an inverse log-linear relation: if free T₄ and triiodothyronine (T₃) levels go down even a little, TSH levels go up a lot.²

TSH secretion is pulsatile and has a circadian rhythm: serum TSH levels are 50% higher at night and early in the morning than during the rest of the day. Thus, repeated measurements in the same patient can vary by as much as half of the reference range.³

WHAT IS THE UPPER LIMIT OF NORMAL FOR TSH?

The upper limit of normal for TSH, defined as the 97.5th percentile, is approximately 4 or 5 mIU/L depending on the laboratory and the population, but some experts believe it should be lower.³

In favor of a lower upper limit: the distribution of serum TSH levels in the healthy general population does not seem to be a typical bell-shaped Gaussian curve, but rather has a tail at the high end. Some argue that some of the individuals with values in the upper end of the normal range may actually have undiagnosed hypothyroidism and that the upper 97.5th percentile cutoff would be 2.5 mIU/L if these people were excluded.⁴ Also, TSH levels higher than 2.5 mIU/L have been associated with a higher prevalence of antithyroid antibodies and a higher risk of clinical hypothyroidism.⁵

On the other hand, lowering the upper limit of normal to 2.5 mIU/L would result in 4 times as many people receiving a diagnosis of subclinical hypothyroidism, or 22 to 28 million people in the United States.^4,6 Thus, lowering the cutoff may lead to unnecessary therapy and could even harm from overtreatment.

Another argument against lowering the upper limit of normal for TSH is that, with age, serum TSH levels shift higher.⁷ The third National Health and Nutrition Education Survey (NHANES III) found that the 97.5th percentile for serum TSH was 3.56 mIU/L for age group 20 to 29 but 7.49 mIU/L for octogenarians.^7,8

It has been suggested that the upper limit of normal for TSH be adjusted for age, race, sex, and iodine intake.³ Currently available TSH reference ranges are not adjusted for these variables, and there is not enough evidence to suggest age-appropriate ranges,⁹ although higher TSH cutoffs for treatment are advised in elderly patients.¹⁰ Interestingly, higher TSH in older people has been linked to lower mortality rates in some studies.¹¹

Authors of the NHANES III⁸ and Hanford Thyroid Disease study¹² have proposed a cutoff of 4.1 mIU/L for the upper limit of normal for serum TSH in patients with negative antithyroid antibodies and normal findings on thyroid ultrasonography.

SUBCLINICAL HYPOTHYROIDISM IS COMMON

In different studies, the prevalence of subclinical hypothyroidism has been as low as 4% and as high as 20%.^1,8,13 The prevalence is higher in women and increases with age.⁸ It is higher in iodine-sufficient areas, and it increases in iodine-deficient areas with iodine supplementation.¹⁴ Genetics also plays a role, as subclinical hypothyroidism is more common in white people than in African Americans.⁸

A difficulty in estimating the prevalence is the disagreement about the cutoff for TSH, which may differ from that in the general population in certain subgroups such as adolescents, the elderly, and pregnant women.^10,15

A VARIETY OF CAUSES

The most common cause of subclinical hypothyroidism, accounting for 60% to 80% of cases, is Hashimoto (autoimmune) thyroiditis,² in which thyroid peroxidase antibodies are usually present.^2,16

Also important to rule out are false-positive elevations due to substances that interfere with TSH assays (eg, heterophile antibodies, rheumatoid factor, biotin, macro-TSH); reversible causes such as the recovery phase of euthyroid sick syndrome; subacute, painless, or postpartum thyroiditis; central hypo- or hyperthyroidism; and thyroid hormone resistance.

SUBCLINICAL HYPOTHYROIDISM CAN RESOLVE OR PROGRESS 


“Subclinical” suggests that the disease is in its early stage, with changes in TSH already apparent but decreases in thyroid hormone levels yet to come.¹⁷ And indeed, subclinical hypothyroidism can progress to overt hypothyroidism,¹⁸ although it has been reported to resolve spontaneously in half of cases within 2 years,¹⁹ typically in patients with TSH values of 4 to 6 mIU/L.²⁰ The rate of progression to overt hypothyroidism is estimated to be 33% to 55% over 10 to 20 years of follow-up.¹⁸

Figure 1 shows the natural history of subclinical hypothyroidism.¹

GUIDELINES FOR SCREENING DIFFER

Guidelines differ on screening for thyroid disease in the general population, owing to lack of large-scale randomized controlled trials showing treatment benefit in otherwise-healthy people with mildly elevated TSH values.

Various professional societies have adopted different criteria for aggressive case-finding in patients at risk of thyroid disease. Risk factors include family history of thyroid disease, neck irradiation, partial thyroidectomy, dyslipidemia, atrial fibrillation, unexplained weight loss, hyperprolactinemia, autoimmune disorders, and use of medications affecting thyroid function.²³

The US Preventive Services Task Force in 2014 found insufficient evidence on the benefits and harms of screening.²⁴

The American Thyroid Association (ATA) recommends screening adults starting at age 35, with repeat testing every 5 years in patients who have no signs or symptoms of hypothyroidism, and more frequently in those who do.²⁵

The American Association of Clinical Endocrinologists recommends screening in women and older patients. Their guidelines and those of the ATA also suggest screening people at high risk of thyroid disease due to risk factors such as history of autoimmune diseases, neck irradiation, or medications affecting thyroid function.²⁶

The American Academy of Family Physicians recommends screening after age 60.¹⁸

The American College of Physicians recommends screening patients over age 50 who have symptoms.¹⁸

Our approach. Although evidence is lacking to recommend routine screening in adults, aggressive case-finding and treatment in patients at risk of thyroid disease can, we believe, offset the risks associated with subclinical hypothyroidism.²⁴

CLINICAL PRESENTATION

About 70% of patients with subclinical hypothyroidism have no symptoms.¹³

Tiredness was more common in subclinical hypothyroid patients with TSH levels lower than 10 mIU/L compared with euthyroid controls in 1 study, but other studies have been unable to replicate this finding.^27,28

Other frequently reported symptoms include dry skin, cognitive slowing, poor memory, muscle weakness, cold intolerance, constipation, puffy eyes, and hoarseness.¹³

The evidence in favor of levothyroxine therapy to improve symptoms in subclinical hypothyroidism has varied, with some studies showing an improvement in symptom scores compared with placebo, while others have not shown any benefit.^29–31

In one study, the average TSH value for patients whose symptoms did not improve with therapy was 4.6 mIU/L.³¹ An explanation for the lack of effect in this group may be that the TSH values for these patients were in the high-normal range. Also, because most subclinical hypothyroid patients have no symptoms, it is difficult to ascertain symptomatic improvement. Though it is possible to conclude that levothyroxine therapy has a limited role in this group, it is important to also consider the suggestive evidence that untreated subclinical hypothyroidism may lead to increased morbidity and mortality.

ADVERSE EFFECTS OF SUBCLINICAL HYPOTHYROIDISM, EFFECTS OF THERAPY

INDIVIDUALIZED MANAGEMENT AND SHARED DECISION-MAKING

The management of subclinical hypothyroidism should be individualized on the basis of extent of thyroid dysfunction, comorbid conditions, risk factors, and patient preference.¹¹⁸ Shared decision-making is key, weighing the risks and benefits of levothyroxine treatment and the patient’s goals.

The risks of treatment should be kept in mind and explained to the patient. Levothyroxine has a narrow therapeutic range, causing a possibility of overreplacement, and a half-life of 7 days that can cause dosing errors to have longer effect.^118,119

Adherence can be a challenge. The drug needs to be taken on an empty stomach because foods and supplements interfere with its absorption.^118,120 In addition, the cost of medication, frequent biochemical monitoring, and possible need for titration can add to financial burden.

When choosing the dose, one should consider the degree of hypothyroidism or TSH elevation and the patient’s weight, and adjust the dose gently.

If the TSH is high-normal

It is proposed that a TSH range of 3 to 5 mIU/L overlaps with normal thyroid function in a great segment of the population, and at this level it is probably not associated with clinically significant consequences. For these reasons, levothyroxine therapy is not thought to be beneficial for those with TSH in this range.

Pollock et al¹²¹ found that, in patients with symptoms suggesting hypothyroidism and TSH values in the upper end of the normal range, there was no improvement in cognitive function or psychological well-being after 12 weeks of levothyroxine therapy.

However, due to the concern for possible adverse maternal and fetal outcomes and low IQ in children of pregnant patients with subclinical hypothyroidism, levothyroxine therapy is advised in those who are pregnant or planning pregnancy who have TSH levels higher than 2.5 mIU/L, especially if they have thyroid peroxidase antibody. Levothyroxine therapy is not recommended for pregnant patients with negative thyroid peroxidase antibody and TSH within the pregnancy-specific range or less than 4 mIU/L if the reference ranges are unavailable.

Keep in mind that, even at these TSH values, there is risk of progression to overt hypothyroidism, especially in the presence of thyroid peroxidase antibody, so patients in this group should be monitored closely.

If TSH is mildly elevated

The evidence to support levothyroxine therapy in patients with subclinical hypothyroidism with TSH levels less than 10 mIU/L remains inconclusive, and the decision to treat should be based on clinical judgment.² The studies that have looked at the benefit of treating subclinical hypothyroidism in terms of cardiac, neuromuscular, cognitive, and neuropsychiatric outcomes have included patients with a wide range of TSH levels, and some of these studies were not stratified on the basis of degree of TSH elevation.

The risk that subclinical hypothyroidism will progress to overt hypothyroidism in patients with TSH higher than 8 mIU/L is high, and in 70% of these patients, the TSH level rises to more than 10 mIU/L within 4 years. Early treatment should be considered if the TSH is higher than 7 or 8 mIU/L.

If TSH is higher than 10 mIU/L

Figure 2 outlines an algorithmic approach to subclinical hypothyroidism in nonpregnant patients as suggested by Peeters.¹²²

Whether subclinical hypothyroidism is clinically important and should be treated remains controversial. Studies have differed in their findings, and although most have found this condition to be associated with a variety of adverse outcomes, large randomized controlled trials are needed to clearly demonstrate its clinical impact in various age groups and the benefit of levothyroxine therapy.

Currently, the best practical approach is to base treatment decisions on the magnitude of elevation of thyroid-stimulating hormone (TSH) and whether the patient has thyroid autoantibodies and associated comorbid conditions.

HIGH TSH, NORMAL FREE T₄ LEVELS

Subclinical hypothyroidism is defined by elevated TSH along with a normal free thyroxine (T₄).¹

The hypothalamic-pituitary-thyroid axis is a balanced homeostatic system, and TSH and thyroid hormone levels have an inverse log-linear relation: if free T₄ and triiodothyronine (T₃) levels go down even a little, TSH levels go up a lot.²

TSH secretion is pulsatile and has a circadian rhythm: serum TSH levels are 50% higher at night and early in the morning than during the rest of the day. Thus, repeated measurements in the same patient can vary by as much as half of the reference range.³

WHAT IS THE UPPER LIMIT OF NORMAL FOR TSH?

The upper limit of normal for TSH, defined as the 97.5th percentile, is approximately 4 or 5 mIU/L depending on the laboratory and the population, but some experts believe it should be lower.³

In favor of a lower upper limit: the distribution of serum TSH levels in the healthy general population does not seem to be a typical bell-shaped Gaussian curve, but rather has a tail at the high end. Some argue that some of the individuals with values in the upper end of the normal range may actually have undiagnosed hypothyroidism and that the upper 97.5th percentile cutoff would be 2.5 mIU/L if these people were excluded.⁴ Also, TSH levels higher than 2.5 mIU/L have been associated with a higher prevalence of antithyroid antibodies and a higher risk of clinical hypothyroidism.⁵

On the other hand, lowering the upper limit of normal to 2.5 mIU/L would result in 4 times as many people receiving a diagnosis of subclinical hypothyroidism, or 22 to 28 million people in the United States.^4,6 Thus, lowering the cutoff may lead to unnecessary therapy and could even harm from overtreatment.

Another argument against lowering the upper limit of normal for TSH is that, with age, serum TSH levels shift higher.⁷ The third National Health and Nutrition Education Survey (NHANES III) found that the 97.5th percentile for serum TSH was 3.56 mIU/L for age group 20 to 29 but 7.49 mIU/L for octogenarians.^7,8

It has been suggested that the upper limit of normal for TSH be adjusted for age, race, sex, and iodine intake.³ Currently available TSH reference ranges are not adjusted for these variables, and there is not enough evidence to suggest age-appropriate ranges,⁹ although higher TSH cutoffs for treatment are advised in elderly patients.¹⁰ Interestingly, higher TSH in older people has been linked to lower mortality rates in some studies.¹¹

Authors of the NHANES III⁸ and Hanford Thyroid Disease study¹² have proposed a cutoff of 4.1 mIU/L for the upper limit of normal for serum TSH in patients with negative antithyroid antibodies and normal findings on thyroid ultrasonography.

SUBCLINICAL HYPOTHYROIDISM IS COMMON

In different studies, the prevalence of subclinical hypothyroidism has been as low as 4% and as high as 20%.^1,8,13 The prevalence is higher in women and increases with age.⁸ It is higher in iodine-sufficient areas, and it increases in iodine-deficient areas with iodine supplementation.¹⁴ Genetics also plays a role, as subclinical hypothyroidism is more common in white people than in African Americans.⁸

A difficulty in estimating the prevalence is the disagreement about the cutoff for TSH, which may differ from that in the general population in certain subgroups such as adolescents, the elderly, and pregnant women.^10,15

A VARIETY OF CAUSES

The most common cause of subclinical hypothyroidism, accounting for 60% to 80% of cases, is Hashimoto (autoimmune) thyroiditis,² in which thyroid peroxidase antibodies are usually present.^2,16

Also important to rule out are false-positive elevations due to substances that interfere with TSH assays (eg, heterophile antibodies, rheumatoid factor, biotin, macro-TSH); reversible causes such as the recovery phase of euthyroid sick syndrome; subacute, painless, or postpartum thyroiditis; central hypo- or hyperthyroidism; and thyroid hormone resistance.

SUBCLINICAL HYPOTHYROIDISM CAN RESOLVE OR PROGRESS 


“Subclinical” suggests that the disease is in its early stage, with changes in TSH already apparent but decreases in thyroid hormone levels yet to come.¹⁷ And indeed, subclinical hypothyroidism can progress to overt hypothyroidism,¹⁸ although it has been reported to resolve spontaneously in half of cases within 2 years,¹⁹ typically in patients with TSH values of 4 to 6 mIU/L.²⁰ The rate of progression to overt hypothyroidism is estimated to be 33% to 55% over 10 to 20 years of follow-up.¹⁸

Figure 1 shows the natural history of subclinical hypothyroidism.¹

GUIDELINES FOR SCREENING DIFFER

Guidelines differ on screening for thyroid disease in the general population, owing to lack of large-scale randomized controlled trials showing treatment benefit in otherwise-healthy people with mildly elevated TSH values.

Various professional societies have adopted different criteria for aggressive case-finding in patients at risk of thyroid disease. Risk factors include family history of thyroid disease, neck irradiation, partial thyroidectomy, dyslipidemia, atrial fibrillation, unexplained weight loss, hyperprolactinemia, autoimmune disorders, and use of medications affecting thyroid function.²³

The US Preventive Services Task Force in 2014 found insufficient evidence on the benefits and harms of screening.²⁴

The American Thyroid Association (ATA) recommends screening adults starting at age 35, with repeat testing every 5 years in patients who have no signs or symptoms of hypothyroidism, and more frequently in those who do.²⁵

The American Association of Clinical Endocrinologists recommends screening in women and older patients. Their guidelines and those of the ATA also suggest screening people at high risk of thyroid disease due to risk factors such as history of autoimmune diseases, neck irradiation, or medications affecting thyroid function.²⁶

The American Academy of Family Physicians recommends screening after age 60.¹⁸

The American College of Physicians recommends screening patients over age 50 who have symptoms.¹⁸

Our approach. Although evidence is lacking to recommend routine screening in adults, aggressive case-finding and treatment in patients at risk of thyroid disease can, we believe, offset the risks associated with subclinical hypothyroidism.²⁴

CLINICAL PRESENTATION

About 70% of patients with subclinical hypothyroidism have no symptoms.¹³

Tiredness was more common in subclinical hypothyroid patients with TSH levels lower than 10 mIU/L compared with euthyroid controls in 1 study, but other studies have been unable to replicate this finding.^27,28

Other frequently reported symptoms include dry skin, cognitive slowing, poor memory, muscle weakness, cold intolerance, constipation, puffy eyes, and hoarseness.¹³

The evidence in favor of levothyroxine therapy to improve symptoms in subclinical hypothyroidism has varied, with some studies showing an improvement in symptom scores compared with placebo, while others have not shown any benefit.^29–31

In one study, the average TSH value for patients whose symptoms did not improve with therapy was 4.6 mIU/L.³¹ An explanation for the lack of effect in this group may be that the TSH values for these patients were in the high-normal range. Also, because most subclinical hypothyroid patients have no symptoms, it is difficult to ascertain symptomatic improvement. Though it is possible to conclude that levothyroxine therapy has a limited role in this group, it is important to also consider the suggestive evidence that untreated subclinical hypothyroidism may lead to increased morbidity and mortality.

ADVERSE EFFECTS OF SUBCLINICAL HYPOTHYROIDISM, EFFECTS OF THERAPY

INDIVIDUALIZED MANAGEMENT AND SHARED DECISION-MAKING

The management of subclinical hypothyroidism should be individualized on the basis of extent of thyroid dysfunction, comorbid conditions, risk factors, and patient preference.¹¹⁸ Shared decision-making is key, weighing the risks and benefits of levothyroxine treatment and the patient’s goals.

The risks of treatment should be kept in mind and explained to the patient. Levothyroxine has a narrow therapeutic range, causing a possibility of overreplacement, and a half-life of 7 days that can cause dosing errors to have longer effect.^118,119

Adherence can be a challenge. The drug needs to be taken on an empty stomach because foods and supplements interfere with its absorption.^118,120 In addition, the cost of medication, frequent biochemical monitoring, and possible need for titration can add to financial burden.

When choosing the dose, one should consider the degree of hypothyroidism or TSH elevation and the patient’s weight, and adjust the dose gently.

If the TSH is high-normal

It is proposed that a TSH range of 3 to 5 mIU/L overlaps with normal thyroid function in a great segment of the population, and at this level it is probably not associated with clinically significant consequences. For these reasons, levothyroxine therapy is not thought to be beneficial for those with TSH in this range.

Pollock et al¹²¹ found that, in patients with symptoms suggesting hypothyroidism and TSH values in the upper end of the normal range, there was no improvement in cognitive function or psychological well-being after 12 weeks of levothyroxine therapy.

However, due to the concern for possible adverse maternal and fetal outcomes and low IQ in children of pregnant patients with subclinical hypothyroidism, levothyroxine therapy is advised in those who are pregnant or planning pregnancy who have TSH levels higher than 2.5 mIU/L, especially if they have thyroid peroxidase antibody. Levothyroxine therapy is not recommended for pregnant patients with negative thyroid peroxidase antibody and TSH within the pregnancy-specific range or less than 4 mIU/L if the reference ranges are unavailable.

Keep in mind that, even at these TSH values, there is risk of progression to overt hypothyroidism, especially in the presence of thyroid peroxidase antibody, so patients in this group should be monitored closely.

If TSH is mildly elevated

The evidence to support levothyroxine therapy in patients with subclinical hypothyroidism with TSH levels less than 10 mIU/L remains inconclusive, and the decision to treat should be based on clinical judgment.² The studies that have looked at the benefit of treating subclinical hypothyroidism in terms of cardiac, neuromuscular, cognitive, and neuropsychiatric outcomes have included patients with a wide range of TSH levels, and some of these studies were not stratified on the basis of degree of TSH elevation.

The risk that subclinical hypothyroidism will progress to overt hypothyroidism in patients with TSH higher than 8 mIU/L is high, and in 70% of these patients, the TSH level rises to more than 10 mIU/L within 4 years. Early treatment should be considered if the TSH is higher than 7 or 8 mIU/L.

If TSH is higher than 10 mIU/L

Figure 2 outlines an algorithmic approach to subclinical hypothyroidism in nonpregnant patients as suggested by Peeters.¹²²

Whether subclinical hypothyroidism is clinically important and should be treated remains controversial. Studies have differed in their findings, and although most have found this condition to be associated with a variety of adverse outcomes, large randomized controlled trials are needed to clearly demonstrate its clinical impact in various age groups and the benefit of levothyroxine therapy.

Currently, the best practical approach is to base treatment decisions on the magnitude of elevation of thyroid-stimulating hormone (TSH) and whether the patient has thyroid autoantibodies and associated comorbid conditions.

HIGH TSH, NORMAL FREE T₄ LEVELS

Subclinical hypothyroidism is defined by elevated TSH along with a normal free thyroxine (T₄).¹

The hypothalamic-pituitary-thyroid axis is a balanced homeostatic system, and TSH and thyroid hormone levels have an inverse log-linear relation: if free T₄ and triiodothyronine (T₃) levels go down even a little, TSH levels go up a lot.²

TSH secretion is pulsatile and has a circadian rhythm: serum TSH levels are 50% higher at night and early in the morning than during the rest of the day. Thus, repeated measurements in the same patient can vary by as much as half of the reference range.³

WHAT IS THE UPPER LIMIT OF NORMAL FOR TSH?

The upper limit of normal for TSH, defined as the 97.5th percentile, is approximately 4 or 5 mIU/L depending on the laboratory and the population, but some experts believe it should be lower.³

In favor of a lower upper limit: the distribution of serum TSH levels in the healthy general population does not seem to be a typical bell-shaped Gaussian curve, but rather has a tail at the high end. Some argue that some of the individuals with values in the upper end of the normal range may actually have undiagnosed hypothyroidism and that the upper 97.5th percentile cutoff would be 2.5 mIU/L if these people were excluded.⁴ Also, TSH levels higher than 2.5 mIU/L have been associated with a higher prevalence of antithyroid antibodies and a higher risk of clinical hypothyroidism.⁵

On the other hand, lowering the upper limit of normal to 2.5 mIU/L would result in 4 times as many people receiving a diagnosis of subclinical hypothyroidism, or 22 to 28 million people in the United States.^4,6 Thus, lowering the cutoff may lead to unnecessary therapy and could even harm from overtreatment.

Another argument against lowering the upper limit of normal for TSH is that, with age, serum TSH levels shift higher.⁷ The third National Health and Nutrition Education Survey (NHANES III) found that the 97.5th percentile for serum TSH was 3.56 mIU/L for age group 20 to 29 but 7.49 mIU/L for octogenarians.^7,8

It has been suggested that the upper limit of normal for TSH be adjusted for age, race, sex, and iodine intake.³ Currently available TSH reference ranges are not adjusted for these variables, and there is not enough evidence to suggest age-appropriate ranges,⁹ although higher TSH cutoffs for treatment are advised in elderly patients.¹⁰ Interestingly, higher TSH in older people has been linked to lower mortality rates in some studies.¹¹

Authors of the NHANES III⁸ and Hanford Thyroid Disease study¹² have proposed a cutoff of 4.1 mIU/L for the upper limit of normal for serum TSH in patients with negative antithyroid antibodies and normal findings on thyroid ultrasonography.

SUBCLINICAL HYPOTHYROIDISM IS COMMON

In different studies, the prevalence of subclinical hypothyroidism has been as low as 4% and as high as 20%.^1,8,13 The prevalence is higher in women and increases with age.⁸ It is higher in iodine-sufficient areas, and it increases in iodine-deficient areas with iodine supplementation.¹⁴ Genetics also plays a role, as subclinical hypothyroidism is more common in white people than in African Americans.⁸

A difficulty in estimating the prevalence is the disagreement about the cutoff for TSH, which may differ from that in the general population in certain subgroups such as adolescents, the elderly, and pregnant women.^10,15

A VARIETY OF CAUSES

The most common cause of subclinical hypothyroidism, accounting for 60% to 80% of cases, is Hashimoto (autoimmune) thyroiditis,² in which thyroid peroxidase antibodies are usually present.^2,16

Also important to rule out are false-positive elevations due to substances that interfere with TSH assays (eg, heterophile antibodies, rheumatoid factor, biotin, macro-TSH); reversible causes such as the recovery phase of euthyroid sick syndrome; subacute, painless, or postpartum thyroiditis; central hypo- or hyperthyroidism; and thyroid hormone resistance.

SUBCLINICAL HYPOTHYROIDISM CAN RESOLVE OR PROGRESS 


“Subclinical” suggests that the disease is in its early stage, with changes in TSH already apparent but decreases in thyroid hormone levels yet to come.¹⁷ And indeed, subclinical hypothyroidism can progress to overt hypothyroidism,¹⁸ although it has been reported to resolve spontaneously in half of cases within 2 years,¹⁹ typically in patients with TSH values of 4 to 6 mIU/L.²⁰ The rate of progression to overt hypothyroidism is estimated to be 33% to 55% over 10 to 20 years of follow-up.¹⁸

Figure 1 shows the natural history of subclinical hypothyroidism.¹

GUIDELINES FOR SCREENING DIFFER

Guidelines differ on screening for thyroid disease in the general population, owing to lack of large-scale randomized controlled trials showing treatment benefit in otherwise-healthy people with mildly elevated TSH values.

Various professional societies have adopted different criteria for aggressive case-finding in patients at risk of thyroid disease. Risk factors include family history of thyroid disease, neck irradiation, partial thyroidectomy, dyslipidemia, atrial fibrillation, unexplained weight loss, hyperprolactinemia, autoimmune disorders, and use of medications affecting thyroid function.²³

The US Preventive Services Task Force in 2014 found insufficient evidence on the benefits and harms of screening.²⁴

The American Thyroid Association (ATA) recommends screening adults starting at age 35, with repeat testing every 5 years in patients who have no signs or symptoms of hypothyroidism, and more frequently in those who do.²⁵

The American Association of Clinical Endocrinologists recommends screening in women and older patients. Their guidelines and those of the ATA also suggest screening people at high risk of thyroid disease due to risk factors such as history of autoimmune diseases, neck irradiation, or medications affecting thyroid function.²⁶

The American Academy of Family Physicians recommends screening after age 60.¹⁸

The American College of Physicians recommends screening patients over age 50 who have symptoms.¹⁸

Our approach. Although evidence is lacking to recommend routine screening in adults, aggressive case-finding and treatment in patients at risk of thyroid disease can, we believe, offset the risks associated with subclinical hypothyroidism.²⁴

CLINICAL PRESENTATION

About 70% of patients with subclinical hypothyroidism have no symptoms.¹³

Tiredness was more common in subclinical hypothyroid patients with TSH levels lower than 10 mIU/L compared with euthyroid controls in 1 study, but other studies have been unable to replicate this finding.^27,28

Other frequently reported symptoms include dry skin, cognitive slowing, poor memory, muscle weakness, cold intolerance, constipation, puffy eyes, and hoarseness.¹³

The evidence in favor of levothyroxine therapy to improve symptoms in subclinical hypothyroidism has varied, with some studies showing an improvement in symptom scores compared with placebo, while others have not shown any benefit.^29–31

In one study, the average TSH value for patients whose symptoms did not improve with therapy was 4.6 mIU/L.³¹ An explanation for the lack of effect in this group may be that the TSH values for these patients were in the high-normal range. Also, because most subclinical hypothyroid patients have no symptoms, it is difficult to ascertain symptomatic improvement. Though it is possible to conclude that levothyroxine therapy has a limited role in this group, it is important to also consider the suggestive evidence that untreated subclinical hypothyroidism may lead to increased morbidity and mortality.

ADVERSE EFFECTS OF SUBCLINICAL HYPOTHYROIDISM, EFFECTS OF THERAPY

INDIVIDUALIZED MANAGEMENT AND SHARED DECISION-MAKING

The management of subclinical hypothyroidism should be individualized on the basis of extent of thyroid dysfunction, comorbid conditions, risk factors, and patient preference.¹¹⁸ Shared decision-making is key, weighing the risks and benefits of levothyroxine treatment and the patient’s goals.

The risks of treatment should be kept in mind and explained to the patient. Levothyroxine has a narrow therapeutic range, causing a possibility of overreplacement, and a half-life of 7 days that can cause dosing errors to have longer effect.^118,119

Adherence can be a challenge. The drug needs to be taken on an empty stomach because foods and supplements interfere with its absorption.^118,120 In addition, the cost of medication, frequent biochemical monitoring, and possible need for titration can add to financial burden.

When choosing the dose, one should consider the degree of hypothyroidism or TSH elevation and the patient’s weight, and adjust the dose gently.

If the TSH is high-normal

It is proposed that a TSH range of 3 to 5 mIU/L overlaps with normal thyroid function in a great segment of the population, and at this level it is probably not associated with clinically significant consequences. For these reasons, levothyroxine therapy is not thought to be beneficial for those with TSH in this range.

Pollock et al¹²¹ found that, in patients with symptoms suggesting hypothyroidism and TSH values in the upper end of the normal range, there was no improvement in cognitive function or psychological well-being after 12 weeks of levothyroxine therapy.

However, due to the concern for possible adverse maternal and fetal outcomes and low IQ in children of pregnant patients with subclinical hypothyroidism, levothyroxine therapy is advised in those who are pregnant or planning pregnancy who have TSH levels higher than 2.5 mIU/L, especially if they have thyroid peroxidase antibody. Levothyroxine therapy is not recommended for pregnant patients with negative thyroid peroxidase antibody and TSH within the pregnancy-specific range or less than 4 mIU/L if the reference ranges are unavailable.

Keep in mind that, even at these TSH values, there is risk of progression to overt hypothyroidism, especially in the presence of thyroid peroxidase antibody, so patients in this group should be monitored closely.

If TSH is mildly elevated

The evidence to support levothyroxine therapy in patients with subclinical hypothyroidism with TSH levels less than 10 mIU/L remains inconclusive, and the decision to treat should be based on clinical judgment.² The studies that have looked at the benefit of treating subclinical hypothyroidism in terms of cardiac, neuromuscular, cognitive, and neuropsychiatric outcomes have included patients with a wide range of TSH levels, and some of these studies were not stratified on the basis of degree of TSH elevation.

The risk that subclinical hypothyroidism will progress to overt hypothyroidism in patients with TSH higher than 8 mIU/L is high, and in 70% of these patients, the TSH level rises to more than 10 mIU/L within 4 years. Early treatment should be considered if the TSH is higher than 7 or 8 mIU/L.

If TSH is higher than 10 mIU/L

Figure 2 outlines an algorithmic approach to subclinical hypothyroidism in nonpregnant patients as suggested by Peeters.¹²²

At a quick read, the messages from these articles may seem contradictory. But the biology is more complex in the setting of endogenous production of T₄ by the thyroid gland, which is regulated by TSH, which in turn is regulated in a feedback loop by the thyroid-produced T₄. In the setting of a fixed replacement dose of exogenous levothyroxine, the provided hormone affects the pituitary production of TSH, which likely will have no significant subsequent effect on the T₄ level. Thus, the feedback control loop is far simpler.

There has not been a definitive study demonstrating that thyroxine supplementation in patients with subclinical hypothyroidism results in a superior clinical outcome. There are hints that this may be the case, and Azim and Nasr cite some of these studies. Recognizing a few markedly different physiologic reasons why the TSH can be slightly elevated and the T₄ normal helps explain the lack of uniform clinical success with supplementation therapy and provides rationales for some management strategies.

Any biological variability in the responsiveness of the thyroid gland to TSH may affect the relationship between the levels of TSH and thyroid gland-released T₄. In theory, if the thyroid receptor has decreased affinity for TSH, a higher TSH concentration will be needed to get the thyroid gland to secrete the level of T₄ that the pituitary sensing mechanism deems normal for that individual. If the receptor affinity was decreased due to a gene polymorphism, this relationship between TSH and T₄ may be stable, and providing exogenous T₄ will result in a lower, “normalized” TSH level but may disrupt the thyroid-pituitary crosstalk and may even produce clinical hyperthyroidism.

A similar scenario exists in the setting of early thyroid gland failure, such as in Hashimoto thyroiditis. But in the latter scenario, the TSH-to-T₄ production relationship may be unstable over time, for as additional thyroid gland is destroyed, T₄ production will continue to decrease, the TSH will increase, and the thyroid gland may ultimately fail and hypothyroidism will occur. Hence the recommendation that in the setting of subclinical hypothyroidism and antiperoxidase antibodies, T₄ and TSH levels should be monitored regularly in order to detect early true thyroid gland failure when the T₄ level can no longer be maintained despite the increased stimulation of the gland by the elevated TSH. Analogous to this may be subclinical hypothyroidism in the elderly, in whom thyroid gland failure may develop, despite an increased TSH, from senescence rather than autoimmunity. What I am suggesting is that the natural history of all patients with subclinical hypothyroidism is not alike, and it thus should not be surprising that there does not seem to be a one-size-fits-all approach to management.

Symptoms in patients with subclinical hypothyroidism have not uniformly improved with T₄ treatment compared with placebo. Notably, most patients with subclinical hypothyroidism experience no symptoms. But consider the extremely common symptom of fatigue, which can be present for a myriad of defined and undefined reasons. This symptom may often lead physicians to check the TSH and, if that is even slightly elevated, to also check the T₄. It may also lead some physicians to routinely check the T₄. Subclinical hypothyroidism is also quite common; thus, by chance alone or because of the circadian timing of checking the TSH, a slightly elevated TSH and fatigue may coexist and yet be unrelated.

Additionally, a positive biochemical response to thyroxine supplementation, such as a lowering of cholesterol, does not prove that the patient was clinically hypothyroid prior to supplementation, any more than lowering a patient’s blood glucose with insulin proves that the patient was diabetic. The management of subclinical hypothyroidism should be nuanced and based on both clinical and laboratory parameters.

At a quick read, the messages from these articles may seem contradictory. But the biology is more complex in the setting of endogenous production of T₄ by the thyroid gland, which is regulated by TSH, which in turn is regulated in a feedback loop by the thyroid-produced T₄. In the setting of a fixed replacement dose of exogenous levothyroxine, the provided hormone affects the pituitary production of TSH, which likely will have no significant subsequent effect on the T₄ level. Thus, the feedback control loop is far simpler.

There has not been a definitive study demonstrating that thyroxine supplementation in patients with subclinical hypothyroidism results in a superior clinical outcome. There are hints that this may be the case, and Azim and Nasr cite some of these studies. Recognizing a few markedly different physiologic reasons why the TSH can be slightly elevated and the T₄ normal helps explain the lack of uniform clinical success with supplementation therapy and provides rationales for some management strategies.

Any biological variability in the responsiveness of the thyroid gland to TSH may affect the relationship between the levels of TSH and thyroid gland-released T₄. In theory, if the thyroid receptor has decreased affinity for TSH, a higher TSH concentration will be needed to get the thyroid gland to secrete the level of T₄ that the pituitary sensing mechanism deems normal for that individual. If the receptor affinity was decreased due to a gene polymorphism, this relationship between TSH and T₄ may be stable, and providing exogenous T₄ will result in a lower, “normalized” TSH level but may disrupt the thyroid-pituitary crosstalk and may even produce clinical hyperthyroidism.

A similar scenario exists in the setting of early thyroid gland failure, such as in Hashimoto thyroiditis. But in the latter scenario, the TSH-to-T₄ production relationship may be unstable over time, for as additional thyroid gland is destroyed, T₄ production will continue to decrease, the TSH will increase, and the thyroid gland may ultimately fail and hypothyroidism will occur. Hence the recommendation that in the setting of subclinical hypothyroidism and antiperoxidase antibodies, T₄ and TSH levels should be monitored regularly in order to detect early true thyroid gland failure when the T₄ level can no longer be maintained despite the increased stimulation of the gland by the elevated TSH. Analogous to this may be subclinical hypothyroidism in the elderly, in whom thyroid gland failure may develop, despite an increased TSH, from senescence rather than autoimmunity. What I am suggesting is that the natural history of all patients with subclinical hypothyroidism is not alike, and it thus should not be surprising that there does not seem to be a one-size-fits-all approach to management.

Symptoms in patients with subclinical hypothyroidism have not uniformly improved with T₄ treatment compared with placebo. Notably, most patients with subclinical hypothyroidism experience no symptoms. But consider the extremely common symptom of fatigue, which can be present for a myriad of defined and undefined reasons. This symptom may often lead physicians to check the TSH and, if that is even slightly elevated, to also check the T₄. It may also lead some physicians to routinely check the T₄. Subclinical hypothyroidism is also quite common; thus, by chance alone or because of the circadian timing of checking the TSH, a slightly elevated TSH and fatigue may coexist and yet be unrelated.

Additionally, a positive biochemical response to thyroxine supplementation, such as a lowering of cholesterol, does not prove that the patient was clinically hypothyroid prior to supplementation, any more than lowering a patient’s blood glucose with insulin proves that the patient was diabetic. The management of subclinical hypothyroidism should be nuanced and based on both clinical and laboratory parameters.

At a quick read, the messages from these articles may seem contradictory. But the biology is more complex in the setting of endogenous production of T₄ by the thyroid gland, which is regulated by TSH, which in turn is regulated in a feedback loop by the thyroid-produced T₄. In the setting of a fixed replacement dose of exogenous levothyroxine, the provided hormone affects the pituitary production of TSH, which likely will have no significant subsequent effect on the T₄ level. Thus, the feedback control loop is far simpler.

There has not been a definitive study demonstrating that thyroxine supplementation in patients with subclinical hypothyroidism results in a superior clinical outcome. There are hints that this may be the case, and Azim and Nasr cite some of these studies. Recognizing a few markedly different physiologic reasons why the TSH can be slightly elevated and the T₄ normal helps explain the lack of uniform clinical success with supplementation therapy and provides rationales for some management strategies.

Any biological variability in the responsiveness of the thyroid gland to TSH may affect the relationship between the levels of TSH and thyroid gland-released T₄. In theory, if the thyroid receptor has decreased affinity for TSH, a higher TSH concentration will be needed to get the thyroid gland to secrete the level of T₄ that the pituitary sensing mechanism deems normal for that individual. If the receptor affinity was decreased due to a gene polymorphism, this relationship between TSH and T₄ may be stable, and providing exogenous T₄ will result in a lower, “normalized” TSH level but may disrupt the thyroid-pituitary crosstalk and may even produce clinical hyperthyroidism.

A similar scenario exists in the setting of early thyroid gland failure, such as in Hashimoto thyroiditis. But in the latter scenario, the TSH-to-T₄ production relationship may be unstable over time, for as additional thyroid gland is destroyed, T₄ production will continue to decrease, the TSH will increase, and the thyroid gland may ultimately fail and hypothyroidism will occur. Hence the recommendation that in the setting of subclinical hypothyroidism and antiperoxidase antibodies, T₄ and TSH levels should be monitored regularly in order to detect early true thyroid gland failure when the T₄ level can no longer be maintained despite the increased stimulation of the gland by the elevated TSH. Analogous to this may be subclinical hypothyroidism in the elderly, in whom thyroid gland failure may develop, despite an increased TSH, from senescence rather than autoimmunity. What I am suggesting is that the natural history of all patients with subclinical hypothyroidism is not alike, and it thus should not be surprising that there does not seem to be a one-size-fits-all approach to management.

Symptoms in patients with subclinical hypothyroidism have not uniformly improved with T₄ treatment compared with placebo. Notably, most patients with subclinical hypothyroidism experience no symptoms. But consider the extremely common symptom of fatigue, which can be present for a myriad of defined and undefined reasons. This symptom may often lead physicians to check the TSH and, if that is even slightly elevated, to also check the T₄. It may also lead some physicians to routinely check the T₄. Subclinical hypothyroidism is also quite common; thus, by chance alone or because of the circadian timing of checking the TSH, a slightly elevated TSH and fatigue may coexist and yet be unrelated.

Additionally, a positive biochemical response to thyroxine supplementation, such as a lowering of cholesterol, does not prove that the patient was clinically hypothyroid prior to supplementation, any more than lowering a patient’s blood glucose with insulin proves that the patient was diabetic. The management of subclinical hypothyroidism should be nuanced and based on both clinical and laboratory parameters.