Clinical question: Does high-flow oxygen therapy result in a decreased rate of intubation for patients with nonhypercapnic acute hypoxemic respiratory failure?

Bottom line: In this underpowered study, the use of high-flow oxygen therapy did not significantly reduce the rate of intubation as compared with standard oxygen therapy or noninvasive positive pressure ventilation in patients with nonhypercapnic acute hypoxemic respiratory failure. However, patients in the high-flow oxygen group had decreased 90-day mortality, as well as an increased number of ventilator-free days. Patients in the high-flow oxygen group also reported less respiratory discomfort and dyspnea than patients in the other 2 groups. (LOE = 1b-)

Reference: Frat J, Thille AW, Mercat A, et al, for the FLORALI Study Group and the REVA Network. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med 2015;372(23):2185-2196.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis: High-flow oxygen therapy uses oxygen delivered via nasal cannula at high flow rates to provide low-level positive pressure and reduce effective deadspace in the airways. Its effectiveness in the treatment of acute hypoxemic respiratory failure has not been established. In this study, investigators compared high-flow oxygen therapy with noninvasive positive pressure ventilation as well as with standard oxygen therapy in patients with nonhypercapnic acute hypoxemic respiratory failure.

Using concealed allocation, patients were randomized into 1 of 3 groups: (1) standard oxygen therapy using a nonrebreather face mask at a flow rate of 10 liters per minute or more; (2) high-flow oxygen therapy provided through a heated humidifier at a rate of 50 liters per minute for at least 2 days; or (3) noninvasive positive pressure ventilation for 8 hours per day for at least 2 days. With all 3 strategies, the goal was to maintain an oxygen saturation level of 92% or more. The 3 groups were similar at baseline with the majority of patients having community-acquired pneumonia as a cause of their acute respiratory failure. Analysis was by intention to treat.

For the primary outcome, the high-flow oxygen therapy group had a lower rate of intubation at 28 days than the other 2 groups, but this difference was not statistically significant (38% in high-flow group, 47% in standard group, 50% in noninvasive ventilation group; P = .18). Of note, the intubation rate in the standard oxygen therapy group was lower than the expected 60%, thus the study was underpowered to detect a difference if it truly exists. The high-flow therapy resulted in reduced 90-day mortality as compared with both standard therapy (hazard ratio [HR] = 2.01, 95% CI 1.01-3.99; P = .046) and noninvasive ventilation (HR = 2.50, 1.31-4.78; P = .006).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does high-flow oxygen therapy result in a decreased rate of intubation for patients with nonhypercapnic acute hypoxemic respiratory failure?

Bottom line: In this underpowered study, the use of high-flow oxygen therapy did not significantly reduce the rate of intubation as compared with standard oxygen therapy or noninvasive positive pressure ventilation in patients with nonhypercapnic acute hypoxemic respiratory failure. However, patients in the high-flow oxygen group had decreased 90-day mortality, as well as an increased number of ventilator-free days. Patients in the high-flow oxygen group also reported less respiratory discomfort and dyspnea than patients in the other 2 groups. (LOE = 1b-)

Reference: Frat J, Thille AW, Mercat A, et al, for the FLORALI Study Group and the REVA Network. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med 2015;372(23):2185-2196.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis: High-flow oxygen therapy uses oxygen delivered via nasal cannula at high flow rates to provide low-level positive pressure and reduce effective deadspace in the airways. Its effectiveness in the treatment of acute hypoxemic respiratory failure has not been established. In this study, investigators compared high-flow oxygen therapy with noninvasive positive pressure ventilation as well as with standard oxygen therapy in patients with nonhypercapnic acute hypoxemic respiratory failure.

Using concealed allocation, patients were randomized into 1 of 3 groups: (1) standard oxygen therapy using a nonrebreather face mask at a flow rate of 10 liters per minute or more; (2) high-flow oxygen therapy provided through a heated humidifier at a rate of 50 liters per minute for at least 2 days; or (3) noninvasive positive pressure ventilation for 8 hours per day for at least 2 days. With all 3 strategies, the goal was to maintain an oxygen saturation level of 92% or more. The 3 groups were similar at baseline with the majority of patients having community-acquired pneumonia as a cause of their acute respiratory failure. Analysis was by intention to treat.

For the primary outcome, the high-flow oxygen therapy group had a lower rate of intubation at 28 days than the other 2 groups, but this difference was not statistically significant (38% in high-flow group, 47% in standard group, 50% in noninvasive ventilation group; P = .18). Of note, the intubation rate in the standard oxygen therapy group was lower than the expected 60%, thus the study was underpowered to detect a difference if it truly exists. The high-flow therapy resulted in reduced 90-day mortality as compared with both standard therapy (hazard ratio [HR] = 2.01, 95% CI 1.01-3.99; P = .046) and noninvasive ventilation (HR = 2.50, 1.31-4.78; P = .006).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does high-flow oxygen therapy result in a decreased rate of intubation for patients with nonhypercapnic acute hypoxemic respiratory failure?

Bottom line: In this underpowered study, the use of high-flow oxygen therapy did not significantly reduce the rate of intubation as compared with standard oxygen therapy or noninvasive positive pressure ventilation in patients with nonhypercapnic acute hypoxemic respiratory failure. However, patients in the high-flow oxygen group had decreased 90-day mortality, as well as an increased number of ventilator-free days. Patients in the high-flow oxygen group also reported less respiratory discomfort and dyspnea than patients in the other 2 groups. (LOE = 1b-)

Reference: Frat J, Thille AW, Mercat A, et al, for the FLORALI Study Group and the REVA Network. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med 2015;372(23):2185-2196.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (ICU only)

Synopsis: High-flow oxygen therapy uses oxygen delivered via nasal cannula at high flow rates to provide low-level positive pressure and reduce effective deadspace in the airways. Its effectiveness in the treatment of acute hypoxemic respiratory failure has not been established. In this study, investigators compared high-flow oxygen therapy with noninvasive positive pressure ventilation as well as with standard oxygen therapy in patients with nonhypercapnic acute hypoxemic respiratory failure.

Using concealed allocation, patients were randomized into 1 of 3 groups: (1) standard oxygen therapy using a nonrebreather face mask at a flow rate of 10 liters per minute or more; (2) high-flow oxygen therapy provided through a heated humidifier at a rate of 50 liters per minute for at least 2 days; or (3) noninvasive positive pressure ventilation for 8 hours per day for at least 2 days. With all 3 strategies, the goal was to maintain an oxygen saturation level of 92% or more. The 3 groups were similar at baseline with the majority of patients having community-acquired pneumonia as a cause of their acute respiratory failure. Analysis was by intention to treat.

For the primary outcome, the high-flow oxygen therapy group had a lower rate of intubation at 28 days than the other 2 groups, but this difference was not statistically significant (38% in high-flow group, 47% in standard group, 50% in noninvasive ventilation group; P = .18). Of note, the intubation rate in the standard oxygen therapy group was lower than the expected 60%, thus the study was underpowered to detect a difference if it truly exists. The high-flow therapy resulted in reduced 90-day mortality as compared with both standard therapy (hazard ratio [HR] = 2.01, 95% CI 1.01-3.99; P = .046) and noninvasive ventilation (HR = 2.50, 1.31-4.78; P = .006).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of a patient navigator to guide hospitalized patients through the health care system reduce 30-day readmission rates?

Bottom line: The use of a community health worker acting as a patient navigator (PN), both during hospitalization and after discharge, to assist patients with coordination of care, follow-up appointments, provider communication, and medication compliance decreases the 30-day readmission rate in older high-risk patients, but increased admissions in younger patients, suggesting that the younger population may require different strategies to decrease their use of hospital-based care. (LOE = 1b-)

Reference: Balaban RB, Galbraith AA, Burns ME, Vialle-Valentin CE, Larochelle MR, Ross-Degnan D. A patient navigator intervention to reduce hospital readmissions among high-risk safety-net patients: a randomized controlled trial. J Gen Intern Med 2015;30(7):907-915.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: This US study took place within a safety-net hospital system in Massachusetts that has a large underserved patient population. The authors enrolled more than 1500 hospitalized patients with at least 1 of 5 risk factors for readmission (older than 60 years, previous hospitalization within the last 6 months, length of stay of 3 days or more, or admission diagnoses of heart failure or chronic obstructive pulmonary disease). Patients in the intervention group were assigned to a hospital-based community health worker, or PN, while patients in the control group received usual care. The PN's primary responsibility was helping the patient navigate through the health care system, including assessing postdischarge needs, assisting with communication with inpatient providers and primary care physicians, confirming and rescheduling follow-up appointments, addressing barriers to taking medications, and assisting with transportation and insurance issues. These services were provided through a hospital visit and at least 3 weekly postdischarge phone calls. Patients in both groups were racially diverse and the majority carried public insurance. The patients older than 60 years were more medically complex, but younger patients had more psychiatric disorders and substance use disorders, as well as higher rates of previous hospitalizations and longer lengths of stay.

Overall, the 30-day readmission rate did not differ significantly between the control and intervention groups, but the study was underpowered given the limits to enrollment during the prespecified period. In an adjusted analysis of the 2 age subgroups, however, readmissions decreased by 4% in older intervention patients and they increased by 12% in younger intervention patients (both differences statistically significant).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of a patient navigator to guide hospitalized patients through the health care system reduce 30-day readmission rates?

Bottom line: The use of a community health worker acting as a patient navigator (PN), both during hospitalization and after discharge, to assist patients with coordination of care, follow-up appointments, provider communication, and medication compliance decreases the 30-day readmission rate in older high-risk patients, but increased admissions in younger patients, suggesting that the younger population may require different strategies to decrease their use of hospital-based care. (LOE = 1b-)

Reference: Balaban RB, Galbraith AA, Burns ME, Vialle-Valentin CE, Larochelle MR, Ross-Degnan D. A patient navigator intervention to reduce hospital readmissions among high-risk safety-net patients: a randomized controlled trial. J Gen Intern Med 2015;30(7):907-915.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: This US study took place within a safety-net hospital system in Massachusetts that has a large underserved patient population. The authors enrolled more than 1500 hospitalized patients with at least 1 of 5 risk factors for readmission (older than 60 years, previous hospitalization within the last 6 months, length of stay of 3 days or more, or admission diagnoses of heart failure or chronic obstructive pulmonary disease). Patients in the intervention group were assigned to a hospital-based community health worker, or PN, while patients in the control group received usual care. The PN's primary responsibility was helping the patient navigate through the health care system, including assessing postdischarge needs, assisting with communication with inpatient providers and primary care physicians, confirming and rescheduling follow-up appointments, addressing barriers to taking medications, and assisting with transportation and insurance issues. These services were provided through a hospital visit and at least 3 weekly postdischarge phone calls. Patients in both groups were racially diverse and the majority carried public insurance. The patients older than 60 years were more medically complex, but younger patients had more psychiatric disorders and substance use disorders, as well as higher rates of previous hospitalizations and longer lengths of stay.

Overall, the 30-day readmission rate did not differ significantly between the control and intervention groups, but the study was underpowered given the limits to enrollment during the prespecified period. In an adjusted analysis of the 2 age subgroups, however, readmissions decreased by 4% in older intervention patients and they increased by 12% in younger intervention patients (both differences statistically significant).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

Clinical question: Does the use of a patient navigator to guide hospitalized patients through the health care system reduce 30-day readmission rates?

Bottom line: The use of a community health worker acting as a patient navigator (PN), both during hospitalization and after discharge, to assist patients with coordination of care, follow-up appointments, provider communication, and medication compliance decreases the 30-day readmission rate in older high-risk patients, but increased admissions in younger patients, suggesting that the younger population may require different strategies to decrease their use of hospital-based care. (LOE = 1b-)

Reference: Balaban RB, Galbraith AA, Burns ME, Vialle-Valentin CE, Larochelle MR, Ross-Degnan D. A patient navigator intervention to reduce hospital readmissions among high-risk safety-net patients: a randomized controlled trial. J Gen Intern Med 2015;30(7):907-915.

Study design: Randomized controlled trial (nonblinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (any location) with outpatient follow-up

Synopsis: This US study took place within a safety-net hospital system in Massachusetts that has a large underserved patient population. The authors enrolled more than 1500 hospitalized patients with at least 1 of 5 risk factors for readmission (older than 60 years, previous hospitalization within the last 6 months, length of stay of 3 days or more, or admission diagnoses of heart failure or chronic obstructive pulmonary disease). Patients in the intervention group were assigned to a hospital-based community health worker, or PN, while patients in the control group received usual care. The PN's primary responsibility was helping the patient navigate through the health care system, including assessing postdischarge needs, assisting with communication with inpatient providers and primary care physicians, confirming and rescheduling follow-up appointments, addressing barriers to taking medications, and assisting with transportation and insurance issues. These services were provided through a hospital visit and at least 3 weekly postdischarge phone calls. Patients in both groups were racially diverse and the majority carried public insurance. The patients older than 60 years were more medically complex, but younger patients had more psychiatric disorders and substance use disorders, as well as higher rates of previous hospitalizations and longer lengths of stay.

Overall, the 30-day readmission rate did not differ significantly between the control and intervention groups, but the study was underpowered given the limits to enrollment during the prespecified period. In an adjusted analysis of the 2 age subgroups, however, readmissions decreased by 4% in older intervention patients and they increased by 12% in younger intervention patients (both differences statistically significant).

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

My 27-year-old patient with a body mass index of 64 kg/m² presented to my clinic with back and leg pain. Unfortunately, I was not the least bit surprised.

When bending over, he developed acute onset of back pain, with radiating pain down the lateral side of his right leg to his foot. Exam and history were consistent with lumbar radiculopathy.

©Ingram Publishing/Thinkstock.com

Over the next several months, the patient had intractable pain in the presence of escalating opioids. The neurosurgeons said that his weight created too high a risk for intraoperative and postoperative complications, with which I agreed.

And so began the work of titrating his pain-modulating agents, along with the significantly less glamorous and substantially more challenging task of helping him lose weight.

He was staunchly opposed to bariatric surgery and could not afford weight loss medications, presenting a bit of an impasse. To me, the fact that his insurance company would have covered his spinal surgery but not his FDA-approved weight loss medications embodies one of the great medical mysteries of modern times.

His mother accompanied him on one of his several visits and chimed in, “He needs to eat bread, doesn’t he?”

One of my common weight loss counseling mantras is “no whites for breakfast, lunch, or dinner.” These whites would include rice, bread, pasta, and potatoes. The airwaves have been crackling for a while with calls to decrease carbohydrate consumption to combat the obesity epidemic and to eat bread only if you’re a duck. As a result, bread consumption has declined worldwide.

So how bad is bread? Are all breads the same?

Luis Serra-Majem and Inmaculada Bautista-Castano of the University of Las Palmas de Gran Canaria, Spain, conducted a systematic review of the impact of bread consumption on obesity and abdominal adiposity (Br. J. Nutr. 2015;113:S29-S35). The authors concluded that white (refined grain) bread, but not whole-grain bread, may be associated with excess abdominal fat.

Proposed hypotheses for how breads impact adiposity differently are:

1. Whole-grain bread increases satiety more than white bread;

2. Whole-grain bread results in lower plasma glucose and insulin responses than white bread;

3. Higher fiber content of whole-grain bread limits glucose absorption more than white bread; and

4. Whole-grain bread may positively influence gut microbiota through a probiotic effect.

My advice to the patient was to restrict calories, avoid carbohydrates, and if bread must be consumed, then it must be whole grain. Baby steps.

But he found religion in this (and in walking) and lost 200 pounds over the next 5 years. Miracles are still possible.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition, nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article. Follow him on Twitter @jonebbert.

My 27-year-old patient with a body mass index of 64 kg/m² presented to my clinic with back and leg pain. Unfortunately, I was not the least bit surprised.

When bending over, he developed acute onset of back pain, with radiating pain down the lateral side of his right leg to his foot. Exam and history were consistent with lumbar radiculopathy.

©Ingram Publishing/Thinkstock.com

Over the next several months, the patient had intractable pain in the presence of escalating opioids. The neurosurgeons said that his weight created too high a risk for intraoperative and postoperative complications, with which I agreed.

And so began the work of titrating his pain-modulating agents, along with the significantly less glamorous and substantially more challenging task of helping him lose weight.

He was staunchly opposed to bariatric surgery and could not afford weight loss medications, presenting a bit of an impasse. To me, the fact that his insurance company would have covered his spinal surgery but not his FDA-approved weight loss medications embodies one of the great medical mysteries of modern times.

His mother accompanied him on one of his several visits and chimed in, “He needs to eat bread, doesn’t he?”

One of my common weight loss counseling mantras is “no whites for breakfast, lunch, or dinner.” These whites would include rice, bread, pasta, and potatoes. The airwaves have been crackling for a while with calls to decrease carbohydrate consumption to combat the obesity epidemic and to eat bread only if you’re a duck. As a result, bread consumption has declined worldwide.

So how bad is bread? Are all breads the same?

Luis Serra-Majem and Inmaculada Bautista-Castano of the University of Las Palmas de Gran Canaria, Spain, conducted a systematic review of the impact of bread consumption on obesity and abdominal adiposity (Br. J. Nutr. 2015;113:S29-S35). The authors concluded that white (refined grain) bread, but not whole-grain bread, may be associated with excess abdominal fat.

Proposed hypotheses for how breads impact adiposity differently are:

1. Whole-grain bread increases satiety more than white bread;

2. Whole-grain bread results in lower plasma glucose and insulin responses than white bread;

3. Higher fiber content of whole-grain bread limits glucose absorption more than white bread; and

4. Whole-grain bread may positively influence gut microbiota through a probiotic effect.

My advice to the patient was to restrict calories, avoid carbohydrates, and if bread must be consumed, then it must be whole grain. Baby steps.

But he found religion in this (and in walking) and lost 200 pounds over the next 5 years. Miracles are still possible.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition, nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article. Follow him on Twitter @jonebbert.

My 27-year-old patient with a body mass index of 64 kg/m² presented to my clinic with back and leg pain. Unfortunately, I was not the least bit surprised.

When bending over, he developed acute onset of back pain, with radiating pain down the lateral side of his right leg to his foot. Exam and history were consistent with lumbar radiculopathy.

©Ingram Publishing/Thinkstock.com

Over the next several months, the patient had intractable pain in the presence of escalating opioids. The neurosurgeons said that his weight created too high a risk for intraoperative and postoperative complications, with which I agreed.

And so began the work of titrating his pain-modulating agents, along with the significantly less glamorous and substantially more challenging task of helping him lose weight.

He was staunchly opposed to bariatric surgery and could not afford weight loss medications, presenting a bit of an impasse. To me, the fact that his insurance company would have covered his spinal surgery but not his FDA-approved weight loss medications embodies one of the great medical mysteries of modern times.

His mother accompanied him on one of his several visits and chimed in, “He needs to eat bread, doesn’t he?”

One of my common weight loss counseling mantras is “no whites for breakfast, lunch, or dinner.” These whites would include rice, bread, pasta, and potatoes. The airwaves have been crackling for a while with calls to decrease carbohydrate consumption to combat the obesity epidemic and to eat bread only if you’re a duck. As a result, bread consumption has declined worldwide.

So how bad is bread? Are all breads the same?

Luis Serra-Majem and Inmaculada Bautista-Castano of the University of Las Palmas de Gran Canaria, Spain, conducted a systematic review of the impact of bread consumption on obesity and abdominal adiposity (Br. J. Nutr. 2015;113:S29-S35). The authors concluded that white (refined grain) bread, but not whole-grain bread, may be associated with excess abdominal fat.

Proposed hypotheses for how breads impact adiposity differently are:

1. Whole-grain bread increases satiety more than white bread;

2. Whole-grain bread results in lower plasma glucose and insulin responses than white bread;

3. Higher fiber content of whole-grain bread limits glucose absorption more than white bread; and

4. Whole-grain bread may positively influence gut microbiota through a probiotic effect.

My advice to the patient was to restrict calories, avoid carbohydrates, and if bread must be consumed, then it must be whole grain. Baby steps.

But he found religion in this (and in walking) and lost 200 pounds over the next 5 years. Miracles are still possible.

Dr. Ebbert is professor of medicine, a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author and do not necessarily represent the views and opinions of the Mayo Clinic. The opinions expressed in this article should not be used to diagnose or treat any medical condition, nor should they be used as a substitute for medical advice from a qualified, board-certified practicing clinician. Dr. Ebbert has no relevant financial disclosures about this article. Follow him on Twitter @jonebbert.

To weary parents, the fact that their child does not want to go to bed at night is both puzzling and exasperating. No matter what age, it is important to have a healthy bedtime for the child’s well-being as well as their caregiver’s!

Sleep, like the “canary in the mine,” is vulnerable to disruption by anything from minor illness to changes in schedule, things viewed on media, or emotions in the home, to life changes such as a new sibling, toilet training, or a new school year. In patients on stimulant medicine resisting bedtime, consider the need to finally eat. Asking about these specifically will help you plan an appropriate time to successfully address bedtime conflicts.

Knowing some basic principles about falling asleep can help your counseling. “Sleep drive” builds up over the day like a coiled spring, making falling asleep easier initially than for wakings later in the night. It also means that a nap too close to bedtime reduces the drive. Avoiding any naps (after age 4 years) and naps lasting past 4 p.m. for children under 4, even in car rides, is crucial. Beware of teens “having trouble falling asleep” who have sneaked in a nap after school!

To optimize sleep drive, calculate age-related sleep needs and, ideally, ask parents to keep a sleep diary for 1-2 weeks, especially checking on naps at daycare. Updated sleep duration standards (preschool 10-13 hours; school age 9-11 hours; teens 8-10 hours (see sleepfoundation.org) show that ranges of total sleep are remarkably stable, but may not meet parents’ ideals for time “off duty.”

If placed in bed when not yet tired, anyone will have trouble falling asleep (phase shift). For a child, lying awake in the dark alone is time for active imaginations to conjure fear of separation (> 4-6 months), monsters (for preschoolers), burglars (for anxious school-aged children), or the next day’s social or academic stresses (for school-aged children to teens). Children with anxiety disorders even worry that they may not get enough sleep! A soothing routine with a story in their bed (not media), a spritzing of “monster spray” or a “bedtime ticket” to cash in for “one more thing” (for those who beg) will usually suffice for preschoolers. A “magic flashlight” lends the child some control to check for monsters, but an “exorcism ritual” by the all-powerful parent can be added if needed. Teens are never too old for a chance to talk or even a story read by the parent (but they won’t ask for this).

A secret to managing bedtime struggles is to start the routine at the time the child is now falling asleep to avoid resistance, and keeping wake-up time appropriate to the new schedule. Once falling asleep within 10 minutes, move bedtime 15 minutes earlier each night to reach the schedule, then maintain 7 days per week (or within 1 hour) to prevent resetting the biological clock. Sorry, no movie nights until 2 a.m. or “sleeping in” on weekends! Teens who resist bedtime may be napping, socializing at the “only time” peers are up, addicted to media, or avoiding family. Their cooperation must be engaged to make a change by staying up all night once, then setting a new schedule, or staying up 1 hour later each night until the desired bedtime is reached.

©deyangeorgiev/thinkstockphotos.com

Because sleep includes being paralyzed (REM stages), evolution encourages animals to sleep together to protect from predators. Sleeping alone requires a great deal of reassurance, such as from a friendly atmosphere, favorite stuffed toy, and familiar routine that implies safety. Children could use a toy, pet, or even a sibling to feel safe. While body contact is the most reassuring, children may not return to sleep from the many normal night wakings without it. Most can be weaned from this dependence by the parent sitting by the bed silently, moving one foot closer to the door each night. A promise to “check on you” in 5 minutes also helps.

Other factors making sleep easier include avoiding caffeine, stimulating medicines, or nicotine as well as exciting games, media, or exercise within 2 hours of bedtime. A quiet, dark, cool but not damp location used only for sleeping is helpful, but not always possible. A white noise generator, fan, or radio on static can help.

Many parents strangely expect their child to give up the pleasures of the day and take themselves to bed! As for other kinds of limit setting, parental company is typically needed for brushing teeth, pajamas, and a story. Ideally, it can be fun as a race or with songs, not a yelling match, which undermines the sense of safety. Setting rules about no electronics in the bedroom, even for charging, after a certain hour is often the only solution (even for adults) to the common struggle over ending media.

Often the bedtime complaint is “curtain calls” after being settled in bed. For children who call out, advise parents wait a few moments before responding, then reassure verbally without entering their room, waiting longer each time. For the child getting out of bed, one parent should lead them back without talking at all as many times as necessary. A reward for staying in bed without calling or coming out can be an extra story the next night and/or a morning reward. Alternatively, close the door and turn off the light if they come out or call out. After a few moments in the dark, give a “second chance” as long as they are quietly in bed. Gating the doorway works well for toddlers – sleeping on the floor is not dangerous!

Families often are ambivalent about asking for bedtime advice, thinking your solutions might be stressful, harmful to their relationship, or will take up their own precious sleep. For many, a prolonged bedtime is the best part of their day. Special Time earlier is often key to enforcing a healthy bedtime. Reassure them that these solutions usually take less than 3 weeks!

For the child, bedtime means giving up on fun but, more importantly, separation from the parent. This separation is harder if negative emotions are left from a day of behavior struggles or parents are even subtly angry at each other. For parents, bedtime means separating from their main pleasure in life. They also may be regretting their interactions during the day. Ambivalence about parting also may come from fears of being alone with their partner due to marital discord, intimate partner violence, chronic arguing, substance use, or simply depression. When simple advice fails, it is important to explore these meanings with families, encourage positive daytime behavior management methods, and avoid conflict in front of the children to resolve bedtime struggles.

Dr. Howard is assistant professor of pediatrics at the Johns Hopkins University School of Medicine, Baltimore, and creator of CHADIS (www.CHADIS.com). She has no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline. E-mail her at [email protected].

To weary parents, the fact that their child does not want to go to bed at night is both puzzling and exasperating. No matter what age, it is important to have a healthy bedtime for the child’s well-being as well as their caregiver’s!

Sleep, like the “canary in the mine,” is vulnerable to disruption by anything from minor illness to changes in schedule, things viewed on media, or emotions in the home, to life changes such as a new sibling, toilet training, or a new school year. In patients on stimulant medicine resisting bedtime, consider the need to finally eat. Asking about these specifically will help you plan an appropriate time to successfully address bedtime conflicts.

Knowing some basic principles about falling asleep can help your counseling. “Sleep drive” builds up over the day like a coiled spring, making falling asleep easier initially than for wakings later in the night. It also means that a nap too close to bedtime reduces the drive. Avoiding any naps (after age 4 years) and naps lasting past 4 p.m. for children under 4, even in car rides, is crucial. Beware of teens “having trouble falling asleep” who have sneaked in a nap after school!

To optimize sleep drive, calculate age-related sleep needs and, ideally, ask parents to keep a sleep diary for 1-2 weeks, especially checking on naps at daycare. Updated sleep duration standards (preschool 10-13 hours; school age 9-11 hours; teens 8-10 hours (see sleepfoundation.org) show that ranges of total sleep are remarkably stable, but may not meet parents’ ideals for time “off duty.”

If placed in bed when not yet tired, anyone will have trouble falling asleep (phase shift). For a child, lying awake in the dark alone is time for active imaginations to conjure fear of separation (> 4-6 months), monsters (for preschoolers), burglars (for anxious school-aged children), or the next day’s social or academic stresses (for school-aged children to teens). Children with anxiety disorders even worry that they may not get enough sleep! A soothing routine with a story in their bed (not media), a spritzing of “monster spray” or a “bedtime ticket” to cash in for “one more thing” (for those who beg) will usually suffice for preschoolers. A “magic flashlight” lends the child some control to check for monsters, but an “exorcism ritual” by the all-powerful parent can be added if needed. Teens are never too old for a chance to talk or even a story read by the parent (but they won’t ask for this).

A secret to managing bedtime struggles is to start the routine at the time the child is now falling asleep to avoid resistance, and keeping wake-up time appropriate to the new schedule. Once falling asleep within 10 minutes, move bedtime 15 minutes earlier each night to reach the schedule, then maintain 7 days per week (or within 1 hour) to prevent resetting the biological clock. Sorry, no movie nights until 2 a.m. or “sleeping in” on weekends! Teens who resist bedtime may be napping, socializing at the “only time” peers are up, addicted to media, or avoiding family. Their cooperation must be engaged to make a change by staying up all night once, then setting a new schedule, or staying up 1 hour later each night until the desired bedtime is reached.

©deyangeorgiev/thinkstockphotos.com

Because sleep includes being paralyzed (REM stages), evolution encourages animals to sleep together to protect from predators. Sleeping alone requires a great deal of reassurance, such as from a friendly atmosphere, favorite stuffed toy, and familiar routine that implies safety. Children could use a toy, pet, or even a sibling to feel safe. While body contact is the most reassuring, children may not return to sleep from the many normal night wakings without it. Most can be weaned from this dependence by the parent sitting by the bed silently, moving one foot closer to the door each night. A promise to “check on you” in 5 minutes also helps.

Other factors making sleep easier include avoiding caffeine, stimulating medicines, or nicotine as well as exciting games, media, or exercise within 2 hours of bedtime. A quiet, dark, cool but not damp location used only for sleeping is helpful, but not always possible. A white noise generator, fan, or radio on static can help.

Many parents strangely expect their child to give up the pleasures of the day and take themselves to bed! As for other kinds of limit setting, parental company is typically needed for brushing teeth, pajamas, and a story. Ideally, it can be fun as a race or with songs, not a yelling match, which undermines the sense of safety. Setting rules about no electronics in the bedroom, even for charging, after a certain hour is often the only solution (even for adults) to the common struggle over ending media.

Often the bedtime complaint is “curtain calls” after being settled in bed. For children who call out, advise parents wait a few moments before responding, then reassure verbally without entering their room, waiting longer each time. For the child getting out of bed, one parent should lead them back without talking at all as many times as necessary. A reward for staying in bed without calling or coming out can be an extra story the next night and/or a morning reward. Alternatively, close the door and turn off the light if they come out or call out. After a few moments in the dark, give a “second chance” as long as they are quietly in bed. Gating the doorway works well for toddlers – sleeping on the floor is not dangerous!

Families often are ambivalent about asking for bedtime advice, thinking your solutions might be stressful, harmful to their relationship, or will take up their own precious sleep. For many, a prolonged bedtime is the best part of their day. Special Time earlier is often key to enforcing a healthy bedtime. Reassure them that these solutions usually take less than 3 weeks!

For the child, bedtime means giving up on fun but, more importantly, separation from the parent. This separation is harder if negative emotions are left from a day of behavior struggles or parents are even subtly angry at each other. For parents, bedtime means separating from their main pleasure in life. They also may be regretting their interactions during the day. Ambivalence about parting also may come from fears of being alone with their partner due to marital discord, intimate partner violence, chronic arguing, substance use, or simply depression. When simple advice fails, it is important to explore these meanings with families, encourage positive daytime behavior management methods, and avoid conflict in front of the children to resolve bedtime struggles.

Dr. Howard is assistant professor of pediatrics at the Johns Hopkins University School of Medicine, Baltimore, and creator of CHADIS (www.CHADIS.com). She has no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline. E-mail her at [email protected].

To weary parents, the fact that their child does not want to go to bed at night is both puzzling and exasperating. No matter what age, it is important to have a healthy bedtime for the child’s well-being as well as their caregiver’s!

Sleep, like the “canary in the mine,” is vulnerable to disruption by anything from minor illness to changes in schedule, things viewed on media, or emotions in the home, to life changes such as a new sibling, toilet training, or a new school year. In patients on stimulant medicine resisting bedtime, consider the need to finally eat. Asking about these specifically will help you plan an appropriate time to successfully address bedtime conflicts.

Knowing some basic principles about falling asleep can help your counseling. “Sleep drive” builds up over the day like a coiled spring, making falling asleep easier initially than for wakings later in the night. It also means that a nap too close to bedtime reduces the drive. Avoiding any naps (after age 4 years) and naps lasting past 4 p.m. for children under 4, even in car rides, is crucial. Beware of teens “having trouble falling asleep” who have sneaked in a nap after school!

To optimize sleep drive, calculate age-related sleep needs and, ideally, ask parents to keep a sleep diary for 1-2 weeks, especially checking on naps at daycare. Updated sleep duration standards (preschool 10-13 hours; school age 9-11 hours; teens 8-10 hours (see sleepfoundation.org) show that ranges of total sleep are remarkably stable, but may not meet parents’ ideals for time “off duty.”

If placed in bed when not yet tired, anyone will have trouble falling asleep (phase shift). For a child, lying awake in the dark alone is time for active imaginations to conjure fear of separation (> 4-6 months), monsters (for preschoolers), burglars (for anxious school-aged children), or the next day’s social or academic stresses (for school-aged children to teens). Children with anxiety disorders even worry that they may not get enough sleep! A soothing routine with a story in their bed (not media), a spritzing of “monster spray” or a “bedtime ticket” to cash in for “one more thing” (for those who beg) will usually suffice for preschoolers. A “magic flashlight” lends the child some control to check for monsters, but an “exorcism ritual” by the all-powerful parent can be added if needed. Teens are never too old for a chance to talk or even a story read by the parent (but they won’t ask for this).

A secret to managing bedtime struggles is to start the routine at the time the child is now falling asleep to avoid resistance, and keeping wake-up time appropriate to the new schedule. Once falling asleep within 10 minutes, move bedtime 15 minutes earlier each night to reach the schedule, then maintain 7 days per week (or within 1 hour) to prevent resetting the biological clock. Sorry, no movie nights until 2 a.m. or “sleeping in” on weekends! Teens who resist bedtime may be napping, socializing at the “only time” peers are up, addicted to media, or avoiding family. Their cooperation must be engaged to make a change by staying up all night once, then setting a new schedule, or staying up 1 hour later each night until the desired bedtime is reached.

©deyangeorgiev/thinkstockphotos.com

Because sleep includes being paralyzed (REM stages), evolution encourages animals to sleep together to protect from predators. Sleeping alone requires a great deal of reassurance, such as from a friendly atmosphere, favorite stuffed toy, and familiar routine that implies safety. Children could use a toy, pet, or even a sibling to feel safe. While body contact is the most reassuring, children may not return to sleep from the many normal night wakings without it. Most can be weaned from this dependence by the parent sitting by the bed silently, moving one foot closer to the door each night. A promise to “check on you” in 5 minutes also helps.

Other factors making sleep easier include avoiding caffeine, stimulating medicines, or nicotine as well as exciting games, media, or exercise within 2 hours of bedtime. A quiet, dark, cool but not damp location used only for sleeping is helpful, but not always possible. A white noise generator, fan, or radio on static can help.

Many parents strangely expect their child to give up the pleasures of the day and take themselves to bed! As for other kinds of limit setting, parental company is typically needed for brushing teeth, pajamas, and a story. Ideally, it can be fun as a race or with songs, not a yelling match, which undermines the sense of safety. Setting rules about no electronics in the bedroom, even for charging, after a certain hour is often the only solution (even for adults) to the common struggle over ending media.

Often the bedtime complaint is “curtain calls” after being settled in bed. For children who call out, advise parents wait a few moments before responding, then reassure verbally without entering their room, waiting longer each time. For the child getting out of bed, one parent should lead them back without talking at all as many times as necessary. A reward for staying in bed without calling or coming out can be an extra story the next night and/or a morning reward. Alternatively, close the door and turn off the light if they come out or call out. After a few moments in the dark, give a “second chance” as long as they are quietly in bed. Gating the doorway works well for toddlers – sleeping on the floor is not dangerous!

Families often are ambivalent about asking for bedtime advice, thinking your solutions might be stressful, harmful to their relationship, or will take up their own precious sleep. For many, a prolonged bedtime is the best part of their day. Special Time earlier is often key to enforcing a healthy bedtime. Reassure them that these solutions usually take less than 3 weeks!

For the child, bedtime means giving up on fun but, more importantly, separation from the parent. This separation is harder if negative emotions are left from a day of behavior struggles or parents are even subtly angry at each other. For parents, bedtime means separating from their main pleasure in life. They also may be regretting their interactions during the day. Ambivalence about parting also may come from fears of being alone with their partner due to marital discord, intimate partner violence, chronic arguing, substance use, or simply depression. When simple advice fails, it is important to explore these meanings with families, encourage positive daytime behavior management methods, and avoid conflict in front of the children to resolve bedtime struggles.

Dr. Howard is assistant professor of pediatrics at the Johns Hopkins University School of Medicine, Baltimore, and creator of CHADIS (www.CHADIS.com). She has no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline. E-mail her at [email protected].

The antibiotic dicloxacillin appears to markedly decrease INR levels in patients taking warfarin, reducing the mean INR to subtherapeutic ranges in the majority who take both drugs concomitantly, according to a research letter to the editor published online July 20 in JAMA.

Adverse interactions between warfarin and other drugs are often suspected, but solid data are lacking. Case reports have suggested that the commonly used antibiotic dicloxacillin reduces warfarin’s anticoagulant effects, but no studies have examined the issue, said Anton Pottegård, Ph.D., of the department of clinical pharmacology, University of Southern Denmark, Odense, and his associates (JAMA 2015;314:296-7).

To further investigate that possibility, the investigators analyzed information in an anticoagulant database covering 7,400 patients treated by three outpatient clinics and 50 general practitioners during a 15-year period. They focused on weekly INR levels recorded for 236 patients (median age, 68 years), most of whom took warfarin because of atrial fibrillation or heart valve replacement.

The mean INR level before dicloxacillin exposure was 2.59, compared with 1.97 after dicloxacillin exposure (P < .001). A total of 144 patients (61%) had subtherapeutic INR levels (< 2.0) during the 2-4 weeks following a course of dicloxacillin, Dr. Pottegård and his associates said.

A similar but less drastic decrease was observed among the 64 patients taking a different anticoagulant, phenprocoumon, who were given dicloxacillin. Mean INR levels dropped from 2.61 before exposure to 2.30 afterward (P = .003), and 41% of the group had subtherapeutic INR levels after taking the antibiotic.

No sponsor was reported for this study. Dr. Pottegård and his associates reported having no relevant financial disclosures.

The antibiotic dicloxacillin appears to markedly decrease INR levels in patients taking warfarin, reducing the mean INR to subtherapeutic ranges in the majority who take both drugs concomitantly, according to a research letter to the editor published online July 20 in JAMA.

Adverse interactions between warfarin and other drugs are often suspected, but solid data are lacking. Case reports have suggested that the commonly used antibiotic dicloxacillin reduces warfarin’s anticoagulant effects, but no studies have examined the issue, said Anton Pottegård, Ph.D., of the department of clinical pharmacology, University of Southern Denmark, Odense, and his associates (JAMA 2015;314:296-7).

To further investigate that possibility, the investigators analyzed information in an anticoagulant database covering 7,400 patients treated by three outpatient clinics and 50 general practitioners during a 15-year period. They focused on weekly INR levels recorded for 236 patients (median age, 68 years), most of whom took warfarin because of atrial fibrillation or heart valve replacement.

The mean INR level before dicloxacillin exposure was 2.59, compared with 1.97 after dicloxacillin exposure (P < .001). A total of 144 patients (61%) had subtherapeutic INR levels (< 2.0) during the 2-4 weeks following a course of dicloxacillin, Dr. Pottegård and his associates said.

A similar but less drastic decrease was observed among the 64 patients taking a different anticoagulant, phenprocoumon, who were given dicloxacillin. Mean INR levels dropped from 2.61 before exposure to 2.30 afterward (P = .003), and 41% of the group had subtherapeutic INR levels after taking the antibiotic.

No sponsor was reported for this study. Dr. Pottegård and his associates reported having no relevant financial disclosures.

The antibiotic dicloxacillin appears to markedly decrease INR levels in patients taking warfarin, reducing the mean INR to subtherapeutic ranges in the majority who take both drugs concomitantly, according to a research letter to the editor published online July 20 in JAMA.

Adverse interactions between warfarin and other drugs are often suspected, but solid data are lacking. Case reports have suggested that the commonly used antibiotic dicloxacillin reduces warfarin’s anticoagulant effects, but no studies have examined the issue, said Anton Pottegård, Ph.D., of the department of clinical pharmacology, University of Southern Denmark, Odense, and his associates (JAMA 2015;314:296-7).

To further investigate that possibility, the investigators analyzed information in an anticoagulant database covering 7,400 patients treated by three outpatient clinics and 50 general practitioners during a 15-year period. They focused on weekly INR levels recorded for 236 patients (median age, 68 years), most of whom took warfarin because of atrial fibrillation or heart valve replacement.

The mean INR level before dicloxacillin exposure was 2.59, compared with 1.97 after dicloxacillin exposure (P < .001). A total of 144 patients (61%) had subtherapeutic INR levels (< 2.0) during the 2-4 weeks following a course of dicloxacillin, Dr. Pottegård and his associates said.

A similar but less drastic decrease was observed among the 64 patients taking a different anticoagulant, phenprocoumon, who were given dicloxacillin. Mean INR levels dropped from 2.61 before exposure to 2.30 afterward (P = .003), and 41% of the group had subtherapeutic INR levels after taking the antibiotic.

No sponsor was reported for this study. Dr. Pottegård and his associates reported having no relevant financial disclosures.

Most of our patients have been or will be exposed to water in a recreational setting this summer. As health care providers, we might not routinely consider illnesses associated with recreational water exposure or discuss preventive strategies; however, the Centers for Disease Control and Prevention has been actively promoting awareness about recreational water illnesses for years. May 18-24, 2015, was the 11th annual observance of Healthy and Safe Swimming Week, formerly known as Recreational Illness and Injury Prevention Week. The focus for 2015 was promoting the role of swimmers, residential pool owners, public health officials, and beach staff in the prevention of drownings, chemical injuries, and outbreaks of illness. One goal was for the swimmer to take a more active role in protecting themselves and preventing the spread of infections to others. For our colleagues, that means educating both parents and children.

To begin our discussion, let’s define recreational water illnesses (RWI). RWIs are caused by a variety of infectious pathogens transmitted by ingestion, inhalation of aerosols or mists, or having contact with contaminated water from both treated (swimming pools, hot tubs, water parks, and fountains) and untreated (lakes, rivers, and oceans) sources of water in recreational venues. RWIs also can be caused by chemicals that have evaporated from water leading to poor indoor air quality. However, I am focusing on the infectious etiologies.

A broad spectrum of infections are associated with RWIs, including infections of the gastrointestinal tract, ear, skin, eye, central nervous system, and wounds. Diarrhea is the most common infection. Implicated pathogens include Giardia, Shigella, norovirus, and Escherichia coli O157:H7, but it is Cryptosporidium that has emerged as the pathogen implicated most often in swimming pool–related outbreaks. Recently published data from the CDC revealed that in 2011-2012, there were 90 recreational-associated outbreaks reported from 32 states and Puerto Rico resulting in 1,788 infections, with 69 outbreaks occurring in treated water venues. Of these, 36 (51%) were caused by Cryptosporidium. Among 21 outbreaks occurring in untreated recreational water, E. coli was responsible for 7 (33%) (MMWR Morb. Mortal. Wkly Rep. 2015;64:668-72)

It’s no surprise diarrhea is the most common illness. Infection can easily occur after swallowing contaminated water. Many erroneously think chlorine kills all pathogens. Cryptosporidium is chlorine tolerant and can persist in treated water with the current recommended levels of chlorine for more than 10 days (J. Water Health 2008;6:513-20). For chlorine-sensitive pathogens, maintenance of the disinfection process must remain intact. What role do swimmers play? Most people have about 0.4 g of feces on their bottoms that can contaminate water when rinsed off. How many people enter a pool with a diarrheal illness? How many may go swimming after having recently recovered from a diarrheal illness and may have asymptomatic shedding? We all have cringed when we see a diapered child in the water. All of these are potential ways for the swimmer to contaminate an adequately treated pool. Additionally, while Cryptosporidium infections are usually self-limited, some individuals, including the immunocompromised host and especially those with advanced HIV and those who are solid organ transplant recipients, may have a protracted course of profuse diarrhea if infected.

While diarrhea maybe the most common RWI, it is not the only one. Acute otitis externa (AOE), more commonly known as “swimmer’s ear,” is one of the most frequent reasons for summer health care encounters. It has been estimated that in the United States in 2007, 2.4 million health care visits resulted in the diagnosis of AOE (MMWR Morb. Mortal. Wkly. Rep. 2011;60:605-9). Visits were highest among children aged 5-9 years; however, adults accounted for 53% of the encounters. Inflammation and infection of the external auditory canal is usually caused by bacteria. Pseudomonas aeruginosa or Staphylococcus aureus are the two most common etiologies. Water is easily introduced into the external auditory canal with recreational water activities, leading to maceration and subsequent infection of the canal. Simply reminding parents to thoroughly dry their child’s ears after water exposure can help prevent AOE.

© kali9/iStockphoto.com

P. aeruginosa also is the agent causing the self-limiting conditions hot tub folliculitis and hot-foot syndrome. Hot tub folliculitis is characterized by the development of tender, pruritic papules and papulopustules on the hips, buttocks, and axillae, usually developing 8-48 hours after exposure to water that has been contaminated because of inadequate chlorination. Hot-foot syndrome is characterized by painful planter nodules (N. Engl. J. Med. 2001;345:335).

Serious diseases are encountered infrequently, but there are some that require more urgent interventions. Primary amebic meningoencephalitis (PAM) is an extremely rare, progressive, and almost always fatal infection of the brain caused by Naegleria fowleri. The pathogen is found in warm freshwater including lakes, rivers, streams, and hot springs. It enters the body through the nose and travels via the olfactory nerve to the brain. Infection usually occurs when individuals swim or dive in warm freshwater. Most cases have been reported in children from Southern states. In 2010, the first case in a northern state was reported from Minnesota, and three additional cases have since been reported in Kansas and Indiana (J. Ped. Infect. Dis. 2014 [doi: 10.1093/jpids/piu103]). Cases also have been reported in two individuals who were regular users of neti pots for sinus irrigation because the irrigating solution was prepared with contaminated tap water (Clin. Infect. Dis. 2012;55:e79-85). Clinical presentation is similar to bacterial meningitis. Helpful diagnostic clues may come from obtaining a history of swimming in freshwater within the 2 weeks prior to presentation, especially during the summer, or the use of nasal or sinus irrigation with untreated tap water. Consultation with an infectious disease specialist is recommended.

Acanthamoeba keratitis is a potentially blinding infection of the cornea that primarily occurs in individuals who wear contact lenses. Risk factors for the infection include swimming, showering, and use of hot tubs while wearing contact lenses. Improper storage and cleansing contacts with tap water are other risk factors. Anyone with corneal trauma and similar water exposures also would be at risk. Clinically, the history combined with a foreign-body sensation, pain, and decreased visual acuity should make one include this infection in the differential diagnosis. Referral to an ophthalmologist is required.

Finally, swimming with an open wound is a portal of entry for Vibrio vulnificus. It usually is associated with consumption of contaminated seafood, especially oysters. In immunocompromised individuals, especially those with chronic liver disease, this bacteria can cause a life-threatening illness leading to bacteremia, septic shock, and development of blistering skin lesions. Infections are fatal in approximately 50% of cases.

The goal of this brief review was not to discourage swimming, but to make your patients and their families healthy swimmers. Here are a few things the CDC is recommending to help them achieve that goal:

• Shower prior to going swimming.

• Do not swallow or drink pool water.

• Take bathroom breaks every hour and rinse off before going back into the water.

• Do not swim if you have diarrhea.

• Wait at least 2 weeks to go swimming if you have had diarrhea.

• Change swim diapers frequently and away from the water.

• Suggest patients download the free CDC app Healthy Swimming for more detailed information and suggest they visit cdc.gov/healthywater/swimming.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She had no relevant financial disclosures. Write to Dr. Word at [email protected].

Most of our patients have been or will be exposed to water in a recreational setting this summer. As health care providers, we might not routinely consider illnesses associated with recreational water exposure or discuss preventive strategies; however, the Centers for Disease Control and Prevention has been actively promoting awareness about recreational water illnesses for years. May 18-24, 2015, was the 11th annual observance of Healthy and Safe Swimming Week, formerly known as Recreational Illness and Injury Prevention Week. The focus for 2015 was promoting the role of swimmers, residential pool owners, public health officials, and beach staff in the prevention of drownings, chemical injuries, and outbreaks of illness. One goal was for the swimmer to take a more active role in protecting themselves and preventing the spread of infections to others. For our colleagues, that means educating both parents and children.

To begin our discussion, let’s define recreational water illnesses (RWI). RWIs are caused by a variety of infectious pathogens transmitted by ingestion, inhalation of aerosols or mists, or having contact with contaminated water from both treated (swimming pools, hot tubs, water parks, and fountains) and untreated (lakes, rivers, and oceans) sources of water in recreational venues. RWIs also can be caused by chemicals that have evaporated from water leading to poor indoor air quality. However, I am focusing on the infectious etiologies.

A broad spectrum of infections are associated with RWIs, including infections of the gastrointestinal tract, ear, skin, eye, central nervous system, and wounds. Diarrhea is the most common infection. Implicated pathogens include Giardia, Shigella, norovirus, and Escherichia coli O157:H7, but it is Cryptosporidium that has emerged as the pathogen implicated most often in swimming pool–related outbreaks. Recently published data from the CDC revealed that in 2011-2012, there were 90 recreational-associated outbreaks reported from 32 states and Puerto Rico resulting in 1,788 infections, with 69 outbreaks occurring in treated water venues. Of these, 36 (51%) were caused by Cryptosporidium. Among 21 outbreaks occurring in untreated recreational water, E. coli was responsible for 7 (33%) (MMWR Morb. Mortal. Wkly Rep. 2015;64:668-72)

It’s no surprise diarrhea is the most common illness. Infection can easily occur after swallowing contaminated water. Many erroneously think chlorine kills all pathogens. Cryptosporidium is chlorine tolerant and can persist in treated water with the current recommended levels of chlorine for more than 10 days (J. Water Health 2008;6:513-20). For chlorine-sensitive pathogens, maintenance of the disinfection process must remain intact. What role do swimmers play? Most people have about 0.4 g of feces on their bottoms that can contaminate water when rinsed off. How many people enter a pool with a diarrheal illness? How many may go swimming after having recently recovered from a diarrheal illness and may have asymptomatic shedding? We all have cringed when we see a diapered child in the water. All of these are potential ways for the swimmer to contaminate an adequately treated pool. Additionally, while Cryptosporidium infections are usually self-limited, some individuals, including the immunocompromised host and especially those with advanced HIV and those who are solid organ transplant recipients, may have a protracted course of profuse diarrhea if infected.

While diarrhea maybe the most common RWI, it is not the only one. Acute otitis externa (AOE), more commonly known as “swimmer’s ear,” is one of the most frequent reasons for summer health care encounters. It has been estimated that in the United States in 2007, 2.4 million health care visits resulted in the diagnosis of AOE (MMWR Morb. Mortal. Wkly. Rep. 2011;60:605-9). Visits were highest among children aged 5-9 years; however, adults accounted for 53% of the encounters. Inflammation and infection of the external auditory canal is usually caused by bacteria. Pseudomonas aeruginosa or Staphylococcus aureus are the two most common etiologies. Water is easily introduced into the external auditory canal with recreational water activities, leading to maceration and subsequent infection of the canal. Simply reminding parents to thoroughly dry their child’s ears after water exposure can help prevent AOE.

© kali9/iStockphoto.com

P. aeruginosa also is the agent causing the self-limiting conditions hot tub folliculitis and hot-foot syndrome. Hot tub folliculitis is characterized by the development of tender, pruritic papules and papulopustules on the hips, buttocks, and axillae, usually developing 8-48 hours after exposure to water that has been contaminated because of inadequate chlorination. Hot-foot syndrome is characterized by painful planter nodules (N. Engl. J. Med. 2001;345:335).

Serious diseases are encountered infrequently, but there are some that require more urgent interventions. Primary amebic meningoencephalitis (PAM) is an extremely rare, progressive, and almost always fatal infection of the brain caused by Naegleria fowleri. The pathogen is found in warm freshwater including lakes, rivers, streams, and hot springs. It enters the body through the nose and travels via the olfactory nerve to the brain. Infection usually occurs when individuals swim or dive in warm freshwater. Most cases have been reported in children from Southern states. In 2010, the first case in a northern state was reported from Minnesota, and three additional cases have since been reported in Kansas and Indiana (J. Ped. Infect. Dis. 2014 [doi: 10.1093/jpids/piu103]). Cases also have been reported in two individuals who were regular users of neti pots for sinus irrigation because the irrigating solution was prepared with contaminated tap water (Clin. Infect. Dis. 2012;55:e79-85). Clinical presentation is similar to bacterial meningitis. Helpful diagnostic clues may come from obtaining a history of swimming in freshwater within the 2 weeks prior to presentation, especially during the summer, or the use of nasal or sinus irrigation with untreated tap water. Consultation with an infectious disease specialist is recommended.

Acanthamoeba keratitis is a potentially blinding infection of the cornea that primarily occurs in individuals who wear contact lenses. Risk factors for the infection include swimming, showering, and use of hot tubs while wearing contact lenses. Improper storage and cleansing contacts with tap water are other risk factors. Anyone with corneal trauma and similar water exposures also would be at risk. Clinically, the history combined with a foreign-body sensation, pain, and decreased visual acuity should make one include this infection in the differential diagnosis. Referral to an ophthalmologist is required.

Finally, swimming with an open wound is a portal of entry for Vibrio vulnificus. It usually is associated with consumption of contaminated seafood, especially oysters. In immunocompromised individuals, especially those with chronic liver disease, this bacteria can cause a life-threatening illness leading to bacteremia, septic shock, and development of blistering skin lesions. Infections are fatal in approximately 50% of cases.

The goal of this brief review was not to discourage swimming, but to make your patients and their families healthy swimmers. Here are a few things the CDC is recommending to help them achieve that goal:

• Shower prior to going swimming.

• Do not swallow or drink pool water.

• Take bathroom breaks every hour and rinse off before going back into the water.

• Do not swim if you have diarrhea.

• Wait at least 2 weeks to go swimming if you have had diarrhea.

• Change swim diapers frequently and away from the water.

• Suggest patients download the free CDC app Healthy Swimming for more detailed information and suggest they visit cdc.gov/healthywater/swimming.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She had no relevant financial disclosures. Write to Dr. Word at [email protected].

Most of our patients have been or will be exposed to water in a recreational setting this summer. As health care providers, we might not routinely consider illnesses associated with recreational water exposure or discuss preventive strategies; however, the Centers for Disease Control and Prevention has been actively promoting awareness about recreational water illnesses for years. May 18-24, 2015, was the 11th annual observance of Healthy and Safe Swimming Week, formerly known as Recreational Illness and Injury Prevention Week. The focus for 2015 was promoting the role of swimmers, residential pool owners, public health officials, and beach staff in the prevention of drownings, chemical injuries, and outbreaks of illness. One goal was for the swimmer to take a more active role in protecting themselves and preventing the spread of infections to others. For our colleagues, that means educating both parents and children.

To begin our discussion, let’s define recreational water illnesses (RWI). RWIs are caused by a variety of infectious pathogens transmitted by ingestion, inhalation of aerosols or mists, or having contact with contaminated water from both treated (swimming pools, hot tubs, water parks, and fountains) and untreated (lakes, rivers, and oceans) sources of water in recreational venues. RWIs also can be caused by chemicals that have evaporated from water leading to poor indoor air quality. However, I am focusing on the infectious etiologies.

A broad spectrum of infections are associated with RWIs, including infections of the gastrointestinal tract, ear, skin, eye, central nervous system, and wounds. Diarrhea is the most common infection. Implicated pathogens include Giardia, Shigella, norovirus, and Escherichia coli O157:H7, but it is Cryptosporidium that has emerged as the pathogen implicated most often in swimming pool–related outbreaks. Recently published data from the CDC revealed that in 2011-2012, there were 90 recreational-associated outbreaks reported from 32 states and Puerto Rico resulting in 1,788 infections, with 69 outbreaks occurring in treated water venues. Of these, 36 (51%) were caused by Cryptosporidium. Among 21 outbreaks occurring in untreated recreational water, E. coli was responsible for 7 (33%) (MMWR Morb. Mortal. Wkly Rep. 2015;64:668-72)

It’s no surprise diarrhea is the most common illness. Infection can easily occur after swallowing contaminated water. Many erroneously think chlorine kills all pathogens. Cryptosporidium is chlorine tolerant and can persist in treated water with the current recommended levels of chlorine for more than 10 days (J. Water Health 2008;6:513-20). For chlorine-sensitive pathogens, maintenance of the disinfection process must remain intact. What role do swimmers play? Most people have about 0.4 g of feces on their bottoms that can contaminate water when rinsed off. How many people enter a pool with a diarrheal illness? How many may go swimming after having recently recovered from a diarrheal illness and may have asymptomatic shedding? We all have cringed when we see a diapered child in the water. All of these are potential ways for the swimmer to contaminate an adequately treated pool. Additionally, while Cryptosporidium infections are usually self-limited, some individuals, including the immunocompromised host and especially those with advanced HIV and those who are solid organ transplant recipients, may have a protracted course of profuse diarrhea if infected.

While diarrhea maybe the most common RWI, it is not the only one. Acute otitis externa (AOE), more commonly known as “swimmer’s ear,” is one of the most frequent reasons for summer health care encounters. It has been estimated that in the United States in 2007, 2.4 million health care visits resulted in the diagnosis of AOE (MMWR Morb. Mortal. Wkly. Rep. 2011;60:605-9). Visits were highest among children aged 5-9 years; however, adults accounted for 53% of the encounters. Inflammation and infection of the external auditory canal is usually caused by bacteria. Pseudomonas aeruginosa or Staphylococcus aureus are the two most common etiologies. Water is easily introduced into the external auditory canal with recreational water activities, leading to maceration and subsequent infection of the canal. Simply reminding parents to thoroughly dry their child’s ears after water exposure can help prevent AOE.

© kali9/iStockphoto.com

P. aeruginosa also is the agent causing the self-limiting conditions hot tub folliculitis and hot-foot syndrome. Hot tub folliculitis is characterized by the development of tender, pruritic papules and papulopustules on the hips, buttocks, and axillae, usually developing 8-48 hours after exposure to water that has been contaminated because of inadequate chlorination. Hot-foot syndrome is characterized by painful planter nodules (N. Engl. J. Med. 2001;345:335).

Serious diseases are encountered infrequently, but there are some that require more urgent interventions. Primary amebic meningoencephalitis (PAM) is an extremely rare, progressive, and almost always fatal infection of the brain caused by Naegleria fowleri. The pathogen is found in warm freshwater including lakes, rivers, streams, and hot springs. It enters the body through the nose and travels via the olfactory nerve to the brain. Infection usually occurs when individuals swim or dive in warm freshwater. Most cases have been reported in children from Southern states. In 2010, the first case in a northern state was reported from Minnesota, and three additional cases have since been reported in Kansas and Indiana (J. Ped. Infect. Dis. 2014 [doi: 10.1093/jpids/piu103]). Cases also have been reported in two individuals who were regular users of neti pots for sinus irrigation because the irrigating solution was prepared with contaminated tap water (Clin. Infect. Dis. 2012;55:e79-85). Clinical presentation is similar to bacterial meningitis. Helpful diagnostic clues may come from obtaining a history of swimming in freshwater within the 2 weeks prior to presentation, especially during the summer, or the use of nasal or sinus irrigation with untreated tap water. Consultation with an infectious disease specialist is recommended.

Acanthamoeba keratitis is a potentially blinding infection of the cornea that primarily occurs in individuals who wear contact lenses. Risk factors for the infection include swimming, showering, and use of hot tubs while wearing contact lenses. Improper storage and cleansing contacts with tap water are other risk factors. Anyone with corneal trauma and similar water exposures also would be at risk. Clinically, the history combined with a foreign-body sensation, pain, and decreased visual acuity should make one include this infection in the differential diagnosis. Referral to an ophthalmologist is required.

Finally, swimming with an open wound is a portal of entry for Vibrio vulnificus. It usually is associated with consumption of contaminated seafood, especially oysters. In immunocompromised individuals, especially those with chronic liver disease, this bacteria can cause a life-threatening illness leading to bacteremia, septic shock, and development of blistering skin lesions. Infections are fatal in approximately 50% of cases.

The goal of this brief review was not to discourage swimming, but to make your patients and their families healthy swimmers. Here are a few things the CDC is recommending to help them achieve that goal:

• Shower prior to going swimming.

• Do not swallow or drink pool water.

• Take bathroom breaks every hour and rinse off before going back into the water.

• Do not swim if you have diarrhea.

• Wait at least 2 weeks to go swimming if you have had diarrhea.

• Change swim diapers frequently and away from the water.

• Suggest patients download the free CDC app Healthy Swimming for more detailed information and suggest they visit cdc.gov/healthywater/swimming.

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She had no relevant financial disclosures. Write to Dr. Word at [email protected].

Navigating the world of autism treatments and staying abreast of the evolving evidence base of a wide array of interventions spanning diverse modalities can be overwhelming for even well-trained clinicians. Parents and caregivers for children with an autism spectrum disorder (ASD) equally face troubles reconciling treatment information often obtained not only from their health care providers, but from family members, friends, and the Internet (where thousands of websites promise “cures” or improvements for ASD/ASD-related symptoms). In this context, families are commonly seeking complementary and alternative treatments for their children. Although some of these treatments are relatively benign, key safety and efficacy issues remain, and parents often act with little to no guidance from their child’s primary care provider. With the increasing prevalence of the use of nontraditional treatments used both with and in place of conventional treatments, you should be prepared to counsel families in making the most informed decisions in the best interest of their child.

Case Summary

Adam is a 15-year-old boy who carries a diagnosis of an ASD accompanied by enduring gastrointestinal troubles (constipation), auditory and tactile sensitivities, and episodes of aggression towards himself and others. Adam is essentially nonverbal and enjoys watching children’s videos repeatedly (Thomas the Train); he attends school in an alternative classroom as his hyperactivity, impulsivity, and susceptibility to behaving in an unpredictable physical manner limits his ability to successfully engage with peers without one-on-one supervision.

In an attempt to address Adam’s challenging behaviors (that haven’t responded significantly to a variety of conventional medications and behavioral strategies), his well-meaning and highly educated parents seek advice. They admit they’ve come across websites that offer treatments with a promise to cure their son’s autism symptoms. Adam’s mother has always preferred “a more natural” approach to her son’s treatment, and she still has vivid memories of the side effects her son experienced on past medications, such as akathisia with risperidone.

Discussion

Adam’s case is not an uncommon scenario encountered by many families who may be experiencing increasing desperation to address their child’s autism-related struggles while being disappointed by conventional treatments. Autism is a complex neurobiologic disorder with a heterogeneous presentation for which there are no well-established pharmacologic treatments to address its core symptoms of social-communication impairments and restricted, repetitive behaviors/interests. With this in mind, it’s not surprising that studies indicate that at least 50% of families with an autistic child have tried complementary and alternative medicine (CAM) treatments. Notably, the higher the child-related stress, the more likely the families are to try CAM interventions (J. Child Neurology 2014;29:360-7) and higher use of CAM is associated with coexisting gastrointestinal problems, seizure disorders, and behavioral problems in youth with autism (Pediatrics 2012;130:S77-S82).

CAM treatments are defined by the National Center for Complementary and Integrative Health (nccih.nih.gov) as “a group of diverse medical and health care systems, practices, and products that are not presently considered to be a part of conventional medicine.” They may include biologically based therapies (dietary supplements, chelation, immune-modulating agents, special diets), mind-body medicine (acupuncture, biofeedback), energy medicine, and manipulative and body-based treatments (massage, chiropractic manipulation). Families who choose CAM interventions for their children with autism tend to try natural products, special diets, and/or mind and body practices.

Reviewing the literature surrounding CAM, there are few randomized controlled trials published, and you should be aware that evidence for most of these interventions is insufficient to make strong recommendations for or against their use. Certainly, some treatments considered as CAM can be effective in treating specific target symptoms that often co-occur in individuals with autism (using melatonin to address sleep difficulties) without major safety issues, but others are potentially dangerous and likely ineffective (chelation therapy, hyperbaric oxygen, mineral solutions). The National Autism Center has published a comprehensive analysis of autism interventions (www.nationalautismcenter.org) that can be helpful for parents and practitioners to make informed treatment decisions; their most recent 2015 review categorizes some CAM treatments as having “emerging” evidence for favorable outcomes (music therapy, massage therapy, exercise) and labels some CAM interventions as having little to no evidence to support their efficacy. Interestingly, gluten-free and casein free diets are included in this latter category. Families are frequently curious about such elimination diets, especially given the buzz in both the popular and scientific press about the gut-brain connection. Although these diets do not have strong evidence to support their use in managing core features of autism, investigators are examining whether there may be a subgroup of children with autism (those with gastrointestinal problems) who may achieve potential benefits. All in all, there’s a need for more robust research on this particular set of treatments. Families should be aware that if they chose to pursue an elimination diet, adherence for children who are inherently picky eaters may be challenging. Furthermore, although commonly labeled as safe, these diets could be linked with potentially harmful adverse effects such as nutritional deficits.

To help guide clinical decision making, it may be helpful for you to first consult the American Academy of Pediatrics 2001 policy statement, “Counseling families who choose complementary and alternative medicine for their child with chronic illness or disability” (Pediatrics 2001;107:598-601) and then consider a range of variables when discussing the use of CAM treatments with families. Some authors classify treatments as being safe, easy, cheap, and sensible (SECS) versus being risky, unrealistic, difficult, and expensive (RUDE) (Contemporary Pediatrics 2004;21:61-72), and using these terms when engaging parents in treatment decisions can be instructive for all parties. For example, there is limited high-quality evidence that omega-3 fatty acid supplementation is effective in treating autism symptoms, but the fact that this can be easy, inexpensive, and relatively safe for families to use may ultimately inform your decision to support a family’s trial of this with close monitoring. Additionally, it is important to explore whether families are seeking to replace other therapies with something novel and new, or are they looking for something to complement existing treatments/services? You should always, while being mindful of a family’s needs, values, and resources, consider first and foremost the use of treatments with established efficacy. Certainly CAM treatments – particularly those that are nonbiologic (pet therapy) – may positively augment standard interventions without potential significant harm.

Clinical Pearl

With the increasing number of parents turning to CAM treatments for their children with autism (particularly when the parents themselves use CAM), you should be prepared to talk with families about their decision making and actively ask families if this is something that they’ve considered. Given that the research on many CAM treatments is in early stages, it’s not unique to perhaps feel ill prepared to make CAM recommendations to families. Often it’s helpful to share this “CAM illiteracy” with families and aim to work together in a nonjudgmental manner to evaluate and select individualized treatment programs based on factors of potential efficacy, safety, cost, and family values. Regardless of the intervention, you should establish, with all patients, reliable methods for documenting past trials of all treatments, evaluating target symptoms, monitoring clinical outcomes, and measuring adverse events.

You should work to provide realistic hope to families and acknowledge that some CAM treatments may work better for some children, but we often don’t have a great sense, from the current state-of-the-science of ASD treatment, as to who these kids may be.

Dr. Dickerson, a child and adolescent psychiatrist, is an assistant professor of psychiatry at the University of Vermont. He is the director of the university’s autism diagnostic clinic. Dr. Dickerson said he had no relevant financial disclosures. Contact Dr. Dickerson at [email protected].

Navigating the world of autism treatments and staying abreast of the evolving evidence base of a wide array of interventions spanning diverse modalities can be overwhelming for even well-trained clinicians. Parents and caregivers for children with an autism spectrum disorder (ASD) equally face troubles reconciling treatment information often obtained not only from their health care providers, but from family members, friends, and the Internet (where thousands of websites promise “cures” or improvements for ASD/ASD-related symptoms). In this context, families are commonly seeking complementary and alternative treatments for their children. Although some of these treatments are relatively benign, key safety and efficacy issues remain, and parents often act with little to no guidance from their child’s primary care provider. With the increasing prevalence of the use of nontraditional treatments used both with and in place of conventional treatments, you should be prepared to counsel families in making the most informed decisions in the best interest of their child.

Case Summary

Adam is a 15-year-old boy who carries a diagnosis of an ASD accompanied by enduring gastrointestinal troubles (constipation), auditory and tactile sensitivities, and episodes of aggression towards himself and others. Adam is essentially nonverbal and enjoys watching children’s videos repeatedly (Thomas the Train); he attends school in an alternative classroom as his hyperactivity, impulsivity, and susceptibility to behaving in an unpredictable physical manner limits his ability to successfully engage with peers without one-on-one supervision.

In an attempt to address Adam’s challenging behaviors (that haven’t responded significantly to a variety of conventional medications and behavioral strategies), his well-meaning and highly educated parents seek advice. They admit they’ve come across websites that offer treatments with a promise to cure their son’s autism symptoms. Adam’s mother has always preferred “a more natural” approach to her son’s treatment, and she still has vivid memories of the side effects her son experienced on past medications, such as akathisia with risperidone.

Discussion

Adam’s case is not an uncommon scenario encountered by many families who may be experiencing increasing desperation to address their child’s autism-related struggles while being disappointed by conventional treatments. Autism is a complex neurobiologic disorder with a heterogeneous presentation for which there are no well-established pharmacologic treatments to address its core symptoms of social-communication impairments and restricted, repetitive behaviors/interests. With this in mind, it’s not surprising that studies indicate that at least 50% of families with an autistic child have tried complementary and alternative medicine (CAM) treatments. Notably, the higher the child-related stress, the more likely the families are to try CAM interventions (J. Child Neurology 2014;29:360-7) and higher use of CAM is associated with coexisting gastrointestinal problems, seizure disorders, and behavioral problems in youth with autism (Pediatrics 2012;130:S77-S82).

CAM treatments are defined by the National Center for Complementary and Integrative Health (nccih.nih.gov) as “a group of diverse medical and health care systems, practices, and products that are not presently considered to be a part of conventional medicine.” They may include biologically based therapies (dietary supplements, chelation, immune-modulating agents, special diets), mind-body medicine (acupuncture, biofeedback), energy medicine, and manipulative and body-based treatments (massage, chiropractic manipulation). Families who choose CAM interventions for their children with autism tend to try natural products, special diets, and/or mind and body practices.

Reviewing the literature surrounding CAM, there are few randomized controlled trials published, and you should be aware that evidence for most of these interventions is insufficient to make strong recommendations for or against their use. Certainly, some treatments considered as CAM can be effective in treating specific target symptoms that often co-occur in individuals with autism (using melatonin to address sleep difficulties) without major safety issues, but others are potentially dangerous and likely ineffective (chelation therapy, hyperbaric oxygen, mineral solutions). The National Autism Center has published a comprehensive analysis of autism interventions (www.nationalautismcenter.org) that can be helpful for parents and practitioners to make informed treatment decisions; their most recent 2015 review categorizes some CAM treatments as having “emerging” evidence for favorable outcomes (music therapy, massage therapy, exercise) and labels some CAM interventions as having little to no evidence to support their efficacy. Interestingly, gluten-free and casein free diets are included in this latter category. Families are frequently curious about such elimination diets, especially given the buzz in both the popular and scientific press about the gut-brain connection. Although these diets do not have strong evidence to support their use in managing core features of autism, investigators are examining whether there may be a subgroup of children with autism (those with gastrointestinal problems) who may achieve potential benefits. All in all, there’s a need for more robust research on this particular set of treatments. Families should be aware that if they chose to pursue an elimination diet, adherence for children who are inherently picky eaters may be challenging. Furthermore, although commonly labeled as safe, these diets could be linked with potentially harmful adverse effects such as nutritional deficits.

To help guide clinical decision making, it may be helpful for you to first consult the American Academy of Pediatrics 2001 policy statement, “Counseling families who choose complementary and alternative medicine for their child with chronic illness or disability” (Pediatrics 2001;107:598-601) and then consider a range of variables when discussing the use of CAM treatments with families. Some authors classify treatments as being safe, easy, cheap, and sensible (SECS) versus being risky, unrealistic, difficult, and expensive (RUDE) (Contemporary Pediatrics 2004;21:61-72), and using these terms when engaging parents in treatment decisions can be instructive for all parties. For example, there is limited high-quality evidence that omega-3 fatty acid supplementation is effective in treating autism symptoms, but the fact that this can be easy, inexpensive, and relatively safe for families to use may ultimately inform your decision to support a family’s trial of this with close monitoring. Additionally, it is important to explore whether families are seeking to replace other therapies with something novel and new, or are they looking for something to complement existing treatments/services? You should always, while being mindful of a family’s needs, values, and resources, consider first and foremost the use of treatments with established efficacy. Certainly CAM treatments – particularly those that are nonbiologic (pet therapy) – may positively augment standard interventions without potential significant harm.

Clinical Pearl

With the increasing number of parents turning to CAM treatments for their children with autism (particularly when the parents themselves use CAM), you should be prepared to talk with families about their decision making and actively ask families if this is something that they’ve considered. Given that the research on many CAM treatments is in early stages, it’s not unique to perhaps feel ill prepared to make CAM recommendations to families. Often it’s helpful to share this “CAM illiteracy” with families and aim to work together in a nonjudgmental manner to evaluate and select individualized treatment programs based on factors of potential efficacy, safety, cost, and family values. Regardless of the intervention, you should establish, with all patients, reliable methods for documenting past trials of all treatments, evaluating target symptoms, monitoring clinical outcomes, and measuring adverse events.

You should work to provide realistic hope to families and acknowledge that some CAM treatments may work better for some children, but we often don’t have a great sense, from the current state-of-the-science of ASD treatment, as to who these kids may be.

Dr. Dickerson, a child and adolescent psychiatrist, is an assistant professor of psychiatry at the University of Vermont. He is the director of the university’s autism diagnostic clinic. Dr. Dickerson said he had no relevant financial disclosures. Contact Dr. Dickerson at [email protected].

Navigating the world of autism treatments and staying abreast of the evolving evidence base of a wide array of interventions spanning diverse modalities can be overwhelming for even well-trained clinicians. Parents and caregivers for children with an autism spectrum disorder (ASD) equally face troubles reconciling treatment information often obtained not only from their health care providers, but from family members, friends, and the Internet (where thousands of websites promise “cures” or improvements for ASD/ASD-related symptoms). In this context, families are commonly seeking complementary and alternative treatments for their children. Although some of these treatments are relatively benign, key safety and efficacy issues remain, and parents often act with little to no guidance from their child’s primary care provider. With the increasing prevalence of the use of nontraditional treatments used both with and in place of conventional treatments, you should be prepared to counsel families in making the most informed decisions in the best interest of their child.

Case Summary

Adam is a 15-year-old boy who carries a diagnosis of an ASD accompanied by enduring gastrointestinal troubles (constipation), auditory and tactile sensitivities, and episodes of aggression towards himself and others. Adam is essentially nonverbal and enjoys watching children’s videos repeatedly (Thomas the Train); he attends school in an alternative classroom as his hyperactivity, impulsivity, and susceptibility to behaving in an unpredictable physical manner limits his ability to successfully engage with peers without one-on-one supervision.

In an attempt to address Adam’s challenging behaviors (that haven’t responded significantly to a variety of conventional medications and behavioral strategies), his well-meaning and highly educated parents seek advice. They admit they’ve come across websites that offer treatments with a promise to cure their son’s autism symptoms. Adam’s mother has always preferred “a more natural” approach to her son’s treatment, and she still has vivid memories of the side effects her son experienced on past medications, such as akathisia with risperidone.

Discussion

Adam’s case is not an uncommon scenario encountered by many families who may be experiencing increasing desperation to address their child’s autism-related struggles while being disappointed by conventional treatments. Autism is a complex neurobiologic disorder with a heterogeneous presentation for which there are no well-established pharmacologic treatments to address its core symptoms of social-communication impairments and restricted, repetitive behaviors/interests. With this in mind, it’s not surprising that studies indicate that at least 50% of families with an autistic child have tried complementary and alternative medicine (CAM) treatments. Notably, the higher the child-related stress, the more likely the families are to try CAM interventions (J. Child Neurology 2014;29:360-7) and higher use of CAM is associated with coexisting gastrointestinal problems, seizure disorders, and behavioral problems in youth with autism (Pediatrics 2012;130:S77-S82).

CAM treatments are defined by the National Center for Complementary and Integrative Health (nccih.nih.gov) as “a group of diverse medical and health care systems, practices, and products that are not presently considered to be a part of conventional medicine.” They may include biologically based therapies (dietary supplements, chelation, immune-modulating agents, special diets), mind-body medicine (acupuncture, biofeedback), energy medicine, and manipulative and body-based treatments (massage, chiropractic manipulation). Families who choose CAM interventions for their children with autism tend to try natural products, special diets, and/or mind and body practices.

Reviewing the literature surrounding CAM, there are few randomized controlled trials published, and you should be aware that evidence for most of these interventions is insufficient to make strong recommendations for or against their use. Certainly, some treatments considered as CAM can be effective in treating specific target symptoms that often co-occur in individuals with autism (using melatonin to address sleep difficulties) without major safety issues, but others are potentially dangerous and likely ineffective (chelation therapy, hyperbaric oxygen, mineral solutions). The National Autism Center has published a comprehensive analysis of autism interventions (www.nationalautismcenter.org) that can be helpful for parents and practitioners to make informed treatment decisions; their most recent 2015 review categorizes some CAM treatments as having “emerging” evidence for favorable outcomes (music therapy, massage therapy, exercise) and labels some CAM interventions as having little to no evidence to support their efficacy. Interestingly, gluten-free and casein free diets are included in this latter category. Families are frequently curious about such elimination diets, especially given the buzz in both the popular and scientific press about the gut-brain connection. Although these diets do not have strong evidence to support their use in managing core features of autism, investigators are examining whether there may be a subgroup of children with autism (those with gastrointestinal problems) who may achieve potential benefits. All in all, there’s a need for more robust research on this particular set of treatments. Families should be aware that if they chose to pursue an elimination diet, adherence for children who are inherently picky eaters may be challenging. Furthermore, although commonly labeled as safe, these diets could be linked with potentially harmful adverse effects such as nutritional deficits.

To help guide clinical decision making, it may be helpful for you to first consult the American Academy of Pediatrics 2001 policy statement, “Counseling families who choose complementary and alternative medicine for their child with chronic illness or disability” (Pediatrics 2001;107:598-601) and then consider a range of variables when discussing the use of CAM treatments with families. Some authors classify treatments as being safe, easy, cheap, and sensible (SECS) versus being risky, unrealistic, difficult, and expensive (RUDE) (Contemporary Pediatrics 2004;21:61-72), and using these terms when engaging parents in treatment decisions can be instructive for all parties. For example, there is limited high-quality evidence that omega-3 fatty acid supplementation is effective in treating autism symptoms, but the fact that this can be easy, inexpensive, and relatively safe for families to use may ultimately inform your decision to support a family’s trial of this with close monitoring. Additionally, it is important to explore whether families are seeking to replace other therapies with something novel and new, or are they looking for something to complement existing treatments/services? You should always, while being mindful of a family’s needs, values, and resources, consider first and foremost the use of treatments with established efficacy. Certainly CAM treatments – particularly those that are nonbiologic (pet therapy) – may positively augment standard interventions without potential significant harm.

Clinical Pearl

With the increasing number of parents turning to CAM treatments for their children with autism (particularly when the parents themselves use CAM), you should be prepared to talk with families about their decision making and actively ask families if this is something that they’ve considered. Given that the research on many CAM treatments is in early stages, it’s not unique to perhaps feel ill prepared to make CAM recommendations to families. Often it’s helpful to share this “CAM illiteracy” with families and aim to work together in a nonjudgmental manner to evaluate and select individualized treatment programs based on factors of potential efficacy, safety, cost, and family values. Regardless of the intervention, you should establish, with all patients, reliable methods for documenting past trials of all treatments, evaluating target symptoms, monitoring clinical outcomes, and measuring adverse events.

You should work to provide realistic hope to families and acknowledge that some CAM treatments may work better for some children, but we often don’t have a great sense, from the current state-of-the-science of ASD treatment, as to who these kids may be.

Dr. Dickerson, a child and adolescent psychiatrist, is an assistant professor of psychiatry at the University of Vermont. He is the director of the university’s autism diagnostic clinic. Dr. Dickerson said he had no relevant financial disclosures. Contact Dr. Dickerson at [email protected].

Carl June, MD

Photo from Penn Medicine

Infusions of modified autologous T cells may improve responses in multiple myeloma (MM) patients undergoing autologous stem cell transplant (auto-SCT), according to research published in Nature Medicine.

Researchers said patients who received the T cells—which were engineered to express an affinity-enhanced T-cell receptor (TCR)—after auto-SCT had a better response rate than is expected for MM patients undergoing auto-SCT. At day 100, the overall response rate was 90%.

The researchers also said the T cells were safe. There were no treatment-related deaths, and all 7 serious adverse events were resolved.

“This study shows us that these TCR-specific T cells are safe and feasible . . . , but it also revealed encouraging antitumor activity and showed impressive, durable T-cell persistence,” said study author Carl June, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

The research was a collaboration between the University of Maryland School of Medicine, the Perelman School of Medicine, and Adaptimmune, a clinical stage biopharmaceutical company that owns the core TCR technology and funded the study.

The study included 20 evaluable patients with advanced MM. They received an average of 2.4 billion autologous T cells 2 days after undergoing auto-SCT.

The T cells were engineered to express an affinity-enhanced TCR recognizing a naturally processed peptide shared by the cancer-testis antigens NY-ESO-1 and LAGE-1. Up to 60% of advanced myelomas have been reported to express NY-ESO-1 and/or LAGE-1, which is correlated with tumor proliferation and poorer outcomes.

Response and survival

“The majority of patients who participated in this trial had a meaningful degree of clinical benefit,” said study author Aaron P. Rapoport, MD, of the University of Maryland School of Medicine in Baltimore.

“Even patients who later relapsed after achieving a complete response to treatment or didn’t have a complete response had periods of disease control that I believe they would not have otherwise experienced. Some patients are still in remission after nearly 3 years.”

Treatment responses were as follows:

A subset of patients received lenalidomide maintenance after day 100, and 1 patient had died by the 180-day mark, as a result of disease progression.

The researchers noted that relapse was associated with a loss of the engineered T cells, which suggests methods for sustaining long-term persistence of the cells could improve outcomes.

At a median follow up of 21.1 months, 75% of patients were still alive, 50% were progression-free, and 25% had died after disease progression.

At a median follow up of 30.1 months, the median progression-free survival was 19.1 months, and the median overall survival was 32.1 months.

Adverse events

There were no treatment-related deaths, and all 7 serious adverse events were resolved. The serious events included grade 3 gastrointestinal graft-vs-host disease (GVHD), grade 3 hypoxia, grade 3 dehydration, grade 4 neutropenia, grade 4 hyponatremia, grade 4 hypotension, and grade 4 pancytopenia.

There were 17 adverse events that were considered probably related to treatment. These were gastrointestinal GVHD (3 grade 3), skin GVHD (2 grade 2), fatigue (1 grade 1), fever (2 grade 1-2), rash (3 grade 1-3), diarrhea (2 grade 1-2), sinus tachycardia (1 grade 1), injection site reaction/extravasation changes (1 grade 1), weakness (1 grade 1), and hypotension (1 grade 3).

“This study suggests that treatment with engineered T cells is not only safe but of potential clinical benefit to patients with certain types of aggressive multiple myeloma,” Dr Rapoport said. “Our findings provide a strong foundation for further research in the field of cellular immunotherapy for myeloma to help achieve even better results for our patients.”

Carl June, MD

Photo from Penn Medicine

Infusions of modified autologous T cells may improve responses in multiple myeloma (MM) patients undergoing autologous stem cell transplant (auto-SCT), according to research published in Nature Medicine.

Researchers said patients who received the T cells—which were engineered to express an affinity-enhanced T-cell receptor (TCR)—after auto-SCT had a better response rate than is expected for MM patients undergoing auto-SCT. At day 100, the overall response rate was 90%.

The researchers also said the T cells were safe. There were no treatment-related deaths, and all 7 serious adverse events were resolved.

“This study shows us that these TCR-specific T cells are safe and feasible . . . , but it also revealed encouraging antitumor activity and showed impressive, durable T-cell persistence,” said study author Carl June, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

The research was a collaboration between the University of Maryland School of Medicine, the Perelman School of Medicine, and Adaptimmune, a clinical stage biopharmaceutical company that owns the core TCR technology and funded the study.

The study included 20 evaluable patients with advanced MM. They received an average of 2.4 billion autologous T cells 2 days after undergoing auto-SCT.

The T cells were engineered to express an affinity-enhanced TCR recognizing a naturally processed peptide shared by the cancer-testis antigens NY-ESO-1 and LAGE-1. Up to 60% of advanced myelomas have been reported to express NY-ESO-1 and/or LAGE-1, which is correlated with tumor proliferation and poorer outcomes.

Response and survival

“The majority of patients who participated in this trial had a meaningful degree of clinical benefit,” said study author Aaron P. Rapoport, MD, of the University of Maryland School of Medicine in Baltimore.

“Even patients who later relapsed after achieving a complete response to treatment or didn’t have a complete response had periods of disease control that I believe they would not have otherwise experienced. Some patients are still in remission after nearly 3 years.”

Treatment responses were as follows:

A subset of patients received lenalidomide maintenance after day 100, and 1 patient had died by the 180-day mark, as a result of disease progression.

The researchers noted that relapse was associated with a loss of the engineered T cells, which suggests methods for sustaining long-term persistence of the cells could improve outcomes.

At a median follow up of 21.1 months, 75% of patients were still alive, 50% were progression-free, and 25% had died after disease progression.

At a median follow up of 30.1 months, the median progression-free survival was 19.1 months, and the median overall survival was 32.1 months.

Adverse events

There were no treatment-related deaths, and all 7 serious adverse events were resolved. The serious events included grade 3 gastrointestinal graft-vs-host disease (GVHD), grade 3 hypoxia, grade 3 dehydration, grade 4 neutropenia, grade 4 hyponatremia, grade 4 hypotension, and grade 4 pancytopenia.

There were 17 adverse events that were considered probably related to treatment. These were gastrointestinal GVHD (3 grade 3), skin GVHD (2 grade 2), fatigue (1 grade 1), fever (2 grade 1-2), rash (3 grade 1-3), diarrhea (2 grade 1-2), sinus tachycardia (1 grade 1), injection site reaction/extravasation changes (1 grade 1), weakness (1 grade 1), and hypotension (1 grade 3).

“This study suggests that treatment with engineered T cells is not only safe but of potential clinical benefit to patients with certain types of aggressive multiple myeloma,” Dr Rapoport said. “Our findings provide a strong foundation for further research in the field of cellular immunotherapy for myeloma to help achieve even better results for our patients.”

Carl June, MD

Photo from Penn Medicine

Infusions of modified autologous T cells may improve responses in multiple myeloma (MM) patients undergoing autologous stem cell transplant (auto-SCT), according to research published in Nature Medicine.

Researchers said patients who received the T cells—which were engineered to express an affinity-enhanced T-cell receptor (TCR)—after auto-SCT had a better response rate than is expected for MM patients undergoing auto-SCT. At day 100, the overall response rate was 90%.

The researchers also said the T cells were safe. There were no treatment-related deaths, and all 7 serious adverse events were resolved.

“This study shows us that these TCR-specific T cells are safe and feasible . . . , but it also revealed encouraging antitumor activity and showed impressive, durable T-cell persistence,” said study author Carl June, MD, of the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.

The research was a collaboration between the University of Maryland School of Medicine, the Perelman School of Medicine, and Adaptimmune, a clinical stage biopharmaceutical company that owns the core TCR technology and funded the study.

The study included 20 evaluable patients with advanced MM. They received an average of 2.4 billion autologous T cells 2 days after undergoing auto-SCT.

The T cells were engineered to express an affinity-enhanced TCR recognizing a naturally processed peptide shared by the cancer-testis antigens NY-ESO-1 and LAGE-1. Up to 60% of advanced myelomas have been reported to express NY-ESO-1 and/or LAGE-1, which is correlated with tumor proliferation and poorer outcomes.

Response and survival

“The majority of patients who participated in this trial had a meaningful degree of clinical benefit,” said study author Aaron P. Rapoport, MD, of the University of Maryland School of Medicine in Baltimore.

“Even patients who later relapsed after achieving a complete response to treatment or didn’t have a complete response had periods of disease control that I believe they would not have otherwise experienced. Some patients are still in remission after nearly 3 years.”

Treatment responses were as follows:

A subset of patients received lenalidomide maintenance after day 100, and 1 patient had died by the 180-day mark, as a result of disease progression.

The researchers noted that relapse was associated with a loss of the engineered T cells, which suggests methods for sustaining long-term persistence of the cells could improve outcomes.

At a median follow up of 21.1 months, 75% of patients were still alive, 50% were progression-free, and 25% had died after disease progression.

At a median follow up of 30.1 months, the median progression-free survival was 19.1 months, and the median overall survival was 32.1 months.

Adverse events

There were no treatment-related deaths, and all 7 serious adverse events were resolved. The serious events included grade 3 gastrointestinal graft-vs-host disease (GVHD), grade 3 hypoxia, grade 3 dehydration, grade 4 neutropenia, grade 4 hyponatremia, grade 4 hypotension, and grade 4 pancytopenia.

There were 17 adverse events that were considered probably related to treatment. These were gastrointestinal GVHD (3 grade 3), skin GVHD (2 grade 2), fatigue (1 grade 1), fever (2 grade 1-2), rash (3 grade 1-3), diarrhea (2 grade 1-2), sinus tachycardia (1 grade 1), injection site reaction/extravasation changes (1 grade 1), weakness (1 grade 1), and hypotension (1 grade 3).

“This study suggests that treatment with engineered T cells is not only safe but of potential clinical benefit to patients with certain types of aggressive multiple myeloma,” Dr Rapoport said. “Our findings provide a strong foundation for further research in the field of cellular immunotherapy for myeloma to help achieve even better results for our patients.”

Wyndham Wilson, MD, PhD

Photo by Larry Young

Responses to the BTK inhibitor ibrutinib differ according to a patient’s subtype of diffuse large B-cell lymphoma (DLBCL), results of a phase 1/2 trial suggest.

The study showed that patients with activated B-cell-like (ABC) DLBCL were more likely to respond to ibrutinib than patients with germinal center B-cell-like (GCB) DLBCL.

“This is the first clinical study to demonstrate the importance of precision medicine in lymphomas,” said Wyndham Wilson, MD, PhD, of the National Cancer Institute in Bethesda, Maryland.

Dr Wilson and his colleagues described the trial in Nature Medicine. The research, which was sponsored by Pharmacyclics, Inc. (the company developing ibrutinib), was previously presented at EHA 2013.

The trial enrolled 80 patients with relapsed or refractory DLBCL. All patients received ibrutinib. Tumor responses occurred in 25% of patients. There were 8 complete responses and 12 partial responses.

After a median follow-up of 11.5 months, the median progression-free survival was 1.6 months, and the median overall survival was 6.4 months.

An analysis of outcomes by disease subtype showed that ibrutinib produced complete or partial responses in 37% (14/38) of patients with ABC DLBCL but only 5% (1/20) of patients with GCB DLBCL.

The researchers speculated that ABC tumors may produce abnormal B-cell receptor signals that promote the survival of cancer cells by activating BTK, which would account for the sensitivity of ABC tumors to ibrutinib.

Based on this study’s results, researchers are conducting an international phase 3 trial of standard chemotherapy with or without ibrutinib in patients with DLBCL, excluding the GCB subtype (NCT01855750).

This is the first time a phase 3 trial has been designed to selectively enroll patients with a particular molecular subtype of DLBCL. The study’s objective is to determine if the addition of ibrutinib to standard chemotherapy can increase the cure rate of patients with ABC DLBCL.

Wyndham Wilson, MD, PhD

Photo by Larry Young

Responses to the BTK inhibitor ibrutinib differ according to a patient’s subtype of diffuse large B-cell lymphoma (DLBCL), results of a phase 1/2 trial suggest.

The study showed that patients with activated B-cell-like (ABC) DLBCL were more likely to respond to ibrutinib than patients with germinal center B-cell-like (GCB) DLBCL.

“This is the first clinical study to demonstrate the importance of precision medicine in lymphomas,” said Wyndham Wilson, MD, PhD, of the National Cancer Institute in Bethesda, Maryland.

Dr Wilson and his colleagues described the trial in Nature Medicine. The research, which was sponsored by Pharmacyclics, Inc. (the company developing ibrutinib), was previously presented at EHA 2013.

The trial enrolled 80 patients with relapsed or refractory DLBCL. All patients received ibrutinib. Tumor responses occurred in 25% of patients. There were 8 complete responses and 12 partial responses.

After a median follow-up of 11.5 months, the median progression-free survival was 1.6 months, and the median overall survival was 6.4 months.

An analysis of outcomes by disease subtype showed that ibrutinib produced complete or partial responses in 37% (14/38) of patients with ABC DLBCL but only 5% (1/20) of patients with GCB DLBCL.

The researchers speculated that ABC tumors may produce abnormal B-cell receptor signals that promote the survival of cancer cells by activating BTK, which would account for the sensitivity of ABC tumors to ibrutinib.

Based on this study’s results, researchers are conducting an international phase 3 trial of standard chemotherapy with or without ibrutinib in patients with DLBCL, excluding the GCB subtype (NCT01855750).

This is the first time a phase 3 trial has been designed to selectively enroll patients with a particular molecular subtype of DLBCL. The study’s objective is to determine if the addition of ibrutinib to standard chemotherapy can increase the cure rate of patients with ABC DLBCL.

Wyndham Wilson, MD, PhD

Photo by Larry Young

Responses to the BTK inhibitor ibrutinib differ according to a patient’s subtype of diffuse large B-cell lymphoma (DLBCL), results of a phase 1/2 trial suggest.

The study showed that patients with activated B-cell-like (ABC) DLBCL were more likely to respond to ibrutinib than patients with germinal center B-cell-like (GCB) DLBCL.

“This is the first clinical study to demonstrate the importance of precision medicine in lymphomas,” said Wyndham Wilson, MD, PhD, of the National Cancer Institute in Bethesda, Maryland.

Dr Wilson and his colleagues described the trial in Nature Medicine. The research, which was sponsored by Pharmacyclics, Inc. (the company developing ibrutinib), was previously presented at EHA 2013.

The trial enrolled 80 patients with relapsed or refractory DLBCL. All patients received ibrutinib. Tumor responses occurred in 25% of patients. There were 8 complete responses and 12 partial responses.

After a median follow-up of 11.5 months, the median progression-free survival was 1.6 months, and the median overall survival was 6.4 months.

An analysis of outcomes by disease subtype showed that ibrutinib produced complete or partial responses in 37% (14/38) of patients with ABC DLBCL but only 5% (1/20) of patients with GCB DLBCL.

The researchers speculated that ABC tumors may produce abnormal B-cell receptor signals that promote the survival of cancer cells by activating BTK, which would account for the sensitivity of ABC tumors to ibrutinib.

Based on this study’s results, researchers are conducting an international phase 3 trial of standard chemotherapy with or without ibrutinib in patients with DLBCL, excluding the GCB subtype (NCT01855750).

This is the first time a phase 3 trial has been designed to selectively enroll patients with a particular molecular subtype of DLBCL. The study’s objective is to determine if the addition of ibrutinib to standard chemotherapy can increase the cure rate of patients with ABC DLBCL.

Vial of testosterone cypionate

for intramuscular injection

Contrary to previous findings, a new study suggests there is no link between testosterone therapy and venous thromboembolism (VTE).

Investigators analyzed more than 30,000 commercially insured men who were age 40 and older, comparing men with VTE to those without the

condition.

Results indicated that exposure to testosterone therapy did not confer an increased risk of VTE.

The investigators reported these results in Mayo Clinic Proceedings.

“In 2014, the [US Food and Drug Administration] required manufacturers to add a warning about potential risks of VTE to the label of all approved testosterone products,” said Jacques Baillargeon, PhD, of the University of Texas Medical Branch at Galveston.

“The warning, however, is based primarily on post-marketing drug surveillance and case reports. To date, there have been no published, comparative, large-scale studies examining the association of testosterone therapy and the risk of VTE.”

With that in mind, Dr Baillargeon and his colleagues conducted a case-control study of 30,572 men age 40 and older. The men were enrolled in one of the nation’s largest commercial insurance programs between January 1, 2007 and December 31, 2012.

Cases were defined as men who had a primary diagnosis of VTE and received an anticoagulant or an intravascular vena cava filter in the 60 days following their diagnoses.

Each case was matched with 3 control subjects by age, geographic region, diagnosis of low testosterone, and diagnosis of any underlying coagulopathy.

The investigators found that being exposed to testosterone therapy in the previous 15 days was not associated with an increased risk of VTE. The adjusted odds ratio was 0.90 for 15 days, and findings were similar for exposure within 30 days and 60 days.

Dr Baillargeon and his colleagues also looked at specific routes of administration for testosterone therapy—topical creams, transdermal patches, and intramuscular injections.

The team found no increased risk of VTE with any of these methods. The adjusted odds ratios were 0.80 for topical, 0.91 for transdermal, and 1.15 for intramuscular administration.

“It is important to acknowledge, for a man who has medically diagnosed low testosterone, that there are clear risks to not receiving testosterone therapy, including osteoporosis, sexual dysfunction, increased amounts of fat tissue, decreased lean muscle mass, possible metabolic syndrome, and cardiovascular disease,” Dr Baillargeon said.

“It’s also important to note that further research needs to be conducted to rigorously assess the long-term risks of testosterone therapy. These findings may help to inform the benefit-risk assessment for men with testosterone deficiency considering treatment.”

Vial of testosterone cypionate

for intramuscular injection

Contrary to previous findings, a new study suggests there is no link between testosterone therapy and venous thromboembolism (VTE).

Investigators analyzed more than 30,000 commercially insured men who were age 40 and older, comparing men with VTE to those without the

condition.

Results indicated that exposure to testosterone therapy did not confer an increased risk of VTE.

The investigators reported these results in Mayo Clinic Proceedings.

“In 2014, the [US Food and Drug Administration] required manufacturers to add a warning about potential risks of VTE to the label of all approved testosterone products,” said Jacques Baillargeon, PhD, of the University of Texas Medical Branch at Galveston.

“The warning, however, is based primarily on post-marketing drug surveillance and case reports. To date, there have been no published, comparative, large-scale studies examining the association of testosterone therapy and the risk of VTE.”

With that in mind, Dr Baillargeon and his colleagues conducted a case-control study of 30,572 men age 40 and older. The men were enrolled in one of the nation’s largest commercial insurance programs between January 1, 2007 and December 31, 2012.

Cases were defined as men who had a primary diagnosis of VTE and received an anticoagulant or an intravascular vena cava filter in the 60 days following their diagnoses.

Each case was matched with 3 control subjects by age, geographic region, diagnosis of low testosterone, and diagnosis of any underlying coagulopathy.

The investigators found that being exposed to testosterone therapy in the previous 15 days was not associated with an increased risk of VTE. The adjusted odds ratio was 0.90 for 15 days, and findings were similar for exposure within 30 days and 60 days.

Dr Baillargeon and his colleagues also looked at specific routes of administration for testosterone therapy—topical creams, transdermal patches, and intramuscular injections.

The team found no increased risk of VTE with any of these methods. The adjusted odds ratios were 0.80 for topical, 0.91 for transdermal, and 1.15 for intramuscular administration.

“It is important to acknowledge, for a man who has medically diagnosed low testosterone, that there are clear risks to not receiving testosterone therapy, including osteoporosis, sexual dysfunction, increased amounts of fat tissue, decreased lean muscle mass, possible metabolic syndrome, and cardiovascular disease,” Dr Baillargeon said.

“It’s also important to note that further research needs to be conducted to rigorously assess the long-term risks of testosterone therapy. These findings may help to inform the benefit-risk assessment for men with testosterone deficiency considering treatment.”

Vial of testosterone cypionate

for intramuscular injection

Contrary to previous findings, a new study suggests there is no link between testosterone therapy and venous thromboembolism (VTE).

Investigators analyzed more than 30,000 commercially insured men who were age 40 and older, comparing men with VTE to those without the

condition.

Results indicated that exposure to testosterone therapy did not confer an increased risk of VTE.

The investigators reported these results in Mayo Clinic Proceedings.

“In 2014, the [US Food and Drug Administration] required manufacturers to add a warning about potential risks of VTE to the label of all approved testosterone products,” said Jacques Baillargeon, PhD, of the University of Texas Medical Branch at Galveston.

“The warning, however, is based primarily on post-marketing drug surveillance and case reports. To date, there have been no published, comparative, large-scale studies examining the association of testosterone therapy and the risk of VTE.”

With that in mind, Dr Baillargeon and his colleagues conducted a case-control study of 30,572 men age 40 and older. The men were enrolled in one of the nation’s largest commercial insurance programs between January 1, 2007 and December 31, 2012.

Cases were defined as men who had a primary diagnosis of VTE and received an anticoagulant or an intravascular vena cava filter in the 60 days following their diagnoses.

Each case was matched with 3 control subjects by age, geographic region, diagnosis of low testosterone, and diagnosis of any underlying coagulopathy.

The investigators found that being exposed to testosterone therapy in the previous 15 days was not associated with an increased risk of VTE. The adjusted odds ratio was 0.90 for 15 days, and findings were similar for exposure within 30 days and 60 days.

Dr Baillargeon and his colleagues also looked at specific routes of administration for testosterone therapy—topical creams, transdermal patches, and intramuscular injections.

The team found no increased risk of VTE with any of these methods. The adjusted odds ratios were 0.80 for topical, 0.91 for transdermal, and 1.15 for intramuscular administration.

“It is important to acknowledge, for a man who has medically diagnosed low testosterone, that there are clear risks to not receiving testosterone therapy, including osteoporosis, sexual dysfunction, increased amounts of fat tissue, decreased lean muscle mass, possible metabolic syndrome, and cardiovascular disease,” Dr Baillargeon said.

“It’s also important to note that further research needs to be conducted to rigorously assess the long-term risks of testosterone therapy. These findings may help to inform the benefit-risk assessment for men with testosterone deficiency considering treatment.”