The Journal of Family Practice

ILLUSTRATIVE CASE

A 21-year-old G1P0 at 35 weeks, 2 days of gestation presents to labor and delivery reporting a “gush of clear fluid.” On exam, you confirm she has preterm rupture of membranes. She is contracting every 3 minutes and has a cervix dilated to 3 cm. Is there any neonatal benefit to providing corticosteroids in this late preterm period?

Approximately 12% of all births in the United States are the result of preterm labor,² and 8% are born in the late preterm period, defined as 34 to 36 weeks’ gestation.³ To reduce the risk of neonatal death and respiratory complications, both the American College of Obstetricians and Gynecologists and the National Institutes of Health recommend a course of corticosteroids between 24 and 34 weeks’ gestation for women at increased risk of preterm delivery.^2,4 Due to a lack of evidence from randomized controlled trials (RCTs) on the benefit of corticosteroids in late preterm labor, there have not been recommendations to extend this period.⁵ However, multiple studies have shown that babies born during the late preterm period have more neonatal complications than term newborns.^6-8

A retrospective chart review of more than 130,000 live births found newborns delivered between 34 and 36 weeks had higher rates of respiratory distress than those delivered at 39 weeks (ventilator use dropped from 3.3% at 34 weeks to 0.3% at 39 weeks and transient tachypnea decreased from 2.4% at 34 weeks to 0.4% at 39 weeks).⁶ Another retrospective review of more than 230,000 newborns, of which 19,000 were born in the late preterm period, revealed that more neonates born between 34 and 36 weeks’ gestation had respiratory distress syndrome than neonates delivered at 39 weeks (10.5% at 34 weeks, 6% at 35 weeks, 2.8% at 36 weeks vs 0.3% at 39 weeks; P<.001 for the trend).⁸

STUDY SUMMARY

Late preterm newborns breathe better with antenatal betamethasone

This randomized placebo-controlled trial examined the effectiveness of betamethasone in preventing neonatal respiratory complications for 2831 women at high probability of preterm delivery between 34 weeks and 36 weeks, 6 days of gestation. “High probability of preterm delivery” was defined as preterm labor with intact membranes and at least 3 cm dilation or 75% cervical effacement; spontaneous rupture of membranes; or anticipated preterm delivery for any other indication either through induction or cesarean section between 24 hours and 7 days after the planned randomization.

Patients were randomly assigned to receive either 2 intramuscular injections (12 mg each) of betamethasone or placebo, 24 hours apart. The 2 doses were successfully given in 60% of the betamethasone group and 59% of the placebo group. In 95% of the cases where the second dose was not given, it was because delivery occurred within 24 hours of the first dose.

The primary outcome was the need for respiratory support within 72 hours of birth, which was defined as one or more of the following: the use of continuous positive airway pressure (CPAP) or high-flow nasal cannula for at least 2 consecutive hours, supplemental oxygen for at least 4 continuous hours, extracorporeal membrane oxygenation (ECMO), or mechanical ventilation.

This study demonstrated clear benefit in neonatal respiratory outcomes when betamethasone vs placebo was used in the late preterm period.

The median time to delivery from enrollment was 31 to 33 hours, and 31.4% underwent cesarean delivery. In the intention-to-treat analysis, the primary outcome was significantly lower in the betamethasone group than in the placebo group (11.6% vs 14.4%; relative risk [RR]=0.80; 95% CI, 0.66-0.97; P=.02; number needed to treat [NNT]=35). Secondary outcomes (severe complications, representing a composite of the use of CPAP or high-flow nasal cannula for at least 12 continuous hours, supplemental oxygen for at least 24 continuous hours, ECMO, mechanical ventilation, stillbirth, or neonatal death within 72 hours after delivery) were also lower in the betamethasone group (8.1% vs 12.1%; RR=0.67; 95% CI, 0.53-0.84; P<.001; NNT=25). The betamethasone group also had a lower risk of transient tachypnea of the newborn (6.7% vs 9.9%; RR=0.68; 95% CI, 0.53-0.87; P=.002).

There were no significant differences in the occurrence of maternal chorioamnionitis (about 2%) or endometritis (about 1%) between the groups. Hypoglycemia in the newborn occurred more in the betamethasone group (24% vs 15%; RR=1.6; 95% CI, 1.37-1.87; P<.001; number needed to harm [NNH]=11). The betamethasone group had 2 neonatal deaths: one from septic shock and the other from a structural cardiac anomaly and arrhythmia.

WHAT’S NEW

Betamethasone makes a difference even in the late, late preterm period

This study demonstrated clear benefit in neonatal respiratory outcomes when betamethasone vs placebo was used in the late preterm period. The findings were similar to those from the Antenatal Steroids for Term Elective Caesarean Section Research Team.⁹ Their trial showed a reduction in respiratory complications in term neonates delivered via elective cesarean section to mothers who received antenatal betamethasone (NNT=37 to prevent admission to a special care nursery with respiratory distress). The findings were also consistent with those of a recent meta-analysis (including this trial) evaluating the occurrence of respiratory complications with the use of antenatal betamethasone in women expected to deliver in the late preterm period or with a planned cesarean delivery at ≥37 weeks’ gestation.¹⁰

CAVEATS

Neonates may develop hypoglycemia

The authors of the study reported an increased risk of hypoglycemia in the neonates receiving antenatal betamethasone. The long-term implications of this are unclear, however, given that there was a reduction in intermediate care nursery and neonatal intensive care unit stays that were 3 days or longer in the betamethasone group. Also, there was no difference in hospital length of stay between the 2 groups. In addition, it’s not clear if there are any long-term neonatal complications of betamethasone use in the late preterm period.

CHALLENGES TO IMPLEMENTATION

Challenges are negligible since betamethasone is readily available

There are minimal challenges to implementing this strategy, as betamethasone is routinely used for preterm labor and is readily available on labor and delivery units.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 21-year-old G1P0 at 35 weeks, 2 days of gestation presents to labor and delivery reporting a “gush of clear fluid.” On exam, you confirm she has preterm rupture of membranes. She is contracting every 3 minutes and has a cervix dilated to 3 cm. Is there any neonatal benefit to providing corticosteroids in this late preterm period?

Approximately 12% of all births in the United States are the result of preterm labor,² and 8% are born in the late preterm period, defined as 34 to 36 weeks’ gestation.³ To reduce the risk of neonatal death and respiratory complications, both the American College of Obstetricians and Gynecologists and the National Institutes of Health recommend a course of corticosteroids between 24 and 34 weeks’ gestation for women at increased risk of preterm delivery.^2,4 Due to a lack of evidence from randomized controlled trials (RCTs) on the benefit of corticosteroids in late preterm labor, there have not been recommendations to extend this period.⁵ However, multiple studies have shown that babies born during the late preterm period have more neonatal complications than term newborns.^6-8

A retrospective chart review of more than 130,000 live births found newborns delivered between 34 and 36 weeks had higher rates of respiratory distress than those delivered at 39 weeks (ventilator use dropped from 3.3% at 34 weeks to 0.3% at 39 weeks and transient tachypnea decreased from 2.4% at 34 weeks to 0.4% at 39 weeks).⁶ Another retrospective review of more than 230,000 newborns, of which 19,000 were born in the late preterm period, revealed that more neonates born between 34 and 36 weeks’ gestation had respiratory distress syndrome than neonates delivered at 39 weeks (10.5% at 34 weeks, 6% at 35 weeks, 2.8% at 36 weeks vs 0.3% at 39 weeks; P<.001 for the trend).⁸

STUDY SUMMARY

Late preterm newborns breathe better with antenatal betamethasone

This randomized placebo-controlled trial examined the effectiveness of betamethasone in preventing neonatal respiratory complications for 2831 women at high probability of preterm delivery between 34 weeks and 36 weeks, 6 days of gestation. “High probability of preterm delivery” was defined as preterm labor with intact membranes and at least 3 cm dilation or 75% cervical effacement; spontaneous rupture of membranes; or anticipated preterm delivery for any other indication either through induction or cesarean section between 24 hours and 7 days after the planned randomization.

Patients were randomly assigned to receive either 2 intramuscular injections (12 mg each) of betamethasone or placebo, 24 hours apart. The 2 doses were successfully given in 60% of the betamethasone group and 59% of the placebo group. In 95% of the cases where the second dose was not given, it was because delivery occurred within 24 hours of the first dose.

The primary outcome was the need for respiratory support within 72 hours of birth, which was defined as one or more of the following: the use of continuous positive airway pressure (CPAP) or high-flow nasal cannula for at least 2 consecutive hours, supplemental oxygen for at least 4 continuous hours, extracorporeal membrane oxygenation (ECMO), or mechanical ventilation.

This study demonstrated clear benefit in neonatal respiratory outcomes when betamethasone vs placebo was used in the late preterm period.

The median time to delivery from enrollment was 31 to 33 hours, and 31.4% underwent cesarean delivery. In the intention-to-treat analysis, the primary outcome was significantly lower in the betamethasone group than in the placebo group (11.6% vs 14.4%; relative risk [RR]=0.80; 95% CI, 0.66-0.97; P=.02; number needed to treat [NNT]=35). Secondary outcomes (severe complications, representing a composite of the use of CPAP or high-flow nasal cannula for at least 12 continuous hours, supplemental oxygen for at least 24 continuous hours, ECMO, mechanical ventilation, stillbirth, or neonatal death within 72 hours after delivery) were also lower in the betamethasone group (8.1% vs 12.1%; RR=0.67; 95% CI, 0.53-0.84; P<.001; NNT=25). The betamethasone group also had a lower risk of transient tachypnea of the newborn (6.7% vs 9.9%; RR=0.68; 95% CI, 0.53-0.87; P=.002).

There were no significant differences in the occurrence of maternal chorioamnionitis (about 2%) or endometritis (about 1%) between the groups. Hypoglycemia in the newborn occurred more in the betamethasone group (24% vs 15%; RR=1.6; 95% CI, 1.37-1.87; P<.001; number needed to harm [NNH]=11). The betamethasone group had 2 neonatal deaths: one from septic shock and the other from a structural cardiac anomaly and arrhythmia.

WHAT’S NEW

Betamethasone makes a difference even in the late, late preterm period

This study demonstrated clear benefit in neonatal respiratory outcomes when betamethasone vs placebo was used in the late preterm period. The findings were similar to those from the Antenatal Steroids for Term Elective Caesarean Section Research Team.⁹ Their trial showed a reduction in respiratory complications in term neonates delivered via elective cesarean section to mothers who received antenatal betamethasone (NNT=37 to prevent admission to a special care nursery with respiratory distress). The findings were also consistent with those of a recent meta-analysis (including this trial) evaluating the occurrence of respiratory complications with the use of antenatal betamethasone in women expected to deliver in the late preterm period or with a planned cesarean delivery at ≥37 weeks’ gestation.¹⁰

CAVEATS

Neonates may develop hypoglycemia

The authors of the study reported an increased risk of hypoglycemia in the neonates receiving antenatal betamethasone. The long-term implications of this are unclear, however, given that there was a reduction in intermediate care nursery and neonatal intensive care unit stays that were 3 days or longer in the betamethasone group. Also, there was no difference in hospital length of stay between the 2 groups. In addition, it’s not clear if there are any long-term neonatal complications of betamethasone use in the late preterm period.

CHALLENGES TO IMPLEMENTATION

Challenges are negligible since betamethasone is readily available

There are minimal challenges to implementing this strategy, as betamethasone is routinely used for preterm labor and is readily available on labor and delivery units.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 21-year-old G1P0 at 35 weeks, 2 days of gestation presents to labor and delivery reporting a “gush of clear fluid.” On exam, you confirm she has preterm rupture of membranes. She is contracting every 3 minutes and has a cervix dilated to 3 cm. Is there any neonatal benefit to providing corticosteroids in this late preterm period?

Approximately 12% of all births in the United States are the result of preterm labor,² and 8% are born in the late preterm period, defined as 34 to 36 weeks’ gestation.³ To reduce the risk of neonatal death and respiratory complications, both the American College of Obstetricians and Gynecologists and the National Institutes of Health recommend a course of corticosteroids between 24 and 34 weeks’ gestation for women at increased risk of preterm delivery.^2,4 Due to a lack of evidence from randomized controlled trials (RCTs) on the benefit of corticosteroids in late preterm labor, there have not been recommendations to extend this period.⁵ However, multiple studies have shown that babies born during the late preterm period have more neonatal complications than term newborns.^6-8

A retrospective chart review of more than 130,000 live births found newborns delivered between 34 and 36 weeks had higher rates of respiratory distress than those delivered at 39 weeks (ventilator use dropped from 3.3% at 34 weeks to 0.3% at 39 weeks and transient tachypnea decreased from 2.4% at 34 weeks to 0.4% at 39 weeks).⁶ Another retrospective review of more than 230,000 newborns, of which 19,000 were born in the late preterm period, revealed that more neonates born between 34 and 36 weeks’ gestation had respiratory distress syndrome than neonates delivered at 39 weeks (10.5% at 34 weeks, 6% at 35 weeks, 2.8% at 36 weeks vs 0.3% at 39 weeks; P<.001 for the trend).⁸

STUDY SUMMARY

Late preterm newborns breathe better with antenatal betamethasone

This randomized placebo-controlled trial examined the effectiveness of betamethasone in preventing neonatal respiratory complications for 2831 women at high probability of preterm delivery between 34 weeks and 36 weeks, 6 days of gestation. “High probability of preterm delivery” was defined as preterm labor with intact membranes and at least 3 cm dilation or 75% cervical effacement; spontaneous rupture of membranes; or anticipated preterm delivery for any other indication either through induction or cesarean section between 24 hours and 7 days after the planned randomization.

Patients were randomly assigned to receive either 2 intramuscular injections (12 mg each) of betamethasone or placebo, 24 hours apart. The 2 doses were successfully given in 60% of the betamethasone group and 59% of the placebo group. In 95% of the cases where the second dose was not given, it was because delivery occurred within 24 hours of the first dose.

The primary outcome was the need for respiratory support within 72 hours of birth, which was defined as one or more of the following: the use of continuous positive airway pressure (CPAP) or high-flow nasal cannula for at least 2 consecutive hours, supplemental oxygen for at least 4 continuous hours, extracorporeal membrane oxygenation (ECMO), or mechanical ventilation.

This study demonstrated clear benefit in neonatal respiratory outcomes when betamethasone vs placebo was used in the late preterm period.

The median time to delivery from enrollment was 31 to 33 hours, and 31.4% underwent cesarean delivery. In the intention-to-treat analysis, the primary outcome was significantly lower in the betamethasone group than in the placebo group (11.6% vs 14.4%; relative risk [RR]=0.80; 95% CI, 0.66-0.97; P=.02; number needed to treat [NNT]=35). Secondary outcomes (severe complications, representing a composite of the use of CPAP or high-flow nasal cannula for at least 12 continuous hours, supplemental oxygen for at least 24 continuous hours, ECMO, mechanical ventilation, stillbirth, or neonatal death within 72 hours after delivery) were also lower in the betamethasone group (8.1% vs 12.1%; RR=0.67; 95% CI, 0.53-0.84; P<.001; NNT=25). The betamethasone group also had a lower risk of transient tachypnea of the newborn (6.7% vs 9.9%; RR=0.68; 95% CI, 0.53-0.87; P=.002).

There were no significant differences in the occurrence of maternal chorioamnionitis (about 2%) or endometritis (about 1%) between the groups. Hypoglycemia in the newborn occurred more in the betamethasone group (24% vs 15%; RR=1.6; 95% CI, 1.37-1.87; P<.001; number needed to harm [NNH]=11). The betamethasone group had 2 neonatal deaths: one from septic shock and the other from a structural cardiac anomaly and arrhythmia.

WHAT’S NEW

Betamethasone makes a difference even in the late, late preterm period

This study demonstrated clear benefit in neonatal respiratory outcomes when betamethasone vs placebo was used in the late preterm period. The findings were similar to those from the Antenatal Steroids for Term Elective Caesarean Section Research Team.⁹ Their trial showed a reduction in respiratory complications in term neonates delivered via elective cesarean section to mothers who received antenatal betamethasone (NNT=37 to prevent admission to a special care nursery with respiratory distress). The findings were also consistent with those of a recent meta-analysis (including this trial) evaluating the occurrence of respiratory complications with the use of antenatal betamethasone in women expected to deliver in the late preterm period or with a planned cesarean delivery at ≥37 weeks’ gestation.¹⁰

CAVEATS

Neonates may develop hypoglycemia

The authors of the study reported an increased risk of hypoglycemia in the neonates receiving antenatal betamethasone. The long-term implications of this are unclear, however, given that there was a reduction in intermediate care nursery and neonatal intensive care unit stays that were 3 days or longer in the betamethasone group. Also, there was no difference in hospital length of stay between the 2 groups. In addition, it’s not clear if there are any long-term neonatal complications of betamethasone use in the late preterm period.

CHALLENGES TO IMPLEMENTATION

Challenges are negligible since betamethasone is readily available

There are minimal challenges to implementing this strategy, as betamethasone is routinely used for preterm labor and is readily available on labor and delivery units.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

THE CASE

A 22-year-old woman presented to the emergency department (ED) with a 24-hour history of nausea, vomiting, diarrhea, generalized abdominal pain, and mild headache. She denied shortness of breath, chest pain, or anxiety, and didn’t have a history of cardiac problems. The physical examination revealed tachycardia (heart rate, 135 beats/min) and a respiratory rate of 24 breaths per minute. The patient was diagnosed with dehydration and was given 3 liters of intravenous (IV) fluids. After fluid administration, her heart rate decreased to 94 beats/min and she was discharged home.

The patient returned to the ED later that same day with recurrent nausea, vomiting, and a mild fever. This time she reported a several week history of palpitations, heat intolerance, agitation, mild cognitive impairment, and difficulty sleeping. Her mother accompanied her to this visit and added that the patient had unintentionally lost 13 pounds over the past 2 weeks. The patient denied pain or enlargement in her neck, obstructive symptoms, hives, pruritus, or changes in vision. Reexamination revealed tachycardia (132 beats/min) with no murmurs, rubs, or gallops; increased respiratory rate (26 breaths/min); and diffuse thyromegaly without distinct nodules. The thyroid was nontender to palpation. The patient was also found to have a fine resting tremor, hyperactive deep tendon reflexes, and clonus in her lower extremities. Bibasilar crackles were noted on lung exam.

THE DIAGNOSIS

An electrocardiogram (EKG) revealed sinus tachycardia with some sinus arrhythmia. A chest radiograph revealed prominent pulmonary vasculature and the presence of Kerley B lines consistent with marked pulmonary edema. Laboratory testing revealed an elevated N-terminal pro b-type natriuretic peptide level of 2420 pg/mL (normal range: <100 pg/mL). Evaluation of thyroid function revealed overt hyperthyroidism with an elevated free thyroxine of 4.6 ng/dL (normal range: 0.8-1.8 ng/dL), a total triiodothyronine of 199 ng/dL (normal range: 60-181 ng/dL), and a suppressed thyroid-stimulating hormone level of <0.02 mcU/mL (normal range: 0.35-5 mcU/mL). A subsequent thyroid ultrasound showed a diffusely enlarged thyroid gland with a thickened isthmus, but no nodules.

The patient’s results were discussed with the on-call endocrinology provider at the time of her revisit to the ED. The patient was started on antithyroid medications (methimazole 20 mg/d) and a beta-blocker (atenolol 25 mg/d). Arrangements were made for an outpatient endocrine consultation within 3 days of her visit to the ED.

Upon evaluation in the outpatient endocrinology clinic, a thyrotropin receptor antibody test was positive, confirming Graves’ disease. The patient was given a diagnosis of thyrotoxicosis secondary to hyperthyroidism due to Graves’ disease. Her marked pulmonary edema was secondary to thyrotoxicosis and aggressive hydration with IV fluids.

DISCUSSION

Hyperthyroidism is a common metabolic disorder with prominent cardiovascular manifestations.¹ Classically, patients with hyperthyroidism develop irritability, heat intolerance, emotional lability, muscle weakness, menstrual abnormalities, and weight loss (despite an increased appetite). Cardiovascular manifestations include palpitations in up to 85% of patients, and dyspnea on exertion and fatigue in approximately 50% of patients.² Hyperthyroidism has also been shown to produce changes in cardiac contractility, myocardial oxygen consumption, cardiac output, blood pressure, and systemic vascular resistance.^3,4 Hyperthyroidism may complicate preexisting cardiac disease or may cause cardiac complications in individuals without structural abnormalities. (Our patient had no known structural abnormalities.)

Hyperthyroidism has been shown to produce changes in cardiac contractility, myocardial oxygen consumption, cardiac output, blood pressure, and systemic vascular resistance.In a small subset of patients with severe hyperthyroidism and exaggerated sinus tachycardia or atrial fibrillation, rate-related left ventricular dysfunction may cause heart failure.⁵ The assessment of thyrotoxic manifestations, especially potential cardiovascular complications, is essential to formulating an appropriate treatment plan.⁶ Cardiac evaluation may require an echocardiogram, EKG, Holter monitor, or myocardial perfusion studies.

Beta-blockers, diuretics among treatment options

Treatment with beta-blockers to reduce heart rate should be first-line therapy.⁷ In patients with overt heart failure involving pulmonary congestion, the use of diuretics may be appropriate.⁸

Our patient continued to take the medications prescribed during her ED visit: methimazole 20 mg/d and atenolol 25 mg/d for her Graves’ disease. A chest radiograph one month later revealed resolution of her pulmonary edema.

THE TAKEAWAY

The cardiovascular manifestations of hyperthyroidism remain some of the most common signs and symptoms of thyroid disease. Pulmonary edema and congestive heart failure, however, are uncommon. Physicians need to be aware of this rare—but important—clinical presentation of a common condition.

THE CASE

A 22-year-old woman presented to the emergency department (ED) with a 24-hour history of nausea, vomiting, diarrhea, generalized abdominal pain, and mild headache. She denied shortness of breath, chest pain, or anxiety, and didn’t have a history of cardiac problems. The physical examination revealed tachycardia (heart rate, 135 beats/min) and a respiratory rate of 24 breaths per minute. The patient was diagnosed with dehydration and was given 3 liters of intravenous (IV) fluids. After fluid administration, her heart rate decreased to 94 beats/min and she was discharged home.

The patient returned to the ED later that same day with recurrent nausea, vomiting, and a mild fever. This time she reported a several week history of palpitations, heat intolerance, agitation, mild cognitive impairment, and difficulty sleeping. Her mother accompanied her to this visit and added that the patient had unintentionally lost 13 pounds over the past 2 weeks. The patient denied pain or enlargement in her neck, obstructive symptoms, hives, pruritus, or changes in vision. Reexamination revealed tachycardia (132 beats/min) with no murmurs, rubs, or gallops; increased respiratory rate (26 breaths/min); and diffuse thyromegaly without distinct nodules. The thyroid was nontender to palpation. The patient was also found to have a fine resting tremor, hyperactive deep tendon reflexes, and clonus in her lower extremities. Bibasilar crackles were noted on lung exam.

THE DIAGNOSIS

An electrocardiogram (EKG) revealed sinus tachycardia with some sinus arrhythmia. A chest radiograph revealed prominent pulmonary vasculature and the presence of Kerley B lines consistent with marked pulmonary edema. Laboratory testing revealed an elevated N-terminal pro b-type natriuretic peptide level of 2420 pg/mL (normal range: <100 pg/mL). Evaluation of thyroid function revealed overt hyperthyroidism with an elevated free thyroxine of 4.6 ng/dL (normal range: 0.8-1.8 ng/dL), a total triiodothyronine of 199 ng/dL (normal range: 60-181 ng/dL), and a suppressed thyroid-stimulating hormone level of <0.02 mcU/mL (normal range: 0.35-5 mcU/mL). A subsequent thyroid ultrasound showed a diffusely enlarged thyroid gland with a thickened isthmus, but no nodules.

The patient’s results were discussed with the on-call endocrinology provider at the time of her revisit to the ED. The patient was started on antithyroid medications (methimazole 20 mg/d) and a beta-blocker (atenolol 25 mg/d). Arrangements were made for an outpatient endocrine consultation within 3 days of her visit to the ED.

Upon evaluation in the outpatient endocrinology clinic, a thyrotropin receptor antibody test was positive, confirming Graves’ disease. The patient was given a diagnosis of thyrotoxicosis secondary to hyperthyroidism due to Graves’ disease. Her marked pulmonary edema was secondary to thyrotoxicosis and aggressive hydration with IV fluids.

DISCUSSION

Hyperthyroidism is a common metabolic disorder with prominent cardiovascular manifestations.¹ Classically, patients with hyperthyroidism develop irritability, heat intolerance, emotional lability, muscle weakness, menstrual abnormalities, and weight loss (despite an increased appetite). Cardiovascular manifestations include palpitations in up to 85% of patients, and dyspnea on exertion and fatigue in approximately 50% of patients.² Hyperthyroidism has also been shown to produce changes in cardiac contractility, myocardial oxygen consumption, cardiac output, blood pressure, and systemic vascular resistance.^3,4 Hyperthyroidism may complicate preexisting cardiac disease or may cause cardiac complications in individuals without structural abnormalities. (Our patient had no known structural abnormalities.)

Hyperthyroidism has been shown to produce changes in cardiac contractility, myocardial oxygen consumption, cardiac output, blood pressure, and systemic vascular resistance.In a small subset of patients with severe hyperthyroidism and exaggerated sinus tachycardia or atrial fibrillation, rate-related left ventricular dysfunction may cause heart failure.⁵ The assessment of thyrotoxic manifestations, especially potential cardiovascular complications, is essential to formulating an appropriate treatment plan.⁶ Cardiac evaluation may require an echocardiogram, EKG, Holter monitor, or myocardial perfusion studies.

Beta-blockers, diuretics among treatment options

Treatment with beta-blockers to reduce heart rate should be first-line therapy.⁷ In patients with overt heart failure involving pulmonary congestion, the use of diuretics may be appropriate.⁸

Our patient continued to take the medications prescribed during her ED visit: methimazole 20 mg/d and atenolol 25 mg/d for her Graves’ disease. A chest radiograph one month later revealed resolution of her pulmonary edema.

THE TAKEAWAY

The cardiovascular manifestations of hyperthyroidism remain some of the most common signs and symptoms of thyroid disease. Pulmonary edema and congestive heart failure, however, are uncommon. Physicians need to be aware of this rare—but important—clinical presentation of a common condition.

THE CASE

A 22-year-old woman presented to the emergency department (ED) with a 24-hour history of nausea, vomiting, diarrhea, generalized abdominal pain, and mild headache. She denied shortness of breath, chest pain, or anxiety, and didn’t have a history of cardiac problems. The physical examination revealed tachycardia (heart rate, 135 beats/min) and a respiratory rate of 24 breaths per minute. The patient was diagnosed with dehydration and was given 3 liters of intravenous (IV) fluids. After fluid administration, her heart rate decreased to 94 beats/min and she was discharged home.

The patient returned to the ED later that same day with recurrent nausea, vomiting, and a mild fever. This time she reported a several week history of palpitations, heat intolerance, agitation, mild cognitive impairment, and difficulty sleeping. Her mother accompanied her to this visit and added that the patient had unintentionally lost 13 pounds over the past 2 weeks. The patient denied pain or enlargement in her neck, obstructive symptoms, hives, pruritus, or changes in vision. Reexamination revealed tachycardia (132 beats/min) with no murmurs, rubs, or gallops; increased respiratory rate (26 breaths/min); and diffuse thyromegaly without distinct nodules. The thyroid was nontender to palpation. The patient was also found to have a fine resting tremor, hyperactive deep tendon reflexes, and clonus in her lower extremities. Bibasilar crackles were noted on lung exam.

THE DIAGNOSIS

An electrocardiogram (EKG) revealed sinus tachycardia with some sinus arrhythmia. A chest radiograph revealed prominent pulmonary vasculature and the presence of Kerley B lines consistent with marked pulmonary edema. Laboratory testing revealed an elevated N-terminal pro b-type natriuretic peptide level of 2420 pg/mL (normal range: <100 pg/mL). Evaluation of thyroid function revealed overt hyperthyroidism with an elevated free thyroxine of 4.6 ng/dL (normal range: 0.8-1.8 ng/dL), a total triiodothyronine of 199 ng/dL (normal range: 60-181 ng/dL), and a suppressed thyroid-stimulating hormone level of <0.02 mcU/mL (normal range: 0.35-5 mcU/mL). A subsequent thyroid ultrasound showed a diffusely enlarged thyroid gland with a thickened isthmus, but no nodules.

The patient’s results were discussed with the on-call endocrinology provider at the time of her revisit to the ED. The patient was started on antithyroid medications (methimazole 20 mg/d) and a beta-blocker (atenolol 25 mg/d). Arrangements were made for an outpatient endocrine consultation within 3 days of her visit to the ED.

Upon evaluation in the outpatient endocrinology clinic, a thyrotropin receptor antibody test was positive, confirming Graves’ disease. The patient was given a diagnosis of thyrotoxicosis secondary to hyperthyroidism due to Graves’ disease. Her marked pulmonary edema was secondary to thyrotoxicosis and aggressive hydration with IV fluids.

DISCUSSION

Hyperthyroidism is a common metabolic disorder with prominent cardiovascular manifestations.¹ Classically, patients with hyperthyroidism develop irritability, heat intolerance, emotional lability, muscle weakness, menstrual abnormalities, and weight loss (despite an increased appetite). Cardiovascular manifestations include palpitations in up to 85% of patients, and dyspnea on exertion and fatigue in approximately 50% of patients.² Hyperthyroidism has also been shown to produce changes in cardiac contractility, myocardial oxygen consumption, cardiac output, blood pressure, and systemic vascular resistance.^3,4 Hyperthyroidism may complicate preexisting cardiac disease or may cause cardiac complications in individuals without structural abnormalities. (Our patient had no known structural abnormalities.)

Hyperthyroidism has been shown to produce changes in cardiac contractility, myocardial oxygen consumption, cardiac output, blood pressure, and systemic vascular resistance.In a small subset of patients with severe hyperthyroidism and exaggerated sinus tachycardia or atrial fibrillation, rate-related left ventricular dysfunction may cause heart failure.⁵ The assessment of thyrotoxic manifestations, especially potential cardiovascular complications, is essential to formulating an appropriate treatment plan.⁶ Cardiac evaluation may require an echocardiogram, EKG, Holter monitor, or myocardial perfusion studies.

Beta-blockers, diuretics among treatment options

Treatment with beta-blockers to reduce heart rate should be first-line therapy.⁷ In patients with overt heart failure involving pulmonary congestion, the use of diuretics may be appropriate.⁸

Our patient continued to take the medications prescribed during her ED visit: methimazole 20 mg/d and atenolol 25 mg/d for her Graves’ disease. A chest radiograph one month later revealed resolution of her pulmonary edema.

THE TAKEAWAY

The cardiovascular manifestations of hyperthyroidism remain some of the most common signs and symptoms of thyroid disease. Pulmonary edema and congestive heart failure, however, are uncommon. Physicians need to be aware of this rare—but important—clinical presentation of a common condition.

THE CASE

A 39-year-old man who worked in construction presented to our clinic with complaints of muscle cramps and muscle pain that had been bothering him for several months. The cramps and pain started in both of his arms and subsequently became diffuse and generalized. He also reported an unintentional 15-pound weight loss.

His exam at that time was unremarkable. He was diagnosed with dehydration and cramping due to overexertion at work. A basic metabolic panel, hemogram, lipid panel, and thyroid stimulating hormone level were ordered. The patient’s triglyceride level, which was 227 mg/dL, was the only significant result (normal level: <150 mg/dL).

The patient’s symptoms continued to worsen until he returned to the clinic 6 months later, again complaining of muscle cramps and pain throughout his body. At that second visit, he also reported profound overall weakness and the development of diffuse muscle twitching, which his wife had observed while he was sleeping. As a result of these worrisome symptoms, he had become anxious and depressed.

A review of his medical record revealed a weight loss of about 20 pounds over the previous year. On exam, he had diffuse fasciculations in all the major muscle groups, including his tongue. The patient’s strength was 4/5 in all muscle groups. His deep tendon reflexes were 3+. He had a negative Babinski reflex (ie, he had downward facing toes with plantar stimulation), and cranial nerves II to XII were all intact. His rapid alternating movements and gait were slow.

THE DIAGNOSIS

Based on the exam, the primary diagnostic consideration for the patient was amyotrophic lateral sclerosis (ALS). Lab tests were ordered and revealed normal calcium and electrolyte levels, a normal erythrocyte sedimentation rate, a normal C-reactive protein level, and a negative test for acetylcholine receptor antibodies. However, the patient had an elevated creatine kinase level of 664 U/L (normal: 30-200 U/L). The patient was sent to a neuromuscular specialist, who identified signs of upper and lower motor neuron disease in all 4 of the patient’s extremities (he had foot drop that had not been present previously) and a very brisk jaw jerk. Along with the tongue fasciculations, the results of the specialist’s physical exam suggested ALS. Four-limb electromyography (EMG) showed widespread fasciculations and some large motor unit potentials and recruitment abnormalities, which were also consistent with ALS. It appeared that the patient’s weight loss was due to both muscle atrophy and the amount of calories burned from his constant twitching.

Extensive testing was done to rule out other potential causes of the patient’s symptoms, including magnetic resonance imaging (MRI) of the spine and brain (which was normal). In addition, the patient’s aldolase level and antineutrophil cytoplasmic antibodies were normal. The patient tested negative for human immunodeficiency virus and antibodies to double-stranded DNA. After serial neurologic exams, the final diagnosis of ALS was made.

DISCUSSION

ALS, also known as Lou Gehrig’s disease, is a degenerative motor neuron disease.^1-3 The incidence in North America is 1.5 to 2.7 per 100,000 per year, and the prevalence is 2.7 to 7.4 per 100,000.⁴ The incidence of ALS increases with each decade of life, especially after age 40, and peaks at 74 years of age.⁴ The male to female ratio is 1:1.5-2.⁴ ALS affects upper and lower motor neurons and is progressive; however, the rate of progression and phenotype vary greatly between individuals.² Most patients with ALS die within 2 to 5 years of onset.⁵

There is no specific test for ALS; the diagnosis is made clinically based on the revised El Escorial World Federation of Neurology criteria, also known as the Airlie House criteria.^2,6,7 These criteria include evidence of lower motor neuron degeneration by clinical, electrophysiologic, or neuropathologic exam; evidence of upper motor neuron disease by clinical exam; progressive spread of symptoms or signs within a region or to other regions (by history or exam); and the absence of electrophysiologic, neuroimaging, or pathologic evidence of other disease processes that could explain the symptoms. If patients have evidence of upper and lower motor neuron disease, they should be reevaluated in 4 weeks to see if symptoms are improving or progressing.

Like our patient, many patients will have an elevated creatine kinase level (some with levels as high as 1000 U/L), and calcium may also be elevated because, rarely, ALS is associated with primary hyperparathyroidism.⁸ Electrophysiologic studies can be helpful in identifying active denervation of lower motor neurons.^4,6,7

The differential diagnosis for ALS includes myasthenia gravis, inclusion-body myositis, multifocal motor neuropathy, benign fasciculations, hereditary spastic paraplegia, primary lateral sclerosis, post-polio progressive muscle atrophy, cervical spondylosis, and multiple sclerosis. A negative acetylcholine receptor antibody test will rule out myasthenia gravis, imaging of the spine can rule out cervical spondylosis, and electrophysiologic testing helps eliminate the other conditions (TABLE 1⁴).

Treatment in specialty clinics can prolong survival

The mainstays of treatment are symptom management, multidisciplinary care (by physicians, physical/occupational/speech therapists, nutritionists, psychologists, psychotherapists, and genetic counselors), palliative care, and counseling about end-of-life issues for patients and family.^1,5 Utilization of an ALS specialty clinic can provide access to all of these services and should be considered, as there is evidence that treatment in such clinics can prolong survival.⁵ The location of ALS specialty clinics can be found on the ALS Association’s Web site at http://www.alsa.org/community/.

Despite treatment, however, ALS is a progressive disease. The prognosis is poor, with a median survival of 2 to 5 years after diagnosis.⁹

The El Escorial World Federation of Neurology criteria for the diagnosis of ALS address how to treat the most common symptoms of ALS that occur as the disease progresses. These symptoms include dyspnea, muscle spasms, spasticity, sialorrhea, and pseudobulbar affect (TABLE 2^1,5).

Our patient was started on baclofen 10 mg 3 times per day (titrated up as needed) for muscle spasms and cramps, which resulted in some improvement of his cramps, but no improvement in the spasms. He was also started on sertraline 50 mg for anxiety and depression. His overall weakness continued to progress, and we recommended that the patient get ankle-foot orthosis braces to help with the mobility impairment caused by foot drop.

We then referred him to an ALS specialty clinic recommended by the neuromuscular specialist. The patient is now enrolled in a clinical trial designed to test a cerebrospinal fluid marker for diagnosis and for a new drug aimed at symptom management.

THE TAKEAWAY

Muscle cramps and pain are early signs of ALS. Although ALS is uncommon, patients who present with muscle cramps and muscle pain should have a creatine kinase test ordered (which, if elevated, should prompt further investigation into ALS as the possible cause). Patients should also undergo a neurologic examination to seek evidence of upper and lower motor neuron disease. They should then be reevaluated in 4 weeks to see if symptoms are improving or progressing. If no improvement is seen and symptoms are progressive, a work-up for ALS should be considered.

The mainstay of treatment for patients with ALS is multidisciplinary symptom management and palliative care. Utilization of an ALS specialty clinic should also be recommended, as it can improve survival.⁵

THE CASE

A 39-year-old man who worked in construction presented to our clinic with complaints of muscle cramps and muscle pain that had been bothering him for several months. The cramps and pain started in both of his arms and subsequently became diffuse and generalized. He also reported an unintentional 15-pound weight loss.

His exam at that time was unremarkable. He was diagnosed with dehydration and cramping due to overexertion at work. A basic metabolic panel, hemogram, lipid panel, and thyroid stimulating hormone level were ordered. The patient’s triglyceride level, which was 227 mg/dL, was the only significant result (normal level: <150 mg/dL).

The patient’s symptoms continued to worsen until he returned to the clinic 6 months later, again complaining of muscle cramps and pain throughout his body. At that second visit, he also reported profound overall weakness and the development of diffuse muscle twitching, which his wife had observed while he was sleeping. As a result of these worrisome symptoms, he had become anxious and depressed.

A review of his medical record revealed a weight loss of about 20 pounds over the previous year. On exam, he had diffuse fasciculations in all the major muscle groups, including his tongue. The patient’s strength was 4/5 in all muscle groups. His deep tendon reflexes were 3+. He had a negative Babinski reflex (ie, he had downward facing toes with plantar stimulation), and cranial nerves II to XII were all intact. His rapid alternating movements and gait were slow.

THE DIAGNOSIS

Based on the exam, the primary diagnostic consideration for the patient was amyotrophic lateral sclerosis (ALS). Lab tests were ordered and revealed normal calcium and electrolyte levels, a normal erythrocyte sedimentation rate, a normal C-reactive protein level, and a negative test for acetylcholine receptor antibodies. However, the patient had an elevated creatine kinase level of 664 U/L (normal: 30-200 U/L). The patient was sent to a neuromuscular specialist, who identified signs of upper and lower motor neuron disease in all 4 of the patient’s extremities (he had foot drop that had not been present previously) and a very brisk jaw jerk. Along with the tongue fasciculations, the results of the specialist’s physical exam suggested ALS. Four-limb electromyography (EMG) showed widespread fasciculations and some large motor unit potentials and recruitment abnormalities, which were also consistent with ALS. It appeared that the patient’s weight loss was due to both muscle atrophy and the amount of calories burned from his constant twitching.

Extensive testing was done to rule out other potential causes of the patient’s symptoms, including magnetic resonance imaging (MRI) of the spine and brain (which was normal). In addition, the patient’s aldolase level and antineutrophil cytoplasmic antibodies were normal. The patient tested negative for human immunodeficiency virus and antibodies to double-stranded DNA. After serial neurologic exams, the final diagnosis of ALS was made.

DISCUSSION

ALS, also known as Lou Gehrig’s disease, is a degenerative motor neuron disease.^1-3 The incidence in North America is 1.5 to 2.7 per 100,000 per year, and the prevalence is 2.7 to 7.4 per 100,000.⁴ The incidence of ALS increases with each decade of life, especially after age 40, and peaks at 74 years of age.⁴ The male to female ratio is 1:1.5-2.⁴ ALS affects upper and lower motor neurons and is progressive; however, the rate of progression and phenotype vary greatly between individuals.² Most patients with ALS die within 2 to 5 years of onset.⁵

There is no specific test for ALS; the diagnosis is made clinically based on the revised El Escorial World Federation of Neurology criteria, also known as the Airlie House criteria.^2,6,7 These criteria include evidence of lower motor neuron degeneration by clinical, electrophysiologic, or neuropathologic exam; evidence of upper motor neuron disease by clinical exam; progressive spread of symptoms or signs within a region or to other regions (by history or exam); and the absence of electrophysiologic, neuroimaging, or pathologic evidence of other disease processes that could explain the symptoms. If patients have evidence of upper and lower motor neuron disease, they should be reevaluated in 4 weeks to see if symptoms are improving or progressing.

Like our patient, many patients will have an elevated creatine kinase level (some with levels as high as 1000 U/L), and calcium may also be elevated because, rarely, ALS is associated with primary hyperparathyroidism.⁸ Electrophysiologic studies can be helpful in identifying active denervation of lower motor neurons.^4,6,7

The differential diagnosis for ALS includes myasthenia gravis, inclusion-body myositis, multifocal motor neuropathy, benign fasciculations, hereditary spastic paraplegia, primary lateral sclerosis, post-polio progressive muscle atrophy, cervical spondylosis, and multiple sclerosis. A negative acetylcholine receptor antibody test will rule out myasthenia gravis, imaging of the spine can rule out cervical spondylosis, and electrophysiologic testing helps eliminate the other conditions (TABLE 1⁴).

Treatment in specialty clinics can prolong survival

The mainstays of treatment are symptom management, multidisciplinary care (by physicians, physical/occupational/speech therapists, nutritionists, psychologists, psychotherapists, and genetic counselors), palliative care, and counseling about end-of-life issues for patients and family.^1,5 Utilization of an ALS specialty clinic can provide access to all of these services and should be considered, as there is evidence that treatment in such clinics can prolong survival.⁵ The location of ALS specialty clinics can be found on the ALS Association’s Web site at http://www.alsa.org/community/.

Despite treatment, however, ALS is a progressive disease. The prognosis is poor, with a median survival of 2 to 5 years after diagnosis.⁹

The El Escorial World Federation of Neurology criteria for the diagnosis of ALS address how to treat the most common symptoms of ALS that occur as the disease progresses. These symptoms include dyspnea, muscle spasms, spasticity, sialorrhea, and pseudobulbar affect (TABLE 2^1,5).

Our patient was started on baclofen 10 mg 3 times per day (titrated up as needed) for muscle spasms and cramps, which resulted in some improvement of his cramps, but no improvement in the spasms. He was also started on sertraline 50 mg for anxiety and depression. His overall weakness continued to progress, and we recommended that the patient get ankle-foot orthosis braces to help with the mobility impairment caused by foot drop.

We then referred him to an ALS specialty clinic recommended by the neuromuscular specialist. The patient is now enrolled in a clinical trial designed to test a cerebrospinal fluid marker for diagnosis and for a new drug aimed at symptom management.

THE TAKEAWAY

Muscle cramps and pain are early signs of ALS. Although ALS is uncommon, patients who present with muscle cramps and muscle pain should have a creatine kinase test ordered (which, if elevated, should prompt further investigation into ALS as the possible cause). Patients should also undergo a neurologic examination to seek evidence of upper and lower motor neuron disease. They should then be reevaluated in 4 weeks to see if symptoms are improving or progressing. If no improvement is seen and symptoms are progressive, a work-up for ALS should be considered.

The mainstay of treatment for patients with ALS is multidisciplinary symptom management and palliative care. Utilization of an ALS specialty clinic should also be recommended, as it can improve survival.⁵

THE CASE

A 39-year-old man who worked in construction presented to our clinic with complaints of muscle cramps and muscle pain that had been bothering him for several months. The cramps and pain started in both of his arms and subsequently became diffuse and generalized. He also reported an unintentional 15-pound weight loss.

His exam at that time was unremarkable. He was diagnosed with dehydration and cramping due to overexertion at work. A basic metabolic panel, hemogram, lipid panel, and thyroid stimulating hormone level were ordered. The patient’s triglyceride level, which was 227 mg/dL, was the only significant result (normal level: <150 mg/dL).

The patient’s symptoms continued to worsen until he returned to the clinic 6 months later, again complaining of muscle cramps and pain throughout his body. At that second visit, he also reported profound overall weakness and the development of diffuse muscle twitching, which his wife had observed while he was sleeping. As a result of these worrisome symptoms, he had become anxious and depressed.

A review of his medical record revealed a weight loss of about 20 pounds over the previous year. On exam, he had diffuse fasciculations in all the major muscle groups, including his tongue. The patient’s strength was 4/5 in all muscle groups. His deep tendon reflexes were 3+. He had a negative Babinski reflex (ie, he had downward facing toes with plantar stimulation), and cranial nerves II to XII were all intact. His rapid alternating movements and gait were slow.

THE DIAGNOSIS

Based on the exam, the primary diagnostic consideration for the patient was amyotrophic lateral sclerosis (ALS). Lab tests were ordered and revealed normal calcium and electrolyte levels, a normal erythrocyte sedimentation rate, a normal C-reactive protein level, and a negative test for acetylcholine receptor antibodies. However, the patient had an elevated creatine kinase level of 664 U/L (normal: 30-200 U/L). The patient was sent to a neuromuscular specialist, who identified signs of upper and lower motor neuron disease in all 4 of the patient’s extremities (he had foot drop that had not been present previously) and a very brisk jaw jerk. Along with the tongue fasciculations, the results of the specialist’s physical exam suggested ALS. Four-limb electromyography (EMG) showed widespread fasciculations and some large motor unit potentials and recruitment abnormalities, which were also consistent with ALS. It appeared that the patient’s weight loss was due to both muscle atrophy and the amount of calories burned from his constant twitching.

Extensive testing was done to rule out other potential causes of the patient’s symptoms, including magnetic resonance imaging (MRI) of the spine and brain (which was normal). In addition, the patient’s aldolase level and antineutrophil cytoplasmic antibodies were normal. The patient tested negative for human immunodeficiency virus and antibodies to double-stranded DNA. After serial neurologic exams, the final diagnosis of ALS was made.

DISCUSSION

ALS, also known as Lou Gehrig’s disease, is a degenerative motor neuron disease.^1-3 The incidence in North America is 1.5 to 2.7 per 100,000 per year, and the prevalence is 2.7 to 7.4 per 100,000.⁴ The incidence of ALS increases with each decade of life, especially after age 40, and peaks at 74 years of age.⁴ The male to female ratio is 1:1.5-2.⁴ ALS affects upper and lower motor neurons and is progressive; however, the rate of progression and phenotype vary greatly between individuals.² Most patients with ALS die within 2 to 5 years of onset.⁵

There is no specific test for ALS; the diagnosis is made clinically based on the revised El Escorial World Federation of Neurology criteria, also known as the Airlie House criteria.^2,6,7 These criteria include evidence of lower motor neuron degeneration by clinical, electrophysiologic, or neuropathologic exam; evidence of upper motor neuron disease by clinical exam; progressive spread of symptoms or signs within a region or to other regions (by history or exam); and the absence of electrophysiologic, neuroimaging, or pathologic evidence of other disease processes that could explain the symptoms. If patients have evidence of upper and lower motor neuron disease, they should be reevaluated in 4 weeks to see if symptoms are improving or progressing.

Like our patient, many patients will have an elevated creatine kinase level (some with levels as high as 1000 U/L), and calcium may also be elevated because, rarely, ALS is associated with primary hyperparathyroidism.⁸ Electrophysiologic studies can be helpful in identifying active denervation of lower motor neurons.^4,6,7

The differential diagnosis for ALS includes myasthenia gravis, inclusion-body myositis, multifocal motor neuropathy, benign fasciculations, hereditary spastic paraplegia, primary lateral sclerosis, post-polio progressive muscle atrophy, cervical spondylosis, and multiple sclerosis. A negative acetylcholine receptor antibody test will rule out myasthenia gravis, imaging of the spine can rule out cervical spondylosis, and electrophysiologic testing helps eliminate the other conditions (TABLE 1⁴).

Treatment in specialty clinics can prolong survival

The mainstays of treatment are symptom management, multidisciplinary care (by physicians, physical/occupational/speech therapists, nutritionists, psychologists, psychotherapists, and genetic counselors), palliative care, and counseling about end-of-life issues for patients and family.^1,5 Utilization of an ALS specialty clinic can provide access to all of these services and should be considered, as there is evidence that treatment in such clinics can prolong survival.⁵ The location of ALS specialty clinics can be found on the ALS Association’s Web site at http://www.alsa.org/community/.

Despite treatment, however, ALS is a progressive disease. The prognosis is poor, with a median survival of 2 to 5 years after diagnosis.⁹

The El Escorial World Federation of Neurology criteria for the diagnosis of ALS address how to treat the most common symptoms of ALS that occur as the disease progresses. These symptoms include dyspnea, muscle spasms, spasticity, sialorrhea, and pseudobulbar affect (TABLE 2^1,5).

Our patient was started on baclofen 10 mg 3 times per day (titrated up as needed) for muscle spasms and cramps, which resulted in some improvement of his cramps, but no improvement in the spasms. He was also started on sertraline 50 mg for anxiety and depression. His overall weakness continued to progress, and we recommended that the patient get ankle-foot orthosis braces to help with the mobility impairment caused by foot drop.

We then referred him to an ALS specialty clinic recommended by the neuromuscular specialist. The patient is now enrolled in a clinical trial designed to test a cerebrospinal fluid marker for diagnosis and for a new drug aimed at symptom management.

THE TAKEAWAY

Muscle cramps and pain are early signs of ALS. Although ALS is uncommon, patients who present with muscle cramps and muscle pain should have a creatine kinase test ordered (which, if elevated, should prompt further investigation into ALS as the possible cause). Patients should also undergo a neurologic examination to seek evidence of upper and lower motor neuron disease. They should then be reevaluated in 4 weeks to see if symptoms are improving or progressing. If no improvement is seen and symptoms are progressive, a work-up for ALS should be considered.

The mainstay of treatment for patients with ALS is multidisciplinary symptom management and palliative care. Utilization of an ALS specialty clinic should also be recommended, as it can improve survival.⁵

A 62-year-old man with end-stage renal disease presented to our dermatology clinic with 2-month-old ulcerations on his distal left ring finger. He was on hemodialysis and had a radiocephalic arteriovenous fistula (AVF) on his left arm. He had been empirically treated elsewhere with oral trimethoprim-sulfamethoxazole for a presumed bacterial infection, without improvement. He was then treated for contact dermatitis with topical clobetasol, which led to ulcer expansion and worsening pain.

At our clinic, the patient reported intermittent pain in his finger and paresthesias during activity and dialysis, but no tenderness of the ulcers. He had atrophy of the intrinsic left hand muscles (his non-dominant hand) with associated weakness. Three weeks earlier, he’d received a blood transfusion for anemia. Afterward, the pain in his hand improved and the ulcers decreased in size.

On exam, the AVF had a palpable thrill over the left forearm. The radial pulses were palpable bilaterally (2+) and the left ulnar artery was palpable, but diminished (1+). The patient’s left hand was cooler than the right (with a slight cyanotic hue and visible intrinsic muscle atrophy) and had decreased sensation to pain and temperature. Four ulcers with dry yellow eschar were located over the dorsal interphalangeal joints (FIGURES 1A AND 1B). They were essentially non-tender, but there was tenderness in the adjacent intact skin. There was violaceous blue edematous congestion noted on the fourth finger, and the distal phalange was constricted, giving it a “pseudoainhum” appearance.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Dialysis access steal syndrome

We suspected dialysis access steal syndrome (also known as AVF steal syndrome), so a duplex ultrasound was performed. The ultrasound was inconclusive. (We couldn’t confirm a limitation in blood flow, nor delineate anatomy.) So, we referred the patient for a thoracic and upper extremity angiogram.

The angiogram demonstrated multifocal, moderate to severe, areas of stenosis at the distal left brachial artery. The radial artery was patent at the level of the wrist, but showed diffuse narrowing beyond the level of the arteriovenous (AV) anastomosis. There was only a faint palmar arch identified on the radial aspect of the hand with digital branches feeding the radial portion of the hand. In contrast, the ulnar artery was not seen within the mid- and distal forearm (FIGURE 2). Palmar branches to the ulnar half of the hand were not identified. The fistula itself didn’t show any stenosis.

Based on these findings, our suspicions of dialysis access steal syndrome were confirmed.

Dialysis access steal syndrome is caused by a significant decrease or reversal of blood flow in the arterial segment distal to the AVF or graft, which is induced by the low resistance of the fistula outflow. Patients with adequate collateral vasculature are able to compensate for the steal effect; however, patients with end-stage renal disease typically have preexisting vascular disease that increases the risk for vascular steal and, ultimately, demand ischemia after placement of an AVF.¹ Interestingly, a steal effect occurs in 73% of patients after AVF construction, yet it is estimated that only 10% of patients demonstrating a steal phenomenon become symptomatic.²

In our patient’s case, the vaso-occlusive properties of topical steroids explain why the superpotent steroid (clobetasol) he was prescribed increased his pain and worsened the underlying problem.

A broad differential; a useful exam maneuver

The differential diagnosis of ulcers includes infection (mainly from bacterial or mycobacterial sources), trauma facilitated by neuropathy (neuropathic ulceration), vasculitis, and ischemia. When the history and physical exam suggest ischemic ulceration, then thromboembolism, thoracic outlet syndrome, vasculitis, atherosclerosis, and steal syndrome become more likely causes.

Signs and symptoms of ischemic steal syndrome are initially subtle and include extremity coolness, neurosensory changes, intrinsic muscle weakness, ulceration, and ultimately, gangrene of the affected extremity.^3,4 A cold, numb, and/or painful hand during dialysis is another clue.³ Factors that increase the likelihood of the syndrome include age >60 years, female sex, and the presence of diabetes or peripheral artery disease.^2,3,5,6

The confirmatory diagnosis of steal syndrome is made via a fistulogram (angiography) with and without manual compression.

One physical exam maneuver that can help make the diagnosis of steal syndrome is manual occlusion of the AVF. If palpable distal pulses disappear when the AVF is patent and reappear when the fistula is occluded with downward pressure, then AVF steal syndrome is likely.⁴ Pain at rest, sensory loss, loss of pulse, and digital gangrene are emergency symptoms that warrant immediate surgical evaluation.³

Tests will confirm suspicions. Doppler ultrasound can be used to assess changes in the blood flow rate of the affected vessels when the AVF is patent vs when it is occluded. Similarly, pulse oximetry can be used with and without AVF occlusion to compare changes in oxygen saturation. The confirmatory diagnosis, however, is made via a fistulogram (angiography) with and without manual compression.⁶ Images taken after dye injection into the AVF show dramatic improvement of distal blood flow with AVF compression.

Treatment requires surgery

Severe steal-related ischemic manifestations that threaten the function and viability of digits require surgical treatment that is primarily directed toward improving distal blood flow and secondarily toward preserving hemodialysis access. Several surgical treatments are commonly used, including access ligation, banding, elongation, distal arterial ligation, and distal revascularization and interval ligation.^2-5,7

Our patient. Distal revascularization was attempted, but unfortunately, the patient’s gangrene was progressive (FIGURE 3) and surgical amputation of the left fourth finger was performed at the metacarpal’s proximal metaphyseal flare. The patient was transitioned to peritoneal dialysis to avoid further ischemia.

CORRESPONDENCE
Sahand Rahnama-Moghadam, MD, Department of Dermatology, Indiana University, 545 Barnhill Drive, Indianapolis, IN 46202; [email protected].

A 62-year-old man with end-stage renal disease presented to our dermatology clinic with 2-month-old ulcerations on his distal left ring finger. He was on hemodialysis and had a radiocephalic arteriovenous fistula (AVF) on his left arm. He had been empirically treated elsewhere with oral trimethoprim-sulfamethoxazole for a presumed bacterial infection, without improvement. He was then treated for contact dermatitis with topical clobetasol, which led to ulcer expansion and worsening pain.

At our clinic, the patient reported intermittent pain in his finger and paresthesias during activity and dialysis, but no tenderness of the ulcers. He had atrophy of the intrinsic left hand muscles (his non-dominant hand) with associated weakness. Three weeks earlier, he’d received a blood transfusion for anemia. Afterward, the pain in his hand improved and the ulcers decreased in size.

On exam, the AVF had a palpable thrill over the left forearm. The radial pulses were palpable bilaterally (2+) and the left ulnar artery was palpable, but diminished (1+). The patient’s left hand was cooler than the right (with a slight cyanotic hue and visible intrinsic muscle atrophy) and had decreased sensation to pain and temperature. Four ulcers with dry yellow eschar were located over the dorsal interphalangeal joints (FIGURES 1A AND 1B). They were essentially non-tender, but there was tenderness in the adjacent intact skin. There was violaceous blue edematous congestion noted on the fourth finger, and the distal phalange was constricted, giving it a “pseudoainhum” appearance.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Dialysis access steal syndrome

We suspected dialysis access steal syndrome (also known as AVF steal syndrome), so a duplex ultrasound was performed. The ultrasound was inconclusive. (We couldn’t confirm a limitation in blood flow, nor delineate anatomy.) So, we referred the patient for a thoracic and upper extremity angiogram.

The angiogram demonstrated multifocal, moderate to severe, areas of stenosis at the distal left brachial artery. The radial artery was patent at the level of the wrist, but showed diffuse narrowing beyond the level of the arteriovenous (AV) anastomosis. There was only a faint palmar arch identified on the radial aspect of the hand with digital branches feeding the radial portion of the hand. In contrast, the ulnar artery was not seen within the mid- and distal forearm (FIGURE 2). Palmar branches to the ulnar half of the hand were not identified. The fistula itself didn’t show any stenosis.

Based on these findings, our suspicions of dialysis access steal syndrome were confirmed.

Dialysis access steal syndrome is caused by a significant decrease or reversal of blood flow in the arterial segment distal to the AVF or graft, which is induced by the low resistance of the fistula outflow. Patients with adequate collateral vasculature are able to compensate for the steal effect; however, patients with end-stage renal disease typically have preexisting vascular disease that increases the risk for vascular steal and, ultimately, demand ischemia after placement of an AVF.¹ Interestingly, a steal effect occurs in 73% of patients after AVF construction, yet it is estimated that only 10% of patients demonstrating a steal phenomenon become symptomatic.²

In our patient’s case, the vaso-occlusive properties of topical steroids explain why the superpotent steroid (clobetasol) he was prescribed increased his pain and worsened the underlying problem.

A broad differential; a useful exam maneuver

The differential diagnosis of ulcers includes infection (mainly from bacterial or mycobacterial sources), trauma facilitated by neuropathy (neuropathic ulceration), vasculitis, and ischemia. When the history and physical exam suggest ischemic ulceration, then thromboembolism, thoracic outlet syndrome, vasculitis, atherosclerosis, and steal syndrome become more likely causes.

Signs and symptoms of ischemic steal syndrome are initially subtle and include extremity coolness, neurosensory changes, intrinsic muscle weakness, ulceration, and ultimately, gangrene of the affected extremity.^3,4 A cold, numb, and/or painful hand during dialysis is another clue.³ Factors that increase the likelihood of the syndrome include age >60 years, female sex, and the presence of diabetes or peripheral artery disease.^2,3,5,6

The confirmatory diagnosis of steal syndrome is made via a fistulogram (angiography) with and without manual compression.

One physical exam maneuver that can help make the diagnosis of steal syndrome is manual occlusion of the AVF. If palpable distal pulses disappear when the AVF is patent and reappear when the fistula is occluded with downward pressure, then AVF steal syndrome is likely.⁴ Pain at rest, sensory loss, loss of pulse, and digital gangrene are emergency symptoms that warrant immediate surgical evaluation.³

Tests will confirm suspicions. Doppler ultrasound can be used to assess changes in the blood flow rate of the affected vessels when the AVF is patent vs when it is occluded. Similarly, pulse oximetry can be used with and without AVF occlusion to compare changes in oxygen saturation. The confirmatory diagnosis, however, is made via a fistulogram (angiography) with and without manual compression.⁶ Images taken after dye injection into the AVF show dramatic improvement of distal blood flow with AVF compression.

Treatment requires surgery

Severe steal-related ischemic manifestations that threaten the function and viability of digits require surgical treatment that is primarily directed toward improving distal blood flow and secondarily toward preserving hemodialysis access. Several surgical treatments are commonly used, including access ligation, banding, elongation, distal arterial ligation, and distal revascularization and interval ligation.^2-5,7

Our patient. Distal revascularization was attempted, but unfortunately, the patient’s gangrene was progressive (FIGURE 3) and surgical amputation of the left fourth finger was performed at the metacarpal’s proximal metaphyseal flare. The patient was transitioned to peritoneal dialysis to avoid further ischemia.

CORRESPONDENCE
Sahand Rahnama-Moghadam, MD, Department of Dermatology, Indiana University, 545 Barnhill Drive, Indianapolis, IN 46202; [email protected].

A 62-year-old man with end-stage renal disease presented to our dermatology clinic with 2-month-old ulcerations on his distal left ring finger. He was on hemodialysis and had a radiocephalic arteriovenous fistula (AVF) on his left arm. He had been empirically treated elsewhere with oral trimethoprim-sulfamethoxazole for a presumed bacterial infection, without improvement. He was then treated for contact dermatitis with topical clobetasol, which led to ulcer expansion and worsening pain.

At our clinic, the patient reported intermittent pain in his finger and paresthesias during activity and dialysis, but no tenderness of the ulcers. He had atrophy of the intrinsic left hand muscles (his non-dominant hand) with associated weakness. Three weeks earlier, he’d received a blood transfusion for anemia. Afterward, the pain in his hand improved and the ulcers decreased in size.

On exam, the AVF had a palpable thrill over the left forearm. The radial pulses were palpable bilaterally (2+) and the left ulnar artery was palpable, but diminished (1+). The patient’s left hand was cooler than the right (with a slight cyanotic hue and visible intrinsic muscle atrophy) and had decreased sensation to pain and temperature. Four ulcers with dry yellow eschar were located over the dorsal interphalangeal joints (FIGURES 1A AND 1B). They were essentially non-tender, but there was tenderness in the adjacent intact skin. There was violaceous blue edematous congestion noted on the fourth finger, and the distal phalange was constricted, giving it a “pseudoainhum” appearance.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Dialysis access steal syndrome

We suspected dialysis access steal syndrome (also known as AVF steal syndrome), so a duplex ultrasound was performed. The ultrasound was inconclusive. (We couldn’t confirm a limitation in blood flow, nor delineate anatomy.) So, we referred the patient for a thoracic and upper extremity angiogram.

The angiogram demonstrated multifocal, moderate to severe, areas of stenosis at the distal left brachial artery. The radial artery was patent at the level of the wrist, but showed diffuse narrowing beyond the level of the arteriovenous (AV) anastomosis. There was only a faint palmar arch identified on the radial aspect of the hand with digital branches feeding the radial portion of the hand. In contrast, the ulnar artery was not seen within the mid- and distal forearm (FIGURE 2). Palmar branches to the ulnar half of the hand were not identified. The fistula itself didn’t show any stenosis.

Based on these findings, our suspicions of dialysis access steal syndrome were confirmed.

Dialysis access steal syndrome is caused by a significant decrease or reversal of blood flow in the arterial segment distal to the AVF or graft, which is induced by the low resistance of the fistula outflow. Patients with adequate collateral vasculature are able to compensate for the steal effect; however, patients with end-stage renal disease typically have preexisting vascular disease that increases the risk for vascular steal and, ultimately, demand ischemia after placement of an AVF.¹ Interestingly, a steal effect occurs in 73% of patients after AVF construction, yet it is estimated that only 10% of patients demonstrating a steal phenomenon become symptomatic.²

In our patient’s case, the vaso-occlusive properties of topical steroids explain why the superpotent steroid (clobetasol) he was prescribed increased his pain and worsened the underlying problem.

A broad differential; a useful exam maneuver

The differential diagnosis of ulcers includes infection (mainly from bacterial or mycobacterial sources), trauma facilitated by neuropathy (neuropathic ulceration), vasculitis, and ischemia. When the history and physical exam suggest ischemic ulceration, then thromboembolism, thoracic outlet syndrome, vasculitis, atherosclerosis, and steal syndrome become more likely causes.

Signs and symptoms of ischemic steal syndrome are initially subtle and include extremity coolness, neurosensory changes, intrinsic muscle weakness, ulceration, and ultimately, gangrene of the affected extremity.^3,4 A cold, numb, and/or painful hand during dialysis is another clue.³ Factors that increase the likelihood of the syndrome include age >60 years, female sex, and the presence of diabetes or peripheral artery disease.^2,3,5,6

The confirmatory diagnosis of steal syndrome is made via a fistulogram (angiography) with and without manual compression.

One physical exam maneuver that can help make the diagnosis of steal syndrome is manual occlusion of the AVF. If palpable distal pulses disappear when the AVF is patent and reappear when the fistula is occluded with downward pressure, then AVF steal syndrome is likely.⁴ Pain at rest, sensory loss, loss of pulse, and digital gangrene are emergency symptoms that warrant immediate surgical evaluation.³

Tests will confirm suspicions. Doppler ultrasound can be used to assess changes in the blood flow rate of the affected vessels when the AVF is patent vs when it is occluded. Similarly, pulse oximetry can be used with and without AVF occlusion to compare changes in oxygen saturation. The confirmatory diagnosis, however, is made via a fistulogram (angiography) with and without manual compression.⁶ Images taken after dye injection into the AVF show dramatic improvement of distal blood flow with AVF compression.

Treatment requires surgery

Severe steal-related ischemic manifestations that threaten the function and viability of digits require surgical treatment that is primarily directed toward improving distal blood flow and secondarily toward preserving hemodialysis access. Several surgical treatments are commonly used, including access ligation, banding, elongation, distal arterial ligation, and distal revascularization and interval ligation.^2-5,7

Our patient. Distal revascularization was attempted, but unfortunately, the patient’s gangrene was progressive (FIGURE 3) and surgical amputation of the left fourth finger was performed at the metacarpal’s proximal metaphyseal flare. The patient was transitioned to peritoneal dialysis to avoid further ischemia.

CORRESPONDENCE
Sahand Rahnama-Moghadam, MD, Department of Dermatology, Indiana University, 545 Barnhill Drive, Indianapolis, IN 46202; [email protected].

EVIDENCE SUMMARY

A systematic review and meta-analysis of 84 moderate- to high-quality RCTs with 24,010 patients evaluated the use of “eHealth” interventions in preventing and treating overweight and obesity in adults 35 to 65 years of age (75% female).¹ The studies included 183 active intervention arms with durations as long as 24 months (64% <6 months, 46% >6 months). The term eHealth included all forms of information technology used to deliver health care, but predominantly the Internet (Web site/Web-based), e-mail, and text messaging. Sixty percent (84) of eHealth interventional arms used one modality and 34% (47) used 2. Some intervention arms included non-eHealth modalities, such as paper-based measures and counseling.

The eHealth interventions were associated with significantly greater weight loss than minimal or no intervention (TABLE).¹ Comparing eHealth interventions with no intervention showed significant differences by eHealth type (P=.05). The greatest weight loss accompanied interventions that combined Web-based measures with a non-eHealth intervention, (mean difference [MD]= −3.7 kg; 95% confidence interval [CI], −4.46 to −2.94), followed by mobile interventions alone (MD= −2.4 kg; 95% CI, −4.09 to −0.71) and Web-based interventions alone (MD= −2.2 kg; 95% CI, −2.98 to −1.44).

Similarly, comparing combined interventions (eHealth + eHealth or eHealth + non-eHealth) with a minimal intervention control showed a trend for difference by eHealth type (P=.005). Only a combination of eHealth with non-eHealth interventions resulted in significantly greater weight loss (Web site + non-eHealth: MD= −2.7 kg; 95% CI, −3.76 to −1.54; text + non-eHealth: MD= −1.8 kg; 95% CI, −2.49 to −1.12; computer + non-eHealth: MD=1.1 kg; 95% CI, −1.36 to −0.89).

Personal coaching plus smartphone monitoring beats interactive app

A 3-arm RCT of 385 overweight and obese participants (mean body mass index [BMI], 35 kg/m²) 18 to 35 years of age compared the effectiveness of weight loss interventions delivered by interactive smartphone application (CP [cell phone]), personal coaching enhanced by smartphone self-monitoring (PC), and usual care (control).² The PC arm attended 6 weekly group sessions and received monthly phone calls. The usual care arm received 3 handouts on healthy eating and physical activity.

The CP arm showed the least amount of weight loss (−0.9 kg, −1.5 kg, and −1.0 kg at 6, 12, and 24 months, respectively) and no significant difference compared with controls at all measurement points. The PC arm had significantly greater weight loss than controls at 6 months (−1.9 kg; 95% CI, −3.17 to −0.67) and significantly greater weight loss than CP at 6 months (−2.2 kg; 95% CI, −3.42 to −0.97) and 12 months (−2.1 kg; 95% CI, −3.94 to −0.27). After 24 months, however, there was no significant difference in mean weight loss among treatment arms.

Automated behavioral program reduced weight and waist circumference

An RCT of 339 prediabetic, overweight, and obese patients 30 to 69 years old (mean BMI, 31 kg/m²) compared the effectiveness of Alive-PD, a fully automated, tailored, behavioral program, to usual care (control) for diabetes prevention.³ In addition to behavioral support, the program included weekly emails, Web-based tracking, a mobile phone app, and automated phone calls.

At 6 months, the intervention group had significantly greater mean weight loss (−3.4 kg vs −1.3 kg; P<.001), mean BMI (−1.1 kg/m² vs −0.4 kg/m²; P<.001), and mean waist circumference (−4.6 cm vs 2.2 cm; P<.001).

Web-based program improves weight loss at 3 months, but not 12 months

An RCT of 65 overweight and obese participants (mean BMI, 32 kg/m²) with at least one cardiovascular risk factor compared the effect of a Web-based program with usual care on weight change at 3, 6, and 12 months.⁴ Participants in the intervention group were provided with Bluetooth-enabled scales and accelerometer activity bands to allow daily uploads. The Web-based program also provided weekly feedback based on the participant’s performance and a food diary.

The Web-based group had significantly greater weight loss at 3 months (mean= −3.4 kg [95% CI, −4.70 to −2.13] vs −0.5 kg [95% CI, −1.55 to 0.52]; P<.001) and 6 months (mean= −3.4 kg [95% CI, −4.95 to −1.98] vs −0.8 kg [95% CI, −2.23 to 0.61]; P=.02). At 12 months, however, the groups showed no significant difference (mean= −2.4 kg [95% CI, −3.48 to −0.97] vs −1.8 kg [95% CI, −3.15 to −0.44]; P=.77).

RECOMMENDATIONS

Guidelines from the American College of Cardiology, American Heart Association, and Obesity Society state that electronically delivered weight-loss programs may be prescribed, but may result in smaller weight loss than face-to-face interventions (SOR: B, moderate evidence from RCTs with some limitations or non-randomized trials).⁵

EVIDENCE SUMMARY

A systematic review and meta-analysis of 84 moderate- to high-quality RCTs with 24,010 patients evaluated the use of “eHealth” interventions in preventing and treating overweight and obesity in adults 35 to 65 years of age (75% female).¹ The studies included 183 active intervention arms with durations as long as 24 months (64% <6 months, 46% >6 months). The term eHealth included all forms of information technology used to deliver health care, but predominantly the Internet (Web site/Web-based), e-mail, and text messaging. Sixty percent (84) of eHealth interventional arms used one modality and 34% (47) used 2. Some intervention arms included non-eHealth modalities, such as paper-based measures and counseling.

The eHealth interventions were associated with significantly greater weight loss than minimal or no intervention (TABLE).¹ Comparing eHealth interventions with no intervention showed significant differences by eHealth type (P=.05). The greatest weight loss accompanied interventions that combined Web-based measures with a non-eHealth intervention, (mean difference [MD]= −3.7 kg; 95% confidence interval [CI], −4.46 to −2.94), followed by mobile interventions alone (MD= −2.4 kg; 95% CI, −4.09 to −0.71) and Web-based interventions alone (MD= −2.2 kg; 95% CI, −2.98 to −1.44).

Similarly, comparing combined interventions (eHealth + eHealth or eHealth + non-eHealth) with a minimal intervention control showed a trend for difference by eHealth type (P=.005). Only a combination of eHealth with non-eHealth interventions resulted in significantly greater weight loss (Web site + non-eHealth: MD= −2.7 kg; 95% CI, −3.76 to −1.54; text + non-eHealth: MD= −1.8 kg; 95% CI, −2.49 to −1.12; computer + non-eHealth: MD=1.1 kg; 95% CI, −1.36 to −0.89).

Personal coaching plus smartphone monitoring beats interactive app

A 3-arm RCT of 385 overweight and obese participants (mean body mass index [BMI], 35 kg/m²) 18 to 35 years of age compared the effectiveness of weight loss interventions delivered by interactive smartphone application (CP [cell phone]), personal coaching enhanced by smartphone self-monitoring (PC), and usual care (control).² The PC arm attended 6 weekly group sessions and received monthly phone calls. The usual care arm received 3 handouts on healthy eating and physical activity.

The CP arm showed the least amount of weight loss (−0.9 kg, −1.5 kg, and −1.0 kg at 6, 12, and 24 months, respectively) and no significant difference compared with controls at all measurement points. The PC arm had significantly greater weight loss than controls at 6 months (−1.9 kg; 95% CI, −3.17 to −0.67) and significantly greater weight loss than CP at 6 months (−2.2 kg; 95% CI, −3.42 to −0.97) and 12 months (−2.1 kg; 95% CI, −3.94 to −0.27). After 24 months, however, there was no significant difference in mean weight loss among treatment arms.

Automated behavioral program reduced weight and waist circumference

An RCT of 339 prediabetic, overweight, and obese patients 30 to 69 years old (mean BMI, 31 kg/m²) compared the effectiveness of Alive-PD, a fully automated, tailored, behavioral program, to usual care (control) for diabetes prevention.³ In addition to behavioral support, the program included weekly emails, Web-based tracking, a mobile phone app, and automated phone calls.

At 6 months, the intervention group had significantly greater mean weight loss (−3.4 kg vs −1.3 kg; P<.001), mean BMI (−1.1 kg/m² vs −0.4 kg/m²; P<.001), and mean waist circumference (−4.6 cm vs 2.2 cm; P<.001).

Web-based program improves weight loss at 3 months, but not 12 months

An RCT of 65 overweight and obese participants (mean BMI, 32 kg/m²) with at least one cardiovascular risk factor compared the effect of a Web-based program with usual care on weight change at 3, 6, and 12 months.⁴ Participants in the intervention group were provided with Bluetooth-enabled scales and accelerometer activity bands to allow daily uploads. The Web-based program also provided weekly feedback based on the participant’s performance and a food diary.

The Web-based group had significantly greater weight loss at 3 months (mean= −3.4 kg [95% CI, −4.70 to −2.13] vs −0.5 kg [95% CI, −1.55 to 0.52]; P<.001) and 6 months (mean= −3.4 kg [95% CI, −4.95 to −1.98] vs −0.8 kg [95% CI, −2.23 to 0.61]; P=.02). At 12 months, however, the groups showed no significant difference (mean= −2.4 kg [95% CI, −3.48 to −0.97] vs −1.8 kg [95% CI, −3.15 to −0.44]; P=.77).

RECOMMENDATIONS

Guidelines from the American College of Cardiology, American Heart Association, and Obesity Society state that electronically delivered weight-loss programs may be prescribed, but may result in smaller weight loss than face-to-face interventions (SOR: B, moderate evidence from RCTs with some limitations or non-randomized trials).⁵

EVIDENCE SUMMARY

A systematic review and meta-analysis of 84 moderate- to high-quality RCTs with 24,010 patients evaluated the use of “eHealth” interventions in preventing and treating overweight and obesity in adults 35 to 65 years of age (75% female).¹ The studies included 183 active intervention arms with durations as long as 24 months (64% <6 months, 46% >6 months). The term eHealth included all forms of information technology used to deliver health care, but predominantly the Internet (Web site/Web-based), e-mail, and text messaging. Sixty percent (84) of eHealth interventional arms used one modality and 34% (47) used 2. Some intervention arms included non-eHealth modalities, such as paper-based measures and counseling.

The eHealth interventions were associated with significantly greater weight loss than minimal or no intervention (TABLE).¹ Comparing eHealth interventions with no intervention showed significant differences by eHealth type (P=.05). The greatest weight loss accompanied interventions that combined Web-based measures with a non-eHealth intervention, (mean difference [MD]= −3.7 kg; 95% confidence interval [CI], −4.46 to −2.94), followed by mobile interventions alone (MD= −2.4 kg; 95% CI, −4.09 to −0.71) and Web-based interventions alone (MD= −2.2 kg; 95% CI, −2.98 to −1.44).

Similarly, comparing combined interventions (eHealth + eHealth or eHealth + non-eHealth) with a minimal intervention control showed a trend for difference by eHealth type (P=.005). Only a combination of eHealth with non-eHealth interventions resulted in significantly greater weight loss (Web site + non-eHealth: MD= −2.7 kg; 95% CI, −3.76 to −1.54; text + non-eHealth: MD= −1.8 kg; 95% CI, −2.49 to −1.12; computer + non-eHealth: MD=1.1 kg; 95% CI, −1.36 to −0.89).

Personal coaching plus smartphone monitoring beats interactive app

A 3-arm RCT of 385 overweight and obese participants (mean body mass index [BMI], 35 kg/m²) 18 to 35 years of age compared the effectiveness of weight loss interventions delivered by interactive smartphone application (CP [cell phone]), personal coaching enhanced by smartphone self-monitoring (PC), and usual care (control).² The PC arm attended 6 weekly group sessions and received monthly phone calls. The usual care arm received 3 handouts on healthy eating and physical activity.

The CP arm showed the least amount of weight loss (−0.9 kg, −1.5 kg, and −1.0 kg at 6, 12, and 24 months, respectively) and no significant difference compared with controls at all measurement points. The PC arm had significantly greater weight loss than controls at 6 months (−1.9 kg; 95% CI, −3.17 to −0.67) and significantly greater weight loss than CP at 6 months (−2.2 kg; 95% CI, −3.42 to −0.97) and 12 months (−2.1 kg; 95% CI, −3.94 to −0.27). After 24 months, however, there was no significant difference in mean weight loss among treatment arms.

Automated behavioral program reduced weight and waist circumference

An RCT of 339 prediabetic, overweight, and obese patients 30 to 69 years old (mean BMI, 31 kg/m²) compared the effectiveness of Alive-PD, a fully automated, tailored, behavioral program, to usual care (control) for diabetes prevention.³ In addition to behavioral support, the program included weekly emails, Web-based tracking, a mobile phone app, and automated phone calls.

At 6 months, the intervention group had significantly greater mean weight loss (−3.4 kg vs −1.3 kg; P<.001), mean BMI (−1.1 kg/m² vs −0.4 kg/m²; P<.001), and mean waist circumference (−4.6 cm vs 2.2 cm; P<.001).

Web-based program improves weight loss at 3 months, but not 12 months

An RCT of 65 overweight and obese participants (mean BMI, 32 kg/m²) with at least one cardiovascular risk factor compared the effect of a Web-based program with usual care on weight change at 3, 6, and 12 months.⁴ Participants in the intervention group were provided with Bluetooth-enabled scales and accelerometer activity bands to allow daily uploads. The Web-based program also provided weekly feedback based on the participant’s performance and a food diary.

The Web-based group had significantly greater weight loss at 3 months (mean= −3.4 kg [95% CI, −4.70 to −2.13] vs −0.5 kg [95% CI, −1.55 to 0.52]; P<.001) and 6 months (mean= −3.4 kg [95% CI, −4.95 to −1.98] vs −0.8 kg [95% CI, −2.23 to 0.61]; P=.02). At 12 months, however, the groups showed no significant difference (mean= −2.4 kg [95% CI, −3.48 to −0.97] vs −1.8 kg [95% CI, −3.15 to −0.44]; P=.77).

RECOMMENDATIONS

Guidelines from the American College of Cardiology, American Heart Association, and Obesity Society state that electronically delivered weight-loss programs may be prescribed, but may result in smaller weight loss than face-to-face interventions (SOR: B, moderate evidence from RCTs with some limitations or non-randomized trials).⁵

When I became a family physician (FP), it never crossed my mind that I would one day be asking school-aged children about bullying. Not so much because bullying didn’t exist, but because I wasn’t aware of the pervasiveness and seriousness of the problem and because there were no professional recommendations to do so.

That said, my family had some first-hand experience with the issue: One of my children was bullied in grade school. When my wife found out, she promptly visited the 2 boys’ homes and told them and their parents that the behavior would stop or else! (She may have used more colorful language.) And it did stop. But times have changed, and so has the nature of bullying, which can now extend beyond the hallway to an entire school body in seconds with a few taps on a cell phone. And the adverse consequences can be significant, as described by McClowry and colleagues.

We need to ask our young patients a single question: "Are you being bullied?"The prevalence of bullying is discouragingly high, estimated to be about 20% in national surveys.¹ Because bullying occurs so frequently, public health, community-based, and school-based approaches, rather than one-on-one office-based interventions, are likely to have the greatest overall impact on decreasing bullying. Randomized trials bear this out, showing that prevention programs in schools can effectively reduce the behavior.^2,3

What is our responsibility as FPs? Screening is a reasonable first step, even in the absence of randomized trials demonstrating benefit. Because there have been no physician office-based trials of screening or interventions for bullying, we must rely on “expert opinion” at this time, with no assurance that what we do will actually help children. Absence of proof of benefit, however, does not mean absence of benefit, and doing nothing will definitely not help anyone. The authors recommend a single screening question: "Are you being bullied?"—especially for children who are at higher risk, such as those with disabilities/special health needs, LGBTQ+ status, and who are under- or overweight.

Clearly we need research to know which interventions truly help these children/adolescents and their parents. In the meantime, however, identifying the problem and offering emotional support are unlikely to harm—and may help. Opening the lines of communication, connecting children and their parents with available community resources, and supporting anti-bullying programs in your schools are additional ways we can make a difference today.

When I became a family physician (FP), it never crossed my mind that I would one day be asking school-aged children about bullying. Not so much because bullying didn’t exist, but because I wasn’t aware of the pervasiveness and seriousness of the problem and because there were no professional recommendations to do so.

That said, my family had some first-hand experience with the issue: One of my children was bullied in grade school. When my wife found out, she promptly visited the 2 boys’ homes and told them and their parents that the behavior would stop or else! (She may have used more colorful language.) And it did stop. But times have changed, and so has the nature of bullying, which can now extend beyond the hallway to an entire school body in seconds with a few taps on a cell phone. And the adverse consequences can be significant, as described by McClowry and colleagues.

We need to ask our young patients a single question: "Are you being bullied?"The prevalence of bullying is discouragingly high, estimated to be about 20% in national surveys.¹ Because bullying occurs so frequently, public health, community-based, and school-based approaches, rather than one-on-one office-based interventions, are likely to have the greatest overall impact on decreasing bullying. Randomized trials bear this out, showing that prevention programs in schools can effectively reduce the behavior.^2,3

What is our responsibility as FPs? Screening is a reasonable first step, even in the absence of randomized trials demonstrating benefit. Because there have been no physician office-based trials of screening or interventions for bullying, we must rely on “expert opinion” at this time, with no assurance that what we do will actually help children. Absence of proof of benefit, however, does not mean absence of benefit, and doing nothing will definitely not help anyone. The authors recommend a single screening question: "Are you being bullied?"—especially for children who are at higher risk, such as those with disabilities/special health needs, LGBTQ+ status, and who are under- or overweight.

Clearly we need research to know which interventions truly help these children/adolescents and their parents. In the meantime, however, identifying the problem and offering emotional support are unlikely to harm—and may help. Opening the lines of communication, connecting children and their parents with available community resources, and supporting anti-bullying programs in your schools are additional ways we can make a difference today.

When I became a family physician (FP), it never crossed my mind that I would one day be asking school-aged children about bullying. Not so much because bullying didn’t exist, but because I wasn’t aware of the pervasiveness and seriousness of the problem and because there were no professional recommendations to do so.

That said, my family had some first-hand experience with the issue: One of my children was bullied in grade school. When my wife found out, she promptly visited the 2 boys’ homes and told them and their parents that the behavior would stop or else! (She may have used more colorful language.) And it did stop. But times have changed, and so has the nature of bullying, which can now extend beyond the hallway to an entire school body in seconds with a few taps on a cell phone. And the adverse consequences can be significant, as described by McClowry and colleagues.

We need to ask our young patients a single question: "Are you being bullied?"The prevalence of bullying is discouragingly high, estimated to be about 20% in national surveys.¹ Because bullying occurs so frequently, public health, community-based, and school-based approaches, rather than one-on-one office-based interventions, are likely to have the greatest overall impact on decreasing bullying. Randomized trials bear this out, showing that prevention programs in schools can effectively reduce the behavior.^2,3

What is our responsibility as FPs? Screening is a reasonable first step, even in the absence of randomized trials demonstrating benefit. Because there have been no physician office-based trials of screening or interventions for bullying, we must rely on “expert opinion” at this time, with no assurance that what we do will actually help children. Absence of proof of benefit, however, does not mean absence of benefit, and doing nothing will definitely not help anyone. The authors recommend a single screening question: "Are you being bullied?"—especially for children who are at higher risk, such as those with disabilities/special health needs, LGBTQ+ status, and who are under- or overweight.

Clearly we need research to know which interventions truly help these children/adolescents and their parents. In the meantime, however, identifying the problem and offering emotional support are unlikely to harm—and may help. Opening the lines of communication, connecting children and their parents with available community resources, and supporting anti-bullying programs in your schools are additional ways we can make a difference today.

CASE › For the third time in 9 months, 28-year-old Joan B comes into the office with complaints of painful, frequent, and urgent urination. Ms B is sexually active and her medical history is otherwise unremarkable. In each of the previous 2 episodes, her urine culture grew Escherichia coli, and she was treated with a 5-day course of nitrofurantoin. At this current visit, she asks about the need for additional work-up, treatment for her symptoms, and whether there is a way to prevent further infections.

Urinary tract infections (UTIs) are the most common bacterial infection in women¹ and account for an estimated 5.4 million primary care office visits and 2.3 million emergency room visits annually.² For women, the lifetime risk of developing a UTI is greater than 50%.³ In one study of UTI in a primary care setting, 36% of women under 55 and 53% of women over 55 had a recurrent infection within a year.⁴ Most women with UTI are treated as outpatients, but 16.7% require hospitalization.⁵ In the United States, direct costs for evaluation and treatment of UTI total $1.6 billion each year.⁵

Accurately characterizing recurrent UTI

Bacteriuria is defined as the presence of 10⁵ colony forming units (ie, viable bacteria) per milliliter of urine collected midstream on 2 consecutive urinations.⁶ UTIs are symptomatic infections of the urinary tract and may involve the urethra, bladder, ureters, or kidneys.⁷ Infections of the lower tract (bladder and urethra) are commonly referred to as cystitis; infections of the upper tract (kidney and ureters) are referred to as pyelonephritis.

Most UTIs are uncomplicated and do not progress to more serious infections. However, patients who are pregnant, have chronic medical conditions (eg, renal insufficiency or use of immunosuppressant medications), urinary obstruction, or calculi may develop complicated UTIs.⁸

Recurrent UTI is an infection that follows resolution of bacteriuria and symptoms of a prior UTI, and the term applies when such an infection occurs within 6 months of the last UTI or when 3 or more UTIs occur within a year.⁷ Recurrent infection can be further characterized as relapse or reinfection. Relapse occurs when the patient has a second UTI caused by the same pathogen within 2 weeks of the original treatment.⁹ Reinfection is a UTI that occurs more than 2 weeks after completion of treatment for the original UTI. The pathogen in a reinfection may be the same one that caused the original UTI or it may be a different agent.⁹

It’s also important to differentiate between recurrent and resistant UTI. In resistant UTI, bacteriuria fails to resolve following 7 to 14 days of appropriate antibiotic treatment.⁹

Factors that increase the risk of recurrent UTI

Premenopausal women

Both modifiable and non-modifiable factors (TABLE 1^10-21) have been associated with increased risk of recurrent UTI in premenopausal women. Among women with specific blood group phenotypes (Lewis non-secretor, in particular), rates of UTI rise secondary to increased adherence of bacteria to epithelial cells in the urinary tract.¹⁰ Other non-modifiable risk factors include congenital urinary tract anomalies, obstruction of the urinary tract, and a history of UTI.^11,12 Women whose mothers had UTIs are at higher risk for recurrent UTI than are women whose mothers had no such history.¹³

Neither cystoscopy nor imaging is routinely recommended for the evaluation of recurrent urinary tract infection.Modifiable risk factors for recurrent UTI include contraceptive use (spermicides, spermicide-coated condoms, and oral contraceptives) and frequency of intercourse (≥4 times/month).¹³ Spermicides alter the normal vaginal flora and lead to increased colonization of E coli, which increases the risk for UTI.¹⁴ Women with recurrent UTIs were 1.27 to 1.45 times more likely to use oral contraceptives than those without recurrent UTIs.¹³ Compared with college women who had not had intercourse during the week, sexually active college women who had engaged in intercourse 3 times had a 2.6-fold increase in relative risk for UTI.¹⁵ Those who had daily intercourse had a 9-fold increase in relative risk of UTI development.¹⁵ This elevated risk is due to trauma to the lower urogenital tract (urethra) and introduction of bacteria into the urethra via mechanical factors.^16,17

Postmenopausal women

Atrophic vaginitis, catheterization, declining functional status, cystocele, incomplete emptying, incontinence, and history of premenopausal UTIs are all risk factors for recurrent UTI in postmenopausal women.^19,20 Decreased estrogen and resulting vaginal atrophy appear to be associated with increased rates of UTI in these women. Additionally, postmenopausal women’s vaginas are more likely to be colonized with E coli and have fewer lactobacilli than those of premenopausal women,²¹ which is thought to predispose them to UTI. These risk factors are summarized in TABLE 1.^10-21

Initial evaluation of recurrent UTI

Patients with recurrent UTI experience signs and symptoms similar to those with isolated uncomplicated UTI: dysuria, frequency, urgency, and hematuria. Focus your history interview on potential causes of complicated UTI (TABLE 2¹⁸). Likewise, perform a pelvic examination to evaluate for predisposing anatomic abnormalities.²² Finally, obtain a urine culture with antibiotic sensitivities to ensure that previous treatment was appropriate and to rule out microbes associated with infected uroliths.¹⁸ Given the low probability of finding abnormalities on cystoscopy or imaging, neither one is routinely recommended for the evaluation of recurrent UTI.¹⁸

Treatment options and precautions

As with isolated UTI, E coli is the most common pathogen in recurrent UTI. However, recurrent UTI is more likely than isolated UTI to result from other pathogens (odds ratio [OR]=1.5; 95% confidence interval [CI], 1.0-2.26), such as Klebsiella, Enterococcus, Proteus, and Citrobacter.²³ Since a patient’s recurrent UTI most likely arises from the same pathogen that caused the prior infection,⁸ start an antibiotic you know is effective against it. Additionally, take into account local resistance rates; antibiotic availability, cost, and adverse effects; and a patient’s drug allergies.

With recurrent UTI, start an antibiotic that's effective against the organism cultured during the prior infection.Preferred antibiotics. Trimethoprim-sulfamethoxazole (TMP-SMX), 160 mg/800 mg twice daily for 3 days, has long been the mainstay of treatment for uncomplicated UTI. Over recent years, however, resistance to TMP-SMX has increased. While it is still appropriate for many situations as first-line treatment, it is not recommended for empiric treatment if local resistance rates are higher than 20%.²⁴ Nitrofurantoin 100 mg twice daily for 5 days has efficacy similar to that of TMP-SMX, but without significant bacterial resistance. While fosfomycin 3 g as a single dose is still recommended as first-line treatment, it is less effective than either TMP-SMX or nitrofurantoin. TABLE 3²⁴ summarizes these ant­ibiotic choices and their efficacies.

Agents to avoid or use only as a last resort. For patients unable to take any of the drugs above, consider beta-lactam antibiotics, although they are typically less effective for this indication. While fluoroquinolones are very effective and have low (but rising) resistance rates, they are also associated with serious and potentially permanent adverse effects. As a result, on May 12, 2016, the Food and Drug Administration issued a Drug Safety Communication recommending that fluoroquinolones be used only in patients without other treatment options.^24,25 Do not use ampicillin or amoxicillin, which lack effectiveness for this indication and are compromised by high levels of bacterial resistance.

Shorter course of treatment? When deciding on the length of treatment for recurrent UTI, remember that shorter antibiotic courses (3-5 days) are associated with similar rates of cure and progression to systemic infections as longer courses (7-10 days). Also, patients adhere better to the shorter treatment regimen and experience fewer adverse effects.^26,27

Standing prescription? Studies have shown that women know when they have a UTI. Therefore, for women who experience recurrent UTI, consider giving them a standing prescription for antibiotics that they can initiate when symptoms arise (TABLE 3²⁴). Patient-initiated treatment yields similar rates of efficacy as physician-initiated treatment, while avoiding the adverse effects and costs associated with preventive strategies²⁸ (which we’ll discuss in a moment).

Time for imaging and referral?

For patients with a high risk of complicated UTI or a surgically amenable condition, either ultrasound or computerized tomography (CT) of the abdomen and pelvis with and without contrast is appropriate to evaluate for anatomic anomalies. While CT is the more sensitive imaging study to identify anomalies, ultrasound is less expensive and minimizes radiation exposure and is therefore also appropriate.¹⁸

Consider referring patients to a urologist if they have an underlying condition that may be amenable to surgery, such as bladder outlet obstruction, cystoceles, urinary tract diverticula, fistulae, pelvic floor dysfunction, ureteral stricture, urolithiasis, or vesicoureteral reflux.¹⁸ Additional risk factors for complicated UTI, which warrant referral as outlined by the Canadian Urologic Association, are summarized in TABLE 2.¹⁸

2 weeks later…and it’s back? Finally, for women who experience recurrent symptoms within 2 weeks of completing treatment, obtain a urine culture with antibiotic sensitivities to ensure that the infecting organism is not one typically associated with urolithiasis (Proteus and Yersinia) and that it is susceptible to planned antibiotic therapy.¹⁸Proteus and Yersinia are urease-positive bacteria that may cause stone formation in the urinary tract system. Evaluate any patient who has a UTI from either organism for urinary tract stones.

Prevention dos and don’ts

Popular myth suggests that recurrent UTIs are more common in patients who do not void after intercourse or who douche, consume caffeinated beverages, or wear non-cotton underwear. Research, however, has failed to show a relationship between any of these factors and recurrent UTIs.^13,18 Physicians should therefore stop recommending that patients modify these behaviors to decrease recurrent infections.

Popular myth suggests that recurrent UTIs are more common in patients who do not void after intercourse, but there's no research that bears this out.Antibiotic prophylaxis decreases the rate of recurrent UTI by 95%.²⁹ It has been recommended for women who have had 2 or more UTIs in the past 6 months²⁹ or 3 or more UTIs in the past year.³⁰ Effective strategies to prevent recurrent UTI are low-dose continuous antibiotic prophylaxis or post-coital antibiotic prophylaxis.

While a test-of-cure culture is not typically recommended following treatment for uncomplicated UTI, you will want to obtain a confirmatory urine culture one to 2 weeks before starting low-dose antibiotic prophylaxis. Base your choice of antibiotic on known patient allergies and previous culture results. Agents typically used are trimethoprim, TMP-SMX, or nitrofurantoin^31,32 (TABLE 4³¹), none of which demonstrated superiority in a Cochrane review.³³ Although the same review showed no optimal duration of treatment,³³ 6 to 24 months of treatment is usually recommended.²⁹

A single dose of antibiotic following intercourse may be as effective as daily low-dose prophylaxis for women whose UTIs are related to sexual activity.³⁴ Studies have shown that single doses of TMP-SMX, nitrofurantoin, cephalexin, or a fluoroquinolone (see earlier notes about FDA warning on fluoroquinolone use) are similarly effective in decreasing the rate of recurrence^35,36 (TABLE 4³¹).

Several non-pharmacologic strategies have been suggested for preventing recurrent UTI—eg, use of cranberry products, lactobacillus, vaginal estrogen in postmenopausal women, methenamine salts, and D-mannose.

A Cochrane review found that cranberry products were less effective in preventing recurrent UTIs than previously thought.A 2012 Cochrane review of 24 studies found that cranberry products were less effective in preventing recurrent UTIs than previously thought, with no statistically significant difference between women who took them and those who did not.³⁷

Results have been mixed in using lactobacilli or probiotics to prevent recurrent UTIs. One study examining the use of lactobacilli to colonize the vaginal flora found a reduction in the number of recurrent infections in premenopausal women taking intravaginal lactobacillus over 12 months.³⁸ A second study, involving postmenopausal women, found that those who were randomized to take lactobacillus tablets for 12 months had more frequent recurrences of UTIs than women randomized to take daily TMP-SMX.³⁹ However, this last study was designed as a non-inferiority trial and its results do not negate the prior study’s findings. Additionally, vaginal estrogen, which is thought to work through colonization of the vagina with lactobacilli, has prevented recurrent UTIs in postmenopausal women.⁴⁰

Ascorbic acid (which is bacteriostatic), methenamine salts (which are hydrolysed to bactericidal ammonia and formaldehyde), and D-mannose (which inhibits bacterial adherence), have been shown—in limited studies—to decrease recurrence of UTIs.^41-43 Further study is necessary to confirm their efficacy in preventing UTIs.

As noted, the only behavioral modifications that have been shown to decrease the risk of recurrent UTI are discontinuing the use of spermicides/spermicide-coated condoms or oral contraceptives, and decreasing the frequency of intercourse.¹³

CASE › Ms. B is started on a 3-day course of TMP-SMX. Further questioning reveals that each of her 3 UTIs followed sexual intercourse. Her physician discusses the options of self-directed therapy using continuous prophylaxis or postcoital prophylaxis, either of which would be an appropriate evidence-based intervention for her. After engaging in shared decision making, she is prescribed TMP-SMX to be taken as a single dose following intercourse in the future.

CORRESPONDENCE
Jeffrey D. Quinlan, MD, FAAFP, Family Medicine, Room A-1038A, 4301 Jones Bridge Road, Bethesda, MD 20814-4712; [email protected].