Antenatal corticosteroid treat-ment prior to preterm birth is the most important pharmacologic intervention available to obstetricians to improve newborn health. Antenatal corticosteroids reduce preterm newborn morbidity and mortality.¹ The American College of Obstetricians and Gynecologists (ACOG) recently has summarized updated recommendations for the use of antenatal steroid treatment.²

ACOG guidance includes:

• “A single course of corticosteroids is recommended for pregnant women between 24 0/7 weeks and 33 6/7 weeks of gestation, including for those with ruptured membranes and multiple gestations.” This guidance is supported by many high-quality trials and meta-analyses.¹
• A single course of corticosteroids “may be considered for pregnant women starting at 23 0/7 weeks of gestation who are at risk of preterm delivery within 7 days.”
• “A single repeat course of antenatal corticosteroids should be considered in women who are less than 34 0/7 weeks of gestation who have an imminent risk of preterm delivery within the next 7 days and whose prior course of antenatal corticosteroids was administered more than 14 days previously.” A repeat course of corticosteroids could be considered as early as 7 days from the prior dose.
• No more than 2 courses of antenatal steroids should be administered.

An important new ACOG recommendation is:

• “A single course of betamethasone is recommended for pregnant women between 34 0/7 and 36 6/7 weeks of gestation at risk of preterm birth within 7 days, and who have not received a previous course of antenatal corticosteroids.”

This recommendation is based, in part, on a high-quality, randomized trial including 2,831 women at high risk for preterm birth between 34 0/7 and 36 6/7 weeks of gestation who were randomly assigned to receive a course of betamethasone or placebo. The newborn and maternal outcomes observed in this study are summarized in the TABLE.³

A few points relevant to the Antenatal Late Preterm Steroids study bear emphasizing. The women enrolled in this trial were at high risk for preterm delivery based on preterm labor with a cervical dilation of ≥3 cm or 75% effacement, spontaneous rupture of the membranes, or a planned late preterm delivery by cesarean or induction. No tocolytics were administered to women in this study, and approximately 40% of the women delivered within 24 hours of entry into the trial and only received 1 dose of corticosteroid or placebo.

Women with multiple gestations, pregestational diabetes, or a prior course of corticosteroids were not included in the trial; therefore, this study cannot guide our clinical practice for these subgroups of women. Of note, betamethasone should not be administered to women in the late preterm who have chorioamnionitis.

Related article:
When could use of antenatal corticosteroids in the late preterm birth period be beneficial?

The investigators calculated that 35 women would need to be treated to prevent one case of the primary outcome: a composite score of the use of respiratory support. Consequently, 34 fetuses who do not benefit from treatment are exposed in utero to betamethasone. Long-term follow-up of infants born to mothers participating in this study is currently underway.

A recent meta-analysis of 3 trials including 3,200 women at high risk for preterm delivery at 34 0/7 to 36 6/7 weeks of gestation reported that the corticosteroid administration reduced newborn risk for transient tachypnea of the newborn (relative risk [RR], 0.72; 95% confidence interval [CI], 0.56−0.92), severe respiratory distress syndrome (RR, 0.60; 95% CI, 0.33−0.94), and use of surfactant (RR, 0.61; 95% CI, 0.38−0.99).⁴

The recommendation to offer a single course of betamethasone for pregnant women between 34 0/7 and 36 6/7 weeks of gestation at risk for preterm birth has not been embraced enthusiastically by all obstetricians. Many experts have emphasized that the known risks of late preterm betamethasone, including neonatal hypoglycemia and the unknown long-term risks of treatment, including suboptimal neurodevelopmental, cardiovascular, and metabolic outcomes should dampen enthusiasm for embracing the new ACOG recommendation.⁵ Experts also emphasize that late preterm newborns are less likely to benefit from antenatal corticosteroid treatment than babies born at less than 34 weeks. Hence, many late preterm newborns will be exposed to a potentially harmful intervention and have only a small chance of benefiting from the treatment.⁶

Many neonatologists believe that for the newborn, the benefits of maternal corticosteroid treatment outweigh the risks.^7–9 In a 30-year follow-up of 534 newborns participating in antenatal corticosteroid trials, treatment had no effect on body size, blood lipids, blood pressure, plasma cortisol, prevalence of diabetes, lung function, history of cardiovascular disease, educational attainment, or socioeconomic status. Corticosteroid treatment was associated with increased insulin secretion in response to a glucose load.¹⁰ In this study, the mothers received treatment at a median of 33 weeks of gestation and births occurred at a median of 35 weeks. Hence this study is relevant to the issue of late preterm corticosteroid treatment.

Balancing risks and benefits is complex. Balancing immediate benefits against long-term risks is most challenging. Regarding antenatal steroid use there are many unknowns, including optimal dose, drug formulation, and timing from treatment to delivery. In addition we need more high-quality data delineating the long-term effects of antenatal corticosteroids on childhood and adult health.

Read about 3 options to use in your practice

Consider these 3 options for your practice

As noted, the Antenatal Late Preterm Steroids trial investigators are pursuing long-term follow-up of the children born after maternal treatment with antenatal glucocorticoids. Both ACOG and the Society for Maternal-Fetal Medicine (SMFM)¹¹ recommend administration of antenatal glucocorticoids to women at high risk for late preterm delivery. However, since some experts are concerned that a great number of babies born late preterm will have been exposed to glucocorticoids, whose long-term risks are not well known, with only a few babies having a modest short-term benefit, 3 options could be considered for your clinical practice.

Related article:
Need for caution before extending the use of antenatal corticosteroids beyond 34 weeks’ gestation

Option 1

Follow the ACOG and SMFM suggestion that all women with a high risk of late preterm birth be offered antenatal corticosteroids. Counsel the mother and family about the potential risks and benefits and involve them in the decision.

Two alternative options are to limit antenatal corticosteroid treatment to subgroups of late preterm babies most likely to benefit from treatment, those born by cesarean delivery and those born at the earliest gestational ages.

Option 2

Limit the use of antenatal corticosteroids in the late preterm to women who are scheduled for a cesarean delivery for an obstetric indication between 34 0/7 weeks and 36 6/7 weeks of gestation. This approach greatly reduces the number of babies born in the late preterm that will be exposed to antenatal corticosteroids and focuses the treatment on a subset of babies who are certain to be born preterm and most likely to benefit.

Option 3

Limit the use of antenatal corticosteroids to women at high risk for preterm birth whose newborns are most likely to benefit from treatment—women at 34 0/7 to 35 6/7 weeks of gestation. Neonates born in the 34th or 35th week of gestation are at higher risk for morbidity than those born in the 36th week of gestation and are likely to derive the greatest benefit from antenatal corticosteroid treatment.^3,12

My advice

Yogi Berra advised, “It is tough to make predictions, especially about the future.” Although ACOG and SMFM have recommended administration of glucocorticoids to women at high risk for late preterm birth, many experts caution that until the long-term effects of antenatal corticosteroids are better characterized we should limit the use of corticosteroids in the late preterm.^5,6,13 My prediction is that long-term follow-up studies will not document significant adverse effects of one course of late preterm antenatal glucocorticoid treatment on children. My advice is to start offering antenatal corticosteroids to some women at high risk for late preterm delivery.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Antenatal corticosteroid treat-ment prior to preterm birth is the most important pharmacologic intervention available to obstetricians to improve newborn health. Antenatal corticosteroids reduce preterm newborn morbidity and mortality.¹ The American College of Obstetricians and Gynecologists (ACOG) recently has summarized updated recommendations for the use of antenatal steroid treatment.²

ACOG guidance includes:

• “A single course of corticosteroids is recommended for pregnant women between 24 0/7 weeks and 33 6/7 weeks of gestation, including for those with ruptured membranes and multiple gestations.” This guidance is supported by many high-quality trials and meta-analyses.¹
• A single course of corticosteroids “may be considered for pregnant women starting at 23 0/7 weeks of gestation who are at risk of preterm delivery within 7 days.”
• “A single repeat course of antenatal corticosteroids should be considered in women who are less than 34 0/7 weeks of gestation who have an imminent risk of preterm delivery within the next 7 days and whose prior course of antenatal corticosteroids was administered more than 14 days previously.” A repeat course of corticosteroids could be considered as early as 7 days from the prior dose.
• No more than 2 courses of antenatal steroids should be administered.

An important new ACOG recommendation is:

• “A single course of betamethasone is recommended for pregnant women between 34 0/7 and 36 6/7 weeks of gestation at risk of preterm birth within 7 days, and who have not received a previous course of antenatal corticosteroids.”

This recommendation is based, in part, on a high-quality, randomized trial including 2,831 women at high risk for preterm birth between 34 0/7 and 36 6/7 weeks of gestation who were randomly assigned to receive a course of betamethasone or placebo. The newborn and maternal outcomes observed in this study are summarized in the TABLE.³

A few points relevant to the Antenatal Late Preterm Steroids study bear emphasizing. The women enrolled in this trial were at high risk for preterm delivery based on preterm labor with a cervical dilation of ≥3 cm or 75% effacement, spontaneous rupture of the membranes, or a planned late preterm delivery by cesarean or induction. No tocolytics were administered to women in this study, and approximately 40% of the women delivered within 24 hours of entry into the trial and only received 1 dose of corticosteroid or placebo.

Women with multiple gestations, pregestational diabetes, or a prior course of corticosteroids were not included in the trial; therefore, this study cannot guide our clinical practice for these subgroups of women. Of note, betamethasone should not be administered to women in the late preterm who have chorioamnionitis.

Related article:
When could use of antenatal corticosteroids in the late preterm birth period be beneficial?

The investigators calculated that 35 women would need to be treated to prevent one case of the primary outcome: a composite score of the use of respiratory support. Consequently, 34 fetuses who do not benefit from treatment are exposed in utero to betamethasone. Long-term follow-up of infants born to mothers participating in this study is currently underway.

A recent meta-analysis of 3 trials including 3,200 women at high risk for preterm delivery at 34 0/7 to 36 6/7 weeks of gestation reported that the corticosteroid administration reduced newborn risk for transient tachypnea of the newborn (relative risk [RR], 0.72; 95% confidence interval [CI], 0.56−0.92), severe respiratory distress syndrome (RR, 0.60; 95% CI, 0.33−0.94), and use of surfactant (RR, 0.61; 95% CI, 0.38−0.99).⁴

The recommendation to offer a single course of betamethasone for pregnant women between 34 0/7 and 36 6/7 weeks of gestation at risk for preterm birth has not been embraced enthusiastically by all obstetricians. Many experts have emphasized that the known risks of late preterm betamethasone, including neonatal hypoglycemia and the unknown long-term risks of treatment, including suboptimal neurodevelopmental, cardiovascular, and metabolic outcomes should dampen enthusiasm for embracing the new ACOG recommendation.⁵ Experts also emphasize that late preterm newborns are less likely to benefit from antenatal corticosteroid treatment than babies born at less than 34 weeks. Hence, many late preterm newborns will be exposed to a potentially harmful intervention and have only a small chance of benefiting from the treatment.⁶

Many neonatologists believe that for the newborn, the benefits of maternal corticosteroid treatment outweigh the risks.^7–9 In a 30-year follow-up of 534 newborns participating in antenatal corticosteroid trials, treatment had no effect on body size, blood lipids, blood pressure, plasma cortisol, prevalence of diabetes, lung function, history of cardiovascular disease, educational attainment, or socioeconomic status. Corticosteroid treatment was associated with increased insulin secretion in response to a glucose load.¹⁰ In this study, the mothers received treatment at a median of 33 weeks of gestation and births occurred at a median of 35 weeks. Hence this study is relevant to the issue of late preterm corticosteroid treatment.

Balancing risks and benefits is complex. Balancing immediate benefits against long-term risks is most challenging. Regarding antenatal steroid use there are many unknowns, including optimal dose, drug formulation, and timing from treatment to delivery. In addition we need more high-quality data delineating the long-term effects of antenatal corticosteroids on childhood and adult health.

Read about 3 options to use in your practice

Consider these 3 options for your practice

As noted, the Antenatal Late Preterm Steroids trial investigators are pursuing long-term follow-up of the children born after maternal treatment with antenatal glucocorticoids. Both ACOG and the Society for Maternal-Fetal Medicine (SMFM)¹¹ recommend administration of antenatal glucocorticoids to women at high risk for late preterm delivery. However, since some experts are concerned that a great number of babies born late preterm will have been exposed to glucocorticoids, whose long-term risks are not well known, with only a few babies having a modest short-term benefit, 3 options could be considered for your clinical practice.

Related article:
Need for caution before extending the use of antenatal corticosteroids beyond 34 weeks’ gestation

Option 1

Follow the ACOG and SMFM suggestion that all women with a high risk of late preterm birth be offered antenatal corticosteroids. Counsel the mother and family about the potential risks and benefits and involve them in the decision.

Two alternative options are to limit antenatal corticosteroid treatment to subgroups of late preterm babies most likely to benefit from treatment, those born by cesarean delivery and those born at the earliest gestational ages.

Option 2

Limit the use of antenatal corticosteroids in the late preterm to women who are scheduled for a cesarean delivery for an obstetric indication between 34 0/7 weeks and 36 6/7 weeks of gestation. This approach greatly reduces the number of babies born in the late preterm that will be exposed to antenatal corticosteroids and focuses the treatment on a subset of babies who are certain to be born preterm and most likely to benefit.

Option 3

Limit the use of antenatal corticosteroids to women at high risk for preterm birth whose newborns are most likely to benefit from treatment—women at 34 0/7 to 35 6/7 weeks of gestation. Neonates born in the 34th or 35th week of gestation are at higher risk for morbidity than those born in the 36th week of gestation and are likely to derive the greatest benefit from antenatal corticosteroid treatment.^3,12

My advice

Yogi Berra advised, “It is tough to make predictions, especially about the future.” Although ACOG and SMFM have recommended administration of glucocorticoids to women at high risk for late preterm birth, many experts caution that until the long-term effects of antenatal corticosteroids are better characterized we should limit the use of corticosteroids in the late preterm.^5,6,13 My prediction is that long-term follow-up studies will not document significant adverse effects of one course of late preterm antenatal glucocorticoid treatment on children. My advice is to start offering antenatal corticosteroids to some women at high risk for late preterm delivery.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Antenatal corticosteroid treat-ment prior to preterm birth is the most important pharmacologic intervention available to obstetricians to improve newborn health. Antenatal corticosteroids reduce preterm newborn morbidity and mortality.¹ The American College of Obstetricians and Gynecologists (ACOG) recently has summarized updated recommendations for the use of antenatal steroid treatment.²

ACOG guidance includes:

• “A single course of corticosteroids is recommended for pregnant women between 24 0/7 weeks and 33 6/7 weeks of gestation, including for those with ruptured membranes and multiple gestations.” This guidance is supported by many high-quality trials and meta-analyses.¹
• A single course of corticosteroids “may be considered for pregnant women starting at 23 0/7 weeks of gestation who are at risk of preterm delivery within 7 days.”
• “A single repeat course of antenatal corticosteroids should be considered in women who are less than 34 0/7 weeks of gestation who have an imminent risk of preterm delivery within the next 7 days and whose prior course of antenatal corticosteroids was administered more than 14 days previously.” A repeat course of corticosteroids could be considered as early as 7 days from the prior dose.
• No more than 2 courses of antenatal steroids should be administered.

An important new ACOG recommendation is:

• “A single course of betamethasone is recommended for pregnant women between 34 0/7 and 36 6/7 weeks of gestation at risk of preterm birth within 7 days, and who have not received a previous course of antenatal corticosteroids.”

This recommendation is based, in part, on a high-quality, randomized trial including 2,831 women at high risk for preterm birth between 34 0/7 and 36 6/7 weeks of gestation who were randomly assigned to receive a course of betamethasone or placebo. The newborn and maternal outcomes observed in this study are summarized in the TABLE.³

A few points relevant to the Antenatal Late Preterm Steroids study bear emphasizing. The women enrolled in this trial were at high risk for preterm delivery based on preterm labor with a cervical dilation of ≥3 cm or 75% effacement, spontaneous rupture of the membranes, or a planned late preterm delivery by cesarean or induction. No tocolytics were administered to women in this study, and approximately 40% of the women delivered within 24 hours of entry into the trial and only received 1 dose of corticosteroid or placebo.

Women with multiple gestations, pregestational diabetes, or a prior course of corticosteroids were not included in the trial; therefore, this study cannot guide our clinical practice for these subgroups of women. Of note, betamethasone should not be administered to women in the late preterm who have chorioamnionitis.

Related article:
When could use of antenatal corticosteroids in the late preterm birth period be beneficial?

The investigators calculated that 35 women would need to be treated to prevent one case of the primary outcome: a composite score of the use of respiratory support. Consequently, 34 fetuses who do not benefit from treatment are exposed in utero to betamethasone. Long-term follow-up of infants born to mothers participating in this study is currently underway.

A recent meta-analysis of 3 trials including 3,200 women at high risk for preterm delivery at 34 0/7 to 36 6/7 weeks of gestation reported that the corticosteroid administration reduced newborn risk for transient tachypnea of the newborn (relative risk [RR], 0.72; 95% confidence interval [CI], 0.56−0.92), severe respiratory distress syndrome (RR, 0.60; 95% CI, 0.33−0.94), and use of surfactant (RR, 0.61; 95% CI, 0.38−0.99).⁴

The recommendation to offer a single course of betamethasone for pregnant women between 34 0/7 and 36 6/7 weeks of gestation at risk for preterm birth has not been embraced enthusiastically by all obstetricians. Many experts have emphasized that the known risks of late preterm betamethasone, including neonatal hypoglycemia and the unknown long-term risks of treatment, including suboptimal neurodevelopmental, cardiovascular, and metabolic outcomes should dampen enthusiasm for embracing the new ACOG recommendation.⁵ Experts also emphasize that late preterm newborns are less likely to benefit from antenatal corticosteroid treatment than babies born at less than 34 weeks. Hence, many late preterm newborns will be exposed to a potentially harmful intervention and have only a small chance of benefiting from the treatment.⁶

Many neonatologists believe that for the newborn, the benefits of maternal corticosteroid treatment outweigh the risks.^7–9 In a 30-year follow-up of 534 newborns participating in antenatal corticosteroid trials, treatment had no effect on body size, blood lipids, blood pressure, plasma cortisol, prevalence of diabetes, lung function, history of cardiovascular disease, educational attainment, or socioeconomic status. Corticosteroid treatment was associated with increased insulin secretion in response to a glucose load.¹⁰ In this study, the mothers received treatment at a median of 33 weeks of gestation and births occurred at a median of 35 weeks. Hence this study is relevant to the issue of late preterm corticosteroid treatment.

Balancing risks and benefits is complex. Balancing immediate benefits against long-term risks is most challenging. Regarding antenatal steroid use there are many unknowns, including optimal dose, drug formulation, and timing from treatment to delivery. In addition we need more high-quality data delineating the long-term effects of antenatal corticosteroids on childhood and adult health.

Read about 3 options to use in your practice

Consider these 3 options for your practice

As noted, the Antenatal Late Preterm Steroids trial investigators are pursuing long-term follow-up of the children born after maternal treatment with antenatal glucocorticoids. Both ACOG and the Society for Maternal-Fetal Medicine (SMFM)¹¹ recommend administration of antenatal glucocorticoids to women at high risk for late preterm delivery. However, since some experts are concerned that a great number of babies born late preterm will have been exposed to glucocorticoids, whose long-term risks are not well known, with only a few babies having a modest short-term benefit, 3 options could be considered for your clinical practice.

Related article:
Need for caution before extending the use of antenatal corticosteroids beyond 34 weeks’ gestation

Option 1

Follow the ACOG and SMFM suggestion that all women with a high risk of late preterm birth be offered antenatal corticosteroids. Counsel the mother and family about the potential risks and benefits and involve them in the decision.

Two alternative options are to limit antenatal corticosteroid treatment to subgroups of late preterm babies most likely to benefit from treatment, those born by cesarean delivery and those born at the earliest gestational ages.

Option 2

Limit the use of antenatal corticosteroids in the late preterm to women who are scheduled for a cesarean delivery for an obstetric indication between 34 0/7 weeks and 36 6/7 weeks of gestation. This approach greatly reduces the number of babies born in the late preterm that will be exposed to antenatal corticosteroids and focuses the treatment on a subset of babies who are certain to be born preterm and most likely to benefit.

Option 3

Limit the use of antenatal corticosteroids to women at high risk for preterm birth whose newborns are most likely to benefit from treatment—women at 34 0/7 to 35 6/7 weeks of gestation. Neonates born in the 34th or 35th week of gestation are at higher risk for morbidity than those born in the 36th week of gestation and are likely to derive the greatest benefit from antenatal corticosteroid treatment.^3,12

My advice

Yogi Berra advised, “It is tough to make predictions, especially about the future.” Although ACOG and SMFM have recommended administration of glucocorticoids to women at high risk for late preterm birth, many experts caution that until the long-term effects of antenatal corticosteroids are better characterized we should limit the use of corticosteroids in the late preterm.^5,6,13 My prediction is that long-term follow-up studies will not document significant adverse effects of one course of late preterm antenatal glucocorticoid treatment on children. My advice is to start offering antenatal corticosteroids to some women at high risk for late preterm delivery.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

ORLANDO – Cushing’s disease may begin to exert its harmful cardiovascular effects quite early, a small pediatric study has found.

Children as young as 6 years old with the disorder already may show signs of cardiovascular remodeling, with stiffer aortas and higher aortic pulse-wave velocity than do age-matched controls, Hailey Blain and Maya Lodish, MD, said at the annual meeting of the Endocrine Society.

Michele G Sullivan

[email protected]

ORLANDO – Cushing’s disease may begin to exert its harmful cardiovascular effects quite early, a small pediatric study has found.

Children as young as 6 years old with the disorder already may show signs of cardiovascular remodeling, with stiffer aortas and higher aortic pulse-wave velocity than do age-matched controls, Hailey Blain and Maya Lodish, MD, said at the annual meeting of the Endocrine Society.

Michele G Sullivan

[email protected]

ORLANDO – Cushing’s disease may begin to exert its harmful cardiovascular effects quite early, a small pediatric study has found.

Children as young as 6 years old with the disorder already may show signs of cardiovascular remodeling, with stiffer aortas and higher aortic pulse-wave velocity than do age-matched controls, Hailey Blain and Maya Lodish, MD, said at the annual meeting of the Endocrine Society.

Michele G Sullivan

[email protected]

Hearing loss and tinnitus (ringing or other noises in the ears or head) have been problematic for military service members and veterans for many years. Military personnel are exposed to high levels of noise in operational and training settings. In spite of hearing conservation efforts, hearing loss and auditory injuries (including tinnitus) continue to occur. Although current military leadership teaches the importance of hearing protection, that was not usually the case until the past few decades. Military leadership provides the means for hearing protection and monitors risk through conservation and hearing readiness programs. Unfortunately, the need for hearing during battle often overrides the expediency of using hearing protective devices.

Military members often equate hearing protection with increased vulnerability, widening the gap between preventive efforts and hearing preservation. It is therefore not surprising that tinnitus and hearing loss have been the 2 most common service-connected disabilities for veterans for a decade.¹ These conditions are irreversible; affected service members and veterans need strategies to cope with distress associated with these chronic conditions. Clinical care often is essential to manage the associated distress and mental health (MH) symptoms, such as sleep disturbance, irritability, isolation, tension, and low mood.

There is no cure for tinnitus, meaning there is no proven method to permanently eliminate or even reduce the perception of tinnitus. Intervention for tinnitus therefore is limited to methods intended to mitigate reactions to tinnitus, with the ultimate goal to facilitate good quality of life in spite of the perception of this unwanted auditory anomaly. These methods include numerous means of utilizing therapeutic sound.² Sound therapy, however, has been shown in controlled trials to be effective only when accompanied by counseling, which often focuses on teaching different coping skills.³ In such instances, MH providers can become an integral part of the hearing health team to assist patients in the management of their tinnitus.

Evidence-Based Practice

Evidence-based research should guide clinical services that are offered for tinnitus. Randomized controlled trials (RCTs) comprise the most important source for such evidence.⁴ Cochrane Reviews uses meta-analyses to examine rigorous RCTs to determine which methods have credible evidence. One of these reviews conducted in 2007 and updated in 2010 concluded that cognitive behavioral therapy (CBT) can improve depression scores and reduce distress for many people with bothersome tinnitus.^5,6 Another Cochrane Review concluded that sound therapy combined with counseling can be beneficial, but on its own, sound therapy has not been shown to result in significant benefit.³ Yet another Cochrane Review focused on using hearing aids with patients who have both hearing loss and bothersome tinnitus; the researchers concluded that “there is currently no evidence to support or refute their use as a more routine intervention for tinnitus.”⁷ However, many patients and clinicians report hearing aids are helpful for coping with tinnitus.

The American Academy of Otolaryngology–Head and Neck Surgery Foundation (AAO-HNSF) published a clinical practice guideline (CPG) for the management of tinnitus.⁸ Developing the CPG involved a comprehensive evaluation of the peer-reviewed literature, including the available Cochrane Reviews, to identify appropriate RCTs to inform evidence-based recommendations. Cognitive behavioral therapy was the only intervention for tinnitus recommended in the CPG. Cognitive behavioral therapy targets emotional response by identifying behaviors, thoughts, and beliefs that may be altered.⁹ For tinnitus, CBT typically includes stress management including relaxation exercises, purposeful distraction, and changing how individuals view and appraise their tinnitus.

Both the CPG and Cochrane Reviews concluded that CBT has the strongest evidence base for reducing effects of tinnitus. It should be noted that the CPG recommended teaching patients basic information about tinnitus management and stated that it was optional (due to limited research evidence) to use sound therapy to augment coping skills training.

Progressive Tinnitus Management

Tinnitus research at the VA National Center for Rehabilitative Auditory Research (NCRAR) has led to the development and refinement of an interdisciplinary program called Progressive Tinnitus Management (PTM). Audiologists and MH providers work together to deliver portions of the protocol. In addition, otolaryngologists are important for patients requiring a medical examination. Audiologists, MH providers, and otolaryngologists comprise the hearing health team for tinnitus management. The PTM program involves 5 stepped-care levels of management, and patients receive only the levels they need.

Level 1 is the referral level, which specifies guidelines for any clinician who encounters patients experiencing tinnitus. The “standard” referral is to audiology for a hearing evaluation (PTM level 2)—every patient reporting tinnitus should have a hearing evaluation and brief tinnitus assessment. Less typical would be an urgent referral to a different provider for certain symptoms such as referral to ENT for sudden hearing loss.

Patients who desire intervention for bothersome tinnitus are offered PTM skills education (level 3). At this level, patients are taught facts and skills that they need to self-manage their tinnitus-related problems. Ideally, the audiologist and MH provider collaborate to deliver the level 3 intervention, which utilizes a 5-session (2 with an audiologist and 3 with a MH provider) problem-solving method. Audiologists explain different forms of sound therapy, and MH providers deliver brief CBT. The research studies and clinics that use PTM have shown that the majority of patients who receive the level 3 skills education interventions have their tinnitus needs met to the degree that they do not desire further services.

Those relatively few patients who desire further services are invited for a PTM interdisciplinary evaluation (level 4), which involves a more in-depth needs evaluation by both an audiologist and a MH provider. Based on the outcome of the level 4 evaluation, clear treatment goals are discussed with the patient. If the patient and providers mutually agree that further intervention is needed, then the patient is offered PTM individualized support (level 5), which involves one-on-one services by an audiologist and/or a MH provider. The providers then build on the lessons taught during level 3 and address barriers to enacting the already discussed skills. The MH provider also may expand on CBT skills that were provided in level 3, offering care such as CBT for insomnia during level 5, depending on the specific needs and desires of the patient.

At the NCRAR, a pilot study and 2 RCTs of PTM have been completed.¹⁰ The first of these 2 RCTs was a clinical effectiveness study of PTM that was conducted in 2 VA audiology clinics: Memphis, Tennessee, and West Haven, Connecticut.¹¹ Patients who came to the clinics signed up for the study if they felt that the PTM level 3 intervention might be helpful. Half of the 300 veterans in the study were enrolled to receive PTM right away, and half were put on a 6-month wait list. The PTM group showed significantly greater benefit than that of the wait-list group.

The second RCT of PTM was motivated by the high number of service members and veterans with a history of traumatic brain injury (TBI), which is strongly associated with tinnitus.¹² The PTM level 3 skills education was administered to participants individually over the telephone by both an audiologist and a psychologist. Participants, located all over the U.S., had bothersome tinnitus, and some had experienced ≥ 1 TBI. They were randomized to receive either Tele-PTM immediately for 6 months or to be put on a 6-month wait list. The Tele-PTM group showed much greater improvement than that of the wait-list group.

Both of these recent RCTs have validated the effectiveness of PTM and demonstrated that PTM should be considered for the practice of evidence-based tinnitus management. PTM is mostly consistent with the AAO-HNSF CPG and provides a structured and defined framework for implementing both assessment and intervention services for patients who report tinnitus. As such, VA Central Office has endorsed PTM as an effective intervention for tinnitus management and has recommended its use at VAMCs. The NCRAR researchers have provided PTM training to hundreds of VA audiologists and MH providers, yet the level of implementation across the VA system of care varies widely.

VA Survey

In 2015, in partnership with the VA Offices of Audiology and Speech Pathology and Mental Health Services, and the Health Services Research & Development/Quality Enhancement Research Initiative (HSR&D/QUERI), the NCRAR conducted a study to examine PTM variation across sites via surveys and/or interviews of VA Audiology and MH programs nationwide.^13,14 The objectives of this study were to: (1) describe current tinnitus-management practices in VAMCs; (2) identify barriers and facilitators to PTM program implementation based on clinics that have fully, partially, or not implemented PTM; and (3) determine readiness to implement PTM within VISN 20 (Northwest states and Alaska).

Clinicians at VAMCs nationwide were surveyed regarding current provision of tinnitus clinical services. Requests were sent to audiology programs and MH programs at 142 major VAMCs along with instructions to complete the online survey. Responses were received from 87 audiologists and 66 MH providers. Clinicians at VAMCs with full PTM, partial PTM, and no-PTM (based on survey results) were then interviewed regarding site-specific barriers and facilitators to implementing and providing PTM, readiness to adopt PTM, and strategies for full PTM implementation.

Key findings from the study demonstrated the following: (1) There is considerable between-site variability in how PTM is implemented, particularly with the delivery of the MH portion of the protocol; (2) audiologists show higher levels of readiness to provide tinnitus services than do MH providers (7% of MH survey respondents vs 62% of audiologists reported their site implementing PTM); (3) 66% of MH survey respondents were interested in receiving training in tinnitus management (note that online PTM training for MH does not yet exist); (4) PTM implementation barriers include audio-visual technology issues, room scheduling, as well as lack of collaboration and colocation between MH and audiology departments, administrative time/support, group facilitator skills, and availability of PTM materials.

Overall, results of this HSR&D/QUERI-funded study suggested the need to develop MH-specific training to support the necessary interdisciplinary engagement. Although a patient workbook is available to order and visual presentation aids may be accessed online, it became clear that lack of MH participation in the inherently interdisciplinary PTM skills education was the most common deviation from PTM.

DoD an VA Questionnaire

In 2014 the DoD Hearing Center of Excellence (HCE) conducted the DoD and VA Tinnitus Evaluation, Management, and Treatment Assessment.¹³ The HCE conducted this questionnaire under the Tinnitus Care Quality Improvement, Process Development, and Implementation Plan, to develop, establish, and implement an interdisciplinary and ongoing process to continually assess and improve the quality and continuum of tinnitus care delivered to service members and veterans at a consistent, enterprise-wide level. The HCE developed the questionnaire to: (1) identify DoD and VA audiologists and otolaryngologists and their institutions providing comprehensive tinnitus care; (2) assess current tinnitus evaluation and management/treatment protocols used; (3) disseminate common practice improvements to all providers for enhancing overall tinnitus evaluation and management/treatment; and (4) evaluate implementation of improvements to include efficiency of implementation and efficacy of improvements.

The questionnaire was administered using SurveyMonkey (San Mateo, CA) and was disseminated by the otolaryngology and audiology consultants to the Army, Navy, and Air Force surgeons general and specialty leaders as well as through VA specialty leaders. Also, the HCE posted the link for the questionnaire on its website for 11 months. A total of 200 providers responded to the questionnaire, of which 13 did not indicate their specialty (eg, otolaryngology) or classification (eg, DoD active duty) and were excluded from data analysis. The 187 qualified respondents included 66 DoD audiologists, 120 VA audiologists, and 1 DoD otolaryngologist.

The questionnaire results indicated that DoD and VA respondents provided tinnitus services for their patients at similar rates (72% of DoD providers and 79% of VA providers). The use of PTM by those same providers, however, was far more widespread in VA (66%) than it was in DoD (37%). Of the providers indicating they did not offer tinnitus clinical services, the main reasons given were lack of necessary training/expertise, lack of time, and insufficient clinical support. The majority of respondents indicated they had training on tinnitus evaluation and/or management and that they were comfortable providing these services; despite this, most providers indicated a need or desire for tinnitus-specific training and education. These results suggested that more support and education for hearing health care providers were needed to implement PTM in VA and, especially, in DoD.

About half of the respondents indicated that psychological/behavioral treatment services, which would correspond to PTM levels 3 and 5, are available for patients at their facility who have tinnitus. It is encouraging to know that some patients with problematic tinnitus are receiving MH services. However, it is essential that patients with any degree of bothersome tinnitus have access to evidence-based clinical services, which would require CBT delivered by a qualified MH provider.

Conclusion

Numerous VA and DoD clinics have begun providing PTM. Individual sites, however, typically adapt the program during the process of implementation.^13,14 The most common adaptation that sites make to PTM is to proceed with level 3 skills education without the assistance of MH, and thus CBT, due to the lack of provider availability. It is unknown what impact this has on the effectiveness of PTM. Skills education forms the heart of PTM and addresses the needs of the majority of patients who seek intervention.

Collaboration with MH is integral to the delivery of PTM. Mental health providers partner in PTM levels 3 and 5 by providing CBT, which has the strongest evidence for reducing tinnitus distress among all interventions and always will be critical to the provision of PTM. Clearly VA MH programs need to increase involvement in veterans’ tinnitus management. Increased involvement may be accomplished by (1) developing training or other materials that increase understanding of MH’s role in addressing tinnitus; (2) developing pathways for coordination of care between audiology and MH providers, including different models of coordination based on individual site needs; and (3) documenting the prevalence of tinnitus-MH comorbidities to empirically justify the need for such coordination between audiology and MH providers.

To address gaps identified in the VA survey and in a similar questionnaire conducted by HCE regarding tinnitus care in VA and DoD, the NCRAR, HCE, and Walter Reed National Military Medical Center are collaborating on several initiatives to improve tinnitus services for service members and veterans.^13-15 These efforts include enhancing service member and veteran access to VA and DoD MH services in PTM.

Hearing loss and tinnitus (ringing or other noises in the ears or head) have been problematic for military service members and veterans for many years. Military personnel are exposed to high levels of noise in operational and training settings. In spite of hearing conservation efforts, hearing loss and auditory injuries (including tinnitus) continue to occur. Although current military leadership teaches the importance of hearing protection, that was not usually the case until the past few decades. Military leadership provides the means for hearing protection and monitors risk through conservation and hearing readiness programs. Unfortunately, the need for hearing during battle often overrides the expediency of using hearing protective devices.

Military members often equate hearing protection with increased vulnerability, widening the gap between preventive efforts and hearing preservation. It is therefore not surprising that tinnitus and hearing loss have been the 2 most common service-connected disabilities for veterans for a decade.¹ These conditions are irreversible; affected service members and veterans need strategies to cope with distress associated with these chronic conditions. Clinical care often is essential to manage the associated distress and mental health (MH) symptoms, such as sleep disturbance, irritability, isolation, tension, and low mood.

There is no cure for tinnitus, meaning there is no proven method to permanently eliminate or even reduce the perception of tinnitus. Intervention for tinnitus therefore is limited to methods intended to mitigate reactions to tinnitus, with the ultimate goal to facilitate good quality of life in spite of the perception of this unwanted auditory anomaly. These methods include numerous means of utilizing therapeutic sound.² Sound therapy, however, has been shown in controlled trials to be effective only when accompanied by counseling, which often focuses on teaching different coping skills.³ In such instances, MH providers can become an integral part of the hearing health team to assist patients in the management of their tinnitus.

Evidence-Based Practice

Evidence-based research should guide clinical services that are offered for tinnitus. Randomized controlled trials (RCTs) comprise the most important source for such evidence.⁴ Cochrane Reviews uses meta-analyses to examine rigorous RCTs to determine which methods have credible evidence. One of these reviews conducted in 2007 and updated in 2010 concluded that cognitive behavioral therapy (CBT) can improve depression scores and reduce distress for many people with bothersome tinnitus.^5,6 Another Cochrane Review concluded that sound therapy combined with counseling can be beneficial, but on its own, sound therapy has not been shown to result in significant benefit.³ Yet another Cochrane Review focused on using hearing aids with patients who have both hearing loss and bothersome tinnitus; the researchers concluded that “there is currently no evidence to support or refute their use as a more routine intervention for tinnitus.”⁷ However, many patients and clinicians report hearing aids are helpful for coping with tinnitus.

The American Academy of Otolaryngology–Head and Neck Surgery Foundation (AAO-HNSF) published a clinical practice guideline (CPG) for the management of tinnitus.⁸ Developing the CPG involved a comprehensive evaluation of the peer-reviewed literature, including the available Cochrane Reviews, to identify appropriate RCTs to inform evidence-based recommendations. Cognitive behavioral therapy was the only intervention for tinnitus recommended in the CPG. Cognitive behavioral therapy targets emotional response by identifying behaviors, thoughts, and beliefs that may be altered.⁹ For tinnitus, CBT typically includes stress management including relaxation exercises, purposeful distraction, and changing how individuals view and appraise their tinnitus.

Both the CPG and Cochrane Reviews concluded that CBT has the strongest evidence base for reducing effects of tinnitus. It should be noted that the CPG recommended teaching patients basic information about tinnitus management and stated that it was optional (due to limited research evidence) to use sound therapy to augment coping skills training.

Progressive Tinnitus Management

Tinnitus research at the VA National Center for Rehabilitative Auditory Research (NCRAR) has led to the development and refinement of an interdisciplinary program called Progressive Tinnitus Management (PTM). Audiologists and MH providers work together to deliver portions of the protocol. In addition, otolaryngologists are important for patients requiring a medical examination. Audiologists, MH providers, and otolaryngologists comprise the hearing health team for tinnitus management. The PTM program involves 5 stepped-care levels of management, and patients receive only the levels they need.

Level 1 is the referral level, which specifies guidelines for any clinician who encounters patients experiencing tinnitus. The “standard” referral is to audiology for a hearing evaluation (PTM level 2)—every patient reporting tinnitus should have a hearing evaluation and brief tinnitus assessment. Less typical would be an urgent referral to a different provider for certain symptoms such as referral to ENT for sudden hearing loss.

Patients who desire intervention for bothersome tinnitus are offered PTM skills education (level 3). At this level, patients are taught facts and skills that they need to self-manage their tinnitus-related problems. Ideally, the audiologist and MH provider collaborate to deliver the level 3 intervention, which utilizes a 5-session (2 with an audiologist and 3 with a MH provider) problem-solving method. Audiologists explain different forms of sound therapy, and MH providers deliver brief CBT. The research studies and clinics that use PTM have shown that the majority of patients who receive the level 3 skills education interventions have their tinnitus needs met to the degree that they do not desire further services.

Those relatively few patients who desire further services are invited for a PTM interdisciplinary evaluation (level 4), which involves a more in-depth needs evaluation by both an audiologist and a MH provider. Based on the outcome of the level 4 evaluation, clear treatment goals are discussed with the patient. If the patient and providers mutually agree that further intervention is needed, then the patient is offered PTM individualized support (level 5), which involves one-on-one services by an audiologist and/or a MH provider. The providers then build on the lessons taught during level 3 and address barriers to enacting the already discussed skills. The MH provider also may expand on CBT skills that were provided in level 3, offering care such as CBT for insomnia during level 5, depending on the specific needs and desires of the patient.

At the NCRAR, a pilot study and 2 RCTs of PTM have been completed.¹⁰ The first of these 2 RCTs was a clinical effectiveness study of PTM that was conducted in 2 VA audiology clinics: Memphis, Tennessee, and West Haven, Connecticut.¹¹ Patients who came to the clinics signed up for the study if they felt that the PTM level 3 intervention might be helpful. Half of the 300 veterans in the study were enrolled to receive PTM right away, and half were put on a 6-month wait list. The PTM group showed significantly greater benefit than that of the wait-list group.

The second RCT of PTM was motivated by the high number of service members and veterans with a history of traumatic brain injury (TBI), which is strongly associated with tinnitus.¹² The PTM level 3 skills education was administered to participants individually over the telephone by both an audiologist and a psychologist. Participants, located all over the U.S., had bothersome tinnitus, and some had experienced ≥ 1 TBI. They were randomized to receive either Tele-PTM immediately for 6 months or to be put on a 6-month wait list. The Tele-PTM group showed much greater improvement than that of the wait-list group.

Both of these recent RCTs have validated the effectiveness of PTM and demonstrated that PTM should be considered for the practice of evidence-based tinnitus management. PTM is mostly consistent with the AAO-HNSF CPG and provides a structured and defined framework for implementing both assessment and intervention services for patients who report tinnitus. As such, VA Central Office has endorsed PTM as an effective intervention for tinnitus management and has recommended its use at VAMCs. The NCRAR researchers have provided PTM training to hundreds of VA audiologists and MH providers, yet the level of implementation across the VA system of care varies widely.

VA Survey

In 2015, in partnership with the VA Offices of Audiology and Speech Pathology and Mental Health Services, and the Health Services Research & Development/Quality Enhancement Research Initiative (HSR&D/QUERI), the NCRAR conducted a study to examine PTM variation across sites via surveys and/or interviews of VA Audiology and MH programs nationwide.^13,14 The objectives of this study were to: (1) describe current tinnitus-management practices in VAMCs; (2) identify barriers and facilitators to PTM program implementation based on clinics that have fully, partially, or not implemented PTM; and (3) determine readiness to implement PTM within VISN 20 (Northwest states and Alaska).

Clinicians at VAMCs nationwide were surveyed regarding current provision of tinnitus clinical services. Requests were sent to audiology programs and MH programs at 142 major VAMCs along with instructions to complete the online survey. Responses were received from 87 audiologists and 66 MH providers. Clinicians at VAMCs with full PTM, partial PTM, and no-PTM (based on survey results) were then interviewed regarding site-specific barriers and facilitators to implementing and providing PTM, readiness to adopt PTM, and strategies for full PTM implementation.

Key findings from the study demonstrated the following: (1) There is considerable between-site variability in how PTM is implemented, particularly with the delivery of the MH portion of the protocol; (2) audiologists show higher levels of readiness to provide tinnitus services than do MH providers (7% of MH survey respondents vs 62% of audiologists reported their site implementing PTM); (3) 66% of MH survey respondents were interested in receiving training in tinnitus management (note that online PTM training for MH does not yet exist); (4) PTM implementation barriers include audio-visual technology issues, room scheduling, as well as lack of collaboration and colocation between MH and audiology departments, administrative time/support, group facilitator skills, and availability of PTM materials.

Overall, results of this HSR&D/QUERI-funded study suggested the need to develop MH-specific training to support the necessary interdisciplinary engagement. Although a patient workbook is available to order and visual presentation aids may be accessed online, it became clear that lack of MH participation in the inherently interdisciplinary PTM skills education was the most common deviation from PTM.

DoD an VA Questionnaire

In 2014 the DoD Hearing Center of Excellence (HCE) conducted the DoD and VA Tinnitus Evaluation, Management, and Treatment Assessment.¹³ The HCE conducted this questionnaire under the Tinnitus Care Quality Improvement, Process Development, and Implementation Plan, to develop, establish, and implement an interdisciplinary and ongoing process to continually assess and improve the quality and continuum of tinnitus care delivered to service members and veterans at a consistent, enterprise-wide level. The HCE developed the questionnaire to: (1) identify DoD and VA audiologists and otolaryngologists and their institutions providing comprehensive tinnitus care; (2) assess current tinnitus evaluation and management/treatment protocols used; (3) disseminate common practice improvements to all providers for enhancing overall tinnitus evaluation and management/treatment; and (4) evaluate implementation of improvements to include efficiency of implementation and efficacy of improvements.

The questionnaire was administered using SurveyMonkey (San Mateo, CA) and was disseminated by the otolaryngology and audiology consultants to the Army, Navy, and Air Force surgeons general and specialty leaders as well as through VA specialty leaders. Also, the HCE posted the link for the questionnaire on its website for 11 months. A total of 200 providers responded to the questionnaire, of which 13 did not indicate their specialty (eg, otolaryngology) or classification (eg, DoD active duty) and were excluded from data analysis. The 187 qualified respondents included 66 DoD audiologists, 120 VA audiologists, and 1 DoD otolaryngologist.

The questionnaire results indicated that DoD and VA respondents provided tinnitus services for their patients at similar rates (72% of DoD providers and 79% of VA providers). The use of PTM by those same providers, however, was far more widespread in VA (66%) than it was in DoD (37%). Of the providers indicating they did not offer tinnitus clinical services, the main reasons given were lack of necessary training/expertise, lack of time, and insufficient clinical support. The majority of respondents indicated they had training on tinnitus evaluation and/or management and that they were comfortable providing these services; despite this, most providers indicated a need or desire for tinnitus-specific training and education. These results suggested that more support and education for hearing health care providers were needed to implement PTM in VA and, especially, in DoD.

About half of the respondents indicated that psychological/behavioral treatment services, which would correspond to PTM levels 3 and 5, are available for patients at their facility who have tinnitus. It is encouraging to know that some patients with problematic tinnitus are receiving MH services. However, it is essential that patients with any degree of bothersome tinnitus have access to evidence-based clinical services, which would require CBT delivered by a qualified MH provider.

Conclusion

Numerous VA and DoD clinics have begun providing PTM. Individual sites, however, typically adapt the program during the process of implementation.^13,14 The most common adaptation that sites make to PTM is to proceed with level 3 skills education without the assistance of MH, and thus CBT, due to the lack of provider availability. It is unknown what impact this has on the effectiveness of PTM. Skills education forms the heart of PTM and addresses the needs of the majority of patients who seek intervention.

Collaboration with MH is integral to the delivery of PTM. Mental health providers partner in PTM levels 3 and 5 by providing CBT, which has the strongest evidence for reducing tinnitus distress among all interventions and always will be critical to the provision of PTM. Clearly VA MH programs need to increase involvement in veterans’ tinnitus management. Increased involvement may be accomplished by (1) developing training or other materials that increase understanding of MH’s role in addressing tinnitus; (2) developing pathways for coordination of care between audiology and MH providers, including different models of coordination based on individual site needs; and (3) documenting the prevalence of tinnitus-MH comorbidities to empirically justify the need for such coordination between audiology and MH providers.

To address gaps identified in the VA survey and in a similar questionnaire conducted by HCE regarding tinnitus care in VA and DoD, the NCRAR, HCE, and Walter Reed National Military Medical Center are collaborating on several initiatives to improve tinnitus services for service members and veterans.^13-15 These efforts include enhancing service member and veteran access to VA and DoD MH services in PTM.

Hearing loss and tinnitus (ringing or other noises in the ears or head) have been problematic for military service members and veterans for many years. Military personnel are exposed to high levels of noise in operational and training settings. In spite of hearing conservation efforts, hearing loss and auditory injuries (including tinnitus) continue to occur. Although current military leadership teaches the importance of hearing protection, that was not usually the case until the past few decades. Military leadership provides the means for hearing protection and monitors risk through conservation and hearing readiness programs. Unfortunately, the need for hearing during battle often overrides the expediency of using hearing protective devices.

Military members often equate hearing protection with increased vulnerability, widening the gap between preventive efforts and hearing preservation. It is therefore not surprising that tinnitus and hearing loss have been the 2 most common service-connected disabilities for veterans for a decade.¹ These conditions are irreversible; affected service members and veterans need strategies to cope with distress associated with these chronic conditions. Clinical care often is essential to manage the associated distress and mental health (MH) symptoms, such as sleep disturbance, irritability, isolation, tension, and low mood.

There is no cure for tinnitus, meaning there is no proven method to permanently eliminate or even reduce the perception of tinnitus. Intervention for tinnitus therefore is limited to methods intended to mitigate reactions to tinnitus, with the ultimate goal to facilitate good quality of life in spite of the perception of this unwanted auditory anomaly. These methods include numerous means of utilizing therapeutic sound.² Sound therapy, however, has been shown in controlled trials to be effective only when accompanied by counseling, which often focuses on teaching different coping skills.³ In such instances, MH providers can become an integral part of the hearing health team to assist patients in the management of their tinnitus.

Evidence-Based Practice

Evidence-based research should guide clinical services that are offered for tinnitus. Randomized controlled trials (RCTs) comprise the most important source for such evidence.⁴ Cochrane Reviews uses meta-analyses to examine rigorous RCTs to determine which methods have credible evidence. One of these reviews conducted in 2007 and updated in 2010 concluded that cognitive behavioral therapy (CBT) can improve depression scores and reduce distress for many people with bothersome tinnitus.^5,6 Another Cochrane Review concluded that sound therapy combined with counseling can be beneficial, but on its own, sound therapy has not been shown to result in significant benefit.³ Yet another Cochrane Review focused on using hearing aids with patients who have both hearing loss and bothersome tinnitus; the researchers concluded that “there is currently no evidence to support or refute their use as a more routine intervention for tinnitus.”⁷ However, many patients and clinicians report hearing aids are helpful for coping with tinnitus.

The American Academy of Otolaryngology–Head and Neck Surgery Foundation (AAO-HNSF) published a clinical practice guideline (CPG) for the management of tinnitus.⁸ Developing the CPG involved a comprehensive evaluation of the peer-reviewed literature, including the available Cochrane Reviews, to identify appropriate RCTs to inform evidence-based recommendations. Cognitive behavioral therapy was the only intervention for tinnitus recommended in the CPG. Cognitive behavioral therapy targets emotional response by identifying behaviors, thoughts, and beliefs that may be altered.⁹ For tinnitus, CBT typically includes stress management including relaxation exercises, purposeful distraction, and changing how individuals view and appraise their tinnitus.

Both the CPG and Cochrane Reviews concluded that CBT has the strongest evidence base for reducing effects of tinnitus. It should be noted that the CPG recommended teaching patients basic information about tinnitus management and stated that it was optional (due to limited research evidence) to use sound therapy to augment coping skills training.

Progressive Tinnitus Management

Tinnitus research at the VA National Center for Rehabilitative Auditory Research (NCRAR) has led to the development and refinement of an interdisciplinary program called Progressive Tinnitus Management (PTM). Audiologists and MH providers work together to deliver portions of the protocol. In addition, otolaryngologists are important for patients requiring a medical examination. Audiologists, MH providers, and otolaryngologists comprise the hearing health team for tinnitus management. The PTM program involves 5 stepped-care levels of management, and patients receive only the levels they need.

Level 1 is the referral level, which specifies guidelines for any clinician who encounters patients experiencing tinnitus. The “standard” referral is to audiology for a hearing evaluation (PTM level 2)—every patient reporting tinnitus should have a hearing evaluation and brief tinnitus assessment. Less typical would be an urgent referral to a different provider for certain symptoms such as referral to ENT for sudden hearing loss.

Patients who desire intervention for bothersome tinnitus are offered PTM skills education (level 3). At this level, patients are taught facts and skills that they need to self-manage their tinnitus-related problems. Ideally, the audiologist and MH provider collaborate to deliver the level 3 intervention, which utilizes a 5-session (2 with an audiologist and 3 with a MH provider) problem-solving method. Audiologists explain different forms of sound therapy, and MH providers deliver brief CBT. The research studies and clinics that use PTM have shown that the majority of patients who receive the level 3 skills education interventions have their tinnitus needs met to the degree that they do not desire further services.

Those relatively few patients who desire further services are invited for a PTM interdisciplinary evaluation (level 4), which involves a more in-depth needs evaluation by both an audiologist and a MH provider. Based on the outcome of the level 4 evaluation, clear treatment goals are discussed with the patient. If the patient and providers mutually agree that further intervention is needed, then the patient is offered PTM individualized support (level 5), which involves one-on-one services by an audiologist and/or a MH provider. The providers then build on the lessons taught during level 3 and address barriers to enacting the already discussed skills. The MH provider also may expand on CBT skills that were provided in level 3, offering care such as CBT for insomnia during level 5, depending on the specific needs and desires of the patient.

At the NCRAR, a pilot study and 2 RCTs of PTM have been completed.¹⁰ The first of these 2 RCTs was a clinical effectiveness study of PTM that was conducted in 2 VA audiology clinics: Memphis, Tennessee, and West Haven, Connecticut.¹¹ Patients who came to the clinics signed up for the study if they felt that the PTM level 3 intervention might be helpful. Half of the 300 veterans in the study were enrolled to receive PTM right away, and half were put on a 6-month wait list. The PTM group showed significantly greater benefit than that of the wait-list group.

The second RCT of PTM was motivated by the high number of service members and veterans with a history of traumatic brain injury (TBI), which is strongly associated with tinnitus.¹² The PTM level 3 skills education was administered to participants individually over the telephone by both an audiologist and a psychologist. Participants, located all over the U.S., had bothersome tinnitus, and some had experienced ≥ 1 TBI. They were randomized to receive either Tele-PTM immediately for 6 months or to be put on a 6-month wait list. The Tele-PTM group showed much greater improvement than that of the wait-list group.

Both of these recent RCTs have validated the effectiveness of PTM and demonstrated that PTM should be considered for the practice of evidence-based tinnitus management. PTM is mostly consistent with the AAO-HNSF CPG and provides a structured and defined framework for implementing both assessment and intervention services for patients who report tinnitus. As such, VA Central Office has endorsed PTM as an effective intervention for tinnitus management and has recommended its use at VAMCs. The NCRAR researchers have provided PTM training to hundreds of VA audiologists and MH providers, yet the level of implementation across the VA system of care varies widely.

VA Survey

In 2015, in partnership with the VA Offices of Audiology and Speech Pathology and Mental Health Services, and the Health Services Research & Development/Quality Enhancement Research Initiative (HSR&D/QUERI), the NCRAR conducted a study to examine PTM variation across sites via surveys and/or interviews of VA Audiology and MH programs nationwide.^13,14 The objectives of this study were to: (1) describe current tinnitus-management practices in VAMCs; (2) identify barriers and facilitators to PTM program implementation based on clinics that have fully, partially, or not implemented PTM; and (3) determine readiness to implement PTM within VISN 20 (Northwest states and Alaska).

Clinicians at VAMCs nationwide were surveyed regarding current provision of tinnitus clinical services. Requests were sent to audiology programs and MH programs at 142 major VAMCs along with instructions to complete the online survey. Responses were received from 87 audiologists and 66 MH providers. Clinicians at VAMCs with full PTM, partial PTM, and no-PTM (based on survey results) were then interviewed regarding site-specific barriers and facilitators to implementing and providing PTM, readiness to adopt PTM, and strategies for full PTM implementation.

Key findings from the study demonstrated the following: (1) There is considerable between-site variability in how PTM is implemented, particularly with the delivery of the MH portion of the protocol; (2) audiologists show higher levels of readiness to provide tinnitus services than do MH providers (7% of MH survey respondents vs 62% of audiologists reported their site implementing PTM); (3) 66% of MH survey respondents were interested in receiving training in tinnitus management (note that online PTM training for MH does not yet exist); (4) PTM implementation barriers include audio-visual technology issues, room scheduling, as well as lack of collaboration and colocation between MH and audiology departments, administrative time/support, group facilitator skills, and availability of PTM materials.

Overall, results of this HSR&D/QUERI-funded study suggested the need to develop MH-specific training to support the necessary interdisciplinary engagement. Although a patient workbook is available to order and visual presentation aids may be accessed online, it became clear that lack of MH participation in the inherently interdisciplinary PTM skills education was the most common deviation from PTM.

DoD an VA Questionnaire

In 2014 the DoD Hearing Center of Excellence (HCE) conducted the DoD and VA Tinnitus Evaluation, Management, and Treatment Assessment.¹³ The HCE conducted this questionnaire under the Tinnitus Care Quality Improvement, Process Development, and Implementation Plan, to develop, establish, and implement an interdisciplinary and ongoing process to continually assess and improve the quality and continuum of tinnitus care delivered to service members and veterans at a consistent, enterprise-wide level. The HCE developed the questionnaire to: (1) identify DoD and VA audiologists and otolaryngologists and their institutions providing comprehensive tinnitus care; (2) assess current tinnitus evaluation and management/treatment protocols used; (3) disseminate common practice improvements to all providers for enhancing overall tinnitus evaluation and management/treatment; and (4) evaluate implementation of improvements to include efficiency of implementation and efficacy of improvements.

The questionnaire was administered using SurveyMonkey (San Mateo, CA) and was disseminated by the otolaryngology and audiology consultants to the Army, Navy, and Air Force surgeons general and specialty leaders as well as through VA specialty leaders. Also, the HCE posted the link for the questionnaire on its website for 11 months. A total of 200 providers responded to the questionnaire, of which 13 did not indicate their specialty (eg, otolaryngology) or classification (eg, DoD active duty) and were excluded from data analysis. The 187 qualified respondents included 66 DoD audiologists, 120 VA audiologists, and 1 DoD otolaryngologist.

The questionnaire results indicated that DoD and VA respondents provided tinnitus services for their patients at similar rates (72% of DoD providers and 79% of VA providers). The use of PTM by those same providers, however, was far more widespread in VA (66%) than it was in DoD (37%). Of the providers indicating they did not offer tinnitus clinical services, the main reasons given were lack of necessary training/expertise, lack of time, and insufficient clinical support. The majority of respondents indicated they had training on tinnitus evaluation and/or management and that they were comfortable providing these services; despite this, most providers indicated a need or desire for tinnitus-specific training and education. These results suggested that more support and education for hearing health care providers were needed to implement PTM in VA and, especially, in DoD.

About half of the respondents indicated that psychological/behavioral treatment services, which would correspond to PTM levels 3 and 5, are available for patients at their facility who have tinnitus. It is encouraging to know that some patients with problematic tinnitus are receiving MH services. However, it is essential that patients with any degree of bothersome tinnitus have access to evidence-based clinical services, which would require CBT delivered by a qualified MH provider.

Conclusion

Numerous VA and DoD clinics have begun providing PTM. Individual sites, however, typically adapt the program during the process of implementation.^13,14 The most common adaptation that sites make to PTM is to proceed with level 3 skills education without the assistance of MH, and thus CBT, due to the lack of provider availability. It is unknown what impact this has on the effectiveness of PTM. Skills education forms the heart of PTM and addresses the needs of the majority of patients who seek intervention.

Collaboration with MH is integral to the delivery of PTM. Mental health providers partner in PTM levels 3 and 5 by providing CBT, which has the strongest evidence for reducing tinnitus distress among all interventions and always will be critical to the provision of PTM. Clearly VA MH programs need to increase involvement in veterans’ tinnitus management. Increased involvement may be accomplished by (1) developing training or other materials that increase understanding of MH’s role in addressing tinnitus; (2) developing pathways for coordination of care between audiology and MH providers, including different models of coordination based on individual site needs; and (3) documenting the prevalence of tinnitus-MH comorbidities to empirically justify the need for such coordination between audiology and MH providers.

To address gaps identified in the VA survey and in a similar questionnaire conducted by HCE regarding tinnitus care in VA and DoD, the NCRAR, HCE, and Walter Reed National Military Medical Center are collaborating on several initiatives to improve tinnitus services for service members and veterans.^13-15 These efforts include enhancing service member and veteran access to VA and DoD MH services in PTM.

Photo by Chad McNeeley

Results of a phase 3 trial revealed similar outcomes in patients who underwent allogeneic hematopoietic stem cell transplant (HSCT) to treat myelodysplastic syndromes (MDS), regardless of the conditioning regimen they received.

Rates of engraftment, graft-vs-host disease (GVHD), relapse, and survival were similar between patients who received reduced-intensity conditioning (RIC) and those who received standard myeloablative conditioning (MAC) before HSCT.

Researchers reported these results in the Journal of Clinical Oncology.

“Our study shed new light on expected benefits of a reduced-intensity conditioning regimen that can be offered as a curative treatment approach, especially in older patients with MDS,” said study author Nicolaus Kröger, MD, of University Hospital Eppendorf in Hamburg, Germany.

Patient characteristics

The study, known as RICMAC, involved 129 patients who underwent HSCT between May 2004 and December 2012 at 18 transplant units in 7 countries.

Patients were randomized in a 1:1 ratio to RIC (n=65) or MAC (n=64) and were stratified according to donor type, age, and blast count.

The median age was 50 (range, 19-64) in the MAC arm and 51 (range, 22-63) in the RIC arm. The median blast percentage was 4% (range, 0-18) and 5% (range, 0-18), respectively.

According to IPSS, most patients in both arms had intermediate-I-risk disease (28 MAC, 25 RIC) or intermediate-II-risk disease (18 MAC, 24 RIC).

Similar numbers of patients in each arm had low cytogenetic risk (24 MAC, 28 RIC), intermediate cytogenetic risk (17 MAC, 13 RIC), and high cytogenetic risk (17 MAC, 18 RIC).

Thirty-three patients in the MAC arm and 32 in the RIC arm received ATG as GVHD prophylaxis.

Patients received grafts from matched related donors (17 MAC, 16 RIC), matched unrelated donors (36 MAC, 38 RIC), or mismatched related/unrelated donors (11 in both arms).

Most patients received peripheral blood stem cell grafts—61 in the MAC arm and 59 in the RIC arm.

Results

The researchers said engraftment was comparable between the arms. There were 4 graft failures in the MAC arm and 3 in the RIC arm (P=0.72). The median time to leukocyte engraftment was 15 days in both arms. The median time to platelet engraftment was 15 days in the RIC arm and 16 in the MAC arm (P=0.33).

There was no significant difference in the cumulative incidence of GVHD between the RIC and MAC arms:

• Grade 2-4 acute GVHD—32.3% and 37.5%, respectively
• Grade 3-4 acute GVHD—15% and 14%, respectively (P=0.35 for between-arm difference for all acute GVHD)
• Chronic GVHD—61.6% and 64.7%, respectively (P=0.76).

Though the occurrence of infection was similar between the MAC and RIC arms (48 and 44, respectively), the rate of infection was higher in the MAC arm than the RIC arm.

The rate of infection in the first 100 days was 6.9 per 100 person-years in the MAC arm and 4.3 in the RIC arm (P=0.002). The rate of infection during the total follow-up was 2.0 per 100 person-years in the MAC arm and 1.4 in the RIC arm (P=0.002).

There was no significant difference between the RIC and MAC arms with regard to the cumulative incidence of nonrelapse mortality after 1 year—16.9% and 25.3%, respectively (P=0.29).

And there was no significant difference in the cumulative incidence of relapse at 2 years—17% and 14.8%, respectively (P=0.6).

The 2-year relapse-free survival rate was similar in the MAC and RIC arms—58.3% and 62.4% (P=0.58)—as was the 2-year overall survival rate—63.2% and 76.3%, respectively (P=0.08). 

Photo by Chad McNeeley

Results of a phase 3 trial revealed similar outcomes in patients who underwent allogeneic hematopoietic stem cell transplant (HSCT) to treat myelodysplastic syndromes (MDS), regardless of the conditioning regimen they received.

Rates of engraftment, graft-vs-host disease (GVHD), relapse, and survival were similar between patients who received reduced-intensity conditioning (RIC) and those who received standard myeloablative conditioning (MAC) before HSCT.

Researchers reported these results in the Journal of Clinical Oncology.

“Our study shed new light on expected benefits of a reduced-intensity conditioning regimen that can be offered as a curative treatment approach, especially in older patients with MDS,” said study author Nicolaus Kröger, MD, of University Hospital Eppendorf in Hamburg, Germany.

Patient characteristics

The study, known as RICMAC, involved 129 patients who underwent HSCT between May 2004 and December 2012 at 18 transplant units in 7 countries.

Patients were randomized in a 1:1 ratio to RIC (n=65) or MAC (n=64) and were stratified according to donor type, age, and blast count.

The median age was 50 (range, 19-64) in the MAC arm and 51 (range, 22-63) in the RIC arm. The median blast percentage was 4% (range, 0-18) and 5% (range, 0-18), respectively.

According to IPSS, most patients in both arms had intermediate-I-risk disease (28 MAC, 25 RIC) or intermediate-II-risk disease (18 MAC, 24 RIC).

Similar numbers of patients in each arm had low cytogenetic risk (24 MAC, 28 RIC), intermediate cytogenetic risk (17 MAC, 13 RIC), and high cytogenetic risk (17 MAC, 18 RIC).

Thirty-three patients in the MAC arm and 32 in the RIC arm received ATG as GVHD prophylaxis.

Patients received grafts from matched related donors (17 MAC, 16 RIC), matched unrelated donors (36 MAC, 38 RIC), or mismatched related/unrelated donors (11 in both arms).

Most patients received peripheral blood stem cell grafts—61 in the MAC arm and 59 in the RIC arm.

Results

The researchers said engraftment was comparable between the arms. There were 4 graft failures in the MAC arm and 3 in the RIC arm (P=0.72). The median time to leukocyte engraftment was 15 days in both arms. The median time to platelet engraftment was 15 days in the RIC arm and 16 in the MAC arm (P=0.33).

There was no significant difference in the cumulative incidence of GVHD between the RIC and MAC arms:

• Grade 2-4 acute GVHD—32.3% and 37.5%, respectively
• Grade 3-4 acute GVHD—15% and 14%, respectively (P=0.35 for between-arm difference for all acute GVHD)
• Chronic GVHD—61.6% and 64.7%, respectively (P=0.76).

Though the occurrence of infection was similar between the MAC and RIC arms (48 and 44, respectively), the rate of infection was higher in the MAC arm than the RIC arm.

The rate of infection in the first 100 days was 6.9 per 100 person-years in the MAC arm and 4.3 in the RIC arm (P=0.002). The rate of infection during the total follow-up was 2.0 per 100 person-years in the MAC arm and 1.4 in the RIC arm (P=0.002).

There was no significant difference between the RIC and MAC arms with regard to the cumulative incidence of nonrelapse mortality after 1 year—16.9% and 25.3%, respectively (P=0.29).

And there was no significant difference in the cumulative incidence of relapse at 2 years—17% and 14.8%, respectively (P=0.6).

The 2-year relapse-free survival rate was similar in the MAC and RIC arms—58.3% and 62.4% (P=0.58)—as was the 2-year overall survival rate—63.2% and 76.3%, respectively (P=0.08). 

Photo by Chad McNeeley

Results of a phase 3 trial revealed similar outcomes in patients who underwent allogeneic hematopoietic stem cell transplant (HSCT) to treat myelodysplastic syndromes (MDS), regardless of the conditioning regimen they received.

Rates of engraftment, graft-vs-host disease (GVHD), relapse, and survival were similar between patients who received reduced-intensity conditioning (RIC) and those who received standard myeloablative conditioning (MAC) before HSCT.

Researchers reported these results in the Journal of Clinical Oncology.

“Our study shed new light on expected benefits of a reduced-intensity conditioning regimen that can be offered as a curative treatment approach, especially in older patients with MDS,” said study author Nicolaus Kröger, MD, of University Hospital Eppendorf in Hamburg, Germany.

Patient characteristics

The study, known as RICMAC, involved 129 patients who underwent HSCT between May 2004 and December 2012 at 18 transplant units in 7 countries.

Patients were randomized in a 1:1 ratio to RIC (n=65) or MAC (n=64) and were stratified according to donor type, age, and blast count.

The median age was 50 (range, 19-64) in the MAC arm and 51 (range, 22-63) in the RIC arm. The median blast percentage was 4% (range, 0-18) and 5% (range, 0-18), respectively.

According to IPSS, most patients in both arms had intermediate-I-risk disease (28 MAC, 25 RIC) or intermediate-II-risk disease (18 MAC, 24 RIC).

Similar numbers of patients in each arm had low cytogenetic risk (24 MAC, 28 RIC), intermediate cytogenetic risk (17 MAC, 13 RIC), and high cytogenetic risk (17 MAC, 18 RIC).

Thirty-three patients in the MAC arm and 32 in the RIC arm received ATG as GVHD prophylaxis.

Patients received grafts from matched related donors (17 MAC, 16 RIC), matched unrelated donors (36 MAC, 38 RIC), or mismatched related/unrelated donors (11 in both arms).

Most patients received peripheral blood stem cell grafts—61 in the MAC arm and 59 in the RIC arm.

Results

The researchers said engraftment was comparable between the arms. There were 4 graft failures in the MAC arm and 3 in the RIC arm (P=0.72). The median time to leukocyte engraftment was 15 days in both arms. The median time to platelet engraftment was 15 days in the RIC arm and 16 in the MAC arm (P=0.33).

There was no significant difference in the cumulative incidence of GVHD between the RIC and MAC arms:

• Grade 2-4 acute GVHD—32.3% and 37.5%, respectively
• Grade 3-4 acute GVHD—15% and 14%, respectively (P=0.35 for between-arm difference for all acute GVHD)
• Chronic GVHD—61.6% and 64.7%, respectively (P=0.76).

Though the occurrence of infection was similar between the MAC and RIC arms (48 and 44, respectively), the rate of infection was higher in the MAC arm than the RIC arm.

The rate of infection in the first 100 days was 6.9 per 100 person-years in the MAC arm and 4.3 in the RIC arm (P=0.002). The rate of infection during the total follow-up was 2.0 per 100 person-years in the MAC arm and 1.4 in the RIC arm (P=0.002).

There was no significant difference between the RIC and MAC arms with regard to the cumulative incidence of nonrelapse mortality after 1 year—16.9% and 25.3%, respectively (P=0.29).

And there was no significant difference in the cumulative incidence of relapse at 2 years—17% and 14.8%, respectively (P=0.6).

The 2-year relapse-free survival rate was similar in the MAC and RIC arms—58.3% and 62.4% (P=0.58)—as was the 2-year overall survival rate—63.2% and 76.3%, respectively (P=0.08). 

General Medical Sciences

The US Food and Drug Administration (FDA) has granted orphan drug designation for SB-525 as a treatment for hemophilia A.

SB-525 is a recombinant adeno-associated virus 2/6 (AAV2/6) vector that expresses a human F8 complementary DNA (cDNA) cassette.

The vector encodes a liver-specific promoter module, and AAV2/6 exhibits liver tropism.

This provides the potential for long-term hepatic production of factor VIII in patients with hemophilia A, according to Sangamo Therapeutics, Inc., the company developing SB-525.

In research presented at the 2016 ASH Annual Meeting (abstract 1173), SB-525 induced the expression of significant levels of human factor VIII in mice and non-human primates (NHPs). SB-525 also corrected the bleeding defect in a mouse model of hemophilia A.

Dosing studies in NHPs demonstrated a robust and reproducible dose response curve, according to researchers. In these animals, mean human factor VIII levels ranged from 5% of normal at the lowest dose to 230% at the highest (AAV doses in the 6 x 10¹¹ – 6 x 10¹² vgs/kg range).

The researchers said the peak circulating human factor VIII levels in these experiments exceeded levels previously reported in NHPs. And this could significantly reduce the dose required to achieve therapeutically relevant levels in human subjects.

Sangamo is planning to open a phase 1/2 trial of SB-525 in adults with hemophilia A later this quarter.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved. 

General Medical Sciences

The US Food and Drug Administration (FDA) has granted orphan drug designation for SB-525 as a treatment for hemophilia A.

SB-525 is a recombinant adeno-associated virus 2/6 (AAV2/6) vector that expresses a human F8 complementary DNA (cDNA) cassette.

The vector encodes a liver-specific promoter module, and AAV2/6 exhibits liver tropism.

This provides the potential for long-term hepatic production of factor VIII in patients with hemophilia A, according to Sangamo Therapeutics, Inc., the company developing SB-525.

In research presented at the 2016 ASH Annual Meeting (abstract 1173), SB-525 induced the expression of significant levels of human factor VIII in mice and non-human primates (NHPs). SB-525 also corrected the bleeding defect in a mouse model of hemophilia A.

Dosing studies in NHPs demonstrated a robust and reproducible dose response curve, according to researchers. In these animals, mean human factor VIII levels ranged from 5% of normal at the lowest dose to 230% at the highest (AAV doses in the 6 x 10¹¹ – 6 x 10¹² vgs/kg range).

The researchers said the peak circulating human factor VIII levels in these experiments exceeded levels previously reported in NHPs. And this could significantly reduce the dose required to achieve therapeutically relevant levels in human subjects.

Sangamo is planning to open a phase 1/2 trial of SB-525 in adults with hemophilia A later this quarter.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved. 

General Medical Sciences

The US Food and Drug Administration (FDA) has granted orphan drug designation for SB-525 as a treatment for hemophilia A.

SB-525 is a recombinant adeno-associated virus 2/6 (AAV2/6) vector that expresses a human F8 complementary DNA (cDNA) cassette.

The vector encodes a liver-specific promoter module, and AAV2/6 exhibits liver tropism.

This provides the potential for long-term hepatic production of factor VIII in patients with hemophilia A, according to Sangamo Therapeutics, Inc., the company developing SB-525.

In research presented at the 2016 ASH Annual Meeting (abstract 1173), SB-525 induced the expression of significant levels of human factor VIII in mice and non-human primates (NHPs). SB-525 also corrected the bleeding defect in a mouse model of hemophilia A.

Dosing studies in NHPs demonstrated a robust and reproducible dose response curve, according to researchers. In these animals, mean human factor VIII levels ranged from 5% of normal at the lowest dose to 230% at the highest (AAV doses in the 6 x 10¹¹ – 6 x 10¹² vgs/kg range).

The researchers said the peak circulating human factor VIII levels in these experiments exceeded levels previously reported in NHPs. And this could significantly reduce the dose required to achieve therapeutically relevant levels in human subjects.

Sangamo is planning to open a phase 1/2 trial of SB-525 in adults with hemophilia A later this quarter.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved. 

Image by Spencer Phillips

The US Food and Drug Administration (FDA) has granted fast track designation to SB-FIX for the treatment of hemophilia B.

SB-FIX is a zinc finger nuclease (ZFN)-mediated genome-editing product candidate.

It is designed to be used as a one-time treatment that will provide stable, continuous production of factor IX (FIX) for the lifetime of the patient.

The ZFN-mediated in vivo genome-editing approach makes use of the albumin gene locus, a highly expressing and liver-specific genomic “safe-harbor site,” that can be edited with ZFNs to accept and express therapeutic genes.

The approach is designed to enable the patient’s liver to permanently produce circulating therapeutic levels of a corrective protein product.

This differs from conventional adeno-associated virus complementary DNA gene therapy approaches, which are non-integrating and may “wash out” of the liver as cells divide and turn over.

Sangamo Therapeutics, Inc., the company developing SB-FIX, has initiated a phase 1/2 trial of SB-FIX in adults with hemophilia B. The trial is open, and subjects are being screened for enrollment.

In addition to fast track designation, SB-FIX has orphan designation from the FDA (granted in 2016).

About fast track designation

The FDA’s fast track program is designed to facilitate the development and expedite the review of products intended to treat or prevent serious or life-threatening conditions and address unmet medical need.

Through the fast track program, a product may be eligible for priority review. In addition, the company developing the product may be allowed to submit sections of the new drug application or biologic license application on a rolling basis as data become available.

Fast track designation also provides the company with opportunities for more frequent meetings and written communications with the FDA.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved. 

Image by Spencer Phillips

The US Food and Drug Administration (FDA) has granted fast track designation to SB-FIX for the treatment of hemophilia B.

SB-FIX is a zinc finger nuclease (ZFN)-mediated genome-editing product candidate.

It is designed to be used as a one-time treatment that will provide stable, continuous production of factor IX (FIX) for the lifetime of the patient.

The ZFN-mediated in vivo genome-editing approach makes use of the albumin gene locus, a highly expressing and liver-specific genomic “safe-harbor site,” that can be edited with ZFNs to accept and express therapeutic genes.

The approach is designed to enable the patient’s liver to permanently produce circulating therapeutic levels of a corrective protein product.

This differs from conventional adeno-associated virus complementary DNA gene therapy approaches, which are non-integrating and may “wash out” of the liver as cells divide and turn over.

Sangamo Therapeutics, Inc., the company developing SB-FIX, has initiated a phase 1/2 trial of SB-FIX in adults with hemophilia B. The trial is open, and subjects are being screened for enrollment.

In addition to fast track designation, SB-FIX has orphan designation from the FDA (granted in 2016).

About fast track designation

The FDA’s fast track program is designed to facilitate the development and expedite the review of products intended to treat or prevent serious or life-threatening conditions and address unmet medical need.

Through the fast track program, a product may be eligible for priority review. In addition, the company developing the product may be allowed to submit sections of the new drug application or biologic license application on a rolling basis as data become available.

Fast track designation also provides the company with opportunities for more frequent meetings and written communications with the FDA.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved. 

Image by Spencer Phillips

The US Food and Drug Administration (FDA) has granted fast track designation to SB-FIX for the treatment of hemophilia B.

SB-FIX is a zinc finger nuclease (ZFN)-mediated genome-editing product candidate.

It is designed to be used as a one-time treatment that will provide stable, continuous production of factor IX (FIX) for the lifetime of the patient.

The ZFN-mediated in vivo genome-editing approach makes use of the albumin gene locus, a highly expressing and liver-specific genomic “safe-harbor site,” that can be edited with ZFNs to accept and express therapeutic genes.

The approach is designed to enable the patient’s liver to permanently produce circulating therapeutic levels of a corrective protein product.

This differs from conventional adeno-associated virus complementary DNA gene therapy approaches, which are non-integrating and may “wash out” of the liver as cells divide and turn over.

Sangamo Therapeutics, Inc., the company developing SB-FIX, has initiated a phase 1/2 trial of SB-FIX in adults with hemophilia B. The trial is open, and subjects are being screened for enrollment.

In addition to fast track designation, SB-FIX has orphan designation from the FDA (granted in 2016).

About fast track designation

The FDA’s fast track program is designed to facilitate the development and expedite the review of products intended to treat or prevent serious or life-threatening conditions and address unmet medical need.

Through the fast track program, a product may be eligible for priority review. In addition, the company developing the product may be allowed to submit sections of the new drug application or biologic license application on a rolling basis as data become available.

Fast track designation also provides the company with opportunities for more frequent meetings and written communications with the FDA.

About orphan designation

The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved. 

Photo by George Hodan

Tablet-based, multimedia-enhanced medical training improves examination results among medical students and residents, according to research published in PLOS ONE.

“Ideally, medical training should be taking place at the patient’s bedside rather than in lecture halls,” said study author Daniel C. Baumgart, MD, PhD, of Charité Medical School at Humboldt-University of Berlin in Germany.

“Communication devices, such as tablet computers, digital assistants, and smartphones, make medical data and learning materials available anywhere and anytime. Therefore, our aim was to study the impact of a systematic integration of such devices into medical teaching and training.”

The researchers studied 55 final-year medical students and medical residents doing an inpatient service rotation. The subjects were assigned to receive a tablet personal computer (PC) with a custom multimedia education software package (n=24) or to a control group (n=31).

The multimedia package tested included the Mobile Medical Educator software package (developed in-house) as well as other multimedia learning materials, such as eBooks, eJournals, slide kits, podcasts, videos, animations, image data, and the American College of Physicians’ validated self-assessment software.

The participants had to complete MKSAP® (medical knowledge self-assessment program) exams at the beginning and the end of their training rotations. The final MKSAP score was the study’s primary endpoint.

The mean MKSAP score improved in the tablet PC group but not the control group. The final mean score was significantly higher in the tablet PC group than the control group—59 and 48, respectively (P<0.001).

When the researchers adjusted their analysis for subjects’ baseline score and potential confounders, the tablet PC group had, on average, 11% better MKSAP test results than the control group (P<0.001).

“We were able to show improvements in internal medicine exam results, which were independent of socio-demographic factors,” Dr Baumgart said. “Participant feedback was particularly positive in relation to an integrated, fully digitized workflow for clinical practice and training.” 

Photo by George Hodan

Tablet-based, multimedia-enhanced medical training improves examination results among medical students and residents, according to research published in PLOS ONE.

“Ideally, medical training should be taking place at the patient’s bedside rather than in lecture halls,” said study author Daniel C. Baumgart, MD, PhD, of Charité Medical School at Humboldt-University of Berlin in Germany.

“Communication devices, such as tablet computers, digital assistants, and smartphones, make medical data and learning materials available anywhere and anytime. Therefore, our aim was to study the impact of a systematic integration of such devices into medical teaching and training.”

The researchers studied 55 final-year medical students and medical residents doing an inpatient service rotation. The subjects were assigned to receive a tablet personal computer (PC) with a custom multimedia education software package (n=24) or to a control group (n=31).

The multimedia package tested included the Mobile Medical Educator software package (developed in-house) as well as other multimedia learning materials, such as eBooks, eJournals, slide kits, podcasts, videos, animations, image data, and the American College of Physicians’ validated self-assessment software.

The participants had to complete MKSAP® (medical knowledge self-assessment program) exams at the beginning and the end of their training rotations. The final MKSAP score was the study’s primary endpoint.

The mean MKSAP score improved in the tablet PC group but not the control group. The final mean score was significantly higher in the tablet PC group than the control group—59 and 48, respectively (P<0.001).

When the researchers adjusted their analysis for subjects’ baseline score and potential confounders, the tablet PC group had, on average, 11% better MKSAP test results than the control group (P<0.001).

“We were able to show improvements in internal medicine exam results, which were independent of socio-demographic factors,” Dr Baumgart said. “Participant feedback was particularly positive in relation to an integrated, fully digitized workflow for clinical practice and training.” 

Photo by George Hodan

Tablet-based, multimedia-enhanced medical training improves examination results among medical students and residents, according to research published in PLOS ONE.

“Ideally, medical training should be taking place at the patient’s bedside rather than in lecture halls,” said study author Daniel C. Baumgart, MD, PhD, of Charité Medical School at Humboldt-University of Berlin in Germany.

“Communication devices, such as tablet computers, digital assistants, and smartphones, make medical data and learning materials available anywhere and anytime. Therefore, our aim was to study the impact of a systematic integration of such devices into medical teaching and training.”

The researchers studied 55 final-year medical students and medical residents doing an inpatient service rotation. The subjects were assigned to receive a tablet personal computer (PC) with a custom multimedia education software package (n=24) or to a control group (n=31).

The multimedia package tested included the Mobile Medical Educator software package (developed in-house) as well as other multimedia learning materials, such as eBooks, eJournals, slide kits, podcasts, videos, animations, image data, and the American College of Physicians’ validated self-assessment software.

The participants had to complete MKSAP® (medical knowledge self-assessment program) exams at the beginning and the end of their training rotations. The final MKSAP score was the study’s primary endpoint.

The mean MKSAP score improved in the tablet PC group but not the control group. The final mean score was significantly higher in the tablet PC group than the control group—59 and 48, respectively (P<0.001).

When the researchers adjusted their analysis for subjects’ baseline score and potential confounders, the tablet PC group had, on average, 11% better MKSAP test results than the control group (P<0.001).

“We were able to show improvements in internal medicine exam results, which were independent of socio-demographic factors,” Dr Baumgart said. “Participant feedback was particularly positive in relation to an integrated, fully digitized workflow for clinical practice and training.” 

Every additional day of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in hospitalized children was associated with a 50% increased risk of developing a complication, reported Rana F. Hamdy, MD, of Children’s National Health System, Washington, and her associates.

That was one of the findings of a study performed to determine the epidemiology, clinical outcomes, and risk factors for treatment failure in pediatric MRSA bacteremia. It took place in three hospitals, one each in Philadelphia, Baltimore, and Salt Lake City.

Courtesy U.S. National Institute of Allergy and Infectious Diseases

[email protected]

Every additional day of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in hospitalized children was associated with a 50% increased risk of developing a complication, reported Rana F. Hamdy, MD, of Children’s National Health System, Washington, and her associates.

That was one of the findings of a study performed to determine the epidemiology, clinical outcomes, and risk factors for treatment failure in pediatric MRSA bacteremia. It took place in three hospitals, one each in Philadelphia, Baltimore, and Salt Lake City.

Courtesy U.S. National Institute of Allergy and Infectious Diseases

[email protected]

Every additional day of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in hospitalized children was associated with a 50% increased risk of developing a complication, reported Rana F. Hamdy, MD, of Children’s National Health System, Washington, and her associates.

That was one of the findings of a study performed to determine the epidemiology, clinical outcomes, and risk factors for treatment failure in pediatric MRSA bacteremia. It took place in three hospitals, one each in Philadelphia, Baltimore, and Salt Lake City.

Courtesy U.S. National Institute of Allergy and Infectious Diseases

[email protected]

A 48-year-old man presents to your office for follow-up of right knee pain that has been bothering him for the past 12 months. He denies any trauma or inciting incident for the pain. On physical exam, he does not have crepitus but does have medial joint line tenderness of his right knee. An MRI shows a partial medial meniscal tear. Do you refer him to physical therapy (PT) or to orthopedics for arthroscopy and repair?

The meniscus—cartilage in the knee joint that provides support, stability, and lubrication to the joint during activity—can tear during a traumatic event or as a result of degeneration over time. Traumatic meniscal tears typically occur in those younger than 30 during sports (eg, basketball, soccer), whereas degenerative meniscal tears generally occur in patients ages 40 to 60.^2,3 The annual incidence of all meniscal tears is 79 per 100,000.⁴ While some clinicians can diagnose traumatic meniscal tears based on history and physical examination, degenerative meniscal tears are more challenging and typically warrant an MRI for confirmation.³

Meniscal tears can be treated either conservatively, with supportive care and exercise, or surgically. Unfortunately, there are no national orthopedic guidelines available to help direct care. In one observational study, 95 of 117 patients (81.2%) were generally satisfied with surgical treatment at four-year follow-up; satisfaction was higher among those with a traumatic meniscal tear than in those with a degenerative tear.⁵

Two systematic reviews of surgery versus nonoperative management or sham therapies found no additional benefit of surgery for meniscal tears in a variety of patients with and without osteoarthritis.^6,7 However, both studies were of only moderate quality, because of the number of patients in the nonoperative groups who ultimately underwent surgery. Neither of the studies directly compared surgery to nonoperative management.^6,7Another investigation—a multicenter, randomized, double-blind, sham-controlled study conducted in Finland involving 146 patients—compared sham surgery to arthroscopic partial meniscectomy. Both groups received instruction on performing post-procedure exercises, and both groups had similar and marked improvement in pain and function.⁸

Clinical practice recommendations devised from a vast systematic review of the literature recommend that the decision for surgery be based on patient-specific factors, such as symptoms, age, mechanism of tear, extent of damage, and occupational/social/activity needs.⁹

STUDY SUMMARY

Exercise is as good as surgery

The current superiority RCT compared exercise therapy to arthroscopic partial meniscectomy. Subjects (ages 35 to 60) presented to the orthopedic department of two hospitals in Norway with unilateral knee pain of more than two months’ duration and an MRI-delineated medial meniscal tear. They were included in the study only if they had radiographic evidence of minimal osteoarthritis (Kellgren-Lawrence classification grade ≤ 2). Exclusion criteria included acute trauma, locked knee, ligament injury, and knee surgery in the same knee within the previous two years.

The primary outcomes were change in patient-reported knee function (as determined by overall Knee injury and Osteoarthritis Outcome Score [KOOS] after two years) and thigh muscle strength at three months (as measured by physiotherapists). The researchers used four of the five KOOS subscales for this analysis: pain, other symptoms (swelling, grinding/noise from the joint, ability to straighten and bend), function in sports/recreation, and knee-related quality of life (QOL). The average score of each subscale was used.

Secondary outcomes included the five individual KOOS subscales (the four previously mentioned, plus activities of daily living [ADLs]), as well as thigh muscle strength and lower-extremity performance test results.

Methods. Testing personnel were blinded to group allocation; participants wore pants or neoprene sleeves to cover surgical scars. A total of 140 patients were randomized to either 12 weeks (24-36 sessions) of exercise therapy alone or a standardized arthroscopic partial meniscectomy; upon discharge, those in the latter group received written and oral encouragement to perform simple exercises at home, two to four times daily, to regain range of motion and reduce swelling.

Results. At two years, the overall mean improvement in KOOS4 score from baseline was similar between the exercise group and the meniscectomy group (25.3 pts vs 24.4 pts, respectively; mean difference [MD], 0.9). Additionally, muscle strength (measured as peak torque flexion and extension and total work flexion and extension) at both three and 12 months showed significant objective improvements favoring exercise therapy.

In the secondary analysis of the KOOS subscale scores, change from baseline was nonsignificant for four of the five (pain, ADL, sports/recreation, and QOL). Only the symptoms subscale had a significant difference favoring exercise therapy (MD, 5.3 pts); this was likely clinically insignificant on a grading scale of 0 to 100.

Of the patients allocated to exercise therapy alone, 19% crossed over and underwent surgery during the two-year study period.

WHAT’S NEW

Head-to-head comparison adds evidence

This is the first trial to directly compare exercise therapy to surgery in patients with meniscal tears. Interestingly, exercise therapy was as effective after a two-year follow-up period and was superior in the short term for thigh muscle strength.¹

The results of this study build on those from the aforementioned smaller study conducted in Finland.⁸ In that study, both groups received instruction for the same graduated exercise plan. The researchers found that exercise was comparable to surgery for meniscal tears in patients with no osteoarthritis.

CAVEATS

What about more severe osteoarthritis?

This trial included patients with no to mild osteoarthritis in addition to their meniscal tear.¹ It is unclear if the results would be maintained in those with more advanced disease. Additionally, 19% of patients crossed over from the exercise group to the surgery group, even though muscle strength improved. Therefore, education about the risks of surgery and the potential lack of benefit is important.

CHALLENGES TO IMPLEMENTATION

Cost and effort of PT

The cost of PT can be a barrier for patients who have adequate insurance coverage for surgery but inadequate coverage for PT. Additionally, exercise therapy requires significant and ongoing time and effort, which may deter those with busy lifestyles. Patients and clinicians may view surgery as an “easier” fix.

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.

Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2017;66[4]:250-252).

A 48-year-old man presents to your office for follow-up of right knee pain that has been bothering him for the past 12 months. He denies any trauma or inciting incident for the pain. On physical exam, he does not have crepitus but does have medial joint line tenderness of his right knee. An MRI shows a partial medial meniscal tear. Do you refer him to physical therapy (PT) or to orthopedics for arthroscopy and repair?

The meniscus—cartilage in the knee joint that provides support, stability, and lubrication to the joint during activity—can tear during a traumatic event or as a result of degeneration over time. Traumatic meniscal tears typically occur in those younger than 30 during sports (eg, basketball, soccer), whereas degenerative meniscal tears generally occur in patients ages 40 to 60.^2,3 The annual incidence of all meniscal tears is 79 per 100,000.⁴ While some clinicians can diagnose traumatic meniscal tears based on history and physical examination, degenerative meniscal tears are more challenging and typically warrant an MRI for confirmation.³

Meniscal tears can be treated either conservatively, with supportive care and exercise, or surgically. Unfortunately, there are no national orthopedic guidelines available to help direct care. In one observational study, 95 of 117 patients (81.2%) were generally satisfied with surgical treatment at four-year follow-up; satisfaction was higher among those with a traumatic meniscal tear than in those with a degenerative tear.⁵

Two systematic reviews of surgery versus nonoperative management or sham therapies found no additional benefit of surgery for meniscal tears in a variety of patients with and without osteoarthritis.^6,7 However, both studies were of only moderate quality, because of the number of patients in the nonoperative groups who ultimately underwent surgery. Neither of the studies directly compared surgery to nonoperative management.^6,7Another investigation—a multicenter, randomized, double-blind, sham-controlled study conducted in Finland involving 146 patients—compared sham surgery to arthroscopic partial meniscectomy. Both groups received instruction on performing post-procedure exercises, and both groups had similar and marked improvement in pain and function.⁸

Clinical practice recommendations devised from a vast systematic review of the literature recommend that the decision for surgery be based on patient-specific factors, such as symptoms, age, mechanism of tear, extent of damage, and occupational/social/activity needs.⁹

STUDY SUMMARY

Exercise is as good as surgery

The current superiority RCT compared exercise therapy to arthroscopic partial meniscectomy. Subjects (ages 35 to 60) presented to the orthopedic department of two hospitals in Norway with unilateral knee pain of more than two months’ duration and an MRI-delineated medial meniscal tear. They were included in the study only if they had radiographic evidence of minimal osteoarthritis (Kellgren-Lawrence classification grade ≤ 2). Exclusion criteria included acute trauma, locked knee, ligament injury, and knee surgery in the same knee within the previous two years.

The primary outcomes were change in patient-reported knee function (as determined by overall Knee injury and Osteoarthritis Outcome Score [KOOS] after two years) and thigh muscle strength at three months (as measured by physiotherapists). The researchers used four of the five KOOS subscales for this analysis: pain, other symptoms (swelling, grinding/noise from the joint, ability to straighten and bend), function in sports/recreation, and knee-related quality of life (QOL). The average score of each subscale was used.

Secondary outcomes included the five individual KOOS subscales (the four previously mentioned, plus activities of daily living [ADLs]), as well as thigh muscle strength and lower-extremity performance test results.

Methods. Testing personnel were blinded to group allocation; participants wore pants or neoprene sleeves to cover surgical scars. A total of 140 patients were randomized to either 12 weeks (24-36 sessions) of exercise therapy alone or a standardized arthroscopic partial meniscectomy; upon discharge, those in the latter group received written and oral encouragement to perform simple exercises at home, two to four times daily, to regain range of motion and reduce swelling.

Results. At two years, the overall mean improvement in KOOS4 score from baseline was similar between the exercise group and the meniscectomy group (25.3 pts vs 24.4 pts, respectively; mean difference [MD], 0.9). Additionally, muscle strength (measured as peak torque flexion and extension and total work flexion and extension) at both three and 12 months showed significant objective improvements favoring exercise therapy.

In the secondary analysis of the KOOS subscale scores, change from baseline was nonsignificant for four of the five (pain, ADL, sports/recreation, and QOL). Only the symptoms subscale had a significant difference favoring exercise therapy (MD, 5.3 pts); this was likely clinically insignificant on a grading scale of 0 to 100.

Of the patients allocated to exercise therapy alone, 19% crossed over and underwent surgery during the two-year study period.

WHAT’S NEW

Head-to-head comparison adds evidence

This is the first trial to directly compare exercise therapy to surgery in patients with meniscal tears. Interestingly, exercise therapy was as effective after a two-year follow-up period and was superior in the short term for thigh muscle strength.¹

The results of this study build on those from the aforementioned smaller study conducted in Finland.⁸ In that study, both groups received instruction for the same graduated exercise plan. The researchers found that exercise was comparable to surgery for meniscal tears in patients with no osteoarthritis.

CAVEATS

What about more severe osteoarthritis?

This trial included patients with no to mild osteoarthritis in addition to their meniscal tear.¹ It is unclear if the results would be maintained in those with more advanced disease. Additionally, 19% of patients crossed over from the exercise group to the surgery group, even though muscle strength improved. Therefore, education about the risks of surgery and the potential lack of benefit is important.

CHALLENGES TO IMPLEMENTATION

Cost and effort of PT

The cost of PT can be a barrier for patients who have adequate insurance coverage for surgery but inadequate coverage for PT. Additionally, exercise therapy requires significant and ongoing time and effort, which may deter those with busy lifestyles. Patients and clinicians may view surgery as an “easier” fix.

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.

Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2017;66[4]:250-252).

A 48-year-old man presents to your office for follow-up of right knee pain that has been bothering him for the past 12 months. He denies any trauma or inciting incident for the pain. On physical exam, he does not have crepitus but does have medial joint line tenderness of his right knee. An MRI shows a partial medial meniscal tear. Do you refer him to physical therapy (PT) or to orthopedics for arthroscopy and repair?

The meniscus—cartilage in the knee joint that provides support, stability, and lubrication to the joint during activity—can tear during a traumatic event or as a result of degeneration over time. Traumatic meniscal tears typically occur in those younger than 30 during sports (eg, basketball, soccer), whereas degenerative meniscal tears generally occur in patients ages 40 to 60.^2,3 The annual incidence of all meniscal tears is 79 per 100,000.⁴ While some clinicians can diagnose traumatic meniscal tears based on history and physical examination, degenerative meniscal tears are more challenging and typically warrant an MRI for confirmation.³

Meniscal tears can be treated either conservatively, with supportive care and exercise, or surgically. Unfortunately, there are no national orthopedic guidelines available to help direct care. In one observational study, 95 of 117 patients (81.2%) were generally satisfied with surgical treatment at four-year follow-up; satisfaction was higher among those with a traumatic meniscal tear than in those with a degenerative tear.⁵

Two systematic reviews of surgery versus nonoperative management or sham therapies found no additional benefit of surgery for meniscal tears in a variety of patients with and without osteoarthritis.^6,7 However, both studies were of only moderate quality, because of the number of patients in the nonoperative groups who ultimately underwent surgery. Neither of the studies directly compared surgery to nonoperative management.^6,7Another investigation—a multicenter, randomized, double-blind, sham-controlled study conducted in Finland involving 146 patients—compared sham surgery to arthroscopic partial meniscectomy. Both groups received instruction on performing post-procedure exercises, and both groups had similar and marked improvement in pain and function.⁸

Clinical practice recommendations devised from a vast systematic review of the literature recommend that the decision for surgery be based on patient-specific factors, such as symptoms, age, mechanism of tear, extent of damage, and occupational/social/activity needs.⁹

STUDY SUMMARY

Exercise is as good as surgery

The current superiority RCT compared exercise therapy to arthroscopic partial meniscectomy. Subjects (ages 35 to 60) presented to the orthopedic department of two hospitals in Norway with unilateral knee pain of more than two months’ duration and an MRI-delineated medial meniscal tear. They were included in the study only if they had radiographic evidence of minimal osteoarthritis (Kellgren-Lawrence classification grade ≤ 2). Exclusion criteria included acute trauma, locked knee, ligament injury, and knee surgery in the same knee within the previous two years.

The primary outcomes were change in patient-reported knee function (as determined by overall Knee injury and Osteoarthritis Outcome Score [KOOS] after two years) and thigh muscle strength at three months (as measured by physiotherapists). The researchers used four of the five KOOS subscales for this analysis: pain, other symptoms (swelling, grinding/noise from the joint, ability to straighten and bend), function in sports/recreation, and knee-related quality of life (QOL). The average score of each subscale was used.

Secondary outcomes included the five individual KOOS subscales (the four previously mentioned, plus activities of daily living [ADLs]), as well as thigh muscle strength and lower-extremity performance test results.

Methods. Testing personnel were blinded to group allocation; participants wore pants or neoprene sleeves to cover surgical scars. A total of 140 patients were randomized to either 12 weeks (24-36 sessions) of exercise therapy alone or a standardized arthroscopic partial meniscectomy; upon discharge, those in the latter group received written and oral encouragement to perform simple exercises at home, two to four times daily, to regain range of motion and reduce swelling.

Results. At two years, the overall mean improvement in KOOS4 score from baseline was similar between the exercise group and the meniscectomy group (25.3 pts vs 24.4 pts, respectively; mean difference [MD], 0.9). Additionally, muscle strength (measured as peak torque flexion and extension and total work flexion and extension) at both three and 12 months showed significant objective improvements favoring exercise therapy.

In the secondary analysis of the KOOS subscale scores, change from baseline was nonsignificant for four of the five (pain, ADL, sports/recreation, and QOL). Only the symptoms subscale had a significant difference favoring exercise therapy (MD, 5.3 pts); this was likely clinically insignificant on a grading scale of 0 to 100.

Of the patients allocated to exercise therapy alone, 19% crossed over and underwent surgery during the two-year study period.

WHAT’S NEW

Head-to-head comparison adds evidence

This is the first trial to directly compare exercise therapy to surgery in patients with meniscal tears. Interestingly, exercise therapy was as effective after a two-year follow-up period and was superior in the short term for thigh muscle strength.¹

The results of this study build on those from the aforementioned smaller study conducted in Finland.⁸ In that study, both groups received instruction for the same graduated exercise plan. The researchers found that exercise was comparable to surgery for meniscal tears in patients with no osteoarthritis.

CAVEATS

What about more severe osteoarthritis?

This trial included patients with no to mild osteoarthritis in addition to their meniscal tear.¹ It is unclear if the results would be maintained in those with more advanced disease. Additionally, 19% of patients crossed over from the exercise group to the surgery group, even though muscle strength improved. Therefore, education about the risks of surgery and the potential lack of benefit is important.

CHALLENGES TO IMPLEMENTATION

Cost and effort of PT

The cost of PT can be a barrier for patients who have adequate insurance coverage for surgery but inadequate coverage for PT. Additionally, exercise therapy requires significant and ongoing time and effort, which may deter those with busy lifestyles. Patients and clinicians may view surgery as an “easier” fix.

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.

Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2017;66[4]:250-252).

CLINICAL QUESTION: What are the benefits and harms of perioperative pharmacological thromboprophylaxis in cancer patients undergoing surgery?

STUDY DESIGN: Systematic review and meta-analysis.

SYNOPSIS: Thirty-nine trials were deemed eligible for inclusion in the meta-analysis. Twenty-five of these were prospective and 14 were retrospective. The overall incidence of deep venous thrombosis (DVT) and pulmonary embolism was 0.9% (across 20 studies) and 0.3% (across 19 studies), respectively. Pharmacologic prophylaxis overall reduced DVT incidence (0.5% vs. 1.2%; relative risk, 0.51; P = .03). Subgroup analysis demonstrated this was significant for abdominal/pelvic surgeries and with low molecular weight heparin. Six studies compared duration of standard prophylaxis (10 days) with extended prophylaxis (4 weeks), with a lower VTE rate in the extended group. Bleeding events were noted in 13 studies and pharmacologic prophylaxis significantly increased bleeding risk (2.7% vs. 8%; RR, 2.51; P less than .0001).

BOTTOM LINE: Perioperative pharmacologic prophylaxis reduces DVT risk in patients with cancer, with greatest risk reduction seen in patients undergoing abdominal/pelvic surgeries. This comes at the cost of increased bleeding complications.

CITATIONS: Guo Q, Huang B, Zhao J, et al. Perioperative pharmacological thromboprophylaxis in patients with cancer: a systematic review and meta-analysis. Ann Surg. 2016 Nov. doi: 10.1097/SLA.0000000000002074.

Dr. Patil is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.

CLINICAL QUESTION: What are the benefits and harms of perioperative pharmacological thromboprophylaxis in cancer patients undergoing surgery?

STUDY DESIGN: Systematic review and meta-analysis.

SYNOPSIS: Thirty-nine trials were deemed eligible for inclusion in the meta-analysis. Twenty-five of these were prospective and 14 were retrospective. The overall incidence of deep venous thrombosis (DVT) and pulmonary embolism was 0.9% (across 20 studies) and 0.3% (across 19 studies), respectively. Pharmacologic prophylaxis overall reduced DVT incidence (0.5% vs. 1.2%; relative risk, 0.51; P = .03). Subgroup analysis demonstrated this was significant for abdominal/pelvic surgeries and with low molecular weight heparin. Six studies compared duration of standard prophylaxis (10 days) with extended prophylaxis (4 weeks), with a lower VTE rate in the extended group. Bleeding events were noted in 13 studies and pharmacologic prophylaxis significantly increased bleeding risk (2.7% vs. 8%; RR, 2.51; P less than .0001).

BOTTOM LINE: Perioperative pharmacologic prophylaxis reduces DVT risk in patients with cancer, with greatest risk reduction seen in patients undergoing abdominal/pelvic surgeries. This comes at the cost of increased bleeding complications.

CITATIONS: Guo Q, Huang B, Zhao J, et al. Perioperative pharmacological thromboprophylaxis in patients with cancer: a systematic review and meta-analysis. Ann Surg. 2016 Nov. doi: 10.1097/SLA.0000000000002074.

Dr. Patil is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.

CLINICAL QUESTION: What are the benefits and harms of perioperative pharmacological thromboprophylaxis in cancer patients undergoing surgery?

STUDY DESIGN: Systematic review and meta-analysis.

SYNOPSIS: Thirty-nine trials were deemed eligible for inclusion in the meta-analysis. Twenty-five of these were prospective and 14 were retrospective. The overall incidence of deep venous thrombosis (DVT) and pulmonary embolism was 0.9% (across 20 studies) and 0.3% (across 19 studies), respectively. Pharmacologic prophylaxis overall reduced DVT incidence (0.5% vs. 1.2%; relative risk, 0.51; P = .03). Subgroup analysis demonstrated this was significant for abdominal/pelvic surgeries and with low molecular weight heparin. Six studies compared duration of standard prophylaxis (10 days) with extended prophylaxis (4 weeks), with a lower VTE rate in the extended group. Bleeding events were noted in 13 studies and pharmacologic prophylaxis significantly increased bleeding risk (2.7% vs. 8%; RR, 2.51; P less than .0001).

BOTTOM LINE: Perioperative pharmacologic prophylaxis reduces DVT risk in patients with cancer, with greatest risk reduction seen in patients undergoing abdominal/pelvic surgeries. This comes at the cost of increased bleeding complications.

CITATIONS: Guo Q, Huang B, Zhao J, et al. Perioperative pharmacological thromboprophylaxis in patients with cancer: a systematic review and meta-analysis. Ann Surg. 2016 Nov. doi: 10.1097/SLA.0000000000002074.

Dr. Patil is a clinical instructor, Division of Hospital Medicine, University of Colorado School of Medicine, Aurora.