NEW ORLEANS – Single ventricle congenital heart disease (CHD) and worse social determinants of health are associated with more behavior problems and less total competency in children, and this relationship is mediated by disease-related chronic stress, self-perception, and family environment.

Those are key findings from a large analysis of existing cross-sectional data presented at the annual meeting of the American Academy of Pediatrics. The study set out to assess what factors mediate the relationship between CHD severity, social determinants of health, and behavioral and emotional outcomes.

“We know that worse CHD severity is associated with worse parent-reported and self-reported behavioral and emotional functioning in children and adolescents survivors,” lead author Asad Qadir, MD, said in an interview. “We may be able to improve and optimize behavioral and emotional outcomes in children with congenital heart disease by taking measures that would decrease their and their caregivers’ disease-related chronic stress, improve family functioning, and improve the self-perception of the child. While social determinants of health are not modifiable, they are important for predicting which children may be at risk for behavior problems.”

Dr. Qadir, a cardiology fellow in the department of pediatrics at Northwestern University, Chicago, and colleagues performed a corollary analysis of the Pediatric Cardiac Quality of Life Inventory Testing study, an international, multicenter, cross-sectional study in which parents and patients with CHD completed questionnaires measuring behavioral and emotional functioning, self-perception, family environment, family coping, posttraumatic stress, and illness-related parenting stress (see Qual Life Res. 2008;17:613-26, Pediatrics. 2010;126[3]:498-508, and Cardiol Young. 2014;[2]:220-8). They assessed the relationships between CHD severity and social determinants of health (predictors), disease-related stress and psychosocial adaptation (mediators), and behavioral and emotional outcomes. They used structural equation modeling to determine the effects of predictors and mediators on outcomes, and created multivariable models for each patient- and parent-reported outcome.

The analysis included 981 patient-parent dyads. Of these, 210 patients had mild biventricular CHD, 620 had moderate biventricular CHD, and 151 had single ventricle CHD. The mean age of patients was 13 years and 55% were male. The researchers found that single ventricle CHD and worse social determinants of health were significant predictors of greater disease-related chronic stress for patients and caregivers and worse psychosocial adaptation in CHD survivors, including self-perception and family functioning constructs of cohesion and expressiveness (P less than .001 for all associations). In addition, single ventricle CHD and worse social determinants of health were associated with worse behavioral and emotional outcomes as reported by patients and parents, including internalizing behaviors, externalizing behaviors, and total competency (P less than .001 for all associations).

In multivariable models for all parent-reported outcomes, significant associations were observed between single ventricle CHD, social determinants of health, disease-related stress, child receiving mental health services, and cohesion/conflict in the family environment (P less than .001). In multivariable models for all patient-reported outcomes, significant associations were seen between single ventricle CHD, self-perception, and cohesion/conflict in the family environment (P less than 0.001).

Patient disease-related stress had the strongest association with externalizing problems, and worse social determinants of health significantly lowered patient-reported total competency.

“Many of the relationships found in the study make intuitive sense,” Dr. Qadir said. “For example, less favorable social determinants of health were associated with more parent disease-related chronic stress, which in turn was associated with parent-reported behavior problems in children. What was surprising was that worse behavioral outcomes were specifically associated with single ventricle disease only. Complex biventricular congenital heart disease patients (CHD that required a surgical- or catheter-based intervention) often have worse behavioral and emotional outcomes, similar to single ventricle patients. However, our model would argue that biventricular congenital heart disease complexity patients have more behavioral and emotional issues not because of their disease complexity, but due to their social determinants of health and the amount of disease-related chronic stress in the child and the parent and the amount of psychosocial adaptation found in the child and parent.”

Parent and patient disease-related chronic stress was not only an important mediator of the effect of CHD severity and social determinants of health on behavioral and emotional outcomes, he added, but it also had indirect effects that were mediated by family cohesion/conflict and patient self-perception.

“These data suggest that for those children with worse social determinants of health and single ventricle congenital heart disease, interventions that mitigate disease-related chronic stress, promote family functioning, and promote self-perception in the child may improve or optimize behavioral and emotional functioning during childhood and adolescence in CHD surgical survivors,” Dr. Qadir concluded.

He acknowledged certain limitations of the analysis, including the fact that it was a corollary cross-sectional analysis of an existing data set. “The results do not reflect possible changes over time,” he added. “There was also selection bias as non-English speakers were excluded, and the study population had a greater percentage of Caucasian and highly educated parents with higher income than the general population, which may affect the generalizability of our results.”

The researchers reported having no relevant financial disclosures.

[email protected]

NEW ORLEANS – Single ventricle congenital heart disease (CHD) and worse social determinants of health are associated with more behavior problems and less total competency in children, and this relationship is mediated by disease-related chronic stress, self-perception, and family environment.

Those are key findings from a large analysis of existing cross-sectional data presented at the annual meeting of the American Academy of Pediatrics. The study set out to assess what factors mediate the relationship between CHD severity, social determinants of health, and behavioral and emotional outcomes.

“We know that worse CHD severity is associated with worse parent-reported and self-reported behavioral and emotional functioning in children and adolescents survivors,” lead author Asad Qadir, MD, said in an interview. “We may be able to improve and optimize behavioral and emotional outcomes in children with congenital heart disease by taking measures that would decrease their and their caregivers’ disease-related chronic stress, improve family functioning, and improve the self-perception of the child. While social determinants of health are not modifiable, they are important for predicting which children may be at risk for behavior problems.”

Dr. Qadir, a cardiology fellow in the department of pediatrics at Northwestern University, Chicago, and colleagues performed a corollary analysis of the Pediatric Cardiac Quality of Life Inventory Testing study, an international, multicenter, cross-sectional study in which parents and patients with CHD completed questionnaires measuring behavioral and emotional functioning, self-perception, family environment, family coping, posttraumatic stress, and illness-related parenting stress (see Qual Life Res. 2008;17:613-26, Pediatrics. 2010;126[3]:498-508, and Cardiol Young. 2014;[2]:220-8). They assessed the relationships between CHD severity and social determinants of health (predictors), disease-related stress and psychosocial adaptation (mediators), and behavioral and emotional outcomes. They used structural equation modeling to determine the effects of predictors and mediators on outcomes, and created multivariable models for each patient- and parent-reported outcome.

The analysis included 981 patient-parent dyads. Of these, 210 patients had mild biventricular CHD, 620 had moderate biventricular CHD, and 151 had single ventricle CHD. The mean age of patients was 13 years and 55% were male. The researchers found that single ventricle CHD and worse social determinants of health were significant predictors of greater disease-related chronic stress for patients and caregivers and worse psychosocial adaptation in CHD survivors, including self-perception and family functioning constructs of cohesion and expressiveness (P less than .001 for all associations). In addition, single ventricle CHD and worse social determinants of health were associated with worse behavioral and emotional outcomes as reported by patients and parents, including internalizing behaviors, externalizing behaviors, and total competency (P less than .001 for all associations).

In multivariable models for all parent-reported outcomes, significant associations were observed between single ventricle CHD, social determinants of health, disease-related stress, child receiving mental health services, and cohesion/conflict in the family environment (P less than .001). In multivariable models for all patient-reported outcomes, significant associations were seen between single ventricle CHD, self-perception, and cohesion/conflict in the family environment (P less than 0.001).

Patient disease-related stress had the strongest association with externalizing problems, and worse social determinants of health significantly lowered patient-reported total competency.

“Many of the relationships found in the study make intuitive sense,” Dr. Qadir said. “For example, less favorable social determinants of health were associated with more parent disease-related chronic stress, which in turn was associated with parent-reported behavior problems in children. What was surprising was that worse behavioral outcomes were specifically associated with single ventricle disease only. Complex biventricular congenital heart disease patients (CHD that required a surgical- or catheter-based intervention) often have worse behavioral and emotional outcomes, similar to single ventricle patients. However, our model would argue that biventricular congenital heart disease complexity patients have more behavioral and emotional issues not because of their disease complexity, but due to their social determinants of health and the amount of disease-related chronic stress in the child and the parent and the amount of psychosocial adaptation found in the child and parent.”

Parent and patient disease-related chronic stress was not only an important mediator of the effect of CHD severity and social determinants of health on behavioral and emotional outcomes, he added, but it also had indirect effects that were mediated by family cohesion/conflict and patient self-perception.

“These data suggest that for those children with worse social determinants of health and single ventricle congenital heart disease, interventions that mitigate disease-related chronic stress, promote family functioning, and promote self-perception in the child may improve or optimize behavioral and emotional functioning during childhood and adolescence in CHD surgical survivors,” Dr. Qadir concluded.

He acknowledged certain limitations of the analysis, including the fact that it was a corollary cross-sectional analysis of an existing data set. “The results do not reflect possible changes over time,” he added. “There was also selection bias as non-English speakers were excluded, and the study population had a greater percentage of Caucasian and highly educated parents with higher income than the general population, which may affect the generalizability of our results.”

The researchers reported having no relevant financial disclosures.

[email protected]

NEW ORLEANS – Single ventricle congenital heart disease (CHD) and worse social determinants of health are associated with more behavior problems and less total competency in children, and this relationship is mediated by disease-related chronic stress, self-perception, and family environment.

Those are key findings from a large analysis of existing cross-sectional data presented at the annual meeting of the American Academy of Pediatrics. The study set out to assess what factors mediate the relationship between CHD severity, social determinants of health, and behavioral and emotional outcomes.

“We know that worse CHD severity is associated with worse parent-reported and self-reported behavioral and emotional functioning in children and adolescents survivors,” lead author Asad Qadir, MD, said in an interview. “We may be able to improve and optimize behavioral and emotional outcomes in children with congenital heart disease by taking measures that would decrease their and their caregivers’ disease-related chronic stress, improve family functioning, and improve the self-perception of the child. While social determinants of health are not modifiable, they are important for predicting which children may be at risk for behavior problems.”

Dr. Qadir, a cardiology fellow in the department of pediatrics at Northwestern University, Chicago, and colleagues performed a corollary analysis of the Pediatric Cardiac Quality of Life Inventory Testing study, an international, multicenter, cross-sectional study in which parents and patients with CHD completed questionnaires measuring behavioral and emotional functioning, self-perception, family environment, family coping, posttraumatic stress, and illness-related parenting stress (see Qual Life Res. 2008;17:613-26, Pediatrics. 2010;126[3]:498-508, and Cardiol Young. 2014;[2]:220-8). They assessed the relationships between CHD severity and social determinants of health (predictors), disease-related stress and psychosocial adaptation (mediators), and behavioral and emotional outcomes. They used structural equation modeling to determine the effects of predictors and mediators on outcomes, and created multivariable models for each patient- and parent-reported outcome.

The analysis included 981 patient-parent dyads. Of these, 210 patients had mild biventricular CHD, 620 had moderate biventricular CHD, and 151 had single ventricle CHD. The mean age of patients was 13 years and 55% were male. The researchers found that single ventricle CHD and worse social determinants of health were significant predictors of greater disease-related chronic stress for patients and caregivers and worse psychosocial adaptation in CHD survivors, including self-perception and family functioning constructs of cohesion and expressiveness (P less than .001 for all associations). In addition, single ventricle CHD and worse social determinants of health were associated with worse behavioral and emotional outcomes as reported by patients and parents, including internalizing behaviors, externalizing behaviors, and total competency (P less than .001 for all associations).

In multivariable models for all parent-reported outcomes, significant associations were observed between single ventricle CHD, social determinants of health, disease-related stress, child receiving mental health services, and cohesion/conflict in the family environment (P less than .001). In multivariable models for all patient-reported outcomes, significant associations were seen between single ventricle CHD, self-perception, and cohesion/conflict in the family environment (P less than 0.001).

Patient disease-related stress had the strongest association with externalizing problems, and worse social determinants of health significantly lowered patient-reported total competency.

“Many of the relationships found in the study make intuitive sense,” Dr. Qadir said. “For example, less favorable social determinants of health were associated with more parent disease-related chronic stress, which in turn was associated with parent-reported behavior problems in children. What was surprising was that worse behavioral outcomes were specifically associated with single ventricle disease only. Complex biventricular congenital heart disease patients (CHD that required a surgical- or catheter-based intervention) often have worse behavioral and emotional outcomes, similar to single ventricle patients. However, our model would argue that biventricular congenital heart disease complexity patients have more behavioral and emotional issues not because of their disease complexity, but due to their social determinants of health and the amount of disease-related chronic stress in the child and the parent and the amount of psychosocial adaptation found in the child and parent.”

Parent and patient disease-related chronic stress was not only an important mediator of the effect of CHD severity and social determinants of health on behavioral and emotional outcomes, he added, but it also had indirect effects that were mediated by family cohesion/conflict and patient self-perception.

“These data suggest that for those children with worse social determinants of health and single ventricle congenital heart disease, interventions that mitigate disease-related chronic stress, promote family functioning, and promote self-perception in the child may improve or optimize behavioral and emotional functioning during childhood and adolescence in CHD surgical survivors,” Dr. Qadir concluded.

He acknowledged certain limitations of the analysis, including the fact that it was a corollary cross-sectional analysis of an existing data set. “The results do not reflect possible changes over time,” he added. “There was also selection bias as non-English speakers were excluded, and the study population had a greater percentage of Caucasian and highly educated parents with higher income than the general population, which may affect the generalizability of our results.”

The researchers reported having no relevant financial disclosures.

[email protected]

Minimally invasive surgical techniques, which have revolutionized modern-day surgery, are the current standard of care for benign hysterectomies.^1-4 Many surgeons use a video-laparoscopic approach, with or without robotic assistance, to perform a hysterectomy. The development of a bladder flap or vesicovaginal surgical space is a critical step for mobilizing the bladder. When properly performed, it allows for appropriate closure of the vaginal cuff while mitigating the risk of urinary bladder damage.

In patients with no prior pelvic surgeries, this vesicovaginal anatomic space is typically developed with ease. However, in patients who have had prior cesarean deliveries (CDs), the presence of vesicouterine adhesions could make this step significantly more challenging. As a result, the risk of bladder injury is higher.^5-8

With the current tide of cesarean birth rates approaching 33% on a national scale, the presence of vesicouterine adhesions is commonly encountered.⁹ These adhesions can distort the anatomy and thereby create more difficult dissections and increase operative time, conversion to laparotomy, and inadvertent cystotomy. Such a challenge also presents an increased risk of injuring adjacent structures.

In this article, we describe an effective method of dissection that is especially useful in the setting of prior CDs. This method involves developing a "new" surgical space lateral and caudal to the vesicocervical space. 

Steps in operative planning

Preoperative evaluation. A thorough preoperative evaluation should be performed for patients planning to undergo a laparoscopic hysterectomy. This includes obtaining details of their medical and surgical history. Access to prior surgical records may help to facilitate planning of the surgical approach. Previous pelvic surgery, such as CD, anterior myomectomy, cesarean scar defect repair, endometriosis treatment, or exploratory laparotomy, may predispose these patients to develop adhesions in the anterior cul-de-sac. Our method of reverse vesicouterine fold dissection can be particularly efficacious in these settings.

Surgical preparation and laparoscopic port placement. In the operative suite, the patient is placed under general anesthesia and positioned in the dorsal lithotomy position.¹⁰ Sterile prep and drapes are used in the standard fashion. A urinary catheter is inserted to maintain a decompressed bladder. A uterine manipulator is inserted with good placement ensured.

Per our practice, we introduce laparoscopic ports in 4 locations. The first incision is made in the umbilicus for the introduction of a 10-mm laparoscope. Three subsequent 5-mm incisions are made in the left and right lower lateral quadrants and medially at the level of the suprapubic region.¹⁰ Upon laparoscopic entry, we perform a comprehensive survey of the abdominopelvic cavity. Adequate mobility of the uterus is confirmed.¹¹ Any posterior uterine adhesions or endometriosis are treated appropriately.¹²

First step in the surgical technique: Lateral dissection

We proceed by first desiccating and cutting the round ligament laterally near the inguinal canal. This technique is carried forward in a caudal direction as the areolar tissue near the obliterated umbilical artery is expanded by the pneumoperitoneum. With a vessel sealing-cutting device, we address the attachments to the adnexa. If the ovaries are to be retained, the utero-ovarian ligament is dessicated and cut. If an oophorectomy is indicated, the infundibulopelvic ligament is dessicated and cut.

Continue to: Using the tip of the vessel sealing...

Using the tip of the vessel sealing-cutting device, the space between the anterior and posterior leaves of the broad ligament is developed and opened. A grasping forceps is then used to elevate the anterior leaf of the broad ligament and maintain medial traction. A space parallel and lateral to the cervix and bladder is then created with blunt dissection.

The inferior and medial direction of this dissection is paramount to avoid injury to nearby structures in the pelvic sidewall. Gradually, this will lead to the identification of the vesciovaginal ligament and then the vesicocervical ligament. The development of these spaces allows for the lateral and inferior displacement of the ureter. These maneuvers can mitigate ureter injury by pushing it away from the planes of dissection during the hysterectomy.

Continued traction is maintained by keeping the medial aspect of the anterior leaf of the broad ligament intact. However, the posterior leaf is dissected next, which further lateralizes the ureter. Now, with the uterine vessels fully exposed, they are thoroughly dessicated and ligated. The same procedure is then performed on the contralateral side.¹¹ (See the box below for links to videos that demonstrate the techniques described here.)

Creating the “new” space

In the “new” space that was partially developed during the lateral dissection, blunt dissection is continued, using a sweeping motion from an inferior-to-superior direction, to extend this avascular space. This is performed bilaterally until both sides are connected from the inferior aspect of the vesicouterine adhesions, if present. This thorough dissection creates what we refer to as a “new” space¹¹ (FIGURE 1).

Medially, the new space is bordered by the vesicocervical-vaginal ligament, also known as the bladder pillar. Its distal landmark is the bladder. The remaining intact anterior leaf of the broad ligament lies adjacent to the space anteriorly. The inner aspect of the obliterated umbilical artery neighbors it laterally. Lastly, the vesicovaginal plane’s posterior margin is the parametrium, which is the region where the ureter courses into the bladder. The paravesical space lies lateral to the obliterated umbilical ligament.

Visualization of this new space is made possible in the laparoscopic setting. The pneumoperitoneum allows for better demarcation of the space. Additionally, laparoscopic views of the anatomic spaces differ from those of the laparotomy view because of the magnification and the insufflation of carbon dioxide gas in the spaces.^13,14 In our experience, approaching the surgery from the “new” space could significantly decrease the risk of genitourinary injuries in patients with anterior cul-de-sac adhesions (FIGURE 2).

Using the reverse vesicouterine fold dissection technique

Among patients with prior CDs, adhesions often are at the level of or superior to the prior CD scar. By creating the new space, safe dissection from a previously untouched area can be accomplished and injury to the urinary bladder can be avoided.

The reverse vesicouterine fold dissection can be performed from this space. Using the previously described blunt sweeping motion from an inferior-to-superior direction, the vesicovaginal and vesicocervical space is further developed from an unscarred plane. This will separate the lowest portion of the bladder from the vagina, cervix, and uterus in a safe manner. Similar to the technique performed during a vaginal hysterectomy, this reverse motion of developing the bladder flap avoids erroneous and blind dissection through the vesicouterine adhesions (FIGURES 3–5).

Continue to: Completing the surgery...

Completing the surgery

Once the bladder is freely mobilized and all adhesions have been dissected, the cervix is circumferentially amputated using monopolar cautery. The vaginal cuff can then be closed from either a laparoscopic or vaginal approach using polyglactin 910 (0-Vicryl) or barbed (V-Loc) suture in a running or interrupted fashion. Our practice uses a 1.5-cm margin depth with each suture. At the end of the surgery, routine cystoscopy is performed to verify distal ureteral patency.¹⁶ Postoperatively, we manage these patients using a fast-track, or enhanced recovery, model.¹⁷

An effective technique in challenging situations

Genitourinary injury is a common complication of hysterectomy.¹⁸ The proximity of the bladder and ureters to the field of dissection during a hysterectomy can be especially challenging when the anatomy is distorted by adhesion formation from prior surgeries. One study demonstrated a 1.3% incidence of urinary tract injuries during laparoscopic hysterectomy.⁶ This included 0.54% ureteral injuries, 0.71% urinary bladder injuries, and 0.06% combined bladder and ureteral injuries.⁶ Particularly among patients with a prior CD, the risk of bladder injury can be significantly heightened.¹⁸

The reverse vesicouterine fold dissection technique that we described offers multiple benefits. By starting the procedure from an untouched and avascular plane, dissection into the plane of the prior adhesions can be circumvented; thus, bleeding is limited and injury to the bladder and ureters is avoided or minimized. By using blunt and sharp dissection, thermal injury and delayed necrosis can be mitigated. Finally, with bladder mobilization well below the colpotomy site, more adequate vaginal tissue is free to be incorporated into the vaginal cuff closure, thereby limiting the risk of cuff dehiscence.¹⁶

While we have found this technique effective for patients with prior cesarean deliveries, it also may be applied to any patient who has a scarred anterior cul-de-sac. This could include patients with prior myomectomy, cesarean scar defect, or endometriosis. Despite the technique being a safeguard against bladder injury, surgeons must still use care in developing the spaces to avoid ureteral injury, especially in a setting of distorted anatomy.

Minimally invasive surgical techniques, which have revolutionized modern-day surgery, are the current standard of care for benign hysterectomies.^1-4 Many surgeons use a video-laparoscopic approach, with or without robotic assistance, to perform a hysterectomy. The development of a bladder flap or vesicovaginal surgical space is a critical step for mobilizing the bladder. When properly performed, it allows for appropriate closure of the vaginal cuff while mitigating the risk of urinary bladder damage.

In patients with no prior pelvic surgeries, this vesicovaginal anatomic space is typically developed with ease. However, in patients who have had prior cesarean deliveries (CDs), the presence of vesicouterine adhesions could make this step significantly more challenging. As a result, the risk of bladder injury is higher.^5-8

With the current tide of cesarean birth rates approaching 33% on a national scale, the presence of vesicouterine adhesions is commonly encountered.⁹ These adhesions can distort the anatomy and thereby create more difficult dissections and increase operative time, conversion to laparotomy, and inadvertent cystotomy. Such a challenge also presents an increased risk of injuring adjacent structures.

In this article, we describe an effective method of dissection that is especially useful in the setting of prior CDs. This method involves developing a "new" surgical space lateral and caudal to the vesicocervical space. 

Steps in operative planning

Preoperative evaluation. A thorough preoperative evaluation should be performed for patients planning to undergo a laparoscopic hysterectomy. This includes obtaining details of their medical and surgical history. Access to prior surgical records may help to facilitate planning of the surgical approach. Previous pelvic surgery, such as CD, anterior myomectomy, cesarean scar defect repair, endometriosis treatment, or exploratory laparotomy, may predispose these patients to develop adhesions in the anterior cul-de-sac. Our method of reverse vesicouterine fold dissection can be particularly efficacious in these settings.

Surgical preparation and laparoscopic port placement. In the operative suite, the patient is placed under general anesthesia and positioned in the dorsal lithotomy position.¹⁰ Sterile prep and drapes are used in the standard fashion. A urinary catheter is inserted to maintain a decompressed bladder. A uterine manipulator is inserted with good placement ensured.

Per our practice, we introduce laparoscopic ports in 4 locations. The first incision is made in the umbilicus for the introduction of a 10-mm laparoscope. Three subsequent 5-mm incisions are made in the left and right lower lateral quadrants and medially at the level of the suprapubic region.¹⁰ Upon laparoscopic entry, we perform a comprehensive survey of the abdominopelvic cavity. Adequate mobility of the uterus is confirmed.¹¹ Any posterior uterine adhesions or endometriosis are treated appropriately.¹²

First step in the surgical technique: Lateral dissection

We proceed by first desiccating and cutting the round ligament laterally near the inguinal canal. This technique is carried forward in a caudal direction as the areolar tissue near the obliterated umbilical artery is expanded by the pneumoperitoneum. With a vessel sealing-cutting device, we address the attachments to the adnexa. If the ovaries are to be retained, the utero-ovarian ligament is dessicated and cut. If an oophorectomy is indicated, the infundibulopelvic ligament is dessicated and cut.

Continue to: Using the tip of the vessel sealing...

Using the tip of the vessel sealing-cutting device, the space between the anterior and posterior leaves of the broad ligament is developed and opened. A grasping forceps is then used to elevate the anterior leaf of the broad ligament and maintain medial traction. A space parallel and lateral to the cervix and bladder is then created with blunt dissection.

The inferior and medial direction of this dissection is paramount to avoid injury to nearby structures in the pelvic sidewall. Gradually, this will lead to the identification of the vesciovaginal ligament and then the vesicocervical ligament. The development of these spaces allows for the lateral and inferior displacement of the ureter. These maneuvers can mitigate ureter injury by pushing it away from the planes of dissection during the hysterectomy.

Continued traction is maintained by keeping the medial aspect of the anterior leaf of the broad ligament intact. However, the posterior leaf is dissected next, which further lateralizes the ureter. Now, with the uterine vessels fully exposed, they are thoroughly dessicated and ligated. The same procedure is then performed on the contralateral side.¹¹ (See the box below for links to videos that demonstrate the techniques described here.)

Creating the “new” space

In the “new” space that was partially developed during the lateral dissection, blunt dissection is continued, using a sweeping motion from an inferior-to-superior direction, to extend this avascular space. This is performed bilaterally until both sides are connected from the inferior aspect of the vesicouterine adhesions, if present. This thorough dissection creates what we refer to as a “new” space¹¹ (FIGURE 1).

Medially, the new space is bordered by the vesicocervical-vaginal ligament, also known as the bladder pillar. Its distal landmark is the bladder. The remaining intact anterior leaf of the broad ligament lies adjacent to the space anteriorly. The inner aspect of the obliterated umbilical artery neighbors it laterally. Lastly, the vesicovaginal plane’s posterior margin is the parametrium, which is the region where the ureter courses into the bladder. The paravesical space lies lateral to the obliterated umbilical ligament.

Visualization of this new space is made possible in the laparoscopic setting. The pneumoperitoneum allows for better demarcation of the space. Additionally, laparoscopic views of the anatomic spaces differ from those of the laparotomy view because of the magnification and the insufflation of carbon dioxide gas in the spaces.^13,14 In our experience, approaching the surgery from the “new” space could significantly decrease the risk of genitourinary injuries in patients with anterior cul-de-sac adhesions (FIGURE 2).

Using the reverse vesicouterine fold dissection technique

Among patients with prior CDs, adhesions often are at the level of or superior to the prior CD scar. By creating the new space, safe dissection from a previously untouched area can be accomplished and injury to the urinary bladder can be avoided.

The reverse vesicouterine fold dissection can be performed from this space. Using the previously described blunt sweeping motion from an inferior-to-superior direction, the vesicovaginal and vesicocervical space is further developed from an unscarred plane. This will separate the lowest portion of the bladder from the vagina, cervix, and uterus in a safe manner. Similar to the technique performed during a vaginal hysterectomy, this reverse motion of developing the bladder flap avoids erroneous and blind dissection through the vesicouterine adhesions (FIGURES 3–5).

Continue to: Completing the surgery...

Completing the surgery

Once the bladder is freely mobilized and all adhesions have been dissected, the cervix is circumferentially amputated using monopolar cautery. The vaginal cuff can then be closed from either a laparoscopic or vaginal approach using polyglactin 910 (0-Vicryl) or barbed (V-Loc) suture in a running or interrupted fashion. Our practice uses a 1.5-cm margin depth with each suture. At the end of the surgery, routine cystoscopy is performed to verify distal ureteral patency.¹⁶ Postoperatively, we manage these patients using a fast-track, or enhanced recovery, model.¹⁷

An effective technique in challenging situations

Genitourinary injury is a common complication of hysterectomy.¹⁸ The proximity of the bladder and ureters to the field of dissection during a hysterectomy can be especially challenging when the anatomy is distorted by adhesion formation from prior surgeries. One study demonstrated a 1.3% incidence of urinary tract injuries during laparoscopic hysterectomy.⁶ This included 0.54% ureteral injuries, 0.71% urinary bladder injuries, and 0.06% combined bladder and ureteral injuries.⁶ Particularly among patients with a prior CD, the risk of bladder injury can be significantly heightened.¹⁸

The reverse vesicouterine fold dissection technique that we described offers multiple benefits. By starting the procedure from an untouched and avascular plane, dissection into the plane of the prior adhesions can be circumvented; thus, bleeding is limited and injury to the bladder and ureters is avoided or minimized. By using blunt and sharp dissection, thermal injury and delayed necrosis can be mitigated. Finally, with bladder mobilization well below the colpotomy site, more adequate vaginal tissue is free to be incorporated into the vaginal cuff closure, thereby limiting the risk of cuff dehiscence.¹⁶

While we have found this technique effective for patients with prior cesarean deliveries, it also may be applied to any patient who has a scarred anterior cul-de-sac. This could include patients with prior myomectomy, cesarean scar defect, or endometriosis. Despite the technique being a safeguard against bladder injury, surgeons must still use care in developing the spaces to avoid ureteral injury, especially in a setting of distorted anatomy.

Minimally invasive surgical techniques, which have revolutionized modern-day surgery, are the current standard of care for benign hysterectomies.^1-4 Many surgeons use a video-laparoscopic approach, with or without robotic assistance, to perform a hysterectomy. The development of a bladder flap or vesicovaginal surgical space is a critical step for mobilizing the bladder. When properly performed, it allows for appropriate closure of the vaginal cuff while mitigating the risk of urinary bladder damage.

In patients with no prior pelvic surgeries, this vesicovaginal anatomic space is typically developed with ease. However, in patients who have had prior cesarean deliveries (CDs), the presence of vesicouterine adhesions could make this step significantly more challenging. As a result, the risk of bladder injury is higher.^5-8

With the current tide of cesarean birth rates approaching 33% on a national scale, the presence of vesicouterine adhesions is commonly encountered.⁹ These adhesions can distort the anatomy and thereby create more difficult dissections and increase operative time, conversion to laparotomy, and inadvertent cystotomy. Such a challenge also presents an increased risk of injuring adjacent structures.

In this article, we describe an effective method of dissection that is especially useful in the setting of prior CDs. This method involves developing a "new" surgical space lateral and caudal to the vesicocervical space. 

Steps in operative planning

Preoperative evaluation. A thorough preoperative evaluation should be performed for patients planning to undergo a laparoscopic hysterectomy. This includes obtaining details of their medical and surgical history. Access to prior surgical records may help to facilitate planning of the surgical approach. Previous pelvic surgery, such as CD, anterior myomectomy, cesarean scar defect repair, endometriosis treatment, or exploratory laparotomy, may predispose these patients to develop adhesions in the anterior cul-de-sac. Our method of reverse vesicouterine fold dissection can be particularly efficacious in these settings.

Surgical preparation and laparoscopic port placement. In the operative suite, the patient is placed under general anesthesia and positioned in the dorsal lithotomy position.¹⁰ Sterile prep and drapes are used in the standard fashion. A urinary catheter is inserted to maintain a decompressed bladder. A uterine manipulator is inserted with good placement ensured.

Per our practice, we introduce laparoscopic ports in 4 locations. The first incision is made in the umbilicus for the introduction of a 10-mm laparoscope. Three subsequent 5-mm incisions are made in the left and right lower lateral quadrants and medially at the level of the suprapubic region.¹⁰ Upon laparoscopic entry, we perform a comprehensive survey of the abdominopelvic cavity. Adequate mobility of the uterus is confirmed.¹¹ Any posterior uterine adhesions or endometriosis are treated appropriately.¹²

First step in the surgical technique: Lateral dissection

We proceed by first desiccating and cutting the round ligament laterally near the inguinal canal. This technique is carried forward in a caudal direction as the areolar tissue near the obliterated umbilical artery is expanded by the pneumoperitoneum. With a vessel sealing-cutting device, we address the attachments to the adnexa. If the ovaries are to be retained, the utero-ovarian ligament is dessicated and cut. If an oophorectomy is indicated, the infundibulopelvic ligament is dessicated and cut.

Continue to: Using the tip of the vessel sealing...

Using the tip of the vessel sealing-cutting device, the space between the anterior and posterior leaves of the broad ligament is developed and opened. A grasping forceps is then used to elevate the anterior leaf of the broad ligament and maintain medial traction. A space parallel and lateral to the cervix and bladder is then created with blunt dissection.

The inferior and medial direction of this dissection is paramount to avoid injury to nearby structures in the pelvic sidewall. Gradually, this will lead to the identification of the vesciovaginal ligament and then the vesicocervical ligament. The development of these spaces allows for the lateral and inferior displacement of the ureter. These maneuvers can mitigate ureter injury by pushing it away from the planes of dissection during the hysterectomy.

Continued traction is maintained by keeping the medial aspect of the anterior leaf of the broad ligament intact. However, the posterior leaf is dissected next, which further lateralizes the ureter. Now, with the uterine vessels fully exposed, they are thoroughly dessicated and ligated. The same procedure is then performed on the contralateral side.¹¹ (See the box below for links to videos that demonstrate the techniques described here.)

Creating the “new” space

In the “new” space that was partially developed during the lateral dissection, blunt dissection is continued, using a sweeping motion from an inferior-to-superior direction, to extend this avascular space. This is performed bilaterally until both sides are connected from the inferior aspect of the vesicouterine adhesions, if present. This thorough dissection creates what we refer to as a “new” space¹¹ (FIGURE 1).

Medially, the new space is bordered by the vesicocervical-vaginal ligament, also known as the bladder pillar. Its distal landmark is the bladder. The remaining intact anterior leaf of the broad ligament lies adjacent to the space anteriorly. The inner aspect of the obliterated umbilical artery neighbors it laterally. Lastly, the vesicovaginal plane’s posterior margin is the parametrium, which is the region where the ureter courses into the bladder. The paravesical space lies lateral to the obliterated umbilical ligament.

Visualization of this new space is made possible in the laparoscopic setting. The pneumoperitoneum allows for better demarcation of the space. Additionally, laparoscopic views of the anatomic spaces differ from those of the laparotomy view because of the magnification and the insufflation of carbon dioxide gas in the spaces.^13,14 In our experience, approaching the surgery from the “new” space could significantly decrease the risk of genitourinary injuries in patients with anterior cul-de-sac adhesions (FIGURE 2).

Using the reverse vesicouterine fold dissection technique

Among patients with prior CDs, adhesions often are at the level of or superior to the prior CD scar. By creating the new space, safe dissection from a previously untouched area can be accomplished and injury to the urinary bladder can be avoided.

The reverse vesicouterine fold dissection can be performed from this space. Using the previously described blunt sweeping motion from an inferior-to-superior direction, the vesicovaginal and vesicocervical space is further developed from an unscarred plane. This will separate the lowest portion of the bladder from the vagina, cervix, and uterus in a safe manner. Similar to the technique performed during a vaginal hysterectomy, this reverse motion of developing the bladder flap avoids erroneous and blind dissection through the vesicouterine adhesions (FIGURES 3–5).

Continue to: Completing the surgery...

Completing the surgery

Once the bladder is freely mobilized and all adhesions have been dissected, the cervix is circumferentially amputated using monopolar cautery. The vaginal cuff can then be closed from either a laparoscopic or vaginal approach using polyglactin 910 (0-Vicryl) or barbed (V-Loc) suture in a running or interrupted fashion. Our practice uses a 1.5-cm margin depth with each suture. At the end of the surgery, routine cystoscopy is performed to verify distal ureteral patency.¹⁶ Postoperatively, we manage these patients using a fast-track, or enhanced recovery, model.¹⁷

An effective technique in challenging situations

Genitourinary injury is a common complication of hysterectomy.¹⁸ The proximity of the bladder and ureters to the field of dissection during a hysterectomy can be especially challenging when the anatomy is distorted by adhesion formation from prior surgeries. One study demonstrated a 1.3% incidence of urinary tract injuries during laparoscopic hysterectomy.⁶ This included 0.54% ureteral injuries, 0.71% urinary bladder injuries, and 0.06% combined bladder and ureteral injuries.⁶ Particularly among patients with a prior CD, the risk of bladder injury can be significantly heightened.¹⁸

The reverse vesicouterine fold dissection technique that we described offers multiple benefits. By starting the procedure from an untouched and avascular plane, dissection into the plane of the prior adhesions can be circumvented; thus, bleeding is limited and injury to the bladder and ureters is avoided or minimized. By using blunt and sharp dissection, thermal injury and delayed necrosis can be mitigated. Finally, with bladder mobilization well below the colpotomy site, more adequate vaginal tissue is free to be incorporated into the vaginal cuff closure, thereby limiting the risk of cuff dehiscence.¹⁶

While we have found this technique effective for patients with prior cesarean deliveries, it also may be applied to any patient who has a scarred anterior cul-de-sac. This could include patients with prior myomectomy, cesarean scar defect, or endometriosis. Despite the technique being a safeguard against bladder injury, surgeons must still use care in developing the spaces to avoid ureteral injury, especially in a setting of distorted anatomy.

Click here to read Hot Topics in Primary Care.

Topics include: 

• Naproxen vs Opioids
• Cluster Headache
• Reducing Cardiovascular Events in Patients with Type 2 Diabetes Mellitus

This supplement offers the opportunity to earn a total of 1 CME credit. 

Credit is awarded for successful completion of the online evaluation at the link below. This link may also be found within the supplement on the first page of the article. 

• Reducing Cardiovascular Events in Your Patients with Type 2 Diabetes Mellitus
  • To receive CME credit, please read the journal article and, upon completion, go to www.pceconsortium.org/CVEvents to complete the online post-test and receive your certificate of credit.

Click here to read Hot Topics in Primary Care.

Topics include: 

• Naproxen vs Opioids
• Cluster Headache
• Reducing Cardiovascular Events in Patients with Type 2 Diabetes Mellitus

This supplement offers the opportunity to earn a total of 1 CME credit. 

Credit is awarded for successful completion of the online evaluation at the link below. This link may also be found within the supplement on the first page of the article. 

• Reducing Cardiovascular Events in Your Patients with Type 2 Diabetes Mellitus
  • To receive CME credit, please read the journal article and, upon completion, go to www.pceconsortium.org/CVEvents to complete the online post-test and receive your certificate of credit.

Click here to read Hot Topics in Primary Care.

Topics include: 

• Naproxen vs Opioids
• Cluster Headache
• Reducing Cardiovascular Events in Patients with Type 2 Diabetes Mellitus

This supplement offers the opportunity to earn a total of 1 CME credit. 

Credit is awarded for successful completion of the online evaluation at the link below. This link may also be found within the supplement on the first page of the article. 

• Reducing Cardiovascular Events in Your Patients with Type 2 Diabetes Mellitus
  • To receive CME credit, please read the journal article and, upon completion, go to www.pceconsortium.org/CVEvents to complete the online post-test and receive your certificate of credit.

Traumatic microbleeds (TMBs) may indicate vascular injury and predict worse outcomes after even minor brain injury, according to a study at the National Institute of Neurological Disorders and Stroke.

The study involved 439 adults with head injuries treated in the emergency department. The participants had magnetic resonance imaging (MRI) scans within 48 hours of the injury and again during 4 subsequent visits. They also completed behavioral and outcome questionnaires.

Microbleeds appear as small dark lesions on MRI scans but are usually too small to be seen on computer tomography (CT) scans. Sometimes they appear as dots (punctate), sometimes they are linear. In previous studies, researchers examined TMBs in the acute phase of traumatic brain injury (TBI) and stroke and found linear-appearing TMBs only in patients with TBI, suggesting that at least linear TMBs are consistent with trauma and might be the result of injured vessels. They conjectured that TMBs seen on MRI might be a form of traumatic vascular injury distinct from primary injury to the axons.

In this study, one-third of the patients had TMBs. More than half (58%) of the participants with severe head injury showed microbleeds, as did 27% of patients with mild injuries. In most patients with microbleeds, they appeared as linear streaks or dotted lesions. The study also revealed that the frontal lobes were the region most likely to show microbleeds.

The researchers controlled for variables known to predict poor outcome, such as trauma level and trauma-related injury on CT. Even so, microbleeds significantly predicted worse outcome. Patients with both punctate and linear TMBs were twice as likely to have disability (Glasgow Outcome Scale-Extended ≤6) on follow-up.

One participant’s family donated his brain for further analysis after he died. Imaging with a more powerful MRI scanner and a detailed histologic analysis allowed the researchers to better understand the pathology.

The researchers found that what appeared as a punctate TMB on MRI corresponded to iron-laden macrophages in the perivascular space surrounding a vascular tree that extended over centimeters. That was surprising, the researchers say. They expected to see iron within the parenchyma, but they also found iron inside macrophages outside of the parenchyma between the vessel and neuropil, tracking alongside vessels.

The researchers say that finding signified that the extent of injury was more extensive than indicated on MRI and had consequences to cellular function over a larger area of brain. In fact, they suggest, punctate and linear TMBs may not be distinct entities: The difference in shape may be “an issue of resolution.”

The researchers conclude that TMBs could be biomarkers for vascular injury. They also note that the leakage of blood from damaged blood vessels can trigger an inflammatory response. The damage to vessels, the disruption of normal pathways of blood flow, and the influx of inflammatory cells could result in secondary injury to the brain tissue due to ischemia.

Thus, TMBs may also be useful biomarkers for identifying which patients are candidates for treatments that reduce ischemic damage or improve microvascular cerebral blood flow.

Traumatic microbleeds (TMBs) may indicate vascular injury and predict worse outcomes after even minor brain injury, according to a study at the National Institute of Neurological Disorders and Stroke.

The study involved 439 adults with head injuries treated in the emergency department. The participants had magnetic resonance imaging (MRI) scans within 48 hours of the injury and again during 4 subsequent visits. They also completed behavioral and outcome questionnaires.

Microbleeds appear as small dark lesions on MRI scans but are usually too small to be seen on computer tomography (CT) scans. Sometimes they appear as dots (punctate), sometimes they are linear. In previous studies, researchers examined TMBs in the acute phase of traumatic brain injury (TBI) and stroke and found linear-appearing TMBs only in patients with TBI, suggesting that at least linear TMBs are consistent with trauma and might be the result of injured vessels. They conjectured that TMBs seen on MRI might be a form of traumatic vascular injury distinct from primary injury to the axons.

In this study, one-third of the patients had TMBs. More than half (58%) of the participants with severe head injury showed microbleeds, as did 27% of patients with mild injuries. In most patients with microbleeds, they appeared as linear streaks or dotted lesions. The study also revealed that the frontal lobes were the region most likely to show microbleeds.

The researchers controlled for variables known to predict poor outcome, such as trauma level and trauma-related injury on CT. Even so, microbleeds significantly predicted worse outcome. Patients with both punctate and linear TMBs were twice as likely to have disability (Glasgow Outcome Scale-Extended ≤6) on follow-up.

One participant’s family donated his brain for further analysis after he died. Imaging with a more powerful MRI scanner and a detailed histologic analysis allowed the researchers to better understand the pathology.

The researchers found that what appeared as a punctate TMB on MRI corresponded to iron-laden macrophages in the perivascular space surrounding a vascular tree that extended over centimeters. That was surprising, the researchers say. They expected to see iron within the parenchyma, but they also found iron inside macrophages outside of the parenchyma between the vessel and neuropil, tracking alongside vessels.

The researchers say that finding signified that the extent of injury was more extensive than indicated on MRI and had consequences to cellular function over a larger area of brain. In fact, they suggest, punctate and linear TMBs may not be distinct entities: The difference in shape may be “an issue of resolution.”

The researchers conclude that TMBs could be biomarkers for vascular injury. They also note that the leakage of blood from damaged blood vessels can trigger an inflammatory response. The damage to vessels, the disruption of normal pathways of blood flow, and the influx of inflammatory cells could result in secondary injury to the brain tissue due to ischemia.

Thus, TMBs may also be useful biomarkers for identifying which patients are candidates for treatments that reduce ischemic damage or improve microvascular cerebral blood flow.

Traumatic microbleeds (TMBs) may indicate vascular injury and predict worse outcomes after even minor brain injury, according to a study at the National Institute of Neurological Disorders and Stroke.

The study involved 439 adults with head injuries treated in the emergency department. The participants had magnetic resonance imaging (MRI) scans within 48 hours of the injury and again during 4 subsequent visits. They also completed behavioral and outcome questionnaires.

Microbleeds appear as small dark lesions on MRI scans but are usually too small to be seen on computer tomography (CT) scans. Sometimes they appear as dots (punctate), sometimes they are linear. In previous studies, researchers examined TMBs in the acute phase of traumatic brain injury (TBI) and stroke and found linear-appearing TMBs only in patients with TBI, suggesting that at least linear TMBs are consistent with trauma and might be the result of injured vessels. They conjectured that TMBs seen on MRI might be a form of traumatic vascular injury distinct from primary injury to the axons.

In this study, one-third of the patients had TMBs. More than half (58%) of the participants with severe head injury showed microbleeds, as did 27% of patients with mild injuries. In most patients with microbleeds, they appeared as linear streaks or dotted lesions. The study also revealed that the frontal lobes were the region most likely to show microbleeds.

The researchers controlled for variables known to predict poor outcome, such as trauma level and trauma-related injury on CT. Even so, microbleeds significantly predicted worse outcome. Patients with both punctate and linear TMBs were twice as likely to have disability (Glasgow Outcome Scale-Extended ≤6) on follow-up.

One participant’s family donated his brain for further analysis after he died. Imaging with a more powerful MRI scanner and a detailed histologic analysis allowed the researchers to better understand the pathology.

The researchers found that what appeared as a punctate TMB on MRI corresponded to iron-laden macrophages in the perivascular space surrounding a vascular tree that extended over centimeters. That was surprising, the researchers say. They expected to see iron within the parenchyma, but they also found iron inside macrophages outside of the parenchyma between the vessel and neuropil, tracking alongside vessels.

The researchers say that finding signified that the extent of injury was more extensive than indicated on MRI and had consequences to cellular function over a larger area of brain. In fact, they suggest, punctate and linear TMBs may not be distinct entities: The difference in shape may be “an issue of resolution.”

The researchers conclude that TMBs could be biomarkers for vascular injury. They also note that the leakage of blood from damaged blood vessels can trigger an inflammatory response. The damage to vessels, the disruption of normal pathways of blood flow, and the influx of inflammatory cells could result in secondary injury to the brain tissue due to ischemia.

Thus, TMBs may also be useful biomarkers for identifying which patients are candidates for treatments that reduce ischemic damage or improve microvascular cerebral blood flow.

The FP noticed a lacy net-like or reticulate appearance and thin brown papules to warty plaques over the trunk and recognized this condition as confluent and reticulated papillomatosis (CARP). A potassium hydroxide (KOH) test of a skin scraping failed to reveal yeast forms or hyphae. The FP determined that a biopsy was not necessary for diagnosis due to the distinct clinical appearance and negative KOH test. However, a biopsy could have distinguished this presentation from similar appearing disorders, including acanthosis nigricans and pityriasis versicolor.

CARP is an uncommon disorder of keratinization that affects adolescents and young adults, and is more common in Caucasians. A classic presentation involves the neck, chest, and abdomen. The differential diagnosis includes acanthosis nigricans and pityriasis versicolor, as well as more rare disorders that include Darier disease and keratosis follicularis.

There appears to be an association between the disorder and weight (specifically, being overweight). In addition, some familial cases have been reported.

Most recently, Dietzia papillomatosis, a gram-positive actinomycete has been implicated as a likely cause, which supports antibiotic therapy as the first-line approach. Minocycline 50 mg bid for 6 weeks clears the papules and plaques for most patients. Azithromycin and clarithromycin are alternatives, with various dosing strategies lasting 6 to 12 weeks. Complete clearance may take months to more than a year. About 15% of patients will experience recurrence.

This patient was treated with minocycline 50 mg bid for 12 weeks, a more common strategy at the time she was diagnosed. This led to complete clearance at 3 months, and she remained clear a year after beginning treatment.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained).

The FP noticed a lacy net-like or reticulate appearance and thin brown papules to warty plaques over the trunk and recognized this condition as confluent and reticulated papillomatosis (CARP). A potassium hydroxide (KOH) test of a skin scraping failed to reveal yeast forms or hyphae. The FP determined that a biopsy was not necessary for diagnosis due to the distinct clinical appearance and negative KOH test. However, a biopsy could have distinguished this presentation from similar appearing disorders, including acanthosis nigricans and pityriasis versicolor.

CARP is an uncommon disorder of keratinization that affects adolescents and young adults, and is more common in Caucasians. A classic presentation involves the neck, chest, and abdomen. The differential diagnosis includes acanthosis nigricans and pityriasis versicolor, as well as more rare disorders that include Darier disease and keratosis follicularis.

There appears to be an association between the disorder and weight (specifically, being overweight). In addition, some familial cases have been reported.

Most recently, Dietzia papillomatosis, a gram-positive actinomycete has been implicated as a likely cause, which supports antibiotic therapy as the first-line approach. Minocycline 50 mg bid for 6 weeks clears the papules and plaques for most patients. Azithromycin and clarithromycin are alternatives, with various dosing strategies lasting 6 to 12 weeks. Complete clearance may take months to more than a year. About 15% of patients will experience recurrence.

This patient was treated with minocycline 50 mg bid for 12 weeks, a more common strategy at the time she was diagnosed. This led to complete clearance at 3 months, and she remained clear a year after beginning treatment.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained).

The FP noticed a lacy net-like or reticulate appearance and thin brown papules to warty plaques over the trunk and recognized this condition as confluent and reticulated papillomatosis (CARP). A potassium hydroxide (KOH) test of a skin scraping failed to reveal yeast forms or hyphae. The FP determined that a biopsy was not necessary for diagnosis due to the distinct clinical appearance and negative KOH test. However, a biopsy could have distinguished this presentation from similar appearing disorders, including acanthosis nigricans and pityriasis versicolor.

CARP is an uncommon disorder of keratinization that affects adolescents and young adults, and is more common in Caucasians. A classic presentation involves the neck, chest, and abdomen. The differential diagnosis includes acanthosis nigricans and pityriasis versicolor, as well as more rare disorders that include Darier disease and keratosis follicularis.

There appears to be an association between the disorder and weight (specifically, being overweight). In addition, some familial cases have been reported.

Most recently, Dietzia papillomatosis, a gram-positive actinomycete has been implicated as a likely cause, which supports antibiotic therapy as the first-line approach. Minocycline 50 mg bid for 6 weeks clears the papules and plaques for most patients. Azithromycin and clarithromycin are alternatives, with various dosing strategies lasting 6 to 12 weeks. Complete clearance may take months to more than a year. About 15% of patients will experience recurrence.

This patient was treated with minocycline 50 mg bid for 12 weeks, a more common strategy at the time she was diagnosed. This led to complete clearance at 3 months, and she remained clear a year after beginning treatment.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained).

A Food and Drug Administration committee voted 14-1, with one abstaining vote, that the benefits of the investigational contraceptive patch AG200-15 (ethinyl estradiol and levonorgestrel; Twirla) sufficiently outweigh the risks to warrant recommendation of approval.

Most of the committee members based their decisions on the need for additional contraceptive options for patients. However, most also expressed concerns about its efficacy and offered suggestions for product labeling that called attention to high rates of unintended pregnancies and increased risk of venous thromboembolism (VTE) in obese women.

The agency’s Bone, Reproductive and Urologic Drugs Advisory Committee reviewed safety and efficacy data for AG200-15, a combined hormonal contraceptive patch developed by Agile Therapeutics. The treatment regimen involves application of a patch to the abdomen, buttock, or upper torso, and the patch is changed weekly for 3 weeks, followed by 1 week without a patch.

Elizabeth Garner, MD, consultant and former chief medical officer of Agile, presented study data on safety and effectiveness of the patch. The key study (known as Study 23) considered by the FDA included 1,736 women aged 35 years and younger. The primary efficacy endpoint was the pregnancy rate in the women who used the patch. Women reported sexual activity and back-up contraception use in e-diaries.

A total of 68 pregnancies occurred in the study population after 15,165 evaluable cycles, yielding an overall Pearl Index of 5.83 across all weight and body mass index groups. Historically, a Pearl Index of 5 has been the standard measure for effectiveness in contraceptive products, with lower being better. The index is defined as the number of pregnancies per 100 woman-years of product use. For example, a Pearl Index of 0.1 means that 1 in 1,000 women who use the same contraceptive method for 1 year becomes pregnant.

A subgroup analysis showed reduced efficacy in women with a higher BMI. The Pearl Index for women with a BMI of less than 30 kg/m² (defined as nonobese) was 4.34, whereas in women with a BMI of 30 kg/m² and higher (defined as obese), the index was 8.64, nearly double that of nonobese women. No significant differences in the index were noted based on race/ethnicity.

The company described the patch as filling a niche and providing an additional alternative for women seeking a noninvasive method of contraception. It proposed a limitation of use (LOU) as part of the product label that would provide detailed information on efficacy based on the Pearl Index for the different categories of BMI and would suggest that the patch may be less effective for women with obesity. Most of the committee members favored use of a LOU statement on the label, but some noted that it might limit prescriptions to nonobese women.

The committee expressed concern over the Pearl data in the study. The FDA has never approved a contraceptive product with a Pearl Index of greater than 5, said Yun Tang, PhD, a statistical reviewer for the agency’s Office of Translational Sciences, who presented the evaluation of the effectiveness of AG200-15.

Key safety concerns raised in discussion included the risk of venous thromboembolism and the risk of unscheduled bleeding. Both of those issues were significantly more common among obese women, said Nneka McNeal-Jackson, MD, clinical reviewer for the FDA, who presented details on the safety profile and risk-benefit considerations for the patch.

Overall, in Study 23, the incidence rate of VTE was 28/10,000 women-years, with cases in five participants. Four of those were deemed related to the patch, and all occurred in obese women.

Virginia C. “Jennie” Leslie, MD, of Oregon Health and Science University, Portland, voted no to recommending approval of the patch mainly because of efficacy concerns. “My goal is to do no harm, and I have concerns regarding efficacy and giving our patients a false sense of hope,” she said.

Even those members who voted yes expressed concerns about the efficacy data and VTE risk in obese women and recommended postmarketing studies and appropriate labeling to help clinicians in shared decision making with their patients.

Esther Eisenberg, MD, of the National Institutes of Health, noted that the patch fills a need, certainly for women with a BMI less than 30 kg/m², and suggested that use be limited to women in that lower BMI category.

Other committee members suggested that the product not be restricted based on BMI, but rather that the LOU provide clear explanations of how effectiveness decreases as BMI increases.

David J. Margolis, MD, of the University of Pennsylvania, Philadelphia, opted to abstain from voting, in part based on concerns about the study design and a lack of additional data from the company.

A Food and Drug Administration committee voted 14-1, with one abstaining vote, that the benefits of the investigational contraceptive patch AG200-15 (ethinyl estradiol and levonorgestrel; Twirla) sufficiently outweigh the risks to warrant recommendation of approval.

Most of the committee members based their decisions on the need for additional contraceptive options for patients. However, most also expressed concerns about its efficacy and offered suggestions for product labeling that called attention to high rates of unintended pregnancies and increased risk of venous thromboembolism (VTE) in obese women.

The agency’s Bone, Reproductive and Urologic Drugs Advisory Committee reviewed safety and efficacy data for AG200-15, a combined hormonal contraceptive patch developed by Agile Therapeutics. The treatment regimen involves application of a patch to the abdomen, buttock, or upper torso, and the patch is changed weekly for 3 weeks, followed by 1 week without a patch.

Elizabeth Garner, MD, consultant and former chief medical officer of Agile, presented study data on safety and effectiveness of the patch. The key study (known as Study 23) considered by the FDA included 1,736 women aged 35 years and younger. The primary efficacy endpoint was the pregnancy rate in the women who used the patch. Women reported sexual activity and back-up contraception use in e-diaries.

A total of 68 pregnancies occurred in the study population after 15,165 evaluable cycles, yielding an overall Pearl Index of 5.83 across all weight and body mass index groups. Historically, a Pearl Index of 5 has been the standard measure for effectiveness in contraceptive products, with lower being better. The index is defined as the number of pregnancies per 100 woman-years of product use. For example, a Pearl Index of 0.1 means that 1 in 1,000 women who use the same contraceptive method for 1 year becomes pregnant.

A subgroup analysis showed reduced efficacy in women with a higher BMI. The Pearl Index for women with a BMI of less than 30 kg/m² (defined as nonobese) was 4.34, whereas in women with a BMI of 30 kg/m² and higher (defined as obese), the index was 8.64, nearly double that of nonobese women. No significant differences in the index were noted based on race/ethnicity.

The company described the patch as filling a niche and providing an additional alternative for women seeking a noninvasive method of contraception. It proposed a limitation of use (LOU) as part of the product label that would provide detailed information on efficacy based on the Pearl Index for the different categories of BMI and would suggest that the patch may be less effective for women with obesity. Most of the committee members favored use of a LOU statement on the label, but some noted that it might limit prescriptions to nonobese women.

The committee expressed concern over the Pearl data in the study. The FDA has never approved a contraceptive product with a Pearl Index of greater than 5, said Yun Tang, PhD, a statistical reviewer for the agency’s Office of Translational Sciences, who presented the evaluation of the effectiveness of AG200-15.

Key safety concerns raised in discussion included the risk of venous thromboembolism and the risk of unscheduled bleeding. Both of those issues were significantly more common among obese women, said Nneka McNeal-Jackson, MD, clinical reviewer for the FDA, who presented details on the safety profile and risk-benefit considerations for the patch.

Overall, in Study 23, the incidence rate of VTE was 28/10,000 women-years, with cases in five participants. Four of those were deemed related to the patch, and all occurred in obese women.

Virginia C. “Jennie” Leslie, MD, of Oregon Health and Science University, Portland, voted no to recommending approval of the patch mainly because of efficacy concerns. “My goal is to do no harm, and I have concerns regarding efficacy and giving our patients a false sense of hope,” she said.

Even those members who voted yes expressed concerns about the efficacy data and VTE risk in obese women and recommended postmarketing studies and appropriate labeling to help clinicians in shared decision making with their patients.

Esther Eisenberg, MD, of the National Institutes of Health, noted that the patch fills a need, certainly for women with a BMI less than 30 kg/m², and suggested that use be limited to women in that lower BMI category.

Other committee members suggested that the product not be restricted based on BMI, but rather that the LOU provide clear explanations of how effectiveness decreases as BMI increases.

David J. Margolis, MD, of the University of Pennsylvania, Philadelphia, opted to abstain from voting, in part based on concerns about the study design and a lack of additional data from the company.

A Food and Drug Administration committee voted 14-1, with one abstaining vote, that the benefits of the investigational contraceptive patch AG200-15 (ethinyl estradiol and levonorgestrel; Twirla) sufficiently outweigh the risks to warrant recommendation of approval.

Most of the committee members based their decisions on the need for additional contraceptive options for patients. However, most also expressed concerns about its efficacy and offered suggestions for product labeling that called attention to high rates of unintended pregnancies and increased risk of venous thromboembolism (VTE) in obese women.

The agency’s Bone, Reproductive and Urologic Drugs Advisory Committee reviewed safety and efficacy data for AG200-15, a combined hormonal contraceptive patch developed by Agile Therapeutics. The treatment regimen involves application of a patch to the abdomen, buttock, or upper torso, and the patch is changed weekly for 3 weeks, followed by 1 week without a patch.

Elizabeth Garner, MD, consultant and former chief medical officer of Agile, presented study data on safety and effectiveness of the patch. The key study (known as Study 23) considered by the FDA included 1,736 women aged 35 years and younger. The primary efficacy endpoint was the pregnancy rate in the women who used the patch. Women reported sexual activity and back-up contraception use in e-diaries.

A total of 68 pregnancies occurred in the study population after 15,165 evaluable cycles, yielding an overall Pearl Index of 5.83 across all weight and body mass index groups. Historically, a Pearl Index of 5 has been the standard measure for effectiveness in contraceptive products, with lower being better. The index is defined as the number of pregnancies per 100 woman-years of product use. For example, a Pearl Index of 0.1 means that 1 in 1,000 women who use the same contraceptive method for 1 year becomes pregnant.

A subgroup analysis showed reduced efficacy in women with a higher BMI. The Pearl Index for women with a BMI of less than 30 kg/m² (defined as nonobese) was 4.34, whereas in women with a BMI of 30 kg/m² and higher (defined as obese), the index was 8.64, nearly double that of nonobese women. No significant differences in the index were noted based on race/ethnicity.

The company described the patch as filling a niche and providing an additional alternative for women seeking a noninvasive method of contraception. It proposed a limitation of use (LOU) as part of the product label that would provide detailed information on efficacy based on the Pearl Index for the different categories of BMI and would suggest that the patch may be less effective for women with obesity. Most of the committee members favored use of a LOU statement on the label, but some noted that it might limit prescriptions to nonobese women.

The committee expressed concern over the Pearl data in the study. The FDA has never approved a contraceptive product with a Pearl Index of greater than 5, said Yun Tang, PhD, a statistical reviewer for the agency’s Office of Translational Sciences, who presented the evaluation of the effectiveness of AG200-15.

Key safety concerns raised in discussion included the risk of venous thromboembolism and the risk of unscheduled bleeding. Both of those issues were significantly more common among obese women, said Nneka McNeal-Jackson, MD, clinical reviewer for the FDA, who presented details on the safety profile and risk-benefit considerations for the patch.

Overall, in Study 23, the incidence rate of VTE was 28/10,000 women-years, with cases in five participants. Four of those were deemed related to the patch, and all occurred in obese women.

Virginia C. “Jennie” Leslie, MD, of Oregon Health and Science University, Portland, voted no to recommending approval of the patch mainly because of efficacy concerns. “My goal is to do no harm, and I have concerns regarding efficacy and giving our patients a false sense of hope,” she said.

Even those members who voted yes expressed concerns about the efficacy data and VTE risk in obese women and recommended postmarketing studies and appropriate labeling to help clinicians in shared decision making with their patients.

Esther Eisenberg, MD, of the National Institutes of Health, noted that the patch fills a need, certainly for women with a BMI less than 30 kg/m², and suggested that use be limited to women in that lower BMI category.

Other committee members suggested that the product not be restricted based on BMI, but rather that the LOU provide clear explanations of how effectiveness decreases as BMI increases.

David J. Margolis, MD, of the University of Pennsylvania, Philadelphia, opted to abstain from voting, in part based on concerns about the study design and a lack of additional data from the company.

A crappy excuse of a database

Have you ever been so impressed with your bowel movement that you’ve been compelled to record the incident for posterity? No? Just us? Well, you may want to reconsider, because a pair of AI tech companies are looking for a few good poop pictures.

Andy/Getty Images

It’s all part of the “Give a S--t” (you can probably guess what we’ve censored out) campaign, a joint venture from Auggi, a gut health start-up, and Seed Health. The companies hope to use photos sent in by regular people to build an app that would help people with chronic gut problems automatically track their own bowel movements. In addition, the photo library could also be used for research into gut-related diseases such as irritable bowl syndrome.

The two companies hope to collect 100,000 photos for their library, which is an absolutely prodigious amount of poop to sort through. But hey, that’s what the AI is for. They already know the AI works, as Auggi created a proof-of-concept library of 36,000 images of faux feces made from blue Play-Doh. The AI was able to recognize consistency according to the Bristol scale basically 100% of the time.

If you’ve been inspired, you can submit your lovely poop pictures here. Seed and Auggi expect contributers to send only one image each, but multiple submissions are welcome. They’ve already received a dozen from LOTME world headquarters. We love a good bowel movement here.

Criminal moon

“The Wolf Man.” “An American Werewolf in London.” “The Howling.” “Teen Wolf.” All terrifying Hollywood tales of bloodthirsty behavior and sanguinary slaughter. (Michael J. Fox as a hirsute homicidal lycan? Okay, maybe not “Teen Wolf.”)

Vlad Gans/Getty Images

And the propellant igniting all that criminal lycanthropy? The full moon.

Any teacher will swear a full moon portends the kind of student behavior that an entire pot of teachers’ lounge coffee can’t counter. And every cop knows it’s going to be a “Training Day” shift when the lunar light shines brightest.

But is the Thin Blue Line truly stretched to snapping during a full moon? New York University’s BetaGov research team looked at the purported “lunar effect” linking crime and the full moon. A lit review revealed mixed findings for and against a criminal lunar effect. The team then collaborated with the Vallejo, Calif., police department to match the moon’s phases with the city’s crime events. They did the same with departments in Canada and Mexico.

The results? A full moon had no effect on Vallejo’s crime rate, or anywhere else in North America.

While the finding eviscerates the moon-induced mayhem hypothesis, cops walking a full-moonlit beat can at least take comfort in this fact: Unlike London, Vallejo is clearly free of American werewolves.

A doctor’s note … of terror

With Halloween upon us, here’s a veddy scary riddle: When is a sports physical not a sports physical?

CheeriesJD/Getty Images

When it’s a haunted house physical.

Specifically, when the haunted house is McKamey Manor in Summertown, Tenn. … and in Huntsville, Ala. That’s right, it can be in two places at the same time. Terrifying.

McKamey Manor is considered by many to be the most terrifying haunted house in the United States, and by some to be a “torture chamber under disguise.”

The “Surivial [we think they misspelled it on purpose to make it even scarier] Horror Challenge” is so terrifying that management requires all participants to have a “completed ‘sports physical’ and doctor’s letter stating you are physically and mentally cleared,” as well as proof of medical insurance. Each paying customer also has to “pass a portable drug test on the day of the show,” according to the McKamey Manor website.

The manor also happens to be the subject of a petition, which currently has over 58,000 signatures, asking state officials in Alabama and Tennessee to shut it down because “some people have had to seek professional psychiatric help and medical care for extensive injuries.”

Ironically, we hear that some of the most traumatized customers have been actual physicians who succumbed to the horrors of Prior Approval Asylum, the EHR Torment Room, and the River of the Damned Maintenance of Certification.

A crappy excuse of a database

Have you ever been so impressed with your bowel movement that you’ve been compelled to record the incident for posterity? No? Just us? Well, you may want to reconsider, because a pair of AI tech companies are looking for a few good poop pictures.

Andy/Getty Images

It’s all part of the “Give a S--t” (you can probably guess what we’ve censored out) campaign, a joint venture from Auggi, a gut health start-up, and Seed Health. The companies hope to use photos sent in by regular people to build an app that would help people with chronic gut problems automatically track their own bowel movements. In addition, the photo library could also be used for research into gut-related diseases such as irritable bowl syndrome.

The two companies hope to collect 100,000 photos for their library, which is an absolutely prodigious amount of poop to sort through. But hey, that’s what the AI is for. They already know the AI works, as Auggi created a proof-of-concept library of 36,000 images of faux feces made from blue Play-Doh. The AI was able to recognize consistency according to the Bristol scale basically 100% of the time.

If you’ve been inspired, you can submit your lovely poop pictures here. Seed and Auggi expect contributers to send only one image each, but multiple submissions are welcome. They’ve already received a dozen from LOTME world headquarters. We love a good bowel movement here.

Criminal moon

“The Wolf Man.” “An American Werewolf in London.” “The Howling.” “Teen Wolf.” All terrifying Hollywood tales of bloodthirsty behavior and sanguinary slaughter. (Michael J. Fox as a hirsute homicidal lycan? Okay, maybe not “Teen Wolf.”)

Vlad Gans/Getty Images

And the propellant igniting all that criminal lycanthropy? The full moon.

Any teacher will swear a full moon portends the kind of student behavior that an entire pot of teachers’ lounge coffee can’t counter. And every cop knows it’s going to be a “Training Day” shift when the lunar light shines brightest.

But is the Thin Blue Line truly stretched to snapping during a full moon? New York University’s BetaGov research team looked at the purported “lunar effect” linking crime and the full moon. A lit review revealed mixed findings for and against a criminal lunar effect. The team then collaborated with the Vallejo, Calif., police department to match the moon’s phases with the city’s crime events. They did the same with departments in Canada and Mexico.

The results? A full moon had no effect on Vallejo’s crime rate, or anywhere else in North America.

While the finding eviscerates the moon-induced mayhem hypothesis, cops walking a full-moonlit beat can at least take comfort in this fact: Unlike London, Vallejo is clearly free of American werewolves.

A doctor’s note … of terror

With Halloween upon us, here’s a veddy scary riddle: When is a sports physical not a sports physical?

CheeriesJD/Getty Images

When it’s a haunted house physical.

Specifically, when the haunted house is McKamey Manor in Summertown, Tenn. … and in Huntsville, Ala. That’s right, it can be in two places at the same time. Terrifying.

McKamey Manor is considered by many to be the most terrifying haunted house in the United States, and by some to be a “torture chamber under disguise.”

The “Surivial [we think they misspelled it on purpose to make it even scarier] Horror Challenge” is so terrifying that management requires all participants to have a “completed ‘sports physical’ and doctor’s letter stating you are physically and mentally cleared,” as well as proof of medical insurance. Each paying customer also has to “pass a portable drug test on the day of the show,” according to the McKamey Manor website.

The manor also happens to be the subject of a petition, which currently has over 58,000 signatures, asking state officials in Alabama and Tennessee to shut it down because “some people have had to seek professional psychiatric help and medical care for extensive injuries.”

Ironically, we hear that some of the most traumatized customers have been actual physicians who succumbed to the horrors of Prior Approval Asylum, the EHR Torment Room, and the River of the Damned Maintenance of Certification.

A crappy excuse of a database

Have you ever been so impressed with your bowel movement that you’ve been compelled to record the incident for posterity? No? Just us? Well, you may want to reconsider, because a pair of AI tech companies are looking for a few good poop pictures.

Andy/Getty Images

It’s all part of the “Give a S--t” (you can probably guess what we’ve censored out) campaign, a joint venture from Auggi, a gut health start-up, and Seed Health. The companies hope to use photos sent in by regular people to build an app that would help people with chronic gut problems automatically track their own bowel movements. In addition, the photo library could also be used for research into gut-related diseases such as irritable bowl syndrome.

The two companies hope to collect 100,000 photos for their library, which is an absolutely prodigious amount of poop to sort through. But hey, that’s what the AI is for. They already know the AI works, as Auggi created a proof-of-concept library of 36,000 images of faux feces made from blue Play-Doh. The AI was able to recognize consistency according to the Bristol scale basically 100% of the time.

If you’ve been inspired, you can submit your lovely poop pictures here. Seed and Auggi expect contributers to send only one image each, but multiple submissions are welcome. They’ve already received a dozen from LOTME world headquarters. We love a good bowel movement here.

Criminal moon

“The Wolf Man.” “An American Werewolf in London.” “The Howling.” “Teen Wolf.” All terrifying Hollywood tales of bloodthirsty behavior and sanguinary slaughter. (Michael J. Fox as a hirsute homicidal lycan? Okay, maybe not “Teen Wolf.”)

Vlad Gans/Getty Images

And the propellant igniting all that criminal lycanthropy? The full moon.

Any teacher will swear a full moon portends the kind of student behavior that an entire pot of teachers’ lounge coffee can’t counter. And every cop knows it’s going to be a “Training Day” shift when the lunar light shines brightest.

But is the Thin Blue Line truly stretched to snapping during a full moon? New York University’s BetaGov research team looked at the purported “lunar effect” linking crime and the full moon. A lit review revealed mixed findings for and against a criminal lunar effect. The team then collaborated with the Vallejo, Calif., police department to match the moon’s phases with the city’s crime events. They did the same with departments in Canada and Mexico.

The results? A full moon had no effect on Vallejo’s crime rate, or anywhere else in North America.

While the finding eviscerates the moon-induced mayhem hypothesis, cops walking a full-moonlit beat can at least take comfort in this fact: Unlike London, Vallejo is clearly free of American werewolves.

A doctor’s note … of terror

With Halloween upon us, here’s a veddy scary riddle: When is a sports physical not a sports physical?

CheeriesJD/Getty Images

When it’s a haunted house physical.

Specifically, when the haunted house is McKamey Manor in Summertown, Tenn. … and in Huntsville, Ala. That’s right, it can be in two places at the same time. Terrifying.

McKamey Manor is considered by many to be the most terrifying haunted house in the United States, and by some to be a “torture chamber under disguise.”

The “Surivial [we think they misspelled it on purpose to make it even scarier] Horror Challenge” is so terrifying that management requires all participants to have a “completed ‘sports physical’ and doctor’s letter stating you are physically and mentally cleared,” as well as proof of medical insurance. Each paying customer also has to “pass a portable drug test on the day of the show,” according to the McKamey Manor website.

The manor also happens to be the subject of a petition, which currently has over 58,000 signatures, asking state officials in Alabama and Tennessee to shut it down because “some people have had to seek professional psychiatric help and medical care for extensive injuries.”

Ironically, we hear that some of the most traumatized customers have been actual physicians who succumbed to the horrors of Prior Approval Asylum, the EHR Torment Room, and the River of the Damned Maintenance of Certification.

Two cases of bacteremia have been described in two patients who received fecal microbiota transplants from the same donor.

Writing in the New England Journal of Medicine, researchers reported the two case studies of extended-spectrum beta-lactamase (ESBL)–producing Escherichia coli bacteremia, one of which ended in the death of the patient. These cases were previously announced by the Food and Drug Administration in a June 2019 safety alert.

Zachariah DeFilipp, MD, from Massachusetts General Hospital at Harvard Medical School, Boston, and coauthors wrote that fecal microbiota transplantation is rarely associated with complications. Placebo-controlled trials and a systematic review have found similar rates of complications in immunocompromised and immunocompetent recipients. Only four cases of gram-negative bacteremia previously have been reported, and in three of these, there was a plausible alternative explanation for the bacteremia.

In this paper, both patients received fecal microbiota transplantation via frozen oral capsules containing donor stool. These capsules were prepared prior to the implementation of screening for ESBL-producing organisms at the institution, and were not retrospectively tested since this expanded donor screening.

The first patient was a 69-year-old man with liver cirrhosis attributed to hepatitis C infection who was enrolled in a trial of fecal microbiota transplantation via oral capsules to treat hepatic encephalopathy. The first sign of the adverse event was a fever and cough, which developed 17 days after the final dose of 15 capsules. He was treated for pneumonia but failed to improve after 2 days, at which time gram-negative rods were discovered in blood cultures taken at the initial presentation.

After admission and further treatment, blood cultures were found to have ESBL-producing E. coli, and after further treatment, the patient was clinically stable. A stool sample taken after treatment was negative for ESBL-producing E. coli.

The second case study was a 73-year-old man with therapy-related myelodysplastic syndrome who was undergoing allogeneic hematopoietic stem cell transplantation and was receiving fecal microbiota transplantation via oral capsule as part of a phase 2 trial.

Eight days after the last dose of oral capsules, and 5 days after the stem-cell infusion, the man developed a fever, chills, febrile neutropenia and showed altered mental status. He was treated with cefepime but developed hypoxia and labored breathing later that evening, which prompted clinicians to intubate and begin mechanical ventilation.

His blood culture results showed gram-negative rods, and meropenem was added to his antibiotic regimen. However, the patient’s condition worsened, and he died of severe sepsis 2 days later with blood cultures confirmed as positive for ESBL-producing E. coli.

A follow-up investigation revealed that both patients received stool from the same donor. Each lot of three capsules from that donor was found to contain ESBL-producing E. coli with a resistance pattern similar to that seen in the two recipients.

Twenty-two patients had received capsules from this donor. Researchers contacted all the recipients and offered them stool screening for ESBL-producing E. coli. Twelve underwent testing, which found that five had samples that grew on ESBL-producing E. coli–selective medium.

The remaining seven patients who had follow-up testing were receiving treatment for recurrent or refractory Clostridioides difficile infection, and four of these grew samples on the selective medium.

“When FMT is successful, the recipient’s metagenomic burden of antimicrobial resistance genes mimics that of the donor,” the authors wrote. “Although we cannot conclusively attribute positive screening results for ESBL-producing organisms in other asymptomatic recipients to FMT, the rates of positive tests are, in our opinion, unexpectedly high and probably represent transmission through FMT.”

The authors said the donor had no risk factors for carriage of multidrug-resistant organism and had previously donated fecal material before the introduction of routine screening for ESBL-producing organisms.

However, they noted that both patients had risk factors for bacteremia, namely advanced cirrhosis and allogeneic hematopoietic stem cell transplantation and they also received oral antibiotics around the time of the fecal microbiota transplantation.

“Despite the infectious complications reported here, the benefits of FMT should be balanced with the associated risks when considering treatment options for patients with recurrent or refractory C. difficile infection,” the authors wrote. “Ongoing assessment of the risks and benefit of FMT research is needed, as are continuing efforts to improve donor screening to limit transmission of microorganisms that could lead to adverse infectious events.”

The American Gastroenterological Association FMT National Registry is a critical effort to track short- and long-term patient outcomes and potential risks associated with FMT. The registry's goal is to track 4,000 patients for 10 years. If you perform FMT, please contribute to this important initiative. Learn more at www.gastro.org/FMTRegistry.

The study was supported by a grant from the American College of Gastroenterology. Three authors declared personal fees and grants from the medical sector outside the submitted work, and two were attached to a diagnostics company involved in the study.

SOURCE: DeFilipp Z et al. N Engl J Med. 2019 Oct 30. doi: 10.1056/NEJMoa1910437.

* This story was updated on Oct. 31, 2019.

Two cases of bacteremia have been described in two patients who received fecal microbiota transplants from the same donor.

Writing in the New England Journal of Medicine, researchers reported the two case studies of extended-spectrum beta-lactamase (ESBL)–producing Escherichia coli bacteremia, one of which ended in the death of the patient. These cases were previously announced by the Food and Drug Administration in a June 2019 safety alert.

Zachariah DeFilipp, MD, from Massachusetts General Hospital at Harvard Medical School, Boston, and coauthors wrote that fecal microbiota transplantation is rarely associated with complications. Placebo-controlled trials and a systematic review have found similar rates of complications in immunocompromised and immunocompetent recipients. Only four cases of gram-negative bacteremia previously have been reported, and in three of these, there was a plausible alternative explanation for the bacteremia.

In this paper, both patients received fecal microbiota transplantation via frozen oral capsules containing donor stool. These capsules were prepared prior to the implementation of screening for ESBL-producing organisms at the institution, and were not retrospectively tested since this expanded donor screening.

The first patient was a 69-year-old man with liver cirrhosis attributed to hepatitis C infection who was enrolled in a trial of fecal microbiota transplantation via oral capsules to treat hepatic encephalopathy. The first sign of the adverse event was a fever and cough, which developed 17 days after the final dose of 15 capsules. He was treated for pneumonia but failed to improve after 2 days, at which time gram-negative rods were discovered in blood cultures taken at the initial presentation.

After admission and further treatment, blood cultures were found to have ESBL-producing E. coli, and after further treatment, the patient was clinically stable. A stool sample taken after treatment was negative for ESBL-producing E. coli.

The second case study was a 73-year-old man with therapy-related myelodysplastic syndrome who was undergoing allogeneic hematopoietic stem cell transplantation and was receiving fecal microbiota transplantation via oral capsule as part of a phase 2 trial.

Eight days after the last dose of oral capsules, and 5 days after the stem-cell infusion, the man developed a fever, chills, febrile neutropenia and showed altered mental status. He was treated with cefepime but developed hypoxia and labored breathing later that evening, which prompted clinicians to intubate and begin mechanical ventilation.

His blood culture results showed gram-negative rods, and meropenem was added to his antibiotic regimen. However, the patient’s condition worsened, and he died of severe sepsis 2 days later with blood cultures confirmed as positive for ESBL-producing E. coli.

A follow-up investigation revealed that both patients received stool from the same donor. Each lot of three capsules from that donor was found to contain ESBL-producing E. coli with a resistance pattern similar to that seen in the two recipients.

Twenty-two patients had received capsules from this donor. Researchers contacted all the recipients and offered them stool screening for ESBL-producing E. coli. Twelve underwent testing, which found that five had samples that grew on ESBL-producing E. coli–selective medium.

The remaining seven patients who had follow-up testing were receiving treatment for recurrent or refractory Clostridioides difficile infection, and four of these grew samples on the selective medium.

“When FMT is successful, the recipient’s metagenomic burden of antimicrobial resistance genes mimics that of the donor,” the authors wrote. “Although we cannot conclusively attribute positive screening results for ESBL-producing organisms in other asymptomatic recipients to FMT, the rates of positive tests are, in our opinion, unexpectedly high and probably represent transmission through FMT.”

The authors said the donor had no risk factors for carriage of multidrug-resistant organism and had previously donated fecal material before the introduction of routine screening for ESBL-producing organisms.

However, they noted that both patients had risk factors for bacteremia, namely advanced cirrhosis and allogeneic hematopoietic stem cell transplantation and they also received oral antibiotics around the time of the fecal microbiota transplantation.

“Despite the infectious complications reported here, the benefits of FMT should be balanced with the associated risks when considering treatment options for patients with recurrent or refractory C. difficile infection,” the authors wrote. “Ongoing assessment of the risks and benefit of FMT research is needed, as are continuing efforts to improve donor screening to limit transmission of microorganisms that could lead to adverse infectious events.”

The American Gastroenterological Association FMT National Registry is a critical effort to track short- and long-term patient outcomes and potential risks associated with FMT. The registry's goal is to track 4,000 patients for 10 years. If you perform FMT, please contribute to this important initiative. Learn more at www.gastro.org/FMTRegistry.

The study was supported by a grant from the American College of Gastroenterology. Three authors declared personal fees and grants from the medical sector outside the submitted work, and two were attached to a diagnostics company involved in the study.

SOURCE: DeFilipp Z et al. N Engl J Med. 2019 Oct 30. doi: 10.1056/NEJMoa1910437.

* This story was updated on Oct. 31, 2019.

Two cases of bacteremia have been described in two patients who received fecal microbiota transplants from the same donor.

Writing in the New England Journal of Medicine, researchers reported the two case studies of extended-spectrum beta-lactamase (ESBL)–producing Escherichia coli bacteremia, one of which ended in the death of the patient. These cases were previously announced by the Food and Drug Administration in a June 2019 safety alert.

Zachariah DeFilipp, MD, from Massachusetts General Hospital at Harvard Medical School, Boston, and coauthors wrote that fecal microbiota transplantation is rarely associated with complications. Placebo-controlled trials and a systematic review have found similar rates of complications in immunocompromised and immunocompetent recipients. Only four cases of gram-negative bacteremia previously have been reported, and in three of these, there was a plausible alternative explanation for the bacteremia.

In this paper, both patients received fecal microbiota transplantation via frozen oral capsules containing donor stool. These capsules were prepared prior to the implementation of screening for ESBL-producing organisms at the institution, and were not retrospectively tested since this expanded donor screening.

The first patient was a 69-year-old man with liver cirrhosis attributed to hepatitis C infection who was enrolled in a trial of fecal microbiota transplantation via oral capsules to treat hepatic encephalopathy. The first sign of the adverse event was a fever and cough, which developed 17 days after the final dose of 15 capsules. He was treated for pneumonia but failed to improve after 2 days, at which time gram-negative rods were discovered in blood cultures taken at the initial presentation.

After admission and further treatment, blood cultures were found to have ESBL-producing E. coli, and after further treatment, the patient was clinically stable. A stool sample taken after treatment was negative for ESBL-producing E. coli.

The second case study was a 73-year-old man with therapy-related myelodysplastic syndrome who was undergoing allogeneic hematopoietic stem cell transplantation and was receiving fecal microbiota transplantation via oral capsule as part of a phase 2 trial.

Eight days after the last dose of oral capsules, and 5 days after the stem-cell infusion, the man developed a fever, chills, febrile neutropenia and showed altered mental status. He was treated with cefepime but developed hypoxia and labored breathing later that evening, which prompted clinicians to intubate and begin mechanical ventilation.

His blood culture results showed gram-negative rods, and meropenem was added to his antibiotic regimen. However, the patient’s condition worsened, and he died of severe sepsis 2 days later with blood cultures confirmed as positive for ESBL-producing E. coli.

A follow-up investigation revealed that both patients received stool from the same donor. Each lot of three capsules from that donor was found to contain ESBL-producing E. coli with a resistance pattern similar to that seen in the two recipients.

Twenty-two patients had received capsules from this donor. Researchers contacted all the recipients and offered them stool screening for ESBL-producing E. coli. Twelve underwent testing, which found that five had samples that grew on ESBL-producing E. coli–selective medium.

The remaining seven patients who had follow-up testing were receiving treatment for recurrent or refractory Clostridioides difficile infection, and four of these grew samples on the selective medium.

“When FMT is successful, the recipient’s metagenomic burden of antimicrobial resistance genes mimics that of the donor,” the authors wrote. “Although we cannot conclusively attribute positive screening results for ESBL-producing organisms in other asymptomatic recipients to FMT, the rates of positive tests are, in our opinion, unexpectedly high and probably represent transmission through FMT.”

The authors said the donor had no risk factors for carriage of multidrug-resistant organism and had previously donated fecal material before the introduction of routine screening for ESBL-producing organisms.

However, they noted that both patients had risk factors for bacteremia, namely advanced cirrhosis and allogeneic hematopoietic stem cell transplantation and they also received oral antibiotics around the time of the fecal microbiota transplantation.

“Despite the infectious complications reported here, the benefits of FMT should be balanced with the associated risks when considering treatment options for patients with recurrent or refractory C. difficile infection,” the authors wrote. “Ongoing assessment of the risks and benefit of FMT research is needed, as are continuing efforts to improve donor screening to limit transmission of microorganisms that could lead to adverse infectious events.”

The American Gastroenterological Association FMT National Registry is a critical effort to track short- and long-term patient outcomes and potential risks associated with FMT. The registry's goal is to track 4,000 patients for 10 years. If you perform FMT, please contribute to this important initiative. Learn more at www.gastro.org/FMTRegistry.

The study was supported by a grant from the American College of Gastroenterology. Three authors declared personal fees and grants from the medical sector outside the submitted work, and two were attached to a diagnostics company involved in the study.

SOURCE: DeFilipp Z et al. N Engl J Med. 2019 Oct 30. doi: 10.1056/NEJMoa1910437.

* This story was updated on Oct. 31, 2019.

Clyde E. Markowitz, MD, is the director of the Multiple Sclerosis Center at Penn Neuroscience Center and an Associate Professor of Neurology at the Perelman School of Medicine at the University of Pennsylvania. We sat down with Dr. Markowitz to talk about different multiple sclerosis (MS) therapies and how to determine when it might be time to switch a patient’s current regimen.

Why would an MS specialist switch a patient from one drug therapy to another?

The main reason we switch a patient from one treatment to another is usually related to an inadequate response to their current treatment. This can be seen when a patient is having new clinical symptoms suggestive of a relapse. Additional situations which would cause us to consider a switch in treatment include if the patient has had a new abnormalities seen on MRI scans, such as new T2 lesions or gadolinium- enhancing lesions. We might also switch a patient due to intolerance towards the medication they are on. For example, if they are experiencing flu-like symptoms or having Gastrointestinal issues.

In addition, the expectation that the treatment should slow the rate of progression may not be adequately demonstrating the desired effect. In that setting, we may consider a switch to a drug with a different mechanism of action to hopefully better control disease progression.

Laboratory abnormalities while on treatment might also be a consideration for a switch in therapy. Elevated LFTs, or low WBCs can occur on DMTs and may require a change in treatment. Patients on Natalizumab, require JC virus antibody testing. If the patient’s JCV Ab status changes from negative to positive or a rising index may require a change in therapy to avoid the development of PML.  

What are some special considerations for patients during a switch in therapy?

We need to take into consideration the patient’s comorbidities. Does the patient have a history of diabetes, hypertension, cardiac concerns or a risk for infectious complications? What is the patient’s age? As individuals age the immune system becomes less robust at fighting infections or surveillance for malignancies. Some of the medications are immunosuppressive and might increase the risk of developing opportunistic infections or cancers.

Family planning should be taken into consideration during the discussion of which medications might be appropriate. Is the patient planning to have a pregnancy in the near future? Some medications might not be appropriate in that case.

Route of administration could be a factor to consider, since there are several medications that are administered as an infusion in a medical office or hospital setting. This could create issues for some patients who are employed and may have to miss work during these infusions. This could be as frequent as monthly or 2-3 times per year. Some patients just starting a new job, may feel uncomfortable taking time off or disclosing that they have MS leading to concerns for job security.

We also consider the side effects of the new treatment. What side effects and safety monitoring are required for a particular medication? Are there frequent blood tests, cardiac monitoring, dermatologic and ophthalmologic monitoring? How will this impact the patient’s quality of life?

In the end, it comes down to the level of monitoring required for a particular treatment, where the patient is in his or her life, and where he or she is in the disease course.

What are some potential complications when switching therapies?

When switching therapies, one of the bigger concerns is how quickly can we get the patient on the new therapy. Some medications when stopped can lead to return of disease activity or possibly lead to a rebound phenomenon with significant inflammatory activity. We focus on transitioning a patient quickly to a new drug that has a rapid mechanism of action thus limiting the amount of time that a patient is without a treatment. However, based on the mechanism of action of the drug you must consider if a wash out is necessary. The question is how quickly can the patient start the new drug thus preventing a rebound phenomenon. Ideally, no wash out would protect the patient best but might have safety concerns depending on the switch drug profile. If the switch was related to concerns for high JC virus antibody titer going off of natalizumab, there may be a need to make sure the patient does not have PML before making the switch. This may require MRIs and CSF analysis prior to switching.

Ultimately, we consider whether the drug we are switching the patient to is going to be more efficacious than the drug that the patient was previously on. We consider the safety and side effect profile of the new medication. We balance the risk of the disease with the risk of the medication. We must factor in the patient’s tolerance for risk as well and make the best decision with all the available factors considered.

Clyde E. Markowitz, MD, is the director of the Multiple Sclerosis Center at Penn Neuroscience Center and an Associate Professor of Neurology at the Perelman School of Medicine at the University of Pennsylvania. We sat down with Dr. Markowitz to talk about different multiple sclerosis (MS) therapies and how to determine when it might be time to switch a patient’s current regimen.

Why would an MS specialist switch a patient from one drug therapy to another?

The main reason we switch a patient from one treatment to another is usually related to an inadequate response to their current treatment. This can be seen when a patient is having new clinical symptoms suggestive of a relapse. Additional situations which would cause us to consider a switch in treatment include if the patient has had a new abnormalities seen on MRI scans, such as new T2 lesions or gadolinium- enhancing lesions. We might also switch a patient due to intolerance towards the medication they are on. For example, if they are experiencing flu-like symptoms or having Gastrointestinal issues.

In addition, the expectation that the treatment should slow the rate of progression may not be adequately demonstrating the desired effect. In that setting, we may consider a switch to a drug with a different mechanism of action to hopefully better control disease progression.

Laboratory abnormalities while on treatment might also be a consideration for a switch in therapy. Elevated LFTs, or low WBCs can occur on DMTs and may require a change in treatment. Patients on Natalizumab, require JC virus antibody testing. If the patient’s JCV Ab status changes from negative to positive or a rising index may require a change in therapy to avoid the development of PML.  

What are some special considerations for patients during a switch in therapy?

We need to take into consideration the patient’s comorbidities. Does the patient have a history of diabetes, hypertension, cardiac concerns or a risk for infectious complications? What is the patient’s age? As individuals age the immune system becomes less robust at fighting infections or surveillance for malignancies. Some of the medications are immunosuppressive and might increase the risk of developing opportunistic infections or cancers.

Family planning should be taken into consideration during the discussion of which medications might be appropriate. Is the patient planning to have a pregnancy in the near future? Some medications might not be appropriate in that case.

Route of administration could be a factor to consider, since there are several medications that are administered as an infusion in a medical office or hospital setting. This could create issues for some patients who are employed and may have to miss work during these infusions. This could be as frequent as monthly or 2-3 times per year. Some patients just starting a new job, may feel uncomfortable taking time off or disclosing that they have MS leading to concerns for job security.

We also consider the side effects of the new treatment. What side effects and safety monitoring are required for a particular medication? Are there frequent blood tests, cardiac monitoring, dermatologic and ophthalmologic monitoring? How will this impact the patient’s quality of life?

In the end, it comes down to the level of monitoring required for a particular treatment, where the patient is in his or her life, and where he or she is in the disease course.

What are some potential complications when switching therapies?

When switching therapies, one of the bigger concerns is how quickly can we get the patient on the new therapy. Some medications when stopped can lead to return of disease activity or possibly lead to a rebound phenomenon with significant inflammatory activity. We focus on transitioning a patient quickly to a new drug that has a rapid mechanism of action thus limiting the amount of time that a patient is without a treatment. However, based on the mechanism of action of the drug you must consider if a wash out is necessary. The question is how quickly can the patient start the new drug thus preventing a rebound phenomenon. Ideally, no wash out would protect the patient best but might have safety concerns depending on the switch drug profile. If the switch was related to concerns for high JC virus antibody titer going off of natalizumab, there may be a need to make sure the patient does not have PML before making the switch. This may require MRIs and CSF analysis prior to switching.

Ultimately, we consider whether the drug we are switching the patient to is going to be more efficacious than the drug that the patient was previously on. We consider the safety and side effect profile of the new medication. We balance the risk of the disease with the risk of the medication. We must factor in the patient’s tolerance for risk as well and make the best decision with all the available factors considered.

Clyde E. Markowitz, MD, is the director of the Multiple Sclerosis Center at Penn Neuroscience Center and an Associate Professor of Neurology at the Perelman School of Medicine at the University of Pennsylvania. We sat down with Dr. Markowitz to talk about different multiple sclerosis (MS) therapies and how to determine when it might be time to switch a patient’s current regimen.

Why would an MS specialist switch a patient from one drug therapy to another?

The main reason we switch a patient from one treatment to another is usually related to an inadequate response to their current treatment. This can be seen when a patient is having new clinical symptoms suggestive of a relapse. Additional situations which would cause us to consider a switch in treatment include if the patient has had a new abnormalities seen on MRI scans, such as new T2 lesions or gadolinium- enhancing lesions. We might also switch a patient due to intolerance towards the medication they are on. For example, if they are experiencing flu-like symptoms or having Gastrointestinal issues.

In addition, the expectation that the treatment should slow the rate of progression may not be adequately demonstrating the desired effect. In that setting, we may consider a switch to a drug with a different mechanism of action to hopefully better control disease progression.

Laboratory abnormalities while on treatment might also be a consideration for a switch in therapy. Elevated LFTs, or low WBCs can occur on DMTs and may require a change in treatment. Patients on Natalizumab, require JC virus antibody testing. If the patient’s JCV Ab status changes from negative to positive or a rising index may require a change in therapy to avoid the development of PML.  

What are some special considerations for patients during a switch in therapy?

We need to take into consideration the patient’s comorbidities. Does the patient have a history of diabetes, hypertension, cardiac concerns or a risk for infectious complications? What is the patient’s age? As individuals age the immune system becomes less robust at fighting infections or surveillance for malignancies. Some of the medications are immunosuppressive and might increase the risk of developing opportunistic infections or cancers.

Family planning should be taken into consideration during the discussion of which medications might be appropriate. Is the patient planning to have a pregnancy in the near future? Some medications might not be appropriate in that case.

Route of administration could be a factor to consider, since there are several medications that are administered as an infusion in a medical office or hospital setting. This could create issues for some patients who are employed and may have to miss work during these infusions. This could be as frequent as monthly or 2-3 times per year. Some patients just starting a new job, may feel uncomfortable taking time off or disclosing that they have MS leading to concerns for job security.

We also consider the side effects of the new treatment. What side effects and safety monitoring are required for a particular medication? Are there frequent blood tests, cardiac monitoring, dermatologic and ophthalmologic monitoring? How will this impact the patient’s quality of life?

In the end, it comes down to the level of monitoring required for a particular treatment, where the patient is in his or her life, and where he or she is in the disease course.

What are some potential complications when switching therapies?

When switching therapies, one of the bigger concerns is how quickly can we get the patient on the new therapy. Some medications when stopped can lead to return of disease activity or possibly lead to a rebound phenomenon with significant inflammatory activity. We focus on transitioning a patient quickly to a new drug that has a rapid mechanism of action thus limiting the amount of time that a patient is without a treatment. However, based on the mechanism of action of the drug you must consider if a wash out is necessary. The question is how quickly can the patient start the new drug thus preventing a rebound phenomenon. Ideally, no wash out would protect the patient best but might have safety concerns depending on the switch drug profile. If the switch was related to concerns for high JC virus antibody titer going off of natalizumab, there may be a need to make sure the patient does not have PML before making the switch. This may require MRIs and CSF analysis prior to switching.

Ultimately, we consider whether the drug we are switching the patient to is going to be more efficacious than the drug that the patient was previously on. We consider the safety and side effect profile of the new medication. We balance the risk of the disease with the risk of the medication. We must factor in the patient’s tolerance for risk as well and make the best decision with all the available factors considered.

NATIONAL HARBOR, MD. – Selecting pharmacologic treatment for migraines remains a challenge despite numerous studies investigating efficacy, cost-benefit analyses, and outcomes.

“There’s very little consistency in study design, making it difficult to make real-world comparisons,” said Carly Rodriguez, PharmD, FAMP, pharmacy director at Moda Health. Dr. Rodriguez presented data on the efficacy and pharmacoeconomic factors of migraine therapy at the annual meeting of the Academy of Managed Care Pharmacy.

The paucity of translatable evidence makes comparing and evaluating newer migraine therapies – such as botulinum toxins and calcitonin gene-related peptide (CGRP) inhibitors – particularly difficult.

These two injectable drug classes are not first-line treatments for migraine; they are currently reserved for patients who are refractory to at least one prophylactic treatment, but they offer important alternatives and additions to therapy.

“OnabotulinumtoxinA makes a good case because it costs less than a single ER visit, but there’s not enough supporting data,” Dr. Rodriguez said. According to a report from the Institute for Clinical and Economic Review (ICER) that evaluated the clinical efficacy and economic impact associated with onabotulinumtoxinA, administering the drug saved $157/headache day averted for 20 baseline headaches per month and $223/headache day avoided for 15 baseline headaches per month.

OnabotulinumtoxinA administration showed a moderate yet significant health benefit in preventing chronic migraines by reducing the number of headache days patients experienced by more than 50%. No benefit for episodic migraines was observed.

Several single- and multicenter studies found that onabotulinumtoxinA produced positive outcomes such as a decreased number of visits to urgent care centers, a lower average number of migraines patients experienced, and improved quality of life.

An ICER report investigating CGRP inhibitors found that the cost of anti-CGRP therapy may not produce viable clinical benefits.

Both botulinum toxins and CGRP inhibitors require prior authorization, and their injectable dosage forms restrict the settings in which they are administered and dispensed. Because botulinum toxins must be administered by a health care professional, the vast majority of these drugs are restricted to medical settings, with brand-to-generic substitution often varying among health plans. For this reason, botulinum toxins rarely appear on formularies. Several health plans consider botulinum toxins interchangeable and may give prescribers options to select the botulinum toxin product of their choice.

According to Dr. Rodriguez, there is some variability as to whether CGRP therapies are available in community pharmacy settings or are restricted to specialty pharmacies. Additionally, some plans consider all CGRP inhibitors to be interchangeable, while others take a more conservative approach.

Overall, generic drugs continue to dominate migraine drug therapy, with triptans leading the way. Generics that are heavily prescribed include beta-blockers, antidepressants, and antiepileptics.

More than 37 million people living in the United States suffer from migraines – approximately 8% of the overall population. Women are four times as likely to have migraines than men.

NATIONAL HARBOR, MD. – Selecting pharmacologic treatment for migraines remains a challenge despite numerous studies investigating efficacy, cost-benefit analyses, and outcomes.

“There’s very little consistency in study design, making it difficult to make real-world comparisons,” said Carly Rodriguez, PharmD, FAMP, pharmacy director at Moda Health. Dr. Rodriguez presented data on the efficacy and pharmacoeconomic factors of migraine therapy at the annual meeting of the Academy of Managed Care Pharmacy.

The paucity of translatable evidence makes comparing and evaluating newer migraine therapies – such as botulinum toxins and calcitonin gene-related peptide (CGRP) inhibitors – particularly difficult.

These two injectable drug classes are not first-line treatments for migraine; they are currently reserved for patients who are refractory to at least one prophylactic treatment, but they offer important alternatives and additions to therapy.

“OnabotulinumtoxinA makes a good case because it costs less than a single ER visit, but there’s not enough supporting data,” Dr. Rodriguez said. According to a report from the Institute for Clinical and Economic Review (ICER) that evaluated the clinical efficacy and economic impact associated with onabotulinumtoxinA, administering the drug saved $157/headache day averted for 20 baseline headaches per month and $223/headache day avoided for 15 baseline headaches per month.

OnabotulinumtoxinA administration showed a moderate yet significant health benefit in preventing chronic migraines by reducing the number of headache days patients experienced by more than 50%. No benefit for episodic migraines was observed.

Several single- and multicenter studies found that onabotulinumtoxinA produced positive outcomes such as a decreased number of visits to urgent care centers, a lower average number of migraines patients experienced, and improved quality of life.

An ICER report investigating CGRP inhibitors found that the cost of anti-CGRP therapy may not produce viable clinical benefits.

Both botulinum toxins and CGRP inhibitors require prior authorization, and their injectable dosage forms restrict the settings in which they are administered and dispensed. Because botulinum toxins must be administered by a health care professional, the vast majority of these drugs are restricted to medical settings, with brand-to-generic substitution often varying among health plans. For this reason, botulinum toxins rarely appear on formularies. Several health plans consider botulinum toxins interchangeable and may give prescribers options to select the botulinum toxin product of their choice.

According to Dr. Rodriguez, there is some variability as to whether CGRP therapies are available in community pharmacy settings or are restricted to specialty pharmacies. Additionally, some plans consider all CGRP inhibitors to be interchangeable, while others take a more conservative approach.

Overall, generic drugs continue to dominate migraine drug therapy, with triptans leading the way. Generics that are heavily prescribed include beta-blockers, antidepressants, and antiepileptics.

More than 37 million people living in the United States suffer from migraines – approximately 8% of the overall population. Women are four times as likely to have migraines than men.

NATIONAL HARBOR, MD. – Selecting pharmacologic treatment for migraines remains a challenge despite numerous studies investigating efficacy, cost-benefit analyses, and outcomes.

“There’s very little consistency in study design, making it difficult to make real-world comparisons,” said Carly Rodriguez, PharmD, FAMP, pharmacy director at Moda Health. Dr. Rodriguez presented data on the efficacy and pharmacoeconomic factors of migraine therapy at the annual meeting of the Academy of Managed Care Pharmacy.

The paucity of translatable evidence makes comparing and evaluating newer migraine therapies – such as botulinum toxins and calcitonin gene-related peptide (CGRP) inhibitors – particularly difficult.

These two injectable drug classes are not first-line treatments for migraine; they are currently reserved for patients who are refractory to at least one prophylactic treatment, but they offer important alternatives and additions to therapy.

“OnabotulinumtoxinA makes a good case because it costs less than a single ER visit, but there’s not enough supporting data,” Dr. Rodriguez said. According to a report from the Institute for Clinical and Economic Review (ICER) that evaluated the clinical efficacy and economic impact associated with onabotulinumtoxinA, administering the drug saved $157/headache day averted for 20 baseline headaches per month and $223/headache day avoided for 15 baseline headaches per month.

OnabotulinumtoxinA administration showed a moderate yet significant health benefit in preventing chronic migraines by reducing the number of headache days patients experienced by more than 50%. No benefit for episodic migraines was observed.

Several single- and multicenter studies found that onabotulinumtoxinA produced positive outcomes such as a decreased number of visits to urgent care centers, a lower average number of migraines patients experienced, and improved quality of life.

An ICER report investigating CGRP inhibitors found that the cost of anti-CGRP therapy may not produce viable clinical benefits.

Both botulinum toxins and CGRP inhibitors require prior authorization, and their injectable dosage forms restrict the settings in which they are administered and dispensed. Because botulinum toxins must be administered by a health care professional, the vast majority of these drugs are restricted to medical settings, with brand-to-generic substitution often varying among health plans. For this reason, botulinum toxins rarely appear on formularies. Several health plans consider botulinum toxins interchangeable and may give prescribers options to select the botulinum toxin product of their choice.

According to Dr. Rodriguez, there is some variability as to whether CGRP therapies are available in community pharmacy settings or are restricted to specialty pharmacies. Additionally, some plans consider all CGRP inhibitors to be interchangeable, while others take a more conservative approach.

Overall, generic drugs continue to dominate migraine drug therapy, with triptans leading the way. Generics that are heavily prescribed include beta-blockers, antidepressants, and antiepileptics.

More than 37 million people living in the United States suffer from migraines – approximately 8% of the overall population. Women are four times as likely to have migraines than men.