In this supplement to CHEST Physician, Dr. Sandra Adams investigates the following topics: 

• Difficult-to-control vs severe asthma
• T2-high inflammatory endotype
• T2-low endotype
• Biologic therapies in severe asthma
• Treatment follow-up and assessment

Click here to read.

Author

Sandra G. Adams, MD, MS, FCCP

Click here to read.

In this supplement to CHEST Physician, Dr. Sandra Adams investigates the following topics: 

• Difficult-to-control vs severe asthma
• T2-high inflammatory endotype
• T2-low endotype
• Biologic therapies in severe asthma
• Treatment follow-up and assessment

Click here to read.

Author

Sandra G. Adams, MD, MS, FCCP

Click here to read.

In this supplement to CHEST Physician, Dr. Sandra Adams investigates the following topics: 

• Difficult-to-control vs severe asthma
• T2-high inflammatory endotype
• T2-low endotype
• Biologic therapies in severe asthma
• Treatment follow-up and assessment

Click here to read.

Author

Sandra G. Adams, MD, MS, FCCP

Click here to read.

As the COVID-19 pandemic continues to chug along, some communities feel it slowing to a pace at which they might feel comfortable about a return to, if not quite “business as usual,” at least “business as sort of normal-ish.” They are ready to accept a level of disease that signals they have reached a steady state. However, in other communities, the virus has picked up speed and is threatening to overwhelm the medical infrastructure. If you are in one of those fortunate and skillfully managed states in which folks are beginning to talk seriously, but with little evidence, that it is time to return to normal, it is probably far too early. Are there any metrics that could be applied to make the decision to ease restrictions more rational?

Courtesy Dr. William G. Wilkoff

Eons ago in pandemic terms, the World Health Organization in Thailand published a list of criteria to aid in determining when a community could consider lifting the limits that seemed to have been effective in halting transmission of the virus (“Transitioning to and maintaining a steady state of low-level or no transmission,” WHO, Thailand, 2020 Apr 18). While much more has been learned about the behavior of the virus since the spring of 2020, the criteria from the WHO in Thailand are worth considering.

Here is my summary of their criteria for returning to normalcy. First, virus transmission is controlled to the point that only sporadic cases and small clusters exist, and that all of these are traceable in origin. Second, health care and public health systems are in place with sufficient capacities to manage a shift from detection to treatment should the case load increase dramatically; this capacity should include detection, testing, isolation, and quarantine. Third, outbreaks in high-risk populations such as nursing homes have been minimized. Fourth, workplace prevention strategies are in place and have been demonstrated to be effective. Fifth, risk of imported cases is at manageable levels. Finally, communities are engaged.

It is hard to argue with the rationale behind each of these criteria. However, the United States is not Thailand, and just thinking about how this country would go about meeting those criteria provides a window into some of the reasons why we have done so poorly and will continue to be challenged in dealing with the pandemic.

First, notice that the criteria make no mention of a vaccine. One gets the sense that from the top down our country is banking too heavily on the effectiveness and widespread delivery of a vaccine. Even if and when a vaccine is developed and delivered, all of these criteria still must be met and kept in mind for a future pandemic.

Second, the criteria call for an effective health care system, but it is abundantly clear that the United States does not have a cohesive health care system and probably won’t for the foreseeable future. The best we can hope for is individual states cobbling together their own systems, which may in turn serve as examples for those states who haven’t had the foresight. We have had a public health system of sorts, but its credibility and effectiveness has been neutered to the point that again we must rely on each state’s ability to see through the haze and create it’s own systems for detection, testing, tracking, isolating, and quarantining – often with little help in materiel support from the federal government. The sliver of good news is that, after a bit of a stumbling start, detecting and limiting the importation of cases from abroad is being addressed.

We continue to hear and see evidence that there are segments of the population who are not engaged in the activities that we have learned are necessary to stabilize the pandemic. My sense is that those people represent a very small minority. But, it is probably large enough to make the route to a steady state on a national level long and painful. This unfortunately is to be expected in a country that was built on a framework of personal freedoms. The best you can hope for in achieving a steady state is to live in one of the states that seems to be achieving the fine balance between personal freedoms and the common good.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

As the COVID-19 pandemic continues to chug along, some communities feel it slowing to a pace at which they might feel comfortable about a return to, if not quite “business as usual,” at least “business as sort of normal-ish.” They are ready to accept a level of disease that signals they have reached a steady state. However, in other communities, the virus has picked up speed and is threatening to overwhelm the medical infrastructure. If you are in one of those fortunate and skillfully managed states in which folks are beginning to talk seriously, but with little evidence, that it is time to return to normal, it is probably far too early. Are there any metrics that could be applied to make the decision to ease restrictions more rational?

Courtesy Dr. William G. Wilkoff

Eons ago in pandemic terms, the World Health Organization in Thailand published a list of criteria to aid in determining when a community could consider lifting the limits that seemed to have been effective in halting transmission of the virus (“Transitioning to and maintaining a steady state of low-level or no transmission,” WHO, Thailand, 2020 Apr 18). While much more has been learned about the behavior of the virus since the spring of 2020, the criteria from the WHO in Thailand are worth considering.

Here is my summary of their criteria for returning to normalcy. First, virus transmission is controlled to the point that only sporadic cases and small clusters exist, and that all of these are traceable in origin. Second, health care and public health systems are in place with sufficient capacities to manage a shift from detection to treatment should the case load increase dramatically; this capacity should include detection, testing, isolation, and quarantine. Third, outbreaks in high-risk populations such as nursing homes have been minimized. Fourth, workplace prevention strategies are in place and have been demonstrated to be effective. Fifth, risk of imported cases is at manageable levels. Finally, communities are engaged.

It is hard to argue with the rationale behind each of these criteria. However, the United States is not Thailand, and just thinking about how this country would go about meeting those criteria provides a window into some of the reasons why we have done so poorly and will continue to be challenged in dealing with the pandemic.

First, notice that the criteria make no mention of a vaccine. One gets the sense that from the top down our country is banking too heavily on the effectiveness and widespread delivery of a vaccine. Even if and when a vaccine is developed and delivered, all of these criteria still must be met and kept in mind for a future pandemic.

Second, the criteria call for an effective health care system, but it is abundantly clear that the United States does not have a cohesive health care system and probably won’t for the foreseeable future. The best we can hope for is individual states cobbling together their own systems, which may in turn serve as examples for those states who haven’t had the foresight. We have had a public health system of sorts, but its credibility and effectiveness has been neutered to the point that again we must rely on each state’s ability to see through the haze and create it’s own systems for detection, testing, tracking, isolating, and quarantining – often with little help in materiel support from the federal government. The sliver of good news is that, after a bit of a stumbling start, detecting and limiting the importation of cases from abroad is being addressed.

We continue to hear and see evidence that there are segments of the population who are not engaged in the activities that we have learned are necessary to stabilize the pandemic. My sense is that those people represent a very small minority. But, it is probably large enough to make the route to a steady state on a national level long and painful. This unfortunately is to be expected in a country that was built on a framework of personal freedoms. The best you can hope for in achieving a steady state is to live in one of the states that seems to be achieving the fine balance between personal freedoms and the common good.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

As the COVID-19 pandemic continues to chug along, some communities feel it slowing to a pace at which they might feel comfortable about a return to, if not quite “business as usual,” at least “business as sort of normal-ish.” They are ready to accept a level of disease that signals they have reached a steady state. However, in other communities, the virus has picked up speed and is threatening to overwhelm the medical infrastructure. If you are in one of those fortunate and skillfully managed states in which folks are beginning to talk seriously, but with little evidence, that it is time to return to normal, it is probably far too early. Are there any metrics that could be applied to make the decision to ease restrictions more rational?

Courtesy Dr. William G. Wilkoff

Eons ago in pandemic terms, the World Health Organization in Thailand published a list of criteria to aid in determining when a community could consider lifting the limits that seemed to have been effective in halting transmission of the virus (“Transitioning to and maintaining a steady state of low-level or no transmission,” WHO, Thailand, 2020 Apr 18). While much more has been learned about the behavior of the virus since the spring of 2020, the criteria from the WHO in Thailand are worth considering.

Here is my summary of their criteria for returning to normalcy. First, virus transmission is controlled to the point that only sporadic cases and small clusters exist, and that all of these are traceable in origin. Second, health care and public health systems are in place with sufficient capacities to manage a shift from detection to treatment should the case load increase dramatically; this capacity should include detection, testing, isolation, and quarantine. Third, outbreaks in high-risk populations such as nursing homes have been minimized. Fourth, workplace prevention strategies are in place and have been demonstrated to be effective. Fifth, risk of imported cases is at manageable levels. Finally, communities are engaged.

It is hard to argue with the rationale behind each of these criteria. However, the United States is not Thailand, and just thinking about how this country would go about meeting those criteria provides a window into some of the reasons why we have done so poorly and will continue to be challenged in dealing with the pandemic.

First, notice that the criteria make no mention of a vaccine. One gets the sense that from the top down our country is banking too heavily on the effectiveness and widespread delivery of a vaccine. Even if and when a vaccine is developed and delivered, all of these criteria still must be met and kept in mind for a future pandemic.

Second, the criteria call for an effective health care system, but it is abundantly clear that the United States does not have a cohesive health care system and probably won’t for the foreseeable future. The best we can hope for is individual states cobbling together their own systems, which may in turn serve as examples for those states who haven’t had the foresight. We have had a public health system of sorts, but its credibility and effectiveness has been neutered to the point that again we must rely on each state’s ability to see through the haze and create it’s own systems for detection, testing, tracking, isolating, and quarantining – often with little help in materiel support from the federal government. The sliver of good news is that, after a bit of a stumbling start, detecting and limiting the importation of cases from abroad is being addressed.

We continue to hear and see evidence that there are segments of the population who are not engaged in the activities that we have learned are necessary to stabilize the pandemic. My sense is that those people represent a very small minority. But, it is probably large enough to make the route to a steady state on a national level long and painful. This unfortunately is to be expected in a country that was built on a framework of personal freedoms. The best you can hope for in achieving a steady state is to live in one of the states that seems to be achieving the fine balance between personal freedoms and the common good.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

Diarrhea affected one in every five patients with inflammatory bowel disease (IBD) and COVID-19, compared with only 7%-10% of all patients with COVID-19 in prior studies, researchers reported in Clinical Gastroenterology and Hepatology.

In a systematic review and meta-analysis of 23 studies incorporating data from 449 patients with IBD and COVID-19, their most common symptoms were fever (affecting 48.3% of patients), cough (46.5%), and diarrhea (20.5%), and diarrhea was approximately twice as prevalent as dyspnea, nausea, abdominal pain, and fatigue, wrote Ferdinando D’Amico of Humanitas University in Milan and his associates. “[S]ymptoms experienced by IBD patients with COVID-19 are similar to those occurring in the general population, except for a higher percentage of diarrhea,” they wrote. This increased prevalence might result from IBD itself or from inflammatory effects of viral gut tropism, they noted. “Currently, the diagnostic–therapeutic approach does not differ between IBD and non-IBD patients, but further studies are needed to evaluate whether fecal research of viral RNA and treatment with IBD drugs may play a role in the management of COVID-19 patients.”

To characterize the clinical presentation and course of patients with IBD and COVID-19, the researchers searched PubMed, Embase, Web of Science, and MedRxiv through July 29, 2020, for keywords related to COVID-19, Crohn’s disease, ulcerative colitis, and IBD. They identified 23 studies presenting clinical data from adults or children with a confirmed IBD diagnosis and least one case of COVID-19. Among 243,760 patients with IBD, 1,028 patients had COVID-19 infection, including 509 patients with Crohn’s disease, 428 patients with ulcerative colitis, 49 patients with indeterminate colitis, and 42 patients for whom the IBD subtype was not recorded.

In all, 0.4% of patients with IBD had COVID-19. Nearly all had been diagnosed by polymerase chain reaction of nasopharyngeal swabs, and approximately 40% also had received chest CT scans. Most were male (56.5%), and 43.5% were older than 65 years. Patients were receiving a wide range of IBD therapies, most commonly anti–tumor necrosis factor (TNF) agents, mesalamine, thiopurine (alone or in combination with biologics), vedolizumab, ustekinumab, steroids, methotrexate, and tofacitinib. Results from six studies indicated that patients with IBD were significantly more likely to be diagnosed with COVID-19 if they were older than 66 years (odds ratio, 21.3) or had other comorbidities (OR, 1.24). The most commonly used drugs for managing COVID-19 were hydroxychloroquine, lopinavir/ritonavir, steroids, antibiotics, chloroquine, tofacitinib, and infliximab.

A total of 30.6% of patients with IBD and COVID-19 were hospitalized, 11.4% stayed in the ICU, 3.7% required mechanical ventilation, and 3.8% died from COVID-19. Significant risk factors for death from COVID-19 included older age, active IBD, and a Charlson Comorbidity Index score above 1. Similarly, risk factors for severe COVID-19 included older age, having two or more comorbidities, receiving systemic steroids, and receiving mesalamine/sulfasalazine. In one study, a recent (3-month) history of corticosteroid treatment was associated with a 60% increase in the risk for severe COVID-19. Other immune-mediated therapies did not show this association. Patients with ulcerative colitis were significantly more likely to be seen in the ED or hospitalized, compared with patients with other forms of IBD (adjusted OR, 12.7).

No funding sources were disclosed. Dr. D’Amico reported having no conflicts of interest. Two coinvestigators disclosed ties to AbbVie, MSD, Schering-Plough, UCB Pharma, and several other pharmaceutical companies.

SOURCE: D’Amico F et al. Clin Gastroenterol Hepatol. 2020 Aug 7. doi: 10.1016/j.cgh.2020.08.003.
 

Diarrhea affected one in every five patients with inflammatory bowel disease (IBD) and COVID-19, compared with only 7%-10% of all patients with COVID-19 in prior studies, researchers reported in Clinical Gastroenterology and Hepatology.

In a systematic review and meta-analysis of 23 studies incorporating data from 449 patients with IBD and COVID-19, their most common symptoms were fever (affecting 48.3% of patients), cough (46.5%), and diarrhea (20.5%), and diarrhea was approximately twice as prevalent as dyspnea, nausea, abdominal pain, and fatigue, wrote Ferdinando D’Amico of Humanitas University in Milan and his associates. “[S]ymptoms experienced by IBD patients with COVID-19 are similar to those occurring in the general population, except for a higher percentage of diarrhea,” they wrote. This increased prevalence might result from IBD itself or from inflammatory effects of viral gut tropism, they noted. “Currently, the diagnostic–therapeutic approach does not differ between IBD and non-IBD patients, but further studies are needed to evaluate whether fecal research of viral RNA and treatment with IBD drugs may play a role in the management of COVID-19 patients.”

To characterize the clinical presentation and course of patients with IBD and COVID-19, the researchers searched PubMed, Embase, Web of Science, and MedRxiv through July 29, 2020, for keywords related to COVID-19, Crohn’s disease, ulcerative colitis, and IBD. They identified 23 studies presenting clinical data from adults or children with a confirmed IBD diagnosis and least one case of COVID-19. Among 243,760 patients with IBD, 1,028 patients had COVID-19 infection, including 509 patients with Crohn’s disease, 428 patients with ulcerative colitis, 49 patients with indeterminate colitis, and 42 patients for whom the IBD subtype was not recorded.

In all, 0.4% of patients with IBD had COVID-19. Nearly all had been diagnosed by polymerase chain reaction of nasopharyngeal swabs, and approximately 40% also had received chest CT scans. Most were male (56.5%), and 43.5% were older than 65 years. Patients were receiving a wide range of IBD therapies, most commonly anti–tumor necrosis factor (TNF) agents, mesalamine, thiopurine (alone or in combination with biologics), vedolizumab, ustekinumab, steroids, methotrexate, and tofacitinib. Results from six studies indicated that patients with IBD were significantly more likely to be diagnosed with COVID-19 if they were older than 66 years (odds ratio, 21.3) or had other comorbidities (OR, 1.24). The most commonly used drugs for managing COVID-19 were hydroxychloroquine, lopinavir/ritonavir, steroids, antibiotics, chloroquine, tofacitinib, and infliximab.

A total of 30.6% of patients with IBD and COVID-19 were hospitalized, 11.4% stayed in the ICU, 3.7% required mechanical ventilation, and 3.8% died from COVID-19. Significant risk factors for death from COVID-19 included older age, active IBD, and a Charlson Comorbidity Index score above 1. Similarly, risk factors for severe COVID-19 included older age, having two or more comorbidities, receiving systemic steroids, and receiving mesalamine/sulfasalazine. In one study, a recent (3-month) history of corticosteroid treatment was associated with a 60% increase in the risk for severe COVID-19. Other immune-mediated therapies did not show this association. Patients with ulcerative colitis were significantly more likely to be seen in the ED or hospitalized, compared with patients with other forms of IBD (adjusted OR, 12.7).

No funding sources were disclosed. Dr. D’Amico reported having no conflicts of interest. Two coinvestigators disclosed ties to AbbVie, MSD, Schering-Plough, UCB Pharma, and several other pharmaceutical companies.

SOURCE: D’Amico F et al. Clin Gastroenterol Hepatol. 2020 Aug 7. doi: 10.1016/j.cgh.2020.08.003.
 

Diarrhea affected one in every five patients with inflammatory bowel disease (IBD) and COVID-19, compared with only 7%-10% of all patients with COVID-19 in prior studies, researchers reported in Clinical Gastroenterology and Hepatology.

In a systematic review and meta-analysis of 23 studies incorporating data from 449 patients with IBD and COVID-19, their most common symptoms were fever (affecting 48.3% of patients), cough (46.5%), and diarrhea (20.5%), and diarrhea was approximately twice as prevalent as dyspnea, nausea, abdominal pain, and fatigue, wrote Ferdinando D’Amico of Humanitas University in Milan and his associates. “[S]ymptoms experienced by IBD patients with COVID-19 are similar to those occurring in the general population, except for a higher percentage of diarrhea,” they wrote. This increased prevalence might result from IBD itself or from inflammatory effects of viral gut tropism, they noted. “Currently, the diagnostic–therapeutic approach does not differ between IBD and non-IBD patients, but further studies are needed to evaluate whether fecal research of viral RNA and treatment with IBD drugs may play a role in the management of COVID-19 patients.”

To characterize the clinical presentation and course of patients with IBD and COVID-19, the researchers searched PubMed, Embase, Web of Science, and MedRxiv through July 29, 2020, for keywords related to COVID-19, Crohn’s disease, ulcerative colitis, and IBD. They identified 23 studies presenting clinical data from adults or children with a confirmed IBD diagnosis and least one case of COVID-19. Among 243,760 patients with IBD, 1,028 patients had COVID-19 infection, including 509 patients with Crohn’s disease, 428 patients with ulcerative colitis, 49 patients with indeterminate colitis, and 42 patients for whom the IBD subtype was not recorded.

In all, 0.4% of patients with IBD had COVID-19. Nearly all had been diagnosed by polymerase chain reaction of nasopharyngeal swabs, and approximately 40% also had received chest CT scans. Most were male (56.5%), and 43.5% were older than 65 years. Patients were receiving a wide range of IBD therapies, most commonly anti–tumor necrosis factor (TNF) agents, mesalamine, thiopurine (alone or in combination with biologics), vedolizumab, ustekinumab, steroids, methotrexate, and tofacitinib. Results from six studies indicated that patients with IBD were significantly more likely to be diagnosed with COVID-19 if they were older than 66 years (odds ratio, 21.3) or had other comorbidities (OR, 1.24). The most commonly used drugs for managing COVID-19 were hydroxychloroquine, lopinavir/ritonavir, steroids, antibiotics, chloroquine, tofacitinib, and infliximab.

A total of 30.6% of patients with IBD and COVID-19 were hospitalized, 11.4% stayed in the ICU, 3.7% required mechanical ventilation, and 3.8% died from COVID-19. Significant risk factors for death from COVID-19 included older age, active IBD, and a Charlson Comorbidity Index score above 1. Similarly, risk factors for severe COVID-19 included older age, having two or more comorbidities, receiving systemic steroids, and receiving mesalamine/sulfasalazine. In one study, a recent (3-month) history of corticosteroid treatment was associated with a 60% increase in the risk for severe COVID-19. Other immune-mediated therapies did not show this association. Patients with ulcerative colitis were significantly more likely to be seen in the ED or hospitalized, compared with patients with other forms of IBD (adjusted OR, 12.7).

No funding sources were disclosed. Dr. D’Amico reported having no conflicts of interest. Two coinvestigators disclosed ties to AbbVie, MSD, Schering-Plough, UCB Pharma, and several other pharmaceutical companies.

SOURCE: D’Amico F et al. Clin Gastroenterol Hepatol. 2020 Aug 7. doi: 10.1016/j.cgh.2020.08.003.
 

A 24-hour continuous subcutaneous infusion of foslevodopa/foscarbidopa improved Parkinson’s disease (PD) motor symptoms during all waking hours for patients with advanced disease, according to a new study. The beneficial effects of these phosphate prodrugs of levodopa and carbidopa were most noticeable in the early morning, results of the phase 1B study showed.

As Parkinson’s disease progresses and dosing of oral levodopa/carbidopa (LD/CD) increases, its therapeutic window narrows, resulting in troublesome dyskinesia at peak drug levels and tremors and rigidity when levels fall.

“Foslevodopa/foscarbidopa shows lower ‘off’ time than oral levodopa/carbidopa, and this was statistically significant. Also, foslevodopa/foscarbidopa (fosL/fosC) showed more ‘on’ time without dyskinesia, compared with oral levodopa/carbidopa. This was also statistically significant,” lead author Sven Stodtmann, PhD, of AbbVie GmbH, Ludwigshafen, Germany, reported in his recorded presentation at the Movement Disorders Society’s 23rd International Congress of Parkinson’s Disease and Movement Disorder (Virtual) 2020.
 

Continuous infusion versus oral therapy

The analysis included 20 patients, and all data from these individuals were collected between 4:30 a.m. and 9:30 p.m.

Participants were 12 men and 8 women, aged 30-80 years, with advanced, idiopathic Parkinson’s disease responsive to levodopa but inadequately controlled on their current stable therapy, having a minimum of 2.5 off hours/day. Mean age was 61.3 plus or minus 10.5 years (range 35-77 years).

In this single-arm, open-label study, they received subcutaneous infusions of personalized therapeutic doses of fosL/fosC 24 hours/day for 28 days after a 10- to 30-day screening period during which they recorded LD/CD doses in a diary and had motor symptoms monitored using a wearable device.

Following the screening period, fosL/fosC doses were titrated over up to 5 days, with subsequent weekly study visits, for a total time on fosL/fosC of 28 days. Drug titration was aimed at maximizing functional on time and minimizing the number of off episodes while minimizing troublesome dyskinesia.

Continuous infusion of fosL/fosC performed better than oral LD/CD on all counts.

“The off time is much lower in the morning for people on foslevodopa/foscarbidopa [compared with oral LD/CD] because this is a 24-hour infusion product,” Dr. Stodtmann explained.

The effect was maintained over the course of the day with little fluctuation with fosL/fosC, off periods never exceeding about 25% between 4:30 a.m. and 9 p.m. For LD/CD, off periods were highest in the early morning and peaked at about 50% on a 3- to 4-hour cycle during the course of the day.

Increased on time without dyskinesia varied between about 60% and 80% during the day with fosL/fosC, showing the greatest difference between fosL/fosC and oral LD/CD in the early morning hours.

“On time with nontroublesome dyskinesia was lower for foscarbidopa/foslevodopa, compared to oral levodopa/carbidopa, but this was not statistically significant,” Dr. Stodtmann said. On time with troublesome dyskinesia followed the same pattern, again, not statistically significant.

Looking at the data another way, the investigators calculated the odds ratios of motor symptoms using fosL/fosC, compared with oral LD/CD. Use of fosL/fosC was associated with a 59% lower risk of being in the off state during the day, compared with oral LD/CD (odds ratio, 0.4; 95% confidence interval, 0.2-0.7; P < .01). Similarly, the probability of being in the on state without dyskinesia was much greater with fosL/fosC (OR, 2.75; 95% CI, 1.08-6.99; P < .05).
 

Encouraging, but more data needed

Indu Subramanian, MD, of the department of neurology at the University of California, Los Angeles, and director of the Parkinson’s Disease Research, Education, and Clinical Center at the West Los Angeles Veterans Affairs Hospital, commented that the field has been waiting to see data on fosL/fosC.

“It seems like it’s pretty reasonable in terms of what the goals were, which is to improve stability of Parkinson’s symptoms, to improve off time and give on time without troublesome dyskinesia,” she said. “So I think those [goals] have been met.”

Dr. Subramanian, who was not involved with the research, said she would have liked to have seen results concerning safety of this drug formulation, which the presentation lacked, “because historically, there have been issues with nodule formation and skin breakdown, things like that, due to the stability of the product in the subcutaneous form. … So, always to my understanding, there has been this search for things that are tolerated in the subcutaneous delivery.”

If this formulation proves safe and tolerable, Dr. Subramanian sees a potential place for it for some patients with advanced Parkinson’s disease.

“Certainly a subcutaneous formulation will be better than something that requires … deep brain surgery or even a pump insertion like Duopa [carbidopa/levodopa enteral suspension, AbbVie] or something like that,” she said. “I think [it] would be beneficial over something with the gut because the gut historically has been a problem to rely on in advanced Parkinson’s patients due to slower transit times, and the gut itself is affected with Parkinson’s disease.”

Dr. Stodtmann and all coauthors are employees of AbbVie, which was the sponsor of the study and was responsible for all aspects of it. Dr. Subramanian has given talks for Acadia Pharmaceuticals and Acorda Therapeutics in the past.

A version of this article originally appeared on Medscape.com.

A 24-hour continuous subcutaneous infusion of foslevodopa/foscarbidopa improved Parkinson’s disease (PD) motor symptoms during all waking hours for patients with advanced disease, according to a new study. The beneficial effects of these phosphate prodrugs of levodopa and carbidopa were most noticeable in the early morning, results of the phase 1B study showed.

As Parkinson’s disease progresses and dosing of oral levodopa/carbidopa (LD/CD) increases, its therapeutic window narrows, resulting in troublesome dyskinesia at peak drug levels and tremors and rigidity when levels fall.

“Foslevodopa/foscarbidopa shows lower ‘off’ time than oral levodopa/carbidopa, and this was statistically significant. Also, foslevodopa/foscarbidopa (fosL/fosC) showed more ‘on’ time without dyskinesia, compared with oral levodopa/carbidopa. This was also statistically significant,” lead author Sven Stodtmann, PhD, of AbbVie GmbH, Ludwigshafen, Germany, reported in his recorded presentation at the Movement Disorders Society’s 23rd International Congress of Parkinson’s Disease and Movement Disorder (Virtual) 2020.
 

Continuous infusion versus oral therapy

The analysis included 20 patients, and all data from these individuals were collected between 4:30 a.m. and 9:30 p.m.

Participants were 12 men and 8 women, aged 30-80 years, with advanced, idiopathic Parkinson’s disease responsive to levodopa but inadequately controlled on their current stable therapy, having a minimum of 2.5 off hours/day. Mean age was 61.3 plus or minus 10.5 years (range 35-77 years).

In this single-arm, open-label study, they received subcutaneous infusions of personalized therapeutic doses of fosL/fosC 24 hours/day for 28 days after a 10- to 30-day screening period during which they recorded LD/CD doses in a diary and had motor symptoms monitored using a wearable device.

Following the screening period, fosL/fosC doses were titrated over up to 5 days, with subsequent weekly study visits, for a total time on fosL/fosC of 28 days. Drug titration was aimed at maximizing functional on time and minimizing the number of off episodes while minimizing troublesome dyskinesia.

Continuous infusion of fosL/fosC performed better than oral LD/CD on all counts.

“The off time is much lower in the morning for people on foslevodopa/foscarbidopa [compared with oral LD/CD] because this is a 24-hour infusion product,” Dr. Stodtmann explained.

The effect was maintained over the course of the day with little fluctuation with fosL/fosC, off periods never exceeding about 25% between 4:30 a.m. and 9 p.m. For LD/CD, off periods were highest in the early morning and peaked at about 50% on a 3- to 4-hour cycle during the course of the day.

Increased on time without dyskinesia varied between about 60% and 80% during the day with fosL/fosC, showing the greatest difference between fosL/fosC and oral LD/CD in the early morning hours.

“On time with nontroublesome dyskinesia was lower for foscarbidopa/foslevodopa, compared to oral levodopa/carbidopa, but this was not statistically significant,” Dr. Stodtmann said. On time with troublesome dyskinesia followed the same pattern, again, not statistically significant.

Looking at the data another way, the investigators calculated the odds ratios of motor symptoms using fosL/fosC, compared with oral LD/CD. Use of fosL/fosC was associated with a 59% lower risk of being in the off state during the day, compared with oral LD/CD (odds ratio, 0.4; 95% confidence interval, 0.2-0.7; P < .01). Similarly, the probability of being in the on state without dyskinesia was much greater with fosL/fosC (OR, 2.75; 95% CI, 1.08-6.99; P < .05).
 

Encouraging, but more data needed

Indu Subramanian, MD, of the department of neurology at the University of California, Los Angeles, and director of the Parkinson’s Disease Research, Education, and Clinical Center at the West Los Angeles Veterans Affairs Hospital, commented that the field has been waiting to see data on fosL/fosC.

“It seems like it’s pretty reasonable in terms of what the goals were, which is to improve stability of Parkinson’s symptoms, to improve off time and give on time without troublesome dyskinesia,” she said. “So I think those [goals] have been met.”

Dr. Subramanian, who was not involved with the research, said she would have liked to have seen results concerning safety of this drug formulation, which the presentation lacked, “because historically, there have been issues with nodule formation and skin breakdown, things like that, due to the stability of the product in the subcutaneous form. … So, always to my understanding, there has been this search for things that are tolerated in the subcutaneous delivery.”

If this formulation proves safe and tolerable, Dr. Subramanian sees a potential place for it for some patients with advanced Parkinson’s disease.

“Certainly a subcutaneous formulation will be better than something that requires … deep brain surgery or even a pump insertion like Duopa [carbidopa/levodopa enteral suspension, AbbVie] or something like that,” she said. “I think [it] would be beneficial over something with the gut because the gut historically has been a problem to rely on in advanced Parkinson’s patients due to slower transit times, and the gut itself is affected with Parkinson’s disease.”

Dr. Stodtmann and all coauthors are employees of AbbVie, which was the sponsor of the study and was responsible for all aspects of it. Dr. Subramanian has given talks for Acadia Pharmaceuticals and Acorda Therapeutics in the past.

A version of this article originally appeared on Medscape.com.

A 24-hour continuous subcutaneous infusion of foslevodopa/foscarbidopa improved Parkinson’s disease (PD) motor symptoms during all waking hours for patients with advanced disease, according to a new study. The beneficial effects of these phosphate prodrugs of levodopa and carbidopa were most noticeable in the early morning, results of the phase 1B study showed.

As Parkinson’s disease progresses and dosing of oral levodopa/carbidopa (LD/CD) increases, its therapeutic window narrows, resulting in troublesome dyskinesia at peak drug levels and tremors and rigidity when levels fall.

“Foslevodopa/foscarbidopa shows lower ‘off’ time than oral levodopa/carbidopa, and this was statistically significant. Also, foslevodopa/foscarbidopa (fosL/fosC) showed more ‘on’ time without dyskinesia, compared with oral levodopa/carbidopa. This was also statistically significant,” lead author Sven Stodtmann, PhD, of AbbVie GmbH, Ludwigshafen, Germany, reported in his recorded presentation at the Movement Disorders Society’s 23rd International Congress of Parkinson’s Disease and Movement Disorder (Virtual) 2020.
 

Continuous infusion versus oral therapy

The analysis included 20 patients, and all data from these individuals were collected between 4:30 a.m. and 9:30 p.m.

Participants were 12 men and 8 women, aged 30-80 years, with advanced, idiopathic Parkinson’s disease responsive to levodopa but inadequately controlled on their current stable therapy, having a minimum of 2.5 off hours/day. Mean age was 61.3 plus or minus 10.5 years (range 35-77 years).

In this single-arm, open-label study, they received subcutaneous infusions of personalized therapeutic doses of fosL/fosC 24 hours/day for 28 days after a 10- to 30-day screening period during which they recorded LD/CD doses in a diary and had motor symptoms monitored using a wearable device.

Following the screening period, fosL/fosC doses were titrated over up to 5 days, with subsequent weekly study visits, for a total time on fosL/fosC of 28 days. Drug titration was aimed at maximizing functional on time and minimizing the number of off episodes while minimizing troublesome dyskinesia.

Continuous infusion of fosL/fosC performed better than oral LD/CD on all counts.

“The off time is much lower in the morning for people on foslevodopa/foscarbidopa [compared with oral LD/CD] because this is a 24-hour infusion product,” Dr. Stodtmann explained.

The effect was maintained over the course of the day with little fluctuation with fosL/fosC, off periods never exceeding about 25% between 4:30 a.m. and 9 p.m. For LD/CD, off periods were highest in the early morning and peaked at about 50% on a 3- to 4-hour cycle during the course of the day.

Increased on time without dyskinesia varied between about 60% and 80% during the day with fosL/fosC, showing the greatest difference between fosL/fosC and oral LD/CD in the early morning hours.

“On time with nontroublesome dyskinesia was lower for foscarbidopa/foslevodopa, compared to oral levodopa/carbidopa, but this was not statistically significant,” Dr. Stodtmann said. On time with troublesome dyskinesia followed the same pattern, again, not statistically significant.

Looking at the data another way, the investigators calculated the odds ratios of motor symptoms using fosL/fosC, compared with oral LD/CD. Use of fosL/fosC was associated with a 59% lower risk of being in the off state during the day, compared with oral LD/CD (odds ratio, 0.4; 95% confidence interval, 0.2-0.7; P < .01). Similarly, the probability of being in the on state without dyskinesia was much greater with fosL/fosC (OR, 2.75; 95% CI, 1.08-6.99; P < .05).
 

Encouraging, but more data needed

Indu Subramanian, MD, of the department of neurology at the University of California, Los Angeles, and director of the Parkinson’s Disease Research, Education, and Clinical Center at the West Los Angeles Veterans Affairs Hospital, commented that the field has been waiting to see data on fosL/fosC.

“It seems like it’s pretty reasonable in terms of what the goals were, which is to improve stability of Parkinson’s symptoms, to improve off time and give on time without troublesome dyskinesia,” she said. “So I think those [goals] have been met.”

Dr. Subramanian, who was not involved with the research, said she would have liked to have seen results concerning safety of this drug formulation, which the presentation lacked, “because historically, there have been issues with nodule formation and skin breakdown, things like that, due to the stability of the product in the subcutaneous form. … So, always to my understanding, there has been this search for things that are tolerated in the subcutaneous delivery.”

If this formulation proves safe and tolerable, Dr. Subramanian sees a potential place for it for some patients with advanced Parkinson’s disease.

“Certainly a subcutaneous formulation will be better than something that requires … deep brain surgery or even a pump insertion like Duopa [carbidopa/levodopa enteral suspension, AbbVie] or something like that,” she said. “I think [it] would be beneficial over something with the gut because the gut historically has been a problem to rely on in advanced Parkinson’s patients due to slower transit times, and the gut itself is affected with Parkinson’s disease.”

Dr. Stodtmann and all coauthors are employees of AbbVie, which was the sponsor of the study and was responsible for all aspects of it. Dr. Subramanian has given talks for Acadia Pharmaceuticals and Acorda Therapeutics in the past.

A version of this article originally appeared on Medscape.com.

The use of minimally invasive gynecologic surgery (MIGS) has grown rapidly over the past 20 years. MIGS, which includes vaginal hysterectomy and laparoscopic hysterectomy, is safe and has fewer complications and a more rapid recovery period than open abdominal surgery.^1,2 In 2005, the role of MIGS was expanded further when the US Food and Drug Administration (FDA) approved robot-assisted surgery for the performance of gynecologic procedures.³ As knowledge and experience in the safe performance of MIGS progresses, the rates for MIGS procedures have skyrocketed and continue to grow. Between 2007 and 2010, laparoscopic hysterectomy rates rose from 23.5% to 30.5%, while robot-assisted laparoscopic hysterectomy rates increased from 0.5% to 9.5%, representing 40% of all hysterectomies.⁴ Due to the benefits of minimally invasive surgery over open abdominal surgery, patient and physician preference for minimally invasive procedures has grown significantly in popularity.^1,5

Because incisions are small in minimally invasive surgery, surgeons have been challenged with removing large specimens through incisions that are much smaller than the presenting pathology. One approach is to use a specimen retrieval bag for specimen extraction. Once the dissection is completed, the specimen is placed within the retrieval bag for removal, thus minimizing exposure of the specimen and its contents to the abdominopelvic cavity and incision.

The use of specimen retrieval devices has been advocated to prevent infection, avoid spillage into the peritoneal cavity, and minimize the risk of port-site metastases in cases of potentially cancerous specimens. Devices include affordable and readily available products, such as nonpowdered gloves, and commercially produced bags.⁶

While the use of specimen containment systems for tissue extraction has been well described in gynecology, the available systems vary widely in construction, size, durability, and shape, potentially leading to confusion and suboptimal bag selection during surgery.⁷ In this article, we review the most common laparoscopic bags available in the United States, provide an overview of bag characteristics, offer practice guidelines for bag selection, and review bag terminology to highlight important concepts for bag selection.

Controversy spurs change

In April 2014, the FDA warned against the use of power morcellation for specimen removal during minimally invasive surgery, citing a prevalence of 1 in 352 unsuspected uterine sarcomas and 1 in 498 unsuspected uterine leiomyosarcomas among women undergoing hysterectomy or myomectomy for presumed benign leiomyoma.⁸ Since then, the risk of occult uterine sarcomas, including leiomyosarcoma, in women undergoing surgery for benign gynecologic indications has been determined to be much lower.

Nonetheless, the clinical importance of contained specimen removal was clearly highlighted and the role of specimen retrieval bags soared to the forefront. Open power morcellation is no longer commonly practiced, and national societies such as the American Association of Gynecologic Laparoscopists (AAGL), the Society of Gynecologic Oncology (SGO), and the American College of Obstetricians and Gynecologists (ACOG) recommend that containment systems be used for safer specimen retrieval during gynecologic surgery.^9-11 After the specimen is placed inside the containment system (typically a specimen bag), the surgeon may deliver the bag through a vaginal colpotomy or through a slightly extended laparoscopic incision to remove bulky specimens using cold-cutting extraction techniques.^12-15

Continue to: Know the pathology’s characteristics...

In most cases, based on imaging studies and physical examination, surgeons have a good idea of what to expect before proceeding with surgery. The 2 most common characteristics used for surgical planning are the specimen size (dimensions) and the tissue type (solid, cystic, soft tissue, or mixed). The mass size can range from less than 1 cm to larger than a 20-week sized fibroid uterus. Assessing the specimen in 3 dimensions is important. Tissue type also is a consideration, as soft and squishy masses, such as ovarian cysts, are easier to deflate and manipulate within the bag compared with solid or calcified tumors, such as a large fibroid uterus or a large dermoid with solid components.

Specimen shape also is a critical determinant for bag selection. Most specimen retrieval bags are tapered to varying degrees, and some have an irregular shape. Long tubular structures, such as fallopian tubes that are composed of soft tissue, fit easily into most bags regardless of bag shape or extent of bag taper, whereas the round shape of a bulky myoma may render certain bags ineffective even if the bag’s entrance accommodates the greatest diameter of the myoma. Often, a round mass will not fully fit into a bag because there is a poor fit between the mass’s shape and the bag’s shape and taper. (We discuss the concept of a poor “fit” below.) Knowing the pathology before starting a procedure can help optimize bag selection, streamline operative flow, and reduce waste.

Overview of laparoscopic bag characteristics and clinical applications

The TABLE lists the most common laparoscopic bags available for purchase in the United States. Details include the trocar size, manufacturer, product name, mouth diameter, volume, bag shape, construction material, and best clinical application.

The following are terms used to refer to the components of a laparoscopic retrieval bag:

• Mouth diameter: diameter at the entrance of a fully opened bag (FIGURE 1)
• Bag volume: the total volume a bag can accommodate when completely full
• Bag rim: characteristics of the rim of the bag when opened (that is, rigid vs soft rim, complete vs partial rim mechanism to hold the bag open) (FIGURE 2)
• Bag shape: the shape of the bag when it is fully opened (square shaped vs cone shaped vs curved bag shape) (FIGURE 2)
• Bag taper (severity and type): extent the bag is tapered from the rim of the bag’s entrance to the base of the bag; categorized by taper severity (minimal, gradual, or steep taper) and type (continuous taper or curved taper) (FIGURE 3)
• Ball fit: the maximum spherical specimen size that completely fits into a bag and allows it to cinch closed (FIGURE 4)
• Bag strength: durability of a bag when placed on tension during specimen extraction (weak, moderate, or extremely durable).

Continue to: Mouth diameter...

Mouth diameter

Bag manufacturers often differentiate bag sizes by indicating “volume” in milliliters. Bag volume, however, offers little clinical value to surgeons, as pelvic mass dimensions are usually measured in centimeters on imaging. Rather, an important characteristic for bag selection is the diameter of the rim of the bag when it is fully opened—the so-called bag mouth diameter. For a specimen to fit, the 2 dimensions of the specimen must be smaller than the dimensions of the bag entrance.

Notably, the number often linked to the specimen bag—as, for example, in the 10-mm Endo Catch bag (Covidien/Medtronic)— describes the width of the shaft of the bag before it is opened rather than the mouth diameter of the opened bag. The number actually correlates with the trocar size necessary for bag insertion rather than with the specimen size that can fit into the bag. Therefore, a 10-mm Endo Catch bag cannot fit a 10-cm mass, but rather requires a trocar size of 10 mm or greater for insertion of the bag. Fully opened, the mouth diameters of the 10-mm Endo Catch bag are roughly 6 cm x 7 cm, which allows for delivery of a 6-cm mass.

Because 2 bags that use the same trocar size for insertion may have vastly differing bag dimensions, the surgeon must know the bag mouth diameters when selecting a bag to remove the presenting pathology. For example, the Inzii 12 (Applied Medical) laparoscopic bag has mouth diameters of 9.7 cm × 13.0 cm, whereas the Anchor TRSROBO-12 (ConMed) has mouth diameters of 6.7 cm × 7.6 cm (TABLE). Although both bags can be inserted through a 12-mm trocar, both bags cannot fit the same size mass for removal.

Shape and taper

Laparoscopic bags come in various shapes (curved, cone, or square shaped), with varying levels of bag taper (steep, gradual, or no taper) (FIGURES 2 and 3). While taper has little impact on long and skinny specimens, taper may hinder successful bagging of bulky or spherical specimens.

Each bag has different grades of taper regardless of mouth diameter or trocar size. For round masses, the steeper the taper, the smaller the mass that can comfortably fit within the bag. This concept is connected to the idea of “ball fit,” explained below.

In addition, bag shape may affect what mass size can fit into the bag. An irregularly shaped curved bag or a bag with a steep taper may be well suited for removal of multiple specimens of varying sizes or soft masses that are malleable enough to conform to the bag’s shape (such as a ruptured ovarian cyst). Alternatively, a square-shaped bag or a bag with minimal taper would better accommodate a round mass.

Ball fit

When thinking about large circular masses, such as myomas or ovarian cysts, one must consider the ball fit. This refers to the maximum spherical size of the specimen that fits completely within a bag while allowing the bag to cinch closed. Generally, this is an estimation that factors in the bag shape, extent of the bag taper, bag mouth diameter, and specimen shape and tissue type. At times, although a mass can fit through the bag’s mouth diameter, a steep taper may prevent the mass from being fully bagged and limit closure of the bag (FIGURE 4).

Curved bags like the Anchor TRSVATS-15 (ConMed), which have a very narrow bottom, are prone to a limited ball fit, and thus the bag mouth diameter will not correlate with the largest mass size that can be fitted within the bag. Therefore, if using a steeply tapered bag for removal of large round masses, do not rely on the bag’s mouth diameter for bag selection. The surgeon must visualize the ball fit within the bag, taking into account the specimen size and shape, bag shape, and bag taper. In these scenarios, using the diameter of the midportion of the opened bag may better reflect the mass size that can fit into that bag.

Bag strength

Bag strength depends on the material used for bag construction. Most laparoscopic bags in the United States are made of 3 different materials: polyurethane, polypropylene, and ripstop nylon.

Polyurethane and polypropylene are synthetic plastic polymers; in bag form they are stretchy and, under extreme force, may tear. They are best used for bagging fluid-filled cysts or soft pliable masses that will not require extensive bag or tissue handling, such as extraction of large leiomyomas. Polyurethane and polypropylene bags are more susceptible to puncture with sharp laparoscopic instruments or scalpels, and care must be taken to avoid accidentally cutting the bag during tissue extraction.

Alternatively, bags made of ripstop nylon are favored for their bag strength. Ripstop nylon is a synthetic fabric that is woven together in a crosshatch pattern that makes it resistant to tearing and ripping. It was developed originally during World War II as a replacement for silk parachutes. Modern applications include its use in sails, kites, and high-quality camping equipment. This material has a favorable strength-to-weight ratio, and, in case of a tear, it is less prone to extension of the tear. For surgical applications, these bags are best used for bagging specimens that will require a lot of bag manipulation and tissue extraction. However, the ripstop fabric takes up more space in the incision than polyurethane or polypropylene, leaving the surgeon with less space for tissue extraction. Thus, as a tradeoff for bag strength, the surgeon may need to extend the incision a little, and a small self-retracting wound retractor may be necessary to allow visibility for safe tissue extraction when using a ripstop nylon bag compared with others.

Continue to: Trocar selection is important...

Trocar selection is important

While considering bag selection, the surgeon also must consider trocar selection to allow for laparoscopic insertion of the bag. Trocar size for bag selection refers to the minimum trocar diameter needed to insert the laparoscopic bag. Most bags are designed to fit into a laparoscopic trocar or into the skin incision that previously housed the trocar. Trocar size does not directly correlate with bag mouth diameter; for example, a 10-mm laparoscopic bag that can be inserted through a 10- or 12-mm trocar size cannot fit a 10-cm mass (see the mouth diameter section above).

A tip to maximize operating room (OR) efficiency is to start off with a larger trocar, such as a 12-mm trocar, if it is known that a laparoscopic bag with a 12-mm trocar size will be used, rather than starting with a 5-mm trocar and upsizing the port site incision. This saves time and offers intraoperative flexibility, allowing for the use of larger instruments and quicker insufflation.

Furthermore, if the specimen has a solid component and tissue extraction is anticipated, consider starting off with a large trocar, one that is larger than the bag’s trocar size since the incision likely will be extended. For example, even if a myoma will fit within a 10-mm laparoscopic bag made of ripstop nylon, using a 15-mm trocar rather than a 10-mm trocar may be considered since the skin and fascial incisions will need to be extended to allow for cold-cut tissue extraction. Starting with the larger 15-mm trocar may offer surgical advantages, such as direct needle delivery of larger needles for myometrial closure after myomectomy or direct removal of smaller myomas through the trocar to avoid bagging multiple specimens.

Putting it all together

To optimize efficiency in the OR for specimen removal, we recommend streamlining OR flow and reducing waste by first considering the specimen size, tissue type, bag shape, and trocar selection. Choose a bag by taking into account the bag mouth diameter and the amount of taper you will need to obtain an appropriate ball fit. If the tissue type is soft and pliable, consider a polyurethane or polypropylene bag and the smallest bag size possible, even if it has a narrow bag shape and taper.

However, if the tissue type is solid, the shape is round, and the mass is large (requiring extensive tissue extraction for removal), consider a bag made of ripstop nylon and factor in the bag shape as well as the bag taper. Using a bag without a steep taper may allow a better fit.

After choosing a laparoscopic bag, select the appropriate trocars necessary for completion of the surgery. Consider starting off with a larger trocar rather than spending the time to upsize a trocar if you plan to use a large bag or intend to extend the trocar incision for a contained tissue extraction. These tips will help optimize efficiency, reduce equipment wastage, and prevent intra-abdominal spillage.

Keep in mind that all procedures, including specimen removal using containment systems, have inherent risks. For example, visualization of the mass within the bag and visualization of vital structures may be hindered by bulkiness of the bag or specimen. There is also a risk of bag compromise and leakage, whether through manipulation of the bag or puncture during specimen extraction. Lastly, even though removing a specimen within a containment system minimizes spillage and reports of in-bag cold-knife tissue extraction in women with histologically proven endometrial cancer have suggested that it is safe, laparoscopic bags have not been proven to prevent the dissemination of malignant tissue fragments.^16,17

Overall, the inherent risks of specimen extraction during minimally invasive surgery are far outweighed by the well-established advantages of laparoscopic surgery, which carries lower risks of surgical complications such as bleeding and infection, shorter hospital stay, and quicker recovery time compared to laparotomy. There is no doubt minimally invasive surgery offers many benefits.

In summary, for best bag selection, it is equally important to know the characteristics of the pathology as it is to know the features of the specimen retrieval systems available at your institution. Understanding both the pathology and the equipment available will allow the surgeon to make the best surgical decisions for the case. ●

The use of minimally invasive gynecologic surgery (MIGS) has grown rapidly over the past 20 years. MIGS, which includes vaginal hysterectomy and laparoscopic hysterectomy, is safe and has fewer complications and a more rapid recovery period than open abdominal surgery.^1,2 In 2005, the role of MIGS was expanded further when the US Food and Drug Administration (FDA) approved robot-assisted surgery for the performance of gynecologic procedures.³ As knowledge and experience in the safe performance of MIGS progresses, the rates for MIGS procedures have skyrocketed and continue to grow. Between 2007 and 2010, laparoscopic hysterectomy rates rose from 23.5% to 30.5%, while robot-assisted laparoscopic hysterectomy rates increased from 0.5% to 9.5%, representing 40% of all hysterectomies.⁴ Due to the benefits of minimally invasive surgery over open abdominal surgery, patient and physician preference for minimally invasive procedures has grown significantly in popularity.^1,5

Because incisions are small in minimally invasive surgery, surgeons have been challenged with removing large specimens through incisions that are much smaller than the presenting pathology. One approach is to use a specimen retrieval bag for specimen extraction. Once the dissection is completed, the specimen is placed within the retrieval bag for removal, thus minimizing exposure of the specimen and its contents to the abdominopelvic cavity and incision.

The use of specimen retrieval devices has been advocated to prevent infection, avoid spillage into the peritoneal cavity, and minimize the risk of port-site metastases in cases of potentially cancerous specimens. Devices include affordable and readily available products, such as nonpowdered gloves, and commercially produced bags.⁶

While the use of specimen containment systems for tissue extraction has been well described in gynecology, the available systems vary widely in construction, size, durability, and shape, potentially leading to confusion and suboptimal bag selection during surgery.⁷ In this article, we review the most common laparoscopic bags available in the United States, provide an overview of bag characteristics, offer practice guidelines for bag selection, and review bag terminology to highlight important concepts for bag selection.

Controversy spurs change

In April 2014, the FDA warned against the use of power morcellation for specimen removal during minimally invasive surgery, citing a prevalence of 1 in 352 unsuspected uterine sarcomas and 1 in 498 unsuspected uterine leiomyosarcomas among women undergoing hysterectomy or myomectomy for presumed benign leiomyoma.⁸ Since then, the risk of occult uterine sarcomas, including leiomyosarcoma, in women undergoing surgery for benign gynecologic indications has been determined to be much lower.

Nonetheless, the clinical importance of contained specimen removal was clearly highlighted and the role of specimen retrieval bags soared to the forefront. Open power morcellation is no longer commonly practiced, and national societies such as the American Association of Gynecologic Laparoscopists (AAGL), the Society of Gynecologic Oncology (SGO), and the American College of Obstetricians and Gynecologists (ACOG) recommend that containment systems be used for safer specimen retrieval during gynecologic surgery.^9-11 After the specimen is placed inside the containment system (typically a specimen bag), the surgeon may deliver the bag through a vaginal colpotomy or through a slightly extended laparoscopic incision to remove bulky specimens using cold-cutting extraction techniques.^12-15

Continue to: Know the pathology’s characteristics...

In most cases, based on imaging studies and physical examination, surgeons have a good idea of what to expect before proceeding with surgery. The 2 most common characteristics used for surgical planning are the specimen size (dimensions) and the tissue type (solid, cystic, soft tissue, or mixed). The mass size can range from less than 1 cm to larger than a 20-week sized fibroid uterus. Assessing the specimen in 3 dimensions is important. Tissue type also is a consideration, as soft and squishy masses, such as ovarian cysts, are easier to deflate and manipulate within the bag compared with solid or calcified tumors, such as a large fibroid uterus or a large dermoid with solid components.

Specimen shape also is a critical determinant for bag selection. Most specimen retrieval bags are tapered to varying degrees, and some have an irregular shape. Long tubular structures, such as fallopian tubes that are composed of soft tissue, fit easily into most bags regardless of bag shape or extent of bag taper, whereas the round shape of a bulky myoma may render certain bags ineffective even if the bag’s entrance accommodates the greatest diameter of the myoma. Often, a round mass will not fully fit into a bag because there is a poor fit between the mass’s shape and the bag’s shape and taper. (We discuss the concept of a poor “fit” below.) Knowing the pathology before starting a procedure can help optimize bag selection, streamline operative flow, and reduce waste.

Overview of laparoscopic bag characteristics and clinical applications

The TABLE lists the most common laparoscopic bags available for purchase in the United States. Details include the trocar size, manufacturer, product name, mouth diameter, volume, bag shape, construction material, and best clinical application.

The following are terms used to refer to the components of a laparoscopic retrieval bag:

• Mouth diameter: diameter at the entrance of a fully opened bag (FIGURE 1)
• Bag volume: the total volume a bag can accommodate when completely full
• Bag rim: characteristics of the rim of the bag when opened (that is, rigid vs soft rim, complete vs partial rim mechanism to hold the bag open) (FIGURE 2)
• Bag shape: the shape of the bag when it is fully opened (square shaped vs cone shaped vs curved bag shape) (FIGURE 2)
• Bag taper (severity and type): extent the bag is tapered from the rim of the bag’s entrance to the base of the bag; categorized by taper severity (minimal, gradual, or steep taper) and type (continuous taper or curved taper) (FIGURE 3)
• Ball fit: the maximum spherical specimen size that completely fits into a bag and allows it to cinch closed (FIGURE 4)
• Bag strength: durability of a bag when placed on tension during specimen extraction (weak, moderate, or extremely durable).

Continue to: Mouth diameter...

Mouth diameter

Bag manufacturers often differentiate bag sizes by indicating “volume” in milliliters. Bag volume, however, offers little clinical value to surgeons, as pelvic mass dimensions are usually measured in centimeters on imaging. Rather, an important characteristic for bag selection is the diameter of the rim of the bag when it is fully opened—the so-called bag mouth diameter. For a specimen to fit, the 2 dimensions of the specimen must be smaller than the dimensions of the bag entrance.

Notably, the number often linked to the specimen bag—as, for example, in the 10-mm Endo Catch bag (Covidien/Medtronic)— describes the width of the shaft of the bag before it is opened rather than the mouth diameter of the opened bag. The number actually correlates with the trocar size necessary for bag insertion rather than with the specimen size that can fit into the bag. Therefore, a 10-mm Endo Catch bag cannot fit a 10-cm mass, but rather requires a trocar size of 10 mm or greater for insertion of the bag. Fully opened, the mouth diameters of the 10-mm Endo Catch bag are roughly 6 cm x 7 cm, which allows for delivery of a 6-cm mass.

Because 2 bags that use the same trocar size for insertion may have vastly differing bag dimensions, the surgeon must know the bag mouth diameters when selecting a bag to remove the presenting pathology. For example, the Inzii 12 (Applied Medical) laparoscopic bag has mouth diameters of 9.7 cm × 13.0 cm, whereas the Anchor TRSROBO-12 (ConMed) has mouth diameters of 6.7 cm × 7.6 cm (TABLE). Although both bags can be inserted through a 12-mm trocar, both bags cannot fit the same size mass for removal.

Shape and taper

Laparoscopic bags come in various shapes (curved, cone, or square shaped), with varying levels of bag taper (steep, gradual, or no taper) (FIGURES 2 and 3). While taper has little impact on long and skinny specimens, taper may hinder successful bagging of bulky or spherical specimens.

Each bag has different grades of taper regardless of mouth diameter or trocar size. For round masses, the steeper the taper, the smaller the mass that can comfortably fit within the bag. This concept is connected to the idea of “ball fit,” explained below.

In addition, bag shape may affect what mass size can fit into the bag. An irregularly shaped curved bag or a bag with a steep taper may be well suited for removal of multiple specimens of varying sizes or soft masses that are malleable enough to conform to the bag’s shape (such as a ruptured ovarian cyst). Alternatively, a square-shaped bag or a bag with minimal taper would better accommodate a round mass.

Ball fit

When thinking about large circular masses, such as myomas or ovarian cysts, one must consider the ball fit. This refers to the maximum spherical size of the specimen that fits completely within a bag while allowing the bag to cinch closed. Generally, this is an estimation that factors in the bag shape, extent of the bag taper, bag mouth diameter, and specimen shape and tissue type. At times, although a mass can fit through the bag’s mouth diameter, a steep taper may prevent the mass from being fully bagged and limit closure of the bag (FIGURE 4).

Curved bags like the Anchor TRSVATS-15 (ConMed), which have a very narrow bottom, are prone to a limited ball fit, and thus the bag mouth diameter will not correlate with the largest mass size that can be fitted within the bag. Therefore, if using a steeply tapered bag for removal of large round masses, do not rely on the bag’s mouth diameter for bag selection. The surgeon must visualize the ball fit within the bag, taking into account the specimen size and shape, bag shape, and bag taper. In these scenarios, using the diameter of the midportion of the opened bag may better reflect the mass size that can fit into that bag.

Bag strength

Bag strength depends on the material used for bag construction. Most laparoscopic bags in the United States are made of 3 different materials: polyurethane, polypropylene, and ripstop nylon.

Polyurethane and polypropylene are synthetic plastic polymers; in bag form they are stretchy and, under extreme force, may tear. They are best used for bagging fluid-filled cysts or soft pliable masses that will not require extensive bag or tissue handling, such as extraction of large leiomyomas. Polyurethane and polypropylene bags are more susceptible to puncture with sharp laparoscopic instruments or scalpels, and care must be taken to avoid accidentally cutting the bag during tissue extraction.

Alternatively, bags made of ripstop nylon are favored for their bag strength. Ripstop nylon is a synthetic fabric that is woven together in a crosshatch pattern that makes it resistant to tearing and ripping. It was developed originally during World War II as a replacement for silk parachutes. Modern applications include its use in sails, kites, and high-quality camping equipment. This material has a favorable strength-to-weight ratio, and, in case of a tear, it is less prone to extension of the tear. For surgical applications, these bags are best used for bagging specimens that will require a lot of bag manipulation and tissue extraction. However, the ripstop fabric takes up more space in the incision than polyurethane or polypropylene, leaving the surgeon with less space for tissue extraction. Thus, as a tradeoff for bag strength, the surgeon may need to extend the incision a little, and a small self-retracting wound retractor may be necessary to allow visibility for safe tissue extraction when using a ripstop nylon bag compared with others.

Continue to: Trocar selection is important...

Trocar selection is important

While considering bag selection, the surgeon also must consider trocar selection to allow for laparoscopic insertion of the bag. Trocar size for bag selection refers to the minimum trocar diameter needed to insert the laparoscopic bag. Most bags are designed to fit into a laparoscopic trocar or into the skin incision that previously housed the trocar. Trocar size does not directly correlate with bag mouth diameter; for example, a 10-mm laparoscopic bag that can be inserted through a 10- or 12-mm trocar size cannot fit a 10-cm mass (see the mouth diameter section above).

A tip to maximize operating room (OR) efficiency is to start off with a larger trocar, such as a 12-mm trocar, if it is known that a laparoscopic bag with a 12-mm trocar size will be used, rather than starting with a 5-mm trocar and upsizing the port site incision. This saves time and offers intraoperative flexibility, allowing for the use of larger instruments and quicker insufflation.

Furthermore, if the specimen has a solid component and tissue extraction is anticipated, consider starting off with a large trocar, one that is larger than the bag’s trocar size since the incision likely will be extended. For example, even if a myoma will fit within a 10-mm laparoscopic bag made of ripstop nylon, using a 15-mm trocar rather than a 10-mm trocar may be considered since the skin and fascial incisions will need to be extended to allow for cold-cut tissue extraction. Starting with the larger 15-mm trocar may offer surgical advantages, such as direct needle delivery of larger needles for myometrial closure after myomectomy or direct removal of smaller myomas through the trocar to avoid bagging multiple specimens.

Putting it all together

To optimize efficiency in the OR for specimen removal, we recommend streamlining OR flow and reducing waste by first considering the specimen size, tissue type, bag shape, and trocar selection. Choose a bag by taking into account the bag mouth diameter and the amount of taper you will need to obtain an appropriate ball fit. If the tissue type is soft and pliable, consider a polyurethane or polypropylene bag and the smallest bag size possible, even if it has a narrow bag shape and taper.

However, if the tissue type is solid, the shape is round, and the mass is large (requiring extensive tissue extraction for removal), consider a bag made of ripstop nylon and factor in the bag shape as well as the bag taper. Using a bag without a steep taper may allow a better fit.

After choosing a laparoscopic bag, select the appropriate trocars necessary for completion of the surgery. Consider starting off with a larger trocar rather than spending the time to upsize a trocar if you plan to use a large bag or intend to extend the trocar incision for a contained tissue extraction. These tips will help optimize efficiency, reduce equipment wastage, and prevent intra-abdominal spillage.

Keep in mind that all procedures, including specimen removal using containment systems, have inherent risks. For example, visualization of the mass within the bag and visualization of vital structures may be hindered by bulkiness of the bag or specimen. There is also a risk of bag compromise and leakage, whether through manipulation of the bag or puncture during specimen extraction. Lastly, even though removing a specimen within a containment system minimizes spillage and reports of in-bag cold-knife tissue extraction in women with histologically proven endometrial cancer have suggested that it is safe, laparoscopic bags have not been proven to prevent the dissemination of malignant tissue fragments.^16,17

Overall, the inherent risks of specimen extraction during minimally invasive surgery are far outweighed by the well-established advantages of laparoscopic surgery, which carries lower risks of surgical complications such as bleeding and infection, shorter hospital stay, and quicker recovery time compared to laparotomy. There is no doubt minimally invasive surgery offers many benefits.

In summary, for best bag selection, it is equally important to know the characteristics of the pathology as it is to know the features of the specimen retrieval systems available at your institution. Understanding both the pathology and the equipment available will allow the surgeon to make the best surgical decisions for the case. ●

The use of minimally invasive gynecologic surgery (MIGS) has grown rapidly over the past 20 years. MIGS, which includes vaginal hysterectomy and laparoscopic hysterectomy, is safe and has fewer complications and a more rapid recovery period than open abdominal surgery.^1,2 In 2005, the role of MIGS was expanded further when the US Food and Drug Administration (FDA) approved robot-assisted surgery for the performance of gynecologic procedures.³ As knowledge and experience in the safe performance of MIGS progresses, the rates for MIGS procedures have skyrocketed and continue to grow. Between 2007 and 2010, laparoscopic hysterectomy rates rose from 23.5% to 30.5%, while robot-assisted laparoscopic hysterectomy rates increased from 0.5% to 9.5%, representing 40% of all hysterectomies.⁴ Due to the benefits of minimally invasive surgery over open abdominal surgery, patient and physician preference for minimally invasive procedures has grown significantly in popularity.^1,5

Because incisions are small in minimally invasive surgery, surgeons have been challenged with removing large specimens through incisions that are much smaller than the presenting pathology. One approach is to use a specimen retrieval bag for specimen extraction. Once the dissection is completed, the specimen is placed within the retrieval bag for removal, thus minimizing exposure of the specimen and its contents to the abdominopelvic cavity and incision.

The use of specimen retrieval devices has been advocated to prevent infection, avoid spillage into the peritoneal cavity, and minimize the risk of port-site metastases in cases of potentially cancerous specimens. Devices include affordable and readily available products, such as nonpowdered gloves, and commercially produced bags.⁶

While the use of specimen containment systems for tissue extraction has been well described in gynecology, the available systems vary widely in construction, size, durability, and shape, potentially leading to confusion and suboptimal bag selection during surgery.⁷ In this article, we review the most common laparoscopic bags available in the United States, provide an overview of bag characteristics, offer practice guidelines for bag selection, and review bag terminology to highlight important concepts for bag selection.

Controversy spurs change

In April 2014, the FDA warned against the use of power morcellation for specimen removal during minimally invasive surgery, citing a prevalence of 1 in 352 unsuspected uterine sarcomas and 1 in 498 unsuspected uterine leiomyosarcomas among women undergoing hysterectomy or myomectomy for presumed benign leiomyoma.⁸ Since then, the risk of occult uterine sarcomas, including leiomyosarcoma, in women undergoing surgery for benign gynecologic indications has been determined to be much lower.

Nonetheless, the clinical importance of contained specimen removal was clearly highlighted and the role of specimen retrieval bags soared to the forefront. Open power morcellation is no longer commonly practiced, and national societies such as the American Association of Gynecologic Laparoscopists (AAGL), the Society of Gynecologic Oncology (SGO), and the American College of Obstetricians and Gynecologists (ACOG) recommend that containment systems be used for safer specimen retrieval during gynecologic surgery.^9-11 After the specimen is placed inside the containment system (typically a specimen bag), the surgeon may deliver the bag through a vaginal colpotomy or through a slightly extended laparoscopic incision to remove bulky specimens using cold-cutting extraction techniques.^12-15

Continue to: Know the pathology’s characteristics...

In most cases, based on imaging studies and physical examination, surgeons have a good idea of what to expect before proceeding with surgery. The 2 most common characteristics used for surgical planning are the specimen size (dimensions) and the tissue type (solid, cystic, soft tissue, or mixed). The mass size can range from less than 1 cm to larger than a 20-week sized fibroid uterus. Assessing the specimen in 3 dimensions is important. Tissue type also is a consideration, as soft and squishy masses, such as ovarian cysts, are easier to deflate and manipulate within the bag compared with solid or calcified tumors, such as a large fibroid uterus or a large dermoid with solid components.

Specimen shape also is a critical determinant for bag selection. Most specimen retrieval bags are tapered to varying degrees, and some have an irregular shape. Long tubular structures, such as fallopian tubes that are composed of soft tissue, fit easily into most bags regardless of bag shape or extent of bag taper, whereas the round shape of a bulky myoma may render certain bags ineffective even if the bag’s entrance accommodates the greatest diameter of the myoma. Often, a round mass will not fully fit into a bag because there is a poor fit between the mass’s shape and the bag’s shape and taper. (We discuss the concept of a poor “fit” below.) Knowing the pathology before starting a procedure can help optimize bag selection, streamline operative flow, and reduce waste.

Overview of laparoscopic bag characteristics and clinical applications

The TABLE lists the most common laparoscopic bags available for purchase in the United States. Details include the trocar size, manufacturer, product name, mouth diameter, volume, bag shape, construction material, and best clinical application.

The following are terms used to refer to the components of a laparoscopic retrieval bag:

• Mouth diameter: diameter at the entrance of a fully opened bag (FIGURE 1)
• Bag volume: the total volume a bag can accommodate when completely full
• Bag rim: characteristics of the rim of the bag when opened (that is, rigid vs soft rim, complete vs partial rim mechanism to hold the bag open) (FIGURE 2)
• Bag shape: the shape of the bag when it is fully opened (square shaped vs cone shaped vs curved bag shape) (FIGURE 2)
• Bag taper (severity and type): extent the bag is tapered from the rim of the bag’s entrance to the base of the bag; categorized by taper severity (minimal, gradual, or steep taper) and type (continuous taper or curved taper) (FIGURE 3)
• Ball fit: the maximum spherical specimen size that completely fits into a bag and allows it to cinch closed (FIGURE 4)
• Bag strength: durability of a bag when placed on tension during specimen extraction (weak, moderate, or extremely durable).

Continue to: Mouth diameter...

Mouth diameter

Bag manufacturers often differentiate bag sizes by indicating “volume” in milliliters. Bag volume, however, offers little clinical value to surgeons, as pelvic mass dimensions are usually measured in centimeters on imaging. Rather, an important characteristic for bag selection is the diameter of the rim of the bag when it is fully opened—the so-called bag mouth diameter. For a specimen to fit, the 2 dimensions of the specimen must be smaller than the dimensions of the bag entrance.

Notably, the number often linked to the specimen bag—as, for example, in the 10-mm Endo Catch bag (Covidien/Medtronic)— describes the width of the shaft of the bag before it is opened rather than the mouth diameter of the opened bag. The number actually correlates with the trocar size necessary for bag insertion rather than with the specimen size that can fit into the bag. Therefore, a 10-mm Endo Catch bag cannot fit a 10-cm mass, but rather requires a trocar size of 10 mm or greater for insertion of the bag. Fully opened, the mouth diameters of the 10-mm Endo Catch bag are roughly 6 cm x 7 cm, which allows for delivery of a 6-cm mass.

Because 2 bags that use the same trocar size for insertion may have vastly differing bag dimensions, the surgeon must know the bag mouth diameters when selecting a bag to remove the presenting pathology. For example, the Inzii 12 (Applied Medical) laparoscopic bag has mouth diameters of 9.7 cm × 13.0 cm, whereas the Anchor TRSROBO-12 (ConMed) has mouth diameters of 6.7 cm × 7.6 cm (TABLE). Although both bags can be inserted through a 12-mm trocar, both bags cannot fit the same size mass for removal.

Shape and taper

Laparoscopic bags come in various shapes (curved, cone, or square shaped), with varying levels of bag taper (steep, gradual, or no taper) (FIGURES 2 and 3). While taper has little impact on long and skinny specimens, taper may hinder successful bagging of bulky or spherical specimens.

Each bag has different grades of taper regardless of mouth diameter or trocar size. For round masses, the steeper the taper, the smaller the mass that can comfortably fit within the bag. This concept is connected to the idea of “ball fit,” explained below.

In addition, bag shape may affect what mass size can fit into the bag. An irregularly shaped curved bag or a bag with a steep taper may be well suited for removal of multiple specimens of varying sizes or soft masses that are malleable enough to conform to the bag’s shape (such as a ruptured ovarian cyst). Alternatively, a square-shaped bag or a bag with minimal taper would better accommodate a round mass.

Ball fit

When thinking about large circular masses, such as myomas or ovarian cysts, one must consider the ball fit. This refers to the maximum spherical size of the specimen that fits completely within a bag while allowing the bag to cinch closed. Generally, this is an estimation that factors in the bag shape, extent of the bag taper, bag mouth diameter, and specimen shape and tissue type. At times, although a mass can fit through the bag’s mouth diameter, a steep taper may prevent the mass from being fully bagged and limit closure of the bag (FIGURE 4).

Curved bags like the Anchor TRSVATS-15 (ConMed), which have a very narrow bottom, are prone to a limited ball fit, and thus the bag mouth diameter will not correlate with the largest mass size that can be fitted within the bag. Therefore, if using a steeply tapered bag for removal of large round masses, do not rely on the bag’s mouth diameter for bag selection. The surgeon must visualize the ball fit within the bag, taking into account the specimen size and shape, bag shape, and bag taper. In these scenarios, using the diameter of the midportion of the opened bag may better reflect the mass size that can fit into that bag.

Bag strength

Bag strength depends on the material used for bag construction. Most laparoscopic bags in the United States are made of 3 different materials: polyurethane, polypropylene, and ripstop nylon.

Polyurethane and polypropylene are synthetic plastic polymers; in bag form they are stretchy and, under extreme force, may tear. They are best used for bagging fluid-filled cysts or soft pliable masses that will not require extensive bag or tissue handling, such as extraction of large leiomyomas. Polyurethane and polypropylene bags are more susceptible to puncture with sharp laparoscopic instruments or scalpels, and care must be taken to avoid accidentally cutting the bag during tissue extraction.

Alternatively, bags made of ripstop nylon are favored for their bag strength. Ripstop nylon is a synthetic fabric that is woven together in a crosshatch pattern that makes it resistant to tearing and ripping. It was developed originally during World War II as a replacement for silk parachutes. Modern applications include its use in sails, kites, and high-quality camping equipment. This material has a favorable strength-to-weight ratio, and, in case of a tear, it is less prone to extension of the tear. For surgical applications, these bags are best used for bagging specimens that will require a lot of bag manipulation and tissue extraction. However, the ripstop fabric takes up more space in the incision than polyurethane or polypropylene, leaving the surgeon with less space for tissue extraction. Thus, as a tradeoff for bag strength, the surgeon may need to extend the incision a little, and a small self-retracting wound retractor may be necessary to allow visibility for safe tissue extraction when using a ripstop nylon bag compared with others.

Continue to: Trocar selection is important...

Trocar selection is important

While considering bag selection, the surgeon also must consider trocar selection to allow for laparoscopic insertion of the bag. Trocar size for bag selection refers to the minimum trocar diameter needed to insert the laparoscopic bag. Most bags are designed to fit into a laparoscopic trocar or into the skin incision that previously housed the trocar. Trocar size does not directly correlate with bag mouth diameter; for example, a 10-mm laparoscopic bag that can be inserted through a 10- or 12-mm trocar size cannot fit a 10-cm mass (see the mouth diameter section above).

A tip to maximize operating room (OR) efficiency is to start off with a larger trocar, such as a 12-mm trocar, if it is known that a laparoscopic bag with a 12-mm trocar size will be used, rather than starting with a 5-mm trocar and upsizing the port site incision. This saves time and offers intraoperative flexibility, allowing for the use of larger instruments and quicker insufflation.

Furthermore, if the specimen has a solid component and tissue extraction is anticipated, consider starting off with a large trocar, one that is larger than the bag’s trocar size since the incision likely will be extended. For example, even if a myoma will fit within a 10-mm laparoscopic bag made of ripstop nylon, using a 15-mm trocar rather than a 10-mm trocar may be considered since the skin and fascial incisions will need to be extended to allow for cold-cut tissue extraction. Starting with the larger 15-mm trocar may offer surgical advantages, such as direct needle delivery of larger needles for myometrial closure after myomectomy or direct removal of smaller myomas through the trocar to avoid bagging multiple specimens.

Putting it all together

To optimize efficiency in the OR for specimen removal, we recommend streamlining OR flow and reducing waste by first considering the specimen size, tissue type, bag shape, and trocar selection. Choose a bag by taking into account the bag mouth diameter and the amount of taper you will need to obtain an appropriate ball fit. If the tissue type is soft and pliable, consider a polyurethane or polypropylene bag and the smallest bag size possible, even if it has a narrow bag shape and taper.

However, if the tissue type is solid, the shape is round, and the mass is large (requiring extensive tissue extraction for removal), consider a bag made of ripstop nylon and factor in the bag shape as well as the bag taper. Using a bag without a steep taper may allow a better fit.

After choosing a laparoscopic bag, select the appropriate trocars necessary for completion of the surgery. Consider starting off with a larger trocar rather than spending the time to upsize a trocar if you plan to use a large bag or intend to extend the trocar incision for a contained tissue extraction. These tips will help optimize efficiency, reduce equipment wastage, and prevent intra-abdominal spillage.

Keep in mind that all procedures, including specimen removal using containment systems, have inherent risks. For example, visualization of the mass within the bag and visualization of vital structures may be hindered by bulkiness of the bag or specimen. There is also a risk of bag compromise and leakage, whether through manipulation of the bag or puncture during specimen extraction. Lastly, even though removing a specimen within a containment system minimizes spillage and reports of in-bag cold-knife tissue extraction in women with histologically proven endometrial cancer have suggested that it is safe, laparoscopic bags have not been proven to prevent the dissemination of malignant tissue fragments.^16,17

Overall, the inherent risks of specimen extraction during minimally invasive surgery are far outweighed by the well-established advantages of laparoscopic surgery, which carries lower risks of surgical complications such as bleeding and infection, shorter hospital stay, and quicker recovery time compared to laparotomy. There is no doubt minimally invasive surgery offers many benefits.

In summary, for best bag selection, it is equally important to know the characteristics of the pathology as it is to know the features of the specimen retrieval systems available at your institution. Understanding both the pathology and the equipment available will allow the surgeon to make the best surgical decisions for the case. ●

A more than 6-point improvement in Headache Impact Test (HIT-6) total score and a 1-2 category improvement in item-specific scores of HIT-6 appeared to be associated with meaningful change in an individual with chronic migraine, recent research suggests.

Using data from the phase 3 PROMISE-2 study, which evaluated intravenous eptinezumab in doses of 100 mg or 300 mg, or placebo every 12 weeks in 1,072 participants for the prevention of chronic migraine, Carrie R. Houts, PhD, director of psychometrics at the Vector Psychometric Group, in Chapel Hill, N.C., and colleagues determined that their finding of 6-point improvement of HIT-6 total score was consistent with other studies. However, they pointed out that little research has been done in evaluating how item-specific scores of HIT-6 impact individuals with chronic migraine. HIT-6 item scores examine whether individuals with headaches experience severe pain, limit their daily activities, have a desire to lie down, feel too tired to do daily activities, felt “fed up or irritated” because of headaches, and feel their headaches limit concentration on work or daily activities.

“The item-specific responder definitions give clinicians and researchers the ability to evaluate and track the impact of headache on specific item-level areas of patients’ lives. These responder definitions provide practical and easily interpreted results that can be used to evaluate treatment benefits over time and to improve clinician-patients communication focus on improvements in key aspects of functioning in individuals with chronic migraine,” Dr. Houts and colleagues wrote in their study, published in the October issue of Headache.

The 6-point value and the 1-2 category improvement values in item-specific scores, they suggested, could be used as a benchmark to help other clinicians and researchers detect meaningful change in individual patients with chronic migraine. Although the user guide for HIT-6 highlights a 5-point change in the total score as clinically meaningful, the authors of the guide do not provide evidence for why the 5-point value signifies clinically meaningful change, they said.
 

Determining thresholds of clinically meaningful change

In their study, Dr. Houts and colleagues used distribution-based methods to gauge responder values for the HIT-6 total score, while item-specific HIT-6 analyses were measured with Patients’ Global Impression of Change (PGIC), reduction in migraine frequency through monthly migraine days (MMDs), and EuroQol 5 dimensions 5 levels visual analog scale (EQ-5D-5L VAS). The researchers also used HIT-6 values from a literature review and from analyses in PROMISE-2 to calculate “a final chronic migraine-specific responder definition value” between baseline and 12 weeks. Participants in the PROMISE-2 study were mostly women (88.2%) and white (91.0%) with a mean age of 40.5 years.

The literature search revealed responder thresholds for the HIT-6 total score in a range between a decrease of 3 points and 8 points. Within PROMISE-2, the HIT-6 total score responder threshold was found to be between –2.6 and –2.2, which the researchers rounded down to a decrease of 3 points. When taking both sets of responder thresholds into account, the researchers calculated the median responder value as –5.5, which was rounded down to a decrease in 6 points in the HIT-6 total score. “[The estimate] appears most appropriate for discriminating between individuals with chronic migraine who have experienced meaningful change over time and those who have not,” Dr. Houts and colleagues said.

For item-specific HIT-6 scores, the mean score changes were –1 points for categories involving severe pain, limiting activities, lying down, and –2 points for categories involving feeling tired, being fed up or irritated, and limiting concentration.

“Taken together, the current chronic migraine-specific results are consistent with values derived from general headache/migraine samples and suggest that a decrease of 6 points or more on the HIT-6 total score would be considered meaningful to chronic migraine patients,” Dr. Houts and colleagues said. “This would translate to approximately a 4-category change on a single item, change on 2 items of approximately 2 and 3 categories, or a 1-category change on 3 or 4 of the 6 items, depending on the initial category.”

The researchers cautioned that the values outlined in the study “should not be used to determine clinically meaningful difference between treatment groups” and that “future work, similar to that reported here, will identify a chronic migraine-specific clinically meaningful difference between treatment groups value.”
 

A better measure of chronic migraine?

In an interview, J. D. Bartleson Jr., MD, a retired neurologist with the Mayo Clinic in Rochester, Minn., questioned why HIT-6 criteria was used in the initial PROMISE-2 study. “There is not a lot of difference between the significant and insignificant categories. Chronic migraine may be better measured with pain severity and number of headache days per month,” he said.

,“It may be appropriate to use just 1 or 2 symptoms for evaluating a given patient’s headache burden,” in terms of clinical application of the study for neurologists, Dr. Bartleson said. He emphasized that more research is needed.

This study was funded by H. Lundbeck A/S, which also provided funding of medical writing and editorial support for the manuscript. Three authors report being employees of Vector Psychometric Group at the time of the study, and the company received funding from H. Lundbeck A/S for their time conducting study-related research. Three other authors report relationships with pharmaceutical companies, medical societies, government agencies, and industry related to the study in the form of consultancies, advisory board memberships, honoraria, research support, stock or stock options, and employment. Dr. Bartleson reports no relevant conflicts of interest.

SOURCE: Houts C et al. Headache. 2020;60(9):2003-13.

A more than 6-point improvement in Headache Impact Test (HIT-6) total score and a 1-2 category improvement in item-specific scores of HIT-6 appeared to be associated with meaningful change in an individual with chronic migraine, recent research suggests.

Using data from the phase 3 PROMISE-2 study, which evaluated intravenous eptinezumab in doses of 100 mg or 300 mg, or placebo every 12 weeks in 1,072 participants for the prevention of chronic migraine, Carrie R. Houts, PhD, director of psychometrics at the Vector Psychometric Group, in Chapel Hill, N.C., and colleagues determined that their finding of 6-point improvement of HIT-6 total score was consistent with other studies. However, they pointed out that little research has been done in evaluating how item-specific scores of HIT-6 impact individuals with chronic migraine. HIT-6 item scores examine whether individuals with headaches experience severe pain, limit their daily activities, have a desire to lie down, feel too tired to do daily activities, felt “fed up or irritated” because of headaches, and feel their headaches limit concentration on work or daily activities.

“The item-specific responder definitions give clinicians and researchers the ability to evaluate and track the impact of headache on specific item-level areas of patients’ lives. These responder definitions provide practical and easily interpreted results that can be used to evaluate treatment benefits over time and to improve clinician-patients communication focus on improvements in key aspects of functioning in individuals with chronic migraine,” Dr. Houts and colleagues wrote in their study, published in the October issue of Headache.

The 6-point value and the 1-2 category improvement values in item-specific scores, they suggested, could be used as a benchmark to help other clinicians and researchers detect meaningful change in individual patients with chronic migraine. Although the user guide for HIT-6 highlights a 5-point change in the total score as clinically meaningful, the authors of the guide do not provide evidence for why the 5-point value signifies clinically meaningful change, they said.
 

Determining thresholds of clinically meaningful change

In their study, Dr. Houts and colleagues used distribution-based methods to gauge responder values for the HIT-6 total score, while item-specific HIT-6 analyses were measured with Patients’ Global Impression of Change (PGIC), reduction in migraine frequency through monthly migraine days (MMDs), and EuroQol 5 dimensions 5 levels visual analog scale (EQ-5D-5L VAS). The researchers also used HIT-6 values from a literature review and from analyses in PROMISE-2 to calculate “a final chronic migraine-specific responder definition value” between baseline and 12 weeks. Participants in the PROMISE-2 study were mostly women (88.2%) and white (91.0%) with a mean age of 40.5 years.

The literature search revealed responder thresholds for the HIT-6 total score in a range between a decrease of 3 points and 8 points. Within PROMISE-2, the HIT-6 total score responder threshold was found to be between –2.6 and –2.2, which the researchers rounded down to a decrease of 3 points. When taking both sets of responder thresholds into account, the researchers calculated the median responder value as –5.5, which was rounded down to a decrease in 6 points in the HIT-6 total score. “[The estimate] appears most appropriate for discriminating between individuals with chronic migraine who have experienced meaningful change over time and those who have not,” Dr. Houts and colleagues said.

For item-specific HIT-6 scores, the mean score changes were –1 points for categories involving severe pain, limiting activities, lying down, and –2 points for categories involving feeling tired, being fed up or irritated, and limiting concentration.

“Taken together, the current chronic migraine-specific results are consistent with values derived from general headache/migraine samples and suggest that a decrease of 6 points or more on the HIT-6 total score would be considered meaningful to chronic migraine patients,” Dr. Houts and colleagues said. “This would translate to approximately a 4-category change on a single item, change on 2 items of approximately 2 and 3 categories, or a 1-category change on 3 or 4 of the 6 items, depending on the initial category.”

The researchers cautioned that the values outlined in the study “should not be used to determine clinically meaningful difference between treatment groups” and that “future work, similar to that reported here, will identify a chronic migraine-specific clinically meaningful difference between treatment groups value.”
 

A better measure of chronic migraine?

In an interview, J. D. Bartleson Jr., MD, a retired neurologist with the Mayo Clinic in Rochester, Minn., questioned why HIT-6 criteria was used in the initial PROMISE-2 study. “There is not a lot of difference between the significant and insignificant categories. Chronic migraine may be better measured with pain severity and number of headache days per month,” he said.

,“It may be appropriate to use just 1 or 2 symptoms for evaluating a given patient’s headache burden,” in terms of clinical application of the study for neurologists, Dr. Bartleson said. He emphasized that more research is needed.

This study was funded by H. Lundbeck A/S, which also provided funding of medical writing and editorial support for the manuscript. Three authors report being employees of Vector Psychometric Group at the time of the study, and the company received funding from H. Lundbeck A/S for their time conducting study-related research. Three other authors report relationships with pharmaceutical companies, medical societies, government agencies, and industry related to the study in the form of consultancies, advisory board memberships, honoraria, research support, stock or stock options, and employment. Dr. Bartleson reports no relevant conflicts of interest.

SOURCE: Houts C et al. Headache. 2020;60(9):2003-13.

A more than 6-point improvement in Headache Impact Test (HIT-6) total score and a 1-2 category improvement in item-specific scores of HIT-6 appeared to be associated with meaningful change in an individual with chronic migraine, recent research suggests.

Using data from the phase 3 PROMISE-2 study, which evaluated intravenous eptinezumab in doses of 100 mg or 300 mg, or placebo every 12 weeks in 1,072 participants for the prevention of chronic migraine, Carrie R. Houts, PhD, director of psychometrics at the Vector Psychometric Group, in Chapel Hill, N.C., and colleagues determined that their finding of 6-point improvement of HIT-6 total score was consistent with other studies. However, they pointed out that little research has been done in evaluating how item-specific scores of HIT-6 impact individuals with chronic migraine. HIT-6 item scores examine whether individuals with headaches experience severe pain, limit their daily activities, have a desire to lie down, feel too tired to do daily activities, felt “fed up or irritated” because of headaches, and feel their headaches limit concentration on work or daily activities.

“The item-specific responder definitions give clinicians and researchers the ability to evaluate and track the impact of headache on specific item-level areas of patients’ lives. These responder definitions provide practical and easily interpreted results that can be used to evaluate treatment benefits over time and to improve clinician-patients communication focus on improvements in key aspects of functioning in individuals with chronic migraine,” Dr. Houts and colleagues wrote in their study, published in the October issue of Headache.

The 6-point value and the 1-2 category improvement values in item-specific scores, they suggested, could be used as a benchmark to help other clinicians and researchers detect meaningful change in individual patients with chronic migraine. Although the user guide for HIT-6 highlights a 5-point change in the total score as clinically meaningful, the authors of the guide do not provide evidence for why the 5-point value signifies clinically meaningful change, they said.
 

Determining thresholds of clinically meaningful change

In their study, Dr. Houts and colleagues used distribution-based methods to gauge responder values for the HIT-6 total score, while item-specific HIT-6 analyses were measured with Patients’ Global Impression of Change (PGIC), reduction in migraine frequency through monthly migraine days (MMDs), and EuroQol 5 dimensions 5 levels visual analog scale (EQ-5D-5L VAS). The researchers also used HIT-6 values from a literature review and from analyses in PROMISE-2 to calculate “a final chronic migraine-specific responder definition value” between baseline and 12 weeks. Participants in the PROMISE-2 study were mostly women (88.2%) and white (91.0%) with a mean age of 40.5 years.

The literature search revealed responder thresholds for the HIT-6 total score in a range between a decrease of 3 points and 8 points. Within PROMISE-2, the HIT-6 total score responder threshold was found to be between –2.6 and –2.2, which the researchers rounded down to a decrease of 3 points. When taking both sets of responder thresholds into account, the researchers calculated the median responder value as –5.5, which was rounded down to a decrease in 6 points in the HIT-6 total score. “[The estimate] appears most appropriate for discriminating between individuals with chronic migraine who have experienced meaningful change over time and those who have not,” Dr. Houts and colleagues said.

For item-specific HIT-6 scores, the mean score changes were –1 points for categories involving severe pain, limiting activities, lying down, and –2 points for categories involving feeling tired, being fed up or irritated, and limiting concentration.

“Taken together, the current chronic migraine-specific results are consistent with values derived from general headache/migraine samples and suggest that a decrease of 6 points or more on the HIT-6 total score would be considered meaningful to chronic migraine patients,” Dr. Houts and colleagues said. “This would translate to approximately a 4-category change on a single item, change on 2 items of approximately 2 and 3 categories, or a 1-category change on 3 or 4 of the 6 items, depending on the initial category.”

The researchers cautioned that the values outlined in the study “should not be used to determine clinically meaningful difference between treatment groups” and that “future work, similar to that reported here, will identify a chronic migraine-specific clinically meaningful difference between treatment groups value.”
 

A better measure of chronic migraine?

In an interview, J. D. Bartleson Jr., MD, a retired neurologist with the Mayo Clinic in Rochester, Minn., questioned why HIT-6 criteria was used in the initial PROMISE-2 study. “There is not a lot of difference between the significant and insignificant categories. Chronic migraine may be better measured with pain severity and number of headache days per month,” he said.

,“It may be appropriate to use just 1 or 2 symptoms for evaluating a given patient’s headache burden,” in terms of clinical application of the study for neurologists, Dr. Bartleson said. He emphasized that more research is needed.

This study was funded by H. Lundbeck A/S, which also provided funding of medical writing and editorial support for the manuscript. Three authors report being employees of Vector Psychometric Group at the time of the study, and the company received funding from H. Lundbeck A/S for their time conducting study-related research. Three other authors report relationships with pharmaceutical companies, medical societies, government agencies, and industry related to the study in the form of consultancies, advisory board memberships, honoraria, research support, stock or stock options, and employment. Dr. Bartleson reports no relevant conflicts of interest.

SOURCE: Houts C et al. Headache. 2020;60(9):2003-13.

The mental health consequences of COVID-19 deaths are likely to overwhelm an already tattered U.S. mental health system, leading to a lack of access, particularly for the most vulnerable, experts warn.

“A second wave of devastation is imminent, attributable to mental health consequences of COVID-19,” write Naomi Simon, MD, and coauthors with the department of psychiatry, New York University.

In a Viewpoint article published in JAMA on Oct. 12, physicians offer some sobering statistics.

Since February 2020, COVID-19 has taken the lives of more than 214,000 Americans. The number of deaths currently attributed to the virus is nearly four times the number of Americans killed during the Vietnam War. The magnitude of death over a short period is a tragedy on a “historic scale,” wrote Dr. Simon and colleagues.

The surge in mental health problems related to COVID-19 deaths will bring further challenges to individuals, families, and communities, including a spike in deaths from suicide and drug overdoses, they warned.

It’s important to consider, they noted, that each COVID-19 death leaves an estimated nine family members bereaved, which is projected to lead to an estimated 2 million bereaved individuals in the United States.

“This interpersonal loss on a massive scale is compounded by societal disruption,” they wrote. The necessary social distancing and quarantine measures implemented to fight the virus have amplified emotional turmoil and have disrupted the ability of personal support networks and communities to come together and grieve.

“Of central concern is the transformation of normal grief and distress into prolonged grief and major depressive disorder and symptoms of posttraumatic stress disorder,” Simon and colleagues said.

“Once established, these conditions can become chronic with additional comorbidities such as substance use disorders. Prolonged grief affects approximately 10% of bereaved individuals, but this is likely an underestimate for grief related to deaths from COVID-19,” they wrote.

As with the first COVID-19 wave, the mental health wave will disproportionately affect Black persons, Hispanic persons, older adults, persons in lower socioeconomic groups of all races and ethnicities, and healthcare workers, they note.

The psychological risks for health care and other essential workers are of particular concern, they say. “Supporting the mental health of these and other essential workforce is critical to readiness for managing recurrent waves of the pandemic,” they stated.

How will the United States manage this impending wave of mental health problems?

“The solution will require increased funding for mental health; widespread screening to identify individuals at highest risk including suicide risk; availability of primary care clinicians and mental health professionals trained to treat those with prolonged grief, depression, traumatic stress, and substance abuse; and a diligent focus on families and communities to creatively restore the approaches by which they have managed tragedy and loss over generations,” the authors wrote.

“History has shown that societies recover from such devastation when leaders and members are joined by a shared purpose, acting in a unified way to facilitate recovery. In such societies, there is a shared understanding that its members must care for one another because the loss of one is a loss for all. Above all, this shared understanding must be restored,” they concluded.

Dr. Simon has received personal fees from Vanda Pharmaceuticals Inc, MGH Psychiatry Academy, Axovant Sciences, Springworks, Praxis Therapeutics, Aptinyx, Genomind, and Wiley (deputy editor, Depression and Anxiety). Saxe has received royalties from Guilford Press for the book Trauma Systems Therapy for Children and Teens (2016). Marmar serves on the scientific advisory board and owns equity in Receptor Life Sciences and serves on the PTSD advisory board for Otsuka Pharmaceutical.
 

A version of this article originally appeared on Medscape.com.

The mental health consequences of COVID-19 deaths are likely to overwhelm an already tattered U.S. mental health system, leading to a lack of access, particularly for the most vulnerable, experts warn.

“A second wave of devastation is imminent, attributable to mental health consequences of COVID-19,” write Naomi Simon, MD, and coauthors with the department of psychiatry, New York University.

In a Viewpoint article published in JAMA on Oct. 12, physicians offer some sobering statistics.

Since February 2020, COVID-19 has taken the lives of more than 214,000 Americans. The number of deaths currently attributed to the virus is nearly four times the number of Americans killed during the Vietnam War. The magnitude of death over a short period is a tragedy on a “historic scale,” wrote Dr. Simon and colleagues.

The surge in mental health problems related to COVID-19 deaths will bring further challenges to individuals, families, and communities, including a spike in deaths from suicide and drug overdoses, they warned.

It’s important to consider, they noted, that each COVID-19 death leaves an estimated nine family members bereaved, which is projected to lead to an estimated 2 million bereaved individuals in the United States.

“This interpersonal loss on a massive scale is compounded by societal disruption,” they wrote. The necessary social distancing and quarantine measures implemented to fight the virus have amplified emotional turmoil and have disrupted the ability of personal support networks and communities to come together and grieve.

“Of central concern is the transformation of normal grief and distress into prolonged grief and major depressive disorder and symptoms of posttraumatic stress disorder,” Simon and colleagues said.

“Once established, these conditions can become chronic with additional comorbidities such as substance use disorders. Prolonged grief affects approximately 10% of bereaved individuals, but this is likely an underestimate for grief related to deaths from COVID-19,” they wrote.

As with the first COVID-19 wave, the mental health wave will disproportionately affect Black persons, Hispanic persons, older adults, persons in lower socioeconomic groups of all races and ethnicities, and healthcare workers, they note.

The psychological risks for health care and other essential workers are of particular concern, they say. “Supporting the mental health of these and other essential workforce is critical to readiness for managing recurrent waves of the pandemic,” they stated.

How will the United States manage this impending wave of mental health problems?

“The solution will require increased funding for mental health; widespread screening to identify individuals at highest risk including suicide risk; availability of primary care clinicians and mental health professionals trained to treat those with prolonged grief, depression, traumatic stress, and substance abuse; and a diligent focus on families and communities to creatively restore the approaches by which they have managed tragedy and loss over generations,” the authors wrote.

“History has shown that societies recover from such devastation when leaders and members are joined by a shared purpose, acting in a unified way to facilitate recovery. In such societies, there is a shared understanding that its members must care for one another because the loss of one is a loss for all. Above all, this shared understanding must be restored,” they concluded.

Dr. Simon has received personal fees from Vanda Pharmaceuticals Inc, MGH Psychiatry Academy, Axovant Sciences, Springworks, Praxis Therapeutics, Aptinyx, Genomind, and Wiley (deputy editor, Depression and Anxiety). Saxe has received royalties from Guilford Press for the book Trauma Systems Therapy for Children and Teens (2016). Marmar serves on the scientific advisory board and owns equity in Receptor Life Sciences and serves on the PTSD advisory board for Otsuka Pharmaceutical.
 

A version of this article originally appeared on Medscape.com.

The mental health consequences of COVID-19 deaths are likely to overwhelm an already tattered U.S. mental health system, leading to a lack of access, particularly for the most vulnerable, experts warn.

“A second wave of devastation is imminent, attributable to mental health consequences of COVID-19,” write Naomi Simon, MD, and coauthors with the department of psychiatry, New York University.

In a Viewpoint article published in JAMA on Oct. 12, physicians offer some sobering statistics.

Since February 2020, COVID-19 has taken the lives of more than 214,000 Americans. The number of deaths currently attributed to the virus is nearly four times the number of Americans killed during the Vietnam War. The magnitude of death over a short period is a tragedy on a “historic scale,” wrote Dr. Simon and colleagues.

The surge in mental health problems related to COVID-19 deaths will bring further challenges to individuals, families, and communities, including a spike in deaths from suicide and drug overdoses, they warned.

It’s important to consider, they noted, that each COVID-19 death leaves an estimated nine family members bereaved, which is projected to lead to an estimated 2 million bereaved individuals in the United States.

“This interpersonal loss on a massive scale is compounded by societal disruption,” they wrote. The necessary social distancing and quarantine measures implemented to fight the virus have amplified emotional turmoil and have disrupted the ability of personal support networks and communities to come together and grieve.

“Of central concern is the transformation of normal grief and distress into prolonged grief and major depressive disorder and symptoms of posttraumatic stress disorder,” Simon and colleagues said.

“Once established, these conditions can become chronic with additional comorbidities such as substance use disorders. Prolonged grief affects approximately 10% of bereaved individuals, but this is likely an underestimate for grief related to deaths from COVID-19,” they wrote.

As with the first COVID-19 wave, the mental health wave will disproportionately affect Black persons, Hispanic persons, older adults, persons in lower socioeconomic groups of all races and ethnicities, and healthcare workers, they note.

The psychological risks for health care and other essential workers are of particular concern, they say. “Supporting the mental health of these and other essential workforce is critical to readiness for managing recurrent waves of the pandemic,” they stated.

How will the United States manage this impending wave of mental health problems?

“The solution will require increased funding for mental health; widespread screening to identify individuals at highest risk including suicide risk; availability of primary care clinicians and mental health professionals trained to treat those with prolonged grief, depression, traumatic stress, and substance abuse; and a diligent focus on families and communities to creatively restore the approaches by which they have managed tragedy and loss over generations,” the authors wrote.

“History has shown that societies recover from such devastation when leaders and members are joined by a shared purpose, acting in a unified way to facilitate recovery. In such societies, there is a shared understanding that its members must care for one another because the loss of one is a loss for all. Above all, this shared understanding must be restored,” they concluded.

Dr. Simon has received personal fees from Vanda Pharmaceuticals Inc, MGH Psychiatry Academy, Axovant Sciences, Springworks, Praxis Therapeutics, Aptinyx, Genomind, and Wiley (deputy editor, Depression and Anxiety). Saxe has received royalties from Guilford Press for the book Trauma Systems Therapy for Children and Teens (2016). Marmar serves on the scientific advisory board and owns equity in Receptor Life Sciences and serves on the PTSD advisory board for Otsuka Pharmaceutical.
 

A version of this article originally appeared on Medscape.com.

Women with HIV and men with HIV who have sex with women (MSW) have substantially different experiences with treatment than men with HIV who have sex with men (MSM), according to findings presented at the HIV Glasgow 2020 Virtual Meeting. MSM had better overall health outcomes than the other two groups, the study found, suggesting that MSW and women have unmet needs that require providers’ attention.

Chinyere Okoli of ViiV Healthcare Global Medical Affairs in Brentford, England, and her associates administered a Web-based survey about HIV-related perceptions and behaviors to 2,389 adults with HIV in 25 countries. The respondents included 1,018 MSM, 479 MSW, and 696 women.

In high-income countries, MSM respondents had been diagnosed a median 9 years earlier, MSW respondents a median 4 years earlier, and women respondents a median 5 years earlier. In middle-income countries, diagnosis was a median 3 years ago for MSM respondents and a median 6 years for MSW and women respondents.

Rates of suboptimal adherence to antiretroviral therapy (ART) were lowest (15.5%) among MSM, compared with MSW (38.8%) and women (28%). Similarly, viral nonsuppression had occurred in only 10.9% of MSM, whereas it had occurred in 43.2% of MSW and 37.1% of women. A little more than one-third (36.5%) of MSM had suboptimal overall health, whereas 47.2% of MSW and 46.2% of women had suboptimal overall health (P < .05).

A similar percentage of MSM (38%) and women (38.2%) reported polypharmacy; both percentages were significantly lower than for MSW (45.1%; P = .020). Yet MSW were less likely than the other two groups to have comorbidities unrelated to HIV: 46.1%, compared with 64.6% of MSM and 56.7% of women (P < .001).

Although a higher proportion (63%) of MSW than MSM (44%) or women (55%) were receiving a multitablet ART regimen, MSW were least likely to consider the impact of side effects when they began ART and were most likely to experience side effects. Only 45% of MSW prioritized minimizing side effects when they began receiving ART, and more than half (52%) were experiencing side effects with their current regimen.

By contrast, a majority of MSM (60%) prioritized minimizing side effects at ART initiation, and only 35% currently had side effects. Women fell in the middle with 48% considering side effects when starting ART and 49% reporting current side effects.

The proportion of respondents who said ART side effects were affecting their lives was not significantly different: 69% of MSM, 73% of MSW, and 74% of women. However, 56% of MSW reported skipping at least one dose in the past month because of side effects, which was more than twice the percentage of MSM (24%; P < .001). One-third of women (33%) reported skipping at least one dose.

MSW were also least comfortable talking to their health care provider about ART side effects: 55% reported discomfort, compared with 34% of MSM and 43% of women. A high majority of MSW (87.9%) said they experienced barriers to talking to their providers about relevant health concerns. The proportion who reported barriers was lower for MSM (59%) and women (72.7%; P < .001).

The substantial differences between MSM and MSW, which were even greater than those between MSW and women, suggest this population has the greatest amount of unmet needs, the researchers concluded. “Acknowledging these differences when planning/administering care can help narrow disparities,” they wrote.
 

A version of this article originally appeared on Medscape.com.

Women with HIV and men with HIV who have sex with women (MSW) have substantially different experiences with treatment than men with HIV who have sex with men (MSM), according to findings presented at the HIV Glasgow 2020 Virtual Meeting. MSM had better overall health outcomes than the other two groups, the study found, suggesting that MSW and women have unmet needs that require providers’ attention.

Chinyere Okoli of ViiV Healthcare Global Medical Affairs in Brentford, England, and her associates administered a Web-based survey about HIV-related perceptions and behaviors to 2,389 adults with HIV in 25 countries. The respondents included 1,018 MSM, 479 MSW, and 696 women.

In high-income countries, MSM respondents had been diagnosed a median 9 years earlier, MSW respondents a median 4 years earlier, and women respondents a median 5 years earlier. In middle-income countries, diagnosis was a median 3 years ago for MSM respondents and a median 6 years for MSW and women respondents.

Rates of suboptimal adherence to antiretroviral therapy (ART) were lowest (15.5%) among MSM, compared with MSW (38.8%) and women (28%). Similarly, viral nonsuppression had occurred in only 10.9% of MSM, whereas it had occurred in 43.2% of MSW and 37.1% of women. A little more than one-third (36.5%) of MSM had suboptimal overall health, whereas 47.2% of MSW and 46.2% of women had suboptimal overall health (P < .05).

A similar percentage of MSM (38%) and women (38.2%) reported polypharmacy; both percentages were significantly lower than for MSW (45.1%; P = .020). Yet MSW were less likely than the other two groups to have comorbidities unrelated to HIV: 46.1%, compared with 64.6% of MSM and 56.7% of women (P < .001).

Although a higher proportion (63%) of MSW than MSM (44%) or women (55%) were receiving a multitablet ART regimen, MSW were least likely to consider the impact of side effects when they began ART and were most likely to experience side effects. Only 45% of MSW prioritized minimizing side effects when they began receiving ART, and more than half (52%) were experiencing side effects with their current regimen.

By contrast, a majority of MSM (60%) prioritized minimizing side effects at ART initiation, and only 35% currently had side effects. Women fell in the middle with 48% considering side effects when starting ART and 49% reporting current side effects.

The proportion of respondents who said ART side effects were affecting their lives was not significantly different: 69% of MSM, 73% of MSW, and 74% of women. However, 56% of MSW reported skipping at least one dose in the past month because of side effects, which was more than twice the percentage of MSM (24%; P < .001). One-third of women (33%) reported skipping at least one dose.

MSW were also least comfortable talking to their health care provider about ART side effects: 55% reported discomfort, compared with 34% of MSM and 43% of women. A high majority of MSW (87.9%) said they experienced barriers to talking to their providers about relevant health concerns. The proportion who reported barriers was lower for MSM (59%) and women (72.7%; P < .001).

The substantial differences between MSM and MSW, which were even greater than those between MSW and women, suggest this population has the greatest amount of unmet needs, the researchers concluded. “Acknowledging these differences when planning/administering care can help narrow disparities,” they wrote.
 

A version of this article originally appeared on Medscape.com.

Women with HIV and men with HIV who have sex with women (MSW) have substantially different experiences with treatment than men with HIV who have sex with men (MSM), according to findings presented at the HIV Glasgow 2020 Virtual Meeting. MSM had better overall health outcomes than the other two groups, the study found, suggesting that MSW and women have unmet needs that require providers’ attention.

Chinyere Okoli of ViiV Healthcare Global Medical Affairs in Brentford, England, and her associates administered a Web-based survey about HIV-related perceptions and behaviors to 2,389 adults with HIV in 25 countries. The respondents included 1,018 MSM, 479 MSW, and 696 women.

In high-income countries, MSM respondents had been diagnosed a median 9 years earlier, MSW respondents a median 4 years earlier, and women respondents a median 5 years earlier. In middle-income countries, diagnosis was a median 3 years ago for MSM respondents and a median 6 years for MSW and women respondents.

Rates of suboptimal adherence to antiretroviral therapy (ART) were lowest (15.5%) among MSM, compared with MSW (38.8%) and women (28%). Similarly, viral nonsuppression had occurred in only 10.9% of MSM, whereas it had occurred in 43.2% of MSW and 37.1% of women. A little more than one-third (36.5%) of MSM had suboptimal overall health, whereas 47.2% of MSW and 46.2% of women had suboptimal overall health (P < .05).

A similar percentage of MSM (38%) and women (38.2%) reported polypharmacy; both percentages were significantly lower than for MSW (45.1%; P = .020). Yet MSW were less likely than the other two groups to have comorbidities unrelated to HIV: 46.1%, compared with 64.6% of MSM and 56.7% of women (P < .001).

Although a higher proportion (63%) of MSW than MSM (44%) or women (55%) were receiving a multitablet ART regimen, MSW were least likely to consider the impact of side effects when they began ART and were most likely to experience side effects. Only 45% of MSW prioritized minimizing side effects when they began receiving ART, and more than half (52%) were experiencing side effects with their current regimen.

By contrast, a majority of MSM (60%) prioritized minimizing side effects at ART initiation, and only 35% currently had side effects. Women fell in the middle with 48% considering side effects when starting ART and 49% reporting current side effects.

The proportion of respondents who said ART side effects were affecting their lives was not significantly different: 69% of MSM, 73% of MSW, and 74% of women. However, 56% of MSW reported skipping at least one dose in the past month because of side effects, which was more than twice the percentage of MSM (24%; P < .001). One-third of women (33%) reported skipping at least one dose.

MSW were also least comfortable talking to their health care provider about ART side effects: 55% reported discomfort, compared with 34% of MSM and 43% of women. A high majority of MSW (87.9%) said they experienced barriers to talking to their providers about relevant health concerns. The proportion who reported barriers was lower for MSM (59%) and women (72.7%; P < .001).

The substantial differences between MSM and MSW, which were even greater than those between MSW and women, suggest this population has the greatest amount of unmet needs, the researchers concluded. “Acknowledging these differences when planning/administering care can help narrow disparities,” they wrote.
 

A version of this article originally appeared on Medscape.com.

Masks, it seems, are effective at blocking the transmission of coronavirus. They’re also pretty good at stultifying consonants. For those specialties not accustomed to wearing a mask all day, it’s frustrating: How many times have you had to repeat yourself today? Or ask your patient to say something again? (Ain’t no one got time to repeat a third time how to do that prednisone taper). Worse, we’re losing important nonverbal cues that help us connect with our patients. How can we be understood when our faces are covered and 6 feet away?

Masks muffle both verbal and nonverbal communication. For soft-spoken or high-pitched speakers, the verbal effect is significant. In particular, masks make hearing consonants more difficult. They can make the “sh,” “th,” “f,” and “s” sounds difficult to distinguish. Typically, we’d use context and lip reading to boost the signal, but this fix is blocked (and the clear mouth-window masks are kinda creepy). 

Masks also prevent us from seeing facial microexpressions, critical information when you are trying to connect with someone or to build trust. A randomized controlled trial published in 2013 indeed showed that doctors wearing a mask were perceived as less empathetic and had diminished relational continuity with patients as compared to doctors not wearing a mask. There are a few things we can do to help. 

Speak more loudly is obvious advice. Loud talking has limitations though, as it can feel rude, and it blunts inflections, which add richness and emotion. (Shouting “THIS WILL ONLY HURT A LITTLE” seems a mixed message). More important than the volume is your choice of words. Try to use simple terms and short sentences. Pause between points. Hit your consonants harder. 

It’s also important that you have their full attention and are giving yours. As much as possible, try to align squared up with patients. Facing your computer exacerbates the problem. Look them in their eyes and be sure they are connected with you before any complex or difficult conversations. Hearing-impaired patients are now sometimes leaving out their aids because it’s too uncomfortable to wear them with their mask. You might ask them to put them back in. Check in with patients and repeat back what you heard them say. This can help with clarity and with connecting. Use your face more: if you’ve ever acted on stage, this would be your on-stage face. Exaggerate your expressions so it’s a little easier for them to read you. 

Lastly, there are apps such as Ava or Google Live Translator, which can transcribe your speech real time. You could then share your screen with the patient so they can read exactly what you’ve said. 

Some of us are natural communicators. Even if you are not, you can mitigate some of our current challenges. I’ll admit, it’s been a bit easier for me than for others. Between my prominent eyebrows and Italian-American upbringing, I can express my way through pretty much any face covering.  If you’d like to learn how to use your hands better, then just watch this little girl: https://youtu.be/Z5wAWyqDrnc.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Masks, it seems, are effective at blocking the transmission of coronavirus. They’re also pretty good at stultifying consonants. For those specialties not accustomed to wearing a mask all day, it’s frustrating: How many times have you had to repeat yourself today? Or ask your patient to say something again? (Ain’t no one got time to repeat a third time how to do that prednisone taper). Worse, we’re losing important nonverbal cues that help us connect with our patients. How can we be understood when our faces are covered and 6 feet away?

Masks muffle both verbal and nonverbal communication. For soft-spoken or high-pitched speakers, the verbal effect is significant. In particular, masks make hearing consonants more difficult. They can make the “sh,” “th,” “f,” and “s” sounds difficult to distinguish. Typically, we’d use context and lip reading to boost the signal, but this fix is blocked (and the clear mouth-window masks are kinda creepy). 

Masks also prevent us from seeing facial microexpressions, critical information when you are trying to connect with someone or to build trust. A randomized controlled trial published in 2013 indeed showed that doctors wearing a mask were perceived as less empathetic and had diminished relational continuity with patients as compared to doctors not wearing a mask. There are a few things we can do to help. 

Speak more loudly is obvious advice. Loud talking has limitations though, as it can feel rude, and it blunts inflections, which add richness and emotion. (Shouting “THIS WILL ONLY HURT A LITTLE” seems a mixed message). More important than the volume is your choice of words. Try to use simple terms and short sentences. Pause between points. Hit your consonants harder. 

It’s also important that you have their full attention and are giving yours. As much as possible, try to align squared up with patients. Facing your computer exacerbates the problem. Look them in their eyes and be sure they are connected with you before any complex or difficult conversations. Hearing-impaired patients are now sometimes leaving out their aids because it’s too uncomfortable to wear them with their mask. You might ask them to put them back in. Check in with patients and repeat back what you heard them say. This can help with clarity and with connecting. Use your face more: if you’ve ever acted on stage, this would be your on-stage face. Exaggerate your expressions so it’s a little easier for them to read you. 

Lastly, there are apps such as Ava or Google Live Translator, which can transcribe your speech real time. You could then share your screen with the patient so they can read exactly what you’ve said. 

Some of us are natural communicators. Even if you are not, you can mitigate some of our current challenges. I’ll admit, it’s been a bit easier for me than for others. Between my prominent eyebrows and Italian-American upbringing, I can express my way through pretty much any face covering.  If you’d like to learn how to use your hands better, then just watch this little girl: https://youtu.be/Z5wAWyqDrnc.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Masks, it seems, are effective at blocking the transmission of coronavirus. They’re also pretty good at stultifying consonants. For those specialties not accustomed to wearing a mask all day, it’s frustrating: How many times have you had to repeat yourself today? Or ask your patient to say something again? (Ain’t no one got time to repeat a third time how to do that prednisone taper). Worse, we’re losing important nonverbal cues that help us connect with our patients. How can we be understood when our faces are covered and 6 feet away?

Masks muffle both verbal and nonverbal communication. For soft-spoken or high-pitched speakers, the verbal effect is significant. In particular, masks make hearing consonants more difficult. They can make the “sh,” “th,” “f,” and “s” sounds difficult to distinguish. Typically, we’d use context and lip reading to boost the signal, but this fix is blocked (and the clear mouth-window masks are kinda creepy). 

Masks also prevent us from seeing facial microexpressions, critical information when you are trying to connect with someone or to build trust. A randomized controlled trial published in 2013 indeed showed that doctors wearing a mask were perceived as less empathetic and had diminished relational continuity with patients as compared to doctors not wearing a mask. There are a few things we can do to help. 

Speak more loudly is obvious advice. Loud talking has limitations though, as it can feel rude, and it blunts inflections, which add richness and emotion. (Shouting “THIS WILL ONLY HURT A LITTLE” seems a mixed message). More important than the volume is your choice of words. Try to use simple terms and short sentences. Pause between points. Hit your consonants harder. 

It’s also important that you have their full attention and are giving yours. As much as possible, try to align squared up with patients. Facing your computer exacerbates the problem. Look them in their eyes and be sure they are connected with you before any complex or difficult conversations. Hearing-impaired patients are now sometimes leaving out their aids because it’s too uncomfortable to wear them with their mask. You might ask them to put them back in. Check in with patients and repeat back what you heard them say. This can help with clarity and with connecting. Use your face more: if you’ve ever acted on stage, this would be your on-stage face. Exaggerate your expressions so it’s a little easier for them to read you. 

Lastly, there are apps such as Ava or Google Live Translator, which can transcribe your speech real time. You could then share your screen with the patient so they can read exactly what you’ve said. 

Some of us are natural communicators. Even if you are not, you can mitigate some of our current challenges. I’ll admit, it’s been a bit easier for me than for others. Between my prominent eyebrows and Italian-American upbringing, I can express my way through pretty much any face covering.  If you’d like to learn how to use your hands better, then just watch this little girl: https://youtu.be/Z5wAWyqDrnc.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected].

Patients with heart failure with preserved ejection fraction (HFpEF) who received sacubitril/valsartan in the PARAGON-HF trial had significant protection against progression of renal dysfunction in a prespecified secondary analysis.

The 2,419 patients with HFpEF who received sacubitril/valsartan (Entresto) had half the rate of the primary adverse renal outcome, compared with the 2,403 patients randomized to valsartan alone in the comparator group, a significant difference, according to the results published online Sept. 29 in Circulation by Finnian R. McCausland, MBBCh, and colleagues.

In absolute terms, sacubitril/valsartan treatment, an angiotensin-receptor/neprilysin inhibitor (ARNI), cut the incidence of the combined renal endpoint – renal death, end-stage renal disease, or at least a 50% drop in estimated glomerular filtration rate (eGFR) – from 2.7% in the control group to 1.4% in the sacubitril/valsartan group during a median follow-up of 35 months.

The absolute difference of 1.3% equated to a number needed to treat of 51 to prevent one of these events.

Also notable was that renal protection from sacubitril/valsartan was equally robust across the range of baseline kidney function.
 

‘An important therapeutic option’

The efficacy “across the spectrum of baseline renal function” indicates treatment with sacubitril/valsartan is “an important therapeutic option to slow renal-function decline in patients with heart failure,” wrote Dr. McCausland, a nephrologist at Brigham and Women’s Hospital in Boston, and colleagues.

The authors’ conclusion is striking because currently no drug class has produced clear evidence for efficacy in HFpEF.

On the other hand, the PARAGON-HF trial that provided the data for this new analysis was statistically neutral for its primary endpoint – a reduction in the combined rate of cardiovascular death and hospitalizations for heart failure – with a P value of .06 and 95% confidence interval of 0.75-1.01.

“Because this difference [in the primary endpoint incidence between the two study group] did not meet the predetermined level of statistical significance, subsequent analyses were considered to be exploratory,” noted the authors of the primary analysis of PARAGON-HF, as reported by Medscape Medical News.

Despite this limitation in interpreting secondary outcomes from the trial, the new report of a significant renal benefit “opens the potential to provide evidence-based treatment for patients with HFpEF,” commented Sheldon W. Tobe, MD, and Stephanie Poon, MD, in an editorial accompanying the latest analysis.

“At the very least, these results are certainly intriguing and suggest that there may be important patient subgroups with HFpEF who might benefit from using sacubitril/valsartan,” they emphasized.
 

First large trial to show renal improvement in HFpEF

The editorialists’ enthusiasm for the implications of the new findings relate in part to the fact that “PARAGON-HF is the first large trial to demonstrate improvement in renal parameters in HFpEF,” they noted.

“The finding that the composite renal outcome did not differ according to baseline eGFR is significant and suggests that the beneficial effect on renal function was indirect, possibly linked to improved cardiac function,” say Dr. Tobe, a nephrologist, and Dr. Poon, a cardiologist, both at Sunnybrook Health Sciences Centre in Toronto.

PARAGON-HF enrolled 4,822 HFpEF patients at 848 centers in 43 countries, and the efficacy analysis included 4,796 patients.

The composite renal outcome was mainly driven by the incidence of a 50% or greater drop from baseline in eGFR, which occurred in 27 patients (1.1%) in the sacubitril/valsartan group and 60 patients (2.5%) who received valsartan alone.

The annual average drop in eGFR during the study was 2.0 mL/min per 1.73m² in the sacubitril/valsartan group and 2.7 mL/min per 1.73m² in the control group.

Although the heart failure community was disappointed that sacubitril/valsartan failed to show a significant benefit for the study’s primary outcome in HFpEF, the combination has become a mainstay of treatment for patients with HFpEF based on its performance in the PARADIGM-HF trial.

And despite the unqualified support sacubitril/valsartan now receives in guidelines and its label as a foundational treatment for HFpEF, the formulation has had a hard time gaining traction in U.S. practice, often because of barriers placed by third-party payers.

PARAGON-HF was sponsored by Novartis, which markets sacubitril/valsartan (Entresto). Dr. McCausland has reported no relevant financial relationships. Dr. Tobe has reported participating on a steering committee for Bayer Fidelio/Figaro studies and being a speaker on behalf of Pfizer and Servier. Dr. Poon has reported being an adviser to Novartis, Boehringer Ingelheim, and Servier.
 

A version of this article originally appeared on Medscape.com.

Patients with heart failure with preserved ejection fraction (HFpEF) who received sacubitril/valsartan in the PARAGON-HF trial had significant protection against progression of renal dysfunction in a prespecified secondary analysis.

The 2,419 patients with HFpEF who received sacubitril/valsartan (Entresto) had half the rate of the primary adverse renal outcome, compared with the 2,403 patients randomized to valsartan alone in the comparator group, a significant difference, according to the results published online Sept. 29 in Circulation by Finnian R. McCausland, MBBCh, and colleagues.

In absolute terms, sacubitril/valsartan treatment, an angiotensin-receptor/neprilysin inhibitor (ARNI), cut the incidence of the combined renal endpoint – renal death, end-stage renal disease, or at least a 50% drop in estimated glomerular filtration rate (eGFR) – from 2.7% in the control group to 1.4% in the sacubitril/valsartan group during a median follow-up of 35 months.

The absolute difference of 1.3% equated to a number needed to treat of 51 to prevent one of these events.

Also notable was that renal protection from sacubitril/valsartan was equally robust across the range of baseline kidney function.
 

‘An important therapeutic option’

The efficacy “across the spectrum of baseline renal function” indicates treatment with sacubitril/valsartan is “an important therapeutic option to slow renal-function decline in patients with heart failure,” wrote Dr. McCausland, a nephrologist at Brigham and Women’s Hospital in Boston, and colleagues.

The authors’ conclusion is striking because currently no drug class has produced clear evidence for efficacy in HFpEF.

On the other hand, the PARAGON-HF trial that provided the data for this new analysis was statistically neutral for its primary endpoint – a reduction in the combined rate of cardiovascular death and hospitalizations for heart failure – with a P value of .06 and 95% confidence interval of 0.75-1.01.

“Because this difference [in the primary endpoint incidence between the two study group] did not meet the predetermined level of statistical significance, subsequent analyses were considered to be exploratory,” noted the authors of the primary analysis of PARAGON-HF, as reported by Medscape Medical News.

Despite this limitation in interpreting secondary outcomes from the trial, the new report of a significant renal benefit “opens the potential to provide evidence-based treatment for patients with HFpEF,” commented Sheldon W. Tobe, MD, and Stephanie Poon, MD, in an editorial accompanying the latest analysis.

“At the very least, these results are certainly intriguing and suggest that there may be important patient subgroups with HFpEF who might benefit from using sacubitril/valsartan,” they emphasized.
 

First large trial to show renal improvement in HFpEF

The editorialists’ enthusiasm for the implications of the new findings relate in part to the fact that “PARAGON-HF is the first large trial to demonstrate improvement in renal parameters in HFpEF,” they noted.

“The finding that the composite renal outcome did not differ according to baseline eGFR is significant and suggests that the beneficial effect on renal function was indirect, possibly linked to improved cardiac function,” say Dr. Tobe, a nephrologist, and Dr. Poon, a cardiologist, both at Sunnybrook Health Sciences Centre in Toronto.

PARAGON-HF enrolled 4,822 HFpEF patients at 848 centers in 43 countries, and the efficacy analysis included 4,796 patients.

The composite renal outcome was mainly driven by the incidence of a 50% or greater drop from baseline in eGFR, which occurred in 27 patients (1.1%) in the sacubitril/valsartan group and 60 patients (2.5%) who received valsartan alone.

The annual average drop in eGFR during the study was 2.0 mL/min per 1.73m² in the sacubitril/valsartan group and 2.7 mL/min per 1.73m² in the control group.

Although the heart failure community was disappointed that sacubitril/valsartan failed to show a significant benefit for the study’s primary outcome in HFpEF, the combination has become a mainstay of treatment for patients with HFpEF based on its performance in the PARADIGM-HF trial.

And despite the unqualified support sacubitril/valsartan now receives in guidelines and its label as a foundational treatment for HFpEF, the formulation has had a hard time gaining traction in U.S. practice, often because of barriers placed by third-party payers.

PARAGON-HF was sponsored by Novartis, which markets sacubitril/valsartan (Entresto). Dr. McCausland has reported no relevant financial relationships. Dr. Tobe has reported participating on a steering committee for Bayer Fidelio/Figaro studies and being a speaker on behalf of Pfizer and Servier. Dr. Poon has reported being an adviser to Novartis, Boehringer Ingelheim, and Servier.
 

A version of this article originally appeared on Medscape.com.

Patients with heart failure with preserved ejection fraction (HFpEF) who received sacubitril/valsartan in the PARAGON-HF trial had significant protection against progression of renal dysfunction in a prespecified secondary analysis.

The 2,419 patients with HFpEF who received sacubitril/valsartan (Entresto) had half the rate of the primary adverse renal outcome, compared with the 2,403 patients randomized to valsartan alone in the comparator group, a significant difference, according to the results published online Sept. 29 in Circulation by Finnian R. McCausland, MBBCh, and colleagues.

In absolute terms, sacubitril/valsartan treatment, an angiotensin-receptor/neprilysin inhibitor (ARNI), cut the incidence of the combined renal endpoint – renal death, end-stage renal disease, or at least a 50% drop in estimated glomerular filtration rate (eGFR) – from 2.7% in the control group to 1.4% in the sacubitril/valsartan group during a median follow-up of 35 months.

The absolute difference of 1.3% equated to a number needed to treat of 51 to prevent one of these events.

Also notable was that renal protection from sacubitril/valsartan was equally robust across the range of baseline kidney function.
 

‘An important therapeutic option’

The efficacy “across the spectrum of baseline renal function” indicates treatment with sacubitril/valsartan is “an important therapeutic option to slow renal-function decline in patients with heart failure,” wrote Dr. McCausland, a nephrologist at Brigham and Women’s Hospital in Boston, and colleagues.

The authors’ conclusion is striking because currently no drug class has produced clear evidence for efficacy in HFpEF.

On the other hand, the PARAGON-HF trial that provided the data for this new analysis was statistically neutral for its primary endpoint – a reduction in the combined rate of cardiovascular death and hospitalizations for heart failure – with a P value of .06 and 95% confidence interval of 0.75-1.01.

“Because this difference [in the primary endpoint incidence between the two study group] did not meet the predetermined level of statistical significance, subsequent analyses were considered to be exploratory,” noted the authors of the primary analysis of PARAGON-HF, as reported by Medscape Medical News.

Despite this limitation in interpreting secondary outcomes from the trial, the new report of a significant renal benefit “opens the potential to provide evidence-based treatment for patients with HFpEF,” commented Sheldon W. Tobe, MD, and Stephanie Poon, MD, in an editorial accompanying the latest analysis.

“At the very least, these results are certainly intriguing and suggest that there may be important patient subgroups with HFpEF who might benefit from using sacubitril/valsartan,” they emphasized.
 

First large trial to show renal improvement in HFpEF

The editorialists’ enthusiasm for the implications of the new findings relate in part to the fact that “PARAGON-HF is the first large trial to demonstrate improvement in renal parameters in HFpEF,” they noted.

“The finding that the composite renal outcome did not differ according to baseline eGFR is significant and suggests that the beneficial effect on renal function was indirect, possibly linked to improved cardiac function,” say Dr. Tobe, a nephrologist, and Dr. Poon, a cardiologist, both at Sunnybrook Health Sciences Centre in Toronto.

PARAGON-HF enrolled 4,822 HFpEF patients at 848 centers in 43 countries, and the efficacy analysis included 4,796 patients.

The composite renal outcome was mainly driven by the incidence of a 50% or greater drop from baseline in eGFR, which occurred in 27 patients (1.1%) in the sacubitril/valsartan group and 60 patients (2.5%) who received valsartan alone.

The annual average drop in eGFR during the study was 2.0 mL/min per 1.73m² in the sacubitril/valsartan group and 2.7 mL/min per 1.73m² in the control group.

Although the heart failure community was disappointed that sacubitril/valsartan failed to show a significant benefit for the study’s primary outcome in HFpEF, the combination has become a mainstay of treatment for patients with HFpEF based on its performance in the PARADIGM-HF trial.

And despite the unqualified support sacubitril/valsartan now receives in guidelines and its label as a foundational treatment for HFpEF, the formulation has had a hard time gaining traction in U.S. practice, often because of barriers placed by third-party payers.

PARAGON-HF was sponsored by Novartis, which markets sacubitril/valsartan (Entresto). Dr. McCausland has reported no relevant financial relationships. Dr. Tobe has reported participating on a steering committee for Bayer Fidelio/Figaro studies and being a speaker on behalf of Pfizer and Servier. Dr. Poon has reported being an adviser to Novartis, Boehringer Ingelheim, and Servier.
 

A version of this article originally appeared on Medscape.com.