THORACIC ONCOLOGY AND CHEST PROCEDURES NETWORK

Interventional Procedures Section

During the last decade, the explosion of technological advancements in the field of interventional pulmonary (IP) has afforded patients the opportunity to undergo novel, minimally invasive diagnostic and therapeutic procedures. However, these unprecedented technological advances have often been introduced without the support of high-quality research on safety and efficacy, and without evaluating their impact on meaningful patient outcomes. Encouraging and participating in high-quality IP research should remain a top priority for those practicing in the field.

CHEST

Structured research networks, such as the UK Pleural Society and more recently the Interventional Pulmonary Outcome Group, have facilitated the transition of IP research from observational case series and single-center experiences to multicenter, randomized controlled trials to generate level I evidence and inform patient care (Laskawiec-Szkonter M, et al. Br J Hosp Med (Lond). 2019 Apr 2;80[4]:186-7) (Maldonado F, et al. J Bronchology Interv Pulmonol. 2019 Jul;26(3):150-2). In the bronchoscopy space, important investigator-initiated clinical trial results anticipated in 2024 include VERITAS (NCT04250194), FROSTBITE2 (NCT05751278), and RELIANT (NCT05705544), among others. These research efforts complement industry-sponsored clinical trials (such as RheSolve, NCT04677465) and aim to emulate the extraordinary track record achieved in the field of pleural disease that has led to recently updated evidence-based guidelines for the management of challenging diseases like malignant pleural effusions, pleural space infections, and pneumothorax (Davies HE, et a l. JAMA. 2012 Jun 13;307[22]:2383-9, Mishra EK, et al. Am J Respir Crit Care Med. 2018 Feb 15;197[4]:502-8) (Rahman NM, et al. N Engl J Med. 2011 Aug 11;365[6]:518-26) (Hallifax RJ, et al. Lancet. 2020 Jul 4;396[10243]:39-49).

Ultimately, the rapidly evolving technological advancements in interventional pulmonology must be supported by research based on high-quality clinical trials, which will be contingent on appropriate trial funding requiring partnership with industry and federal funding agencies. Only through such collaboration can researchers design robust clinical trials based on complex methodology, which will advance patient care and lead to improved patient outcomes.

– Jennifer D. Duke, MD

Section Fellow-in-Training

– Fabien Maldonado, MD, MSc, FCCP

Section Member

THORACIC ONCOLOGY AND CHEST PROCEDURES NETWORK

Interventional Procedures Section

During the last decade, the explosion of technological advancements in the field of interventional pulmonary (IP) has afforded patients the opportunity to undergo novel, minimally invasive diagnostic and therapeutic procedures. However, these unprecedented technological advances have often been introduced without the support of high-quality research on safety and efficacy, and without evaluating their impact on meaningful patient outcomes. Encouraging and participating in high-quality IP research should remain a top priority for those practicing in the field.

CHEST

Structured research networks, such as the UK Pleural Society and more recently the Interventional Pulmonary Outcome Group, have facilitated the transition of IP research from observational case series and single-center experiences to multicenter, randomized controlled trials to generate level I evidence and inform patient care (Laskawiec-Szkonter M, et al. Br J Hosp Med (Lond). 2019 Apr 2;80[4]:186-7) (Maldonado F, et al. J Bronchology Interv Pulmonol. 2019 Jul;26(3):150-2). In the bronchoscopy space, important investigator-initiated clinical trial results anticipated in 2024 include VERITAS (NCT04250194), FROSTBITE2 (NCT05751278), and RELIANT (NCT05705544), among others. These research efforts complement industry-sponsored clinical trials (such as RheSolve, NCT04677465) and aim to emulate the extraordinary track record achieved in the field of pleural disease that has led to recently updated evidence-based guidelines for the management of challenging diseases like malignant pleural effusions, pleural space infections, and pneumothorax (Davies HE, et a l. JAMA. 2012 Jun 13;307[22]:2383-9, Mishra EK, et al. Am J Respir Crit Care Med. 2018 Feb 15;197[4]:502-8) (Rahman NM, et al. N Engl J Med. 2011 Aug 11;365[6]:518-26) (Hallifax RJ, et al. Lancet. 2020 Jul 4;396[10243]:39-49).

Ultimately, the rapidly evolving technological advancements in interventional pulmonology must be supported by research based on high-quality clinical trials, which will be contingent on appropriate trial funding requiring partnership with industry and federal funding agencies. Only through such collaboration can researchers design robust clinical trials based on complex methodology, which will advance patient care and lead to improved patient outcomes.

– Jennifer D. Duke, MD

Section Fellow-in-Training

– Fabien Maldonado, MD, MSc, FCCP

Section Member

THORACIC ONCOLOGY AND CHEST PROCEDURES NETWORK

Interventional Procedures Section

During the last decade, the explosion of technological advancements in the field of interventional pulmonary (IP) has afforded patients the opportunity to undergo novel, minimally invasive diagnostic and therapeutic procedures. However, these unprecedented technological advances have often been introduced without the support of high-quality research on safety and efficacy, and without evaluating their impact on meaningful patient outcomes. Encouraging and participating in high-quality IP research should remain a top priority for those practicing in the field.

CHEST

Structured research networks, such as the UK Pleural Society and more recently the Interventional Pulmonary Outcome Group, have facilitated the transition of IP research from observational case series and single-center experiences to multicenter, randomized controlled trials to generate level I evidence and inform patient care (Laskawiec-Szkonter M, et al. Br J Hosp Med (Lond). 2019 Apr 2;80[4]:186-7) (Maldonado F, et al. J Bronchology Interv Pulmonol. 2019 Jul;26(3):150-2). In the bronchoscopy space, important investigator-initiated clinical trial results anticipated in 2024 include VERITAS (NCT04250194), FROSTBITE2 (NCT05751278), and RELIANT (NCT05705544), among others. These research efforts complement industry-sponsored clinical trials (such as RheSolve, NCT04677465) and aim to emulate the extraordinary track record achieved in the field of pleural disease that has led to recently updated evidence-based guidelines for the management of challenging diseases like malignant pleural effusions, pleural space infections, and pneumothorax (Davies HE, et a l. JAMA. 2012 Jun 13;307[22]:2383-9, Mishra EK, et al. Am J Respir Crit Care Med. 2018 Feb 15;197[4]:502-8) (Rahman NM, et al. N Engl J Med. 2011 Aug 11;365[6]:518-26) (Hallifax RJ, et al. Lancet. 2020 Jul 4;396[10243]:39-49).

Ultimately, the rapidly evolving technological advancements in interventional pulmonology must be supported by research based on high-quality clinical trials, which will be contingent on appropriate trial funding requiring partnership with industry and federal funding agencies. Only through such collaboration can researchers design robust clinical trials based on complex methodology, which will advance patient care and lead to improved patient outcomes.

– Jennifer D. Duke, MD

Section Fellow-in-Training

– Fabien Maldonado, MD, MSc, FCCP

Section Member

DIFFUSE LUNG DISEASE AND LUNG TRANSPLANT NETWORK

Interstitial Lung Disease Section

Interstitial lung diseases (ILD) are a heterogeneous group of fibro-inflammatory disorders that can be progressive despite available therapies. The cornerstones of pharmacologic therapy include immunosuppression and antifibrotics.

CHEST

Data on the use of rituximab, a B-lymphocyte-depleting monoclonal antibody, often utilized as rescue therapy in progressive and severe ILD, was limited until recently. The RECITAL trial reported the first randomized controlled trial investigating rituximab in severe or progressive autoimmune ILD. Though rituximab was not superior to cyclophosphamide, both agents improved forced vital capacity (FVC) at 24 weeks and respiratory-related quality of life. Rituximab was associated with less adverse events and lower corticosteroid exposure (Maher et al. Lancet Respir Med. 2023;11:45-54). In the DESIRES trial, patients with systemic sclerosis-associated ILD treated with rituximab had preservation of FVC at 24 and 48 weeks compared to placebo (Ebata et al. Lancet Rheumatol. 2021;3:e489-97; Lancet Rheumatol. 2022;4:e546-55). The EVER-ILD investigators compared mycophenolate mofetil (MMF) alone vs addition of rituximab in patients with autoimmune and idiopathic nonspecific interstitial pneumonia (NSIP). Combination therapy was superior to MMF alone in improving FVC and progression-free survival. Combination regimen was well tolerated though nonserious viral and bacterial infections were more frequent (Mankikian et al. Eur Respir J. 2023;61[6]:2202071).

These findings, primarily in autoimmune ILD, are promising and provide clinicians with evidence for utilizing rituximab in patients with severe and progressive ILD. Nonetheless, they highlight the need for additional research and standardized guidance regarding the target population who stands to most benefit from rituximab.
 

–Tessy K. Paul, MD

Section Member-at-Large

–Tejaswini Kulkarni, MD, MBBS, FCCP

Section Chair

DIFFUSE LUNG DISEASE AND LUNG TRANSPLANT NETWORK

Interstitial Lung Disease Section

Interstitial lung diseases (ILD) are a heterogeneous group of fibro-inflammatory disorders that can be progressive despite available therapies. The cornerstones of pharmacologic therapy include immunosuppression and antifibrotics.

CHEST

Data on the use of rituximab, a B-lymphocyte-depleting monoclonal antibody, often utilized as rescue therapy in progressive and severe ILD, was limited until recently. The RECITAL trial reported the first randomized controlled trial investigating rituximab in severe or progressive autoimmune ILD. Though rituximab was not superior to cyclophosphamide, both agents improved forced vital capacity (FVC) at 24 weeks and respiratory-related quality of life. Rituximab was associated with less adverse events and lower corticosteroid exposure (Maher et al. Lancet Respir Med. 2023;11:45-54). In the DESIRES trial, patients with systemic sclerosis-associated ILD treated with rituximab had preservation of FVC at 24 and 48 weeks compared to placebo (Ebata et al. Lancet Rheumatol. 2021;3:e489-97; Lancet Rheumatol. 2022;4:e546-55). The EVER-ILD investigators compared mycophenolate mofetil (MMF) alone vs addition of rituximab in patients with autoimmune and idiopathic nonspecific interstitial pneumonia (NSIP). Combination therapy was superior to MMF alone in improving FVC and progression-free survival. Combination regimen was well tolerated though nonserious viral and bacterial infections were more frequent (Mankikian et al. Eur Respir J. 2023;61[6]:2202071).

These findings, primarily in autoimmune ILD, are promising and provide clinicians with evidence for utilizing rituximab in patients with severe and progressive ILD. Nonetheless, they highlight the need for additional research and standardized guidance regarding the target population who stands to most benefit from rituximab.
 

–Tessy K. Paul, MD

Section Member-at-Large

–Tejaswini Kulkarni, MD, MBBS, FCCP

Section Chair

DIFFUSE LUNG DISEASE AND LUNG TRANSPLANT NETWORK

Interstitial Lung Disease Section

Interstitial lung diseases (ILD) are a heterogeneous group of fibro-inflammatory disorders that can be progressive despite available therapies. The cornerstones of pharmacologic therapy include immunosuppression and antifibrotics.

CHEST

Data on the use of rituximab, a B-lymphocyte-depleting monoclonal antibody, often utilized as rescue therapy in progressive and severe ILD, was limited until recently. The RECITAL trial reported the first randomized controlled trial investigating rituximab in severe or progressive autoimmune ILD. Though rituximab was not superior to cyclophosphamide, both agents improved forced vital capacity (FVC) at 24 weeks and respiratory-related quality of life. Rituximab was associated with less adverse events and lower corticosteroid exposure (Maher et al. Lancet Respir Med. 2023;11:45-54). In the DESIRES trial, patients with systemic sclerosis-associated ILD treated with rituximab had preservation of FVC at 24 and 48 weeks compared to placebo (Ebata et al. Lancet Rheumatol. 2021;3:e489-97; Lancet Rheumatol. 2022;4:e546-55). The EVER-ILD investigators compared mycophenolate mofetil (MMF) alone vs addition of rituximab in patients with autoimmune and idiopathic nonspecific interstitial pneumonia (NSIP). Combination therapy was superior to MMF alone in improving FVC and progression-free survival. Combination regimen was well tolerated though nonserious viral and bacterial infections were more frequent (Mankikian et al. Eur Respir J. 2023;61[6]:2202071).

These findings, primarily in autoimmune ILD, are promising and provide clinicians with evidence for utilizing rituximab in patients with severe and progressive ILD. Nonetheless, they highlight the need for additional research and standardized guidance regarding the target population who stands to most benefit from rituximab.
 

–Tessy K. Paul, MD

Section Member-at-Large

–Tejaswini Kulkarni, MD, MBBS, FCCP

Section Chair

APP Intersection

Postgraduate training for advanced practice providers (APPs) has existed in one form or another since the genesis of the allied professions. They are typically referred to as residencies, fellowships, postgraduate programs, and transition-to-practice.

The desire and necessity for these programs has increased in the past decade with workforce changes; namely the increasing number of nurse practitioners (NPs) graduating with fewer years of experience at the bedside compared with previous eras, a similar decrease in patient contact hours for graduating PAs, the transition of physician colleagues from employers to employees and the subsequent change in priorities in training new graduate APPs, and resident work hour restrictions necessitating more APPs to staff inpatient units and work in various specialties.

CHEST

The goal of these programs is to provide postgraduate training to physician assistants/associates (PAs) and NPs across myriad medical specialties to both newly graduated APPs and those looking to transition specialties. Current programs exist in family medicine, emergency medicine, urgent care, critical care medicine, pulmonary medicine, oncology, surgery, and various surgical subspecialties, to name a few. Program length is highly variable, though most programs advertise as lasting around 12 months, with varying ratios of clinical and didactic education. Postgraduate APP programs are largely advertise as salaried, benefitted positions, though usually at a rate below that of a so-called “direct hire” due to the protected learning time associated with the postgraduate training year.

CHEST

Accreditation for these programs is still disjointed, although unifying efforts have been made as of late, and is currently available through the Advanced Practice Provider Fellowship Accreditation, Association of Postgraduate Physician Assistant Programs, ARC-PA, the Accreditation Commission for Education in Nursing, and the Consortium for Advanced Practice Providers. Other organizations, such as the Association of Post Graduate APRN Programs, host regular conferences to discuss the formulation of postgraduate APP education curricula and program development.

While accreditation offers guidance for fledgling programs, many utilize the standards published by the American College of Graduate Medical Education to ensure that appropriate clinical milestones are being met and that a common language among APPs and physicians who are involved in the evaluation of the postgraduate APP trainee is being used. Programs also seek to utilize other well-established curricula and certification programs published by various national and international organizations. A key distinction from physician postgraduate training is that there is currently no fiscal or legislative support for postgraduate APP programs; these issues have been cited as reasons for the limited scope and number of programs.

When starting APP Fellowship programs, it is important to consider why this would be beneficial to a specific division and health care organization. Usually, fellowship programs develop out of a need to train and retain APPs. It is no secret that turnover and retention of skilled APPs is a nationwide problem associated with significant costs to organizations. The ability to retain fellowship-trained APPs will result in cost savings due to the reduction in onboarding time and orientation costs, as these APP fellows finish their programs ready to be fully productive team members.

Additional considerations for the development of an APP fellowship include improving access to care and increasing the quality of the care provided. Fellowship programs encourage a smoother transition to practice by offering more support through education, closer evaluation, and frequent feedback, which improves competence and confidence of these providers. A supported APP is more likely to practice to the fullest extent of their license and have improved personal and professional satisfaction, leading to employee retention and better patient care.

When developing a budget for these types of programs, it is important to include the full-time equivalent (FTE) for the fellow, benefits, onboarding/licensure, simulations, and fellowship faculty costs.

Faculty compensation varies by institution but can include salary support, FTE reduction, and nonclinical appointments. Tracking metrics such as fellow billing, length of stay, and access to care during the fellowship year are helpful to highlight the benefit of these programs to the organization.

Initiating a program like those described may seem like a Herculean feat, but motivated individuals have been able to accomplish similar goals in both adequately and poorly resourced areas. For those aspiring to start a postgraduate APP program at their instruction, these authors suggest the following approach.

First, identify your institution’s need for such a program. Next, define your curriculum, evaluation process, and expectations. Then, create buy-in from stakeholders, including administrative and clinical personnel. Finally, focus on recruitment. Seeking accreditation may be challenging for new programs, but identifying the accreditation standard you plan to pursue early will pay dividends when the time comes for the program to apply. Those starting down this path should realistically expect an 18- to 24-month period between their first efforts and the start of the first class.

“APP Intersection” is a new quarterly column focusing on areas of interest for the entire chest medicine health care team.

APP Intersection

Postgraduate training for advanced practice providers (APPs) has existed in one form or another since the genesis of the allied professions. They are typically referred to as residencies, fellowships, postgraduate programs, and transition-to-practice.

The desire and necessity for these programs has increased in the past decade with workforce changes; namely the increasing number of nurse practitioners (NPs) graduating with fewer years of experience at the bedside compared with previous eras, a similar decrease in patient contact hours for graduating PAs, the transition of physician colleagues from employers to employees and the subsequent change in priorities in training new graduate APPs, and resident work hour restrictions necessitating more APPs to staff inpatient units and work in various specialties.

CHEST

The goal of these programs is to provide postgraduate training to physician assistants/associates (PAs) and NPs across myriad medical specialties to both newly graduated APPs and those looking to transition specialties. Current programs exist in family medicine, emergency medicine, urgent care, critical care medicine, pulmonary medicine, oncology, surgery, and various surgical subspecialties, to name a few. Program length is highly variable, though most programs advertise as lasting around 12 months, with varying ratios of clinical and didactic education. Postgraduate APP programs are largely advertise as salaried, benefitted positions, though usually at a rate below that of a so-called “direct hire” due to the protected learning time associated with the postgraduate training year.

CHEST

Accreditation for these programs is still disjointed, although unifying efforts have been made as of late, and is currently available through the Advanced Practice Provider Fellowship Accreditation, Association of Postgraduate Physician Assistant Programs, ARC-PA, the Accreditation Commission for Education in Nursing, and the Consortium for Advanced Practice Providers. Other organizations, such as the Association of Post Graduate APRN Programs, host regular conferences to discuss the formulation of postgraduate APP education curricula and program development.

While accreditation offers guidance for fledgling programs, many utilize the standards published by the American College of Graduate Medical Education to ensure that appropriate clinical milestones are being met and that a common language among APPs and physicians who are involved in the evaluation of the postgraduate APP trainee is being used. Programs also seek to utilize other well-established curricula and certification programs published by various national and international organizations. A key distinction from physician postgraduate training is that there is currently no fiscal or legislative support for postgraduate APP programs; these issues have been cited as reasons for the limited scope and number of programs.

When starting APP Fellowship programs, it is important to consider why this would be beneficial to a specific division and health care organization. Usually, fellowship programs develop out of a need to train and retain APPs. It is no secret that turnover and retention of skilled APPs is a nationwide problem associated with significant costs to organizations. The ability to retain fellowship-trained APPs will result in cost savings due to the reduction in onboarding time and orientation costs, as these APP fellows finish their programs ready to be fully productive team members.

Additional considerations for the development of an APP fellowship include improving access to care and increasing the quality of the care provided. Fellowship programs encourage a smoother transition to practice by offering more support through education, closer evaluation, and frequent feedback, which improves competence and confidence of these providers. A supported APP is more likely to practice to the fullest extent of their license and have improved personal and professional satisfaction, leading to employee retention and better patient care.

When developing a budget for these types of programs, it is important to include the full-time equivalent (FTE) for the fellow, benefits, onboarding/licensure, simulations, and fellowship faculty costs.

Faculty compensation varies by institution but can include salary support, FTE reduction, and nonclinical appointments. Tracking metrics such as fellow billing, length of stay, and access to care during the fellowship year are helpful to highlight the benefit of these programs to the organization.

Initiating a program like those described may seem like a Herculean feat, but motivated individuals have been able to accomplish similar goals in both adequately and poorly resourced areas. For those aspiring to start a postgraduate APP program at their instruction, these authors suggest the following approach.

First, identify your institution’s need for such a program. Next, define your curriculum, evaluation process, and expectations. Then, create buy-in from stakeholders, including administrative and clinical personnel. Finally, focus on recruitment. Seeking accreditation may be challenging for new programs, but identifying the accreditation standard you plan to pursue early will pay dividends when the time comes for the program to apply. Those starting down this path should realistically expect an 18- to 24-month period between their first efforts and the start of the first class.

“APP Intersection” is a new quarterly column focusing on areas of interest for the entire chest medicine health care team.

APP Intersection

Postgraduate training for advanced practice providers (APPs) has existed in one form or another since the genesis of the allied professions. They are typically referred to as residencies, fellowships, postgraduate programs, and transition-to-practice.

The desire and necessity for these programs has increased in the past decade with workforce changes; namely the increasing number of nurse practitioners (NPs) graduating with fewer years of experience at the bedside compared with previous eras, a similar decrease in patient contact hours for graduating PAs, the transition of physician colleagues from employers to employees and the subsequent change in priorities in training new graduate APPs, and resident work hour restrictions necessitating more APPs to staff inpatient units and work in various specialties.

CHEST

The goal of these programs is to provide postgraduate training to physician assistants/associates (PAs) and NPs across myriad medical specialties to both newly graduated APPs and those looking to transition specialties. Current programs exist in family medicine, emergency medicine, urgent care, critical care medicine, pulmonary medicine, oncology, surgery, and various surgical subspecialties, to name a few. Program length is highly variable, though most programs advertise as lasting around 12 months, with varying ratios of clinical and didactic education. Postgraduate APP programs are largely advertise as salaried, benefitted positions, though usually at a rate below that of a so-called “direct hire” due to the protected learning time associated with the postgraduate training year.

CHEST

Accreditation for these programs is still disjointed, although unifying efforts have been made as of late, and is currently available through the Advanced Practice Provider Fellowship Accreditation, Association of Postgraduate Physician Assistant Programs, ARC-PA, the Accreditation Commission for Education in Nursing, and the Consortium for Advanced Practice Providers. Other organizations, such as the Association of Post Graduate APRN Programs, host regular conferences to discuss the formulation of postgraduate APP education curricula and program development.

While accreditation offers guidance for fledgling programs, many utilize the standards published by the American College of Graduate Medical Education to ensure that appropriate clinical milestones are being met and that a common language among APPs and physicians who are involved in the evaluation of the postgraduate APP trainee is being used. Programs also seek to utilize other well-established curricula and certification programs published by various national and international organizations. A key distinction from physician postgraduate training is that there is currently no fiscal or legislative support for postgraduate APP programs; these issues have been cited as reasons for the limited scope and number of programs.

When starting APP Fellowship programs, it is important to consider why this would be beneficial to a specific division and health care organization. Usually, fellowship programs develop out of a need to train and retain APPs. It is no secret that turnover and retention of skilled APPs is a nationwide problem associated with significant costs to organizations. The ability to retain fellowship-trained APPs will result in cost savings due to the reduction in onboarding time and orientation costs, as these APP fellows finish their programs ready to be fully productive team members.

Additional considerations for the development of an APP fellowship include improving access to care and increasing the quality of the care provided. Fellowship programs encourage a smoother transition to practice by offering more support through education, closer evaluation, and frequent feedback, which improves competence and confidence of these providers. A supported APP is more likely to practice to the fullest extent of their license and have improved personal and professional satisfaction, leading to employee retention and better patient care.

When developing a budget for these types of programs, it is important to include the full-time equivalent (FTE) for the fellow, benefits, onboarding/licensure, simulations, and fellowship faculty costs.

Faculty compensation varies by institution but can include salary support, FTE reduction, and nonclinical appointments. Tracking metrics such as fellow billing, length of stay, and access to care during the fellowship year are helpful to highlight the benefit of these programs to the organization.

Initiating a program like those described may seem like a Herculean feat, but motivated individuals have been able to accomplish similar goals in both adequately and poorly resourced areas. For those aspiring to start a postgraduate APP program at their instruction, these authors suggest the following approach.

First, identify your institution’s need for such a program. Next, define your curriculum, evaluation process, and expectations. Then, create buy-in from stakeholders, including administrative and clinical personnel. Finally, focus on recruitment. Seeking accreditation may be challenging for new programs, but identifying the accreditation standard you plan to pursue early will pay dividends when the time comes for the program to apply. Those starting down this path should realistically expect an 18- to 24-month period between their first efforts and the start of the first class.

“APP Intersection” is a new quarterly column focusing on areas of interest for the entire chest medicine health care team.

Patients with calcium pyrophosphate deposition (CPPD) disease, also known as pseudogout, have an 80% higher risk for fracture than individuals who do not have the disease, according to a new analysis.

This trend was driven by wrist fractures, where there was a more than threefold increased risk.

Previous studies identified an association between CPPD and low bone mineral density, and there is growing evidence suggesting that the dysregulation of osteoprotegerin — a molecule that is important in the regulation of osteoclasts — may be associated with early-onset CPPD, noted Sara K. Tedeschi, MD, MPH, the lead author of the study and head of crystal-induced arthritic diseases at Brigham and Women’s Hospital, Boston, Massachusetts.

However, CPPD’s association with fracture risk has yet to be explored.

In the study, Dr. Tedeschi and colleagues used Mass General Brigham electronic health record (EHR) data from 1991 to 2023 to identify 1148 individuals with acute calcium pyrophosphate (CPP) crystal arthritis. The index date was defined as the first documentation of pseudogout or synovial fluid CPP crystals. These patients were matched to 3730 comparators based on healthcare encounters within 30 days of the index date of a patient with CPPD. Patients were also matched based on the year of their first EHR encounter. Patients with a fracture documented prior to the index date were excluded from the analysis.

The primary outcome was the first fracture of the humerus, knee, wrist, hip, or pelvis, detected via published algorithms using diagnostic and procedural codes.

The research was published on January 14 in Arthritis & Rheumatology.

Although participants were not matched on age or sex, the average age was 73, and most participants were female. In total, 83.1% of participants in the CPPD group and 80.0% of those in the control group were White.

After adjustment for confounding factors including age, sex, comorbidities, and glucocorticoid use, CPPD was associated with an 80% higher risk for any fracture (hazard risk [HR], 1.8). Fracture risk was highest for the wrist (HR, 3.6).

Patients with CPPD had a 40% higher risk to experience a humerus or pelvis fracture and a 30% higher risk for hip fractures, but the results were not statistically significant.

The results were similar for sensitivity analyses that excluded patients who were prescribed glucocorticoids, treatment for osteoporosis, or had a diagnosis of rheumatoid arthritis.

Asked to comment, John D. FitzGerald, MD, PhD, clinical chief of rheumatology at the University of California, Los Angeles, noted that these associations were “convincing and strong. I thought it was a very good study and important work. CPPD is common and osteoporosis is common, so better understanding the connection is important.”

It’s still not clear why the risk for wrist fractures was highest, but Dr. Tedeschi had two hypotheses. The researchers were unable to assess for falls in this dataset, but it’s possible that patients with CPPD experiencing joint pain could fall and try to brace themselves with an outstretched arm, leading to a wrist fracture.

CPPD also commonly affects the wrist, “so it’s possible that if CPPD is affecting the wrist and if there is an association between CPPD and low bone density, maybe there’s particularly low bone density at the wrist,” she said.

Dr. FitzGerald agreed that both hypotheses were plausible, but “with the retrospective study, there could be a lot of things that are unobserved or unexplained,” he added.

Dr. Tedeschi is interested in exploring what could be causing the association with an increased fracture risk in future research.

“I hope this draws attention to the fact that people with CPPD can have related medical problems that are outside of their joints,” added Dr. Tedeschi. “Thinking about routine screening for osteopenia and osteoporosis could be a good first step in patients with CPPD.”

The study was funded by grants from the US National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Tedeschi has worked as a consultant for Novartis. Dr. FitzGerald reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Patients with calcium pyrophosphate deposition (CPPD) disease, also known as pseudogout, have an 80% higher risk for fracture than individuals who do not have the disease, according to a new analysis.

This trend was driven by wrist fractures, where there was a more than threefold increased risk.

Previous studies identified an association between CPPD and low bone mineral density, and there is growing evidence suggesting that the dysregulation of osteoprotegerin — a molecule that is important in the regulation of osteoclasts — may be associated with early-onset CPPD, noted Sara K. Tedeschi, MD, MPH, the lead author of the study and head of crystal-induced arthritic diseases at Brigham and Women’s Hospital, Boston, Massachusetts.

However, CPPD’s association with fracture risk has yet to be explored.

In the study, Dr. Tedeschi and colleagues used Mass General Brigham electronic health record (EHR) data from 1991 to 2023 to identify 1148 individuals with acute calcium pyrophosphate (CPP) crystal arthritis. The index date was defined as the first documentation of pseudogout or synovial fluid CPP crystals. These patients were matched to 3730 comparators based on healthcare encounters within 30 days of the index date of a patient with CPPD. Patients were also matched based on the year of their first EHR encounter. Patients with a fracture documented prior to the index date were excluded from the analysis.

The primary outcome was the first fracture of the humerus, knee, wrist, hip, or pelvis, detected via published algorithms using diagnostic and procedural codes.

The research was published on January 14 in Arthritis & Rheumatology.

Although participants were not matched on age or sex, the average age was 73, and most participants were female. In total, 83.1% of participants in the CPPD group and 80.0% of those in the control group were White.

After adjustment for confounding factors including age, sex, comorbidities, and glucocorticoid use, CPPD was associated with an 80% higher risk for any fracture (hazard risk [HR], 1.8). Fracture risk was highest for the wrist (HR, 3.6).

Patients with CPPD had a 40% higher risk to experience a humerus or pelvis fracture and a 30% higher risk for hip fractures, but the results were not statistically significant.

The results were similar for sensitivity analyses that excluded patients who were prescribed glucocorticoids, treatment for osteoporosis, or had a diagnosis of rheumatoid arthritis.

Asked to comment, John D. FitzGerald, MD, PhD, clinical chief of rheumatology at the University of California, Los Angeles, noted that these associations were “convincing and strong. I thought it was a very good study and important work. CPPD is common and osteoporosis is common, so better understanding the connection is important.”

It’s still not clear why the risk for wrist fractures was highest, but Dr. Tedeschi had two hypotheses. The researchers were unable to assess for falls in this dataset, but it’s possible that patients with CPPD experiencing joint pain could fall and try to brace themselves with an outstretched arm, leading to a wrist fracture.

CPPD also commonly affects the wrist, “so it’s possible that if CPPD is affecting the wrist and if there is an association between CPPD and low bone density, maybe there’s particularly low bone density at the wrist,” she said.

Dr. FitzGerald agreed that both hypotheses were plausible, but “with the retrospective study, there could be a lot of things that are unobserved or unexplained,” he added.

Dr. Tedeschi is interested in exploring what could be causing the association with an increased fracture risk in future research.

“I hope this draws attention to the fact that people with CPPD can have related medical problems that are outside of their joints,” added Dr. Tedeschi. “Thinking about routine screening for osteopenia and osteoporosis could be a good first step in patients with CPPD.”

The study was funded by grants from the US National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Tedeschi has worked as a consultant for Novartis. Dr. FitzGerald reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Patients with calcium pyrophosphate deposition (CPPD) disease, also known as pseudogout, have an 80% higher risk for fracture than individuals who do not have the disease, according to a new analysis.

This trend was driven by wrist fractures, where there was a more than threefold increased risk.

Previous studies identified an association between CPPD and low bone mineral density, and there is growing evidence suggesting that the dysregulation of osteoprotegerin — a molecule that is important in the regulation of osteoclasts — may be associated with early-onset CPPD, noted Sara K. Tedeschi, MD, MPH, the lead author of the study and head of crystal-induced arthritic diseases at Brigham and Women’s Hospital, Boston, Massachusetts.

However, CPPD’s association with fracture risk has yet to be explored.

In the study, Dr. Tedeschi and colleagues used Mass General Brigham electronic health record (EHR) data from 1991 to 2023 to identify 1148 individuals with acute calcium pyrophosphate (CPP) crystal arthritis. The index date was defined as the first documentation of pseudogout or synovial fluid CPP crystals. These patients were matched to 3730 comparators based on healthcare encounters within 30 days of the index date of a patient with CPPD. Patients were also matched based on the year of their first EHR encounter. Patients with a fracture documented prior to the index date were excluded from the analysis.

The primary outcome was the first fracture of the humerus, knee, wrist, hip, or pelvis, detected via published algorithms using diagnostic and procedural codes.

The research was published on January 14 in Arthritis & Rheumatology.

Although participants were not matched on age or sex, the average age was 73, and most participants were female. In total, 83.1% of participants in the CPPD group and 80.0% of those in the control group were White.

After adjustment for confounding factors including age, sex, comorbidities, and glucocorticoid use, CPPD was associated with an 80% higher risk for any fracture (hazard risk [HR], 1.8). Fracture risk was highest for the wrist (HR, 3.6).

Patients with CPPD had a 40% higher risk to experience a humerus or pelvis fracture and a 30% higher risk for hip fractures, but the results were not statistically significant.

The results were similar for sensitivity analyses that excluded patients who were prescribed glucocorticoids, treatment for osteoporosis, or had a diagnosis of rheumatoid arthritis.

Asked to comment, John D. FitzGerald, MD, PhD, clinical chief of rheumatology at the University of California, Los Angeles, noted that these associations were “convincing and strong. I thought it was a very good study and important work. CPPD is common and osteoporosis is common, so better understanding the connection is important.”

It’s still not clear why the risk for wrist fractures was highest, but Dr. Tedeschi had two hypotheses. The researchers were unable to assess for falls in this dataset, but it’s possible that patients with CPPD experiencing joint pain could fall and try to brace themselves with an outstretched arm, leading to a wrist fracture.

CPPD also commonly affects the wrist, “so it’s possible that if CPPD is affecting the wrist and if there is an association between CPPD and low bone density, maybe there’s particularly low bone density at the wrist,” she said.

Dr. FitzGerald agreed that both hypotheses were plausible, but “with the retrospective study, there could be a lot of things that are unobserved or unexplained,” he added.

Dr. Tedeschi is interested in exploring what could be causing the association with an increased fracture risk in future research.

“I hope this draws attention to the fact that people with CPPD can have related medical problems that are outside of their joints,” added Dr. Tedeschi. “Thinking about routine screening for osteopenia and osteoporosis could be a good first step in patients with CPPD.”

The study was funded by grants from the US National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Tedeschi has worked as a consultant for Novartis. Dr. FitzGerald reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

A two-step screening, using a risk score and biomarkers, can identify patients with diabetes at a higher risk for heart failure who will most likely benefit from preventive drugs.

METHODOLOGY:

• Researchers compared screening methods and downstream risk for heart failure in 5 years, particularly those without atherosclerotic cardiovascular disease (ASCVD).
• They pooled data from 4889 patients (age ≥ 40 years, about half women) with diabetes, no heart failure at baseline, and no signs of ASCVD. All patients had undergone screening to determine their heart failure risk level.
• Researchers assessed the heart failure risk for patients without ASCVD with one-step screening strategies:
• —Clinical risk score (WATCH-DM risk score)
• —Biomarker tests (N-terminal pro-B-type natriuretic peptide [NT-proBNP]) or high-sensitivity cardiac troponin [hs-cTn)
• —Echocardiography
• They next assessed a sequential two-step strategy, using the second test only for those deemed low risk by the first, with a combination of two tests (WATCH-DM/NT-proBNP, NT-proBNP/hs-cTn, or NT-proBNP/echocardiography), the second used for those deemed low-risk by the first test.
• The primary outcome was incident heart failure during the 5-year follow-up. The researchers also assessed the cost-effectiveness of screening and subsequent treatment of high-risk patients with a sodium-glucose cotransporter 2 inhibitor.

TAKEAWAY:

• Overall, 301 (6.2%) heart failure events occurred among participants without ASCVD.
• Of the heart failure events, 53%-71% occurred among participants deemed high risk by a one-step screening strategy, but 75%-89% occurred among patients assessed as high risk in two steps.
• The risk for incident heart failure was 3.0- to 3.6-fold higher in the high- vs low-risk group identified using a two-step screening approach.
• Among the two-step strategies, the WATCH-DM score first, followed by selective NT-proBNP testing for patients deemed low risk by the first test, was the most efficient, with the fewest tests and lowest screening cost.

IN PRACTICE:

“Matching effective but expensive preventive therapies to the highest-risk individuals who are most likely to benefit would be an efficient and cost-effective strategy for heart failure prevention,” the authors wrote.

SOURCE:

The study, led by Kershaw Patel of the Houston Methodist Academic Institute, was published online in Circulation.

LIMITATIONS:

The study findings may not be generalized, as the study included older adults with a high burden of comorbidities. This study may have missed some individuals with diabetes by defining it with fasting plasma glucose, which was consistently available across cohort studies, instead of with the limited A1c data. Moreover, the screening strategies used did not consider other important prognostic factors, such as diabetes duration and socioeconomic status.

DISCLOSURES:

Two authors declared receiving research support from the National Heart, Lung, and Blood Institute. Several authors disclosed financial relationships with multiple pharmaceutical device and medical publishing companies in the form of receiving personal fees; serving in various capacities such as consultants, members of advisory boards, steering committees, or executive committees; and other ties.

A version of this article appeared on Medscape.com.

TOPLINE:

A two-step screening, using a risk score and biomarkers, can identify patients with diabetes at a higher risk for heart failure who will most likely benefit from preventive drugs.

METHODOLOGY:

• Researchers compared screening methods and downstream risk for heart failure in 5 years, particularly those without atherosclerotic cardiovascular disease (ASCVD).
• They pooled data from 4889 patients (age ≥ 40 years, about half women) with diabetes, no heart failure at baseline, and no signs of ASCVD. All patients had undergone screening to determine their heart failure risk level.
• Researchers assessed the heart failure risk for patients without ASCVD with one-step screening strategies:
• —Clinical risk score (WATCH-DM risk score)
• —Biomarker tests (N-terminal pro-B-type natriuretic peptide [NT-proBNP]) or high-sensitivity cardiac troponin [hs-cTn)
• —Echocardiography
• They next assessed a sequential two-step strategy, using the second test only for those deemed low risk by the first, with a combination of two tests (WATCH-DM/NT-proBNP, NT-proBNP/hs-cTn, or NT-proBNP/echocardiography), the second used for those deemed low-risk by the first test.
• The primary outcome was incident heart failure during the 5-year follow-up. The researchers also assessed the cost-effectiveness of screening and subsequent treatment of high-risk patients with a sodium-glucose cotransporter 2 inhibitor.

TAKEAWAY:

• Overall, 301 (6.2%) heart failure events occurred among participants without ASCVD.
• Of the heart failure events, 53%-71% occurred among participants deemed high risk by a one-step screening strategy, but 75%-89% occurred among patients assessed as high risk in two steps.
• The risk for incident heart failure was 3.0- to 3.6-fold higher in the high- vs low-risk group identified using a two-step screening approach.
• Among the two-step strategies, the WATCH-DM score first, followed by selective NT-proBNP testing for patients deemed low risk by the first test, was the most efficient, with the fewest tests and lowest screening cost.

IN PRACTICE:

“Matching effective but expensive preventive therapies to the highest-risk individuals who are most likely to benefit would be an efficient and cost-effective strategy for heart failure prevention,” the authors wrote.

SOURCE:

The study, led by Kershaw Patel of the Houston Methodist Academic Institute, was published online in Circulation.

LIMITATIONS:

The study findings may not be generalized, as the study included older adults with a high burden of comorbidities. This study may have missed some individuals with diabetes by defining it with fasting plasma glucose, which was consistently available across cohort studies, instead of with the limited A1c data. Moreover, the screening strategies used did not consider other important prognostic factors, such as diabetes duration and socioeconomic status.

DISCLOSURES:

Two authors declared receiving research support from the National Heart, Lung, and Blood Institute. Several authors disclosed financial relationships with multiple pharmaceutical device and medical publishing companies in the form of receiving personal fees; serving in various capacities such as consultants, members of advisory boards, steering committees, or executive committees; and other ties.

A version of this article appeared on Medscape.com.

TOPLINE:

A two-step screening, using a risk score and biomarkers, can identify patients with diabetes at a higher risk for heart failure who will most likely benefit from preventive drugs.

METHODOLOGY:

• Researchers compared screening methods and downstream risk for heart failure in 5 years, particularly those without atherosclerotic cardiovascular disease (ASCVD).
• They pooled data from 4889 patients (age ≥ 40 years, about half women) with diabetes, no heart failure at baseline, and no signs of ASCVD. All patients had undergone screening to determine their heart failure risk level.
• Researchers assessed the heart failure risk for patients without ASCVD with one-step screening strategies:
• —Clinical risk score (WATCH-DM risk score)
• —Biomarker tests (N-terminal pro-B-type natriuretic peptide [NT-proBNP]) or high-sensitivity cardiac troponin [hs-cTn)
• —Echocardiography
• They next assessed a sequential two-step strategy, using the second test only for those deemed low risk by the first, with a combination of two tests (WATCH-DM/NT-proBNP, NT-proBNP/hs-cTn, or NT-proBNP/echocardiography), the second used for those deemed low-risk by the first test.
• The primary outcome was incident heart failure during the 5-year follow-up. The researchers also assessed the cost-effectiveness of screening and subsequent treatment of high-risk patients with a sodium-glucose cotransporter 2 inhibitor.

TAKEAWAY:

• Overall, 301 (6.2%) heart failure events occurred among participants without ASCVD.
• Of the heart failure events, 53%-71% occurred among participants deemed high risk by a one-step screening strategy, but 75%-89% occurred among patients assessed as high risk in two steps.
• The risk for incident heart failure was 3.0- to 3.6-fold higher in the high- vs low-risk group identified using a two-step screening approach.
• Among the two-step strategies, the WATCH-DM score first, followed by selective NT-proBNP testing for patients deemed low risk by the first test, was the most efficient, with the fewest tests and lowest screening cost.

IN PRACTICE:

“Matching effective but expensive preventive therapies to the highest-risk individuals who are most likely to benefit would be an efficient and cost-effective strategy for heart failure prevention,” the authors wrote.

SOURCE:

The study, led by Kershaw Patel of the Houston Methodist Academic Institute, was published online in Circulation.

LIMITATIONS:

The study findings may not be generalized, as the study included older adults with a high burden of comorbidities. This study may have missed some individuals with diabetes by defining it with fasting plasma glucose, which was consistently available across cohort studies, instead of with the limited A1c data. Moreover, the screening strategies used did not consider other important prognostic factors, such as diabetes duration and socioeconomic status.

DISCLOSURES:

Two authors declared receiving research support from the National Heart, Lung, and Blood Institute. Several authors disclosed financial relationships with multiple pharmaceutical device and medical publishing companies in the form of receiving personal fees; serving in various capacities such as consultants, members of advisory boards, steering committees, or executive committees; and other ties.

A version of this article appeared on Medscape.com.

South Korea’s gastric cancer screening (GC) program has reduced disease-related mortality by 41%.

Japan’s? Not at all.

These findings suggest that the benefits of nationwide gastric cancer screening may vary widely between countries while offering insights into program best practices, reported lead author Dianqin Sun, a PhD candidate at the University Medical Center, Rotterdam, the Netherlands, and colleagues.

Mr. Sun

“Despite the lack of evidence from randomized controlled trials, South Korea and Japan, two countries with a high GC incidence, have been at the forefront of GC secondary prevention and have implemented nationwide organized GC screening programs for decades using endoscopy or upper gastrointestinal series,” the investigators wrote in Gastroenterology.

Although individual-level data from both programs supports their efficacy in reducing GC-related death, the investigators noted that these studies have been limited by volunteer bias, and population-level data remain scarce.

To address this knowledge gap, Mr. Sun and colleagues used the flexible synthetic control method to determine how screening programs affected GC mortality rate, as well as a composite mortality rate for esophageal cancer and peptic ulcer.

“The concept of the synthetic control method is to construct a synthetic control for the treated country by deriving a weighted average of multiple control countries without intervention,” the investigators wrote. “The weight of controls is determined in a data-driven way to minimize the differences in preintervention outcomes (i.e., GC mortality before the introduction of nationwide screening) and other covariates associated with GC mortality between the treated country and the synthetic control.”

This approach revealed starkly different benefits for South Korea and Japan.

Compared with the synthetic control, South Korea’s screening program was associated with a 17% reduction in GC mortality risk on average, with risk dropping as far as 41% after the 15th year of screening. The Korean program was also associated with a 28% reduction in mortality from esophageal cancer and peptic ulcer, with this rate decreasing as much as 53% after 15 years of screening.

In sharp contrast, Japan’s mortality rates for GC and the other GI diseases were not significantly different from the synthetic control after 34 years of screening.

The investigators suggested several possible factors behind the lack of benefit in Japan, including the absence of a recommendation for endoscopic screening until 2014. In 2015, just 19% of municipalities in Japan were using endoscopy for screening, compared with more than 72% in South Korea in 2011. Furthermore, guideline adherence and screening program adherence are lower in Japan, they noted.

“Therefore, the findings in our study may have been expected,” the investigators wrote. “However, it is important to note that certain covariates were unavailable for the analysis in Japan, which may have introduced potential biases, the directions of which are unclear. Further studies are needed to compare the screening impact in South Korea and Japan.”

Meanwhile, the present results could guide screening programs around the world, Mr. Sun and colleagues suggested.

“This [study] highlights the significance of a well-planned organizational structure and evidence-based decision making when organized screening is started,” they wrote. “With a quasi-experimental design, this study will facilitate triangulating current observational evidence and provide valuable insights while the GC screening randomized controlled trials are still underway. The data and experience from South Korea and Japan will inform GC screening policy in other countries.”

The investigators disclosed no conflicts of interest.

South Korea’s gastric cancer screening (GC) program has reduced disease-related mortality by 41%.

Japan’s? Not at all.

These findings suggest that the benefits of nationwide gastric cancer screening may vary widely between countries while offering insights into program best practices, reported lead author Dianqin Sun, a PhD candidate at the University Medical Center, Rotterdam, the Netherlands, and colleagues.

Mr. Sun

“Despite the lack of evidence from randomized controlled trials, South Korea and Japan, two countries with a high GC incidence, have been at the forefront of GC secondary prevention and have implemented nationwide organized GC screening programs for decades using endoscopy or upper gastrointestinal series,” the investigators wrote in Gastroenterology.

Although individual-level data from both programs supports their efficacy in reducing GC-related death, the investigators noted that these studies have been limited by volunteer bias, and population-level data remain scarce.

To address this knowledge gap, Mr. Sun and colleagues used the flexible synthetic control method to determine how screening programs affected GC mortality rate, as well as a composite mortality rate for esophageal cancer and peptic ulcer.

“The concept of the synthetic control method is to construct a synthetic control for the treated country by deriving a weighted average of multiple control countries without intervention,” the investigators wrote. “The weight of controls is determined in a data-driven way to minimize the differences in preintervention outcomes (i.e., GC mortality before the introduction of nationwide screening) and other covariates associated with GC mortality between the treated country and the synthetic control.”

This approach revealed starkly different benefits for South Korea and Japan.

Compared with the synthetic control, South Korea’s screening program was associated with a 17% reduction in GC mortality risk on average, with risk dropping as far as 41% after the 15th year of screening. The Korean program was also associated with a 28% reduction in mortality from esophageal cancer and peptic ulcer, with this rate decreasing as much as 53% after 15 years of screening.

In sharp contrast, Japan’s mortality rates for GC and the other GI diseases were not significantly different from the synthetic control after 34 years of screening.

The investigators suggested several possible factors behind the lack of benefit in Japan, including the absence of a recommendation for endoscopic screening until 2014. In 2015, just 19% of municipalities in Japan were using endoscopy for screening, compared with more than 72% in South Korea in 2011. Furthermore, guideline adherence and screening program adherence are lower in Japan, they noted.

“Therefore, the findings in our study may have been expected,” the investigators wrote. “However, it is important to note that certain covariates were unavailable for the analysis in Japan, which may have introduced potential biases, the directions of which are unclear. Further studies are needed to compare the screening impact in South Korea and Japan.”

Meanwhile, the present results could guide screening programs around the world, Mr. Sun and colleagues suggested.

“This [study] highlights the significance of a well-planned organizational structure and evidence-based decision making when organized screening is started,” they wrote. “With a quasi-experimental design, this study will facilitate triangulating current observational evidence and provide valuable insights while the GC screening randomized controlled trials are still underway. The data and experience from South Korea and Japan will inform GC screening policy in other countries.”

The investigators disclosed no conflicts of interest.

South Korea’s gastric cancer screening (GC) program has reduced disease-related mortality by 41%.

Japan’s? Not at all.

These findings suggest that the benefits of nationwide gastric cancer screening may vary widely between countries while offering insights into program best practices, reported lead author Dianqin Sun, a PhD candidate at the University Medical Center, Rotterdam, the Netherlands, and colleagues.

Mr. Sun

“Despite the lack of evidence from randomized controlled trials, South Korea and Japan, two countries with a high GC incidence, have been at the forefront of GC secondary prevention and have implemented nationwide organized GC screening programs for decades using endoscopy or upper gastrointestinal series,” the investigators wrote in Gastroenterology.

Although individual-level data from both programs supports their efficacy in reducing GC-related death, the investigators noted that these studies have been limited by volunteer bias, and population-level data remain scarce.

To address this knowledge gap, Mr. Sun and colleagues used the flexible synthetic control method to determine how screening programs affected GC mortality rate, as well as a composite mortality rate for esophageal cancer and peptic ulcer.

“The concept of the synthetic control method is to construct a synthetic control for the treated country by deriving a weighted average of multiple control countries without intervention,” the investigators wrote. “The weight of controls is determined in a data-driven way to minimize the differences in preintervention outcomes (i.e., GC mortality before the introduction of nationwide screening) and other covariates associated with GC mortality between the treated country and the synthetic control.”

This approach revealed starkly different benefits for South Korea and Japan.

Compared with the synthetic control, South Korea’s screening program was associated with a 17% reduction in GC mortality risk on average, with risk dropping as far as 41% after the 15th year of screening. The Korean program was also associated with a 28% reduction in mortality from esophageal cancer and peptic ulcer, with this rate decreasing as much as 53% after 15 years of screening.

In sharp contrast, Japan’s mortality rates for GC and the other GI diseases were not significantly different from the synthetic control after 34 years of screening.

The investigators suggested several possible factors behind the lack of benefit in Japan, including the absence of a recommendation for endoscopic screening until 2014. In 2015, just 19% of municipalities in Japan were using endoscopy for screening, compared with more than 72% in South Korea in 2011. Furthermore, guideline adherence and screening program adherence are lower in Japan, they noted.

“Therefore, the findings in our study may have been expected,” the investigators wrote. “However, it is important to note that certain covariates were unavailable for the analysis in Japan, which may have introduced potential biases, the directions of which are unclear. Further studies are needed to compare the screening impact in South Korea and Japan.”

Meanwhile, the present results could guide screening programs around the world, Mr. Sun and colleagues suggested.

“This [study] highlights the significance of a well-planned organizational structure and evidence-based decision making when organized screening is started,” they wrote. “With a quasi-experimental design, this study will facilitate triangulating current observational evidence and provide valuable insights while the GC screening randomized controlled trials are still underway. The data and experience from South Korea and Japan will inform GC screening policy in other countries.”

The investigators disclosed no conflicts of interest.

Recent research highlights the potential role of an atypical antipsychotic to treat anxiety, a prevalent and undertreated symptom in bipolar I disorder (BPD). Notably, investigators said, the drug comes without the typical metabolic side effects, including weight gain, associated with this drug class.

A post hoc analysis of pooled data from two trials comparing two different doses of cariprazine (Vraylar) to placebo showed it was consistently effective not only in alleviating bipolar depression but also in improving symptoms of anxiety.

“Since this was a post hoc analysis, one has to be careful about not overstating the findings,” said study investigator Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, and head of the Mood Disorders Psychopharmacology Unit.

“But what we can say is that anxiety has been an under-researched, undertreated symptom dimension in BPD, and these findings about cariprazine are very promising,” said Dr. McIntyre, chair and executive director of the Brain and Cognition Discovery Foundation, also in Toronto.

The analysis was published in International Clinical Psychopharmacology) and was presented as a poster at the 2023 Neuroscience Education Institute, Colorado Springs, Colorado.
 

Ubiquitous, Common, Hazardous

Anxiety in BPD is “ubiquitous, common, and hazardous,” Dr. McIntyre said. “We talk so much about depression and mania as cardinal presentations, but someone could make a case that in that trifecta, we’re missing anxiety.”

In patients with BPD and anxiety, “the index episode is much more difficult to treat, there’s a longer time to remission, lower rates of recovery, and a shorter time to recurrence,” noted Dr. McIntyre, chair of the board of the Depression and Bipolar Support Alliance.

Anxiety also may “represent a portent of other things that can add more to the trouble, like alcohol, illicit drugs, or cannabis use — especially now that cannabis is no longer illegal,” Dr. McIntyre said.

Unfortunately, he said, “there hasn’t been an organized, systematic approach to developing a therapy for anxiety in BPD.” Rather, patients are prescribed benzodiazepines, gabapentinoids, or selective serotonin reuptake inhibitors, all of which have limitations, he added.

Some atypical antipsychotics such as quetiapine have been shown to be helpful with anxiety but “have a lot of baggage and side effects — especially sedation, somnolence, weight gain, and metabolic problems,” Dr. McIntyre noted.

Cariprazine is a dopamine D3-preferring D3/D2 partial agonist, a serotonin 5-HT1A receptor partial agonist, and 5-HT2B receptor antagonist, which has shown anxiolytic-like activity in rodent models.

It was approved by the US Food and Drug Administration to treat mania, depression, and mixed episodes of BPD in 2015 and BPD in 2019.

Dr. McIntyre and his team believed there was an opportunity in the completed randomized controlled trials of cariprazine in BPD to conduct a post hoc analysis of its impact on anxiety.
 

‘Cornerstone Mood Stabilizer’

The researchers pooled data from two phase 3, randomized, double-blind, placebo-controlled studies in adults with BPD experiencing a current major depressive episode.

The pooled intention-to-treat population consisted of 952 patients with BPD (mean age, ~43 years; 62% female) randomized to receive either 1.5 mg/d, 3 mg/d of cariprazine, or placebo. Patients were divided into two subsets: Lower or higher anxiety (defined as a Hamilton Anxiety Rating Scale [HAM-A] total score of < 18 and ≥ 18, respectively). Patients also completed the Montgomery-Åsberg Rating Scale (MADRS).

A third of the patients received a placebo, a third received the 1.5 mg/d dose, and a third received the 3 mg/d dose. Demographic and baseline characteristics were similar between the subsets.

Results showed there was a statistically significant change in HAM-A total score for cariprazine 1.5 mg/d (P = .0027). The investigators also found a statistically significant change in MADRS total score change for cariprazine 1.5 mg (P = .0200) in the higher anxiety subset. The rate of remission was significantly greater for cariprazine 1.5 mg/d in the higher and lower anxiety subsets (P = .0172 and P = .0004, respectively).

In addition, the change in HAM-A total score change was statistically significant for cariprazine 1.5 mg/d in the higher anxiety subgroup (P = .0105) and the 3 mg/d dose in the lower anxiety subgroup (P = .0441).

Dr. McIntyre hopes these findings can be replicated in other trials.

“Clinically, I find that many patients who take cariprazine don’t require as many benzodiazepines or other medications for anxiety, and it’s one of the better-tolerated medications without metabolic complications or weight gain, so it’s become a cornerstone mood stabilizer,” he said.
 

Polypharmacy Avoided

Another recent study retrospectively analyzed medical records of close to 40 adult patients with BPD I who were receiving treatment with aripiprazole for bipolar depression and then switched to cariprazine.

“We wanted to conduct a study in depressed patients who had gained weight on aripiprazole and then directly switched to cariprazine. It improved their mood and helped mitigate weight gain, thereby avoiding polypharmacy of additional antidepressants and weight loss agents,” said study investigator Maxwell Zachary Price, a medical student at Hackensack Meridian School of Medicine, Nutley, New Jersey.

“In our general outpatient psychiatry practice, we’ve treated many adult patients with oral aripiprazole for maintenance of BPD,” the study’s senior investigator, Richard Price, MD, clinical assistant professor of psychiatry at Weill Cornell Medical College, New York City, added.

Aripiprazole is associated with weight gain. Moreover, aripiprazole “hasn’t shown efficacy in managing BPD,” he said.

Most patients in Dr. Price’s practice are insured through Medicaid, which mandates treatment with aripiprazole before covering cariprazine. “We noticed their weight had been creeping up over the years, and they also were experiencing depressive symptoms,” he said.

The requirement to initiate treatment with aripiprazole before switching to cariprazine offered Dr. Price an opportunity to compare the two agents in this real-world setting by retrospectively reviewing the charts of 37 patients with BPD (23 females and 14 males who made the switch). The patients had been taking aripiprazole for a mean duration of 94.9 weeks and had experienced a mean increase in body weight of 16.1% ± 12.3% on aripiprazole before switching.

Patients who were taking 2 mg-10 mg of aripiprazole were switched to 1.5 mg of cariprazine, while those taking ≥ 15 mg of aripiprazole were switched to 3 mg of cariprazine.

“Patients tolerated the switch well and maintained stability during the transition,” and “no patients discontinued cariprazine during the study,” Dr. Price said.

After a mean duration of 36.7 weeks (range, 1-127 weeks), the patients showed a decrease in Clinical Global Impression-Bipolar Severity of Illness Scale score from a mean of 5.0 ± 0.9 to a mean of 2.8 ± 0.7 (t = −12.75, P < .00001).

The patients’ weight dropped from a mean of 90.3± 21.5 kg on aripiprazole to a mean of 83.9 ± 19.2 kg on cariprazine (t = −4.22, P < .001).

Two patients experienced initial nausea that resolved by taking the medication with food, and two experienced initial restlessness that resolved with dosage reduction.

“We found that the patients were lighter in mood, body habitus and weight, and less agitated and their mental alertness and concentration improved as well,” said Dr. Price. He hopes that further research in randomized blinded trials will corroborate the findings.
 

Hypothesis-Generating Research

Joseph Cerimele, MD, MPH, associate professor of psychiatry and behavioral sciences, University of Washington, Division of Population Health, UW Medicine, Seattle, Washington, said the research findings are “hypothesis-generating.”

Dr. Ciremele, who wasn’t involved with either study, said many clinicians and researchers are trying to tailor treatment options to match patient characteristics, and these studies and other similar research, “help us all ask questions related to concurrent symptoms in bipolar depression.”

However, the post hoc analysis was a secondary analysis of an efficacy trial where individuals with concurrent anxiety disorders were excluded. “So, a next step might be to evaluate this and other treatments in individuals with BPD and concurrent anxiety disorders,” he said.

The study by Jain et al was funded by AbbVie. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics Inc., Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. Dr. McIntyre is the CEO of Braxia Scientific Corp. His coauthors’ disclosures are listed in the original paper. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus. Mr. Price and Dr. Cerimele reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Recent research highlights the potential role of an atypical antipsychotic to treat anxiety, a prevalent and undertreated symptom in bipolar I disorder (BPD). Notably, investigators said, the drug comes without the typical metabolic side effects, including weight gain, associated with this drug class.

A post hoc analysis of pooled data from two trials comparing two different doses of cariprazine (Vraylar) to placebo showed it was consistently effective not only in alleviating bipolar depression but also in improving symptoms of anxiety.

“Since this was a post hoc analysis, one has to be careful about not overstating the findings,” said study investigator Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, and head of the Mood Disorders Psychopharmacology Unit.

“But what we can say is that anxiety has been an under-researched, undertreated symptom dimension in BPD, and these findings about cariprazine are very promising,” said Dr. McIntyre, chair and executive director of the Brain and Cognition Discovery Foundation, also in Toronto.

The analysis was published in International Clinical Psychopharmacology) and was presented as a poster at the 2023 Neuroscience Education Institute, Colorado Springs, Colorado.
 

Ubiquitous, Common, Hazardous

Anxiety in BPD is “ubiquitous, common, and hazardous,” Dr. McIntyre said. “We talk so much about depression and mania as cardinal presentations, but someone could make a case that in that trifecta, we’re missing anxiety.”

In patients with BPD and anxiety, “the index episode is much more difficult to treat, there’s a longer time to remission, lower rates of recovery, and a shorter time to recurrence,” noted Dr. McIntyre, chair of the board of the Depression and Bipolar Support Alliance.

Anxiety also may “represent a portent of other things that can add more to the trouble, like alcohol, illicit drugs, or cannabis use — especially now that cannabis is no longer illegal,” Dr. McIntyre said.

Unfortunately, he said, “there hasn’t been an organized, systematic approach to developing a therapy for anxiety in BPD.” Rather, patients are prescribed benzodiazepines, gabapentinoids, or selective serotonin reuptake inhibitors, all of which have limitations, he added.

Some atypical antipsychotics such as quetiapine have been shown to be helpful with anxiety but “have a lot of baggage and side effects — especially sedation, somnolence, weight gain, and metabolic problems,” Dr. McIntyre noted.

Cariprazine is a dopamine D3-preferring D3/D2 partial agonist, a serotonin 5-HT1A receptor partial agonist, and 5-HT2B receptor antagonist, which has shown anxiolytic-like activity in rodent models.

It was approved by the US Food and Drug Administration to treat mania, depression, and mixed episodes of BPD in 2015 and BPD in 2019.

Dr. McIntyre and his team believed there was an opportunity in the completed randomized controlled trials of cariprazine in BPD to conduct a post hoc analysis of its impact on anxiety.
 

‘Cornerstone Mood Stabilizer’

The researchers pooled data from two phase 3, randomized, double-blind, placebo-controlled studies in adults with BPD experiencing a current major depressive episode.

The pooled intention-to-treat population consisted of 952 patients with BPD (mean age, ~43 years; 62% female) randomized to receive either 1.5 mg/d, 3 mg/d of cariprazine, or placebo. Patients were divided into two subsets: Lower or higher anxiety (defined as a Hamilton Anxiety Rating Scale [HAM-A] total score of < 18 and ≥ 18, respectively). Patients also completed the Montgomery-Åsberg Rating Scale (MADRS).

A third of the patients received a placebo, a third received the 1.5 mg/d dose, and a third received the 3 mg/d dose. Demographic and baseline characteristics were similar between the subsets.

Results showed there was a statistically significant change in HAM-A total score for cariprazine 1.5 mg/d (P = .0027). The investigators also found a statistically significant change in MADRS total score change for cariprazine 1.5 mg (P = .0200) in the higher anxiety subset. The rate of remission was significantly greater for cariprazine 1.5 mg/d in the higher and lower anxiety subsets (P = .0172 and P = .0004, respectively).

In addition, the change in HAM-A total score change was statistically significant for cariprazine 1.5 mg/d in the higher anxiety subgroup (P = .0105) and the 3 mg/d dose in the lower anxiety subgroup (P = .0441).

Dr. McIntyre hopes these findings can be replicated in other trials.

“Clinically, I find that many patients who take cariprazine don’t require as many benzodiazepines or other medications for anxiety, and it’s one of the better-tolerated medications without metabolic complications or weight gain, so it’s become a cornerstone mood stabilizer,” he said.
 

Polypharmacy Avoided

Another recent study retrospectively analyzed medical records of close to 40 adult patients with BPD I who were receiving treatment with aripiprazole for bipolar depression and then switched to cariprazine.

“We wanted to conduct a study in depressed patients who had gained weight on aripiprazole and then directly switched to cariprazine. It improved their mood and helped mitigate weight gain, thereby avoiding polypharmacy of additional antidepressants and weight loss agents,” said study investigator Maxwell Zachary Price, a medical student at Hackensack Meridian School of Medicine, Nutley, New Jersey.

“In our general outpatient psychiatry practice, we’ve treated many adult patients with oral aripiprazole for maintenance of BPD,” the study’s senior investigator, Richard Price, MD, clinical assistant professor of psychiatry at Weill Cornell Medical College, New York City, added.

Aripiprazole is associated with weight gain. Moreover, aripiprazole “hasn’t shown efficacy in managing BPD,” he said.

Most patients in Dr. Price’s practice are insured through Medicaid, which mandates treatment with aripiprazole before covering cariprazine. “We noticed their weight had been creeping up over the years, and they also were experiencing depressive symptoms,” he said.

The requirement to initiate treatment with aripiprazole before switching to cariprazine offered Dr. Price an opportunity to compare the two agents in this real-world setting by retrospectively reviewing the charts of 37 patients with BPD (23 females and 14 males who made the switch). The patients had been taking aripiprazole for a mean duration of 94.9 weeks and had experienced a mean increase in body weight of 16.1% ± 12.3% on aripiprazole before switching.

Patients who were taking 2 mg-10 mg of aripiprazole were switched to 1.5 mg of cariprazine, while those taking ≥ 15 mg of aripiprazole were switched to 3 mg of cariprazine.

“Patients tolerated the switch well and maintained stability during the transition,” and “no patients discontinued cariprazine during the study,” Dr. Price said.

After a mean duration of 36.7 weeks (range, 1-127 weeks), the patients showed a decrease in Clinical Global Impression-Bipolar Severity of Illness Scale score from a mean of 5.0 ± 0.9 to a mean of 2.8 ± 0.7 (t = −12.75, P < .00001).

The patients’ weight dropped from a mean of 90.3± 21.5 kg on aripiprazole to a mean of 83.9 ± 19.2 kg on cariprazine (t = −4.22, P < .001).

Two patients experienced initial nausea that resolved by taking the medication with food, and two experienced initial restlessness that resolved with dosage reduction.

“We found that the patients were lighter in mood, body habitus and weight, and less agitated and their mental alertness and concentration improved as well,” said Dr. Price. He hopes that further research in randomized blinded trials will corroborate the findings.
 

Hypothesis-Generating Research

Joseph Cerimele, MD, MPH, associate professor of psychiatry and behavioral sciences, University of Washington, Division of Population Health, UW Medicine, Seattle, Washington, said the research findings are “hypothesis-generating.”

Dr. Ciremele, who wasn’t involved with either study, said many clinicians and researchers are trying to tailor treatment options to match patient characteristics, and these studies and other similar research, “help us all ask questions related to concurrent symptoms in bipolar depression.”

However, the post hoc analysis was a secondary analysis of an efficacy trial where individuals with concurrent anxiety disorders were excluded. “So, a next step might be to evaluate this and other treatments in individuals with BPD and concurrent anxiety disorders,” he said.

The study by Jain et al was funded by AbbVie. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics Inc., Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. Dr. McIntyre is the CEO of Braxia Scientific Corp. His coauthors’ disclosures are listed in the original paper. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus. Mr. Price and Dr. Cerimele reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Recent research highlights the potential role of an atypical antipsychotic to treat anxiety, a prevalent and undertreated symptom in bipolar I disorder (BPD). Notably, investigators said, the drug comes without the typical metabolic side effects, including weight gain, associated with this drug class.

A post hoc analysis of pooled data from two trials comparing two different doses of cariprazine (Vraylar) to placebo showed it was consistently effective not only in alleviating bipolar depression but also in improving symptoms of anxiety.

“Since this was a post hoc analysis, one has to be careful about not overstating the findings,” said study investigator Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, and head of the Mood Disorders Psychopharmacology Unit.

“But what we can say is that anxiety has been an under-researched, undertreated symptom dimension in BPD, and these findings about cariprazine are very promising,” said Dr. McIntyre, chair and executive director of the Brain and Cognition Discovery Foundation, also in Toronto.

The analysis was published in International Clinical Psychopharmacology) and was presented as a poster at the 2023 Neuroscience Education Institute, Colorado Springs, Colorado.
 

Ubiquitous, Common, Hazardous

Anxiety in BPD is “ubiquitous, common, and hazardous,” Dr. McIntyre said. “We talk so much about depression and mania as cardinal presentations, but someone could make a case that in that trifecta, we’re missing anxiety.”

In patients with BPD and anxiety, “the index episode is much more difficult to treat, there’s a longer time to remission, lower rates of recovery, and a shorter time to recurrence,” noted Dr. McIntyre, chair of the board of the Depression and Bipolar Support Alliance.

Anxiety also may “represent a portent of other things that can add more to the trouble, like alcohol, illicit drugs, or cannabis use — especially now that cannabis is no longer illegal,” Dr. McIntyre said.

Unfortunately, he said, “there hasn’t been an organized, systematic approach to developing a therapy for anxiety in BPD.” Rather, patients are prescribed benzodiazepines, gabapentinoids, or selective serotonin reuptake inhibitors, all of which have limitations, he added.

Some atypical antipsychotics such as quetiapine have been shown to be helpful with anxiety but “have a lot of baggage and side effects — especially sedation, somnolence, weight gain, and metabolic problems,” Dr. McIntyre noted.

Cariprazine is a dopamine D3-preferring D3/D2 partial agonist, a serotonin 5-HT1A receptor partial agonist, and 5-HT2B receptor antagonist, which has shown anxiolytic-like activity in rodent models.

It was approved by the US Food and Drug Administration to treat mania, depression, and mixed episodes of BPD in 2015 and BPD in 2019.

Dr. McIntyre and his team believed there was an opportunity in the completed randomized controlled trials of cariprazine in BPD to conduct a post hoc analysis of its impact on anxiety.
 

‘Cornerstone Mood Stabilizer’

The researchers pooled data from two phase 3, randomized, double-blind, placebo-controlled studies in adults with BPD experiencing a current major depressive episode.

The pooled intention-to-treat population consisted of 952 patients with BPD (mean age, ~43 years; 62% female) randomized to receive either 1.5 mg/d, 3 mg/d of cariprazine, or placebo. Patients were divided into two subsets: Lower or higher anxiety (defined as a Hamilton Anxiety Rating Scale [HAM-A] total score of < 18 and ≥ 18, respectively). Patients also completed the Montgomery-Åsberg Rating Scale (MADRS).

A third of the patients received a placebo, a third received the 1.5 mg/d dose, and a third received the 3 mg/d dose. Demographic and baseline characteristics were similar between the subsets.

Results showed there was a statistically significant change in HAM-A total score for cariprazine 1.5 mg/d (P = .0027). The investigators also found a statistically significant change in MADRS total score change for cariprazine 1.5 mg (P = .0200) in the higher anxiety subset. The rate of remission was significantly greater for cariprazine 1.5 mg/d in the higher and lower anxiety subsets (P = .0172 and P = .0004, respectively).

In addition, the change in HAM-A total score change was statistically significant for cariprazine 1.5 mg/d in the higher anxiety subgroup (P = .0105) and the 3 mg/d dose in the lower anxiety subgroup (P = .0441).

Dr. McIntyre hopes these findings can be replicated in other trials.

“Clinically, I find that many patients who take cariprazine don’t require as many benzodiazepines or other medications for anxiety, and it’s one of the better-tolerated medications without metabolic complications or weight gain, so it’s become a cornerstone mood stabilizer,” he said.
 

Polypharmacy Avoided

Another recent study retrospectively analyzed medical records of close to 40 adult patients with BPD I who were receiving treatment with aripiprazole for bipolar depression and then switched to cariprazine.

“We wanted to conduct a study in depressed patients who had gained weight on aripiprazole and then directly switched to cariprazine. It improved their mood and helped mitigate weight gain, thereby avoiding polypharmacy of additional antidepressants and weight loss agents,” said study investigator Maxwell Zachary Price, a medical student at Hackensack Meridian School of Medicine, Nutley, New Jersey.

“In our general outpatient psychiatry practice, we’ve treated many adult patients with oral aripiprazole for maintenance of BPD,” the study’s senior investigator, Richard Price, MD, clinical assistant professor of psychiatry at Weill Cornell Medical College, New York City, added.

Aripiprazole is associated with weight gain. Moreover, aripiprazole “hasn’t shown efficacy in managing BPD,” he said.

Most patients in Dr. Price’s practice are insured through Medicaid, which mandates treatment with aripiprazole before covering cariprazine. “We noticed their weight had been creeping up over the years, and they also were experiencing depressive symptoms,” he said.

The requirement to initiate treatment with aripiprazole before switching to cariprazine offered Dr. Price an opportunity to compare the two agents in this real-world setting by retrospectively reviewing the charts of 37 patients with BPD (23 females and 14 males who made the switch). The patients had been taking aripiprazole for a mean duration of 94.9 weeks and had experienced a mean increase in body weight of 16.1% ± 12.3% on aripiprazole before switching.

Patients who were taking 2 mg-10 mg of aripiprazole were switched to 1.5 mg of cariprazine, while those taking ≥ 15 mg of aripiprazole were switched to 3 mg of cariprazine.

“Patients tolerated the switch well and maintained stability during the transition,” and “no patients discontinued cariprazine during the study,” Dr. Price said.

After a mean duration of 36.7 weeks (range, 1-127 weeks), the patients showed a decrease in Clinical Global Impression-Bipolar Severity of Illness Scale score from a mean of 5.0 ± 0.9 to a mean of 2.8 ± 0.7 (t = −12.75, P < .00001).

The patients’ weight dropped from a mean of 90.3± 21.5 kg on aripiprazole to a mean of 83.9 ± 19.2 kg on cariprazine (t = −4.22, P < .001).

Two patients experienced initial nausea that resolved by taking the medication with food, and two experienced initial restlessness that resolved with dosage reduction.

“We found that the patients were lighter in mood, body habitus and weight, and less agitated and their mental alertness and concentration improved as well,” said Dr. Price. He hopes that further research in randomized blinded trials will corroborate the findings.
 

Hypothesis-Generating Research

Joseph Cerimele, MD, MPH, associate professor of psychiatry and behavioral sciences, University of Washington, Division of Population Health, UW Medicine, Seattle, Washington, said the research findings are “hypothesis-generating.”

Dr. Ciremele, who wasn’t involved with either study, said many clinicians and researchers are trying to tailor treatment options to match patient characteristics, and these studies and other similar research, “help us all ask questions related to concurrent symptoms in bipolar depression.”

However, the post hoc analysis was a secondary analysis of an efficacy trial where individuals with concurrent anxiety disorders were excluded. “So, a next step might be to evaluate this and other treatments in individuals with BPD and concurrent anxiety disorders,” he said.

The study by Jain et al was funded by AbbVie. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics Inc., Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. Dr. McIntyre is the CEO of Braxia Scientific Corp. His coauthors’ disclosures are listed in the original paper. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus. Mr. Price and Dr. Cerimele reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

A few weeks ago, I made a patient who lost 100 pounds following a sleeve gastrectomy 9 months prior feel bad because I told her she lost too much weight. As I spoke to her, I realized that she found it hard to make life changes and that the surgery was a huge aide in changing her life and her lifestyle. I ended up apologizing for initially saying she lost too much weight.

For the first time in her life, she was successful in losing weight and keeping it off. The surgery allowed her body to defend a lower body weight by altering the secretion of gut hormones that lead to satiety in the brain. It’s not her fault that her body responded so well!

I asked her to be on my next orientation virtual meeting with prospective weight management patients to urge those with a body mass index (BMI) > 40 to consider bariatric surgery as the most effective durable and safe treatment for their degree of obesity.

Metabolic bariatric surgery, primarily sleeve gastrectomy and Roux-en-Y gastric bypass , alters the gut hormone milieu such that the body defends a lower mass of adipose tissue and a lower weight. We have learned what it takes to alter body weight defense to a healthy lower weight by studying why metabolic bariatric surgery works so well. It turns out that there are several hormones secreted by the gut that allow the brain to register fullness.

One of these gut hormones, glucagon-like peptide (GLP)-1, has been researched as an analog to help reduce body weight by 16% and has also been shown to reduce cardiovascular risk in the SELECT trial, as published in The New England Journal of Medicine (NEJM).

It’s the first weight loss medication to be shown in a cardiovascular outcomes trial to be superior to placebo in reduction of major cardiovascular events, including cardiovascular deaths, nonfatal myocardial infarction, and nonfatal stroke. The results presented at the 2023 American Heart Association meetings in Philadelphia ended in wholehearted applause by a “standing only” audience even before the presentation’s conclusion.

As we pave the way for nutrient-stimulated hormone (NuSH) therapies to be prescribed to all Americans with a BMI > 30 to improve health, we need to remember what these medications actually do. We used to think that metabolic bariatric surgery worked by restricting the stomach contents and malabsorbing nutrients. We now know that the surgeries work by altering NuSH secretion, allowing for less secretion of the hunger hormone ghrelin and more secretion of GLP-1, glucose-dependent insulinotropic polypeptide (GIP), peptide YY (PYY), cholecystokinin (CCK), oxyntomodulin (OXM), and other satiety hormones with less food ingestion.

They have pleiotropic effects on many organ systems in the body, including the brain, heart, adipose tissue, and liver. They decrease inflammation and also increase satiety and delay gastric emptying. None of these effects automatically produce weight loss, but they certainly aid in the adoption of a healthier body weight and better health. The weight loss occurs because these medications steer the body toward behavioral changes that promote weight loss.

As we delve into the SELECT trial results, a 20% reduction in major cardiovascular events was accompanied by an average weight loss of 9.6%, without a behavioral component added to either the placebo or intervention arms, as is usual in antiobesity agent trials.

Does this mean that primary care providers (PCPs) don’t have to educate patients on behavior change, diet, and exercise therapy? Well, if we consider obesity a disease as we do type 2 diabetes and dyslipidemia or hypertension, then no — PCPs don’t have to, just like they don’t in treating these other diseases.

However, we should rethink this practice. The recently published SURMOUNT-3 trial looked at another NuSH, tirzepatide, with intensive behavioral therapy; it resulted in a 26.6% weight loss, which is comparable to results with bariatric surgery. The SURMOUNT-1 trial of tirzepatide with nonintensive behavioral therapy resulted in a 20.9% weight loss, which is still substantial, but SURMOUNT-3 showed how much more is achievable with robust behavior-change therapy.

In other words, it’s time that PCPs provide education on behavior change to maximize the power of the medications prescribed in practice for the most common diseases suffered in the United States: obesity, type 2 diabetes, cardiovascular disease, and hypertension. These are all chronic, relapsing diseases. Medication alone will improve numbers (weight, blood glucose, A1c, and blood pressure), but a relapsing disease continues relentlessly as patients age to overcome the medications prescribed.

Today I made another patient feel bad because she lost over 100 pounds on semaglutide (Wegovy) 2.4 mg over 1 year, reducing her BMI from 57 to 36. She wanted to keep losing, so I recommended sleeve gastrectomy to lose more weight. I told her she could always restart the Wegovy after the procedure if needed.

We really don’t have an answer to this issue of NuSH therapy not getting to goal and bariatric surgery following medication therapy. The reality is that bariatric surgery should be considered a safe, effective treatment for extreme obesity somewhere along the trajectory of treatments starting with behavior (diet, exercise) and medications. It is still considered a last resort, and for some, just too aggressive.

We have learned much about the incretin hormones and what they can accomplish for obesity from studying bariatric — now called metabolic — surgery. Surgery should be seen as we see stent placement for angina, only more effective for longevity. The COURAGE trial, published in 2007 in NEJM, showed that when compared with medication treatment alone for angina, stent placement plus medications resulted in no difference in mortality after a 7-year follow-up period. Compare this to bariatric surgery, which in many retrospective analyses shows a 20% reduction in cardiovascular mortality after 20-year follow-up (Swedish Obesity Study). In the United States, there are 2 million stent procedures performed per year vs 250,000 bariatric surgical procedures. There are millions of Americans with a BMI > 40 and, yes, millions of Americans with angina. I think I make my point that we need to do more bariatric surgeries to effectively treat extreme obesity.

The solution to this negligent medical practice in obesity treatment is to empower PCPs to treat obesity (at least uncomplicated obesity) and refer to obesity medicine practices for complicated obesity with multiple complications, such as type 2 diabetes and cardiovascular disease, and to refer to obesity medicine practices with a surgical component for BMIs > 40 or > 35 with type 2 diabetes, sleep apnea, and/or cardiovascular disease or other serious conditions.

How do we empower PCPs? Insurance coverage of NuSH therapies due to life-saving properties — as evidenced by the SELECT trial — without prior authorizations; and education on how and why metabolic surgery works, as well as education on behavioral approaches, such as healthy diet and exercise, as a core therapy for all BMI categories.

It’s time.

Caroline Apovian, MD, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Altimmune; Cowen and Company; Currax Pharmaceuticals; EPG Communication Holdings; Gelesis, Srl; L-Nutra; and NeuroBo Pharmaceuticals. Received research grant from: National Institutes of Health; Patient-Centered Outcomes Research Institute; and GI Dynamics. Received income in an amount equal to or greater than $250 from: Altimmune; Cowen and Company; NeuroBo Pharmaceuticals; and Novo Nordisk.

A version of this article appeared on Medscape.com.

A few weeks ago, I made a patient who lost 100 pounds following a sleeve gastrectomy 9 months prior feel bad because I told her she lost too much weight. As I spoke to her, I realized that she found it hard to make life changes and that the surgery was a huge aide in changing her life and her lifestyle. I ended up apologizing for initially saying she lost too much weight.

For the first time in her life, she was successful in losing weight and keeping it off. The surgery allowed her body to defend a lower body weight by altering the secretion of gut hormones that lead to satiety in the brain. It’s not her fault that her body responded so well!

I asked her to be on my next orientation virtual meeting with prospective weight management patients to urge those with a body mass index (BMI) > 40 to consider bariatric surgery as the most effective durable and safe treatment for their degree of obesity.

Metabolic bariatric surgery, primarily sleeve gastrectomy and Roux-en-Y gastric bypass , alters the gut hormone milieu such that the body defends a lower mass of adipose tissue and a lower weight. We have learned what it takes to alter body weight defense to a healthy lower weight by studying why metabolic bariatric surgery works so well. It turns out that there are several hormones secreted by the gut that allow the brain to register fullness.

One of these gut hormones, glucagon-like peptide (GLP)-1, has been researched as an analog to help reduce body weight by 16% and has also been shown to reduce cardiovascular risk in the SELECT trial, as published in The New England Journal of Medicine (NEJM).

It’s the first weight loss medication to be shown in a cardiovascular outcomes trial to be superior to placebo in reduction of major cardiovascular events, including cardiovascular deaths, nonfatal myocardial infarction, and nonfatal stroke. The results presented at the 2023 American Heart Association meetings in Philadelphia ended in wholehearted applause by a “standing only” audience even before the presentation’s conclusion.

As we pave the way for nutrient-stimulated hormone (NuSH) therapies to be prescribed to all Americans with a BMI > 30 to improve health, we need to remember what these medications actually do. We used to think that metabolic bariatric surgery worked by restricting the stomach contents and malabsorbing nutrients. We now know that the surgeries work by altering NuSH secretion, allowing for less secretion of the hunger hormone ghrelin and more secretion of GLP-1, glucose-dependent insulinotropic polypeptide (GIP), peptide YY (PYY), cholecystokinin (CCK), oxyntomodulin (OXM), and other satiety hormones with less food ingestion.

They have pleiotropic effects on many organ systems in the body, including the brain, heart, adipose tissue, and liver. They decrease inflammation and also increase satiety and delay gastric emptying. None of these effects automatically produce weight loss, but they certainly aid in the adoption of a healthier body weight and better health. The weight loss occurs because these medications steer the body toward behavioral changes that promote weight loss.

As we delve into the SELECT trial results, a 20% reduction in major cardiovascular events was accompanied by an average weight loss of 9.6%, without a behavioral component added to either the placebo or intervention arms, as is usual in antiobesity agent trials.

Does this mean that primary care providers (PCPs) don’t have to educate patients on behavior change, diet, and exercise therapy? Well, if we consider obesity a disease as we do type 2 diabetes and dyslipidemia or hypertension, then no — PCPs don’t have to, just like they don’t in treating these other diseases.

However, we should rethink this practice. The recently published SURMOUNT-3 trial looked at another NuSH, tirzepatide, with intensive behavioral therapy; it resulted in a 26.6% weight loss, which is comparable to results with bariatric surgery. The SURMOUNT-1 trial of tirzepatide with nonintensive behavioral therapy resulted in a 20.9% weight loss, which is still substantial, but SURMOUNT-3 showed how much more is achievable with robust behavior-change therapy.

In other words, it’s time that PCPs provide education on behavior change to maximize the power of the medications prescribed in practice for the most common diseases suffered in the United States: obesity, type 2 diabetes, cardiovascular disease, and hypertension. These are all chronic, relapsing diseases. Medication alone will improve numbers (weight, blood glucose, A1c, and blood pressure), but a relapsing disease continues relentlessly as patients age to overcome the medications prescribed.

Today I made another patient feel bad because she lost over 100 pounds on semaglutide (Wegovy) 2.4 mg over 1 year, reducing her BMI from 57 to 36. She wanted to keep losing, so I recommended sleeve gastrectomy to lose more weight. I told her she could always restart the Wegovy after the procedure if needed.

We really don’t have an answer to this issue of NuSH therapy not getting to goal and bariatric surgery following medication therapy. The reality is that bariatric surgery should be considered a safe, effective treatment for extreme obesity somewhere along the trajectory of treatments starting with behavior (diet, exercise) and medications. It is still considered a last resort, and for some, just too aggressive.

We have learned much about the incretin hormones and what they can accomplish for obesity from studying bariatric — now called metabolic — surgery. Surgery should be seen as we see stent placement for angina, only more effective for longevity. The COURAGE trial, published in 2007 in NEJM, showed that when compared with medication treatment alone for angina, stent placement plus medications resulted in no difference in mortality after a 7-year follow-up period. Compare this to bariatric surgery, which in many retrospective analyses shows a 20% reduction in cardiovascular mortality after 20-year follow-up (Swedish Obesity Study). In the United States, there are 2 million stent procedures performed per year vs 250,000 bariatric surgical procedures. There are millions of Americans with a BMI > 40 and, yes, millions of Americans with angina. I think I make my point that we need to do more bariatric surgeries to effectively treat extreme obesity.

The solution to this negligent medical practice in obesity treatment is to empower PCPs to treat obesity (at least uncomplicated obesity) and refer to obesity medicine practices for complicated obesity with multiple complications, such as type 2 diabetes and cardiovascular disease, and to refer to obesity medicine practices with a surgical component for BMIs > 40 or > 35 with type 2 diabetes, sleep apnea, and/or cardiovascular disease or other serious conditions.

How do we empower PCPs? Insurance coverage of NuSH therapies due to life-saving properties — as evidenced by the SELECT trial — without prior authorizations; and education on how and why metabolic surgery works, as well as education on behavioral approaches, such as healthy diet and exercise, as a core therapy for all BMI categories.

It’s time.

Caroline Apovian, MD, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Altimmune; Cowen and Company; Currax Pharmaceuticals; EPG Communication Holdings; Gelesis, Srl; L-Nutra; and NeuroBo Pharmaceuticals. Received research grant from: National Institutes of Health; Patient-Centered Outcomes Research Institute; and GI Dynamics. Received income in an amount equal to or greater than $250 from: Altimmune; Cowen and Company; NeuroBo Pharmaceuticals; and Novo Nordisk.

A version of this article appeared on Medscape.com.

A few weeks ago, I made a patient who lost 100 pounds following a sleeve gastrectomy 9 months prior feel bad because I told her she lost too much weight. As I spoke to her, I realized that she found it hard to make life changes and that the surgery was a huge aide in changing her life and her lifestyle. I ended up apologizing for initially saying she lost too much weight.

For the first time in her life, she was successful in losing weight and keeping it off. The surgery allowed her body to defend a lower body weight by altering the secretion of gut hormones that lead to satiety in the brain. It’s not her fault that her body responded so well!

I asked her to be on my next orientation virtual meeting with prospective weight management patients to urge those with a body mass index (BMI) > 40 to consider bariatric surgery as the most effective durable and safe treatment for their degree of obesity.

Metabolic bariatric surgery, primarily sleeve gastrectomy and Roux-en-Y gastric bypass , alters the gut hormone milieu such that the body defends a lower mass of adipose tissue and a lower weight. We have learned what it takes to alter body weight defense to a healthy lower weight by studying why metabolic bariatric surgery works so well. It turns out that there are several hormones secreted by the gut that allow the brain to register fullness.

One of these gut hormones, glucagon-like peptide (GLP)-1, has been researched as an analog to help reduce body weight by 16% and has also been shown to reduce cardiovascular risk in the SELECT trial, as published in The New England Journal of Medicine (NEJM).

It’s the first weight loss medication to be shown in a cardiovascular outcomes trial to be superior to placebo in reduction of major cardiovascular events, including cardiovascular deaths, nonfatal myocardial infarction, and nonfatal stroke. The results presented at the 2023 American Heart Association meetings in Philadelphia ended in wholehearted applause by a “standing only” audience even before the presentation’s conclusion.

As we pave the way for nutrient-stimulated hormone (NuSH) therapies to be prescribed to all Americans with a BMI > 30 to improve health, we need to remember what these medications actually do. We used to think that metabolic bariatric surgery worked by restricting the stomach contents and malabsorbing nutrients. We now know that the surgeries work by altering NuSH secretion, allowing for less secretion of the hunger hormone ghrelin and more secretion of GLP-1, glucose-dependent insulinotropic polypeptide (GIP), peptide YY (PYY), cholecystokinin (CCK), oxyntomodulin (OXM), and other satiety hormones with less food ingestion.

They have pleiotropic effects on many organ systems in the body, including the brain, heart, adipose tissue, and liver. They decrease inflammation and also increase satiety and delay gastric emptying. None of these effects automatically produce weight loss, but they certainly aid in the adoption of a healthier body weight and better health. The weight loss occurs because these medications steer the body toward behavioral changes that promote weight loss.

As we delve into the SELECT trial results, a 20% reduction in major cardiovascular events was accompanied by an average weight loss of 9.6%, without a behavioral component added to either the placebo or intervention arms, as is usual in antiobesity agent trials.

Does this mean that primary care providers (PCPs) don’t have to educate patients on behavior change, diet, and exercise therapy? Well, if we consider obesity a disease as we do type 2 diabetes and dyslipidemia or hypertension, then no — PCPs don’t have to, just like they don’t in treating these other diseases.

However, we should rethink this practice. The recently published SURMOUNT-3 trial looked at another NuSH, tirzepatide, with intensive behavioral therapy; it resulted in a 26.6% weight loss, which is comparable to results with bariatric surgery. The SURMOUNT-1 trial of tirzepatide with nonintensive behavioral therapy resulted in a 20.9% weight loss, which is still substantial, but SURMOUNT-3 showed how much more is achievable with robust behavior-change therapy.

In other words, it’s time that PCPs provide education on behavior change to maximize the power of the medications prescribed in practice for the most common diseases suffered in the United States: obesity, type 2 diabetes, cardiovascular disease, and hypertension. These are all chronic, relapsing diseases. Medication alone will improve numbers (weight, blood glucose, A1c, and blood pressure), but a relapsing disease continues relentlessly as patients age to overcome the medications prescribed.

Today I made another patient feel bad because she lost over 100 pounds on semaglutide (Wegovy) 2.4 mg over 1 year, reducing her BMI from 57 to 36. She wanted to keep losing, so I recommended sleeve gastrectomy to lose more weight. I told her she could always restart the Wegovy after the procedure if needed.

We really don’t have an answer to this issue of NuSH therapy not getting to goal and bariatric surgery following medication therapy. The reality is that bariatric surgery should be considered a safe, effective treatment for extreme obesity somewhere along the trajectory of treatments starting with behavior (diet, exercise) and medications. It is still considered a last resort, and for some, just too aggressive.

We have learned much about the incretin hormones and what they can accomplish for obesity from studying bariatric — now called metabolic — surgery. Surgery should be seen as we see stent placement for angina, only more effective for longevity. The COURAGE trial, published in 2007 in NEJM, showed that when compared with medication treatment alone for angina, stent placement plus medications resulted in no difference in mortality after a 7-year follow-up period. Compare this to bariatric surgery, which in many retrospective analyses shows a 20% reduction in cardiovascular mortality after 20-year follow-up (Swedish Obesity Study). In the United States, there are 2 million stent procedures performed per year vs 250,000 bariatric surgical procedures. There are millions of Americans with a BMI > 40 and, yes, millions of Americans with angina. I think I make my point that we need to do more bariatric surgeries to effectively treat extreme obesity.

The solution to this negligent medical practice in obesity treatment is to empower PCPs to treat obesity (at least uncomplicated obesity) and refer to obesity medicine practices for complicated obesity with multiple complications, such as type 2 diabetes and cardiovascular disease, and to refer to obesity medicine practices with a surgical component for BMIs > 40 or > 35 with type 2 diabetes, sleep apnea, and/or cardiovascular disease or other serious conditions.

How do we empower PCPs? Insurance coverage of NuSH therapies due to life-saving properties — as evidenced by the SELECT trial — without prior authorizations; and education on how and why metabolic surgery works, as well as education on behavioral approaches, such as healthy diet and exercise, as a core therapy for all BMI categories.

It’s time.

Caroline Apovian, MD, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Altimmune; Cowen and Company; Currax Pharmaceuticals; EPG Communication Holdings; Gelesis, Srl; L-Nutra; and NeuroBo Pharmaceuticals. Received research grant from: National Institutes of Health; Patient-Centered Outcomes Research Institute; and GI Dynamics. Received income in an amount equal to or greater than $250 from: Altimmune; Cowen and Company; NeuroBo Pharmaceuticals; and Novo Nordisk.

A version of this article appeared on Medscape.com.

Iloperidone, a second-generation antipsychotic used to treat schizophrenia, appears to be safe and effective in the treatment of bipolar mania, new research suggested.

Results of the phase 3 randomized double-blind placebo-controlled trial show patients with bipolar mania who received iloperidone had significantly greater change from baseline to 4 weeks on the Young Mania Rating Scale (YMRS) compared with placebo, an improvement detected as early as 14 days from the initial dose.

The incidence of akathisia and extrapyramidal symptoms (EPS) was low in the treatment group, and the medication was well-tolerated.

“This study provides evidence that iloperidone improves the symptoms of bipolar mania in adults and can be a useful treatment option for people with bipolar disorder,” the investigators, led by Rosarelis Torres, PhD, of Vanda Pharmaceuticals, and colleagues wrote.

The study was published online in the Journal of Clinical Psychiatry.
 

Early Improvement

Iloperidone was first approved by the US Food and Drug Administration in 2009 for treatment of schizophrenia.

The current study included 414 participants (mean age, 43 years; 56% male) across 17 US and international sites. Patients with psychotic features received a fixed daily dose of 24 mg of iloperidone (n = 206) or placebo (n = 208).

Participants completed a screening period of up to 7 days before randomization, followed by a 1-day baseline evaluation period and a 28-day treatment phase.

The primary efficacy endpoint was change from baseline to week 4 on the YMRS (vs placebo), while secondary efficacy endpoints included change from baseline on the Clinical Global Impressions-Severity and Clinical Global Impression of Change scales (CGI-S and CGI-C, respectively).

Compared with placebo, iloperidone was associated with significant improvement of mania symptoms at week 4, with a mean reduction on the YMRS scale of −4.0 (P = .000008), and significant decreases on the CGI-S (mean, −0.4; P = .0005) and CGI-C scales (mean, −0.5; P = .0002).

Statistically significant differences between iloperidone and placebo were observed as early as day 14 and continued through days 21 and 28.

Post hoc analyses found no difference in efficacy even when patients who had received benzodiazepines were excluded, regardless of the presence or absence of psychotic features at baseline.
 

Favorable Akathisia Profile

As for safety, 68% of patients in the iloperidone group experienced at least one adverse event, compared with 49% of patients in the placebo group.

Patients in the treatment group had a higher rate of withdrawal from the study than those in the placebo group (32.9% vs 27.1%), and more patients in the iloperidone group experienced treatment-emergent adverse events (TEAEs) leading to study drug discontinuation (8.7% vs 5.3%). However, no TEAEs associated with discontinuation occurred in more than two patients in either group, and none of the participants experienced any AE leading to death.

The most common adverse events (AEs) were tachycardia (18%), dizziness (11%), dry mouth (9%), increased alanine aminotransferase (7%), nasal congestion (6%), weight gain (6%), and somnolence (5%).

Five serious AEs were reported in four participants in the treatment group and one in the placebo group. Two were identified as related to the study medication. These included sedation and spontaneous penile erection.

Changes from baseline in clinical laboratory parameters were not largely different between the groups, but there were post-randomization changes in QT interval in three iloperidone patients. The incidence of orthostatic response was also higher for iloperidone vs placebo.

Although “much improved compared to early antipsychotics, SGAs can still cause considerable adverse motor side effects,” the authors wrote. “However, among all SGAs, iloperidone’s akathisia profile is favorable.”

Antipsychotic-induced akathisia has been reported more frequently in patients with bipolar disorder than in those with schizophrenia treated with the same medication, investigators noted.

One study limitation is the fact that long-term efficacy in the prevention of manic or depressive episodes was not assessed.
 

Potential Second-Line Treatment

Commenting on the study, Richard Louis Price, MD, assistant professor of psychiatry, at Weill Cornell Medical College, New York City, said the findings suggest iloperidone may be “modestly effective” for patients with bipolar 1 mania or mixed episodes.

“It’s helpful to have new treatment options, especially for patients who have difficulty tolerating other agents,” said Dr. Price, who was not involved with the study.

Also commenting on the research, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, noted iloperidone’s “interesting antipsychotic pharmacodynamic,” highlighting the drug’s high-binding affinity for serotonin 5HT_2A and dopamine D₂ and D₃ receptors, as well as the noradrenergic α₁ receptors.

The drug’s profile “suggests benefit in manic features and agitation, perhaps with a lower propensity to EPS, which is especially important in persons at higher risk, like persons living with bipolar disorder,” Dr. McIntyre said.

Dr. McIntyre, who was not involved with the study, added iloperidone could be a second-line therapy because of its tolerability profile, provided the study results can be replicated.

“When considering alternatives with similar efficacy, absence of titration (or simple titration) minimal to no weight gain, no orthostatic hypotension, and no potential concerns with QT, those alternatives would have to be considered first-line, assuming that the study results are replicated,” he said.

This study was funded by Vanda Pharmaceuticals. The authors’ disclosures are listed in the original paper. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine Biosciences, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies Inc., NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. McIntyre is the CEO of Braxia Scientific Corp. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus.

A version of this article appeared on Medscape.com.

Iloperidone, a second-generation antipsychotic used to treat schizophrenia, appears to be safe and effective in the treatment of bipolar mania, new research suggested.

Results of the phase 3 randomized double-blind placebo-controlled trial show patients with bipolar mania who received iloperidone had significantly greater change from baseline to 4 weeks on the Young Mania Rating Scale (YMRS) compared with placebo, an improvement detected as early as 14 days from the initial dose.

The incidence of akathisia and extrapyramidal symptoms (EPS) was low in the treatment group, and the medication was well-tolerated.

“This study provides evidence that iloperidone improves the symptoms of bipolar mania in adults and can be a useful treatment option for people with bipolar disorder,” the investigators, led by Rosarelis Torres, PhD, of Vanda Pharmaceuticals, and colleagues wrote.

The study was published online in the Journal of Clinical Psychiatry.
 

Early Improvement

Iloperidone was first approved by the US Food and Drug Administration in 2009 for treatment of schizophrenia.

The current study included 414 participants (mean age, 43 years; 56% male) across 17 US and international sites. Patients with psychotic features received a fixed daily dose of 24 mg of iloperidone (n = 206) or placebo (n = 208).

Participants completed a screening period of up to 7 days before randomization, followed by a 1-day baseline evaluation period and a 28-day treatment phase.

The primary efficacy endpoint was change from baseline to week 4 on the YMRS (vs placebo), while secondary efficacy endpoints included change from baseline on the Clinical Global Impressions-Severity and Clinical Global Impression of Change scales (CGI-S and CGI-C, respectively).

Compared with placebo, iloperidone was associated with significant improvement of mania symptoms at week 4, with a mean reduction on the YMRS scale of −4.0 (P = .000008), and significant decreases on the CGI-S (mean, −0.4; P = .0005) and CGI-C scales (mean, −0.5; P = .0002).

Statistically significant differences between iloperidone and placebo were observed as early as day 14 and continued through days 21 and 28.

Post hoc analyses found no difference in efficacy even when patients who had received benzodiazepines were excluded, regardless of the presence or absence of psychotic features at baseline.
 

Favorable Akathisia Profile

As for safety, 68% of patients in the iloperidone group experienced at least one adverse event, compared with 49% of patients in the placebo group.

Patients in the treatment group had a higher rate of withdrawal from the study than those in the placebo group (32.9% vs 27.1%), and more patients in the iloperidone group experienced treatment-emergent adverse events (TEAEs) leading to study drug discontinuation (8.7% vs 5.3%). However, no TEAEs associated with discontinuation occurred in more than two patients in either group, and none of the participants experienced any AE leading to death.

The most common adverse events (AEs) were tachycardia (18%), dizziness (11%), dry mouth (9%), increased alanine aminotransferase (7%), nasal congestion (6%), weight gain (6%), and somnolence (5%).

Five serious AEs were reported in four participants in the treatment group and one in the placebo group. Two were identified as related to the study medication. These included sedation and spontaneous penile erection.

Changes from baseline in clinical laboratory parameters were not largely different between the groups, but there were post-randomization changes in QT interval in three iloperidone patients. The incidence of orthostatic response was also higher for iloperidone vs placebo.

Although “much improved compared to early antipsychotics, SGAs can still cause considerable adverse motor side effects,” the authors wrote. “However, among all SGAs, iloperidone’s akathisia profile is favorable.”

Antipsychotic-induced akathisia has been reported more frequently in patients with bipolar disorder than in those with schizophrenia treated with the same medication, investigators noted.

One study limitation is the fact that long-term efficacy in the prevention of manic or depressive episodes was not assessed.
 

Potential Second-Line Treatment

Commenting on the study, Richard Louis Price, MD, assistant professor of psychiatry, at Weill Cornell Medical College, New York City, said the findings suggest iloperidone may be “modestly effective” for patients with bipolar 1 mania or mixed episodes.

“It’s helpful to have new treatment options, especially for patients who have difficulty tolerating other agents,” said Dr. Price, who was not involved with the study.

Also commenting on the research, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, noted iloperidone’s “interesting antipsychotic pharmacodynamic,” highlighting the drug’s high-binding affinity for serotonin 5HT_2A and dopamine D₂ and D₃ receptors, as well as the noradrenergic α₁ receptors.

The drug’s profile “suggests benefit in manic features and agitation, perhaps with a lower propensity to EPS, which is especially important in persons at higher risk, like persons living with bipolar disorder,” Dr. McIntyre said.

Dr. McIntyre, who was not involved with the study, added iloperidone could be a second-line therapy because of its tolerability profile, provided the study results can be replicated.

“When considering alternatives with similar efficacy, absence of titration (or simple titration) minimal to no weight gain, no orthostatic hypotension, and no potential concerns with QT, those alternatives would have to be considered first-line, assuming that the study results are replicated,” he said.

This study was funded by Vanda Pharmaceuticals. The authors’ disclosures are listed in the original paper. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine Biosciences, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies Inc., NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. McIntyre is the CEO of Braxia Scientific Corp. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus.

A version of this article appeared on Medscape.com.

Iloperidone, a second-generation antipsychotic used to treat schizophrenia, appears to be safe and effective in the treatment of bipolar mania, new research suggested.

Results of the phase 3 randomized double-blind placebo-controlled trial show patients with bipolar mania who received iloperidone had significantly greater change from baseline to 4 weeks on the Young Mania Rating Scale (YMRS) compared with placebo, an improvement detected as early as 14 days from the initial dose.

The incidence of akathisia and extrapyramidal symptoms (EPS) was low in the treatment group, and the medication was well-tolerated.

“This study provides evidence that iloperidone improves the symptoms of bipolar mania in adults and can be a useful treatment option for people with bipolar disorder,” the investigators, led by Rosarelis Torres, PhD, of Vanda Pharmaceuticals, and colleagues wrote.

The study was published online in the Journal of Clinical Psychiatry.
 

Early Improvement

Iloperidone was first approved by the US Food and Drug Administration in 2009 for treatment of schizophrenia.

The current study included 414 participants (mean age, 43 years; 56% male) across 17 US and international sites. Patients with psychotic features received a fixed daily dose of 24 mg of iloperidone (n = 206) or placebo (n = 208).

Participants completed a screening period of up to 7 days before randomization, followed by a 1-day baseline evaluation period and a 28-day treatment phase.

The primary efficacy endpoint was change from baseline to week 4 on the YMRS (vs placebo), while secondary efficacy endpoints included change from baseline on the Clinical Global Impressions-Severity and Clinical Global Impression of Change scales (CGI-S and CGI-C, respectively).

Compared with placebo, iloperidone was associated with significant improvement of mania symptoms at week 4, with a mean reduction on the YMRS scale of −4.0 (P = .000008), and significant decreases on the CGI-S (mean, −0.4; P = .0005) and CGI-C scales (mean, −0.5; P = .0002).

Statistically significant differences between iloperidone and placebo were observed as early as day 14 and continued through days 21 and 28.

Post hoc analyses found no difference in efficacy even when patients who had received benzodiazepines were excluded, regardless of the presence or absence of psychotic features at baseline.
 

Favorable Akathisia Profile

As for safety, 68% of patients in the iloperidone group experienced at least one adverse event, compared with 49% of patients in the placebo group.

Patients in the treatment group had a higher rate of withdrawal from the study than those in the placebo group (32.9% vs 27.1%), and more patients in the iloperidone group experienced treatment-emergent adverse events (TEAEs) leading to study drug discontinuation (8.7% vs 5.3%). However, no TEAEs associated with discontinuation occurred in more than two patients in either group, and none of the participants experienced any AE leading to death.

The most common adverse events (AEs) were tachycardia (18%), dizziness (11%), dry mouth (9%), increased alanine aminotransferase (7%), nasal congestion (6%), weight gain (6%), and somnolence (5%).

Five serious AEs were reported in four participants in the treatment group and one in the placebo group. Two were identified as related to the study medication. These included sedation and spontaneous penile erection.

Changes from baseline in clinical laboratory parameters were not largely different between the groups, but there were post-randomization changes in QT interval in three iloperidone patients. The incidence of orthostatic response was also higher for iloperidone vs placebo.

Although “much improved compared to early antipsychotics, SGAs can still cause considerable adverse motor side effects,” the authors wrote. “However, among all SGAs, iloperidone’s akathisia profile is favorable.”

Antipsychotic-induced akathisia has been reported more frequently in patients with bipolar disorder than in those with schizophrenia treated with the same medication, investigators noted.

One study limitation is the fact that long-term efficacy in the prevention of manic or depressive episodes was not assessed.
 

Potential Second-Line Treatment

Commenting on the study, Richard Louis Price, MD, assistant professor of psychiatry, at Weill Cornell Medical College, New York City, said the findings suggest iloperidone may be “modestly effective” for patients with bipolar 1 mania or mixed episodes.

“It’s helpful to have new treatment options, especially for patients who have difficulty tolerating other agents,” said Dr. Price, who was not involved with the study.

Also commenting on the research, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, noted iloperidone’s “interesting antipsychotic pharmacodynamic,” highlighting the drug’s high-binding affinity for serotonin 5HT_2A and dopamine D₂ and D₃ receptors, as well as the noradrenergic α₁ receptors.

The drug’s profile “suggests benefit in manic features and agitation, perhaps with a lower propensity to EPS, which is especially important in persons at higher risk, like persons living with bipolar disorder,” Dr. McIntyre said.

Dr. McIntyre, who was not involved with the study, added iloperidone could be a second-line therapy because of its tolerability profile, provided the study results can be replicated.

“When considering alternatives with similar efficacy, absence of titration (or simple titration) minimal to no weight gain, no orthostatic hypotension, and no potential concerns with QT, those alternatives would have to be considered first-line, assuming that the study results are replicated,” he said.

This study was funded by Vanda Pharmaceuticals. The authors’ disclosures are listed in the original paper. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine Biosciences, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies Inc., NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. McIntyre is the CEO of Braxia Scientific Corp. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus.

A version of this article appeared on Medscape.com.

A former colleague once told me that there are few primary care procedures more satisfying for the patient and physician than removing part of an ingrown toenail. I disagree, but I performed this procedure quite a few times during my residency and first few years in practice. The patient would usually have been in pain for days to weeks and have tried soaking their foot or putting wisps of cotton under the ingrown nail edge, without relief. I would draw up a syringe of lidocaine with epinephrine and perform a digital block on the affected toe. After waiting 5-10 minutes for the toe to become numb, I would clean the area, use a nail elevator to push the cuticle off the nail plate, and lift up the lateral edge of the plate. I would then cut the lateral edge with a nail splitter and remove the cut nail fragment with a hemostat. Finally, after an inspection to make sure that I hadn›t left any pieces behind, I or my nurse would apply petrolatum gauze and a bandage.

I don’t do toenails anymore. Because this procedure was requested every several weeks at most, the offices where I worked weren’t organized to make it easy to do; sometimes my medical assistants didn’t know what supplies were needed or where to find them. Adding up the time it took to obtain consent, wait for the local anesthetic to take effect, and do the procedure, it was more efficient for me to see two or three patients for medication checkups and refer toenail problems to a podiatrist instead. The same thing happened with circumcisions on infants who, for whatever reason, hadn›t had them done in the hospital. After a few years of doing these, I decided it would be easier to send these patients to pediatric urologists.

My choice to reduce my scope of practice during the early part of my career mirrored a national trend among graduating family medicine residents. I value the joint injections, laceration repairs, biopsies, and other skin procedures that remain in my repertoire for the change of pace and saving my patients more costly visits to specialists with long waiting lists. In fact, a previous study showed that family physicians who provide more comprehensive care generate lower healthcare spending and fewer hospitalizations than those with a narrower scope of practice.

A recent evaluation of Comprehensive Primary Care Plus, one of several alternative payment models that the Centers for Medicare & Medicaid Services has piloted over the past decade, found that it modestly reduced emergency department visits and inpatient costs but didn’t save money after accounting for additional dollars going to primary care. However, when researchers looked at six specific services — immunizations, behavioral counseling, laceration management, skin lesion removal, joint or tendon injections, and point-of-care ultrasound — they found that patients who saw physicians who provided more of these had lower care costs and sought less acute care outside of the office. On average, independent-practice physicians provided more services than physicians who practiced at sites affiliated with hospitals or health systems. That makes sense: While health systems bring in more income for procedures performed in their operating rooms and subspecialists› offices, private practices do better by keeping services in-house.

Supporting physicians in maintaining the broadest possible scope of practice is, in my opinion, the missing piece in the federal government’s initiatives to strengthen primary care. Investing in primary care training programs and paying practices for care coordination are necessary but insufficient steps if family physicians are expected to improve population health and bend the cost curve.

Dr. Lin is Associate Director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

A former colleague once told me that there are few primary care procedures more satisfying for the patient and physician than removing part of an ingrown toenail. I disagree, but I performed this procedure quite a few times during my residency and first few years in practice. The patient would usually have been in pain for days to weeks and have tried soaking their foot or putting wisps of cotton under the ingrown nail edge, without relief. I would draw up a syringe of lidocaine with epinephrine and perform a digital block on the affected toe. After waiting 5-10 minutes for the toe to become numb, I would clean the area, use a nail elevator to push the cuticle off the nail plate, and lift up the lateral edge of the plate. I would then cut the lateral edge with a nail splitter and remove the cut nail fragment with a hemostat. Finally, after an inspection to make sure that I hadn›t left any pieces behind, I or my nurse would apply petrolatum gauze and a bandage.

I don’t do toenails anymore. Because this procedure was requested every several weeks at most, the offices where I worked weren’t organized to make it easy to do; sometimes my medical assistants didn’t know what supplies were needed or where to find them. Adding up the time it took to obtain consent, wait for the local anesthetic to take effect, and do the procedure, it was more efficient for me to see two or three patients for medication checkups and refer toenail problems to a podiatrist instead. The same thing happened with circumcisions on infants who, for whatever reason, hadn›t had them done in the hospital. After a few years of doing these, I decided it would be easier to send these patients to pediatric urologists.

My choice to reduce my scope of practice during the early part of my career mirrored a national trend among graduating family medicine residents. I value the joint injections, laceration repairs, biopsies, and other skin procedures that remain in my repertoire for the change of pace and saving my patients more costly visits to specialists with long waiting lists. In fact, a previous study showed that family physicians who provide more comprehensive care generate lower healthcare spending and fewer hospitalizations than those with a narrower scope of practice.

A recent evaluation of Comprehensive Primary Care Plus, one of several alternative payment models that the Centers for Medicare & Medicaid Services has piloted over the past decade, found that it modestly reduced emergency department visits and inpatient costs but didn’t save money after accounting for additional dollars going to primary care. However, when researchers looked at six specific services — immunizations, behavioral counseling, laceration management, skin lesion removal, joint or tendon injections, and point-of-care ultrasound — they found that patients who saw physicians who provided more of these had lower care costs and sought less acute care outside of the office. On average, independent-practice physicians provided more services than physicians who practiced at sites affiliated with hospitals or health systems. That makes sense: While health systems bring in more income for procedures performed in their operating rooms and subspecialists› offices, private practices do better by keeping services in-house.

Supporting physicians in maintaining the broadest possible scope of practice is, in my opinion, the missing piece in the federal government’s initiatives to strengthen primary care. Investing in primary care training programs and paying practices for care coordination are necessary but insufficient steps if family physicians are expected to improve population health and bend the cost curve.

Dr. Lin is Associate Director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

A former colleague once told me that there are few primary care procedures more satisfying for the patient and physician than removing part of an ingrown toenail. I disagree, but I performed this procedure quite a few times during my residency and first few years in practice. The patient would usually have been in pain for days to weeks and have tried soaking their foot or putting wisps of cotton under the ingrown nail edge, without relief. I would draw up a syringe of lidocaine with epinephrine and perform a digital block on the affected toe. After waiting 5-10 minutes for the toe to become numb, I would clean the area, use a nail elevator to push the cuticle off the nail plate, and lift up the lateral edge of the plate. I would then cut the lateral edge with a nail splitter and remove the cut nail fragment with a hemostat. Finally, after an inspection to make sure that I hadn›t left any pieces behind, I or my nurse would apply petrolatum gauze and a bandage.

I don’t do toenails anymore. Because this procedure was requested every several weeks at most, the offices where I worked weren’t organized to make it easy to do; sometimes my medical assistants didn’t know what supplies were needed or where to find them. Adding up the time it took to obtain consent, wait for the local anesthetic to take effect, and do the procedure, it was more efficient for me to see two or three patients for medication checkups and refer toenail problems to a podiatrist instead. The same thing happened with circumcisions on infants who, for whatever reason, hadn›t had them done in the hospital. After a few years of doing these, I decided it would be easier to send these patients to pediatric urologists.

My choice to reduce my scope of practice during the early part of my career mirrored a national trend among graduating family medicine residents. I value the joint injections, laceration repairs, biopsies, and other skin procedures that remain in my repertoire for the change of pace and saving my patients more costly visits to specialists with long waiting lists. In fact, a previous study showed that family physicians who provide more comprehensive care generate lower healthcare spending and fewer hospitalizations than those with a narrower scope of practice.

A recent evaluation of Comprehensive Primary Care Plus, one of several alternative payment models that the Centers for Medicare & Medicaid Services has piloted over the past decade, found that it modestly reduced emergency department visits and inpatient costs but didn’t save money after accounting for additional dollars going to primary care. However, when researchers looked at six specific services — immunizations, behavioral counseling, laceration management, skin lesion removal, joint or tendon injections, and point-of-care ultrasound — they found that patients who saw physicians who provided more of these had lower care costs and sought less acute care outside of the office. On average, independent-practice physicians provided more services than physicians who practiced at sites affiliated with hospitals or health systems. That makes sense: While health systems bring in more income for procedures performed in their operating rooms and subspecialists› offices, private practices do better by keeping services in-house.

Supporting physicians in maintaining the broadest possible scope of practice is, in my opinion, the missing piece in the federal government’s initiatives to strengthen primary care. Investing in primary care training programs and paying practices for care coordination are necessary but insufficient steps if family physicians are expected to improve population health and bend the cost curve.

Dr. Lin is Associate Director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.