Pulmonary Vascular Disease Section

Restoration of RV function in PAH: Is it the holy grail to improve mortality and long-term outcomes?

Pulmonary arterial hypertension (PAH) remains an incurable disease, and clinical progression is inevitable. Despite several therapeutic advances, PAH continues to be associated with high mortality. Even mild increases in mean pulmonary arterial pressure (mPAP) have been shown to directly impact outcomes (Maron BA, et al. Circulation. 2016 Mar 29;133[13]:1240), leading to a change in the hemodynamic definition of PAH (mPAP > 20 mm Hg) at the 2018 World Symposium on Pulmonary Hypertension (WSPH) (Galiè N, et al. Eur Respir J. 2019;53[1]:1801889). The WSPH also recommended a more aggressive and proactive approach to move patients to “low-risk” status.

Elevated mPAP results in increased RV afterload with subsequent RV dysfunction and consequent abnormal remodeling, which is associated with poor outcomes. Reversal of RV remodeling has been demonstrated in patients after PEA for CTEPH and/or lung transplantation for PAH (D’Armini AM, et al. J Thorac Cardiovasc Surg. 2007;133:162).

Vijay Balasubramanian, MD, FCCP, Chair
Jean M. Elwing, MD, FCCP, Ex-Officio

Pulmonary Vascular Disease Section

Restoration of RV function in PAH: Is it the holy grail to improve mortality and long-term outcomes?

Pulmonary arterial hypertension (PAH) remains an incurable disease, and clinical progression is inevitable. Despite several therapeutic advances, PAH continues to be associated with high mortality. Even mild increases in mean pulmonary arterial pressure (mPAP) have been shown to directly impact outcomes (Maron BA, et al. Circulation. 2016 Mar 29;133[13]:1240), leading to a change in the hemodynamic definition of PAH (mPAP > 20 mm Hg) at the 2018 World Symposium on Pulmonary Hypertension (WSPH) (Galiè N, et al. Eur Respir J. 2019;53[1]:1801889). The WSPH also recommended a more aggressive and proactive approach to move patients to “low-risk” status.

Elevated mPAP results in increased RV afterload with subsequent RV dysfunction and consequent abnormal remodeling, which is associated with poor outcomes. Reversal of RV remodeling has been demonstrated in patients after PEA for CTEPH and/or lung transplantation for PAH (D’Armini AM, et al. J Thorac Cardiovasc Surg. 2007;133:162).

Vijay Balasubramanian, MD, FCCP, Chair
Jean M. Elwing, MD, FCCP, Ex-Officio

Pulmonary Vascular Disease Section

Restoration of RV function in PAH: Is it the holy grail to improve mortality and long-term outcomes?

Pulmonary arterial hypertension (PAH) remains an incurable disease, and clinical progression is inevitable. Despite several therapeutic advances, PAH continues to be associated with high mortality. Even mild increases in mean pulmonary arterial pressure (mPAP) have been shown to directly impact outcomes (Maron BA, et al. Circulation. 2016 Mar 29;133[13]:1240), leading to a change in the hemodynamic definition of PAH (mPAP > 20 mm Hg) at the 2018 World Symposium on Pulmonary Hypertension (WSPH) (Galiè N, et al. Eur Respir J. 2019;53[1]:1801889). The WSPH also recommended a more aggressive and proactive approach to move patients to “low-risk” status.

Elevated mPAP results in increased RV afterload with subsequent RV dysfunction and consequent abnormal remodeling, which is associated with poor outcomes. Reversal of RV remodeling has been demonstrated in patients after PEA for CTEPH and/or lung transplantation for PAH (D’Armini AM, et al. J Thorac Cardiovasc Surg. 2007;133:162).

Vijay Balasubramanian, MD, FCCP, Chair
Jean M. Elwing, MD, FCCP, Ex-Officio

Interventional Procedures Section

Role of EBUS for staging and prognostication in patients with lung cancer

Lung cancer is the leading cause of cancer-related deaths worldwide and forms of a large burden of cancer-related mortality in the United States. With the rapid advent of new disease-directed therapy, including molecular and targeted therapies, the outlook for management of lung cancer has changed dramatically over the last decade. The choice of therapy, as well as prognosis, is dependent on the stage at diagnosis. It is thus imperative that we accurately differentiate between stages I, II, and III disease by assessment of hilar and mediastinal lymph nodes.

Traditionally, CT and PET/CT scans have been the mainstay to assess stage, with patients with abnormal lymph nodes or high risk of nodal metastasis (≥ T2 disease or “central” location) undergoing invasive mediastinal evaluation (Silvestri, et al. Chest. 2013 May;143(5 Suppl):e211S). The decision to perform invasive mediastinal staging for T1 tumors remains a matter of discussion. DuComb and colleagues, in their study demonstrated a high rate of N2 metastasis (8.1%) even amongst those with T1 tumors, which was independent of tumor location (DuComb, et al. Chest. 2020 Nov;158[5]:2192). This rate is consistent with previous reported rates ranging from 6.9% to 13% of N2 disease in patients with no radiographic evidence of lymph node metastasis (Gonzalez-Stawinski, et al. J Thorac Cardiovasc Surg. 2003 Dec;126[6]:1900; Bao, et al. J Thorac Dis. 2014;6[12]:1697; Shin, et al. Eur Respir J. 2019;53[3]:1801508). The above indicates a possible role of invasive mediastinal staging using EBUS-TBNA in patients with T1 disease to accurately stage the disease prior to curative intent treatment.

Abhinav Agrawal, MD, FCCP, Member-at-Large
Ellen Volker, MD, MSPH, FCCP, Member-at-Large

Interventional Procedures Section

Role of EBUS for staging and prognostication in patients with lung cancer

Lung cancer is the leading cause of cancer-related deaths worldwide and forms of a large burden of cancer-related mortality in the United States. With the rapid advent of new disease-directed therapy, including molecular and targeted therapies, the outlook for management of lung cancer has changed dramatically over the last decade. The choice of therapy, as well as prognosis, is dependent on the stage at diagnosis. It is thus imperative that we accurately differentiate between stages I, II, and III disease by assessment of hilar and mediastinal lymph nodes.

Traditionally, CT and PET/CT scans have been the mainstay to assess stage, with patients with abnormal lymph nodes or high risk of nodal metastasis (≥ T2 disease or “central” location) undergoing invasive mediastinal evaluation (Silvestri, et al. Chest. 2013 May;143(5 Suppl):e211S). The decision to perform invasive mediastinal staging for T1 tumors remains a matter of discussion. DuComb and colleagues, in their study demonstrated a high rate of N2 metastasis (8.1%) even amongst those with T1 tumors, which was independent of tumor location (DuComb, et al. Chest. 2020 Nov;158[5]:2192). This rate is consistent with previous reported rates ranging from 6.9% to 13% of N2 disease in patients with no radiographic evidence of lymph node metastasis (Gonzalez-Stawinski, et al. J Thorac Cardiovasc Surg. 2003 Dec;126[6]:1900; Bao, et al. J Thorac Dis. 2014;6[12]:1697; Shin, et al. Eur Respir J. 2019;53[3]:1801508). The above indicates a possible role of invasive mediastinal staging using EBUS-TBNA in patients with T1 disease to accurately stage the disease prior to curative intent treatment.

Abhinav Agrawal, MD, FCCP, Member-at-Large
Ellen Volker, MD, MSPH, FCCP, Member-at-Large

Interventional Procedures Section

Role of EBUS for staging and prognostication in patients with lung cancer

Lung cancer is the leading cause of cancer-related deaths worldwide and forms of a large burden of cancer-related mortality in the United States. With the rapid advent of new disease-directed therapy, including molecular and targeted therapies, the outlook for management of lung cancer has changed dramatically over the last decade. The choice of therapy, as well as prognosis, is dependent on the stage at diagnosis. It is thus imperative that we accurately differentiate between stages I, II, and III disease by assessment of hilar and mediastinal lymph nodes.

Traditionally, CT and PET/CT scans have been the mainstay to assess stage, with patients with abnormal lymph nodes or high risk of nodal metastasis (≥ T2 disease or “central” location) undergoing invasive mediastinal evaluation (Silvestri, et al. Chest. 2013 May;143(5 Suppl):e211S). The decision to perform invasive mediastinal staging for T1 tumors remains a matter of discussion. DuComb and colleagues, in their study demonstrated a high rate of N2 metastasis (8.1%) even amongst those with T1 tumors, which was independent of tumor location (DuComb, et al. Chest. 2020 Nov;158[5]:2192). This rate is consistent with previous reported rates ranging from 6.9% to 13% of N2 disease in patients with no radiographic evidence of lymph node metastasis (Gonzalez-Stawinski, et al. J Thorac Cardiovasc Surg. 2003 Dec;126[6]:1900; Bao, et al. J Thorac Dis. 2014;6[12]:1697; Shin, et al. Eur Respir J. 2019;53[3]:1801508). The above indicates a possible role of invasive mediastinal staging using EBUS-TBNA in patients with T1 disease to accurately stage the disease prior to curative intent treatment.

Abhinav Agrawal, MD, FCCP, Member-at-Large
Ellen Volker, MD, MSPH, FCCP, Member-at-Large

Patients with rheumatoid arthritis or inflammatory bowel disease (IBD) taking a tumor necrosis factor–alpha inhibitor (TNFi) have about a two-fold higher risk of developing psoriasis, compared with patients receiving conventional treatment, according to a new study published in JAMA Dermatology.

Despite this finding, the authors of the large Danish nationwide cohort study noted that TNFi-induced psoriasis is still a rare adverse event. “Practitioners and patients should be aware and observant of the potential for TNFi-associated psoriasis during TNFi treatment but keep in mind that the absolute risk appears to be low,” David Thein, MB, of the department of dermatology at Bispebjerg Hospital, University of Copenhagen, and colleagues wrote in the study.

They analyzed 109,085 patients with RA and IBD enrolled in Danish national registries between 1995 and 2018 without a previous diagnosis of psoriasis, who received either TNFi (20,910 patients) or conventional treatments (108,024 patients) and were followed for 5 years. They were a mean of 50 years old when they started treatment, 62% were women, with 87.8% of patients in the TNFi group receiving prior conventional therapy and 1% of patients in the conventional therapy group receiving prior TNFi treatment.

The investigators assessed the risk of developing any psoriasis, nonpustular psoriasis, and pustular psoriasis in the two groups using ICD-10 codes as well as a record of two consecutive prescriptions for topical vitamin D analogs.

Overall, 1,471 patients (1.4%) developed psoriasis of any type; 1,332 had non-pustular psoriasis, 127 had palmoplantar pustulosis, and 12 had generalized pustulosis.

The incidence rate of developing any psoriasis was 3.0 per 1,000 patient-years (95% confidence interval, 2.9-3.2) for patients receiving conventional therapy and 7.8 per 1,000 patient-years (95% CI, 7.5-8.9) for patients receiving TNFi treatment. Compared with conventional treatment, the risk of developing nonpustular psoriasis was twofold higher among patients receiving TNFi treatment (hazard ratio, 2.12; 95% CI, 1.87-2.40; P < .001). The risk of developing pustular psoriasis was more than sixfold higher among those on a TNFi (HR, 6.50; 95% CI, 4.60-9.23; P < .001).

Dr. Thein and colleagues estimated that the exposure needed to harm 1 additional patient was 241 patient-years for any psoriasis type, 342 patient-years for nonpustular psoriasis, and 909 patient-years for pustular psoriasis, with an estimated absolute risk difference of 5 per 1,000 patient-years.
 

Best evidence to date on risk

Asked to comment on the study findings, Anthony Fernandez, MD, PhD, director of medical dermatology at the Cleveland Clinic, said that he applauded the researchers for performing this well-designed study to determine the risk of TNF inhibitor–induced psoriasis in patients with RA and IBD.

The strengths of the study include excluding patients with a history of psoriasis to rule out disease recurrence and having a large comparator group of patients with IBD and RA who were taking medications other than TNF inhibitors, while one limitation was the potential accuracy of the ICD-10 codes used as the basis for diagnosing psoriasis. “It’s probably closer to the truth of what the true risk is compared to studies done in the past,” he said in an interview.

Dr. Fernandez noted that the results aren’t likely to change how dermatologists, rheumatologists, or gastroenterologists practice, but the message to stay the course in initially treating TNFi-induced psoriasis also holds value. “We don’t need to change anything in our clinical practice when it comes to TNF-alpha inhibitors.”

For patients with RA or IBD who develop TNFi-induced psoriasis with disease that is well controlled with TNFi treatment, keeping them on that treatment is a priority, Dr. Fernandez explained. “The first and foremost goal is, if the TNF inhibitor is working very well to control the disease that it was prescribed for, then you exhaust your efforts to try to control the psoriasis and allow those patients to stay on the TNF inhibitor.”

In his experience, most patients with RA and IBD who develop TNFi-induced psoriasis are controlled with topical medications. Switching to another TNFi is not recommended, he noted, as patients are “likely to have that reaction with any TNF inhibitor.”

However, Dr. Fernandez said that won’t be an option for all patients with RA and IBD. “In some patients you do simply have to stop the TNF inhibitor” and try an alternative treatment with a different mechanism of action.

The cause of TNFi-induced psoriasis is still not well understood. “There certainly is evidence to support that interferon alpha production by plasmacytoid dendritic cells is playing some role in this phenomenon,” but there is “more to the story” and unanswered questions remain, Dr. Fernandez said.

What’s most interesting about this phenomenon, he added, is that “patients can develop it at any time when exposed to a TNF inhibitor.” For instance, most patients develop drug reactions within 2­-3 weeks of starting a treatment, but TNFi-induced psoriasis can appear after a single dose or several years after initiating treatment.

“Why so few patients, and why is there such variability in terms of how long they’re on the TNF inhibitor before the reaction occurs?” he asked. “That really points to ... some other trigger besides exposure to the TNF inhibitor needed for the initiation of this reaction.”

He noted that it would be valuable to identify triggers – or the most likely triggers – which would be challenging, but could “potentially impact clinical practice.”

The authors reported personal and institutional relationships in the form of personal and institutional research grants, honoraria, personal fees, investigator fees paid to university, consultancies, and speaker’s bureau positions for a variety of pharmaceutical companies, data companies, hospitals, and foundations. Dr. Fernandez reported he has nonbranded speaking, consulting, and research relationships with AbbVie and Novartis; and is a consultant for UCB, Bristol-Myers Squibb, and Boehringer Ingelheim on related products.

Patients with rheumatoid arthritis or inflammatory bowel disease (IBD) taking a tumor necrosis factor–alpha inhibitor (TNFi) have about a two-fold higher risk of developing psoriasis, compared with patients receiving conventional treatment, according to a new study published in JAMA Dermatology.

Despite this finding, the authors of the large Danish nationwide cohort study noted that TNFi-induced psoriasis is still a rare adverse event. “Practitioners and patients should be aware and observant of the potential for TNFi-associated psoriasis during TNFi treatment but keep in mind that the absolute risk appears to be low,” David Thein, MB, of the department of dermatology at Bispebjerg Hospital, University of Copenhagen, and colleagues wrote in the study.

They analyzed 109,085 patients with RA and IBD enrolled in Danish national registries between 1995 and 2018 without a previous diagnosis of psoriasis, who received either TNFi (20,910 patients) or conventional treatments (108,024 patients) and were followed for 5 years. They were a mean of 50 years old when they started treatment, 62% were women, with 87.8% of patients in the TNFi group receiving prior conventional therapy and 1% of patients in the conventional therapy group receiving prior TNFi treatment.

The investigators assessed the risk of developing any psoriasis, nonpustular psoriasis, and pustular psoriasis in the two groups using ICD-10 codes as well as a record of two consecutive prescriptions for topical vitamin D analogs.

Overall, 1,471 patients (1.4%) developed psoriasis of any type; 1,332 had non-pustular psoriasis, 127 had palmoplantar pustulosis, and 12 had generalized pustulosis.

The incidence rate of developing any psoriasis was 3.0 per 1,000 patient-years (95% confidence interval, 2.9-3.2) for patients receiving conventional therapy and 7.8 per 1,000 patient-years (95% CI, 7.5-8.9) for patients receiving TNFi treatment. Compared with conventional treatment, the risk of developing nonpustular psoriasis was twofold higher among patients receiving TNFi treatment (hazard ratio, 2.12; 95% CI, 1.87-2.40; P < .001). The risk of developing pustular psoriasis was more than sixfold higher among those on a TNFi (HR, 6.50; 95% CI, 4.60-9.23; P < .001).

Dr. Thein and colleagues estimated that the exposure needed to harm 1 additional patient was 241 patient-years for any psoriasis type, 342 patient-years for nonpustular psoriasis, and 909 patient-years for pustular psoriasis, with an estimated absolute risk difference of 5 per 1,000 patient-years.
 

Best evidence to date on risk

Asked to comment on the study findings, Anthony Fernandez, MD, PhD, director of medical dermatology at the Cleveland Clinic, said that he applauded the researchers for performing this well-designed study to determine the risk of TNF inhibitor–induced psoriasis in patients with RA and IBD.

The strengths of the study include excluding patients with a history of psoriasis to rule out disease recurrence and having a large comparator group of patients with IBD and RA who were taking medications other than TNF inhibitors, while one limitation was the potential accuracy of the ICD-10 codes used as the basis for diagnosing psoriasis. “It’s probably closer to the truth of what the true risk is compared to studies done in the past,” he said in an interview.

Dr. Fernandez noted that the results aren’t likely to change how dermatologists, rheumatologists, or gastroenterologists practice, but the message to stay the course in initially treating TNFi-induced psoriasis also holds value. “We don’t need to change anything in our clinical practice when it comes to TNF-alpha inhibitors.”

For patients with RA or IBD who develop TNFi-induced psoriasis with disease that is well controlled with TNFi treatment, keeping them on that treatment is a priority, Dr. Fernandez explained. “The first and foremost goal is, if the TNF inhibitor is working very well to control the disease that it was prescribed for, then you exhaust your efforts to try to control the psoriasis and allow those patients to stay on the TNF inhibitor.”

In his experience, most patients with RA and IBD who develop TNFi-induced psoriasis are controlled with topical medications. Switching to another TNFi is not recommended, he noted, as patients are “likely to have that reaction with any TNF inhibitor.”

However, Dr. Fernandez said that won’t be an option for all patients with RA and IBD. “In some patients you do simply have to stop the TNF inhibitor” and try an alternative treatment with a different mechanism of action.

The cause of TNFi-induced psoriasis is still not well understood. “There certainly is evidence to support that interferon alpha production by plasmacytoid dendritic cells is playing some role in this phenomenon,” but there is “more to the story” and unanswered questions remain, Dr. Fernandez said.

What’s most interesting about this phenomenon, he added, is that “patients can develop it at any time when exposed to a TNF inhibitor.” For instance, most patients develop drug reactions within 2­-3 weeks of starting a treatment, but TNFi-induced psoriasis can appear after a single dose or several years after initiating treatment.

“Why so few patients, and why is there such variability in terms of how long they’re on the TNF inhibitor before the reaction occurs?” he asked. “That really points to ... some other trigger besides exposure to the TNF inhibitor needed for the initiation of this reaction.”

He noted that it would be valuable to identify triggers – or the most likely triggers – which would be challenging, but could “potentially impact clinical practice.”

The authors reported personal and institutional relationships in the form of personal and institutional research grants, honoraria, personal fees, investigator fees paid to university, consultancies, and speaker’s bureau positions for a variety of pharmaceutical companies, data companies, hospitals, and foundations. Dr. Fernandez reported he has nonbranded speaking, consulting, and research relationships with AbbVie and Novartis; and is a consultant for UCB, Bristol-Myers Squibb, and Boehringer Ingelheim on related products.

Patients with rheumatoid arthritis or inflammatory bowel disease (IBD) taking a tumor necrosis factor–alpha inhibitor (TNFi) have about a two-fold higher risk of developing psoriasis, compared with patients receiving conventional treatment, according to a new study published in JAMA Dermatology.

Despite this finding, the authors of the large Danish nationwide cohort study noted that TNFi-induced psoriasis is still a rare adverse event. “Practitioners and patients should be aware and observant of the potential for TNFi-associated psoriasis during TNFi treatment but keep in mind that the absolute risk appears to be low,” David Thein, MB, of the department of dermatology at Bispebjerg Hospital, University of Copenhagen, and colleagues wrote in the study.

They analyzed 109,085 patients with RA and IBD enrolled in Danish national registries between 1995 and 2018 without a previous diagnosis of psoriasis, who received either TNFi (20,910 patients) or conventional treatments (108,024 patients) and were followed for 5 years. They were a mean of 50 years old when they started treatment, 62% were women, with 87.8% of patients in the TNFi group receiving prior conventional therapy and 1% of patients in the conventional therapy group receiving prior TNFi treatment.

The investigators assessed the risk of developing any psoriasis, nonpustular psoriasis, and pustular psoriasis in the two groups using ICD-10 codes as well as a record of two consecutive prescriptions for topical vitamin D analogs.

Overall, 1,471 patients (1.4%) developed psoriasis of any type; 1,332 had non-pustular psoriasis, 127 had palmoplantar pustulosis, and 12 had generalized pustulosis.

The incidence rate of developing any psoriasis was 3.0 per 1,000 patient-years (95% confidence interval, 2.9-3.2) for patients receiving conventional therapy and 7.8 per 1,000 patient-years (95% CI, 7.5-8.9) for patients receiving TNFi treatment. Compared with conventional treatment, the risk of developing nonpustular psoriasis was twofold higher among patients receiving TNFi treatment (hazard ratio, 2.12; 95% CI, 1.87-2.40; P < .001). The risk of developing pustular psoriasis was more than sixfold higher among those on a TNFi (HR, 6.50; 95% CI, 4.60-9.23; P < .001).

Dr. Thein and colleagues estimated that the exposure needed to harm 1 additional patient was 241 patient-years for any psoriasis type, 342 patient-years for nonpustular psoriasis, and 909 patient-years for pustular psoriasis, with an estimated absolute risk difference of 5 per 1,000 patient-years.
 

Best evidence to date on risk

Asked to comment on the study findings, Anthony Fernandez, MD, PhD, director of medical dermatology at the Cleveland Clinic, said that he applauded the researchers for performing this well-designed study to determine the risk of TNF inhibitor–induced psoriasis in patients with RA and IBD.

The strengths of the study include excluding patients with a history of psoriasis to rule out disease recurrence and having a large comparator group of patients with IBD and RA who were taking medications other than TNF inhibitors, while one limitation was the potential accuracy of the ICD-10 codes used as the basis for diagnosing psoriasis. “It’s probably closer to the truth of what the true risk is compared to studies done in the past,” he said in an interview.

Dr. Fernandez noted that the results aren’t likely to change how dermatologists, rheumatologists, or gastroenterologists practice, but the message to stay the course in initially treating TNFi-induced psoriasis also holds value. “We don’t need to change anything in our clinical practice when it comes to TNF-alpha inhibitors.”

For patients with RA or IBD who develop TNFi-induced psoriasis with disease that is well controlled with TNFi treatment, keeping them on that treatment is a priority, Dr. Fernandez explained. “The first and foremost goal is, if the TNF inhibitor is working very well to control the disease that it was prescribed for, then you exhaust your efforts to try to control the psoriasis and allow those patients to stay on the TNF inhibitor.”

In his experience, most patients with RA and IBD who develop TNFi-induced psoriasis are controlled with topical medications. Switching to another TNFi is not recommended, he noted, as patients are “likely to have that reaction with any TNF inhibitor.”

However, Dr. Fernandez said that won’t be an option for all patients with RA and IBD. “In some patients you do simply have to stop the TNF inhibitor” and try an alternative treatment with a different mechanism of action.

The cause of TNFi-induced psoriasis is still not well understood. “There certainly is evidence to support that interferon alpha production by plasmacytoid dendritic cells is playing some role in this phenomenon,” but there is “more to the story” and unanswered questions remain, Dr. Fernandez said.

What’s most interesting about this phenomenon, he added, is that “patients can develop it at any time when exposed to a TNF inhibitor.” For instance, most patients develop drug reactions within 2­-3 weeks of starting a treatment, but TNFi-induced psoriasis can appear after a single dose or several years after initiating treatment.

“Why so few patients, and why is there such variability in terms of how long they’re on the TNF inhibitor before the reaction occurs?” he asked. “That really points to ... some other trigger besides exposure to the TNF inhibitor needed for the initiation of this reaction.”

He noted that it would be valuable to identify triggers – or the most likely triggers – which would be challenging, but could “potentially impact clinical practice.”

The authors reported personal and institutional relationships in the form of personal and institutional research grants, honoraria, personal fees, investigator fees paid to university, consultancies, and speaker’s bureau positions for a variety of pharmaceutical companies, data companies, hospitals, and foundations. Dr. Fernandez reported he has nonbranded speaking, consulting, and research relationships with AbbVie and Novartis; and is a consultant for UCB, Bristol-Myers Squibb, and Boehringer Ingelheim on related products.

Compulsivity is a significant contributor to disability and poor quality of life for individuals with trichotillomania (TTM) and skin-picking disorder (SPD), based on data from 91 adults.

Although body-focused repetitive behaviors (BFRBs), specifically trichotillomania and skin-picking disorder, are similar in clinical presentation to aspects of obsessive-compulsive disorder (OCD), the role of compulsivity in TTM and SPD has not been well studied, wrote Jon E. Grant, MD, of the University of Chicago and colleagues.

In a study published in the Journal of Psychiatric Research, the authors recruited 69 women and 22 men who met DSM-5 criteria for TTM and SPD. Participants completed diagnostic interviews, symptom inventories, and measures of disability/functioning. Compulsivity was measured using the 15-item Cambridge-Chicago Compulsivity Trait Scale (CHI-T). The average age of the participants was 30.9 years; 48 had TTM, 37 had SPD, and 2 had both conditions.

Overall, total CHI-T scores were significantly correlated with worse disability and quality of life, based on the Quality of Life Inventory (P = .0278) and the Sheehan Disability Scale (P = .0085) but not with severity of TTM or SPD symptoms. TTM and SPD symptoms were assessed using the Massachusetts General Hospital Hair Pulling Scale and the Skin Picking Symptom Symptom Assessment Scale.

“In the current study, we did not find a link between conventional symptom severity measures for BFRBs and disability or quality of life, whereas trans-diagnostic compulsivity did correlate with these clinically important parameters,” the researchers wrote in their discussion. “These findings might suggest the current symptom measures for BFRBs are not including an important aspect of the disease and that a fuller understanding of these symptoms requires measurement of compulsivity. Including validated measures of compulsivity in clinical trials of therapy or medication would also seem to be important for future work,” they said.

The study findings were limited by several factors including the use of a community sample that may not generalize to a clinical setting, the researchers noted. Other limitations include the cross-sectional design, which prevents conclusions about causality, the lack of a control group, and the relatively small sample size, they said.

However, the study is the first known to use a validated compulsivity measure to assess BFRBs, and the results suggest a clinically relevant impact of compulsivity on both psychosocial dysfunction and poor quality of life in this patient population, with possible implications for treatment, the researchers wrote.

The study received no outside funding. Lead author Dr. Grant disclosed research grants from Otsuka and Biohaven Pharmaceuticals, yearly compensation from Springer Publishing for acting as editor in chief of the Journal of Gambling Studies, and royalties from Oxford University Press, American Psychiatric Publishing, Norton Press, and McGraw Hill.

Compulsivity is a significant contributor to disability and poor quality of life for individuals with trichotillomania (TTM) and skin-picking disorder (SPD), based on data from 91 adults.

Although body-focused repetitive behaviors (BFRBs), specifically trichotillomania and skin-picking disorder, are similar in clinical presentation to aspects of obsessive-compulsive disorder (OCD), the role of compulsivity in TTM and SPD has not been well studied, wrote Jon E. Grant, MD, of the University of Chicago and colleagues.

In a study published in the Journal of Psychiatric Research, the authors recruited 69 women and 22 men who met DSM-5 criteria for TTM and SPD. Participants completed diagnostic interviews, symptom inventories, and measures of disability/functioning. Compulsivity was measured using the 15-item Cambridge-Chicago Compulsivity Trait Scale (CHI-T). The average age of the participants was 30.9 years; 48 had TTM, 37 had SPD, and 2 had both conditions.

Overall, total CHI-T scores were significantly correlated with worse disability and quality of life, based on the Quality of Life Inventory (P = .0278) and the Sheehan Disability Scale (P = .0085) but not with severity of TTM or SPD symptoms. TTM and SPD symptoms were assessed using the Massachusetts General Hospital Hair Pulling Scale and the Skin Picking Symptom Symptom Assessment Scale.

“In the current study, we did not find a link between conventional symptom severity measures for BFRBs and disability or quality of life, whereas trans-diagnostic compulsivity did correlate with these clinically important parameters,” the researchers wrote in their discussion. “These findings might suggest the current symptom measures for BFRBs are not including an important aspect of the disease and that a fuller understanding of these symptoms requires measurement of compulsivity. Including validated measures of compulsivity in clinical trials of therapy or medication would also seem to be important for future work,” they said.

The study findings were limited by several factors including the use of a community sample that may not generalize to a clinical setting, the researchers noted. Other limitations include the cross-sectional design, which prevents conclusions about causality, the lack of a control group, and the relatively small sample size, they said.

However, the study is the first known to use a validated compulsivity measure to assess BFRBs, and the results suggest a clinically relevant impact of compulsivity on both psychosocial dysfunction and poor quality of life in this patient population, with possible implications for treatment, the researchers wrote.

The study received no outside funding. Lead author Dr. Grant disclosed research grants from Otsuka and Biohaven Pharmaceuticals, yearly compensation from Springer Publishing for acting as editor in chief of the Journal of Gambling Studies, and royalties from Oxford University Press, American Psychiatric Publishing, Norton Press, and McGraw Hill.

Compulsivity is a significant contributor to disability and poor quality of life for individuals with trichotillomania (TTM) and skin-picking disorder (SPD), based on data from 91 adults.

Although body-focused repetitive behaviors (BFRBs), specifically trichotillomania and skin-picking disorder, are similar in clinical presentation to aspects of obsessive-compulsive disorder (OCD), the role of compulsivity in TTM and SPD has not been well studied, wrote Jon E. Grant, MD, of the University of Chicago and colleagues.

In a study published in the Journal of Psychiatric Research, the authors recruited 69 women and 22 men who met DSM-5 criteria for TTM and SPD. Participants completed diagnostic interviews, symptom inventories, and measures of disability/functioning. Compulsivity was measured using the 15-item Cambridge-Chicago Compulsivity Trait Scale (CHI-T). The average age of the participants was 30.9 years; 48 had TTM, 37 had SPD, and 2 had both conditions.

Overall, total CHI-T scores were significantly correlated with worse disability and quality of life, based on the Quality of Life Inventory (P = .0278) and the Sheehan Disability Scale (P = .0085) but not with severity of TTM or SPD symptoms. TTM and SPD symptoms were assessed using the Massachusetts General Hospital Hair Pulling Scale and the Skin Picking Symptom Symptom Assessment Scale.

“In the current study, we did not find a link between conventional symptom severity measures for BFRBs and disability or quality of life, whereas trans-diagnostic compulsivity did correlate with these clinically important parameters,” the researchers wrote in their discussion. “These findings might suggest the current symptom measures for BFRBs are not including an important aspect of the disease and that a fuller understanding of these symptoms requires measurement of compulsivity. Including validated measures of compulsivity in clinical trials of therapy or medication would also seem to be important for future work,” they said.

The study findings were limited by several factors including the use of a community sample that may not generalize to a clinical setting, the researchers noted. Other limitations include the cross-sectional design, which prevents conclusions about causality, the lack of a control group, and the relatively small sample size, they said.

However, the study is the first known to use a validated compulsivity measure to assess BFRBs, and the results suggest a clinically relevant impact of compulsivity on both psychosocial dysfunction and poor quality of life in this patient population, with possible implications for treatment, the researchers wrote.

The study received no outside funding. Lead author Dr. Grant disclosed research grants from Otsuka and Biohaven Pharmaceuticals, yearly compensation from Springer Publishing for acting as editor in chief of the Journal of Gambling Studies, and royalties from Oxford University Press, American Psychiatric Publishing, Norton Press, and McGraw Hill.

Multiple media outlets and numerous children’s professional organizations are discussing the child and adolescent mental health crisis. Finally, society at large seems to be taking notice that our kids are not okay, and that they haven’t been okay for a long time.

Over the past 5-7 years, both in my practice in tertiary children’s hospital emergency departments and in primary care pediatrics, I have seen a disturbing decline in kids’ mental well-being. What can a primary care physician do to make a difference? How do we capitalize on these discussions about mental health and illness now that it is rising to a priority status?

The U.S. Preventive Services Task Force recently drafted a statement of recommendations specifically discussing anxiety in children and adolescents. It shows supporting evidence that there is a moderate benefit to screening children 8-18 years old for anxiety. We know from the 2018-2019 National Survey of Children’s Health that almost 8% of children/adolescents ages 3-17 years old have an anxiety disorder. And among those 13-18 years old, the lifetime prevalence rises to nearly 33%, according to National Institutes of Health statistics.

Childhood anxiety unquestionably increases the chances of persistent anxiety or depression in adulthood. I have followed children who had excessive social anxiety from age 3 or 4 who progressed to generalized anxiety disorder as adolescents, usually when no intervention was done or when the family waited for the child to “outgrow” it. The DSM-5 has six separate categories for anxiety disorders in children and adolescents: generalized anxiety disorder, separation anxiety disorder, specific phobias, social phobia, agoraphobia, and panic disorder. Unfortunately, these illnesses cannot be wished away.
 

Screening, diagnosis, and follow-up

A few simple screening tools can be used to check for anxiety in children and adolescents. These include SCARED (Screen for Child Anxiety Related Emotional Disorders), GAD-7 (Generalized Anxiety Disorder-7), and/or the PHQ-A (Patient Health Questionnaire for Adolescents). Keep in mind that a screening tool is just that – a screen. Diagnostic confirmation and follow-up are appropriate after a positive screen. I like all of these particular screens as they are easy to administer and can be incorporated into a busy practice without extra training to administer. They are also easy for parents and patients to complete prior to a visit or during a visit.

Ideally, after a positive screen, the next step is to consult a child and adolescent psychiatrist (CAP); however, according to statistics from the American Academy of Child and Adolescent Psychiatry (AACAP), there are only 8,300 CAPs in the United States. The reality is that not a single state in the entire country has a “mostly sufficient supply” of CAP’s (defined as ≥ 47 per 100,000 children). In fact, most have a “severe shortage,” defined as 1-17 per 100,000 children

Adding a child/adolescent therapist is also necessary for patients 8 years old and up, but the harsh truth is that it may take up to several months before the child is seen. If a patient is in a rural or other underserved area, it may be even longer.

So, what does this mean for primary care physicians? When you are faced with a positive screening for childhood anxiety, the next step is “tag, you’re it!” Understandably, this is frightening for many physicians who feel unqualified.

Don’t be afraid! Like the old adage says, a journey of a thousand miles begins with a single step. Starting the conversation with patients and families is foremost. Physicians must be first in line to end the stigma surrounding mental illness, and the easiest way to do that is to start the conversation. Remember that anxiety in kids can present as classic fear or worry, but it also can present as irritability, anger outbursts, and attention issues. There have been so many patients referred to me for “being out of control” or “always angry” or “probable ADHD” who turned out to have significant anxiety.

Part of a routine medical evaluation includes obtaining personal, family, and social history; there should be no difference when considering an anxiety disorder. Obtaining information about family history, personality traits, environmental components, early attachment issues, developmental history, parental style, parental conflict, occupants in the home, any adverse childhood events, and history of child maltreatment is crucial. Assessing other risk factors, including socioeconomic status, race, ethnicity, and gender, is key as well. I have seen families literally breathe a sigh of relief when these questions are asked. Parents feel heard and seen. And, equally significant, so does the child/adolescent.
 

The ‘Big 4’

An in-depth assessment of patient and family lifestyle factors such as nutrition, sleep, physical activity/exercise, and screen time habits is also basic and essential. This kind of evaluation usually cannot be done in the typical 15-minute visit and often will need to be done over several patient visits. I have had numerous conversations with my patients regarding what I call the “Big 4” – simple but not easy concepts and actions. They include nutrition, sleep, exercise, and screen time. Parents will look at me and say, “I can’t believe I never thought of this!” Some of my favorite moments with patients over the years have involved partnering with the patient and family and encouraging them to do the “simple” but not “easy” things.

Nutrition

Does the child have proper nutrition? That is not meant to be an exercise in labeling foods as “good” or “bad” but meant to confirm whether there is a balance of different foods. It’s also a way of exploring whether there are family meals in the home. Family meals have been shown to have a protective factor for children’s social development and emotional regulation.

Sleep

Review the child’s sleep habits, such as difficulty falling/staying asleep, bedtime routine (soothing, relaxing activities vs. the opposite), nightmares, snoring, nighttime cough, etc. The physical sleeping environment is important as well. Is it quiet? Is it a crowded room?

Exercise

Discuss physical activity with the family. Is there time for the child to play outside without a defined goal? So much of a child’s day is structured, in school or with after-school activities, but can the kid simply be a kid? Does the family take walks together? Is it safe to play outside?

Screen time

Reviewing screen time is important for multiple reasons, especially because the more time spent in front of a TV, computer, or video game, the less time there is to be physically active. Numerous experts, including the American Academy of Pediatrics, recommend limits on screen time for children. For adolescents, there appears to be some evidence that excessive screen time contributes to depression/anxiety.

I am not embarrassed to say that with my own kids I felt so strongly about screen time that we did not own any kind of video games or iPad (that was theirs alone), and they spent the summers until they turned 14 building a two-story bamboo fort in our backyard instead of vegging out in front of the TV or computer. It didn’t hurt them a bit; one is an engineer and the other is in nursing school.

It is easy to see that lifestyle factors can come into play with childhood anxiety and are often ignored in the clinical setting. They do not involve technologically advanced techniques or procedures, which are more likely to be reimbursed. They are straightforward – but not easy – concepts, and require active participation from the patient and family. Some of my most exciting moments with families is when they return for follow up and say, “It worked!”

We need to be as comfortable taking care of a child’s mind and spirit as we are taking care of a child’s physical body. Is this easy in a busy office? No. Is this easy in a 15-minute visit? No. Is this easy with poor reimbursement from insurance companies? No. Is it necessary? Unequivocally YES. Start the conversation.

Tag, you’re it!
 

Dr. Contrucci is an assistant professor of pediatrics, clinical education department, Philadelphia College of Osteopathic Medicine, Georgia Campus, Suwanee. She disclosed no relevant conflict of interest.

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

Multiple media outlets and numerous children’s professional organizations are discussing the child and adolescent mental health crisis. Finally, society at large seems to be taking notice that our kids are not okay, and that they haven’t been okay for a long time.

Over the past 5-7 years, both in my practice in tertiary children’s hospital emergency departments and in primary care pediatrics, I have seen a disturbing decline in kids’ mental well-being. What can a primary care physician do to make a difference? How do we capitalize on these discussions about mental health and illness now that it is rising to a priority status?

The U.S. Preventive Services Task Force recently drafted a statement of recommendations specifically discussing anxiety in children and adolescents. It shows supporting evidence that there is a moderate benefit to screening children 8-18 years old for anxiety. We know from the 2018-2019 National Survey of Children’s Health that almost 8% of children/adolescents ages 3-17 years old have an anxiety disorder. And among those 13-18 years old, the lifetime prevalence rises to nearly 33%, according to National Institutes of Health statistics.

Childhood anxiety unquestionably increases the chances of persistent anxiety or depression in adulthood. I have followed children who had excessive social anxiety from age 3 or 4 who progressed to generalized anxiety disorder as adolescents, usually when no intervention was done or when the family waited for the child to “outgrow” it. The DSM-5 has six separate categories for anxiety disorders in children and adolescents: generalized anxiety disorder, separation anxiety disorder, specific phobias, social phobia, agoraphobia, and panic disorder. Unfortunately, these illnesses cannot be wished away.
 

Screening, diagnosis, and follow-up

A few simple screening tools can be used to check for anxiety in children and adolescents. These include SCARED (Screen for Child Anxiety Related Emotional Disorders), GAD-7 (Generalized Anxiety Disorder-7), and/or the PHQ-A (Patient Health Questionnaire for Adolescents). Keep in mind that a screening tool is just that – a screen. Diagnostic confirmation and follow-up are appropriate after a positive screen. I like all of these particular screens as they are easy to administer and can be incorporated into a busy practice without extra training to administer. They are also easy for parents and patients to complete prior to a visit or during a visit.

Ideally, after a positive screen, the next step is to consult a child and adolescent psychiatrist (CAP); however, according to statistics from the American Academy of Child and Adolescent Psychiatry (AACAP), there are only 8,300 CAPs in the United States. The reality is that not a single state in the entire country has a “mostly sufficient supply” of CAP’s (defined as ≥ 47 per 100,000 children). In fact, most have a “severe shortage,” defined as 1-17 per 100,000 children

Adding a child/adolescent therapist is also necessary for patients 8 years old and up, but the harsh truth is that it may take up to several months before the child is seen. If a patient is in a rural or other underserved area, it may be even longer.

So, what does this mean for primary care physicians? When you are faced with a positive screening for childhood anxiety, the next step is “tag, you’re it!” Understandably, this is frightening for many physicians who feel unqualified.

Don’t be afraid! Like the old adage says, a journey of a thousand miles begins with a single step. Starting the conversation with patients and families is foremost. Physicians must be first in line to end the stigma surrounding mental illness, and the easiest way to do that is to start the conversation. Remember that anxiety in kids can present as classic fear or worry, but it also can present as irritability, anger outbursts, and attention issues. There have been so many patients referred to me for “being out of control” or “always angry” or “probable ADHD” who turned out to have significant anxiety.

Part of a routine medical evaluation includes obtaining personal, family, and social history; there should be no difference when considering an anxiety disorder. Obtaining information about family history, personality traits, environmental components, early attachment issues, developmental history, parental style, parental conflict, occupants in the home, any adverse childhood events, and history of child maltreatment is crucial. Assessing other risk factors, including socioeconomic status, race, ethnicity, and gender, is key as well. I have seen families literally breathe a sigh of relief when these questions are asked. Parents feel heard and seen. And, equally significant, so does the child/adolescent.
 

The ‘Big 4’

An in-depth assessment of patient and family lifestyle factors such as nutrition, sleep, physical activity/exercise, and screen time habits is also basic and essential. This kind of evaluation usually cannot be done in the typical 15-minute visit and often will need to be done over several patient visits. I have had numerous conversations with my patients regarding what I call the “Big 4” – simple but not easy concepts and actions. They include nutrition, sleep, exercise, and screen time. Parents will look at me and say, “I can’t believe I never thought of this!” Some of my favorite moments with patients over the years have involved partnering with the patient and family and encouraging them to do the “simple” but not “easy” things.

Nutrition

Does the child have proper nutrition? That is not meant to be an exercise in labeling foods as “good” or “bad” but meant to confirm whether there is a balance of different foods. It’s also a way of exploring whether there are family meals in the home. Family meals have been shown to have a protective factor for children’s social development and emotional regulation.

Sleep

Review the child’s sleep habits, such as difficulty falling/staying asleep, bedtime routine (soothing, relaxing activities vs. the opposite), nightmares, snoring, nighttime cough, etc. The physical sleeping environment is important as well. Is it quiet? Is it a crowded room?

Exercise

Discuss physical activity with the family. Is there time for the child to play outside without a defined goal? So much of a child’s day is structured, in school or with after-school activities, but can the kid simply be a kid? Does the family take walks together? Is it safe to play outside?

Screen time

Reviewing screen time is important for multiple reasons, especially because the more time spent in front of a TV, computer, or video game, the less time there is to be physically active. Numerous experts, including the American Academy of Pediatrics, recommend limits on screen time for children. For adolescents, there appears to be some evidence that excessive screen time contributes to depression/anxiety.

I am not embarrassed to say that with my own kids I felt so strongly about screen time that we did not own any kind of video games or iPad (that was theirs alone), and they spent the summers until they turned 14 building a two-story bamboo fort in our backyard instead of vegging out in front of the TV or computer. It didn’t hurt them a bit; one is an engineer and the other is in nursing school.

It is easy to see that lifestyle factors can come into play with childhood anxiety and are often ignored in the clinical setting. They do not involve technologically advanced techniques or procedures, which are more likely to be reimbursed. They are straightforward – but not easy – concepts, and require active participation from the patient and family. Some of my most exciting moments with families is when they return for follow up and say, “It worked!”

We need to be as comfortable taking care of a child’s mind and spirit as we are taking care of a child’s physical body. Is this easy in a busy office? No. Is this easy in a 15-minute visit? No. Is this easy with poor reimbursement from insurance companies? No. Is it necessary? Unequivocally YES. Start the conversation.

Tag, you’re it!
 

Dr. Contrucci is an assistant professor of pediatrics, clinical education department, Philadelphia College of Osteopathic Medicine, Georgia Campus, Suwanee. She disclosed no relevant conflict of interest.

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

Multiple media outlets and numerous children’s professional organizations are discussing the child and adolescent mental health crisis. Finally, society at large seems to be taking notice that our kids are not okay, and that they haven’t been okay for a long time.

Over the past 5-7 years, both in my practice in tertiary children’s hospital emergency departments and in primary care pediatrics, I have seen a disturbing decline in kids’ mental well-being. What can a primary care physician do to make a difference? How do we capitalize on these discussions about mental health and illness now that it is rising to a priority status?

The U.S. Preventive Services Task Force recently drafted a statement of recommendations specifically discussing anxiety in children and adolescents. It shows supporting evidence that there is a moderate benefit to screening children 8-18 years old for anxiety. We know from the 2018-2019 National Survey of Children’s Health that almost 8% of children/adolescents ages 3-17 years old have an anxiety disorder. And among those 13-18 years old, the lifetime prevalence rises to nearly 33%, according to National Institutes of Health statistics.

Childhood anxiety unquestionably increases the chances of persistent anxiety or depression in adulthood. I have followed children who had excessive social anxiety from age 3 or 4 who progressed to generalized anxiety disorder as adolescents, usually when no intervention was done or when the family waited for the child to “outgrow” it. The DSM-5 has six separate categories for anxiety disorders in children and adolescents: generalized anxiety disorder, separation anxiety disorder, specific phobias, social phobia, agoraphobia, and panic disorder. Unfortunately, these illnesses cannot be wished away.
 

Screening, diagnosis, and follow-up

A few simple screening tools can be used to check for anxiety in children and adolescents. These include SCARED (Screen for Child Anxiety Related Emotional Disorders), GAD-7 (Generalized Anxiety Disorder-7), and/or the PHQ-A (Patient Health Questionnaire for Adolescents). Keep in mind that a screening tool is just that – a screen. Diagnostic confirmation and follow-up are appropriate after a positive screen. I like all of these particular screens as they are easy to administer and can be incorporated into a busy practice without extra training to administer. They are also easy for parents and patients to complete prior to a visit or during a visit.

Ideally, after a positive screen, the next step is to consult a child and adolescent psychiatrist (CAP); however, according to statistics from the American Academy of Child and Adolescent Psychiatry (AACAP), there are only 8,300 CAPs in the United States. The reality is that not a single state in the entire country has a “mostly sufficient supply” of CAP’s (defined as ≥ 47 per 100,000 children). In fact, most have a “severe shortage,” defined as 1-17 per 100,000 children

Adding a child/adolescent therapist is also necessary for patients 8 years old and up, but the harsh truth is that it may take up to several months before the child is seen. If a patient is in a rural or other underserved area, it may be even longer.

So, what does this mean for primary care physicians? When you are faced with a positive screening for childhood anxiety, the next step is “tag, you’re it!” Understandably, this is frightening for many physicians who feel unqualified.

Don’t be afraid! Like the old adage says, a journey of a thousand miles begins with a single step. Starting the conversation with patients and families is foremost. Physicians must be first in line to end the stigma surrounding mental illness, and the easiest way to do that is to start the conversation. Remember that anxiety in kids can present as classic fear or worry, but it also can present as irritability, anger outbursts, and attention issues. There have been so many patients referred to me for “being out of control” or “always angry” or “probable ADHD” who turned out to have significant anxiety.

Part of a routine medical evaluation includes obtaining personal, family, and social history; there should be no difference when considering an anxiety disorder. Obtaining information about family history, personality traits, environmental components, early attachment issues, developmental history, parental style, parental conflict, occupants in the home, any adverse childhood events, and history of child maltreatment is crucial. Assessing other risk factors, including socioeconomic status, race, ethnicity, and gender, is key as well. I have seen families literally breathe a sigh of relief when these questions are asked. Parents feel heard and seen. And, equally significant, so does the child/adolescent.
 

The ‘Big 4’

An in-depth assessment of patient and family lifestyle factors such as nutrition, sleep, physical activity/exercise, and screen time habits is also basic and essential. This kind of evaluation usually cannot be done in the typical 15-minute visit and often will need to be done over several patient visits. I have had numerous conversations with my patients regarding what I call the “Big 4” – simple but not easy concepts and actions. They include nutrition, sleep, exercise, and screen time. Parents will look at me and say, “I can’t believe I never thought of this!” Some of my favorite moments with patients over the years have involved partnering with the patient and family and encouraging them to do the “simple” but not “easy” things.

Nutrition

Does the child have proper nutrition? That is not meant to be an exercise in labeling foods as “good” or “bad” but meant to confirm whether there is a balance of different foods. It’s also a way of exploring whether there are family meals in the home. Family meals have been shown to have a protective factor for children’s social development and emotional regulation.

Sleep

Review the child’s sleep habits, such as difficulty falling/staying asleep, bedtime routine (soothing, relaxing activities vs. the opposite), nightmares, snoring, nighttime cough, etc. The physical sleeping environment is important as well. Is it quiet? Is it a crowded room?

Exercise

Discuss physical activity with the family. Is there time for the child to play outside without a defined goal? So much of a child’s day is structured, in school or with after-school activities, but can the kid simply be a kid? Does the family take walks together? Is it safe to play outside?

Screen time

Reviewing screen time is important for multiple reasons, especially because the more time spent in front of a TV, computer, or video game, the less time there is to be physically active. Numerous experts, including the American Academy of Pediatrics, recommend limits on screen time for children. For adolescents, there appears to be some evidence that excessive screen time contributes to depression/anxiety.

I am not embarrassed to say that with my own kids I felt so strongly about screen time that we did not own any kind of video games or iPad (that was theirs alone), and they spent the summers until they turned 14 building a two-story bamboo fort in our backyard instead of vegging out in front of the TV or computer. It didn’t hurt them a bit; one is an engineer and the other is in nursing school.

It is easy to see that lifestyle factors can come into play with childhood anxiety and are often ignored in the clinical setting. They do not involve technologically advanced techniques or procedures, which are more likely to be reimbursed. They are straightforward – but not easy – concepts, and require active participation from the patient and family. Some of my most exciting moments with families is when they return for follow up and say, “It worked!”

We need to be as comfortable taking care of a child’s mind and spirit as we are taking care of a child’s physical body. Is this easy in a busy office? No. Is this easy in a 15-minute visit? No. Is this easy with poor reimbursement from insurance companies? No. Is it necessary? Unequivocally YES. Start the conversation.

Tag, you’re it!
 

Dr. Contrucci is an assistant professor of pediatrics, clinical education department, Philadelphia College of Osteopathic Medicine, Georgia Campus, Suwanee. She disclosed no relevant conflict of interest.

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

The Centers for Medicare & Medicaid Services has announced a new, voluntary alternative payment model, which will replace the Oncology Care Model (OCM) that ended on June 30.

The OCM’s successor, known as the Enhancing Oncology Model (EOM), will begin next year on July 1, and run for 5 years.

Like the OCM, the EOM will align payment incentives with care quality, and focus on value-based, patient-centered care for those undergoing chemotherapy based on 6-month episodes of care. The EOM will focus on health equity, and participants will include oncology practices that treat Medicare beneficiaries receiving chemotherapy for seven types of cancer: breast cancer, chronic leukemia, lung cancer, lymphoma, multiple myeloma, prostate cancer, and small intestine/colorectal cancer.

The new model will build on lessons learned from the OCM, incorporating successful elements of the previous model, such as patient navigation and care planning, and will introduce new elements, including gradually implementing electronic Patient-Reported Outcomes and activities that promote health equity.

In a statement, CMS Administrator Chiquita Brooks-LaSure noted that the EOM will “incentivize participating oncology practices – including those in rural and underserved areas – to improve the provision of high-quality, coordinated care that addresses patients’ social needs and improves patient and caregiver support.”

The goal, Ms. Brooks-LaSure added, is to address “stark inequities in the ability of people with cancer across race, gender, region, and income to access cancer screening, diagnostics, and treatment. CMS is working to advance President Biden’s Cancer Moonshot goals by helping Medicare cancer patients better navigate a challenging and often overwhelming journey.”
 

Applauds and concerns

The American Society of Clinical Oncology, the Association of Community Cancer Centers, and the Community Oncology Alliance all issued statements applauding the new model and the fact that it is voluntary. But they have also voiced several concerns.

The COA, for example, noted that the CMS Innovation Center plans to cut the Monthly Enhanced Oncology Services payments in the EOM by more than half ($70 vs $160 for the OCM), but at the same time, expects more work from practices.

While COA is “extremely supportive” of screening for health-related social needs and electronic patient-reported outcomes, “it seems unfair to burden practices with more work but pay less for it, particularly as practices are dealing with the return of the Medicare sequester cut, inflation, and ongoing COVID-19 practice challenges,” Ted Okon, executive director of COA, wrote in a statement.

COA also expressed concern with the 1-year gap between the end of the OCM and the start of EOM.

“During this time practices will have to shoulder the extensive investments and operational changes put in place to benefit patients without reimbursement,” Mr. Okon said.

ASCO echoed COA’s concerns and the ACCC expressed unease with some of the structural elements of the program.

The EOM includes two risk arrangements with different degrees of downside risk. However, requiring participants to accept downside risk from the start of the model “will be a significant barrier to enrollment given the current reimbursement landscape,” the ACCC said in a statement. This risk “may not make financial sense for smaller oncology programs, particularly those who care for underserved patients and those that have not previously participated in OCM.”

Instead, CMS should “endeavor to provide as much information on proposed payment methodologies, cost data, and benchmark amounts as early as possible so that practices can make informed decisions around participation,” the ACCC wrote.
 

An improvement over OCM?

The OCM represented the largest alternative payment model to address value-based payment for cancer care. More than 3,200 oncologists and 201 physician practices voluntarily entered the program, which lasted 6 years.

But since its implementation, studies assessing the success of the program have yielded mixed results.

A 2018 analysis, for instance, revealed that one large community practice saved Medicare $3 million over a year after adopting the OCM.

However, a 2021 study found that, while community practices experienced lower drug costs in lung and prostate cancer and lower office-based costs after implementing the program, the difference was not statistically significant when accounting for all costs.

Another analysis also revealed more mixed results, reporting cost reductions for all cancers, but also finding those savings were offset by administrative expenses. Overall, this study found the OCM led to a $155 million net loss to Medicare over 4 years.
 

Will the EOM improve upon the OCM?

According to the CMS, “the central goal of EOM is to better support patients and improve their care experience.”

Participating Physician Group Practices will take accountability for health care quality and total spending during 6-month episodes of care for Medicare patients with certain cancers.

CMS will give participants the option to bill for Monthly Enhanced Oncology Services payment for services provided to eligible beneficiaries. This payment will be higher for beneficiaries dually eligible for Medicare and Medicaid.

EOM participants will have the opportunity to earn a retrospective performance-based payment based on quality and savings. Participants will be required to take on downside risk from the start of the model, with the potential to owe CMS a performance-based recoupment.

EOM participants will be required to implement participant redesign activities, including 24/7 access to care, patient navigation, care planning, use of evidence-based guidelines, use of electronic Patient Reported Outcomes, screening for health-related social needs, use of data for quality improvement, and use of certified electronic health record technology.

“No one should have to battle cancer without access to high-quality, coordinated care,” said Health & Human Services Secretary Xavier Becerra, in a statement. “With this new Innovation Center model for oncology care, we are delivering on President Biden’s call to action to mobilize every option to address cancer, and creating a system of care that supports all patients and their families.”

A detailed payment methodology paper will be published for EOM this summer and will be available on the Innovation Center’s website.

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

The Centers for Medicare & Medicaid Services has announced a new, voluntary alternative payment model, which will replace the Oncology Care Model (OCM) that ended on June 30.

The OCM’s successor, known as the Enhancing Oncology Model (EOM), will begin next year on July 1, and run for 5 years.

Like the OCM, the EOM will align payment incentives with care quality, and focus on value-based, patient-centered care for those undergoing chemotherapy based on 6-month episodes of care. The EOM will focus on health equity, and participants will include oncology practices that treat Medicare beneficiaries receiving chemotherapy for seven types of cancer: breast cancer, chronic leukemia, lung cancer, lymphoma, multiple myeloma, prostate cancer, and small intestine/colorectal cancer.

The new model will build on lessons learned from the OCM, incorporating successful elements of the previous model, such as patient navigation and care planning, and will introduce new elements, including gradually implementing electronic Patient-Reported Outcomes and activities that promote health equity.

In a statement, CMS Administrator Chiquita Brooks-LaSure noted that the EOM will “incentivize participating oncology practices – including those in rural and underserved areas – to improve the provision of high-quality, coordinated care that addresses patients’ social needs and improves patient and caregiver support.”

The goal, Ms. Brooks-LaSure added, is to address “stark inequities in the ability of people with cancer across race, gender, region, and income to access cancer screening, diagnostics, and treatment. CMS is working to advance President Biden’s Cancer Moonshot goals by helping Medicare cancer patients better navigate a challenging and often overwhelming journey.”
 

Applauds and concerns

The American Society of Clinical Oncology, the Association of Community Cancer Centers, and the Community Oncology Alliance all issued statements applauding the new model and the fact that it is voluntary. But they have also voiced several concerns.

The COA, for example, noted that the CMS Innovation Center plans to cut the Monthly Enhanced Oncology Services payments in the EOM by more than half ($70 vs $160 for the OCM), but at the same time, expects more work from practices.

While COA is “extremely supportive” of screening for health-related social needs and electronic patient-reported outcomes, “it seems unfair to burden practices with more work but pay less for it, particularly as practices are dealing with the return of the Medicare sequester cut, inflation, and ongoing COVID-19 practice challenges,” Ted Okon, executive director of COA, wrote in a statement.

COA also expressed concern with the 1-year gap between the end of the OCM and the start of EOM.

“During this time practices will have to shoulder the extensive investments and operational changes put in place to benefit patients without reimbursement,” Mr. Okon said.

ASCO echoed COA’s concerns and the ACCC expressed unease with some of the structural elements of the program.

The EOM includes two risk arrangements with different degrees of downside risk. However, requiring participants to accept downside risk from the start of the model “will be a significant barrier to enrollment given the current reimbursement landscape,” the ACCC said in a statement. This risk “may not make financial sense for smaller oncology programs, particularly those who care for underserved patients and those that have not previously participated in OCM.”

Instead, CMS should “endeavor to provide as much information on proposed payment methodologies, cost data, and benchmark amounts as early as possible so that practices can make informed decisions around participation,” the ACCC wrote.
 

An improvement over OCM?

The OCM represented the largest alternative payment model to address value-based payment for cancer care. More than 3,200 oncologists and 201 physician practices voluntarily entered the program, which lasted 6 years.

But since its implementation, studies assessing the success of the program have yielded mixed results.

A 2018 analysis, for instance, revealed that one large community practice saved Medicare $3 million over a year after adopting the OCM.

However, a 2021 study found that, while community practices experienced lower drug costs in lung and prostate cancer and lower office-based costs after implementing the program, the difference was not statistically significant when accounting for all costs.

Another analysis also revealed more mixed results, reporting cost reductions for all cancers, but also finding those savings were offset by administrative expenses. Overall, this study found the OCM led to a $155 million net loss to Medicare over 4 years.
 

Will the EOM improve upon the OCM?

According to the CMS, “the central goal of EOM is to better support patients and improve their care experience.”

Participating Physician Group Practices will take accountability for health care quality and total spending during 6-month episodes of care for Medicare patients with certain cancers.

CMS will give participants the option to bill for Monthly Enhanced Oncology Services payment for services provided to eligible beneficiaries. This payment will be higher for beneficiaries dually eligible for Medicare and Medicaid.

EOM participants will have the opportunity to earn a retrospective performance-based payment based on quality and savings. Participants will be required to take on downside risk from the start of the model, with the potential to owe CMS a performance-based recoupment.

EOM participants will be required to implement participant redesign activities, including 24/7 access to care, patient navigation, care planning, use of evidence-based guidelines, use of electronic Patient Reported Outcomes, screening for health-related social needs, use of data for quality improvement, and use of certified electronic health record technology.

“No one should have to battle cancer without access to high-quality, coordinated care,” said Health & Human Services Secretary Xavier Becerra, in a statement. “With this new Innovation Center model for oncology care, we are delivering on President Biden’s call to action to mobilize every option to address cancer, and creating a system of care that supports all patients and their families.”

A detailed payment methodology paper will be published for EOM this summer and will be available on the Innovation Center’s website.

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

The Centers for Medicare & Medicaid Services has announced a new, voluntary alternative payment model, which will replace the Oncology Care Model (OCM) that ended on June 30.

The OCM’s successor, known as the Enhancing Oncology Model (EOM), will begin next year on July 1, and run for 5 years.

Like the OCM, the EOM will align payment incentives with care quality, and focus on value-based, patient-centered care for those undergoing chemotherapy based on 6-month episodes of care. The EOM will focus on health equity, and participants will include oncology practices that treat Medicare beneficiaries receiving chemotherapy for seven types of cancer: breast cancer, chronic leukemia, lung cancer, lymphoma, multiple myeloma, prostate cancer, and small intestine/colorectal cancer.

The new model will build on lessons learned from the OCM, incorporating successful elements of the previous model, such as patient navigation and care planning, and will introduce new elements, including gradually implementing electronic Patient-Reported Outcomes and activities that promote health equity.

In a statement, CMS Administrator Chiquita Brooks-LaSure noted that the EOM will “incentivize participating oncology practices – including those in rural and underserved areas – to improve the provision of high-quality, coordinated care that addresses patients’ social needs and improves patient and caregiver support.”

The goal, Ms. Brooks-LaSure added, is to address “stark inequities in the ability of people with cancer across race, gender, region, and income to access cancer screening, diagnostics, and treatment. CMS is working to advance President Biden’s Cancer Moonshot goals by helping Medicare cancer patients better navigate a challenging and often overwhelming journey.”
 

Applauds and concerns

The American Society of Clinical Oncology, the Association of Community Cancer Centers, and the Community Oncology Alliance all issued statements applauding the new model and the fact that it is voluntary. But they have also voiced several concerns.

The COA, for example, noted that the CMS Innovation Center plans to cut the Monthly Enhanced Oncology Services payments in the EOM by more than half ($70 vs $160 for the OCM), but at the same time, expects more work from practices.

While COA is “extremely supportive” of screening for health-related social needs and electronic patient-reported outcomes, “it seems unfair to burden practices with more work but pay less for it, particularly as practices are dealing with the return of the Medicare sequester cut, inflation, and ongoing COVID-19 practice challenges,” Ted Okon, executive director of COA, wrote in a statement.

COA also expressed concern with the 1-year gap between the end of the OCM and the start of EOM.

“During this time practices will have to shoulder the extensive investments and operational changes put in place to benefit patients without reimbursement,” Mr. Okon said.

ASCO echoed COA’s concerns and the ACCC expressed unease with some of the structural elements of the program.

The EOM includes two risk arrangements with different degrees of downside risk. However, requiring participants to accept downside risk from the start of the model “will be a significant barrier to enrollment given the current reimbursement landscape,” the ACCC said in a statement. This risk “may not make financial sense for smaller oncology programs, particularly those who care for underserved patients and those that have not previously participated in OCM.”

Instead, CMS should “endeavor to provide as much information on proposed payment methodologies, cost data, and benchmark amounts as early as possible so that practices can make informed decisions around participation,” the ACCC wrote.
 

An improvement over OCM?

The OCM represented the largest alternative payment model to address value-based payment for cancer care. More than 3,200 oncologists and 201 physician practices voluntarily entered the program, which lasted 6 years.

But since its implementation, studies assessing the success of the program have yielded mixed results.

A 2018 analysis, for instance, revealed that one large community practice saved Medicare $3 million over a year after adopting the OCM.

However, a 2021 study found that, while community practices experienced lower drug costs in lung and prostate cancer and lower office-based costs after implementing the program, the difference was not statistically significant when accounting for all costs.

Another analysis also revealed more mixed results, reporting cost reductions for all cancers, but also finding those savings were offset by administrative expenses. Overall, this study found the OCM led to a $155 million net loss to Medicare over 4 years.
 

Will the EOM improve upon the OCM?

According to the CMS, “the central goal of EOM is to better support patients and improve their care experience.”

Participating Physician Group Practices will take accountability for health care quality and total spending during 6-month episodes of care for Medicare patients with certain cancers.

CMS will give participants the option to bill for Monthly Enhanced Oncology Services payment for services provided to eligible beneficiaries. This payment will be higher for beneficiaries dually eligible for Medicare and Medicaid.

EOM participants will have the opportunity to earn a retrospective performance-based payment based on quality and savings. Participants will be required to take on downside risk from the start of the model, with the potential to owe CMS a performance-based recoupment.

EOM participants will be required to implement participant redesign activities, including 24/7 access to care, patient navigation, care planning, use of evidence-based guidelines, use of electronic Patient Reported Outcomes, screening for health-related social needs, use of data for quality improvement, and use of certified electronic health record technology.

“No one should have to battle cancer without access to high-quality, coordinated care,” said Health & Human Services Secretary Xavier Becerra, in a statement. “With this new Innovation Center model for oncology care, we are delivering on President Biden’s call to action to mobilize every option to address cancer, and creating a system of care that supports all patients and their families.”

A detailed payment methodology paper will be published for EOM this summer and will be available on the Innovation Center’s website.

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

Among transgender youth who receive puberty-delaying or gender-affirming hormone therapy, bone mineral density (BMD) is lower relative to age-based norms, and this is true regardless of gender assignment at birth.

The problem worsens as the time during which these patients receive sex steroid hormones increases. So far, the “bone mineral density effects of these therapies are understudied,” warned Natalie Nokoff, MD, who presented a cross-sectional study at the annual meeting of the Endocrine Society.

The study of bone density is part of a larger body of research being conducted by Dr. Nokoff and her co-investigators on the long-term health effects of gender-affirming therapy in children and adolescents. In one of several recent studies, transgender youths taking gonadotropin-releasing hormone (GnRH) agonists, which effectively block puberty, were shown to be at greater risk of adverse changes in body composition and markers of cardiometabolic health than youths who were not taking them.

“We need more information on the optimal length of treatment with puberty-delaying medications before either discontinuation or introduction of gender-affirming hormones,” said Dr. Nokoff, an assistant professor of pediatrics and endocrinology at the University of Colorado School of Medicine, Aurora.

In this study, 56 transgender youth underwent total body dual-energy x-ray absorptiometry (DEXA). The patients ranged in age from 10 years to almost 20 years. Just over half (53%) were assigned female sex at birth.

The mean Z scores, signifying deviation from age-matched norms, were lower regardless of current use or past use of GnRH agonists in both transgender males or transgender females, relative to age-matched norms.

Asked to comment, Michele A. O’Connell, MBBCh, department of endocrinology and diabetes, Royal Children’s Hospital, Victoria, Australia, said the risk of bone loss is real.

“Monitoring of bone health is recommended for all transgender-diverse adolescents treated with gonadotropin-releasing hormone agonists,” said Dr. O’Connell. He referred to multiple guidelines, including those issued by the World Professional Association of Transgender Health in 2012 and those from the Endocrine Society that were issued in 2017.
 

Inverse correlation between duration of GnRH agonist therapy and Z scores

In Dr. Nokoff’s study, for transgender males, the BMD Z score was reduced 0.2 relative to male norms and by 0.4 relative to female norms. For transgender females, the scores were reduced by 0.4 relative to male norms and by 0.2 relative to female norms.

Among transgender males who were taking testosterone and who had previously been exposed to GnRH agonists, the Z score was significantly lower than those taking testosterone alone (P = .004). There were no differences in Z score for transgender females taking estradiol alone relative to estradiol with current or past use of GnRH agonists.

There was a significant inverse correlation for duration of GnRH agonist therapy and Z scores for transgender females relative to male norms (P = .005) or female norms (P = .029). However, Z scores were unrelated to length of time receiving testosterone or estradiol therapy or to sex steroid concentrations.

The number of children and adolescents taking puberty-delaying or gender-affirming therapies is increasing. Although reliable data are limited, the exploration of gender identify appears to have become more common with the growing social acceptance of gender dysphoria. That term refers to a sense of unease among individuals who feel that their biological sex does not match their gender identity, according to Dr. Nokoff.

“It is now estimated that 2% of youths identify as transgender,” she said.

Findings from studies investigating the relationship between gender-affirming therapy and bone loss among adults have not been consistent. In a single-center study that followed 543 transgender men and 711 transgender women who had undergone DEXA scanning at baseline prior to starting hormone therapy, there did not appear to be any substantial negative effects on lumbar bone density over time (J Bone Min Res. 2018 Dec;34:447-54).

For adolescents, there is growing evidence of the risk of bone loss in relation to gender-affirming therapy, but there is limited agreement on clinical risks and how they can be avoided. Relevant variables include genetics and diet, as well as the types, doses, and length of time receiving gender-affirming therapy.
 

Monitor bone in transgender youth; Use vitamin D and weight-bearing exercise

Dr. O’Connell is the first author of a recent summary of the pharmacologic management of trans and gender-diverse adolescents. That summary covered multiple topics in addition to risk of bone loss, including the impact on growth, cognition, and mental health (J Clin Endocrinol Metab. 2022 Jan;107:241-257).

Overall, she believes that bone health should be monitored for children receiving puberty-delaying or gender-affirming therapies but agrees with Dr. Nokoff that the clinical impact remains poorly defined.

“Long-term follow-up studies will be required to assess the impact, if any, on functional outcomes such as fracture risk,” she reported. Still, she encouraged use of standard ways of improving bone health, including adequate vitamin D intake and weight-bearing exercise.

Dr. Nokoff and Dr. O’Connell have disclosed no relevant financial relationships.

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

Among transgender youth who receive puberty-delaying or gender-affirming hormone therapy, bone mineral density (BMD) is lower relative to age-based norms, and this is true regardless of gender assignment at birth.

The problem worsens as the time during which these patients receive sex steroid hormones increases. So far, the “bone mineral density effects of these therapies are understudied,” warned Natalie Nokoff, MD, who presented a cross-sectional study at the annual meeting of the Endocrine Society.

The study of bone density is part of a larger body of research being conducted by Dr. Nokoff and her co-investigators on the long-term health effects of gender-affirming therapy in children and adolescents. In one of several recent studies, transgender youths taking gonadotropin-releasing hormone (GnRH) agonists, which effectively block puberty, were shown to be at greater risk of adverse changes in body composition and markers of cardiometabolic health than youths who were not taking them.

“We need more information on the optimal length of treatment with puberty-delaying medications before either discontinuation or introduction of gender-affirming hormones,” said Dr. Nokoff, an assistant professor of pediatrics and endocrinology at the University of Colorado School of Medicine, Aurora.

In this study, 56 transgender youth underwent total body dual-energy x-ray absorptiometry (DEXA). The patients ranged in age from 10 years to almost 20 years. Just over half (53%) were assigned female sex at birth.

The mean Z scores, signifying deviation from age-matched norms, were lower regardless of current use or past use of GnRH agonists in both transgender males or transgender females, relative to age-matched norms.

Asked to comment, Michele A. O’Connell, MBBCh, department of endocrinology and diabetes, Royal Children’s Hospital, Victoria, Australia, said the risk of bone loss is real.

“Monitoring of bone health is recommended for all transgender-diverse adolescents treated with gonadotropin-releasing hormone agonists,” said Dr. O’Connell. He referred to multiple guidelines, including those issued by the World Professional Association of Transgender Health in 2012 and those from the Endocrine Society that were issued in 2017.
 

Inverse correlation between duration of GnRH agonist therapy and Z scores

In Dr. Nokoff’s study, for transgender males, the BMD Z score was reduced 0.2 relative to male norms and by 0.4 relative to female norms. For transgender females, the scores were reduced by 0.4 relative to male norms and by 0.2 relative to female norms.

Among transgender males who were taking testosterone and who had previously been exposed to GnRH agonists, the Z score was significantly lower than those taking testosterone alone (P = .004). There were no differences in Z score for transgender females taking estradiol alone relative to estradiol with current or past use of GnRH agonists.

There was a significant inverse correlation for duration of GnRH agonist therapy and Z scores for transgender females relative to male norms (P = .005) or female norms (P = .029). However, Z scores were unrelated to length of time receiving testosterone or estradiol therapy or to sex steroid concentrations.

The number of children and adolescents taking puberty-delaying or gender-affirming therapies is increasing. Although reliable data are limited, the exploration of gender identify appears to have become more common with the growing social acceptance of gender dysphoria. That term refers to a sense of unease among individuals who feel that their biological sex does not match their gender identity, according to Dr. Nokoff.

“It is now estimated that 2% of youths identify as transgender,” she said.

Findings from studies investigating the relationship between gender-affirming therapy and bone loss among adults have not been consistent. In a single-center study that followed 543 transgender men and 711 transgender women who had undergone DEXA scanning at baseline prior to starting hormone therapy, there did not appear to be any substantial negative effects on lumbar bone density over time (J Bone Min Res. 2018 Dec;34:447-54).

For adolescents, there is growing evidence of the risk of bone loss in relation to gender-affirming therapy, but there is limited agreement on clinical risks and how they can be avoided. Relevant variables include genetics and diet, as well as the types, doses, and length of time receiving gender-affirming therapy.
 

Monitor bone in transgender youth; Use vitamin D and weight-bearing exercise

Dr. O’Connell is the first author of a recent summary of the pharmacologic management of trans and gender-diverse adolescents. That summary covered multiple topics in addition to risk of bone loss, including the impact on growth, cognition, and mental health (J Clin Endocrinol Metab. 2022 Jan;107:241-257).

Overall, she believes that bone health should be monitored for children receiving puberty-delaying or gender-affirming therapies but agrees with Dr. Nokoff that the clinical impact remains poorly defined.

“Long-term follow-up studies will be required to assess the impact, if any, on functional outcomes such as fracture risk,” she reported. Still, she encouraged use of standard ways of improving bone health, including adequate vitamin D intake and weight-bearing exercise.

Dr. Nokoff and Dr. O’Connell have disclosed no relevant financial relationships.

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

Among transgender youth who receive puberty-delaying or gender-affirming hormone therapy, bone mineral density (BMD) is lower relative to age-based norms, and this is true regardless of gender assignment at birth.

The problem worsens as the time during which these patients receive sex steroid hormones increases. So far, the “bone mineral density effects of these therapies are understudied,” warned Natalie Nokoff, MD, who presented a cross-sectional study at the annual meeting of the Endocrine Society.

The study of bone density is part of a larger body of research being conducted by Dr. Nokoff and her co-investigators on the long-term health effects of gender-affirming therapy in children and adolescents. In one of several recent studies, transgender youths taking gonadotropin-releasing hormone (GnRH) agonists, which effectively block puberty, were shown to be at greater risk of adverse changes in body composition and markers of cardiometabolic health than youths who were not taking them.

“We need more information on the optimal length of treatment with puberty-delaying medications before either discontinuation or introduction of gender-affirming hormones,” said Dr. Nokoff, an assistant professor of pediatrics and endocrinology at the University of Colorado School of Medicine, Aurora.

In this study, 56 transgender youth underwent total body dual-energy x-ray absorptiometry (DEXA). The patients ranged in age from 10 years to almost 20 years. Just over half (53%) were assigned female sex at birth.

The mean Z scores, signifying deviation from age-matched norms, were lower regardless of current use or past use of GnRH agonists in both transgender males or transgender females, relative to age-matched norms.

Asked to comment, Michele A. O’Connell, MBBCh, department of endocrinology and diabetes, Royal Children’s Hospital, Victoria, Australia, said the risk of bone loss is real.

“Monitoring of bone health is recommended for all transgender-diverse adolescents treated with gonadotropin-releasing hormone agonists,” said Dr. O’Connell. He referred to multiple guidelines, including those issued by the World Professional Association of Transgender Health in 2012 and those from the Endocrine Society that were issued in 2017.
 

Inverse correlation between duration of GnRH agonist therapy and Z scores

In Dr. Nokoff’s study, for transgender males, the BMD Z score was reduced 0.2 relative to male norms and by 0.4 relative to female norms. For transgender females, the scores were reduced by 0.4 relative to male norms and by 0.2 relative to female norms.

Among transgender males who were taking testosterone and who had previously been exposed to GnRH agonists, the Z score was significantly lower than those taking testosterone alone (P = .004). There were no differences in Z score for transgender females taking estradiol alone relative to estradiol with current or past use of GnRH agonists.

There was a significant inverse correlation for duration of GnRH agonist therapy and Z scores for transgender females relative to male norms (P = .005) or female norms (P = .029). However, Z scores were unrelated to length of time receiving testosterone or estradiol therapy or to sex steroid concentrations.

The number of children and adolescents taking puberty-delaying or gender-affirming therapies is increasing. Although reliable data are limited, the exploration of gender identify appears to have become more common with the growing social acceptance of gender dysphoria. That term refers to a sense of unease among individuals who feel that their biological sex does not match their gender identity, according to Dr. Nokoff.

“It is now estimated that 2% of youths identify as transgender,” she said.

Findings from studies investigating the relationship between gender-affirming therapy and bone loss among adults have not been consistent. In a single-center study that followed 543 transgender men and 711 transgender women who had undergone DEXA scanning at baseline prior to starting hormone therapy, there did not appear to be any substantial negative effects on lumbar bone density over time (J Bone Min Res. 2018 Dec;34:447-54).

For adolescents, there is growing evidence of the risk of bone loss in relation to gender-affirming therapy, but there is limited agreement on clinical risks and how they can be avoided. Relevant variables include genetics and diet, as well as the types, doses, and length of time receiving gender-affirming therapy.
 

Monitor bone in transgender youth; Use vitamin D and weight-bearing exercise

Dr. O’Connell is the first author of a recent summary of the pharmacologic management of trans and gender-diverse adolescents. That summary covered multiple topics in addition to risk of bone loss, including the impact on growth, cognition, and mental health (J Clin Endocrinol Metab. 2022 Jan;107:241-257).

Overall, she believes that bone health should be monitored for children receiving puberty-delaying or gender-affirming therapies but agrees with Dr. Nokoff that the clinical impact remains poorly defined.

“Long-term follow-up studies will be required to assess the impact, if any, on functional outcomes such as fracture risk,” she reported. Still, she encouraged use of standard ways of improving bone health, including adequate vitamin D intake and weight-bearing exercise.

Dr. Nokoff and Dr. O’Connell have disclosed no relevant financial relationships.

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

GLASGOW – Individuals given COVID-19 vaccination may experience a wide range of dermatologic reactions, some of which may be life-threatening, reveals a prospective Indian study that suggests histopathological assessment is key to understanding the cause.

Studying more than 130 patients who presented with vaccine-related dermatologic reactions, the researchers found that the most common acute adverse events were acute urticaria, generalized pruritus, and maculopapular rash.

Dermal hypersensitivity reactions occurred within 3 days of vaccination, which suggests the culprit is an immediate type 1 hypersensitivity reaction, said study presenter Alpana Mohta, MD, department of dermatology, Sardar Patel Medical College, Bikaner, Rajasthan, India. Most of the patients had received the AstraZeneca vaccine, she said.

The most common delayed events were pityriasis rosea and lichen planus, which occurred within 3-4 weeks of vaccination and could be a result of delayed hypersensitivity or a T cell–mediated skin reaction caused by “molecular mimicry with a viral epitope,” Dr. Mohta said.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 5.

Dr. Mohta said that, given the “surge” in the number of people who have been vaccinated, it is “imperative as dermatologists” to maintain a “very high index of suspicion to differentiate reactions caused by vaccination” from other causes, and a proper assessment should be performed in “every patient” who presents with a possible reaction.

She also emphasized that “since so many clinical [COVID-19] variants are being encountered,” histopathological assessment could “help in better understanding the underlying pathophysiology” of every reaction.

Dr. Mohta began her presentation by explaining that India is running one of the “world’s largest vaccination drives” for COVID-19, with almost 90% of adults fully vaccinated.

She added that studies have indicated that the incidence of cutaneous adverse reactions following COVID-19 vaccination ranges from 1.0% to 1.9% and that dermatologists have encountered a “plethora” of related reactions.

Dr. Mohta emphasized that the “myriad presentations” of these reactions means that correlating clinical and pathological findings is “key” to understanding the underlying pathophysiology.

She and her colleagues therefore conducted a prospective, hospital-based study of patients who self-reported mucocutaneous adverse reactions from April to December 2021, within 4 weeks of receiving a COVID-19 vaccine.

They gathered information on the patients’ signs and symptoms, as well as the date of vaccine administration and the type of vaccine given, alongside a detailed medical history, including previous allergies, prior COVID-19 infection, and any comorbidities.

The patients also underwent a clinical examination and laboratory investigations, and their cases were assessed by two senior dermatologists to determine whether the association between the adverse event and COVID-19 vaccination was likely causal.

Dr. Mohta said that 132 adult patients, with an average age of 38.2 years, were identified as having vaccine-related reactions.

This included 84 (63.6%) patients with a mild reaction, defined as resolving with symptomatic treatment; 43 (32.6%) patients with a moderate reaction, defined as extensive and lasting for more than 4 weeks; and five (3.8%) patients with severe reactions, defined as systemic and potentially life-threatening.

The mild group included 21 patients with acute urticaria, with a mean onset of 1.2 days following vaccination, as well as 20 cases of maculopapular rash, with a mean onset of 2.4 days; 18 cases of pityriasis rosea, with a mean onset of 17.4 days; and nine cases of eruptive pseudoangioma, with a mean onset of 3.5 days.

There were 16 cases of lichen planus in the moderate group, with a mean onset of 22.7 days after COVID-19 vaccination; nine cases of herpes zoster, with a mean onset of 15.3 days; and one case of pityriasis lichenoides et varioliformis acuta (PLEVA), among others.

The severe group included two cases of erythroderma, with a mean onset of 9 days after vaccination; one case of drug rash with eosinophilia and systemic symptoms (DRESS), with a mean onset of 20 days; and one case each of subacute cutaneous lupus erythematosus (SCLE) and bullous pemphigoid, with mean onsets of 15 days and 14 days, respectively.

Turning to the histopathological results, Dr. Mohta explained that only 57 patients from their cohort agreed to have a skin biopsy.

Results of those skin biopsies showed that 21 (36.8%) patients had vaccine-related eruption of papules and plaques, predominantly spongiotic dermatitis. This correlated with the clinical diagnoses of pityriasis rosea, maculopapular and papulosquamous rash, and DRESS.

Lichenoid and interface dermatitis were seen in 13 (22.8%) patients, which correlated with the clinical diagnoses of lichen planus, PLEVA, and SCLE. Eleven (19.3%) patients had a dermal hypersensitivity reaction, equated to the clinical diagnoses of urticaria, and eruptive pseudoangioma.

Dr. Mohta acknowledged that the study was limited by the inability to calculate the “true prevalence of vaccine-associated reactions,” and because immunohistochemistry was not performed.

Session chair Saleem Taibjee, MD, department of dermatology, Dorset County Hospital NHS Foundation Trust, Dorchester, United Kingdom, congratulated Dr. Mohta on her “very interesting” presentation, highlighting their “extensive experience in such a large cohort of patients.”

He asked what type of COVID-19 vaccines the patients had received, and whether Dr. Mohta could provide any “insights into which patients you can safely give the vaccine again to, and those [to whom] you may avoid giving further doses.”

Dr. Mohta said that the majority of the patients in the study received the AstraZeneca COVID-19 vaccine, as that was the one most commonly used in India at the time, with around 30 patients receiving the Indian Covishield version of the AstraZeneca vaccine. (The two-dose AstraZeneca vaccine, which is cheaper to manufacture and easier to store at typical refrigerated temperatures than mRNA-based vaccines, has been authorized by the World Health Organization, the European Medicines Agency, and over 50 countries but has not been authorized in the United States.)

She added that none of the patients in the study with mild-to-moderate skin reactions were advised against receiving further doses” but that those with severe reactions “were advised not to take any further doses.”

Consequently, in the case of mild reactions, “further doses are not a contraindication,” Dr. Mohta said, but patients with more severe reactions should be considered on a “case by case basis.”

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

GLASGOW – Individuals given COVID-19 vaccination may experience a wide range of dermatologic reactions, some of which may be life-threatening, reveals a prospective Indian study that suggests histopathological assessment is key to understanding the cause.

Studying more than 130 patients who presented with vaccine-related dermatologic reactions, the researchers found that the most common acute adverse events were acute urticaria, generalized pruritus, and maculopapular rash.

Dermal hypersensitivity reactions occurred within 3 days of vaccination, which suggests the culprit is an immediate type 1 hypersensitivity reaction, said study presenter Alpana Mohta, MD, department of dermatology, Sardar Patel Medical College, Bikaner, Rajasthan, India. Most of the patients had received the AstraZeneca vaccine, she said.

The most common delayed events were pityriasis rosea and lichen planus, which occurred within 3-4 weeks of vaccination and could be a result of delayed hypersensitivity or a T cell–mediated skin reaction caused by “molecular mimicry with a viral epitope,” Dr. Mohta said.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 5.

Dr. Mohta said that, given the “surge” in the number of people who have been vaccinated, it is “imperative as dermatologists” to maintain a “very high index of suspicion to differentiate reactions caused by vaccination” from other causes, and a proper assessment should be performed in “every patient” who presents with a possible reaction.

She also emphasized that “since so many clinical [COVID-19] variants are being encountered,” histopathological assessment could “help in better understanding the underlying pathophysiology” of every reaction.

Dr. Mohta began her presentation by explaining that India is running one of the “world’s largest vaccination drives” for COVID-19, with almost 90% of adults fully vaccinated.

She added that studies have indicated that the incidence of cutaneous adverse reactions following COVID-19 vaccination ranges from 1.0% to 1.9% and that dermatologists have encountered a “plethora” of related reactions.

Dr. Mohta emphasized that the “myriad presentations” of these reactions means that correlating clinical and pathological findings is “key” to understanding the underlying pathophysiology.

She and her colleagues therefore conducted a prospective, hospital-based study of patients who self-reported mucocutaneous adverse reactions from April to December 2021, within 4 weeks of receiving a COVID-19 vaccine.

They gathered information on the patients’ signs and symptoms, as well as the date of vaccine administration and the type of vaccine given, alongside a detailed medical history, including previous allergies, prior COVID-19 infection, and any comorbidities.

The patients also underwent a clinical examination and laboratory investigations, and their cases were assessed by two senior dermatologists to determine whether the association between the adverse event and COVID-19 vaccination was likely causal.

Dr. Mohta said that 132 adult patients, with an average age of 38.2 years, were identified as having vaccine-related reactions.

This included 84 (63.6%) patients with a mild reaction, defined as resolving with symptomatic treatment; 43 (32.6%) patients with a moderate reaction, defined as extensive and lasting for more than 4 weeks; and five (3.8%) patients with severe reactions, defined as systemic and potentially life-threatening.

The mild group included 21 patients with acute urticaria, with a mean onset of 1.2 days following vaccination, as well as 20 cases of maculopapular rash, with a mean onset of 2.4 days; 18 cases of pityriasis rosea, with a mean onset of 17.4 days; and nine cases of eruptive pseudoangioma, with a mean onset of 3.5 days.

There were 16 cases of lichen planus in the moderate group, with a mean onset of 22.7 days after COVID-19 vaccination; nine cases of herpes zoster, with a mean onset of 15.3 days; and one case of pityriasis lichenoides et varioliformis acuta (PLEVA), among others.

The severe group included two cases of erythroderma, with a mean onset of 9 days after vaccination; one case of drug rash with eosinophilia and systemic symptoms (DRESS), with a mean onset of 20 days; and one case each of subacute cutaneous lupus erythematosus (SCLE) and bullous pemphigoid, with mean onsets of 15 days and 14 days, respectively.

Turning to the histopathological results, Dr. Mohta explained that only 57 patients from their cohort agreed to have a skin biopsy.

Results of those skin biopsies showed that 21 (36.8%) patients had vaccine-related eruption of papules and plaques, predominantly spongiotic dermatitis. This correlated with the clinical diagnoses of pityriasis rosea, maculopapular and papulosquamous rash, and DRESS.

Lichenoid and interface dermatitis were seen in 13 (22.8%) patients, which correlated with the clinical diagnoses of lichen planus, PLEVA, and SCLE. Eleven (19.3%) patients had a dermal hypersensitivity reaction, equated to the clinical diagnoses of urticaria, and eruptive pseudoangioma.

Dr. Mohta acknowledged that the study was limited by the inability to calculate the “true prevalence of vaccine-associated reactions,” and because immunohistochemistry was not performed.

Session chair Saleem Taibjee, MD, department of dermatology, Dorset County Hospital NHS Foundation Trust, Dorchester, United Kingdom, congratulated Dr. Mohta on her “very interesting” presentation, highlighting their “extensive experience in such a large cohort of patients.”

He asked what type of COVID-19 vaccines the patients had received, and whether Dr. Mohta could provide any “insights into which patients you can safely give the vaccine again to, and those [to whom] you may avoid giving further doses.”

Dr. Mohta said that the majority of the patients in the study received the AstraZeneca COVID-19 vaccine, as that was the one most commonly used in India at the time, with around 30 patients receiving the Indian Covishield version of the AstraZeneca vaccine. (The two-dose AstraZeneca vaccine, which is cheaper to manufacture and easier to store at typical refrigerated temperatures than mRNA-based vaccines, has been authorized by the World Health Organization, the European Medicines Agency, and over 50 countries but has not been authorized in the United States.)

She added that none of the patients in the study with mild-to-moderate skin reactions were advised against receiving further doses” but that those with severe reactions “were advised not to take any further doses.”

Consequently, in the case of mild reactions, “further doses are not a contraindication,” Dr. Mohta said, but patients with more severe reactions should be considered on a “case by case basis.”

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

GLASGOW – Individuals given COVID-19 vaccination may experience a wide range of dermatologic reactions, some of which may be life-threatening, reveals a prospective Indian study that suggests histopathological assessment is key to understanding the cause.

Studying more than 130 patients who presented with vaccine-related dermatologic reactions, the researchers found that the most common acute adverse events were acute urticaria, generalized pruritus, and maculopapular rash.

Dermal hypersensitivity reactions occurred within 3 days of vaccination, which suggests the culprit is an immediate type 1 hypersensitivity reaction, said study presenter Alpana Mohta, MD, department of dermatology, Sardar Patel Medical College, Bikaner, Rajasthan, India. Most of the patients had received the AstraZeneca vaccine, she said.

The most common delayed events were pityriasis rosea and lichen planus, which occurred within 3-4 weeks of vaccination and could be a result of delayed hypersensitivity or a T cell–mediated skin reaction caused by “molecular mimicry with a viral epitope,” Dr. Mohta said.

The research was presented at the British Association of Dermatologists (BAD) 2022 Annual Meeting on July 5.

Dr. Mohta said that, given the “surge” in the number of people who have been vaccinated, it is “imperative as dermatologists” to maintain a “very high index of suspicion to differentiate reactions caused by vaccination” from other causes, and a proper assessment should be performed in “every patient” who presents with a possible reaction.

She also emphasized that “since so many clinical [COVID-19] variants are being encountered,” histopathological assessment could “help in better understanding the underlying pathophysiology” of every reaction.

Dr. Mohta began her presentation by explaining that India is running one of the “world’s largest vaccination drives” for COVID-19, with almost 90% of adults fully vaccinated.

She added that studies have indicated that the incidence of cutaneous adverse reactions following COVID-19 vaccination ranges from 1.0% to 1.9% and that dermatologists have encountered a “plethora” of related reactions.

Dr. Mohta emphasized that the “myriad presentations” of these reactions means that correlating clinical and pathological findings is “key” to understanding the underlying pathophysiology.

She and her colleagues therefore conducted a prospective, hospital-based study of patients who self-reported mucocutaneous adverse reactions from April to December 2021, within 4 weeks of receiving a COVID-19 vaccine.

They gathered information on the patients’ signs and symptoms, as well as the date of vaccine administration and the type of vaccine given, alongside a detailed medical history, including previous allergies, prior COVID-19 infection, and any comorbidities.

The patients also underwent a clinical examination and laboratory investigations, and their cases were assessed by two senior dermatologists to determine whether the association between the adverse event and COVID-19 vaccination was likely causal.

Dr. Mohta said that 132 adult patients, with an average age of 38.2 years, were identified as having vaccine-related reactions.

This included 84 (63.6%) patients with a mild reaction, defined as resolving with symptomatic treatment; 43 (32.6%) patients with a moderate reaction, defined as extensive and lasting for more than 4 weeks; and five (3.8%) patients with severe reactions, defined as systemic and potentially life-threatening.

The mild group included 21 patients with acute urticaria, with a mean onset of 1.2 days following vaccination, as well as 20 cases of maculopapular rash, with a mean onset of 2.4 days; 18 cases of pityriasis rosea, with a mean onset of 17.4 days; and nine cases of eruptive pseudoangioma, with a mean onset of 3.5 days.

There were 16 cases of lichen planus in the moderate group, with a mean onset of 22.7 days after COVID-19 vaccination; nine cases of herpes zoster, with a mean onset of 15.3 days; and one case of pityriasis lichenoides et varioliformis acuta (PLEVA), among others.

The severe group included two cases of erythroderma, with a mean onset of 9 days after vaccination; one case of drug rash with eosinophilia and systemic symptoms (DRESS), with a mean onset of 20 days; and one case each of subacute cutaneous lupus erythematosus (SCLE) and bullous pemphigoid, with mean onsets of 15 days and 14 days, respectively.

Turning to the histopathological results, Dr. Mohta explained that only 57 patients from their cohort agreed to have a skin biopsy.

Results of those skin biopsies showed that 21 (36.8%) patients had vaccine-related eruption of papules and plaques, predominantly spongiotic dermatitis. This correlated with the clinical diagnoses of pityriasis rosea, maculopapular and papulosquamous rash, and DRESS.

Lichenoid and interface dermatitis were seen in 13 (22.8%) patients, which correlated with the clinical diagnoses of lichen planus, PLEVA, and SCLE. Eleven (19.3%) patients had a dermal hypersensitivity reaction, equated to the clinical diagnoses of urticaria, and eruptive pseudoangioma.

Dr. Mohta acknowledged that the study was limited by the inability to calculate the “true prevalence of vaccine-associated reactions,” and because immunohistochemistry was not performed.

Session chair Saleem Taibjee, MD, department of dermatology, Dorset County Hospital NHS Foundation Trust, Dorchester, United Kingdom, congratulated Dr. Mohta on her “very interesting” presentation, highlighting their “extensive experience in such a large cohort of patients.”

He asked what type of COVID-19 vaccines the patients had received, and whether Dr. Mohta could provide any “insights into which patients you can safely give the vaccine again to, and those [to whom] you may avoid giving further doses.”

Dr. Mohta said that the majority of the patients in the study received the AstraZeneca COVID-19 vaccine, as that was the one most commonly used in India at the time, with around 30 patients receiving the Indian Covishield version of the AstraZeneca vaccine. (The two-dose AstraZeneca vaccine, which is cheaper to manufacture and easier to store at typical refrigerated temperatures than mRNA-based vaccines, has been authorized by the World Health Organization, the European Medicines Agency, and over 50 countries but has not been authorized in the United States.)

She added that none of the patients in the study with mild-to-moderate skin reactions were advised against receiving further doses” but that those with severe reactions “were advised not to take any further doses.”

Consequently, in the case of mild reactions, “further doses are not a contraindication,” Dr. Mohta said, but patients with more severe reactions should be considered on a “case by case basis.”

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

A large case-control study finds the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is broader than previously determined from prior analyses showing associations with breast, ovarian, prostate, and pancreatic cancers. The finding, published in JAMA Oncology suggests a possible broader clinical relevance for BRCA1 and BRCA2 genetic testing.

Pathogenic variants in BRCA1 were found to be associated with biliary tract cancer, in BRCA2 with esophageal cancer, and in BRCA1/2 with gastric cancer.

“The results suggest the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is likely broader than that determined from previous analysis of largely European ancestry cohorts,” wrote authors who were led by Yukihide Momozawa, DVM, PhD, RIKEN Center for Integrative Medical Sciences, Japan.

“These risk association findings, together with our analysis of an association with family history of cancer and clinical phenotypes, are relevant for developing and adapting guidelines about genetic testing, treatment options, and treatability with PARP [poly adenosine diphosphate-ribose polymerase] inhibitors for each cancer type,” the authors wrote.

Dr. Momozawa and associates conducted a large-scale sequencing study across 14 common cancer types in 63,828 patients (mean age 64 years, 42% female) and 37,086 controls on data drawn from a Japanese nationwide biobank between April 2003 and March 2018. They estimated the risk of each cancer type and determined clinical characteristics associated with pathogenic variant carrier status, while also investigating the utility of family history in detecting patients with pathogenic variants.

Three hundred fifteen pathogenic variants were identified. An odds ratios of greater than 4.0 (with P < 1 × 10−4 as the threshold of significance) for the pathogenic variants were found for biliary tract cancer (OR, 17.4; 95% confidence interval, 5.8-51.9) in BRCA1, esophageal cancer (OR, 5.6; 95% CI, 2.9-11.0) in BRCA2, and gastric cancer (OR, 5.2; 95% CI, 2.6-10.5) in BRCA1, and (OR, 4.7; 95% CI, 3.1-7.1) in BRCA2. Two other cancer types were found to be associated with BRCA1, and four other cancer types with BRCA2. Enrichment of carrier patients was shown in biliary tract, female breast, ovarian, and prostate cancers in accordance with increased numbers of reported cancer types in relatives.

Male patients with breast cancer had a very high carrier frequency of pathogenic variants in BRCA2 (18.9%), but not BRCA1 (1.89%). Patients with ovarian cancer showed the next highest proportion (BRCA1, 4.86%; BRCA2, 3.42%). Frequency exceeding 1% was seen for several other cancer types (two cancer types for BRCA1, four cancer types for BRCA2). More than one cancer types was identified in 4,128 patients (6.3%). Carrier frequency of pathogenic variants in BRCA1 was 0.44% with one cancer type, 0.85% with two cancer types, and 0.69% with three cancer types. It was 0.97%, 1.40%, and 1.74%, respectively, in BRCA2.

“The results of this large-scale registry-based case-control study suggest that pathogenic variants in BRCA1 and BRCA2 were associated with the risk of seven cancer types. These results indicate broader clinical relevance of BRCA1 and BRCA2 genetic testing,” the authors wrote.

PARP inhibitors were developed based on the mechanism in BRCA1 and BRCA2 of homologous recombination repair defects associated with pathogenic variants. PARP inhibitors have been found to have therapeutic efficacy also in pathogenic variants found to be enriched in prostate and pancreatic cancers. While risk for additional cancer types (for example, biliary tract cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, and stomach cancer) has been reported after analyzing family members for the presence of pathogenic variants and performing case-control analyses, evidence for an association with these cancer types has not been considered sufficient for them to be adopted into clinical management guidelines, the authors wrote.

In an interview, Dr. Momozawa said that BRCA1 and BRCA2 genetic testing should be expanded in Japan. “But further studies are needed to reveal how much. If a clinical trial of a PARP inhibitor for these three cancer types reveals its clinical utility, the importance of this expansion will increase.”

Dr. Momozawa and associates state that while their selection of controls without a family history of cancer affects the generalizability of the study results, the estimated cumulative risks were comparable with those based on prospective cohorts, suggesting the study design did not greatly affect the results.

A large case-control study finds the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is broader than previously determined from prior analyses showing associations with breast, ovarian, prostate, and pancreatic cancers. The finding, published in JAMA Oncology suggests a possible broader clinical relevance for BRCA1 and BRCA2 genetic testing.

Pathogenic variants in BRCA1 were found to be associated with biliary tract cancer, in BRCA2 with esophageal cancer, and in BRCA1/2 with gastric cancer.

“The results suggest the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is likely broader than that determined from previous analysis of largely European ancestry cohorts,” wrote authors who were led by Yukihide Momozawa, DVM, PhD, RIKEN Center for Integrative Medical Sciences, Japan.

“These risk association findings, together with our analysis of an association with family history of cancer and clinical phenotypes, are relevant for developing and adapting guidelines about genetic testing, treatment options, and treatability with PARP [poly adenosine diphosphate-ribose polymerase] inhibitors for each cancer type,” the authors wrote.

Dr. Momozawa and associates conducted a large-scale sequencing study across 14 common cancer types in 63,828 patients (mean age 64 years, 42% female) and 37,086 controls on data drawn from a Japanese nationwide biobank between April 2003 and March 2018. They estimated the risk of each cancer type and determined clinical characteristics associated with pathogenic variant carrier status, while also investigating the utility of family history in detecting patients with pathogenic variants.

Three hundred fifteen pathogenic variants were identified. An odds ratios of greater than 4.0 (with P < 1 × 10−4 as the threshold of significance) for the pathogenic variants were found for biliary tract cancer (OR, 17.4; 95% confidence interval, 5.8-51.9) in BRCA1, esophageal cancer (OR, 5.6; 95% CI, 2.9-11.0) in BRCA2, and gastric cancer (OR, 5.2; 95% CI, 2.6-10.5) in BRCA1, and (OR, 4.7; 95% CI, 3.1-7.1) in BRCA2. Two other cancer types were found to be associated with BRCA1, and four other cancer types with BRCA2. Enrichment of carrier patients was shown in biliary tract, female breast, ovarian, and prostate cancers in accordance with increased numbers of reported cancer types in relatives.

Male patients with breast cancer had a very high carrier frequency of pathogenic variants in BRCA2 (18.9%), but not BRCA1 (1.89%). Patients with ovarian cancer showed the next highest proportion (BRCA1, 4.86%; BRCA2, 3.42%). Frequency exceeding 1% was seen for several other cancer types (two cancer types for BRCA1, four cancer types for BRCA2). More than one cancer types was identified in 4,128 patients (6.3%). Carrier frequency of pathogenic variants in BRCA1 was 0.44% with one cancer type, 0.85% with two cancer types, and 0.69% with three cancer types. It was 0.97%, 1.40%, and 1.74%, respectively, in BRCA2.

“The results of this large-scale registry-based case-control study suggest that pathogenic variants in BRCA1 and BRCA2 were associated with the risk of seven cancer types. These results indicate broader clinical relevance of BRCA1 and BRCA2 genetic testing,” the authors wrote.

PARP inhibitors were developed based on the mechanism in BRCA1 and BRCA2 of homologous recombination repair defects associated with pathogenic variants. PARP inhibitors have been found to have therapeutic efficacy also in pathogenic variants found to be enriched in prostate and pancreatic cancers. While risk for additional cancer types (for example, biliary tract cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, and stomach cancer) has been reported after analyzing family members for the presence of pathogenic variants and performing case-control analyses, evidence for an association with these cancer types has not been considered sufficient for them to be adopted into clinical management guidelines, the authors wrote.

In an interview, Dr. Momozawa said that BRCA1 and BRCA2 genetic testing should be expanded in Japan. “But further studies are needed to reveal how much. If a clinical trial of a PARP inhibitor for these three cancer types reveals its clinical utility, the importance of this expansion will increase.”

Dr. Momozawa and associates state that while their selection of controls without a family history of cancer affects the generalizability of the study results, the estimated cumulative risks were comparable with those based on prospective cohorts, suggesting the study design did not greatly affect the results.

A large case-control study finds the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is broader than previously determined from prior analyses showing associations with breast, ovarian, prostate, and pancreatic cancers. The finding, published in JAMA Oncology suggests a possible broader clinical relevance for BRCA1 and BRCA2 genetic testing.

Pathogenic variants in BRCA1 were found to be associated with biliary tract cancer, in BRCA2 with esophageal cancer, and in BRCA1/2 with gastric cancer.

“The results suggest the range of cancer types associated with pathogenic variants in BRCA1 and BRCA2 is likely broader than that determined from previous analysis of largely European ancestry cohorts,” wrote authors who were led by Yukihide Momozawa, DVM, PhD, RIKEN Center for Integrative Medical Sciences, Japan.

“These risk association findings, together with our analysis of an association with family history of cancer and clinical phenotypes, are relevant for developing and adapting guidelines about genetic testing, treatment options, and treatability with PARP [poly adenosine diphosphate-ribose polymerase] inhibitors for each cancer type,” the authors wrote.

Dr. Momozawa and associates conducted a large-scale sequencing study across 14 common cancer types in 63,828 patients (mean age 64 years, 42% female) and 37,086 controls on data drawn from a Japanese nationwide biobank between April 2003 and March 2018. They estimated the risk of each cancer type and determined clinical characteristics associated with pathogenic variant carrier status, while also investigating the utility of family history in detecting patients with pathogenic variants.

Three hundred fifteen pathogenic variants were identified. An odds ratios of greater than 4.0 (with P < 1 × 10−4 as the threshold of significance) for the pathogenic variants were found for biliary tract cancer (OR, 17.4; 95% confidence interval, 5.8-51.9) in BRCA1, esophageal cancer (OR, 5.6; 95% CI, 2.9-11.0) in BRCA2, and gastric cancer (OR, 5.2; 95% CI, 2.6-10.5) in BRCA1, and (OR, 4.7; 95% CI, 3.1-7.1) in BRCA2. Two other cancer types were found to be associated with BRCA1, and four other cancer types with BRCA2. Enrichment of carrier patients was shown in biliary tract, female breast, ovarian, and prostate cancers in accordance with increased numbers of reported cancer types in relatives.

Male patients with breast cancer had a very high carrier frequency of pathogenic variants in BRCA2 (18.9%), but not BRCA1 (1.89%). Patients with ovarian cancer showed the next highest proportion (BRCA1, 4.86%; BRCA2, 3.42%). Frequency exceeding 1% was seen for several other cancer types (two cancer types for BRCA1, four cancer types for BRCA2). More than one cancer types was identified in 4,128 patients (6.3%). Carrier frequency of pathogenic variants in BRCA1 was 0.44% with one cancer type, 0.85% with two cancer types, and 0.69% with three cancer types. It was 0.97%, 1.40%, and 1.74%, respectively, in BRCA2.

“The results of this large-scale registry-based case-control study suggest that pathogenic variants in BRCA1 and BRCA2 were associated with the risk of seven cancer types. These results indicate broader clinical relevance of BRCA1 and BRCA2 genetic testing,” the authors wrote.

PARP inhibitors were developed based on the mechanism in BRCA1 and BRCA2 of homologous recombination repair defects associated with pathogenic variants. PARP inhibitors have been found to have therapeutic efficacy also in pathogenic variants found to be enriched in prostate and pancreatic cancers. While risk for additional cancer types (for example, biliary tract cancer, cervical cancer, colorectal cancer, endometrial cancer, esophageal cancer, and stomach cancer) has been reported after analyzing family members for the presence of pathogenic variants and performing case-control analyses, evidence for an association with these cancer types has not been considered sufficient for them to be adopted into clinical management guidelines, the authors wrote.

In an interview, Dr. Momozawa said that BRCA1 and BRCA2 genetic testing should be expanded in Japan. “But further studies are needed to reveal how much. If a clinical trial of a PARP inhibitor for these three cancer types reveals its clinical utility, the importance of this expansion will increase.”

Dr. Momozawa and associates state that while their selection of controls without a family history of cancer affects the generalizability of the study results, the estimated cumulative risks were comparable with those based on prospective cohorts, suggesting the study design did not greatly affect the results.

In the United States, the cost of brand-name medications for treating epilepsy soared during the period 2010-2018, while the cost of generic antiseizure medications (ASMs) decreased, a new analysis shows.

After adjustment for inflation, the cost of a 1-year supply of brand-name ASMs grew 277%, while generics became 42% less expensive.

“Our study makes transparent striking trends in brand name prescribing patterns,” the study team wrote.

Since 2010, the costs for brand-name ASMs have “consistently” increased. Costs were particularly boosted by increases in prescriptions for lacosamide (Vimpat), in addition to a “steep increase in the cost per pill, with brand-name drugs costing 10 times more than their generic counterparts,” first author Samuel Waller Terman, MD, of the University of Michigan, Ann Arbor, added in a news release.

The study was published online  in Neurology.
 

Is a 10-fold increase in cost worth it?

To evaluate trends in ASM prescriptions and costs, the researchers used a random sample of 20% of Medicare beneficiaries with coverage from 2008 to 2018. There were 77,000 to 133,000 patients with epilepsy each year.

Over time, likely because of increasing availability of generics, brand-name ASMs made up a smaller proportion of pills prescribed, from 56% in 2008 to 14% in 2018, but still made up 79% of prescription drug costs in 2018.

The annual cost of brand-name ASMs rose from $2,800 in 2008 to $10,700 in 2018, while the cost of generic drugs decreased from $800 to $460 during that time.

An increased number of prescriptions for lacosamide was responsible for 45% of the total increase in brand-name costs.

As of 2018, lacosamide comprised 30% of all brand-name pill supply (followed by pregabalin, at 15%) and 30% of all brand-name costs (followed by clobazam and pregabalin, both at 9%), the investigators reported.

Brand-name antiepileptic drug costs decreased from 2008 to 2010, but after the introduction of lacosamide, total brand-name costs steadily rose from $72 million in 2010 (in 2018 dollars) to $256 million in 2018, they noted.

Because the dataset consists of a 20% random Medicare sample, total Medicare costs for brand-name ASMs for beneficiaries with epilepsy alone likely rose from roughly $360 million in 2010 to $1.3 billion in 2018, they added.

“Clinicians must remain cognizant of this societal cost magnitude when judging whether the 10-fold increased expense per pill for brand name medications is worth the possible benefits,” they wrote.

“While newer-generation drugs have potential advantages such as limited drug interactions and different side effect profiles, there have been conflicting studies on whether they are cost effective,” Dr. Terman noted in a news release.
 

A barrier to treatment

The authors of an accompanying editorial propose that the problem of prescription drug costs could be solved through a combination of competition and government regulation of prices. Patients and physicians are the most important stakeholders in this issue.

“When something represents 14% of the total use, but contributes 79% of the cost, it would be wise to consider alternatives, assuming that these alternatives are not of lower quality,” wrote Wyatt Bensken, with Case Western Reserve University, Cleveland, and Iván Sánchez Fernández, MD, with Boston Medical Center.

“When there are several ASMs with a similar mechanism of action, similar efficacy, similar safety and tolerability profile, and different costs, it would be unwise to choose the more expensive alternative just because it is newer,” they said.

This study, they added, provides data to “understand, and begin to act, on the challenging problem of the cost of prescription ASMs. After all, what is the point of having a large number of ASMs if their cost severely limits their use?”

A limitation of the study is that only Medicare prescription claims were included, so the results may not apply to younger patients with private insurance.

The study received no direct funding. The authors and editorialists have disclosed no relevant financial relationships.

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

In the United States, the cost of brand-name medications for treating epilepsy soared during the period 2010-2018, while the cost of generic antiseizure medications (ASMs) decreased, a new analysis shows.

After adjustment for inflation, the cost of a 1-year supply of brand-name ASMs grew 277%, while generics became 42% less expensive.

“Our study makes transparent striking trends in brand name prescribing patterns,” the study team wrote.

Since 2010, the costs for brand-name ASMs have “consistently” increased. Costs were particularly boosted by increases in prescriptions for lacosamide (Vimpat), in addition to a “steep increase in the cost per pill, with brand-name drugs costing 10 times more than their generic counterparts,” first author Samuel Waller Terman, MD, of the University of Michigan, Ann Arbor, added in a news release.

The study was published online  in Neurology.
 

Is a 10-fold increase in cost worth it?

To evaluate trends in ASM prescriptions and costs, the researchers used a random sample of 20% of Medicare beneficiaries with coverage from 2008 to 2018. There were 77,000 to 133,000 patients with epilepsy each year.

Over time, likely because of increasing availability of generics, brand-name ASMs made up a smaller proportion of pills prescribed, from 56% in 2008 to 14% in 2018, but still made up 79% of prescription drug costs in 2018.

The annual cost of brand-name ASMs rose from $2,800 in 2008 to $10,700 in 2018, while the cost of generic drugs decreased from $800 to $460 during that time.

An increased number of prescriptions for lacosamide was responsible for 45% of the total increase in brand-name costs.

As of 2018, lacosamide comprised 30% of all brand-name pill supply (followed by pregabalin, at 15%) and 30% of all brand-name costs (followed by clobazam and pregabalin, both at 9%), the investigators reported.

Brand-name antiepileptic drug costs decreased from 2008 to 2010, but after the introduction of lacosamide, total brand-name costs steadily rose from $72 million in 2010 (in 2018 dollars) to $256 million in 2018, they noted.

Because the dataset consists of a 20% random Medicare sample, total Medicare costs for brand-name ASMs for beneficiaries with epilepsy alone likely rose from roughly $360 million in 2010 to $1.3 billion in 2018, they added.

“Clinicians must remain cognizant of this societal cost magnitude when judging whether the 10-fold increased expense per pill for brand name medications is worth the possible benefits,” they wrote.

“While newer-generation drugs have potential advantages such as limited drug interactions and different side effect profiles, there have been conflicting studies on whether they are cost effective,” Dr. Terman noted in a news release.
 

A barrier to treatment

The authors of an accompanying editorial propose that the problem of prescription drug costs could be solved through a combination of competition and government regulation of prices. Patients and physicians are the most important stakeholders in this issue.

“When something represents 14% of the total use, but contributes 79% of the cost, it would be wise to consider alternatives, assuming that these alternatives are not of lower quality,” wrote Wyatt Bensken, with Case Western Reserve University, Cleveland, and Iván Sánchez Fernández, MD, with Boston Medical Center.

“When there are several ASMs with a similar mechanism of action, similar efficacy, similar safety and tolerability profile, and different costs, it would be unwise to choose the more expensive alternative just because it is newer,” they said.

This study, they added, provides data to “understand, and begin to act, on the challenging problem of the cost of prescription ASMs. After all, what is the point of having a large number of ASMs if their cost severely limits their use?”

A limitation of the study is that only Medicare prescription claims were included, so the results may not apply to younger patients with private insurance.

The study received no direct funding. The authors and editorialists have disclosed no relevant financial relationships.

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

In the United States, the cost of brand-name medications for treating epilepsy soared during the period 2010-2018, while the cost of generic antiseizure medications (ASMs) decreased, a new analysis shows.

After adjustment for inflation, the cost of a 1-year supply of brand-name ASMs grew 277%, while generics became 42% less expensive.

“Our study makes transparent striking trends in brand name prescribing patterns,” the study team wrote.

Since 2010, the costs for brand-name ASMs have “consistently” increased. Costs were particularly boosted by increases in prescriptions for lacosamide (Vimpat), in addition to a “steep increase in the cost per pill, with brand-name drugs costing 10 times more than their generic counterparts,” first author Samuel Waller Terman, MD, of the University of Michigan, Ann Arbor, added in a news release.

The study was published online  in Neurology.
 

Is a 10-fold increase in cost worth it?

To evaluate trends in ASM prescriptions and costs, the researchers used a random sample of 20% of Medicare beneficiaries with coverage from 2008 to 2018. There were 77,000 to 133,000 patients with epilepsy each year.

Over time, likely because of increasing availability of generics, brand-name ASMs made up a smaller proportion of pills prescribed, from 56% in 2008 to 14% in 2018, but still made up 79% of prescription drug costs in 2018.

The annual cost of brand-name ASMs rose from $2,800 in 2008 to $10,700 in 2018, while the cost of generic drugs decreased from $800 to $460 during that time.

An increased number of prescriptions for lacosamide was responsible for 45% of the total increase in brand-name costs.

As of 2018, lacosamide comprised 30% of all brand-name pill supply (followed by pregabalin, at 15%) and 30% of all brand-name costs (followed by clobazam and pregabalin, both at 9%), the investigators reported.

Brand-name antiepileptic drug costs decreased from 2008 to 2010, but after the introduction of lacosamide, total brand-name costs steadily rose from $72 million in 2010 (in 2018 dollars) to $256 million in 2018, they noted.

Because the dataset consists of a 20% random Medicare sample, total Medicare costs for brand-name ASMs for beneficiaries with epilepsy alone likely rose from roughly $360 million in 2010 to $1.3 billion in 2018, they added.

“Clinicians must remain cognizant of this societal cost magnitude when judging whether the 10-fold increased expense per pill for brand name medications is worth the possible benefits,” they wrote.

“While newer-generation drugs have potential advantages such as limited drug interactions and different side effect profiles, there have been conflicting studies on whether they are cost effective,” Dr. Terman noted in a news release.
 

A barrier to treatment

The authors of an accompanying editorial propose that the problem of prescription drug costs could be solved through a combination of competition and government regulation of prices. Patients and physicians are the most important stakeholders in this issue.

“When something represents 14% of the total use, but contributes 79% of the cost, it would be wise to consider alternatives, assuming that these alternatives are not of lower quality,” wrote Wyatt Bensken, with Case Western Reserve University, Cleveland, and Iván Sánchez Fernández, MD, with Boston Medical Center.

“When there are several ASMs with a similar mechanism of action, similar efficacy, similar safety and tolerability profile, and different costs, it would be unwise to choose the more expensive alternative just because it is newer,” they said.

This study, they added, provides data to “understand, and begin to act, on the challenging problem of the cost of prescription ASMs. After all, what is the point of having a large number of ASMs if their cost severely limits their use?”

A limitation of the study is that only Medicare prescription claims were included, so the results may not apply to younger patients with private insurance.

The study received no direct funding. The authors and editorialists have disclosed no relevant financial relationships.

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