To the Editor:

Ultra-late melanoma recurrence represents a minority of cases in which the quiescent period lasts longer than 15 years, and epidemiologic studies have reported recurrence rates of 6% to 10% during the ultra-late period.¹ Even more uncommon are cases that span many decades (eg, >30 years), but all are useful in understanding the cellular behavior leading to the reactivation of fully excised melanomas. Few cases have been reported in which recurrence occurs more than 35 years after the original diagnosis of melanoma. Unfortunately, mechanisms underlying this long stable quiescence and subsequent reactivation are poorly understood, which is why it is important to identify and document cases. We present a case of local recurrence of cutaneous melanoma on the patient’s lower back after a 49-year disease-free period.

A 78-year-old White woman presented to a private dermatology office for a full-body skin examination. She had a medical history of a cutaneous melanoma that had been removed on the lower back 49 years prior; Parkinson disease of 10 years’ duration; and an enlarged thyroid nodule with decreased thyrotropin and hyperthyroidism, atrial fibrillation, mitral valve prolapse, osteoarthritis in the knees, and actinic keratoses, all of which were chronic conditions lasting years to decades. She was taking several medications for these medical conditions. Her surgical history included a hysterectomy, hip replacement, hernia repair, cardioversion, and tonsillectomy in childhood. Her family medical history included breast cancer in her paternal grandmother and aunt; hypertension in her father; and sarcoma in her mother at 78 years of age, which initially was identified in the sacrum and metastasized to the lungs causing death. No family history of melanoma or other skin cancers was reported. Prior to the original diagnosis of melanoma at 29 years of age, she had no history of skin cancer or any other medical condition other than acne. The patient did report spending a great deal of time in the sun during high school.

The patient reported developing the original cutaneous melanoma during her second pregnancy at 29 years of age and recalled that it was excised with wide margins. There had been a mole on her back that was present for years but changed in size during pregnancy, prompting the original visit to the primary care physician for evaluation. Remarkably, the original pathology report was obtained from the patient and revealed a specimen consisting of a 3.7×1.7-cm skin ellipse averaging 0.7 cm in thickness. In the center of the specimen was a 0.6-cm, round, raised, pigmented lesion that revealed moderately frequent mitoses on microscopic evaluation. It was determined by the pathologist to be a malignant tumor, and the report stated that the surgical margins appeared clear.

Physical examination at the current presentation 49 years later revealed an even-bordered 2-mm black macule that was located approximately 1 cm from the original melanoma excision scar line (Figure). A biopsy was performed and sent to a dermatopathologist. Microscopic evaluation revealed nests, islands, and sheets of atypical epithelioid melanocytes extending through the dermis between collagen bundles. The melanocytes varied in size and shape with moderate nuclear pleomorphism present. Scattered mitotic figures and necrotic melanocytes were present, which most likely represented cutaneous satellite metastases of melanoma. Subsequent chest radiography, full-body positron emission tomography, and standard laboratory blood tests were unremarkable except for an enlarged right thyroid gland and moderate cardiomegaly. The patient was sent to a surgical oncologist for excision with wide surgical margins, and she elected not to have a sentinel lymph node biopsy. At follow-up 3, 6, 12, and 24 months later, there were no signs of recurrence based on direct clinical examination. The patient subsequently was lost to follow-up.

Recurrence rates of melanoma vary by stage and age at diagnosis, but prior studies have reported a recurrence rate of approximately 6% after 10 or more years following the initial diagnosis.² Ultra-late recurrences of approximately 4 decades or more are extremely rare. A PubMed search of articles indexed for MEDLINE using the terms melanoma and ultra-late recurrence revealed 4 reported cases with a quiescent period of 38 or more years.^3-6 All cases were metastatic melanomas in women; spanned 38, 40, 41, and 45 years from the initial melanoma diagnosis to recurrence; and all of the recurrences except one were regional or distal metastatic lesions (eg, lymph node, brain). In one case, both the original and recurrent lesions occurred on the left elbow.⁶ The original lesions occurred on the legs, elbow, and back of the neck, and there were no notable concomitant medical conditions. The patients were aged 72, 73, 73, and 84 years at recurrence.^3-6 However, generalizations from these cases are limited given the potential for selection bias (eg, men may be less likely to visit a clinic for follow-up and nevi examination) and the likelihood that many cases of ultra-late melanoma recurrence are unrecognized or unreported.

More recently, genomic analyses on melanoma lesions occurring 30 years apart confirmed that the second lesion was indeed a recurrence, although with numerous additional mutations.⁷ The specific mechanisms underlying the dormancy and subsequent reemergence of metastatic lesions are unclear, but there may be aberrations in the skin beyond histopathologic margins that represent an early phase of disease that are histologically unrecognizable and may lay dormant for many years before reemerging in response to external or immunologic changes.⁸ Alternatively, recurrences may be associated with lymphatic or hematogenous emboli, or there may be a tendency for melanomas to metastasize to inflamed or scarred tissue representing a tropism of the malignant melanocytes.⁹

It also is worth highlighting the concomitant diagnosis of Parkinson disease in our patient. In recent years, Parkinson disease has been linked to melanoma in both epidemiologic and genetic studies. For example, one large-scale study found a 50% increased risk for developing Parkinson disease in patients with melanoma (and vice versa), and this finding has been replicated in other studies.¹⁰ Moreover, patients with Parkinson disease have a 2-fold increase in their risk for developing melanoma, demonstrating that it is a bidirectional pathway. Not surprisingly, associations between melanin and neuromelanin pathways have been identified as a potential link between these diseases, and scientists are in the process of understanding the genetic components of both.¹⁰ It is unknown if specific genetic mutations contributed to both diseases in our case, but follow-up genetic testing on the recurrent melanoma specimen currently is being pursued.

The 49-year quiescent period in our case of recurrent cutaneous malignant melanoma potentially represents the longest ultra-late recurrence of melanoma in the literature to date based on a review of indexed publications. Moreover, it is relatively unique compared to other similar cases in that the recurrence was within a centimeter of the original excisional scar. Most metastases occur in locoregional lymph nodes or the lungs³; therefore, it is unusual to find one so close to the original lesion, especially one that occurred decades later. Factors associated with ultra-late recurrences are unknown, primarily because of the rarity of these cases as well as the biases and other factors that limit existing studies. However, genetic sequencing may provide information regarding these factors and related processes. Genetic sequencing specifically points to a small cell group remaining after excision of the primary tumor, which mutates while proliferating. Low antigenicity and tolerance to immunity during the quiescent period may explain the long duration of dormancy.⁶ More recently, there have been efforts to identify immunohistochemical signatures that may predict late recurrences, though the data are preliminary in nature.¹¹

Given the latency period and location of the recurrence, our case demonstrates that even fully excised melanomas may recur locally many decades later, hence patients should be aware of the importance of a lifetime of vigilance after being diagnosed with melanoma.

To the Editor:

Ultra-late melanoma recurrence represents a minority of cases in which the quiescent period lasts longer than 15 years, and epidemiologic studies have reported recurrence rates of 6% to 10% during the ultra-late period.¹ Even more uncommon are cases that span many decades (eg, >30 years), but all are useful in understanding the cellular behavior leading to the reactivation of fully excised melanomas. Few cases have been reported in which recurrence occurs more than 35 years after the original diagnosis of melanoma. Unfortunately, mechanisms underlying this long stable quiescence and subsequent reactivation are poorly understood, which is why it is important to identify and document cases. We present a case of local recurrence of cutaneous melanoma on the patient’s lower back after a 49-year disease-free period.

A 78-year-old White woman presented to a private dermatology office for a full-body skin examination. She had a medical history of a cutaneous melanoma that had been removed on the lower back 49 years prior; Parkinson disease of 10 years’ duration; and an enlarged thyroid nodule with decreased thyrotropin and hyperthyroidism, atrial fibrillation, mitral valve prolapse, osteoarthritis in the knees, and actinic keratoses, all of which were chronic conditions lasting years to decades. She was taking several medications for these medical conditions. Her surgical history included a hysterectomy, hip replacement, hernia repair, cardioversion, and tonsillectomy in childhood. Her family medical history included breast cancer in her paternal grandmother and aunt; hypertension in her father; and sarcoma in her mother at 78 years of age, which initially was identified in the sacrum and metastasized to the lungs causing death. No family history of melanoma or other skin cancers was reported. Prior to the original diagnosis of melanoma at 29 years of age, she had no history of skin cancer or any other medical condition other than acne. The patient did report spending a great deal of time in the sun during high school.

The patient reported developing the original cutaneous melanoma during her second pregnancy at 29 years of age and recalled that it was excised with wide margins. There had been a mole on her back that was present for years but changed in size during pregnancy, prompting the original visit to the primary care physician for evaluation. Remarkably, the original pathology report was obtained from the patient and revealed a specimen consisting of a 3.7×1.7-cm skin ellipse averaging 0.7 cm in thickness. In the center of the specimen was a 0.6-cm, round, raised, pigmented lesion that revealed moderately frequent mitoses on microscopic evaluation. It was determined by the pathologist to be a malignant tumor, and the report stated that the surgical margins appeared clear.

Physical examination at the current presentation 49 years later revealed an even-bordered 2-mm black macule that was located approximately 1 cm from the original melanoma excision scar line (Figure). A biopsy was performed and sent to a dermatopathologist. Microscopic evaluation revealed nests, islands, and sheets of atypical epithelioid melanocytes extending through the dermis between collagen bundles. The melanocytes varied in size and shape with moderate nuclear pleomorphism present. Scattered mitotic figures and necrotic melanocytes were present, which most likely represented cutaneous satellite metastases of melanoma. Subsequent chest radiography, full-body positron emission tomography, and standard laboratory blood tests were unremarkable except for an enlarged right thyroid gland and moderate cardiomegaly. The patient was sent to a surgical oncologist for excision with wide surgical margins, and she elected not to have a sentinel lymph node biopsy. At follow-up 3, 6, 12, and 24 months later, there were no signs of recurrence based on direct clinical examination. The patient subsequently was lost to follow-up.

Recurrence rates of melanoma vary by stage and age at diagnosis, but prior studies have reported a recurrence rate of approximately 6% after 10 or more years following the initial diagnosis.² Ultra-late recurrences of approximately 4 decades or more are extremely rare. A PubMed search of articles indexed for MEDLINE using the terms melanoma and ultra-late recurrence revealed 4 reported cases with a quiescent period of 38 or more years.^3-6 All cases were metastatic melanomas in women; spanned 38, 40, 41, and 45 years from the initial melanoma diagnosis to recurrence; and all of the recurrences except one were regional or distal metastatic lesions (eg, lymph node, brain). In one case, both the original and recurrent lesions occurred on the left elbow.⁶ The original lesions occurred on the legs, elbow, and back of the neck, and there were no notable concomitant medical conditions. The patients were aged 72, 73, 73, and 84 years at recurrence.^3-6 However, generalizations from these cases are limited given the potential for selection bias (eg, men may be less likely to visit a clinic for follow-up and nevi examination) and the likelihood that many cases of ultra-late melanoma recurrence are unrecognized or unreported.

More recently, genomic analyses on melanoma lesions occurring 30 years apart confirmed that the second lesion was indeed a recurrence, although with numerous additional mutations.⁷ The specific mechanisms underlying the dormancy and subsequent reemergence of metastatic lesions are unclear, but there may be aberrations in the skin beyond histopathologic margins that represent an early phase of disease that are histologically unrecognizable and may lay dormant for many years before reemerging in response to external or immunologic changes.⁸ Alternatively, recurrences may be associated with lymphatic or hematogenous emboli, or there may be a tendency for melanomas to metastasize to inflamed or scarred tissue representing a tropism of the malignant melanocytes.⁹

It also is worth highlighting the concomitant diagnosis of Parkinson disease in our patient. In recent years, Parkinson disease has been linked to melanoma in both epidemiologic and genetic studies. For example, one large-scale study found a 50% increased risk for developing Parkinson disease in patients with melanoma (and vice versa), and this finding has been replicated in other studies.¹⁰ Moreover, patients with Parkinson disease have a 2-fold increase in their risk for developing melanoma, demonstrating that it is a bidirectional pathway. Not surprisingly, associations between melanin and neuromelanin pathways have been identified as a potential link between these diseases, and scientists are in the process of understanding the genetic components of both.¹⁰ It is unknown if specific genetic mutations contributed to both diseases in our case, but follow-up genetic testing on the recurrent melanoma specimen currently is being pursued.

The 49-year quiescent period in our case of recurrent cutaneous malignant melanoma potentially represents the longest ultra-late recurrence of melanoma in the literature to date based on a review of indexed publications. Moreover, it is relatively unique compared to other similar cases in that the recurrence was within a centimeter of the original excisional scar. Most metastases occur in locoregional lymph nodes or the lungs³; therefore, it is unusual to find one so close to the original lesion, especially one that occurred decades later. Factors associated with ultra-late recurrences are unknown, primarily because of the rarity of these cases as well as the biases and other factors that limit existing studies. However, genetic sequencing may provide information regarding these factors and related processes. Genetic sequencing specifically points to a small cell group remaining after excision of the primary tumor, which mutates while proliferating. Low antigenicity and tolerance to immunity during the quiescent period may explain the long duration of dormancy.⁶ More recently, there have been efforts to identify immunohistochemical signatures that may predict late recurrences, though the data are preliminary in nature.¹¹

Given the latency period and location of the recurrence, our case demonstrates that even fully excised melanomas may recur locally many decades later, hence patients should be aware of the importance of a lifetime of vigilance after being diagnosed with melanoma.

To the Editor:

Ultra-late melanoma recurrence represents a minority of cases in which the quiescent period lasts longer than 15 years, and epidemiologic studies have reported recurrence rates of 6% to 10% during the ultra-late period.¹ Even more uncommon are cases that span many decades (eg, >30 years), but all are useful in understanding the cellular behavior leading to the reactivation of fully excised melanomas. Few cases have been reported in which recurrence occurs more than 35 years after the original diagnosis of melanoma. Unfortunately, mechanisms underlying this long stable quiescence and subsequent reactivation are poorly understood, which is why it is important to identify and document cases. We present a case of local recurrence of cutaneous melanoma on the patient’s lower back after a 49-year disease-free period.

A 78-year-old White woman presented to a private dermatology office for a full-body skin examination. She had a medical history of a cutaneous melanoma that had been removed on the lower back 49 years prior; Parkinson disease of 10 years’ duration; and an enlarged thyroid nodule with decreased thyrotropin and hyperthyroidism, atrial fibrillation, mitral valve prolapse, osteoarthritis in the knees, and actinic keratoses, all of which were chronic conditions lasting years to decades. She was taking several medications for these medical conditions. Her surgical history included a hysterectomy, hip replacement, hernia repair, cardioversion, and tonsillectomy in childhood. Her family medical history included breast cancer in her paternal grandmother and aunt; hypertension in her father; and sarcoma in her mother at 78 years of age, which initially was identified in the sacrum and metastasized to the lungs causing death. No family history of melanoma or other skin cancers was reported. Prior to the original diagnosis of melanoma at 29 years of age, she had no history of skin cancer or any other medical condition other than acne. The patient did report spending a great deal of time in the sun during high school.

The patient reported developing the original cutaneous melanoma during her second pregnancy at 29 years of age and recalled that it was excised with wide margins. There had been a mole on her back that was present for years but changed in size during pregnancy, prompting the original visit to the primary care physician for evaluation. Remarkably, the original pathology report was obtained from the patient and revealed a specimen consisting of a 3.7×1.7-cm skin ellipse averaging 0.7 cm in thickness. In the center of the specimen was a 0.6-cm, round, raised, pigmented lesion that revealed moderately frequent mitoses on microscopic evaluation. It was determined by the pathologist to be a malignant tumor, and the report stated that the surgical margins appeared clear.

Physical examination at the current presentation 49 years later revealed an even-bordered 2-mm black macule that was located approximately 1 cm from the original melanoma excision scar line (Figure). A biopsy was performed and sent to a dermatopathologist. Microscopic evaluation revealed nests, islands, and sheets of atypical epithelioid melanocytes extending through the dermis between collagen bundles. The melanocytes varied in size and shape with moderate nuclear pleomorphism present. Scattered mitotic figures and necrotic melanocytes were present, which most likely represented cutaneous satellite metastases of melanoma. Subsequent chest radiography, full-body positron emission tomography, and standard laboratory blood tests were unremarkable except for an enlarged right thyroid gland and moderate cardiomegaly. The patient was sent to a surgical oncologist for excision with wide surgical margins, and she elected not to have a sentinel lymph node biopsy. At follow-up 3, 6, 12, and 24 months later, there were no signs of recurrence based on direct clinical examination. The patient subsequently was lost to follow-up.

Recurrence rates of melanoma vary by stage and age at diagnosis, but prior studies have reported a recurrence rate of approximately 6% after 10 or more years following the initial diagnosis.² Ultra-late recurrences of approximately 4 decades or more are extremely rare. A PubMed search of articles indexed for MEDLINE using the terms melanoma and ultra-late recurrence revealed 4 reported cases with a quiescent period of 38 or more years.^3-6 All cases were metastatic melanomas in women; spanned 38, 40, 41, and 45 years from the initial melanoma diagnosis to recurrence; and all of the recurrences except one were regional or distal metastatic lesions (eg, lymph node, brain). In one case, both the original and recurrent lesions occurred on the left elbow.⁶ The original lesions occurred on the legs, elbow, and back of the neck, and there were no notable concomitant medical conditions. The patients were aged 72, 73, 73, and 84 years at recurrence.^3-6 However, generalizations from these cases are limited given the potential for selection bias (eg, men may be less likely to visit a clinic for follow-up and nevi examination) and the likelihood that many cases of ultra-late melanoma recurrence are unrecognized or unreported.

More recently, genomic analyses on melanoma lesions occurring 30 years apart confirmed that the second lesion was indeed a recurrence, although with numerous additional mutations.⁷ The specific mechanisms underlying the dormancy and subsequent reemergence of metastatic lesions are unclear, but there may be aberrations in the skin beyond histopathologic margins that represent an early phase of disease that are histologically unrecognizable and may lay dormant for many years before reemerging in response to external or immunologic changes.⁸ Alternatively, recurrences may be associated with lymphatic or hematogenous emboli, or there may be a tendency for melanomas to metastasize to inflamed or scarred tissue representing a tropism of the malignant melanocytes.⁹

It also is worth highlighting the concomitant diagnosis of Parkinson disease in our patient. In recent years, Parkinson disease has been linked to melanoma in both epidemiologic and genetic studies. For example, one large-scale study found a 50% increased risk for developing Parkinson disease in patients with melanoma (and vice versa), and this finding has been replicated in other studies.¹⁰ Moreover, patients with Parkinson disease have a 2-fold increase in their risk for developing melanoma, demonstrating that it is a bidirectional pathway. Not surprisingly, associations between melanin and neuromelanin pathways have been identified as a potential link between these diseases, and scientists are in the process of understanding the genetic components of both.¹⁰ It is unknown if specific genetic mutations contributed to both diseases in our case, but follow-up genetic testing on the recurrent melanoma specimen currently is being pursued.

The 49-year quiescent period in our case of recurrent cutaneous malignant melanoma potentially represents the longest ultra-late recurrence of melanoma in the literature to date based on a review of indexed publications. Moreover, it is relatively unique compared to other similar cases in that the recurrence was within a centimeter of the original excisional scar. Most metastases occur in locoregional lymph nodes or the lungs³; therefore, it is unusual to find one so close to the original lesion, especially one that occurred decades later. Factors associated with ultra-late recurrences are unknown, primarily because of the rarity of these cases as well as the biases and other factors that limit existing studies. However, genetic sequencing may provide information regarding these factors and related processes. Genetic sequencing specifically points to a small cell group remaining after excision of the primary tumor, which mutates while proliferating. Low antigenicity and tolerance to immunity during the quiescent period may explain the long duration of dormancy.⁶ More recently, there have been efforts to identify immunohistochemical signatures that may predict late recurrences, though the data are preliminary in nature.¹¹

Given the latency period and location of the recurrence, our case demonstrates that even fully excised melanomas may recur locally many decades later, hence patients should be aware of the importance of a lifetime of vigilance after being diagnosed with melanoma.

Eosinophil-guided corticosteroid therapy for patients with chronic obstructive pulmonary disease (COPD) is equivalent in efficacy to standard of care therapy, but the eosinophil-guided therapy may help mitigate the harmful side effects associated with even short courses of corticosteroids, investigators said in a primary care–based randomized trial.

Among patients in 14 primary care practices in the United Kingdom who experienced COPD exacerbations, the proportion of patients who experienced treatment failure at day 28 was 27% for those who were randomized to receive prednisolone only when blood eosinophil counts on a point-of-care assay equaled or exceeded 2%, compared with 34% of all patients randomized to standard of care.

The relative risk for treatment failure using the eosinophil-guided approach was 0.82, which did not reach statistical significance, but indicated noninferiority for the biomarker-based dosing method, Mona Bafadhel, MD, of King’s College London, reported on behalf of colleagues in the Stratified Treatment to Reduce Risk in COPD (STARR2) trial.

“The STARR2 trial showed that eosinophil-guided prescription in primary care is safe and is not associated with worsening outcomes. This is the largest primary care multicenter trial, and probably adds another 20% to the literature base for exacerbations in COPD,” she said in an oral abstract presentation at the European Respiratory Society 2022 Congress.

“A personalized endotype-based treatment with oral prednisolone is possible in patients with COPD and I think should be now part of clinical guidelines,” she added.
 

Too much of a good thing

Although systemic corticosteroids are the universal treatment for COPD exacerbations, the drugs are also known to increase harm, with studies showing that cumulative doses of oral corticosteroids in COPD patients is associated with an increased risk for death. In addition, systemic corticosteroids are the third most common cause of adverse events leading to hospitalization, behind only chemotherapy and antibiotic use leading to  Clostridioides difficile infections, Dr. Bafadhel said.

“And of course, corticosteroids are associated with significant harmful effects, including a five-times increased risk of sepsis, three-times increased risk of [venous thromboembolism], and a twice-increased risk of fracture,” she said.

Dr. Bafadhel and colleagues had previously shown in the single-center BEAT-COPD study that peripheral blood eosinophils at the time of a moderate COPD exacerbation could be used to safely direct oral corticosteroid therapy. She also pointed to a 2019 multicenter open-label study showing that eosinophil-guided care was noninferior to standard prescribing of oral corticosteroids for patients with severe exacerbations.
 

Primary care study

The investigators conducted the current study to test whether eosinophil-guided therapy at the point of care in a primary practice setting was efficacious, with the ultimate goal of encouraging changes in guidelines.

They recruited patients with COPD exacerbations from 14 general practices in Oxfordshire and Buckinghamshire in the Thames Valley.

The patients were randomly assigned to receive either standard of care or the biomarker-guided intervention for 14 days. In this arm, patients with eosinophil counts of 2% or greater received matched prednisolone, while patients with counts below 2% received placebo. The patients were blinded to the assigned drug.

A total of 203 exacerbations among 152 patients were evenly allocated to treatment or control groups. The mean patient age was 71. Of the 102 exacerbations allocated to eosinophil-guided therapy, 34 were treated with placebo.

As noted before, in the intention-to-treat analysis the primary outcome of the treatment failure rate, defined as any need for antibiotics and/or steroids at one month, was 27% in the biomarker-guided arm and 34% in the standard care arm.

“In the per-protocol analysis we also demonstrated that there was a suggestion that there is possible superiority of using blood eosinophil-directed oral corticosteroid prescriptions at the time of acute exacerbation using the point-of-care eosinophil test,” Dr. Bafadhel said.

There were no significant differences in the secondary outcomes of mean change in forced expiratory volume in 1 second (FEV₁), COPD Assessment Test scores from exacerbation to follow-up, and symptoms according to a visual analog scale. 

Invited discussant Dave Singh, MD, of the University of Manchester, England, asked Dr. Bafadhel how the data she presented supported her conclusions about the potential benefits of eosinophil-guided therapy, given that the P values were nonsignificant.

“The primary outcome was powered on noninferiority, and of course what we’ve shown is that it’s not any worse, it’s not any better, but of course it’s the effect of how many courses of steroids you can reduce in that population,” Dr. Bafadhel replied.

She noted that although the investigators have not performed an economic analysis to determine how many adverse events might be avoided using the biomarker-guided approach, “we do know that some of these patients who are given prednisolone, their comorbidities of diabetes worsened, for example.”

In the online Q&A for the presentation, Sohail Ansari, MD, from the Mid and South Essex NHS Foundation Trust in the United Kingdom, said that many patients in primary care practices receive “rescue packs” containing antibiotics and steroids, but may not be equipped to know when they should use the steroids and therefore may overuse them.

“Perhaps community-based, adequately resourced respiratory teams [may] be a way forward, but it will need adequate investment and commitment,” he wrote.

The trial was supported by the University of Oxford and National Institute for Health and Care Research, UK. Dr. Bafadhel reported grant and research support from the National Institute for Health and Care Research, Asthma & Lung UK, AstraZeneca, and Roche, and honoraria or fees from others. Dr. Singh reported speaking fees, honoraria, and research grants from multiple companies. Dr. Ansari reported no conflicts of interest.

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

Eosinophil-guided corticosteroid therapy for patients with chronic obstructive pulmonary disease (COPD) is equivalent in efficacy to standard of care therapy, but the eosinophil-guided therapy may help mitigate the harmful side effects associated with even short courses of corticosteroids, investigators said in a primary care–based randomized trial.

Among patients in 14 primary care practices in the United Kingdom who experienced COPD exacerbations, the proportion of patients who experienced treatment failure at day 28 was 27% for those who were randomized to receive prednisolone only when blood eosinophil counts on a point-of-care assay equaled or exceeded 2%, compared with 34% of all patients randomized to standard of care.

The relative risk for treatment failure using the eosinophil-guided approach was 0.82, which did not reach statistical significance, but indicated noninferiority for the biomarker-based dosing method, Mona Bafadhel, MD, of King’s College London, reported on behalf of colleagues in the Stratified Treatment to Reduce Risk in COPD (STARR2) trial.

“The STARR2 trial showed that eosinophil-guided prescription in primary care is safe and is not associated with worsening outcomes. This is the largest primary care multicenter trial, and probably adds another 20% to the literature base for exacerbations in COPD,” she said in an oral abstract presentation at the European Respiratory Society 2022 Congress.

“A personalized endotype-based treatment with oral prednisolone is possible in patients with COPD and I think should be now part of clinical guidelines,” she added.
 

Too much of a good thing

Although systemic corticosteroids are the universal treatment for COPD exacerbations, the drugs are also known to increase harm, with studies showing that cumulative doses of oral corticosteroids in COPD patients is associated with an increased risk for death. In addition, systemic corticosteroids are the third most common cause of adverse events leading to hospitalization, behind only chemotherapy and antibiotic use leading to  Clostridioides difficile infections, Dr. Bafadhel said.

“And of course, corticosteroids are associated with significant harmful effects, including a five-times increased risk of sepsis, three-times increased risk of [venous thromboembolism], and a twice-increased risk of fracture,” she said.

Dr. Bafadhel and colleagues had previously shown in the single-center BEAT-COPD study that peripheral blood eosinophils at the time of a moderate COPD exacerbation could be used to safely direct oral corticosteroid therapy. She also pointed to a 2019 multicenter open-label study showing that eosinophil-guided care was noninferior to standard prescribing of oral corticosteroids for patients with severe exacerbations.
 

Primary care study

The investigators conducted the current study to test whether eosinophil-guided therapy at the point of care in a primary practice setting was efficacious, with the ultimate goal of encouraging changes in guidelines.

They recruited patients with COPD exacerbations from 14 general practices in Oxfordshire and Buckinghamshire in the Thames Valley.

The patients were randomly assigned to receive either standard of care or the biomarker-guided intervention for 14 days. In this arm, patients with eosinophil counts of 2% or greater received matched prednisolone, while patients with counts below 2% received placebo. The patients were blinded to the assigned drug.

A total of 203 exacerbations among 152 patients were evenly allocated to treatment or control groups. The mean patient age was 71. Of the 102 exacerbations allocated to eosinophil-guided therapy, 34 were treated with placebo.

As noted before, in the intention-to-treat analysis the primary outcome of the treatment failure rate, defined as any need for antibiotics and/or steroids at one month, was 27% in the biomarker-guided arm and 34% in the standard care arm.

“In the per-protocol analysis we also demonstrated that there was a suggestion that there is possible superiority of using blood eosinophil-directed oral corticosteroid prescriptions at the time of acute exacerbation using the point-of-care eosinophil test,” Dr. Bafadhel said.

There were no significant differences in the secondary outcomes of mean change in forced expiratory volume in 1 second (FEV₁), COPD Assessment Test scores from exacerbation to follow-up, and symptoms according to a visual analog scale. 

Invited discussant Dave Singh, MD, of the University of Manchester, England, asked Dr. Bafadhel how the data she presented supported her conclusions about the potential benefits of eosinophil-guided therapy, given that the P values were nonsignificant.

“The primary outcome was powered on noninferiority, and of course what we’ve shown is that it’s not any worse, it’s not any better, but of course it’s the effect of how many courses of steroids you can reduce in that population,” Dr. Bafadhel replied.

She noted that although the investigators have not performed an economic analysis to determine how many adverse events might be avoided using the biomarker-guided approach, “we do know that some of these patients who are given prednisolone, their comorbidities of diabetes worsened, for example.”

In the online Q&A for the presentation, Sohail Ansari, MD, from the Mid and South Essex NHS Foundation Trust in the United Kingdom, said that many patients in primary care practices receive “rescue packs” containing antibiotics and steroids, but may not be equipped to know when they should use the steroids and therefore may overuse them.

“Perhaps community-based, adequately resourced respiratory teams [may] be a way forward, but it will need adequate investment and commitment,” he wrote.

The trial was supported by the University of Oxford and National Institute for Health and Care Research, UK. Dr. Bafadhel reported grant and research support from the National Institute for Health and Care Research, Asthma & Lung UK, AstraZeneca, and Roche, and honoraria or fees from others. Dr. Singh reported speaking fees, honoraria, and research grants from multiple companies. Dr. Ansari reported no conflicts of interest.

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

Eosinophil-guided corticosteroid therapy for patients with chronic obstructive pulmonary disease (COPD) is equivalent in efficacy to standard of care therapy, but the eosinophil-guided therapy may help mitigate the harmful side effects associated with even short courses of corticosteroids, investigators said in a primary care–based randomized trial.

Among patients in 14 primary care practices in the United Kingdom who experienced COPD exacerbations, the proportion of patients who experienced treatment failure at day 28 was 27% for those who were randomized to receive prednisolone only when blood eosinophil counts on a point-of-care assay equaled or exceeded 2%, compared with 34% of all patients randomized to standard of care.

The relative risk for treatment failure using the eosinophil-guided approach was 0.82, which did not reach statistical significance, but indicated noninferiority for the biomarker-based dosing method, Mona Bafadhel, MD, of King’s College London, reported on behalf of colleagues in the Stratified Treatment to Reduce Risk in COPD (STARR2) trial.

“The STARR2 trial showed that eosinophil-guided prescription in primary care is safe and is not associated with worsening outcomes. This is the largest primary care multicenter trial, and probably adds another 20% to the literature base for exacerbations in COPD,” she said in an oral abstract presentation at the European Respiratory Society 2022 Congress.

“A personalized endotype-based treatment with oral prednisolone is possible in patients with COPD and I think should be now part of clinical guidelines,” she added.
 

Too much of a good thing

Although systemic corticosteroids are the universal treatment for COPD exacerbations, the drugs are also known to increase harm, with studies showing that cumulative doses of oral corticosteroids in COPD patients is associated with an increased risk for death. In addition, systemic corticosteroids are the third most common cause of adverse events leading to hospitalization, behind only chemotherapy and antibiotic use leading to  Clostridioides difficile infections, Dr. Bafadhel said.

“And of course, corticosteroids are associated with significant harmful effects, including a five-times increased risk of sepsis, three-times increased risk of [venous thromboembolism], and a twice-increased risk of fracture,” she said.

Dr. Bafadhel and colleagues had previously shown in the single-center BEAT-COPD study that peripheral blood eosinophils at the time of a moderate COPD exacerbation could be used to safely direct oral corticosteroid therapy. She also pointed to a 2019 multicenter open-label study showing that eosinophil-guided care was noninferior to standard prescribing of oral corticosteroids for patients with severe exacerbations.
 

Primary care study

The investigators conducted the current study to test whether eosinophil-guided therapy at the point of care in a primary practice setting was efficacious, with the ultimate goal of encouraging changes in guidelines.

They recruited patients with COPD exacerbations from 14 general practices in Oxfordshire and Buckinghamshire in the Thames Valley.

The patients were randomly assigned to receive either standard of care or the biomarker-guided intervention for 14 days. In this arm, patients with eosinophil counts of 2% or greater received matched prednisolone, while patients with counts below 2% received placebo. The patients were blinded to the assigned drug.

A total of 203 exacerbations among 152 patients were evenly allocated to treatment or control groups. The mean patient age was 71. Of the 102 exacerbations allocated to eosinophil-guided therapy, 34 were treated with placebo.

As noted before, in the intention-to-treat analysis the primary outcome of the treatment failure rate, defined as any need for antibiotics and/or steroids at one month, was 27% in the biomarker-guided arm and 34% in the standard care arm.

“In the per-protocol analysis we also demonstrated that there was a suggestion that there is possible superiority of using blood eosinophil-directed oral corticosteroid prescriptions at the time of acute exacerbation using the point-of-care eosinophil test,” Dr. Bafadhel said.

There were no significant differences in the secondary outcomes of mean change in forced expiratory volume in 1 second (FEV₁), COPD Assessment Test scores from exacerbation to follow-up, and symptoms according to a visual analog scale. 

Invited discussant Dave Singh, MD, of the University of Manchester, England, asked Dr. Bafadhel how the data she presented supported her conclusions about the potential benefits of eosinophil-guided therapy, given that the P values were nonsignificant.

“The primary outcome was powered on noninferiority, and of course what we’ve shown is that it’s not any worse, it’s not any better, but of course it’s the effect of how many courses of steroids you can reduce in that population,” Dr. Bafadhel replied.

She noted that although the investigators have not performed an economic analysis to determine how many adverse events might be avoided using the biomarker-guided approach, “we do know that some of these patients who are given prednisolone, their comorbidities of diabetes worsened, for example.”

In the online Q&A for the presentation, Sohail Ansari, MD, from the Mid and South Essex NHS Foundation Trust in the United Kingdom, said that many patients in primary care practices receive “rescue packs” containing antibiotics and steroids, but may not be equipped to know when they should use the steroids and therefore may overuse them.

“Perhaps community-based, adequately resourced respiratory teams [may] be a way forward, but it will need adequate investment and commitment,” he wrote.

The trial was supported by the University of Oxford and National Institute for Health and Care Research, UK. Dr. Bafadhel reported grant and research support from the National Institute for Health and Care Research, Asthma & Lung UK, AstraZeneca, and Roche, and honoraria or fees from others. Dr. Singh reported speaking fees, honoraria, and research grants from multiple companies. Dr. Ansari reported no conflicts of interest.

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

Current or former smokers who have clinically significant respiratory symptoms but no spirometric evidence of airway obstruction are often treated with dual bronchodilators commonly prescribed for patients with chronic obstructive pulmonary disease (COPD).

But as results of the randomized RETHINC (Redefining Therapy In Early COPD for the Pulmonary Trials Cooperative) trial showed, bronchodilator therapy was no better than placebo at reducing respiratory symptoms in smokers, reported MeiLan K. Han, MD, from the University of Michigan, Ann Arbor, on behalf of colleagues in the RETHINC study group.

“Many tobacco-exposed symptomatic individuals are currently being treated. We don’t know if this is because physicians just aren’t doing spirometry and assuming COPD or they strongly believe that there’s a benefit, but the bottom line is that we really need to do spirometry to understand who benefits from bronchodilators, and we need further research to understand how to treat this specific group of patients because there truly is pathogenesis and disease burden,” Dr. Han said in an oral abstract presentation at the annual congress of the European Respiratory Society.

The study results were also published online in the New England Journal of Medicine to coincide with the presentation.

In an editorial accompanying the study, Don D. Sin, MD, MPH, from the University of British Columbia, Vancouver, commented that the study shows that “long-acting bronchodilators do not appear to be effective for the treatment of symptomatic persons with a smoking history and preserved lung function on spirometry; these medications should most likely be reserved for patients with COPD who have clinically significant airflow limitation,” and that “respiratory symptoms in tobacco-exposed persons are common but are highly variable over time.”

Dave Singh, MD, from the University of Manchester (England), the invited discussant, called it “a very important negative study.”
 

Not up to GOLD standard

Current or former smokers who are symptomatic, with COPD Assessment Test (CAT) scores of at least 10 despite having preserved function on spirometry, have been shown to have higher prospective rates of respiratory disease exacerbations and increased sputum total mucin concentrations. Approximately 43% of such patients are treated with bronchodilators, and 23% are treated with inhaled corticosteroids (ICS), Dr. Han noted.

Her group hypothesized that ever-smokers with spirometric values that fall within the normal range – that is, a postbronchodilator FEV1/FVC ratio of 70 or greater – would still derive benefit from long-acting bronchodilator therapy, even though these patients are currently excluded from Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations.

To test this, they conducted a 12-week, multicenter, randomized, parallel-group study in which patients were assigned to receive either indacaterol (27.5 mcg) and glycopyrrolate (15.6 mcg) inhaled twice daily or placebo.

They enrolled adults aged 40-80 years with a minimum of 10 pack-years of smoking history, postbronchodilator FEV₁/FVC ratio of 70 or greater, and CAT scores of 10 or greater. Patients with known concomitant lung disease, a primary diagnosis of asthma, or body mass index lower than 15 or higher than 40 and those being concomitantly treated with long-acting beta₂-agonists or muscarinic antagonists or a short-acting combination were excluded, although patients were allowed to be on a short-acting beta-agonist.

A total of 535 participants were randomized, but COVID-19 pandemic–imposed obstacles resulted in a modified intention-to-treat population of 277 patients assigned to receive the active treatment and 244 assigned to receive placebo.

There was no difference between the groups for the primary outcome of an at least 4-point decrease in St. George’s Respiratory Questionnaire scores in patients who did not experience treatment failure, defined as an increase in respiratory symptoms requiring treatment with active long-acting bronchodilators or ICS.

The primary endpoint was seen in 56.4% of patients in the bronchodilator group, and 59% of controls.

Although there was greater improvement in pulmonary function from baseline in the treatment group, compared with the placebo group, the improvements did not correlate with similar improvements in symptoms, Dr. Han said.

There were 4 serious adverse events in the bronchodilator group and 11 in the placebo group, but none of the events were deemed to be related to the assigned treatments.

Dr. Han acknowledged limitations of the study, which may have included symptoms driven by other factors such as cardiac disease, suggesting that if such patients had been identified and excluded, a stronger effect might have been seen for the active treatment.

In addition, the study was underpowered to look at the subgroup of participants with chronic bronchitis, and the 12 weeks of the study may have been too short to see improvements in symptoms.

In his editorial, Dr. Sin noted that the study showed that cough and sputum production rather than exertion dyspnea are the primary symptoms among ever-smokers.

“Although bronchodilators are effective in ameliorating breathlessness and improving exercise tolerance, they are generally ineffective for cough,” he wrote. “Existing drugs for the treatment of COPD, such as inhaled glucocorticoids or phosphodiesterase-4 inhibitors, or new therapeutics such as P2X3 receptor antagonists may be more effective for the treatment of cough and sputum production related to smoking and could be considered for future evaluations in this patient population.”

The study was supported by the National Heart, Lung, and Blood Institute, the National Center for Advancing Translational Sciences, and Sunovion Pharmaceuticals. Novartis Pharmaceuticals donated the trial medication and placebo. Dr. Han disclosed grant/research support and honoraria or consulting fees from various companies. Dr. Singh reported speaking fees, honoraria, and research grants from multiple companies. Dr. Sin reported having no conflicts of interest to disclose.

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

Current or former smokers who have clinically significant respiratory symptoms but no spirometric evidence of airway obstruction are often treated with dual bronchodilators commonly prescribed for patients with chronic obstructive pulmonary disease (COPD).

But as results of the randomized RETHINC (Redefining Therapy In Early COPD for the Pulmonary Trials Cooperative) trial showed, bronchodilator therapy was no better than placebo at reducing respiratory symptoms in smokers, reported MeiLan K. Han, MD, from the University of Michigan, Ann Arbor, on behalf of colleagues in the RETHINC study group.

“Many tobacco-exposed symptomatic individuals are currently being treated. We don’t know if this is because physicians just aren’t doing spirometry and assuming COPD or they strongly believe that there’s a benefit, but the bottom line is that we really need to do spirometry to understand who benefits from bronchodilators, and we need further research to understand how to treat this specific group of patients because there truly is pathogenesis and disease burden,” Dr. Han said in an oral abstract presentation at the annual congress of the European Respiratory Society.

The study results were also published online in the New England Journal of Medicine to coincide with the presentation.

In an editorial accompanying the study, Don D. Sin, MD, MPH, from the University of British Columbia, Vancouver, commented that the study shows that “long-acting bronchodilators do not appear to be effective for the treatment of symptomatic persons with a smoking history and preserved lung function on spirometry; these medications should most likely be reserved for patients with COPD who have clinically significant airflow limitation,” and that “respiratory symptoms in tobacco-exposed persons are common but are highly variable over time.”

Dave Singh, MD, from the University of Manchester (England), the invited discussant, called it “a very important negative study.”
 

Not up to GOLD standard

Current or former smokers who are symptomatic, with COPD Assessment Test (CAT) scores of at least 10 despite having preserved function on spirometry, have been shown to have higher prospective rates of respiratory disease exacerbations and increased sputum total mucin concentrations. Approximately 43% of such patients are treated with bronchodilators, and 23% are treated with inhaled corticosteroids (ICS), Dr. Han noted.

Her group hypothesized that ever-smokers with spirometric values that fall within the normal range – that is, a postbronchodilator FEV1/FVC ratio of 70 or greater – would still derive benefit from long-acting bronchodilator therapy, even though these patients are currently excluded from Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations.

To test this, they conducted a 12-week, multicenter, randomized, parallel-group study in which patients were assigned to receive either indacaterol (27.5 mcg) and glycopyrrolate (15.6 mcg) inhaled twice daily or placebo.

They enrolled adults aged 40-80 years with a minimum of 10 pack-years of smoking history, postbronchodilator FEV₁/FVC ratio of 70 or greater, and CAT scores of 10 or greater. Patients with known concomitant lung disease, a primary diagnosis of asthma, or body mass index lower than 15 or higher than 40 and those being concomitantly treated with long-acting beta₂-agonists or muscarinic antagonists or a short-acting combination were excluded, although patients were allowed to be on a short-acting beta-agonist.

A total of 535 participants were randomized, but COVID-19 pandemic–imposed obstacles resulted in a modified intention-to-treat population of 277 patients assigned to receive the active treatment and 244 assigned to receive placebo.

There was no difference between the groups for the primary outcome of an at least 4-point decrease in St. George’s Respiratory Questionnaire scores in patients who did not experience treatment failure, defined as an increase in respiratory symptoms requiring treatment with active long-acting bronchodilators or ICS.

The primary endpoint was seen in 56.4% of patients in the bronchodilator group, and 59% of controls.

Although there was greater improvement in pulmonary function from baseline in the treatment group, compared with the placebo group, the improvements did not correlate with similar improvements in symptoms, Dr. Han said.

There were 4 serious adverse events in the bronchodilator group and 11 in the placebo group, but none of the events were deemed to be related to the assigned treatments.

Dr. Han acknowledged limitations of the study, which may have included symptoms driven by other factors such as cardiac disease, suggesting that if such patients had been identified and excluded, a stronger effect might have been seen for the active treatment.

In addition, the study was underpowered to look at the subgroup of participants with chronic bronchitis, and the 12 weeks of the study may have been too short to see improvements in symptoms.

In his editorial, Dr. Sin noted that the study showed that cough and sputum production rather than exertion dyspnea are the primary symptoms among ever-smokers.

“Although bronchodilators are effective in ameliorating breathlessness and improving exercise tolerance, they are generally ineffective for cough,” he wrote. “Existing drugs for the treatment of COPD, such as inhaled glucocorticoids or phosphodiesterase-4 inhibitors, or new therapeutics such as P2X3 receptor antagonists may be more effective for the treatment of cough and sputum production related to smoking and could be considered for future evaluations in this patient population.”

The study was supported by the National Heart, Lung, and Blood Institute, the National Center for Advancing Translational Sciences, and Sunovion Pharmaceuticals. Novartis Pharmaceuticals donated the trial medication and placebo. Dr. Han disclosed grant/research support and honoraria or consulting fees from various companies. Dr. Singh reported speaking fees, honoraria, and research grants from multiple companies. Dr. Sin reported having no conflicts of interest to disclose.

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

Current or former smokers who have clinically significant respiratory symptoms but no spirometric evidence of airway obstruction are often treated with dual bronchodilators commonly prescribed for patients with chronic obstructive pulmonary disease (COPD).

But as results of the randomized RETHINC (Redefining Therapy In Early COPD for the Pulmonary Trials Cooperative) trial showed, bronchodilator therapy was no better than placebo at reducing respiratory symptoms in smokers, reported MeiLan K. Han, MD, from the University of Michigan, Ann Arbor, on behalf of colleagues in the RETHINC study group.

“Many tobacco-exposed symptomatic individuals are currently being treated. We don’t know if this is because physicians just aren’t doing spirometry and assuming COPD or they strongly believe that there’s a benefit, but the bottom line is that we really need to do spirometry to understand who benefits from bronchodilators, and we need further research to understand how to treat this specific group of patients because there truly is pathogenesis and disease burden,” Dr. Han said in an oral abstract presentation at the annual congress of the European Respiratory Society.

The study results were also published online in the New England Journal of Medicine to coincide with the presentation.

In an editorial accompanying the study, Don D. Sin, MD, MPH, from the University of British Columbia, Vancouver, commented that the study shows that “long-acting bronchodilators do not appear to be effective for the treatment of symptomatic persons with a smoking history and preserved lung function on spirometry; these medications should most likely be reserved for patients with COPD who have clinically significant airflow limitation,” and that “respiratory symptoms in tobacco-exposed persons are common but are highly variable over time.”

Dave Singh, MD, from the University of Manchester (England), the invited discussant, called it “a very important negative study.”
 

Not up to GOLD standard

Current or former smokers who are symptomatic, with COPD Assessment Test (CAT) scores of at least 10 despite having preserved function on spirometry, have been shown to have higher prospective rates of respiratory disease exacerbations and increased sputum total mucin concentrations. Approximately 43% of such patients are treated with bronchodilators, and 23% are treated with inhaled corticosteroids (ICS), Dr. Han noted.

Her group hypothesized that ever-smokers with spirometric values that fall within the normal range – that is, a postbronchodilator FEV1/FVC ratio of 70 or greater – would still derive benefit from long-acting bronchodilator therapy, even though these patients are currently excluded from Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations.

To test this, they conducted a 12-week, multicenter, randomized, parallel-group study in which patients were assigned to receive either indacaterol (27.5 mcg) and glycopyrrolate (15.6 mcg) inhaled twice daily or placebo.

They enrolled adults aged 40-80 years with a minimum of 10 pack-years of smoking history, postbronchodilator FEV₁/FVC ratio of 70 or greater, and CAT scores of 10 or greater. Patients with known concomitant lung disease, a primary diagnosis of asthma, or body mass index lower than 15 or higher than 40 and those being concomitantly treated with long-acting beta₂-agonists or muscarinic antagonists or a short-acting combination were excluded, although patients were allowed to be on a short-acting beta-agonist.

A total of 535 participants were randomized, but COVID-19 pandemic–imposed obstacles resulted in a modified intention-to-treat population of 277 patients assigned to receive the active treatment and 244 assigned to receive placebo.

There was no difference between the groups for the primary outcome of an at least 4-point decrease in St. George’s Respiratory Questionnaire scores in patients who did not experience treatment failure, defined as an increase in respiratory symptoms requiring treatment with active long-acting bronchodilators or ICS.

The primary endpoint was seen in 56.4% of patients in the bronchodilator group, and 59% of controls.

Although there was greater improvement in pulmonary function from baseline in the treatment group, compared with the placebo group, the improvements did not correlate with similar improvements in symptoms, Dr. Han said.

There were 4 serious adverse events in the bronchodilator group and 11 in the placebo group, but none of the events were deemed to be related to the assigned treatments.

Dr. Han acknowledged limitations of the study, which may have included symptoms driven by other factors such as cardiac disease, suggesting that if such patients had been identified and excluded, a stronger effect might have been seen for the active treatment.

In addition, the study was underpowered to look at the subgroup of participants with chronic bronchitis, and the 12 weeks of the study may have been too short to see improvements in symptoms.

In his editorial, Dr. Sin noted that the study showed that cough and sputum production rather than exertion dyspnea are the primary symptoms among ever-smokers.

“Although bronchodilators are effective in ameliorating breathlessness and improving exercise tolerance, they are generally ineffective for cough,” he wrote. “Existing drugs for the treatment of COPD, such as inhaled glucocorticoids or phosphodiesterase-4 inhibitors, or new therapeutics such as P2X3 receptor antagonists may be more effective for the treatment of cough and sputum production related to smoking and could be considered for future evaluations in this patient population.”

The study was supported by the National Heart, Lung, and Blood Institute, the National Center for Advancing Translational Sciences, and Sunovion Pharmaceuticals. Novartis Pharmaceuticals donated the trial medication and placebo. Dr. Han disclosed grant/research support and honoraria or consulting fees from various companies. Dr. Singh reported speaking fees, honoraria, and research grants from multiple companies. Dr. Sin reported having no conflicts of interest to disclose.

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

Recruiting health care workers is a challenge these days for both private practice and hospital employers, and competition can be fierce. In order to be competitive, employers need to review the package they are offering potential candidates and understand that it’s more than just compensation and benefits that matter.

When all else is equal, contract language can end up being the difference between capturing or losing a candidate.

As someone who reviews physician contracts extensively, there are some common examples of language that may cause a candidate to choose a different position.
 

Probationary period

Although every employer wants to find out if they like the physician or midlevel employee that they have just hired before fully committing, the inclusion of a probationary period (usually 90 days) is offensive to a candidate, especially one with a choice of contracts.

Essentially, the employer is asking the employee to (potentially) relocate, go through the credentialing process, and turn down other potential offers, all for the possibility that they could easily be terminated. Probationary periods typically allow an employee to be immediately terminated without notice or cause, which can then leave them stranded without a paycheck (and with a new home and/or other recent commitments).

Moreover, contracts with probationary periods tend to terminate the employee without covering any tail costs or clarifying that the employer will not enforce restrictive provisions (even if unlikely to be legally enforceable based on the short relationship).

It is important to understand that the process of a person finding a new position, which includes interviewing, contract negotiation, and credentialing, can take up to 6 months. For this reason, probationary provisions create real job insecurity for a candidate.

Entering into a new affiliation is a leap of faith both for the employer and the employee. If the circumstances do not work out, the employer should fairly compensate the employee for the notice period and ask them not to return to work or otherwise allow them to keep working the notice period while they search for a new position.
 

Acceleration of notice

Another objectionable provision that employers like to include in their contracts is one which allows the employer to accelerate and immediately terminate an employee who has given proper notice.

The contract will contain a standard notice provision, but when the health care professional submits notice, their last date is suddenly accelerated, and they are released without further compensation, notice, or benefits. This type of provision is particularly offensive to health care employees who take the step of giving proper contractual notice and, similar to the probationary language, can create real job insecurity for an employee who suddenly loses their paycheck and has no new job to start.

Medical workers should be paid for the entire notice period whether or not they are allowed to work. Unfortunately, this type of provision is sometimes hidden in contracts and not noticed by employees, who tend to focus on the notice provision itself. I consider this provision to be a red flag about the employer when I review clients’ contracts.
 

Malpractice tail

Although many employers will claim it is not unusual for an employee to pay for their own malpractice tail, in the current marketplace, the payment of tail can be a deciding factor in whether a candidate accepts a contract.

At a minimum, employers should consider paying for the tail under circumstances where they non-renew a contract, terminate without cause, or the contract is terminated for the employer’s breach. Similarly, I like to seek out payment of the tail by the employer where the contract is terminated owing to a change in the law, use of a force majeure provision, loss of the employer’s hospital contract, or similar provisions where termination is outside the control of the employee.

Employers should also consider a provision where they share the cost of a tail or cover the entire cost on the basis of years of service in order to stand out to a potential candidate.
 

Noncompete provisions

I do not find noncompete provisions to be generally unacceptable when properly written; however, employers should reevaluate the reasonableness of their noncompete language frequently, because such language can make the difference in whether a candidate accepts a contract.

A reasonable noncompete that only protects the employer as necessary and does not restrict the reasonable practice of medicine is always preferable and can be the deciding factor for a candidate. Tying enforcement of a noncompete to reasons for termination (similar to the tail) can also make a positive difference in a candidate’s review of a contract.

Egregious noncompetes, where the candidate is simply informed that the language is “not negotiable,” are unlikely to be compelling to a candidate with other options.
 

Specifics on location, call, schedule

One item potential employees find extremely frustrating about contracts is when it fails to include promises made regarding location, call, and schedule.

These particular items affect a physician’s expectations about a job, including commute time, family life, and lifestyle. An employer or recruiter that makes a lot of promises on these points but won’t commit to the details in writing (or at least offer mutual agreement on these issues) can cause an uncertain candidate to choose the job that offers greater certainty.

There are many provisions of a contract that can make a difference to a particular job applicant. A savvy employer seeking to capture a particular health care professional should find out what the specific goals and needs of the candidate might be and consider adjusting the contract to best satisfy the candidate.

At the end of the day, however, at least for those physicians and others reviewing contracts that are fairly equivalent, it may be the fairness of the contract provisions that end up being the deciding factor.

Ms. Adler is Health Law Group Practice Leader for the law firm Roetzel in Chicago. She reported no relevant conflicts of interest.

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

Recruiting health care workers is a challenge these days for both private practice and hospital employers, and competition can be fierce. In order to be competitive, employers need to review the package they are offering potential candidates and understand that it’s more than just compensation and benefits that matter.

When all else is equal, contract language can end up being the difference between capturing or losing a candidate.

As someone who reviews physician contracts extensively, there are some common examples of language that may cause a candidate to choose a different position.
 

Probationary period

Although every employer wants to find out if they like the physician or midlevel employee that they have just hired before fully committing, the inclusion of a probationary period (usually 90 days) is offensive to a candidate, especially one with a choice of contracts.

Essentially, the employer is asking the employee to (potentially) relocate, go through the credentialing process, and turn down other potential offers, all for the possibility that they could easily be terminated. Probationary periods typically allow an employee to be immediately terminated without notice or cause, which can then leave them stranded without a paycheck (and with a new home and/or other recent commitments).

Moreover, contracts with probationary periods tend to terminate the employee without covering any tail costs or clarifying that the employer will not enforce restrictive provisions (even if unlikely to be legally enforceable based on the short relationship).

It is important to understand that the process of a person finding a new position, which includes interviewing, contract negotiation, and credentialing, can take up to 6 months. For this reason, probationary provisions create real job insecurity for a candidate.

Entering into a new affiliation is a leap of faith both for the employer and the employee. If the circumstances do not work out, the employer should fairly compensate the employee for the notice period and ask them not to return to work or otherwise allow them to keep working the notice period while they search for a new position.
 

Acceleration of notice

Another objectionable provision that employers like to include in their contracts is one which allows the employer to accelerate and immediately terminate an employee who has given proper notice.

The contract will contain a standard notice provision, but when the health care professional submits notice, their last date is suddenly accelerated, and they are released without further compensation, notice, or benefits. This type of provision is particularly offensive to health care employees who take the step of giving proper contractual notice and, similar to the probationary language, can create real job insecurity for an employee who suddenly loses their paycheck and has no new job to start.

Medical workers should be paid for the entire notice period whether or not they are allowed to work. Unfortunately, this type of provision is sometimes hidden in contracts and not noticed by employees, who tend to focus on the notice provision itself. I consider this provision to be a red flag about the employer when I review clients’ contracts.
 

Malpractice tail

Although many employers will claim it is not unusual for an employee to pay for their own malpractice tail, in the current marketplace, the payment of tail can be a deciding factor in whether a candidate accepts a contract.

At a minimum, employers should consider paying for the tail under circumstances where they non-renew a contract, terminate without cause, or the contract is terminated for the employer’s breach. Similarly, I like to seek out payment of the tail by the employer where the contract is terminated owing to a change in the law, use of a force majeure provision, loss of the employer’s hospital contract, or similar provisions where termination is outside the control of the employee.

Employers should also consider a provision where they share the cost of a tail or cover the entire cost on the basis of years of service in order to stand out to a potential candidate.
 

Noncompete provisions

I do not find noncompete provisions to be generally unacceptable when properly written; however, employers should reevaluate the reasonableness of their noncompete language frequently, because such language can make the difference in whether a candidate accepts a contract.

A reasonable noncompete that only protects the employer as necessary and does not restrict the reasonable practice of medicine is always preferable and can be the deciding factor for a candidate. Tying enforcement of a noncompete to reasons for termination (similar to the tail) can also make a positive difference in a candidate’s review of a contract.

Egregious noncompetes, where the candidate is simply informed that the language is “not negotiable,” are unlikely to be compelling to a candidate with other options.
 

Specifics on location, call, schedule

One item potential employees find extremely frustrating about contracts is when it fails to include promises made regarding location, call, and schedule.

These particular items affect a physician’s expectations about a job, including commute time, family life, and lifestyle. An employer or recruiter that makes a lot of promises on these points but won’t commit to the details in writing (or at least offer mutual agreement on these issues) can cause an uncertain candidate to choose the job that offers greater certainty.

There are many provisions of a contract that can make a difference to a particular job applicant. A savvy employer seeking to capture a particular health care professional should find out what the specific goals and needs of the candidate might be and consider adjusting the contract to best satisfy the candidate.

At the end of the day, however, at least for those physicians and others reviewing contracts that are fairly equivalent, it may be the fairness of the contract provisions that end up being the deciding factor.

Ms. Adler is Health Law Group Practice Leader for the law firm Roetzel in Chicago. She reported no relevant conflicts of interest.

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

Recruiting health care workers is a challenge these days for both private practice and hospital employers, and competition can be fierce. In order to be competitive, employers need to review the package they are offering potential candidates and understand that it’s more than just compensation and benefits that matter.

When all else is equal, contract language can end up being the difference between capturing or losing a candidate.

As someone who reviews physician contracts extensively, there are some common examples of language that may cause a candidate to choose a different position.
 

Probationary period

Although every employer wants to find out if they like the physician or midlevel employee that they have just hired before fully committing, the inclusion of a probationary period (usually 90 days) is offensive to a candidate, especially one with a choice of contracts.

Essentially, the employer is asking the employee to (potentially) relocate, go through the credentialing process, and turn down other potential offers, all for the possibility that they could easily be terminated. Probationary periods typically allow an employee to be immediately terminated without notice or cause, which can then leave them stranded without a paycheck (and with a new home and/or other recent commitments).

Moreover, contracts with probationary periods tend to terminate the employee without covering any tail costs or clarifying that the employer will not enforce restrictive provisions (even if unlikely to be legally enforceable based on the short relationship).

It is important to understand that the process of a person finding a new position, which includes interviewing, contract negotiation, and credentialing, can take up to 6 months. For this reason, probationary provisions create real job insecurity for a candidate.

Entering into a new affiliation is a leap of faith both for the employer and the employee. If the circumstances do not work out, the employer should fairly compensate the employee for the notice period and ask them not to return to work or otherwise allow them to keep working the notice period while they search for a new position.
 

Acceleration of notice

Another objectionable provision that employers like to include in their contracts is one which allows the employer to accelerate and immediately terminate an employee who has given proper notice.

The contract will contain a standard notice provision, but when the health care professional submits notice, their last date is suddenly accelerated, and they are released without further compensation, notice, or benefits. This type of provision is particularly offensive to health care employees who take the step of giving proper contractual notice and, similar to the probationary language, can create real job insecurity for an employee who suddenly loses their paycheck and has no new job to start.

Medical workers should be paid for the entire notice period whether or not they are allowed to work. Unfortunately, this type of provision is sometimes hidden in contracts and not noticed by employees, who tend to focus on the notice provision itself. I consider this provision to be a red flag about the employer when I review clients’ contracts.
 

Malpractice tail

Although many employers will claim it is not unusual for an employee to pay for their own malpractice tail, in the current marketplace, the payment of tail can be a deciding factor in whether a candidate accepts a contract.

At a minimum, employers should consider paying for the tail under circumstances where they non-renew a contract, terminate without cause, or the contract is terminated for the employer’s breach. Similarly, I like to seek out payment of the tail by the employer where the contract is terminated owing to a change in the law, use of a force majeure provision, loss of the employer’s hospital contract, or similar provisions where termination is outside the control of the employee.

Employers should also consider a provision where they share the cost of a tail or cover the entire cost on the basis of years of service in order to stand out to a potential candidate.
 

Noncompete provisions

I do not find noncompete provisions to be generally unacceptable when properly written; however, employers should reevaluate the reasonableness of their noncompete language frequently, because such language can make the difference in whether a candidate accepts a contract.

A reasonable noncompete that only protects the employer as necessary and does not restrict the reasonable practice of medicine is always preferable and can be the deciding factor for a candidate. Tying enforcement of a noncompete to reasons for termination (similar to the tail) can also make a positive difference in a candidate’s review of a contract.

Egregious noncompetes, where the candidate is simply informed that the language is “not negotiable,” are unlikely to be compelling to a candidate with other options.
 

Specifics on location, call, schedule

One item potential employees find extremely frustrating about contracts is when it fails to include promises made regarding location, call, and schedule.

These particular items affect a physician’s expectations about a job, including commute time, family life, and lifestyle. An employer or recruiter that makes a lot of promises on these points but won’t commit to the details in writing (or at least offer mutual agreement on these issues) can cause an uncertain candidate to choose the job that offers greater certainty.

There are many provisions of a contract that can make a difference to a particular job applicant. A savvy employer seeking to capture a particular health care professional should find out what the specific goals and needs of the candidate might be and consider adjusting the contract to best satisfy the candidate.

At the end of the day, however, at least for those physicians and others reviewing contracts that are fairly equivalent, it may be the fairness of the contract provisions that end up being the deciding factor.

Ms. Adler is Health Law Group Practice Leader for the law firm Roetzel in Chicago. She reported no relevant conflicts of interest.

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

A sedentary lifestyle has already been linked with an increased risk for breast cancer based on data from observational studies, but a new study with different methodology  provides stronger evidence of causality.

The results of the new study suggest that greater overall physical activity levels, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk, said the authors.

Viktor Cap/Thinkstock

“Increasing physical activity and reducing sedentary time are already recommended for cancer prevention. Our study adds further evidence that such behavioral changes are likely to lower the incidence of future breast cancer rates,” Suzanne C. Dixon-Suen, PhD, of Cancer Council Victoria, Melbourne, and colleagues reported on behalf of the Breast Cancer Association Consortium (BCAC).

The findings were published online in the British Journal of Sports Medicine.

The investigators used individual-level BCAC case-control data and performed two-sample Mendelian randomization – a study method that assesses causality by using genetic variants as proxies for particular risk factors. In this case, genetic variants were used as proxies for lifelong physical activity levels and sedentary behaviors.

“[Genetic] instruments were single-nucleotide polymorphisms (SNPs) associated in UK Biobank [genomewide association studies] with overall physical activity (all movement), vigorous physical activity, or sedentary time” as assessed by a wrist-worn accelerometer.

Patients with greater genetic predisposition to higher overall activity levels had a 41% lower overall breast cancer risk (odds ratio, 0.59), the team reported. Genetically predicted vigorous activity was associated with a 38% lower risk of premenopausal and perimenopausal breast cancer (OR, 0.62 for 3 or more days vs. 0 days of self-reported days per week).

Conversely, greater genetically predicted sedentary time was associated with a 77%  higher risk of hormone receptor–negative breast cancer risk (OR, 1.77), including triple-negative breast cancer, for which the risk was 104% higher (OR, 2.04).

The findings were generally consistent across disease types and stages, and were unchanged after factoring in “the production by a single gene of two or more apparently unrelated effects (pleiotropy), such as smoking and overweight, for example,” according to a press release from the journal.

The investigators included data from 130,957 women of European ancestry. Of those, 69,838 had invasive disease, 6,667 had in situ tumors, and 54,452 were controls without breast cancer. The case-control groups included 23,999 pre-/perimenopausal women with invasive breast cancer and 17,686 women without, and 45,839 postmenopausal women with breast cancer and 36,766 without.

A number of plausible biological explanations for the findings exist, the authors noted, adding that convincing evidence suggests there are causal pathways between physical activity and breast cancer risk, including overweight and obesity, disordered metabolism, sex hormones, and inflammation.

Furthermore, the researchers reported, “mechanisms linking sedentary time and cancer are likely to at least partially overlap with those underpinning the physical activity relationship.”

For the future, they suggested that “[a] stronger cancer-control focus on physical activity and sedentary time as modifiable cancer risk factors is warranted, given the heavy burden of disease attributed to the most common cancer in women.”

This study was funded by multiple international sources. Dr. Dixon-Suen reported no relevant financial relationships. Several coauthors disclosed relationships with industry.

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

A sedentary lifestyle has already been linked with an increased risk for breast cancer based on data from observational studies, but a new study with different methodology  provides stronger evidence of causality.

The results of the new study suggest that greater overall physical activity levels, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk, said the authors.

Viktor Cap/Thinkstock

“Increasing physical activity and reducing sedentary time are already recommended for cancer prevention. Our study adds further evidence that such behavioral changes are likely to lower the incidence of future breast cancer rates,” Suzanne C. Dixon-Suen, PhD, of Cancer Council Victoria, Melbourne, and colleagues reported on behalf of the Breast Cancer Association Consortium (BCAC).

The findings were published online in the British Journal of Sports Medicine.

The investigators used individual-level BCAC case-control data and performed two-sample Mendelian randomization – a study method that assesses causality by using genetic variants as proxies for particular risk factors. In this case, genetic variants were used as proxies for lifelong physical activity levels and sedentary behaviors.

“[Genetic] instruments were single-nucleotide polymorphisms (SNPs) associated in UK Biobank [genomewide association studies] with overall physical activity (all movement), vigorous physical activity, or sedentary time” as assessed by a wrist-worn accelerometer.

Patients with greater genetic predisposition to higher overall activity levels had a 41% lower overall breast cancer risk (odds ratio, 0.59), the team reported. Genetically predicted vigorous activity was associated with a 38% lower risk of premenopausal and perimenopausal breast cancer (OR, 0.62 for 3 or more days vs. 0 days of self-reported days per week).

Conversely, greater genetically predicted sedentary time was associated with a 77%  higher risk of hormone receptor–negative breast cancer risk (OR, 1.77), including triple-negative breast cancer, for which the risk was 104% higher (OR, 2.04).

The findings were generally consistent across disease types and stages, and were unchanged after factoring in “the production by a single gene of two or more apparently unrelated effects (pleiotropy), such as smoking and overweight, for example,” according to a press release from the journal.

The investigators included data from 130,957 women of European ancestry. Of those, 69,838 had invasive disease, 6,667 had in situ tumors, and 54,452 were controls without breast cancer. The case-control groups included 23,999 pre-/perimenopausal women with invasive breast cancer and 17,686 women without, and 45,839 postmenopausal women with breast cancer and 36,766 without.

A number of plausible biological explanations for the findings exist, the authors noted, adding that convincing evidence suggests there are causal pathways between physical activity and breast cancer risk, including overweight and obesity, disordered metabolism, sex hormones, and inflammation.

Furthermore, the researchers reported, “mechanisms linking sedentary time and cancer are likely to at least partially overlap with those underpinning the physical activity relationship.”

For the future, they suggested that “[a] stronger cancer-control focus on physical activity and sedentary time as modifiable cancer risk factors is warranted, given the heavy burden of disease attributed to the most common cancer in women.”

This study was funded by multiple international sources. Dr. Dixon-Suen reported no relevant financial relationships. Several coauthors disclosed relationships with industry.

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

A sedentary lifestyle has already been linked with an increased risk for breast cancer based on data from observational studies, but a new study with different methodology  provides stronger evidence of causality.

The results of the new study suggest that greater overall physical activity levels, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk, said the authors.

Viktor Cap/Thinkstock

“Increasing physical activity and reducing sedentary time are already recommended for cancer prevention. Our study adds further evidence that such behavioral changes are likely to lower the incidence of future breast cancer rates,” Suzanne C. Dixon-Suen, PhD, of Cancer Council Victoria, Melbourne, and colleagues reported on behalf of the Breast Cancer Association Consortium (BCAC).

The findings were published online in the British Journal of Sports Medicine.

The investigators used individual-level BCAC case-control data and performed two-sample Mendelian randomization – a study method that assesses causality by using genetic variants as proxies for particular risk factors. In this case, genetic variants were used as proxies for lifelong physical activity levels and sedentary behaviors.

“[Genetic] instruments were single-nucleotide polymorphisms (SNPs) associated in UK Biobank [genomewide association studies] with overall physical activity (all movement), vigorous physical activity, or sedentary time” as assessed by a wrist-worn accelerometer.

Patients with greater genetic predisposition to higher overall activity levels had a 41% lower overall breast cancer risk (odds ratio, 0.59), the team reported. Genetically predicted vigorous activity was associated with a 38% lower risk of premenopausal and perimenopausal breast cancer (OR, 0.62 for 3 or more days vs. 0 days of self-reported days per week).

Conversely, greater genetically predicted sedentary time was associated with a 77%  higher risk of hormone receptor–negative breast cancer risk (OR, 1.77), including triple-negative breast cancer, for which the risk was 104% higher (OR, 2.04).

The findings were generally consistent across disease types and stages, and were unchanged after factoring in “the production by a single gene of two or more apparently unrelated effects (pleiotropy), such as smoking and overweight, for example,” according to a press release from the journal.

The investigators included data from 130,957 women of European ancestry. Of those, 69,838 had invasive disease, 6,667 had in situ tumors, and 54,452 were controls without breast cancer. The case-control groups included 23,999 pre-/perimenopausal women with invasive breast cancer and 17,686 women without, and 45,839 postmenopausal women with breast cancer and 36,766 without.

A number of plausible biological explanations for the findings exist, the authors noted, adding that convincing evidence suggests there are causal pathways between physical activity and breast cancer risk, including overweight and obesity, disordered metabolism, sex hormones, and inflammation.

Furthermore, the researchers reported, “mechanisms linking sedentary time and cancer are likely to at least partially overlap with those underpinning the physical activity relationship.”

For the future, they suggested that “[a] stronger cancer-control focus on physical activity and sedentary time as modifiable cancer risk factors is warranted, given the heavy burden of disease attributed to the most common cancer in women.”

This study was funded by multiple international sources. Dr. Dixon-Suen reported no relevant financial relationships. Several coauthors disclosed relationships with industry.

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

A former health care worker who is now pursuing a career in adult entertainment helped one of her regular clients toward a cancer diagnosis, after urging him to get checked out by a doctor.

For 7 years, Belle Grace had been working with children and adults diagnosed with autism. But during the COVID-19 pandemic, like many other people, she began to look for alternative streams of revenue.

In May 2020, Ms. Grace created a profile on the adult content subscription site OnlyFans.

“I was taking some time off of work and found myself on OnlyFans as a bit of a side hustle,” said Ms. Grace. “It wasn’t until I started earning five times more than my standard wage that I decided to go full-time and make that career change.”

She soon built up a regular clientele, hosting intimate video chats.

While video chatting with one of her loyal subscribers, Ms. Grace noticed something different about his testicles. Hesitantly, she mentioned that one testicle was a lot larger than the other – a change she hadn’t noticed before during their 2 years of interacting.

Ms. Grace says she was nervous about bringing up the subject with her subscriber. She suggested that he should see a doctor to have his testicles checked out, but her client didn’t go right away.

Ms. Grace says he waited a couple of months to go in for a check-up because he was slightly embarrassed. When he finally went to the doctor, he was given a diagnosis of testicular cancer.

Although Ms. Grace says that the conversation with her subscriber was a bit awkward, she’s happy she gathered the courage to bring it to his attention.

Testicular cancer is relatively rare, but it usually has a good prognosis – the survival rate is about 95%, according to Alexander Kutikov, MD, professor of surgical oncology at Fox Chase Cancer Center in Philadelphia.

Dr. Kutikov emphasized that men shouldn’t wait if they notice any changes in their genitals. The quicker they go see a doctor, the better the outcome is likely to be if it does turn out to be something serious.

For testicular cancer, “the treatment can be much more simple if it’s caught early – avoiding chemotherapy and avoiding major surgery,” Dr. Kutikov said.

“But even testicular cancers that present after they have spread can be cured. So a delay is suboptimal, but it’s not as devastating as some other cancers,” he added.

Most men who are diagnosed with testicular cancer present after noticing changes in the scrotum where one testicle feels and looks different from the other, Dr. Kutikov commented. In addition, there is usually a very firm mass or nodule that can be felt under the skin.

“Another common symptom is back pain, because testicular cancer can go to the lymph nodes in the back as well,” he said.

Dr. Kutikov says it all comes down to being aware of your body and noticing any major changes.

Ms. Grace suggests that sexual intimacy offers an opportunity for noting physical changes, “because you and your sexual partner are able to see each other’s bodies in the most intimate [manner].”

“People should be telling their partners if they notice any changes,” she says, for example, on their skin, such as sores or rashes, or lumps under the skin. “Even a change in a mole could be essential for your partner’s health,” she said.

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

A former health care worker who is now pursuing a career in adult entertainment helped one of her regular clients toward a cancer diagnosis, after urging him to get checked out by a doctor.

For 7 years, Belle Grace had been working with children and adults diagnosed with autism. But during the COVID-19 pandemic, like many other people, she began to look for alternative streams of revenue.

In May 2020, Ms. Grace created a profile on the adult content subscription site OnlyFans.

“I was taking some time off of work and found myself on OnlyFans as a bit of a side hustle,” said Ms. Grace. “It wasn’t until I started earning five times more than my standard wage that I decided to go full-time and make that career change.”

She soon built up a regular clientele, hosting intimate video chats.

While video chatting with one of her loyal subscribers, Ms. Grace noticed something different about his testicles. Hesitantly, she mentioned that one testicle was a lot larger than the other – a change she hadn’t noticed before during their 2 years of interacting.

Ms. Grace says she was nervous about bringing up the subject with her subscriber. She suggested that he should see a doctor to have his testicles checked out, but her client didn’t go right away.

Ms. Grace says he waited a couple of months to go in for a check-up because he was slightly embarrassed. When he finally went to the doctor, he was given a diagnosis of testicular cancer.

Although Ms. Grace says that the conversation with her subscriber was a bit awkward, she’s happy she gathered the courage to bring it to his attention.

Testicular cancer is relatively rare, but it usually has a good prognosis – the survival rate is about 95%, according to Alexander Kutikov, MD, professor of surgical oncology at Fox Chase Cancer Center in Philadelphia.

Dr. Kutikov emphasized that men shouldn’t wait if they notice any changes in their genitals. The quicker they go see a doctor, the better the outcome is likely to be if it does turn out to be something serious.

For testicular cancer, “the treatment can be much more simple if it’s caught early – avoiding chemotherapy and avoiding major surgery,” Dr. Kutikov said.

“But even testicular cancers that present after they have spread can be cured. So a delay is suboptimal, but it’s not as devastating as some other cancers,” he added.

Most men who are diagnosed with testicular cancer present after noticing changes in the scrotum where one testicle feels and looks different from the other, Dr. Kutikov commented. In addition, there is usually a very firm mass or nodule that can be felt under the skin.

“Another common symptom is back pain, because testicular cancer can go to the lymph nodes in the back as well,” he said.

Dr. Kutikov says it all comes down to being aware of your body and noticing any major changes.

Ms. Grace suggests that sexual intimacy offers an opportunity for noting physical changes, “because you and your sexual partner are able to see each other’s bodies in the most intimate [manner].”

“People should be telling their partners if they notice any changes,” she says, for example, on their skin, such as sores or rashes, or lumps under the skin. “Even a change in a mole could be essential for your partner’s health,” she said.

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

A former health care worker who is now pursuing a career in adult entertainment helped one of her regular clients toward a cancer diagnosis, after urging him to get checked out by a doctor.

For 7 years, Belle Grace had been working with children and adults diagnosed with autism. But during the COVID-19 pandemic, like many other people, she began to look for alternative streams of revenue.

In May 2020, Ms. Grace created a profile on the adult content subscription site OnlyFans.

“I was taking some time off of work and found myself on OnlyFans as a bit of a side hustle,” said Ms. Grace. “It wasn’t until I started earning five times more than my standard wage that I decided to go full-time and make that career change.”

She soon built up a regular clientele, hosting intimate video chats.

While video chatting with one of her loyal subscribers, Ms. Grace noticed something different about his testicles. Hesitantly, she mentioned that one testicle was a lot larger than the other – a change she hadn’t noticed before during their 2 years of interacting.

Ms. Grace says she was nervous about bringing up the subject with her subscriber. She suggested that he should see a doctor to have his testicles checked out, but her client didn’t go right away.

Ms. Grace says he waited a couple of months to go in for a check-up because he was slightly embarrassed. When he finally went to the doctor, he was given a diagnosis of testicular cancer.

Although Ms. Grace says that the conversation with her subscriber was a bit awkward, she’s happy she gathered the courage to bring it to his attention.

Testicular cancer is relatively rare, but it usually has a good prognosis – the survival rate is about 95%, according to Alexander Kutikov, MD, professor of surgical oncology at Fox Chase Cancer Center in Philadelphia.

Dr. Kutikov emphasized that men shouldn’t wait if they notice any changes in their genitals. The quicker they go see a doctor, the better the outcome is likely to be if it does turn out to be something serious.

For testicular cancer, “the treatment can be much more simple if it’s caught early – avoiding chemotherapy and avoiding major surgery,” Dr. Kutikov said.

“But even testicular cancers that present after they have spread can be cured. So a delay is suboptimal, but it’s not as devastating as some other cancers,” he added.

Most men who are diagnosed with testicular cancer present after noticing changes in the scrotum where one testicle feels and looks different from the other, Dr. Kutikov commented. In addition, there is usually a very firm mass or nodule that can be felt under the skin.

“Another common symptom is back pain, because testicular cancer can go to the lymph nodes in the back as well,” he said.

Dr. Kutikov says it all comes down to being aware of your body and noticing any major changes.

Ms. Grace suggests that sexual intimacy offers an opportunity for noting physical changes, “because you and your sexual partner are able to see each other’s bodies in the most intimate [manner].”

“People should be telling their partners if they notice any changes,” she says, for example, on their skin, such as sores or rashes, or lumps under the skin. “Even a change in a mole could be essential for your partner’s health,” she said.

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

The end of August brought a small-but-second-consecutive increase in weekly COVID-19 cases among children, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

New cases rose by 4.6% for the week of Aug. 26 to Sept. 1, following a week in which cases increased by almost 9%, as the second half of August basically reversed the two consecutive weeks of decreases during the first half of the month, based on the AAP/CHA data collected from state and territorial health departments.

Similar trends can be seen for emergency department visits, with the exception of children aged 0-11 years, whose ED visit rates have continued to fall since late July. Children aged 12-15, however, had a 7-day average of 4.4% of ED visits with diagnosed COVID on Aug. 25, compared with 3.1% for Aug. 12. Children aged 16-17 years were at 3.4% on Aug. 27, compared with 3.1% as late as Aug. 15, the Centers for Disease Control and Prevention reported.

Hospital admissions with confirmed COVID-19, reported only for children aged 0-17 years, also reflect the late-August trend of increased cases. New hospitalizations dropped from 0.46 per 100,000 population on July 30 to 0.40 per 100,000 on Aug. 19 but have since risen to 0.44 per 100,000 as of Aug. 27, the CDC said on its COVID Data Tracker.

Initial vaccinations, meanwhile, have declined since early August for all children, according to a separate report from the AAP. A look at CDC data for two specific days – the first and last Mondays of the month – shows that those aged under 5 received 12,982 doses on Aug. 1, compared with 5,824 doses on Aug. 29. Over that same time, initial vaccinations in 5- to 11-year-olds went from 9,058 to 2,879, while among those aged 12-17 they dropped from 4,245 to 1,226.

Cumulatively, 5.5% of all children under age 5 had received at least one dose and 1.3% were fully vaccinated by Aug. 30, compared with 38.1% and 30.7%, respectively, of those aged 5-11 and 70.7% and 60.5% of 12- to 17-year-olds, the CDC said.

[email protected]

The end of August brought a small-but-second-consecutive increase in weekly COVID-19 cases among children, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

New cases rose by 4.6% for the week of Aug. 26 to Sept. 1, following a week in which cases increased by almost 9%, as the second half of August basically reversed the two consecutive weeks of decreases during the first half of the month, based on the AAP/CHA data collected from state and territorial health departments.

Similar trends can be seen for emergency department visits, with the exception of children aged 0-11 years, whose ED visit rates have continued to fall since late July. Children aged 12-15, however, had a 7-day average of 4.4% of ED visits with diagnosed COVID on Aug. 25, compared with 3.1% for Aug. 12. Children aged 16-17 years were at 3.4% on Aug. 27, compared with 3.1% as late as Aug. 15, the Centers for Disease Control and Prevention reported.

Hospital admissions with confirmed COVID-19, reported only for children aged 0-17 years, also reflect the late-August trend of increased cases. New hospitalizations dropped from 0.46 per 100,000 population on July 30 to 0.40 per 100,000 on Aug. 19 but have since risen to 0.44 per 100,000 as of Aug. 27, the CDC said on its COVID Data Tracker.

Initial vaccinations, meanwhile, have declined since early August for all children, according to a separate report from the AAP. A look at CDC data for two specific days – the first and last Mondays of the month – shows that those aged under 5 received 12,982 doses on Aug. 1, compared with 5,824 doses on Aug. 29. Over that same time, initial vaccinations in 5- to 11-year-olds went from 9,058 to 2,879, while among those aged 12-17 they dropped from 4,245 to 1,226.

Cumulatively, 5.5% of all children under age 5 had received at least one dose and 1.3% were fully vaccinated by Aug. 30, compared with 38.1% and 30.7%, respectively, of those aged 5-11 and 70.7% and 60.5% of 12- to 17-year-olds, the CDC said.

[email protected]

The end of August brought a small-but-second-consecutive increase in weekly COVID-19 cases among children, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

New cases rose by 4.6% for the week of Aug. 26 to Sept. 1, following a week in which cases increased by almost 9%, as the second half of August basically reversed the two consecutive weeks of decreases during the first half of the month, based on the AAP/CHA data collected from state and territorial health departments.

Similar trends can be seen for emergency department visits, with the exception of children aged 0-11 years, whose ED visit rates have continued to fall since late July. Children aged 12-15, however, had a 7-day average of 4.4% of ED visits with diagnosed COVID on Aug. 25, compared with 3.1% for Aug. 12. Children aged 16-17 years were at 3.4% on Aug. 27, compared with 3.1% as late as Aug. 15, the Centers for Disease Control and Prevention reported.

Hospital admissions with confirmed COVID-19, reported only for children aged 0-17 years, also reflect the late-August trend of increased cases. New hospitalizations dropped from 0.46 per 100,000 population on July 30 to 0.40 per 100,000 on Aug. 19 but have since risen to 0.44 per 100,000 as of Aug. 27, the CDC said on its COVID Data Tracker.

Initial vaccinations, meanwhile, have declined since early August for all children, according to a separate report from the AAP. A look at CDC data for two specific days – the first and last Mondays of the month – shows that those aged under 5 received 12,982 doses on Aug. 1, compared with 5,824 doses on Aug. 29. Over that same time, initial vaccinations in 5- to 11-year-olds went from 9,058 to 2,879, while among those aged 12-17 they dropped from 4,245 to 1,226.

Cumulatively, 5.5% of all children under age 5 had received at least one dose and 1.3% were fully vaccinated by Aug. 30, compared with 38.1% and 30.7%, respectively, of those aged 5-11 and 70.7% and 60.5% of 12- to 17-year-olds, the CDC said.

[email protected]

When Michael McGrath, MD, medical director of the Ohana Luxury Alcohol Rehab on the Big Island of Hawaii, trains primary care physicians, he tells them that talking with patients about substance use disorders is like having a stressful, weird conversation. But it’s a courageous one, because of the stigma associated with drug and alcohol disorders.

Dr. McGrath starts the conversation with patients by expressing that physicians now understand that addiction is a disease – one for which the patient isn’t responsible. He explains that there’s both a genetic and a nature/nurture component of the disorder and assures them that he won’t judge or abandon them but rather help them find treatment and make sure they get on the path to wellness.

It’s all too common to see patients with a substance use disorder in today’s primary care population. According to Medscape’s Physicians’ Views on Today’s Divisive Social Issues Report 2022, 42% of physicians see patients with a substance use disorder often in their practices. However, identifying substance use disorders and treating or referring patients for them is a complex problem.

According to the Recovery Research Institute, a leading nonprofit orgnaization from Massachusetts General Hospital dedicated to advancing addiction treatment and recovery, about 20 million people in the United States suffer from a substance use disorder. More than half (54%) need assistance with their recovery. The National Institute on Drug Abuse reports that substance abuse and addiction cost society more than $740 billion annually in workplace productivity, health care, and crime-related expenses.

Despite the challenges, physician experts provide advice on how to treat and help patients who have substance use disorders more effectively.
 

A courageous conversation

Often, the primary care physician or emergency physician is the first to be aware of a patient’s problem with a substance or a relapse. In many communities where shortages of specialized physicians and nonphysician treatment options for substance use disorders aren’t available, there’s usually limited time and resources to help patients with these disorders.

Patients often sense doctors are rushed and may not be interested in hearing about their drug or alcohol problems. Reddit threads are filled with stories like that of user “Cyralek,” who say that the two doctors they’ve seen since quitting drinking didn’t show much interest in the problem beyond ordering liver function tests.

In a nationwide study by researchers at Washington University School of Medicine, St. Louis, 80% of patients who met the diagnostic criteria for substance use disorder visited a doctor, hospital, or clinic for some reason over the past year. Only 1 in 10 were encouraged to cut back on drinking or receive any form of treatment or referral for substance misuse.

Emma Gordon, founder of a salvage yard in Los Angeles, says she used to abuse alcohol and that it affected every aspect of her life. Her brother tried to intervene, but nothing worked until she finally told a physician. “I admitted my problem and felt incredibly calm when she reacted as though it was all normal. I believe that was my first step to becoming a better me. I was thankful I had gone to see a doctor,” says Ms. Gordon.

Though physicians in primary care may not have more than a 15-minute appointment slot, seizing the opportunity to initiate a substance use disorder conversation when warranted is crucial, says Dr. McGrath. The CAGE-AID screening tool, which includes questions such as, “Have you ever felt you ought to cut down on your drinking or drug use?” is an excellent starter. Dr. McGrath also advises primary care clinicians to lower the threshold of concern to a single positive answer rather than several.

Doctors aren’t necessarily rewarded for the time it takes to develop a rapport with patients and to have a conversation that leads to asking, “How much are you drinking?”

“The system in primary care isn’t set up that way,” said Lucy McBride, MD, an internist in Washington, D.C.
 

Patients don’t often ask for help

In a perfect world, patients struggling with a substance use disorder would present with a request to discontinue using drugs or alcohol, as Ms. Gordon did. While that does happen sometimes, the onus is on the physician to screen for substance misuse.

“Remember, this is the disease that tells you that you don’t have a disease,” Dr. McGrath says. He also says that the use of screening instruments is a bare minimum. When patients are in the throes of a substance use disorder, the prefrontal cortex doesn’t work effectively. Dr. McGrath says there’s an alteration of consciousness so that the patient doesn’t realize the extent of the disease. “Often simply asking the patient is falling far short. It’s the biggest mistake I see,” he says.

Self-reporting from the patient may be unreliable. “That would be like a patient coming in and saying, ‘My blood sugar is 700, and I want you to give me some insulin,’ ” Dr. McGrath says. Instead, clinicians in the field need a more objective measurement.

Perhaps that means asking the patient to bring in a significant other at the next visit or digging deeper into the conversation about alcohol and drugs and their role in the patient’s life. And to really have an impact, Dr. McGrath said, the clinician should talk to the patient about referral for further evaluation.

“You have to get collateral history; that’s the goldmine for the clinician,” Dr. McGrath says. “It may take a few more minutes or mean talking to a family member, but it can make the difference between life and death.”

“I am thankful to my doctor who discussed this [substance use disorder] with me in detail,” says Ronald Williams, another Angeleno who braved the difficult discussion with his doctor. Mr. Williams says his doctor explained it in a good way and that if the doctor hadn’t guided him empathetically, the conversation might not have gone as well.

“We check patients’ cholesterol. We get them on the scale. But there is no blood test to discover how much they’re drinking, no PCR to test for social anxiety, no MRI that distinguishes between their recreational marijuana use and marijuana abuse,” said Dr. McBride.
 

Check the prescription drugs they’re taking

Another thing Dr. McGrath recommends is for primary care physicians to check the prescription drug monitoring program (PDMP) database in their state to help be alerted to a patient with a substance use disorder. The CDC’s PMPD guidelines recommend that the clinician check on a patient every 3 months or each time they write an opioid prescription. Assigning a staff member or a nurse to check the database can help uncover a history of doctor-shopping or use of controlled substances.

“There’s been a lot of times I’ve gone on self-report, and I’ve been bamboozled because I don’t have a truth-o-meter, and I can’t tell when a patient is telling the truth,” says Dr. McGrath.

He is also a huge proponent of point-of-service screening. Patients can urinate in a cup that has amino assay strips on the side, like an immediate COVID-19 test, or they can spit into a saliva cup. “It’s really beneficial for the patient and the clinician to know right then at the point of service if there is a substance present and what it is,” Dr. McGrath said.

It can be part of the larger conversation once a problem with substances has been uncovered. The clinician can say something like, “Let’s see where you are right now today as far as what you have in your system and where we should go from here.”
 

Other barriers physicians face

Many physicians may feel unprepared to meet the needs of patients with substance use disorders or prescribe medication that blunts cravings and reduces the urge to drink without the need for special training. Scientists at the National Institutes of Health found that only 1.6% of people with a substance use disorder were prescribed medication to help control it.

In the largest study on how primary care physicians address substance use disorders, fewer than 20% described themselves as very prepared to identify alcoholism or illegal drug use. Since most patients prefer to seek treatment from their primary care doctor, at least initially, not being prepared is a problem.

Although referral for specialty addiction treatment is recommended for patients with severe substance use disorders, primary care physicians with appropriate experience, training, and support can provide some of these services. “In an ideal world I wouldn’t have to refer patients out, since they’re much more likely to talk with their primary care provider about sensitive, intimate topics,” says Dr. McBride.
 

The issue of reimbursement

Billing for substance use disorder counseling or coordination of care is still challenging, and how to get compensated remains a conundrum for many physicians. Reimbursement may not adequately compensate providers for the additional time and staff needed, but some changes have been positive.

For instance, the American Society for Addiction Medicine reports that in 2022, Medicare expanded the physician fee schedule for opioid and SUD counseling to include reimbursement for telemedicine services.

Learning the billing CPT codes for various addiction treatments and counseling, or having a billing service that understands them, is crucial to reimbursement and keeping revenue running smoothly.

At the very least, developing relationships with treatment centers and specialists in the community can help physicians with referrals and with determining the level of care needed. Physicians can help facilitate that care with routine reassessment and frequent follow-ups, as well as by requesting reports from the treatment facility, continuing treatment of medical conditions, and reinforcing the importance of continued substance use disorder treatment.

Dr. McBride says that primary care physicians can and should make their office a safe, blame-free medical home for patients with substance use disorders. “Patients also need to understand they should bring their whole selves to the doctor – to talk about their sleep, what they consume, their depression, and not just about alcohol, but their relationship with it, and other substances,” she says.

“There needs to be time to talk about it.”

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

When Michael McGrath, MD, medical director of the Ohana Luxury Alcohol Rehab on the Big Island of Hawaii, trains primary care physicians, he tells them that talking with patients about substance use disorders is like having a stressful, weird conversation. But it’s a courageous one, because of the stigma associated with drug and alcohol disorders.

Dr. McGrath starts the conversation with patients by expressing that physicians now understand that addiction is a disease – one for which the patient isn’t responsible. He explains that there’s both a genetic and a nature/nurture component of the disorder and assures them that he won’t judge or abandon them but rather help them find treatment and make sure they get on the path to wellness.

It’s all too common to see patients with a substance use disorder in today’s primary care population. According to Medscape’s Physicians’ Views on Today’s Divisive Social Issues Report 2022, 42% of physicians see patients with a substance use disorder often in their practices. However, identifying substance use disorders and treating or referring patients for them is a complex problem.

According to the Recovery Research Institute, a leading nonprofit orgnaization from Massachusetts General Hospital dedicated to advancing addiction treatment and recovery, about 20 million people in the United States suffer from a substance use disorder. More than half (54%) need assistance with their recovery. The National Institute on Drug Abuse reports that substance abuse and addiction cost society more than $740 billion annually in workplace productivity, health care, and crime-related expenses.

Despite the challenges, physician experts provide advice on how to treat and help patients who have substance use disorders more effectively.
 

A courageous conversation

Often, the primary care physician or emergency physician is the first to be aware of a patient’s problem with a substance or a relapse. In many communities where shortages of specialized physicians and nonphysician treatment options for substance use disorders aren’t available, there’s usually limited time and resources to help patients with these disorders.

Patients often sense doctors are rushed and may not be interested in hearing about their drug or alcohol problems. Reddit threads are filled with stories like that of user “Cyralek,” who say that the two doctors they’ve seen since quitting drinking didn’t show much interest in the problem beyond ordering liver function tests.

In a nationwide study by researchers at Washington University School of Medicine, St. Louis, 80% of patients who met the diagnostic criteria for substance use disorder visited a doctor, hospital, or clinic for some reason over the past year. Only 1 in 10 were encouraged to cut back on drinking or receive any form of treatment or referral for substance misuse.

Emma Gordon, founder of a salvage yard in Los Angeles, says she used to abuse alcohol and that it affected every aspect of her life. Her brother tried to intervene, but nothing worked until she finally told a physician. “I admitted my problem and felt incredibly calm when she reacted as though it was all normal. I believe that was my first step to becoming a better me. I was thankful I had gone to see a doctor,” says Ms. Gordon.

Though physicians in primary care may not have more than a 15-minute appointment slot, seizing the opportunity to initiate a substance use disorder conversation when warranted is crucial, says Dr. McGrath. The CAGE-AID screening tool, which includes questions such as, “Have you ever felt you ought to cut down on your drinking or drug use?” is an excellent starter. Dr. McGrath also advises primary care clinicians to lower the threshold of concern to a single positive answer rather than several.

Doctors aren’t necessarily rewarded for the time it takes to develop a rapport with patients and to have a conversation that leads to asking, “How much are you drinking?”

“The system in primary care isn’t set up that way,” said Lucy McBride, MD, an internist in Washington, D.C.
 

Patients don’t often ask for help

In a perfect world, patients struggling with a substance use disorder would present with a request to discontinue using drugs or alcohol, as Ms. Gordon did. While that does happen sometimes, the onus is on the physician to screen for substance misuse.

“Remember, this is the disease that tells you that you don’t have a disease,” Dr. McGrath says. He also says that the use of screening instruments is a bare minimum. When patients are in the throes of a substance use disorder, the prefrontal cortex doesn’t work effectively. Dr. McGrath says there’s an alteration of consciousness so that the patient doesn’t realize the extent of the disease. “Often simply asking the patient is falling far short. It’s the biggest mistake I see,” he says.

Self-reporting from the patient may be unreliable. “That would be like a patient coming in and saying, ‘My blood sugar is 700, and I want you to give me some insulin,’ ” Dr. McGrath says. Instead, clinicians in the field need a more objective measurement.

Perhaps that means asking the patient to bring in a significant other at the next visit or digging deeper into the conversation about alcohol and drugs and their role in the patient’s life. And to really have an impact, Dr. McGrath said, the clinician should talk to the patient about referral for further evaluation.

“You have to get collateral history; that’s the goldmine for the clinician,” Dr. McGrath says. “It may take a few more minutes or mean talking to a family member, but it can make the difference between life and death.”

“I am thankful to my doctor who discussed this [substance use disorder] with me in detail,” says Ronald Williams, another Angeleno who braved the difficult discussion with his doctor. Mr. Williams says his doctor explained it in a good way and that if the doctor hadn’t guided him empathetically, the conversation might not have gone as well.

“We check patients’ cholesterol. We get them on the scale. But there is no blood test to discover how much they’re drinking, no PCR to test for social anxiety, no MRI that distinguishes between their recreational marijuana use and marijuana abuse,” said Dr. McBride.
 

Check the prescription drugs they’re taking

Another thing Dr. McGrath recommends is for primary care physicians to check the prescription drug monitoring program (PDMP) database in their state to help be alerted to a patient with a substance use disorder. The CDC’s PMPD guidelines recommend that the clinician check on a patient every 3 months or each time they write an opioid prescription. Assigning a staff member or a nurse to check the database can help uncover a history of doctor-shopping or use of controlled substances.

“There’s been a lot of times I’ve gone on self-report, and I’ve been bamboozled because I don’t have a truth-o-meter, and I can’t tell when a patient is telling the truth,” says Dr. McGrath.

He is also a huge proponent of point-of-service screening. Patients can urinate in a cup that has amino assay strips on the side, like an immediate COVID-19 test, or they can spit into a saliva cup. “It’s really beneficial for the patient and the clinician to know right then at the point of service if there is a substance present and what it is,” Dr. McGrath said.

It can be part of the larger conversation once a problem with substances has been uncovered. The clinician can say something like, “Let’s see where you are right now today as far as what you have in your system and where we should go from here.”
 

Other barriers physicians face

Many physicians may feel unprepared to meet the needs of patients with substance use disorders or prescribe medication that blunts cravings and reduces the urge to drink without the need for special training. Scientists at the National Institutes of Health found that only 1.6% of people with a substance use disorder were prescribed medication to help control it.

In the largest study on how primary care physicians address substance use disorders, fewer than 20% described themselves as very prepared to identify alcoholism or illegal drug use. Since most patients prefer to seek treatment from their primary care doctor, at least initially, not being prepared is a problem.

Although referral for specialty addiction treatment is recommended for patients with severe substance use disorders, primary care physicians with appropriate experience, training, and support can provide some of these services. “In an ideal world I wouldn’t have to refer patients out, since they’re much more likely to talk with their primary care provider about sensitive, intimate topics,” says Dr. McBride.
 

The issue of reimbursement

Billing for substance use disorder counseling or coordination of care is still challenging, and how to get compensated remains a conundrum for many physicians. Reimbursement may not adequately compensate providers for the additional time and staff needed, but some changes have been positive.

For instance, the American Society for Addiction Medicine reports that in 2022, Medicare expanded the physician fee schedule for opioid and SUD counseling to include reimbursement for telemedicine services.

Learning the billing CPT codes for various addiction treatments and counseling, or having a billing service that understands them, is crucial to reimbursement and keeping revenue running smoothly.

At the very least, developing relationships with treatment centers and specialists in the community can help physicians with referrals and with determining the level of care needed. Physicians can help facilitate that care with routine reassessment and frequent follow-ups, as well as by requesting reports from the treatment facility, continuing treatment of medical conditions, and reinforcing the importance of continued substance use disorder treatment.

Dr. McBride says that primary care physicians can and should make their office a safe, blame-free medical home for patients with substance use disorders. “Patients also need to understand they should bring their whole selves to the doctor – to talk about their sleep, what they consume, their depression, and not just about alcohol, but their relationship with it, and other substances,” she says.

“There needs to be time to talk about it.”

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

When Michael McGrath, MD, medical director of the Ohana Luxury Alcohol Rehab on the Big Island of Hawaii, trains primary care physicians, he tells them that talking with patients about substance use disorders is like having a stressful, weird conversation. But it’s a courageous one, because of the stigma associated with drug and alcohol disorders.

Dr. McGrath starts the conversation with patients by expressing that physicians now understand that addiction is a disease – one for which the patient isn’t responsible. He explains that there’s both a genetic and a nature/nurture component of the disorder and assures them that he won’t judge or abandon them but rather help them find treatment and make sure they get on the path to wellness.

It’s all too common to see patients with a substance use disorder in today’s primary care population. According to Medscape’s Physicians’ Views on Today’s Divisive Social Issues Report 2022, 42% of physicians see patients with a substance use disorder often in their practices. However, identifying substance use disorders and treating or referring patients for them is a complex problem.

According to the Recovery Research Institute, a leading nonprofit orgnaization from Massachusetts General Hospital dedicated to advancing addiction treatment and recovery, about 20 million people in the United States suffer from a substance use disorder. More than half (54%) need assistance with their recovery. The National Institute on Drug Abuse reports that substance abuse and addiction cost society more than $740 billion annually in workplace productivity, health care, and crime-related expenses.

Despite the challenges, physician experts provide advice on how to treat and help patients who have substance use disorders more effectively.
 

A courageous conversation

Often, the primary care physician or emergency physician is the first to be aware of a patient’s problem with a substance or a relapse. In many communities where shortages of specialized physicians and nonphysician treatment options for substance use disorders aren’t available, there’s usually limited time and resources to help patients with these disorders.

Patients often sense doctors are rushed and may not be interested in hearing about their drug or alcohol problems. Reddit threads are filled with stories like that of user “Cyralek,” who say that the two doctors they’ve seen since quitting drinking didn’t show much interest in the problem beyond ordering liver function tests.

In a nationwide study by researchers at Washington University School of Medicine, St. Louis, 80% of patients who met the diagnostic criteria for substance use disorder visited a doctor, hospital, or clinic for some reason over the past year. Only 1 in 10 were encouraged to cut back on drinking or receive any form of treatment or referral for substance misuse.

Emma Gordon, founder of a salvage yard in Los Angeles, says she used to abuse alcohol and that it affected every aspect of her life. Her brother tried to intervene, but nothing worked until she finally told a physician. “I admitted my problem and felt incredibly calm when she reacted as though it was all normal. I believe that was my first step to becoming a better me. I was thankful I had gone to see a doctor,” says Ms. Gordon.

Though physicians in primary care may not have more than a 15-minute appointment slot, seizing the opportunity to initiate a substance use disorder conversation when warranted is crucial, says Dr. McGrath. The CAGE-AID screening tool, which includes questions such as, “Have you ever felt you ought to cut down on your drinking or drug use?” is an excellent starter. Dr. McGrath also advises primary care clinicians to lower the threshold of concern to a single positive answer rather than several.

Doctors aren’t necessarily rewarded for the time it takes to develop a rapport with patients and to have a conversation that leads to asking, “How much are you drinking?”

“The system in primary care isn’t set up that way,” said Lucy McBride, MD, an internist in Washington, D.C.
 

Patients don’t often ask for help

In a perfect world, patients struggling with a substance use disorder would present with a request to discontinue using drugs or alcohol, as Ms. Gordon did. While that does happen sometimes, the onus is on the physician to screen for substance misuse.

“Remember, this is the disease that tells you that you don’t have a disease,” Dr. McGrath says. He also says that the use of screening instruments is a bare minimum. When patients are in the throes of a substance use disorder, the prefrontal cortex doesn’t work effectively. Dr. McGrath says there’s an alteration of consciousness so that the patient doesn’t realize the extent of the disease. “Often simply asking the patient is falling far short. It’s the biggest mistake I see,” he says.

Self-reporting from the patient may be unreliable. “That would be like a patient coming in and saying, ‘My blood sugar is 700, and I want you to give me some insulin,’ ” Dr. McGrath says. Instead, clinicians in the field need a more objective measurement.

Perhaps that means asking the patient to bring in a significant other at the next visit or digging deeper into the conversation about alcohol and drugs and their role in the patient’s life. And to really have an impact, Dr. McGrath said, the clinician should talk to the patient about referral for further evaluation.

“You have to get collateral history; that’s the goldmine for the clinician,” Dr. McGrath says. “It may take a few more minutes or mean talking to a family member, but it can make the difference between life and death.”

“I am thankful to my doctor who discussed this [substance use disorder] with me in detail,” says Ronald Williams, another Angeleno who braved the difficult discussion with his doctor. Mr. Williams says his doctor explained it in a good way and that if the doctor hadn’t guided him empathetically, the conversation might not have gone as well.

“We check patients’ cholesterol. We get them on the scale. But there is no blood test to discover how much they’re drinking, no PCR to test for social anxiety, no MRI that distinguishes between their recreational marijuana use and marijuana abuse,” said Dr. McBride.
 

Check the prescription drugs they’re taking

Another thing Dr. McGrath recommends is for primary care physicians to check the prescription drug monitoring program (PDMP) database in their state to help be alerted to a patient with a substance use disorder. The CDC’s PMPD guidelines recommend that the clinician check on a patient every 3 months or each time they write an opioid prescription. Assigning a staff member or a nurse to check the database can help uncover a history of doctor-shopping or use of controlled substances.

“There’s been a lot of times I’ve gone on self-report, and I’ve been bamboozled because I don’t have a truth-o-meter, and I can’t tell when a patient is telling the truth,” says Dr. McGrath.

He is also a huge proponent of point-of-service screening. Patients can urinate in a cup that has amino assay strips on the side, like an immediate COVID-19 test, or they can spit into a saliva cup. “It’s really beneficial for the patient and the clinician to know right then at the point of service if there is a substance present and what it is,” Dr. McGrath said.

It can be part of the larger conversation once a problem with substances has been uncovered. The clinician can say something like, “Let’s see where you are right now today as far as what you have in your system and where we should go from here.”
 

Other barriers physicians face

Many physicians may feel unprepared to meet the needs of patients with substance use disorders or prescribe medication that blunts cravings and reduces the urge to drink without the need for special training. Scientists at the National Institutes of Health found that only 1.6% of people with a substance use disorder were prescribed medication to help control it.

In the largest study on how primary care physicians address substance use disorders, fewer than 20% described themselves as very prepared to identify alcoholism or illegal drug use. Since most patients prefer to seek treatment from their primary care doctor, at least initially, not being prepared is a problem.

Although referral for specialty addiction treatment is recommended for patients with severe substance use disorders, primary care physicians with appropriate experience, training, and support can provide some of these services. “In an ideal world I wouldn’t have to refer patients out, since they’re much more likely to talk with their primary care provider about sensitive, intimate topics,” says Dr. McBride.
 

The issue of reimbursement

Billing for substance use disorder counseling or coordination of care is still challenging, and how to get compensated remains a conundrum for many physicians. Reimbursement may not adequately compensate providers for the additional time and staff needed, but some changes have been positive.

For instance, the American Society for Addiction Medicine reports that in 2022, Medicare expanded the physician fee schedule for opioid and SUD counseling to include reimbursement for telemedicine services.

Learning the billing CPT codes for various addiction treatments and counseling, or having a billing service that understands them, is crucial to reimbursement and keeping revenue running smoothly.

At the very least, developing relationships with treatment centers and specialists in the community can help physicians with referrals and with determining the level of care needed. Physicians can help facilitate that care with routine reassessment and frequent follow-ups, as well as by requesting reports from the treatment facility, continuing treatment of medical conditions, and reinforcing the importance of continued substance use disorder treatment.

Dr. McBride says that primary care physicians can and should make their office a safe, blame-free medical home for patients with substance use disorders. “Patients also need to understand they should bring their whole selves to the doctor – to talk about their sleep, what they consume, their depression, and not just about alcohol, but their relationship with it, and other substances,” she says.

“There needs to be time to talk about it.”

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

In recent weeks, the COVID-19 vaccine arsenal has grown more robust. Here’s what you need to know:

Variant-specific boosters. On September 1, the Advisory Committee on Immunization Practices (ACIP) adopted a recommendation for a booster of either a new bivalent Pfizer-BioNTech COVID-19 vaccine (for individuals ages 12 years and older) or bivalent Moderna COVID-19 vaccine (for individuals ages 18 years and older) at least 2 months after receipt of a primary series or prior monovalent booster dose. Both bivalent vaccines were recently approved by the Food and Drug Administration (FDA) under an Emergency Use Authorization (EUA) and offer protection against one of the more common circulating strains of SARS-COV-2 (BA.1) while boosting immunity to the original strain. Both options are approved only as booster shots, not as an original COVID vaccine series.¹

Novavax vaccine. This summer, the FDA issued an EUA for the Novavax COVID-19 vaccine in adults and a later EUA for adolescents (ages 12 to 17 years).² Novavax is the fourth vaccine available to combat COVID-19 infection. This newest addition to the COVID armamentarium consists of coronavirus protein subunits, produced using recombinant technology, and a matrix adjuvant. The primary series consists of 2 doses administered at least 3 weeks apart.^3,4

A few caveats: The Novavax vaccine comes in 10-dose vials, which should be kept refrigerated until use. Once the first dose is used, the vial should be discarded after 6 hours. This may present some scheduling and logistical issues. Also, the Novavax vaccine is not currently approved for use in children younger than 12 years, or as a booster to other vaccines.^3,4

The effectiveness and safety of the Novavax vaccine appears to be comparable to that of the other vaccines approved to date, although measuring vaccine effectiveness is a tricky business given the rapid mutation of the virus and changing dominant strains.^3,4 The Novavax vaccine’s efficacy against currently circulating Omicron variants of the virus (eg, BA.2.12.1, BA.4, BA.5) remains to be determined.

As far as safety, preliminary studies indicate that Novavax may be associated with rare cases of myocarditis.^3,4 Myocarditis can result from the COVID infection itself at an overall rate of 1 to 2 per 1000, which is 16 times the rate in adults without COVID.⁵

Could it provide reassurance to the hesitant? The Novavax COVID vaccine was developed using a vaccine platform and production process similar to that of other commonly administered vaccines, such as hepatitis B vaccine and human papillomavirus vaccine. This may make it an appealing option for patients who have shown hesitancy toward new vaccine technologies.

And, of course, there are the Pfizer and Moderna vaccines. Currently, there are 2 vaccines approved under the normal licensing process for adults, both of which are mRNA-based vaccines: Pfizer/BioNTech (Comirnaty) for those ages 12 years and older and Moderna (Spikevax) for those ages 18 and older. A third COVID vaccine option is manufactured by Johnson & Johnson (Janssen) and uses an adenovirus platform. The FDA revised its EUA in May to limit its use.⁶ The Johnson & Johnson vaccine has been associated with rare but serious reactions called thrombosis with thrombocytopenia. ACIP recommends all other vaccines in preference to the Johnson & Johnson vaccine.

For more on COVID vaccination for patients of all ages, see: www.cdc.gov/vaccines/covid-19/downloads/COVID-19-immunization-schedule-ages-6months-older.pdf

In recent weeks, the COVID-19 vaccine arsenal has grown more robust. Here’s what you need to know:

Variant-specific boosters. On September 1, the Advisory Committee on Immunization Practices (ACIP) adopted a recommendation for a booster of either a new bivalent Pfizer-BioNTech COVID-19 vaccine (for individuals ages 12 years and older) or bivalent Moderna COVID-19 vaccine (for individuals ages 18 years and older) at least 2 months after receipt of a primary series or prior monovalent booster dose. Both bivalent vaccines were recently approved by the Food and Drug Administration (FDA) under an Emergency Use Authorization (EUA) and offer protection against one of the more common circulating strains of SARS-COV-2 (BA.1) while boosting immunity to the original strain. Both options are approved only as booster shots, not as an original COVID vaccine series.¹

Novavax vaccine. This summer, the FDA issued an EUA for the Novavax COVID-19 vaccine in adults and a later EUA for adolescents (ages 12 to 17 years).² Novavax is the fourth vaccine available to combat COVID-19 infection. This newest addition to the COVID armamentarium consists of coronavirus protein subunits, produced using recombinant technology, and a matrix adjuvant. The primary series consists of 2 doses administered at least 3 weeks apart.^3,4

A few caveats: The Novavax vaccine comes in 10-dose vials, which should be kept refrigerated until use. Once the first dose is used, the vial should be discarded after 6 hours. This may present some scheduling and logistical issues. Also, the Novavax vaccine is not currently approved for use in children younger than 12 years, or as a booster to other vaccines.^3,4

The effectiveness and safety of the Novavax vaccine appears to be comparable to that of the other vaccines approved to date, although measuring vaccine effectiveness is a tricky business given the rapid mutation of the virus and changing dominant strains.^3,4 The Novavax vaccine’s efficacy against currently circulating Omicron variants of the virus (eg, BA.2.12.1, BA.4, BA.5) remains to be determined.

As far as safety, preliminary studies indicate that Novavax may be associated with rare cases of myocarditis.^3,4 Myocarditis can result from the COVID infection itself at an overall rate of 1 to 2 per 1000, which is 16 times the rate in adults without COVID.⁵

Could it provide reassurance to the hesitant? The Novavax COVID vaccine was developed using a vaccine platform and production process similar to that of other commonly administered vaccines, such as hepatitis B vaccine and human papillomavirus vaccine. This may make it an appealing option for patients who have shown hesitancy toward new vaccine technologies.

And, of course, there are the Pfizer and Moderna vaccines. Currently, there are 2 vaccines approved under the normal licensing process for adults, both of which are mRNA-based vaccines: Pfizer/BioNTech (Comirnaty) for those ages 12 years and older and Moderna (Spikevax) for those ages 18 and older. A third COVID vaccine option is manufactured by Johnson & Johnson (Janssen) and uses an adenovirus platform. The FDA revised its EUA in May to limit its use.⁶ The Johnson & Johnson vaccine has been associated with rare but serious reactions called thrombosis with thrombocytopenia. ACIP recommends all other vaccines in preference to the Johnson & Johnson vaccine.

For more on COVID vaccination for patients of all ages, see: www.cdc.gov/vaccines/covid-19/downloads/COVID-19-immunization-schedule-ages-6months-older.pdf

In recent weeks, the COVID-19 vaccine arsenal has grown more robust. Here’s what you need to know:

Variant-specific boosters. On September 1, the Advisory Committee on Immunization Practices (ACIP) adopted a recommendation for a booster of either a new bivalent Pfizer-BioNTech COVID-19 vaccine (for individuals ages 12 years and older) or bivalent Moderna COVID-19 vaccine (for individuals ages 18 years and older) at least 2 months after receipt of a primary series or prior monovalent booster dose. Both bivalent vaccines were recently approved by the Food and Drug Administration (FDA) under an Emergency Use Authorization (EUA) and offer protection against one of the more common circulating strains of SARS-COV-2 (BA.1) while boosting immunity to the original strain. Both options are approved only as booster shots, not as an original COVID vaccine series.¹

Novavax vaccine. This summer, the FDA issued an EUA for the Novavax COVID-19 vaccine in adults and a later EUA for adolescents (ages 12 to 17 years).² Novavax is the fourth vaccine available to combat COVID-19 infection. This newest addition to the COVID armamentarium consists of coronavirus protein subunits, produced using recombinant technology, and a matrix adjuvant. The primary series consists of 2 doses administered at least 3 weeks apart.^3,4

A few caveats: The Novavax vaccine comes in 10-dose vials, which should be kept refrigerated until use. Once the first dose is used, the vial should be discarded after 6 hours. This may present some scheduling and logistical issues. Also, the Novavax vaccine is not currently approved for use in children younger than 12 years, or as a booster to other vaccines.^3,4

The effectiveness and safety of the Novavax vaccine appears to be comparable to that of the other vaccines approved to date, although measuring vaccine effectiveness is a tricky business given the rapid mutation of the virus and changing dominant strains.^3,4 The Novavax vaccine’s efficacy against currently circulating Omicron variants of the virus (eg, BA.2.12.1, BA.4, BA.5) remains to be determined.

As far as safety, preliminary studies indicate that Novavax may be associated with rare cases of myocarditis.^3,4 Myocarditis can result from the COVID infection itself at an overall rate of 1 to 2 per 1000, which is 16 times the rate in adults without COVID.⁵

Could it provide reassurance to the hesitant? The Novavax COVID vaccine was developed using a vaccine platform and production process similar to that of other commonly administered vaccines, such as hepatitis B vaccine and human papillomavirus vaccine. This may make it an appealing option for patients who have shown hesitancy toward new vaccine technologies.

And, of course, there are the Pfizer and Moderna vaccines. Currently, there are 2 vaccines approved under the normal licensing process for adults, both of which are mRNA-based vaccines: Pfizer/BioNTech (Comirnaty) for those ages 12 years and older and Moderna (Spikevax) for those ages 18 and older. A third COVID vaccine option is manufactured by Johnson & Johnson (Janssen) and uses an adenovirus platform. The FDA revised its EUA in May to limit its use.⁶ The Johnson & Johnson vaccine has been associated with rare but serious reactions called thrombosis with thrombocytopenia. ACIP recommends all other vaccines in preference to the Johnson & Johnson vaccine.

For more on COVID vaccination for patients of all ages, see: www.cdc.gov/vaccines/covid-19/downloads/COVID-19-immunization-schedule-ages-6months-older.pdf

Caring for patients with short bowel syndrome (SBS) requires a multidisciplinary approach involving dietitians, nurses, surgeons, gastroenterologists or internists, and social workers experienced in SBS care, according to a clinical practice update expert review from the American Gastroenterological Association.

Kishore Iyer, MD, from Mount Sinai Hospital New York; John K. DiBaise, MD, from Mayo Clinic in Scottsdale, Ariz.; and Alberto Rubio-Tapia, MD, from the Cleveland Clinic, Ohio, developed 12 best practice advice statements based on available evidence. The items focus on adult patients with SBS; however, there was some overlap with the management of pediatric SBS. The review was published online in Clinical Gastroenterology and Hepatology.
 

Defining SBS

One update concerns defining SBS. The authors recommend that surgeons performing massive resections should report the residual bowel length, rather than the length of bowel resected.

“It is only the former that dictates outcome,” they wrote.

There is general agreement that a residual small intestinal length of 200 cm or less meets criteria for SBS. Measurement should be taken from “along the antimesenteric border of unstretched bowel, from the duodenojejunal flexure to the ileocecal junction, the site of any small bowel–colon anastomosis, or to the end-ostomy.”

Based on the residual bowel length, patients can be classified into three groups: end-jejunostomy, jejuno-colic, and jejuno-ileo-colic.
 

Assessing nutritional status

A dietitian experienced in SBS should perform a thorough nutritional assessment on all SBS patients. Long-term monitoring should include laboratory studies checking electrolytes and liver and kidney function, fluid balance, weight change, serum micronutrients, and bone density. Bone density should be repeated periodically, every 2-3 years.

Fluid and electrolyte problems may affect outcomes for SBS patients, particularly for those without a colon.
 

Adjusting diets

Most adult patients with SBS have significant malabsorption, so dietary intake “must be increased by at least 50% from their estimated needs,” the authors wrote. It’s best if the patient consumes the increased quantity throughout the day in 5-6 meals, they noted.

An experienced dietitian should counsel the patient based on the patient’s eating preferences. Incorporating preferences can help increase compliance with the adjustments that may become necessary based on symptoms, stool output, and weight.
 

Using pharmacologic therapy

Using antisecretory medications, including proton pump inhibitors or histamine-2 receptor antagonists, helps reduce gastric secretions, the damage of acid on the upper gut mucosa, and the function of pancreatic exocrine enzymes.

Antidiarrheals reduce intestinal motility but also cause a slight reduction in intestinal secretion. Common agents include loperamide, diphenoxylate with atropine, codeine, and tincture of opium. The review authors say loperamide should get preference over opiate drugs because it is not addictive or sedative.

Use of antidiarrheals should be guided by their effect on stool output.

“Loperamide and codeine may have a synergistic effect when used together,” the authors wrote.

Clonidine, which can be given transdermally, has also shown some benefit in treating high-output stool losses, presumably because of its effects on intestinal motility and secretion.

Weighing risks and benefits of teduglutide

The glucagonlike peptide–2 teduglutide is of particular interest for its ability to help improve intestinal absorption and hopefully wean patients off parenteral nutrition and some will achieve enteral autonomy, the authors wrote. “The very short half-life of native GLP-2 has been extended to allow daily subcutaneous injection in the recombinant molecule, teduglutide.”

However, because teduglutide is a growth factor and can boost the growth of polyps and cancer, it is contraindicated in patients with active gastrointestinal malignancies. Patients should undergo colonoscopy before treatment and periodically thereafter, the authors advised. The benefits of its use in patients with nongastrointestinal malignancy should be weighed carefully with these risks.

“The significant side effects of teduglutide and the cost mandate that teduglutide is employed only after optimizing diet and the more conventional SBS treatments described previously in carefully selected patients with [short bowel syndrome–intestinal failure],” the authors wrote.
 

Dosing drugs effectively

Medications in tablet form need to dissolve before being absorbed. Most oral medications are absorbed within the proximal jejunum, so they can be used in patients with SBS.

“However,” the authors noted, “sustained- and delayed-release medications should be avoided.”

They suggested that, when applicable, alternatives such as liquids and topical medications should be considered, as should the monitoring of medication levels in the blood.

If a patient does not respond, approaches to consider may include increasing a dose, changing dose frequency, or changing drug formulation or route of administration, such as intravenous, subcutaneous, or transdermal.
 

Including parenteral nutrition and oral rehydration

Almost all patients with SBS will need parenteral nutrition (PN) support following resection, and few will be able to stop it before discharge from the hospital.

“Although more than 50% of adults with SBS are able to be weaned completely from PN within 5 years of diagnosis, the probability of eliminating PN use is less than 6% if not successfully accomplished in the first 2 years following the individual’s last bowel resection,” the authors wrote.

For long-term PN, tunneled central venous catheters are preferred over peripherally inserted central venous catheters because of the higher risk of thrombosis and issues related to self-administration of PN with the central catheters. Also, tunneled catheters are preferred over totally implanted devices, or ports, for long-term patients because the main benefit of the port is not realized given that the device needs to be continually accessed and exchanged weekly.

“When calculating PN volume and content, changes in the patient’s weight, laboratory results, stool or ostomy output, urine output, and complaints of thirst should be monitored,” the authors noted.

The authors also discussed oral rehydration solution because patients lose more water and sodium from their stoma than they take in by mouth. Careful consideration of the glucose and sodium levels in oral fluids is important because inappropriate fluids will exacerbate fluid losses in SBS. For example, hypotonic (including water, tea, coffee, alcohol) and hypertonic (including fruit juices and sodas) solutions should be limited.

“A major misconception on the part of patients is that they should drink large quantities of water; however, this generally leads to an increase in ostomy output and creates a vicious cycle further exacerbating fluid and electrolyte disturbances,” they wrote, instead advising glucose–electrolyte rehydration solution to enhance absorption and reduce secretion.
 

Preventing complications

“A knowledge of these complications is critical for those caring for these patients to be able to not only identify and treat them when they occur but also to prevent their occurrence whenever possible,” the authors wrote. Although they considered it beyond the scope of the review to outline every complication, they indicated some complications and management strategies via an included table. These complications can include cirrhosis, osteoporosis, acute kidney disease, and central venous catheter–related infection or occlusion.

Considering further surgery or intestinal transplantation

The authors noted that any further surgery should be carefully considered, with the following three contexts having possible value: “(1) to recruit unused distal bowel, (2) to augment the function of residual bowel through specific lengthening and tapering operations, or (3) to slow intestinal transit.”

Surgeons involved in managing SBS may need to confront complex intra-abdominal problems such as massive desmoid tumors, mesenteric ischemia, or complex enterocutaneous fistulae; a multidisciplinary intestinal rehabilitation team may be better able to help these patients. The authors noted that care for patients starts even before the first operation, by taking every measure to avoid massive bowel resection and the resulting SBS.

The authors noted the importance of early referral for intestinal transplantation consideration for patients with refractory dependency on parenteral nutrition or even onset of parenteral nutrition failure, which refers to complications such as intestinal failure–associated liver disease.

“At present, nearly 50% of patients being considered for ITX are also requiring simultaneous liver replacement, indicating late referral for ITX,” they wrote, citing a data from a report by the Centers for Medicare and Medicaid.

They also noted that data have shown short- and medium-term outcomes are steadily improving; however, long-term outcomes have been challenged by opportunistic infections, long-term graft attrition, and other impediments that may be preventing early referral for intestinal transplantation.
 

Educating patients, caregivers

Long-term PN may restrict activity for patients, but patients and caregivers should know about some modifications.

One is to cycle the PN over 10-14 hours overnight to allow freedom from the infusion pump during the day. Infusion pumps can be programmable, and some can be carried in a backpack for infusing during the day.

Authors recommend patient support groups, such as the Oley Foundation, which can help with issues surrounding body image and travel.

Because of the relative rarity of SBS, nonspecialist physicians may care for patients without a dedicated multidisciplinary team and may need education support in managing patients with complex care needs. One source the authors recommend is the Learn Intestinal Failure Tele-ECHO (Expanding Community Healthcare Outcomes) (LIFT-ECHO) project. The LIFT-ECHO project has become an online educational community with case-based learning in SBS, intestinal failure, and PN.

The authors disclose relationships with Takeda, Zealand, VectivBio, Napo, and Hanmi.

Caring for patients with short bowel syndrome (SBS) requires a multidisciplinary approach involving dietitians, nurses, surgeons, gastroenterologists or internists, and social workers experienced in SBS care, according to a clinical practice update expert review from the American Gastroenterological Association.

Kishore Iyer, MD, from Mount Sinai Hospital New York; John K. DiBaise, MD, from Mayo Clinic in Scottsdale, Ariz.; and Alberto Rubio-Tapia, MD, from the Cleveland Clinic, Ohio, developed 12 best practice advice statements based on available evidence. The items focus on adult patients with SBS; however, there was some overlap with the management of pediatric SBS. The review was published online in Clinical Gastroenterology and Hepatology.
 

Defining SBS

One update concerns defining SBS. The authors recommend that surgeons performing massive resections should report the residual bowel length, rather than the length of bowel resected.

“It is only the former that dictates outcome,” they wrote.

There is general agreement that a residual small intestinal length of 200 cm or less meets criteria for SBS. Measurement should be taken from “along the antimesenteric border of unstretched bowel, from the duodenojejunal flexure to the ileocecal junction, the site of any small bowel–colon anastomosis, or to the end-ostomy.”

Based on the residual bowel length, patients can be classified into three groups: end-jejunostomy, jejuno-colic, and jejuno-ileo-colic.
 

Assessing nutritional status

A dietitian experienced in SBS should perform a thorough nutritional assessment on all SBS patients. Long-term monitoring should include laboratory studies checking electrolytes and liver and kidney function, fluid balance, weight change, serum micronutrients, and bone density. Bone density should be repeated periodically, every 2-3 years.

Fluid and electrolyte problems may affect outcomes for SBS patients, particularly for those without a colon.
 

Adjusting diets

Most adult patients with SBS have significant malabsorption, so dietary intake “must be increased by at least 50% from their estimated needs,” the authors wrote. It’s best if the patient consumes the increased quantity throughout the day in 5-6 meals, they noted.

An experienced dietitian should counsel the patient based on the patient’s eating preferences. Incorporating preferences can help increase compliance with the adjustments that may become necessary based on symptoms, stool output, and weight.
 

Using pharmacologic therapy

Using antisecretory medications, including proton pump inhibitors or histamine-2 receptor antagonists, helps reduce gastric secretions, the damage of acid on the upper gut mucosa, and the function of pancreatic exocrine enzymes.

Antidiarrheals reduce intestinal motility but also cause a slight reduction in intestinal secretion. Common agents include loperamide, diphenoxylate with atropine, codeine, and tincture of opium. The review authors say loperamide should get preference over opiate drugs because it is not addictive or sedative.

Use of antidiarrheals should be guided by their effect on stool output.

“Loperamide and codeine may have a synergistic effect when used together,” the authors wrote.

Clonidine, which can be given transdermally, has also shown some benefit in treating high-output stool losses, presumably because of its effects on intestinal motility and secretion.

Weighing risks and benefits of teduglutide

The glucagonlike peptide–2 teduglutide is of particular interest for its ability to help improve intestinal absorption and hopefully wean patients off parenteral nutrition and some will achieve enteral autonomy, the authors wrote. “The very short half-life of native GLP-2 has been extended to allow daily subcutaneous injection in the recombinant molecule, teduglutide.”

However, because teduglutide is a growth factor and can boost the growth of polyps and cancer, it is contraindicated in patients with active gastrointestinal malignancies. Patients should undergo colonoscopy before treatment and periodically thereafter, the authors advised. The benefits of its use in patients with nongastrointestinal malignancy should be weighed carefully with these risks.

“The significant side effects of teduglutide and the cost mandate that teduglutide is employed only after optimizing diet and the more conventional SBS treatments described previously in carefully selected patients with [short bowel syndrome–intestinal failure],” the authors wrote.
 

Dosing drugs effectively

Medications in tablet form need to dissolve before being absorbed. Most oral medications are absorbed within the proximal jejunum, so they can be used in patients with SBS.

“However,” the authors noted, “sustained- and delayed-release medications should be avoided.”

They suggested that, when applicable, alternatives such as liquids and topical medications should be considered, as should the monitoring of medication levels in the blood.

If a patient does not respond, approaches to consider may include increasing a dose, changing dose frequency, or changing drug formulation or route of administration, such as intravenous, subcutaneous, or transdermal.
 

Including parenteral nutrition and oral rehydration

Almost all patients with SBS will need parenteral nutrition (PN) support following resection, and few will be able to stop it before discharge from the hospital.

“Although more than 50% of adults with SBS are able to be weaned completely from PN within 5 years of diagnosis, the probability of eliminating PN use is less than 6% if not successfully accomplished in the first 2 years following the individual’s last bowel resection,” the authors wrote.

For long-term PN, tunneled central venous catheters are preferred over peripherally inserted central venous catheters because of the higher risk of thrombosis and issues related to self-administration of PN with the central catheters. Also, tunneled catheters are preferred over totally implanted devices, or ports, for long-term patients because the main benefit of the port is not realized given that the device needs to be continually accessed and exchanged weekly.

“When calculating PN volume and content, changes in the patient’s weight, laboratory results, stool or ostomy output, urine output, and complaints of thirst should be monitored,” the authors noted.

The authors also discussed oral rehydration solution because patients lose more water and sodium from their stoma than they take in by mouth. Careful consideration of the glucose and sodium levels in oral fluids is important because inappropriate fluids will exacerbate fluid losses in SBS. For example, hypotonic (including water, tea, coffee, alcohol) and hypertonic (including fruit juices and sodas) solutions should be limited.

“A major misconception on the part of patients is that they should drink large quantities of water; however, this generally leads to an increase in ostomy output and creates a vicious cycle further exacerbating fluid and electrolyte disturbances,” they wrote, instead advising glucose–electrolyte rehydration solution to enhance absorption and reduce secretion.
 

Preventing complications

“A knowledge of these complications is critical for those caring for these patients to be able to not only identify and treat them when they occur but also to prevent their occurrence whenever possible,” the authors wrote. Although they considered it beyond the scope of the review to outline every complication, they indicated some complications and management strategies via an included table. These complications can include cirrhosis, osteoporosis, acute kidney disease, and central venous catheter–related infection or occlusion.

Considering further surgery or intestinal transplantation

The authors noted that any further surgery should be carefully considered, with the following three contexts having possible value: “(1) to recruit unused distal bowel, (2) to augment the function of residual bowel through specific lengthening and tapering operations, or (3) to slow intestinal transit.”

Surgeons involved in managing SBS may need to confront complex intra-abdominal problems such as massive desmoid tumors, mesenteric ischemia, or complex enterocutaneous fistulae; a multidisciplinary intestinal rehabilitation team may be better able to help these patients. The authors noted that care for patients starts even before the first operation, by taking every measure to avoid massive bowel resection and the resulting SBS.

The authors noted the importance of early referral for intestinal transplantation consideration for patients with refractory dependency on parenteral nutrition or even onset of parenteral nutrition failure, which refers to complications such as intestinal failure–associated liver disease.

“At present, nearly 50% of patients being considered for ITX are also requiring simultaneous liver replacement, indicating late referral for ITX,” they wrote, citing a data from a report by the Centers for Medicare and Medicaid.

They also noted that data have shown short- and medium-term outcomes are steadily improving; however, long-term outcomes have been challenged by opportunistic infections, long-term graft attrition, and other impediments that may be preventing early referral for intestinal transplantation.
 

Educating patients, caregivers

Long-term PN may restrict activity for patients, but patients and caregivers should know about some modifications.

One is to cycle the PN over 10-14 hours overnight to allow freedom from the infusion pump during the day. Infusion pumps can be programmable, and some can be carried in a backpack for infusing during the day.

Authors recommend patient support groups, such as the Oley Foundation, which can help with issues surrounding body image and travel.

Because of the relative rarity of SBS, nonspecialist physicians may care for patients without a dedicated multidisciplinary team and may need education support in managing patients with complex care needs. One source the authors recommend is the Learn Intestinal Failure Tele-ECHO (Expanding Community Healthcare Outcomes) (LIFT-ECHO) project. The LIFT-ECHO project has become an online educational community with case-based learning in SBS, intestinal failure, and PN.

The authors disclose relationships with Takeda, Zealand, VectivBio, Napo, and Hanmi.

Caring for patients with short bowel syndrome (SBS) requires a multidisciplinary approach involving dietitians, nurses, surgeons, gastroenterologists or internists, and social workers experienced in SBS care, according to a clinical practice update expert review from the American Gastroenterological Association.

Kishore Iyer, MD, from Mount Sinai Hospital New York; John K. DiBaise, MD, from Mayo Clinic in Scottsdale, Ariz.; and Alberto Rubio-Tapia, MD, from the Cleveland Clinic, Ohio, developed 12 best practice advice statements based on available evidence. The items focus on adult patients with SBS; however, there was some overlap with the management of pediatric SBS. The review was published online in Clinical Gastroenterology and Hepatology.
 

Defining SBS

One update concerns defining SBS. The authors recommend that surgeons performing massive resections should report the residual bowel length, rather than the length of bowel resected.

“It is only the former that dictates outcome,” they wrote.

There is general agreement that a residual small intestinal length of 200 cm or less meets criteria for SBS. Measurement should be taken from “along the antimesenteric border of unstretched bowel, from the duodenojejunal flexure to the ileocecal junction, the site of any small bowel–colon anastomosis, or to the end-ostomy.”

Based on the residual bowel length, patients can be classified into three groups: end-jejunostomy, jejuno-colic, and jejuno-ileo-colic.
 

Assessing nutritional status

A dietitian experienced in SBS should perform a thorough nutritional assessment on all SBS patients. Long-term monitoring should include laboratory studies checking electrolytes and liver and kidney function, fluid balance, weight change, serum micronutrients, and bone density. Bone density should be repeated periodically, every 2-3 years.

Fluid and electrolyte problems may affect outcomes for SBS patients, particularly for those without a colon.
 

Adjusting diets

Most adult patients with SBS have significant malabsorption, so dietary intake “must be increased by at least 50% from their estimated needs,” the authors wrote. It’s best if the patient consumes the increased quantity throughout the day in 5-6 meals, they noted.

An experienced dietitian should counsel the patient based on the patient’s eating preferences. Incorporating preferences can help increase compliance with the adjustments that may become necessary based on symptoms, stool output, and weight.
 

Using pharmacologic therapy

Using antisecretory medications, including proton pump inhibitors or histamine-2 receptor antagonists, helps reduce gastric secretions, the damage of acid on the upper gut mucosa, and the function of pancreatic exocrine enzymes.

Antidiarrheals reduce intestinal motility but also cause a slight reduction in intestinal secretion. Common agents include loperamide, diphenoxylate with atropine, codeine, and tincture of opium. The review authors say loperamide should get preference over opiate drugs because it is not addictive or sedative.

Use of antidiarrheals should be guided by their effect on stool output.

“Loperamide and codeine may have a synergistic effect when used together,” the authors wrote.

Clonidine, which can be given transdermally, has also shown some benefit in treating high-output stool losses, presumably because of its effects on intestinal motility and secretion.

Weighing risks and benefits of teduglutide

The glucagonlike peptide–2 teduglutide is of particular interest for its ability to help improve intestinal absorption and hopefully wean patients off parenteral nutrition and some will achieve enteral autonomy, the authors wrote. “The very short half-life of native GLP-2 has been extended to allow daily subcutaneous injection in the recombinant molecule, teduglutide.”

However, because teduglutide is a growth factor and can boost the growth of polyps and cancer, it is contraindicated in patients with active gastrointestinal malignancies. Patients should undergo colonoscopy before treatment and periodically thereafter, the authors advised. The benefits of its use in patients with nongastrointestinal malignancy should be weighed carefully with these risks.

“The significant side effects of teduglutide and the cost mandate that teduglutide is employed only after optimizing diet and the more conventional SBS treatments described previously in carefully selected patients with [short bowel syndrome–intestinal failure],” the authors wrote.
 

Dosing drugs effectively

Medications in tablet form need to dissolve before being absorbed. Most oral medications are absorbed within the proximal jejunum, so they can be used in patients with SBS.

“However,” the authors noted, “sustained- and delayed-release medications should be avoided.”

They suggested that, when applicable, alternatives such as liquids and topical medications should be considered, as should the monitoring of medication levels in the blood.

If a patient does not respond, approaches to consider may include increasing a dose, changing dose frequency, or changing drug formulation or route of administration, such as intravenous, subcutaneous, or transdermal.
 

Including parenteral nutrition and oral rehydration

Almost all patients with SBS will need parenteral nutrition (PN) support following resection, and few will be able to stop it before discharge from the hospital.

“Although more than 50% of adults with SBS are able to be weaned completely from PN within 5 years of diagnosis, the probability of eliminating PN use is less than 6% if not successfully accomplished in the first 2 years following the individual’s last bowel resection,” the authors wrote.

For long-term PN, tunneled central venous catheters are preferred over peripherally inserted central venous catheters because of the higher risk of thrombosis and issues related to self-administration of PN with the central catheters. Also, tunneled catheters are preferred over totally implanted devices, or ports, for long-term patients because the main benefit of the port is not realized given that the device needs to be continually accessed and exchanged weekly.

“When calculating PN volume and content, changes in the patient’s weight, laboratory results, stool or ostomy output, urine output, and complaints of thirst should be monitored,” the authors noted.

The authors also discussed oral rehydration solution because patients lose more water and sodium from their stoma than they take in by mouth. Careful consideration of the glucose and sodium levels in oral fluids is important because inappropriate fluids will exacerbate fluid losses in SBS. For example, hypotonic (including water, tea, coffee, alcohol) and hypertonic (including fruit juices and sodas) solutions should be limited.

“A major misconception on the part of patients is that they should drink large quantities of water; however, this generally leads to an increase in ostomy output and creates a vicious cycle further exacerbating fluid and electrolyte disturbances,” they wrote, instead advising glucose–electrolyte rehydration solution to enhance absorption and reduce secretion.
 

Preventing complications

“A knowledge of these complications is critical for those caring for these patients to be able to not only identify and treat them when they occur but also to prevent their occurrence whenever possible,” the authors wrote. Although they considered it beyond the scope of the review to outline every complication, they indicated some complications and management strategies via an included table. These complications can include cirrhosis, osteoporosis, acute kidney disease, and central venous catheter–related infection or occlusion.

Considering further surgery or intestinal transplantation

The authors noted that any further surgery should be carefully considered, with the following three contexts having possible value: “(1) to recruit unused distal bowel, (2) to augment the function of residual bowel through specific lengthening and tapering operations, or (3) to slow intestinal transit.”

Surgeons involved in managing SBS may need to confront complex intra-abdominal problems such as massive desmoid tumors, mesenteric ischemia, or complex enterocutaneous fistulae; a multidisciplinary intestinal rehabilitation team may be better able to help these patients. The authors noted that care for patients starts even before the first operation, by taking every measure to avoid massive bowel resection and the resulting SBS.

The authors noted the importance of early referral for intestinal transplantation consideration for patients with refractory dependency on parenteral nutrition or even onset of parenteral nutrition failure, which refers to complications such as intestinal failure–associated liver disease.

“At present, nearly 50% of patients being considered for ITX are also requiring simultaneous liver replacement, indicating late referral for ITX,” they wrote, citing a data from a report by the Centers for Medicare and Medicaid.

They also noted that data have shown short- and medium-term outcomes are steadily improving; however, long-term outcomes have been challenged by opportunistic infections, long-term graft attrition, and other impediments that may be preventing early referral for intestinal transplantation.
 

Educating patients, caregivers

Long-term PN may restrict activity for patients, but patients and caregivers should know about some modifications.

One is to cycle the PN over 10-14 hours overnight to allow freedom from the infusion pump during the day. Infusion pumps can be programmable, and some can be carried in a backpack for infusing during the day.

Authors recommend patient support groups, such as the Oley Foundation, which can help with issues surrounding body image and travel.

Because of the relative rarity of SBS, nonspecialist physicians may care for patients without a dedicated multidisciplinary team and may need education support in managing patients with complex care needs. One source the authors recommend is the Learn Intestinal Failure Tele-ECHO (Expanding Community Healthcare Outcomes) (LIFT-ECHO) project. The LIFT-ECHO project has become an online educational community with case-based learning in SBS, intestinal failure, and PN.

The authors disclose relationships with Takeda, Zealand, VectivBio, Napo, and Hanmi.