The risk for serious liver injury with obeticholic acid (Ocaliva, Intercept Pharmaceuticals) has prompted the U.S. Food and Drug Administration to restrict its use in patients with primary biliary cholangitis (PBC) and advanced cirrhosis.  

The agency has added a new contraindication to the obeticholic acid prescribing information and patient medication guide stating that the drug should not be used in patients with PBC and advanced cirrhosis. 

The boxed warning on the label has also been revised to include this information.

For patients with PBC who do not have advanced cirrhosis, the FDA believes the benefits of Ocaliva outweigh the risks, based on the original clinical trials.

Five years ago, the FDA granted accelerated approval to obeticholic acid in combination with ursodeoxycholic acid (UDCA) in adults who fail to respond adequately to UDCA, or as a monotherapy in adults who cannot tolerate UDCA.  

Since then, the FDA has identified 25 cases of serious liver injury leading to liver decompensation or liver failure in patients with PBC and cirrhosis who were taking obeticholic acid at recommended doses.

According to the FDA, 18 of the cases happened in patients with PBC and compensated cirrhosis who experienced liver injury that led to decompensation. Ten of these patients had evidence or suspicion of portal hypertension at baseline; in the other eight patients, it was unclear whether portal hypertension was present.

PBC was not expected to progress rapidly in these patients, yet they experienced accelerated clinical deterioration within months of starting obeticholic acid, the FDA said.

The median time to liver decompensation after initiating treatment was 4 months (range, 2 weeks to 10 months). Four patients with PBC and compensated cirrhosis needed a liver transplant within 1.3 years after starting obeticholic acid, and one patient died from liver failure.

The other seven cases of serious liver injury occurred in patients with PBC and decompensated cirrhosis, two of whom died. 

Although there was a temporal relationship between starting obeticholic acid and liver injury, it is difficult to distinguish a drug-induced effect from disease progression in the patients with advanced baseline liver disease, the FDA cautioned.

The median time to a new decompensation event after starting the drug was 2.5 months (range, 10 days to 8 months).

Before starting obeticholic acid, clinicians should determine whether a patient with PBC has advanced cirrhosis as the drug is now contraindicated in these patients, the FDA said.

During obeticholic acid treatment, patients should be routinely monitored for progression of PBC with laboratory and clinical assessments to determine whether the drug needs to be discontinued.

The medication should be permanently discontinued in patients with cirrhosis who progress to advanced cirrhosis.

Patients should also be monitored for clinically significant liver-related adverse reactions that may manifest as development of acute-on-chronic liver disease with nausea, vomiting, diarrhea, jaundice, scleral icterus, and/or dark urine.

Obeticholic acid should be stopped permanently in any patient who develops these symptoms, the FDA advised.

Health care professionals are encouraged to report adverse events or side effects related to the use of obeticholic acid to MedWatch, FDA’s adverse event reporting site.

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

The risk for serious liver injury with obeticholic acid (Ocaliva, Intercept Pharmaceuticals) has prompted the U.S. Food and Drug Administration to restrict its use in patients with primary biliary cholangitis (PBC) and advanced cirrhosis.  

The agency has added a new contraindication to the obeticholic acid prescribing information and patient medication guide stating that the drug should not be used in patients with PBC and advanced cirrhosis. 

The boxed warning on the label has also been revised to include this information.

For patients with PBC who do not have advanced cirrhosis, the FDA believes the benefits of Ocaliva outweigh the risks, based on the original clinical trials.

Five years ago, the FDA granted accelerated approval to obeticholic acid in combination with ursodeoxycholic acid (UDCA) in adults who fail to respond adequately to UDCA, or as a monotherapy in adults who cannot tolerate UDCA.  

Since then, the FDA has identified 25 cases of serious liver injury leading to liver decompensation or liver failure in patients with PBC and cirrhosis who were taking obeticholic acid at recommended doses.

According to the FDA, 18 of the cases happened in patients with PBC and compensated cirrhosis who experienced liver injury that led to decompensation. Ten of these patients had evidence or suspicion of portal hypertension at baseline; in the other eight patients, it was unclear whether portal hypertension was present.

PBC was not expected to progress rapidly in these patients, yet they experienced accelerated clinical deterioration within months of starting obeticholic acid, the FDA said.

The median time to liver decompensation after initiating treatment was 4 months (range, 2 weeks to 10 months). Four patients with PBC and compensated cirrhosis needed a liver transplant within 1.3 years after starting obeticholic acid, and one patient died from liver failure.

The other seven cases of serious liver injury occurred in patients with PBC and decompensated cirrhosis, two of whom died. 

Although there was a temporal relationship between starting obeticholic acid and liver injury, it is difficult to distinguish a drug-induced effect from disease progression in the patients with advanced baseline liver disease, the FDA cautioned.

The median time to a new decompensation event after starting the drug was 2.5 months (range, 10 days to 8 months).

Before starting obeticholic acid, clinicians should determine whether a patient with PBC has advanced cirrhosis as the drug is now contraindicated in these patients, the FDA said.

During obeticholic acid treatment, patients should be routinely monitored for progression of PBC with laboratory and clinical assessments to determine whether the drug needs to be discontinued.

The medication should be permanently discontinued in patients with cirrhosis who progress to advanced cirrhosis.

Patients should also be monitored for clinically significant liver-related adverse reactions that may manifest as development of acute-on-chronic liver disease with nausea, vomiting, diarrhea, jaundice, scleral icterus, and/or dark urine.

Obeticholic acid should be stopped permanently in any patient who develops these symptoms, the FDA advised.

Health care professionals are encouraged to report adverse events or side effects related to the use of obeticholic acid to MedWatch, FDA’s adverse event reporting site.

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

The risk for serious liver injury with obeticholic acid (Ocaliva, Intercept Pharmaceuticals) has prompted the U.S. Food and Drug Administration to restrict its use in patients with primary biliary cholangitis (PBC) and advanced cirrhosis.  

The agency has added a new contraindication to the obeticholic acid prescribing information and patient medication guide stating that the drug should not be used in patients with PBC and advanced cirrhosis. 

The boxed warning on the label has also been revised to include this information.

For patients with PBC who do not have advanced cirrhosis, the FDA believes the benefits of Ocaliva outweigh the risks, based on the original clinical trials.

Five years ago, the FDA granted accelerated approval to obeticholic acid in combination with ursodeoxycholic acid (UDCA) in adults who fail to respond adequately to UDCA, or as a monotherapy in adults who cannot tolerate UDCA.  

Since then, the FDA has identified 25 cases of serious liver injury leading to liver decompensation or liver failure in patients with PBC and cirrhosis who were taking obeticholic acid at recommended doses.

According to the FDA, 18 of the cases happened in patients with PBC and compensated cirrhosis who experienced liver injury that led to decompensation. Ten of these patients had evidence or suspicion of portal hypertension at baseline; in the other eight patients, it was unclear whether portal hypertension was present.

PBC was not expected to progress rapidly in these patients, yet they experienced accelerated clinical deterioration within months of starting obeticholic acid, the FDA said.

The median time to liver decompensation after initiating treatment was 4 months (range, 2 weeks to 10 months). Four patients with PBC and compensated cirrhosis needed a liver transplant within 1.3 years after starting obeticholic acid, and one patient died from liver failure.

The other seven cases of serious liver injury occurred in patients with PBC and decompensated cirrhosis, two of whom died. 

Although there was a temporal relationship between starting obeticholic acid and liver injury, it is difficult to distinguish a drug-induced effect from disease progression in the patients with advanced baseline liver disease, the FDA cautioned.

The median time to a new decompensation event after starting the drug was 2.5 months (range, 10 days to 8 months).

Before starting obeticholic acid, clinicians should determine whether a patient with PBC has advanced cirrhosis as the drug is now contraindicated in these patients, the FDA said.

During obeticholic acid treatment, patients should be routinely monitored for progression of PBC with laboratory and clinical assessments to determine whether the drug needs to be discontinued.

The medication should be permanently discontinued in patients with cirrhosis who progress to advanced cirrhosis.

Patients should also be monitored for clinically significant liver-related adverse reactions that may manifest as development of acute-on-chronic liver disease with nausea, vomiting, diarrhea, jaundice, scleral icterus, and/or dark urine.

Obeticholic acid should be stopped permanently in any patient who develops these symptoms, the FDA advised.

Health care professionals are encouraged to report adverse events or side effects related to the use of obeticholic acid to MedWatch, FDA’s adverse event reporting site.

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

A single treatment with a commercially available 1,060-nm diode laser that features integrated skin cooling was found to be safe and effective for the reduction of unwanted fat of the abdomen and flanks, a small single-center study showed.

Nonsurgical fat reduction was the third-most common nonsurgical aesthetic procedure in the United States in 2018 and includes lasers, high-intensity focused ultrasound, radiofrequency, photobiomodulation therapy, and cryolipolysis, according to 2018 data from the American Society for Aesthetic Plastic Surgery.

“Our study is unique because we used a 1,060-nm diode laser with integrated skin cooling to evaluate the efficacy and safety of its use for the reduction of unwanted fat of the abdomen and flanks,” lead study author Alison S. Kang, MD, told this news organization following the annual conference of the American Society for Laser Medicine and Surgery, where the data were presented. “A 1,060-nm laser works by delivering controlled thermal energy between 42 °C and 47 °C, temperatures at which adipocytes are permanently destroyed,” she explained.

Dr. Kang and Suzanne Kilmer, MD, both of the Laser & Skin Surgery Center of Northern California, Sacramento, enrolled 28 women and 2 men into the study. Each study participant received a single treatment with Venus Bliss, a 1,060-nm diode laser with four laser applicators and a built-in skin-cooling mechanism. Half received treatment of the flanks delivered at up to 1.4 watts per cm² on each diode for 25 minutes, while the other 15 received treatment of the abdomen with the same energy settings. Photos and ultrasound images were taken at baseline, 6 weeks, and 12 weeks, and the investigators administered a satisfaction questionnaire upon study exit. The primary endpoint was efficacy, defined as the percentage of correctly identified posttreatment photographs by three blinded reviewers (one plastic surgeon and two dermatologists). Secondary endpoints of interest were change in adipose thickness on ultrasound, subject satisfaction, and adverse events.

After losing 1 patient to follow-up, 29 completed the study. Dr. Kang reported that the blinded evaluators could identify the pretreatment image, compared with the posttreatment image in an average of 67% of patients. Between baseline and 12 weeks, the ultrasound images showed an average reduction in the adipose layer of 9% on the abdomen and 7% on the flank, while the average self-reported pain score based on the Wong-Baker FACES Pain Rating Scale was 2 out of 10 among those in the abdomen treatment group and 2.6 out of 10 among those in the flank treatment group.

In addition, 76% of subjects stated they were “satisfied” to “very satisfied” with the treatment, and 79% stated that they would recommend this treatment to a friend. The most common posttreatment responses in both groups were erythema and trace edema, but no serious or permanent adverse events were observed.

Dr. Kang acknowledged certain limitations of the study, including its small sample size. “Only one treatment was performed in our study, so it is unclear if multiple treatments will improve efficacy or if multiple treatments will have no effect on efficacy,” she said.

The work won a “best of session early career-clinical” abstract award from the ASLMS.

The study was funded by Venus Concept, the manufacturer of the Venus Bliss laser. Dr. Kang reported having no relevant financial disclosures. Dr. Kilmer has received grants and honoraria from Venus Concept.

[email protected]

A single treatment with a commercially available 1,060-nm diode laser that features integrated skin cooling was found to be safe and effective for the reduction of unwanted fat of the abdomen and flanks, a small single-center study showed.

Nonsurgical fat reduction was the third-most common nonsurgical aesthetic procedure in the United States in 2018 and includes lasers, high-intensity focused ultrasound, radiofrequency, photobiomodulation therapy, and cryolipolysis, according to 2018 data from the American Society for Aesthetic Plastic Surgery.

“Our study is unique because we used a 1,060-nm diode laser with integrated skin cooling to evaluate the efficacy and safety of its use for the reduction of unwanted fat of the abdomen and flanks,” lead study author Alison S. Kang, MD, told this news organization following the annual conference of the American Society for Laser Medicine and Surgery, where the data were presented. “A 1,060-nm laser works by delivering controlled thermal energy between 42 °C and 47 °C, temperatures at which adipocytes are permanently destroyed,” she explained.

Dr. Kang and Suzanne Kilmer, MD, both of the Laser & Skin Surgery Center of Northern California, Sacramento, enrolled 28 women and 2 men into the study. Each study participant received a single treatment with Venus Bliss, a 1,060-nm diode laser with four laser applicators and a built-in skin-cooling mechanism. Half received treatment of the flanks delivered at up to 1.4 watts per cm² on each diode for 25 minutes, while the other 15 received treatment of the abdomen with the same energy settings. Photos and ultrasound images were taken at baseline, 6 weeks, and 12 weeks, and the investigators administered a satisfaction questionnaire upon study exit. The primary endpoint was efficacy, defined as the percentage of correctly identified posttreatment photographs by three blinded reviewers (one plastic surgeon and two dermatologists). Secondary endpoints of interest were change in adipose thickness on ultrasound, subject satisfaction, and adverse events.

After losing 1 patient to follow-up, 29 completed the study. Dr. Kang reported that the blinded evaluators could identify the pretreatment image, compared with the posttreatment image in an average of 67% of patients. Between baseline and 12 weeks, the ultrasound images showed an average reduction in the adipose layer of 9% on the abdomen and 7% on the flank, while the average self-reported pain score based on the Wong-Baker FACES Pain Rating Scale was 2 out of 10 among those in the abdomen treatment group and 2.6 out of 10 among those in the flank treatment group.

In addition, 76% of subjects stated they were “satisfied” to “very satisfied” with the treatment, and 79% stated that they would recommend this treatment to a friend. The most common posttreatment responses in both groups were erythema and trace edema, but no serious or permanent adverse events were observed.

Dr. Kang acknowledged certain limitations of the study, including its small sample size. “Only one treatment was performed in our study, so it is unclear if multiple treatments will improve efficacy or if multiple treatments will have no effect on efficacy,” she said.

The work won a “best of session early career-clinical” abstract award from the ASLMS.

The study was funded by Venus Concept, the manufacturer of the Venus Bliss laser. Dr. Kang reported having no relevant financial disclosures. Dr. Kilmer has received grants and honoraria from Venus Concept.

[email protected]

A single treatment with a commercially available 1,060-nm diode laser that features integrated skin cooling was found to be safe and effective for the reduction of unwanted fat of the abdomen and flanks, a small single-center study showed.

Nonsurgical fat reduction was the third-most common nonsurgical aesthetic procedure in the United States in 2018 and includes lasers, high-intensity focused ultrasound, radiofrequency, photobiomodulation therapy, and cryolipolysis, according to 2018 data from the American Society for Aesthetic Plastic Surgery.

“Our study is unique because we used a 1,060-nm diode laser with integrated skin cooling to evaluate the efficacy and safety of its use for the reduction of unwanted fat of the abdomen and flanks,” lead study author Alison S. Kang, MD, told this news organization following the annual conference of the American Society for Laser Medicine and Surgery, where the data were presented. “A 1,060-nm laser works by delivering controlled thermal energy between 42 °C and 47 °C, temperatures at which adipocytes are permanently destroyed,” she explained.

Dr. Kang and Suzanne Kilmer, MD, both of the Laser & Skin Surgery Center of Northern California, Sacramento, enrolled 28 women and 2 men into the study. Each study participant received a single treatment with Venus Bliss, a 1,060-nm diode laser with four laser applicators and a built-in skin-cooling mechanism. Half received treatment of the flanks delivered at up to 1.4 watts per cm² on each diode for 25 minutes, while the other 15 received treatment of the abdomen with the same energy settings. Photos and ultrasound images were taken at baseline, 6 weeks, and 12 weeks, and the investigators administered a satisfaction questionnaire upon study exit. The primary endpoint was efficacy, defined as the percentage of correctly identified posttreatment photographs by three blinded reviewers (one plastic surgeon and two dermatologists). Secondary endpoints of interest were change in adipose thickness on ultrasound, subject satisfaction, and adverse events.

After losing 1 patient to follow-up, 29 completed the study. Dr. Kang reported that the blinded evaluators could identify the pretreatment image, compared with the posttreatment image in an average of 67% of patients. Between baseline and 12 weeks, the ultrasound images showed an average reduction in the adipose layer of 9% on the abdomen and 7% on the flank, while the average self-reported pain score based on the Wong-Baker FACES Pain Rating Scale was 2 out of 10 among those in the abdomen treatment group and 2.6 out of 10 among those in the flank treatment group.

In addition, 76% of subjects stated they were “satisfied” to “very satisfied” with the treatment, and 79% stated that they would recommend this treatment to a friend. The most common posttreatment responses in both groups were erythema and trace edema, but no serious or permanent adverse events were observed.

Dr. Kang acknowledged certain limitations of the study, including its small sample size. “Only one treatment was performed in our study, so it is unclear if multiple treatments will improve efficacy or if multiple treatments will have no effect on efficacy,” she said.

The work won a “best of session early career-clinical” abstract award from the ASLMS.

The study was funded by Venus Concept, the manufacturer of the Venus Bliss laser. Dr. Kang reported having no relevant financial disclosures. Dr. Kilmer has received grants and honoraria from Venus Concept.

[email protected]

The long-term benefits of endocrine therapy in premenopausal breast cancer appear to differ according to whether patients are categorized as high or low molecular risk using the 70-gene signature (MammaPrint).

Based upon data from patients who had participated in the Stockholm tamoxifen (STO-5) trial, high-risk patients significantly benefited from goserelin treatment, whereas low-risk patients benefited more from tamoxifen treatment when compared with no endocrine therapy.

“Goserelin, tamoxifen, and the combination of the two, reduced the 20-year risk of distant occurrences and fatal breast cancer, compared to no endocrine therapy,” Annelie Johansson, MSc, said at the European Society for Medical Oncology: Breast Cancer virtual meeting.

“Our findings indicate that the long-term endocrine therapy benefit in premenopausal patients is influenced by molecular risk classification and thus tumor characteristics,” she added.

Ms. Johansson, a postdoctoral researcher in genomic breast cancer at the Karolinska Institutet in Stockholm, reported the results of the analysis as a late-breaking abstract at the meeting.

“I think this is an innovative translational study trying to use the multigene assay results to look at differential endocrine therapy effects,” said Prudence Francis, MD, the invited discussant for study.

However, there are relatively few patients in the various subgroups being tested, she added. “We’ve also got short duration of tamoxifen, only 2 years, we’ve got prior chemotherapy in some patients and absence of HER2 therapy, all of which might influence outcomes.”

As a result, Dr. Francis, who is head of medical oncology at the Peter MacCallum Cancer Centre and a consultant Medical Oncologist at St. Vincent’s Hospital Melbourne, called the findings purely “hypothesis generating.”
 

Study details and results

The analysis was based on data from the STO-5 trial, which had recruited just over 900 patients between 1990 and 1997. Patients were stratified according to their lymph node status and some received chemotherapy with or without locoregional radiotherapy before being randomized to one of four study arms: goserelin alone, tamoxifen alone, the combination of the two, or no endocrine therapy.

Ms. Johansson noted that they were able to obtain the primary tumor blocks from 729 patients in the past year, of whom 610 were estrogen receptor positive. The analysis according to the 70-gene signature was then based on data from 465 patients: 131 had been treated with goserelin, 105 with tamoxifen, 120 with both, and 109 had received no endocrine treatment.

We have complete 20-year follow-up from high-quality Swedish National registries,” Ms. Johansson said, observing that the median age in the trial was 46 years.

Before stratifying patients into high and low risk using the 70-gene signature, the risk for having a distant recurrence, compared with no endocrine therapy was reduced by 52% with goserelin (hazard ratio, .48), 41% with tamoxifen (HR, 0.59), and 33% with both in combination (HR, 0.67).

After stratification, however, goserelin was associated with a 78% reduction of distant recurrence versus no endocrine treatment in high-risk patients (HR, 0.22) and a 20% reduction in low-risk patients (HR, 0.80).

Results in high- and low-risk patients with tamoxifen versus no endocrine treatment were a respective 31% reduction (HR, 0.69) and 62% reduction (HR, 0.38), and a respective 36% (HR, 0.64) and 28% (HR, 0.72) for the combination.

A further analysis was performed to compare between the active treatment arms, and this suggested a greater benefit of goserelin in patients at high risk when compared with both tamoxifen (HR, 0.30) and the combination (HR, 0.33).

Dr. Francis commented: “it is a bit surprising to find that goserelin appeared to be also better than the combination,” and it is something that the research team is looking into.

“One hypothesis might be if you look how the different treatments are working,” Ms. Johansson said. “Goserelin is very efficient in lowering the estrogen levels in premenopausal patients, suppressing the ovarian production of estrogen whereas tamoxifen can act both as an antagonist and agonist.

“So, we are thinking that maybe the addition of tamoxifen, with the agonistic properties of tamoxifen, might then make the goserelin not as efficient. But that’s of course, just a hypothesis right now and we need to look into this further,” she said.

The work was funded by The Swedish Research Council (Vetenskapsrådet), The Swedish Research Council for Health, Working life and Welfare, and the Swedish Cancer Society (Cancerfonden). Ms. Johansson had no personal disclosures; one of the coauthors was a coinventor of MammaPrint. Dr. Francis disclosed receiving travel support for overseas lectures from Ipsen and Novartis and acting as a medical oncology editor for Elsevier.

The long-term benefits of endocrine therapy in premenopausal breast cancer appear to differ according to whether patients are categorized as high or low molecular risk using the 70-gene signature (MammaPrint).

Based upon data from patients who had participated in the Stockholm tamoxifen (STO-5) trial, high-risk patients significantly benefited from goserelin treatment, whereas low-risk patients benefited more from tamoxifen treatment when compared with no endocrine therapy.

“Goserelin, tamoxifen, and the combination of the two, reduced the 20-year risk of distant occurrences and fatal breast cancer, compared to no endocrine therapy,” Annelie Johansson, MSc, said at the European Society for Medical Oncology: Breast Cancer virtual meeting.

“Our findings indicate that the long-term endocrine therapy benefit in premenopausal patients is influenced by molecular risk classification and thus tumor characteristics,” she added.

Ms. Johansson, a postdoctoral researcher in genomic breast cancer at the Karolinska Institutet in Stockholm, reported the results of the analysis as a late-breaking abstract at the meeting.

“I think this is an innovative translational study trying to use the multigene assay results to look at differential endocrine therapy effects,” said Prudence Francis, MD, the invited discussant for study.

However, there are relatively few patients in the various subgroups being tested, she added. “We’ve also got short duration of tamoxifen, only 2 years, we’ve got prior chemotherapy in some patients and absence of HER2 therapy, all of which might influence outcomes.”

As a result, Dr. Francis, who is head of medical oncology at the Peter MacCallum Cancer Centre and a consultant Medical Oncologist at St. Vincent’s Hospital Melbourne, called the findings purely “hypothesis generating.”
 

Study details and results

The analysis was based on data from the STO-5 trial, which had recruited just over 900 patients between 1990 and 1997. Patients were stratified according to their lymph node status and some received chemotherapy with or without locoregional radiotherapy before being randomized to one of four study arms: goserelin alone, tamoxifen alone, the combination of the two, or no endocrine therapy.

Ms. Johansson noted that they were able to obtain the primary tumor blocks from 729 patients in the past year, of whom 610 were estrogen receptor positive. The analysis according to the 70-gene signature was then based on data from 465 patients: 131 had been treated with goserelin, 105 with tamoxifen, 120 with both, and 109 had received no endocrine treatment.

We have complete 20-year follow-up from high-quality Swedish National registries,” Ms. Johansson said, observing that the median age in the trial was 46 years.

Before stratifying patients into high and low risk using the 70-gene signature, the risk for having a distant recurrence, compared with no endocrine therapy was reduced by 52% with goserelin (hazard ratio, .48), 41% with tamoxifen (HR, 0.59), and 33% with both in combination (HR, 0.67).

After stratification, however, goserelin was associated with a 78% reduction of distant recurrence versus no endocrine treatment in high-risk patients (HR, 0.22) and a 20% reduction in low-risk patients (HR, 0.80).

Results in high- and low-risk patients with tamoxifen versus no endocrine treatment were a respective 31% reduction (HR, 0.69) and 62% reduction (HR, 0.38), and a respective 36% (HR, 0.64) and 28% (HR, 0.72) for the combination.

A further analysis was performed to compare between the active treatment arms, and this suggested a greater benefit of goserelin in patients at high risk when compared with both tamoxifen (HR, 0.30) and the combination (HR, 0.33).

Dr. Francis commented: “it is a bit surprising to find that goserelin appeared to be also better than the combination,” and it is something that the research team is looking into.

“One hypothesis might be if you look how the different treatments are working,” Ms. Johansson said. “Goserelin is very efficient in lowering the estrogen levels in premenopausal patients, suppressing the ovarian production of estrogen whereas tamoxifen can act both as an antagonist and agonist.

“So, we are thinking that maybe the addition of tamoxifen, with the agonistic properties of tamoxifen, might then make the goserelin not as efficient. But that’s of course, just a hypothesis right now and we need to look into this further,” she said.

The work was funded by The Swedish Research Council (Vetenskapsrådet), The Swedish Research Council for Health, Working life and Welfare, and the Swedish Cancer Society (Cancerfonden). Ms. Johansson had no personal disclosures; one of the coauthors was a coinventor of MammaPrint. Dr. Francis disclosed receiving travel support for overseas lectures from Ipsen and Novartis and acting as a medical oncology editor for Elsevier.

The long-term benefits of endocrine therapy in premenopausal breast cancer appear to differ according to whether patients are categorized as high or low molecular risk using the 70-gene signature (MammaPrint).

Based upon data from patients who had participated in the Stockholm tamoxifen (STO-5) trial, high-risk patients significantly benefited from goserelin treatment, whereas low-risk patients benefited more from tamoxifen treatment when compared with no endocrine therapy.

“Goserelin, tamoxifen, and the combination of the two, reduced the 20-year risk of distant occurrences and fatal breast cancer, compared to no endocrine therapy,” Annelie Johansson, MSc, said at the European Society for Medical Oncology: Breast Cancer virtual meeting.

“Our findings indicate that the long-term endocrine therapy benefit in premenopausal patients is influenced by molecular risk classification and thus tumor characteristics,” she added.

Ms. Johansson, a postdoctoral researcher in genomic breast cancer at the Karolinska Institutet in Stockholm, reported the results of the analysis as a late-breaking abstract at the meeting.

“I think this is an innovative translational study trying to use the multigene assay results to look at differential endocrine therapy effects,” said Prudence Francis, MD, the invited discussant for study.

However, there are relatively few patients in the various subgroups being tested, she added. “We’ve also got short duration of tamoxifen, only 2 years, we’ve got prior chemotherapy in some patients and absence of HER2 therapy, all of which might influence outcomes.”

As a result, Dr. Francis, who is head of medical oncology at the Peter MacCallum Cancer Centre and a consultant Medical Oncologist at St. Vincent’s Hospital Melbourne, called the findings purely “hypothesis generating.”
 

Study details and results

The analysis was based on data from the STO-5 trial, which had recruited just over 900 patients between 1990 and 1997. Patients were stratified according to their lymph node status and some received chemotherapy with or without locoregional radiotherapy before being randomized to one of four study arms: goserelin alone, tamoxifen alone, the combination of the two, or no endocrine therapy.

Ms. Johansson noted that they were able to obtain the primary tumor blocks from 729 patients in the past year, of whom 610 were estrogen receptor positive. The analysis according to the 70-gene signature was then based on data from 465 patients: 131 had been treated with goserelin, 105 with tamoxifen, 120 with both, and 109 had received no endocrine treatment.

We have complete 20-year follow-up from high-quality Swedish National registries,” Ms. Johansson said, observing that the median age in the trial was 46 years.

Before stratifying patients into high and low risk using the 70-gene signature, the risk for having a distant recurrence, compared with no endocrine therapy was reduced by 52% with goserelin (hazard ratio, .48), 41% with tamoxifen (HR, 0.59), and 33% with both in combination (HR, 0.67).

After stratification, however, goserelin was associated with a 78% reduction of distant recurrence versus no endocrine treatment in high-risk patients (HR, 0.22) and a 20% reduction in low-risk patients (HR, 0.80).

Results in high- and low-risk patients with tamoxifen versus no endocrine treatment were a respective 31% reduction (HR, 0.69) and 62% reduction (HR, 0.38), and a respective 36% (HR, 0.64) and 28% (HR, 0.72) for the combination.

A further analysis was performed to compare between the active treatment arms, and this suggested a greater benefit of goserelin in patients at high risk when compared with both tamoxifen (HR, 0.30) and the combination (HR, 0.33).

Dr. Francis commented: “it is a bit surprising to find that goserelin appeared to be also better than the combination,” and it is something that the research team is looking into.

“One hypothesis might be if you look how the different treatments are working,” Ms. Johansson said. “Goserelin is very efficient in lowering the estrogen levels in premenopausal patients, suppressing the ovarian production of estrogen whereas tamoxifen can act both as an antagonist and agonist.

“So, we are thinking that maybe the addition of tamoxifen, with the agonistic properties of tamoxifen, might then make the goserelin not as efficient. But that’s of course, just a hypothesis right now and we need to look into this further,” she said.

The work was funded by The Swedish Research Council (Vetenskapsrådet), The Swedish Research Council for Health, Working life and Welfare, and the Swedish Cancer Society (Cancerfonden). Ms. Johansson had no personal disclosures; one of the coauthors was a coinventor of MammaPrint. Dr. Francis disclosed receiving travel support for overseas lectures from Ipsen and Novartis and acting as a medical oncology editor for Elsevier.

Many Mohs surgeons are struggling on the job, and women seem to be especially vulnerable, a new survey suggests.

In a measurement of well-being, 40% of members of the American College of Mohs

Surgery (ACMS) who responded to the survey – and 52% of women – scored at a level considered “at-risk” for adverse outcomes, such as poor quality of life.

“I didn’t think the numbers were going to be that high,” said study author Kemi O. Awe, MD, PhD, a dermatology resident at the University of Alabama at Birmingham, especially in light of Mohs surgery’s reputation as being an especially desirable field in dermatology. She presented the findings at the annual meeting of the ACMS.

Dr. Awe, who hopes to become a Mohs surgeon herself, said in an interview that she launched the study in part to understand how colleagues are faring. “Dermatology is known as a specialty that has a good lifestyle and less stress, but the rate of burnout is actually going up.”

For the study, Dr. Awe and colleagues sent a survey to ACMS members between October and December 2020. The 91 respondents had an average age of 46, and 58% were male. Most practiced in academic facilities (56%), while the rest worked in private practice (39%) or multispecialty (4%) practices. Almost all (89%) were married or in partnerships.

The survey calculated scores on the expanded Physician Well Being Index, a validated tool for measuring physician distress. Forty percent of 68 respondents to this part of the survey got a score of 3 or higher, which the study describes as “a threshold for respondents who are ‘at-risk’ of adverse outcomes such as poor quality of life, depression, and a high level of fatigue.”

Women were more likely to be considered at risk (52%) than men (28%). “This isn’t different than what’s already out there: Female physicians are more likely to be burned out compared to men,” Dr. Awe said.

Compared with their male counterparts, female Mohs surgeons were more likely to say that time at work, malpractice concerns, insurance reimbursement, and compensation structure negatively affected their well-being (P ≤ .05).

It’s unclear whether there’s a well-being gender gap among dermatologists overall, however. Dr. Awe highlighted a 2019 survey of 108 dermatologists that found no significant difference in overall burnout between men and women – about 42% of both genders reported symptoms. But the survey did find that “dermatologists with children living at home had significantly higher levels of burnout,” with a P value of .03.

Dr. Awe said the findings offer insight into what to look out for when pursuing a career as a Mohs surgeon. “There’s potentially excess stress about being a Mohs surgeon,” she said, although the field also has a reputation as being fulfilling and rewarding.

In an interview, Stanford (Calif.) University dermatologist Zakia Rahman, MD, praised the study and said it “certainly provides a framework to address professional fulfillment amongst Mohs surgeons.”

For now, dermatologists can focus on strategies that can reduce burnout in the field, Sailesh Konda, MD, a Mohs surgeon at the Univeristy of Florida, Gainesville, said in an interview. Dr. Konda highlighted a report published in 2020 that, he said, "recommended focusing on incremental changes that help restore autonomy and control over work, connecting with colleagues within dermatology and the broader medical community, developing self-awareness and recognition of a perfectionist mindset, and restoring meaning and joy to patient care.”*

No funding is reported for the study. Dr. Awe, Dr. Rahman, and Dr. Konda have no relevant disclosures.

*This story was updated on June 2 for clarity.

Many Mohs surgeons are struggling on the job, and women seem to be especially vulnerable, a new survey suggests.

In a measurement of well-being, 40% of members of the American College of Mohs

Surgery (ACMS) who responded to the survey – and 52% of women – scored at a level considered “at-risk” for adverse outcomes, such as poor quality of life.

“I didn’t think the numbers were going to be that high,” said study author Kemi O. Awe, MD, PhD, a dermatology resident at the University of Alabama at Birmingham, especially in light of Mohs surgery’s reputation as being an especially desirable field in dermatology. She presented the findings at the annual meeting of the ACMS.

Dr. Awe, who hopes to become a Mohs surgeon herself, said in an interview that she launched the study in part to understand how colleagues are faring. “Dermatology is known as a specialty that has a good lifestyle and less stress, but the rate of burnout is actually going up.”

For the study, Dr. Awe and colleagues sent a survey to ACMS members between October and December 2020. The 91 respondents had an average age of 46, and 58% were male. Most practiced in academic facilities (56%), while the rest worked in private practice (39%) or multispecialty (4%) practices. Almost all (89%) were married or in partnerships.

The survey calculated scores on the expanded Physician Well Being Index, a validated tool for measuring physician distress. Forty percent of 68 respondents to this part of the survey got a score of 3 or higher, which the study describes as “a threshold for respondents who are ‘at-risk’ of adverse outcomes such as poor quality of life, depression, and a high level of fatigue.”

Women were more likely to be considered at risk (52%) than men (28%). “This isn’t different than what’s already out there: Female physicians are more likely to be burned out compared to men,” Dr. Awe said.

Compared with their male counterparts, female Mohs surgeons were more likely to say that time at work, malpractice concerns, insurance reimbursement, and compensation structure negatively affected their well-being (P ≤ .05).

It’s unclear whether there’s a well-being gender gap among dermatologists overall, however. Dr. Awe highlighted a 2019 survey of 108 dermatologists that found no significant difference in overall burnout between men and women – about 42% of both genders reported symptoms. But the survey did find that “dermatologists with children living at home had significantly higher levels of burnout,” with a P value of .03.

Dr. Awe said the findings offer insight into what to look out for when pursuing a career as a Mohs surgeon. “There’s potentially excess stress about being a Mohs surgeon,” she said, although the field also has a reputation as being fulfilling and rewarding.

In an interview, Stanford (Calif.) University dermatologist Zakia Rahman, MD, praised the study and said it “certainly provides a framework to address professional fulfillment amongst Mohs surgeons.”

For now, dermatologists can focus on strategies that can reduce burnout in the field, Sailesh Konda, MD, a Mohs surgeon at the Univeristy of Florida, Gainesville, said in an interview. Dr. Konda highlighted a report published in 2020 that, he said, "recommended focusing on incremental changes that help restore autonomy and control over work, connecting with colleagues within dermatology and the broader medical community, developing self-awareness and recognition of a perfectionist mindset, and restoring meaning and joy to patient care.”*

No funding is reported for the study. Dr. Awe, Dr. Rahman, and Dr. Konda have no relevant disclosures.

*This story was updated on June 2 for clarity.

Many Mohs surgeons are struggling on the job, and women seem to be especially vulnerable, a new survey suggests.

In a measurement of well-being, 40% of members of the American College of Mohs

Surgery (ACMS) who responded to the survey – and 52% of women – scored at a level considered “at-risk” for adverse outcomes, such as poor quality of life.

“I didn’t think the numbers were going to be that high,” said study author Kemi O. Awe, MD, PhD, a dermatology resident at the University of Alabama at Birmingham, especially in light of Mohs surgery’s reputation as being an especially desirable field in dermatology. She presented the findings at the annual meeting of the ACMS.

Dr. Awe, who hopes to become a Mohs surgeon herself, said in an interview that she launched the study in part to understand how colleagues are faring. “Dermatology is known as a specialty that has a good lifestyle and less stress, but the rate of burnout is actually going up.”

For the study, Dr. Awe and colleagues sent a survey to ACMS members between October and December 2020. The 91 respondents had an average age of 46, and 58% were male. Most practiced in academic facilities (56%), while the rest worked in private practice (39%) or multispecialty (4%) practices. Almost all (89%) were married or in partnerships.

The survey calculated scores on the expanded Physician Well Being Index, a validated tool for measuring physician distress. Forty percent of 68 respondents to this part of the survey got a score of 3 or higher, which the study describes as “a threshold for respondents who are ‘at-risk’ of adverse outcomes such as poor quality of life, depression, and a high level of fatigue.”

Women were more likely to be considered at risk (52%) than men (28%). “This isn’t different than what’s already out there: Female physicians are more likely to be burned out compared to men,” Dr. Awe said.

Compared with their male counterparts, female Mohs surgeons were more likely to say that time at work, malpractice concerns, insurance reimbursement, and compensation structure negatively affected their well-being (P ≤ .05).

It’s unclear whether there’s a well-being gender gap among dermatologists overall, however. Dr. Awe highlighted a 2019 survey of 108 dermatologists that found no significant difference in overall burnout between men and women – about 42% of both genders reported symptoms. But the survey did find that “dermatologists with children living at home had significantly higher levels of burnout,” with a P value of .03.

Dr. Awe said the findings offer insight into what to look out for when pursuing a career as a Mohs surgeon. “There’s potentially excess stress about being a Mohs surgeon,” she said, although the field also has a reputation as being fulfilling and rewarding.

In an interview, Stanford (Calif.) University dermatologist Zakia Rahman, MD, praised the study and said it “certainly provides a framework to address professional fulfillment amongst Mohs surgeons.”

For now, dermatologists can focus on strategies that can reduce burnout in the field, Sailesh Konda, MD, a Mohs surgeon at the Univeristy of Florida, Gainesville, said in an interview. Dr. Konda highlighted a report published in 2020 that, he said, "recommended focusing on incremental changes that help restore autonomy and control over work, connecting with colleagues within dermatology and the broader medical community, developing self-awareness and recognition of a perfectionist mindset, and restoring meaning and joy to patient care.”*

No funding is reported for the study. Dr. Awe, Dr. Rahman, and Dr. Konda have no relevant disclosures.

*This story was updated on June 2 for clarity.

Converge 2021 session

LAMA’s DRAMA: Left AMA – Documentation and Rules of AMA

Presenter

Venkatrao Medarametla, MD, SFHM

Session summary

Most hospitalists equate LAMA (left against medical advice) patients with noncompliance and stop at that. During the recent SHM Converge conference session on LAMA, Dr. Venkatrao Medarametla, medical director for hospital medicine at Baystate Medical Center, Springfield, Mass., delved into the etiology and pathophysiology of LAMA discharges.

According to Dr. Medarametla, LAMA accounts for 1.4% of all discharges amounting to more than 500,000 discharges per year nationwide. LAMA discharges are at high risk for readmissions (20%-40% higher), have longer length of stay on readmission, higher morbidity and mortality (10% higher), and result in higher costs of care (56% higher).

The reasons for LAMA discharges could be broadly divided into patient and provider factors. Patient factors include refusal to wait for administrative delays, extenuating domestic and social concerns, conflicts with care providers, disagreement with providers’ judgment of health status, mistrust of the health system, substance dependence with inadequate treatment for withdrawal, patient’s perception of respect, stereotyping or stigma, and even ambiance and diet at the hospital.

Provider factors include conflict with the patient, concerns of legal and ethical responsibilities, formally distancing from nonstandard plan, and deflecting blame for worse outcomes.

Faced with a LAMA discharge, the important role of a hospitalist is to assess capacity. Help may be sought from other specialists such as psychiatrists and geriatricians. Some of the best practices also include a clear discussion of risks of outpatient treatment, exploration of safe alternative care plans, patient-centered care, shared decision-making (e.g., needle exchange), and harm reduction.

Dr. Medarametla advised hospitalists not to rely on the AMA forms the patients are asked to sign for liability protection. The forms may not stand up to legal scrutiny. Excellent documentation regarding the details of discussions with the patient, and determination of capacity encompassing the patients’ understanding, reasoning, and insight should be made. Hospitalists can also assess the barriers and mitigate them. Appropriate outpatient and alternative treatment plans should be explored. Postdischarge care and follow ups also should be facilitated.

According to Dr. Medarametla, another myth about AMA discharge is that insurance will not pay for it. About 57% of a survey sample of attendings and residents believed the same, and 66% heard other providers telling patients that insurance would not cover the AMA discharges. In a multicentric study of 526 patients, payment was refused only in 4.1% of AMA cases, mostly for administrative reasons.

Another prevalent myth is that patients who leave AMA will lose their right to follow up. Prescriptions also could be given to LAMA patients provided hospitalists adhere to detailed and relevant documentation. Overall, the session was very interesting and informative.
 

Key takeaways

• There are patient and provider factors leading to LAMA.
• Patients signing an AMA form does not provide legal protection for providers, but a stream-lined discharge process and a detailed documentation are likely to.
• There is no evidence that insurance companies will not pay for LAMA discharges.
• LAMA patients could be given prescriptions and follow up as long as they are well documented.

References

Schaefer G et al. Financial responsibility of hospitalized patients who left against medical advice: Medical urban legend? J Gen Intern Med. 2012 Jul;27(7):825-30. doi: 10.1007/s11606-012-1984-x.

Wigder H et al. Insurance companies refusing payment for patients who leave the emergency department against medical advice is a myth. Ann Emerg Med. 2010 Apr;55(4):393. doi: 10.1016/j.annemergmed.2009.11.024.

Dr. Kumar is a hospitalist in Port Huron, Mich. He is a member of the editorial advisory board for the Hospitalist.

Converge 2021 session

LAMA’s DRAMA: Left AMA – Documentation and Rules of AMA

Presenter

Venkatrao Medarametla, MD, SFHM

Session summary

Most hospitalists equate LAMA (left against medical advice) patients with noncompliance and stop at that. During the recent SHM Converge conference session on LAMA, Dr. Venkatrao Medarametla, medical director for hospital medicine at Baystate Medical Center, Springfield, Mass., delved into the etiology and pathophysiology of LAMA discharges.

According to Dr. Medarametla, LAMA accounts for 1.4% of all discharges amounting to more than 500,000 discharges per year nationwide. LAMA discharges are at high risk for readmissions (20%-40% higher), have longer length of stay on readmission, higher morbidity and mortality (10% higher), and result in higher costs of care (56% higher).

The reasons for LAMA discharges could be broadly divided into patient and provider factors. Patient factors include refusal to wait for administrative delays, extenuating domestic and social concerns, conflicts with care providers, disagreement with providers’ judgment of health status, mistrust of the health system, substance dependence with inadequate treatment for withdrawal, patient’s perception of respect, stereotyping or stigma, and even ambiance and diet at the hospital.

Provider factors include conflict with the patient, concerns of legal and ethical responsibilities, formally distancing from nonstandard plan, and deflecting blame for worse outcomes.

Faced with a LAMA discharge, the important role of a hospitalist is to assess capacity. Help may be sought from other specialists such as psychiatrists and geriatricians. Some of the best practices also include a clear discussion of risks of outpatient treatment, exploration of safe alternative care plans, patient-centered care, shared decision-making (e.g., needle exchange), and harm reduction.

Dr. Medarametla advised hospitalists not to rely on the AMA forms the patients are asked to sign for liability protection. The forms may not stand up to legal scrutiny. Excellent documentation regarding the details of discussions with the patient, and determination of capacity encompassing the patients’ understanding, reasoning, and insight should be made. Hospitalists can also assess the barriers and mitigate them. Appropriate outpatient and alternative treatment plans should be explored. Postdischarge care and follow ups also should be facilitated.

According to Dr. Medarametla, another myth about AMA discharge is that insurance will not pay for it. About 57% of a survey sample of attendings and residents believed the same, and 66% heard other providers telling patients that insurance would not cover the AMA discharges. In a multicentric study of 526 patients, payment was refused only in 4.1% of AMA cases, mostly for administrative reasons.

Another prevalent myth is that patients who leave AMA will lose their right to follow up. Prescriptions also could be given to LAMA patients provided hospitalists adhere to detailed and relevant documentation. Overall, the session was very interesting and informative.
 

Key takeaways

• There are patient and provider factors leading to LAMA.
• Patients signing an AMA form does not provide legal protection for providers, but a stream-lined discharge process and a detailed documentation are likely to.
• There is no evidence that insurance companies will not pay for LAMA discharges.
• LAMA patients could be given prescriptions and follow up as long as they are well documented.

References

Schaefer G et al. Financial responsibility of hospitalized patients who left against medical advice: Medical urban legend? J Gen Intern Med. 2012 Jul;27(7):825-30. doi: 10.1007/s11606-012-1984-x.

Wigder H et al. Insurance companies refusing payment for patients who leave the emergency department against medical advice is a myth. Ann Emerg Med. 2010 Apr;55(4):393. doi: 10.1016/j.annemergmed.2009.11.024.

Dr. Kumar is a hospitalist in Port Huron, Mich. He is a member of the editorial advisory board for the Hospitalist.

Converge 2021 session

LAMA’s DRAMA: Left AMA – Documentation and Rules of AMA

Presenter

Venkatrao Medarametla, MD, SFHM

Session summary

Most hospitalists equate LAMA (left against medical advice) patients with noncompliance and stop at that. During the recent SHM Converge conference session on LAMA, Dr. Venkatrao Medarametla, medical director for hospital medicine at Baystate Medical Center, Springfield, Mass., delved into the etiology and pathophysiology of LAMA discharges.

According to Dr. Medarametla, LAMA accounts for 1.4% of all discharges amounting to more than 500,000 discharges per year nationwide. LAMA discharges are at high risk for readmissions (20%-40% higher), have longer length of stay on readmission, higher morbidity and mortality (10% higher), and result in higher costs of care (56% higher).

The reasons for LAMA discharges could be broadly divided into patient and provider factors. Patient factors include refusal to wait for administrative delays, extenuating domestic and social concerns, conflicts with care providers, disagreement with providers’ judgment of health status, mistrust of the health system, substance dependence with inadequate treatment for withdrawal, patient’s perception of respect, stereotyping or stigma, and even ambiance and diet at the hospital.

Provider factors include conflict with the patient, concerns of legal and ethical responsibilities, formally distancing from nonstandard plan, and deflecting blame for worse outcomes.

Faced with a LAMA discharge, the important role of a hospitalist is to assess capacity. Help may be sought from other specialists such as psychiatrists and geriatricians. Some of the best practices also include a clear discussion of risks of outpatient treatment, exploration of safe alternative care plans, patient-centered care, shared decision-making (e.g., needle exchange), and harm reduction.

Dr. Medarametla advised hospitalists not to rely on the AMA forms the patients are asked to sign for liability protection. The forms may not stand up to legal scrutiny. Excellent documentation regarding the details of discussions with the patient, and determination of capacity encompassing the patients’ understanding, reasoning, and insight should be made. Hospitalists can also assess the barriers and mitigate them. Appropriate outpatient and alternative treatment plans should be explored. Postdischarge care and follow ups also should be facilitated.

According to Dr. Medarametla, another myth about AMA discharge is that insurance will not pay for it. About 57% of a survey sample of attendings and residents believed the same, and 66% heard other providers telling patients that insurance would not cover the AMA discharges. In a multicentric study of 526 patients, payment was refused only in 4.1% of AMA cases, mostly for administrative reasons.

Another prevalent myth is that patients who leave AMA will lose their right to follow up. Prescriptions also could be given to LAMA patients provided hospitalists adhere to detailed and relevant documentation. Overall, the session was very interesting and informative.
 

Key takeaways

• There are patient and provider factors leading to LAMA.
• Patients signing an AMA form does not provide legal protection for providers, but a stream-lined discharge process and a detailed documentation are likely to.
• There is no evidence that insurance companies will not pay for LAMA discharges.
• LAMA patients could be given prescriptions and follow up as long as they are well documented.

References

Schaefer G et al. Financial responsibility of hospitalized patients who left against medical advice: Medical urban legend? J Gen Intern Med. 2012 Jul;27(7):825-30. doi: 10.1007/s11606-012-1984-x.

Wigder H et al. Insurance companies refusing payment for patients who leave the emergency department against medical advice is a myth. Ann Emerg Med. 2010 Apr;55(4):393. doi: 10.1016/j.annemergmed.2009.11.024.

Dr. Kumar is a hospitalist in Port Huron, Mich. He is a member of the editorial advisory board for the Hospitalist.

For children with spinal muscular atrophy (SMA), gene therapy with onasemnogene abeparvovec (Zolgensma, Novartis) provides long-lasting benefits with a favorable safety profile, new long-term follow-up data show. At a median of 5.2 years since receiving the approved therapeutic dose, onasemnogene abeparvovec provided “sustained, durable efficacy, with all patients alive and without the need for permanent ventilation,” reported Jerry Mendell, MD, with the Center for Gene Therapy, Nationwide Children’s Hospital, Columbus, Ohio, and colleagues.

The study was published online May 17 in JAMA Neurology.
 

Single infusion

SMA is a rare genetic disease that can lead to paralysis, breathing difficulty, and death. The disorder is caused by a mutation in the survival motor neuron 1 (SMN1) gene, which encodes the SMN protein critical for maintenance and function of motor neurons.

In 2019, Zolgensma was approved in the United States for children with SMA and younger than 2 years of age.

Zolgensma is an adeno-associated virus vector-based gene therapy that addresses the genetic root cause of SMA by replacing the defective or missing SMN1 gene to halt disease progression. A single, one-time intravenous infusion results in expression of the SMN protein motor neurons, which improves chances of survival, as well as muscle movement and function.

In the phase 1 START study, 15 infants with SMA type 1 were treated with either a low or therapeutic dose of Zolgensma at Nationwide Children’s Hospital between 2014 and 2017.

The START long-term follow-up study (START LTFU) is an ongoing, observational study assessing safety and durability of response over 15 years in 13 of the infants; three infants received the low dose and 10 received the approved high dose.

Prior to baseline, four patients (40%) in the therapeutic dose cohort required noninvasive ventilatory support, and six (60%) did not require regular ventilatory support, which did not change in long-term follow-up.

All 10 patients who received the therapeutic dose remained alive and without the need for permanent ventilation up to 6.2 years after dosing, Dr. Mendell and colleagues report.

These patients also maintained previously acquired motor milestones. Two patients attained the new milestone of “standing with assistance” without the use of nusinersen (Spinraza, Biogen). 

Serious adverse events occurred in eight patients (62%), none of which resulted in study discontinuation or death. The most common serious adverse events were related to the underlying SMA disease process and included acute respiratory failure (31%), pneumonia (31%), dehydration (23%), respiratory distress (15%), and bronchiolitis (15%).

Importantly, the investigators noted, no new safety signals or “adverse events of special interest” emerged during follow-up, including liver function enzyme elevations, new incidences of malignancy or hematologic disorders, and new incidences or exacerbations of existing neurologic or autoimmune disorders.

The investigators acknowledged that this follow-up study is limited by the small sample size of the patient population and confounded by treatment with nusinersen in several patients. “However, given that the two patients who acquired the new motor milestone of standing with assistance did not receive nusinersen at any time, this benefit can be attributed solely to onasemnogene abeparvovec,” Dr. Mendell and colleagues said. 

The study was supported by Novartis Gene Therapies. Dr. Mendell and several co-investigators have disclosed financial relationships with the company.

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

For children with spinal muscular atrophy (SMA), gene therapy with onasemnogene abeparvovec (Zolgensma, Novartis) provides long-lasting benefits with a favorable safety profile, new long-term follow-up data show. At a median of 5.2 years since receiving the approved therapeutic dose, onasemnogene abeparvovec provided “sustained, durable efficacy, with all patients alive and without the need for permanent ventilation,” reported Jerry Mendell, MD, with the Center for Gene Therapy, Nationwide Children’s Hospital, Columbus, Ohio, and colleagues.

The study was published online May 17 in JAMA Neurology.
 

Single infusion

SMA is a rare genetic disease that can lead to paralysis, breathing difficulty, and death. The disorder is caused by a mutation in the survival motor neuron 1 (SMN1) gene, which encodes the SMN protein critical for maintenance and function of motor neurons.

In 2019, Zolgensma was approved in the United States for children with SMA and younger than 2 years of age.

Zolgensma is an adeno-associated virus vector-based gene therapy that addresses the genetic root cause of SMA by replacing the defective or missing SMN1 gene to halt disease progression. A single, one-time intravenous infusion results in expression of the SMN protein motor neurons, which improves chances of survival, as well as muscle movement and function.

In the phase 1 START study, 15 infants with SMA type 1 were treated with either a low or therapeutic dose of Zolgensma at Nationwide Children’s Hospital between 2014 and 2017.

The START long-term follow-up study (START LTFU) is an ongoing, observational study assessing safety and durability of response over 15 years in 13 of the infants; three infants received the low dose and 10 received the approved high dose.

Prior to baseline, four patients (40%) in the therapeutic dose cohort required noninvasive ventilatory support, and six (60%) did not require regular ventilatory support, which did not change in long-term follow-up.

All 10 patients who received the therapeutic dose remained alive and without the need for permanent ventilation up to 6.2 years after dosing, Dr. Mendell and colleagues report.

These patients also maintained previously acquired motor milestones. Two patients attained the new milestone of “standing with assistance” without the use of nusinersen (Spinraza, Biogen). 

Serious adverse events occurred in eight patients (62%), none of which resulted in study discontinuation or death. The most common serious adverse events were related to the underlying SMA disease process and included acute respiratory failure (31%), pneumonia (31%), dehydration (23%), respiratory distress (15%), and bronchiolitis (15%).

Importantly, the investigators noted, no new safety signals or “adverse events of special interest” emerged during follow-up, including liver function enzyme elevations, new incidences of malignancy or hematologic disorders, and new incidences or exacerbations of existing neurologic or autoimmune disorders.

The investigators acknowledged that this follow-up study is limited by the small sample size of the patient population and confounded by treatment with nusinersen in several patients. “However, given that the two patients who acquired the new motor milestone of standing with assistance did not receive nusinersen at any time, this benefit can be attributed solely to onasemnogene abeparvovec,” Dr. Mendell and colleagues said. 

The study was supported by Novartis Gene Therapies. Dr. Mendell and several co-investigators have disclosed financial relationships with the company.

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

For children with spinal muscular atrophy (SMA), gene therapy with onasemnogene abeparvovec (Zolgensma, Novartis) provides long-lasting benefits with a favorable safety profile, new long-term follow-up data show. At a median of 5.2 years since receiving the approved therapeutic dose, onasemnogene abeparvovec provided “sustained, durable efficacy, with all patients alive and without the need for permanent ventilation,” reported Jerry Mendell, MD, with the Center for Gene Therapy, Nationwide Children’s Hospital, Columbus, Ohio, and colleagues.

The study was published online May 17 in JAMA Neurology.
 

Single infusion

SMA is a rare genetic disease that can lead to paralysis, breathing difficulty, and death. The disorder is caused by a mutation in the survival motor neuron 1 (SMN1) gene, which encodes the SMN protein critical for maintenance and function of motor neurons.

In 2019, Zolgensma was approved in the United States for children with SMA and younger than 2 years of age.

Zolgensma is an adeno-associated virus vector-based gene therapy that addresses the genetic root cause of SMA by replacing the defective or missing SMN1 gene to halt disease progression. A single, one-time intravenous infusion results in expression of the SMN protein motor neurons, which improves chances of survival, as well as muscle movement and function.

In the phase 1 START study, 15 infants with SMA type 1 were treated with either a low or therapeutic dose of Zolgensma at Nationwide Children’s Hospital between 2014 and 2017.

The START long-term follow-up study (START LTFU) is an ongoing, observational study assessing safety and durability of response over 15 years in 13 of the infants; three infants received the low dose and 10 received the approved high dose.

Prior to baseline, four patients (40%) in the therapeutic dose cohort required noninvasive ventilatory support, and six (60%) did not require regular ventilatory support, which did not change in long-term follow-up.

All 10 patients who received the therapeutic dose remained alive and without the need for permanent ventilation up to 6.2 years after dosing, Dr. Mendell and colleagues report.

These patients also maintained previously acquired motor milestones. Two patients attained the new milestone of “standing with assistance” without the use of nusinersen (Spinraza, Biogen). 

Serious adverse events occurred in eight patients (62%), none of which resulted in study discontinuation or death. The most common serious adverse events were related to the underlying SMA disease process and included acute respiratory failure (31%), pneumonia (31%), dehydration (23%), respiratory distress (15%), and bronchiolitis (15%).

Importantly, the investigators noted, no new safety signals or “adverse events of special interest” emerged during follow-up, including liver function enzyme elevations, new incidences of malignancy or hematologic disorders, and new incidences or exacerbations of existing neurologic or autoimmune disorders.

The investigators acknowledged that this follow-up study is limited by the small sample size of the patient population and confounded by treatment with nusinersen in several patients. “However, given that the two patients who acquired the new motor milestone of standing with assistance did not receive nusinersen at any time, this benefit can be attributed solely to onasemnogene abeparvovec,” Dr. Mendell and colleagues said. 

The study was supported by Novartis Gene Therapies. Dr. Mendell and several co-investigators have disclosed financial relationships with the company.

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

When the COVID-19 pandemic forced behavioral health providers to stop seeing patients in person and instead hold therapy sessions remotely, the switch produced an unintended, positive consequence: Fewer patients skipped appointments.

RichLegg/E+

That had long been a problem in mental health care. Some outpatient programs previously had no-show rates as high as 60%, according to several studies.

Only 9% of psychiatrists reported that all patients kept their appointments before the pandemic, according to an American Psychiatric Association report. Once providers switched to telepsychiatry, that number increased to 32%.

Not only that, but providers and patients say teletherapy has largely been an effective lifeline for people struggling with anxiety, depression, and other psychological issues during an extraordinarily difficult time, even though it created a new set of challenges.

Many providers say they plan to continue offering teletherapy after the pandemic. Some states are making permanent the temporary pandemic rules that allow providers to be reimbursed at the same rates as for in-person visits, which is welcome news to practitioners who take patients’ insurance.

“We are in a mental health crisis right now, so more people are struggling and may be more open to accessing services,” said psychologist Allison Dempsey, PhD, associate professor at University of Colorado at Denver, Aurora. “It’s much easier to connect from your living room.”

The problem for patients who didn’t show up was often as simple as a canceled ride, said Jody Long, a clinical social worker who studied the 60% rate of no-shows or late cancellations at the University of Tennessee Health Science Center psychiatric clinic in Memphis.

But sometimes it was the health problem itself. Mr. Long remembers seeing a first-time patient drive around the parking lot and then exit. The patient later called and told Mr. Long, “I just could not get out of the car; please forgive me and reschedule me.”

Mr. Long, now an assistant professor at Jacksonville (Ala.) State University, said that incident changed his perspective. “I realized when you’re having panic attacks or anxiety attacks or suffering from major depressive disorder, it’s hard,” he said. “It’s like you have built up these walls for protection and then all of a sudden you’re having to let these walls down.”

Absences strain providers whose bosses set billing and productivity expectations and those in private practice who lose billable hours, said Dr. Dempsey, who directs a program to provide mental health care for families of babies with serious medical complications. Psychotherapists often overbooked patients with the expectation that some would not show up.

Now Dr. Dempsey and colleagues no longer need to overbook. When patients don’t show up, staffers can sometimes contact a patient right away and hold the session. Other times, they can reschedule them for later that day or a different day.

And telepsychiatry performs as well as, if not better than, face-to-face delivery of mental health services, according to a World Journal of Psychiatry review of 452 studies.

Virtual visits can also save patients money, because they might not need to travel, take time off work, or pay for child care, said Jay Shore, MD, MPH, chairperson of the American Psychiatric Association’s telepsychiatry committee and a psychiatrist at the University of Colorado.

Dr. Shore started examining the potential of video conferencing to reach rural patients in the late ’90s and concluded that patients and providers can virtually build rapport, which he said is fundamental for effective therapy and medicine management.

But before the pandemic, almost 64% of psychiatrists had never used telehealth, according to the psychiatric association. Amid widespread skepticism, providers then had to do “10 years of implementations in 10 days,” said Dr. Shore, who has consulted with Dr. Dempsey and other providers.

Dr. Dempsey and colleagues faced a steep learning curve. She said she recently held a video therapy session with a mother who “seemed very out of it” before disappearing from the screen while her baby was crying.

She wondered if the patient’s exit was related to the stress of new motherhood or “something more concerning,” like addiction. She thinks she might have better understood the woman’s condition had they been in the same room. The patient called Dr. Dempsey’s team that night and told them she had relapsed into drug use and been taken to the emergency room. The mental health providers directed her to a treatment program, Dr. Dempsey said.

“We spent a lot of time reviewing what happened with that case and thinking about what we need to do differently,” Dr. Dempsey said.

Providers now routinely ask for the name of someone to call if they lose a connection and can no longer reach the patient.

In another session, Dr. Dempsey noticed that a patient seemed guarded and saw her partner hovering in the background. She said she worried about the possibility of domestic violence or “some other form of controlling behavior.”

In such cases, Dr. Dempsey called after the appointments or sent the patients secure messages to their online health portal. She asked if they felt safe and suggested they talk in person.

Such inability to maintain privacy remains a concern.

In a Walmart parking lot recently, psychologist Kristy Keefe, PsyD, of Western Illinois University, Macomb, heard a patient talking with her therapist from her car. Dr. Keefe said she wondered if the patient “had no other safe place to go to.”

To avoid that scenario, Dr. Keefe does 30-minute consultations with patients before their first telehealth appointment. She asks if they have space to talk where no one can overhear them and makes sure they have sufficient internet access and know how to use video conferencing.

To ensure that she, too, was prepared, Dr. Keefe upgraded her WiFi router, purchased two white-noise machines to drown out her conversations, and placed a stop sign on her door during appointments so her 5-year-old son knew she was seeing patients.

Dr. Keefe concluded that audio alone sometimes works better than video, which often lags. Over the phone, she and her psychology students “got really sensitive to tone fluctuations” in a patient’s voice and were better able to “pick up the emotion” than with video conferencing.

With those telehealth visits, her 20% no-show rate evaporated.

Kate Barnes, a 29-year-old middle school teacher in Fayetteville, Ark., who struggles with anxiety and depression, also has found visits easier by phone than by Zoom, because she doesn’t feel like a spotlight is on her.

“I can focus more on what I want to say,” she said.

In one of Dr. Keefe’s video sessions, though, a patient reached out, touched the camera and started to cry as she said how appreciative she was that someone was there, Dr. Keefe recalled.

“I am so very thankful that they had something in this terrible time of loss and trauma and isolation,” said Dr. Keefe.

Demand for mental health services will likely continue even after the lifting of all COVID restrictions. About 41% of adults were suffering from anxiety or depression in January, compared with about 11% 2 years before, according to data from the U.S. Census Bureau and the National Health Interview Survey.

“That is not going to go away with snapping our fingers,” Dr. Dempsey said.

After the pandemic, Dr. Shore said, providers should review data from the past year and determine when virtual care or in-person care is more effective. He also said the health care industry needs to work to bridge the digital divide that exists because of lack of access to devices and broadband internet.

Even though Ms. Barnes said she did not see teletherapy as less effective than in-person therapy, she would like to return to seeing her therapist in person.

“When you are in person with someone, you can pick up on their body language better,” she said. “It’s a lot harder over a video call to do that.”

KHN  (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at  KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

When the COVID-19 pandemic forced behavioral health providers to stop seeing patients in person and instead hold therapy sessions remotely, the switch produced an unintended, positive consequence: Fewer patients skipped appointments.

RichLegg/E+

That had long been a problem in mental health care. Some outpatient programs previously had no-show rates as high as 60%, according to several studies.

Only 9% of psychiatrists reported that all patients kept their appointments before the pandemic, according to an American Psychiatric Association report. Once providers switched to telepsychiatry, that number increased to 32%.

Not only that, but providers and patients say teletherapy has largely been an effective lifeline for people struggling with anxiety, depression, and other psychological issues during an extraordinarily difficult time, even though it created a new set of challenges.

Many providers say they plan to continue offering teletherapy after the pandemic. Some states are making permanent the temporary pandemic rules that allow providers to be reimbursed at the same rates as for in-person visits, which is welcome news to practitioners who take patients’ insurance.

“We are in a mental health crisis right now, so more people are struggling and may be more open to accessing services,” said psychologist Allison Dempsey, PhD, associate professor at University of Colorado at Denver, Aurora. “It’s much easier to connect from your living room.”

The problem for patients who didn’t show up was often as simple as a canceled ride, said Jody Long, a clinical social worker who studied the 60% rate of no-shows or late cancellations at the University of Tennessee Health Science Center psychiatric clinic in Memphis.

But sometimes it was the health problem itself. Mr. Long remembers seeing a first-time patient drive around the parking lot and then exit. The patient later called and told Mr. Long, “I just could not get out of the car; please forgive me and reschedule me.”

Mr. Long, now an assistant professor at Jacksonville (Ala.) State University, said that incident changed his perspective. “I realized when you’re having panic attacks or anxiety attacks or suffering from major depressive disorder, it’s hard,” he said. “It’s like you have built up these walls for protection and then all of a sudden you’re having to let these walls down.”

Absences strain providers whose bosses set billing and productivity expectations and those in private practice who lose billable hours, said Dr. Dempsey, who directs a program to provide mental health care for families of babies with serious medical complications. Psychotherapists often overbooked patients with the expectation that some would not show up.

Now Dr. Dempsey and colleagues no longer need to overbook. When patients don’t show up, staffers can sometimes contact a patient right away and hold the session. Other times, they can reschedule them for later that day or a different day.

And telepsychiatry performs as well as, if not better than, face-to-face delivery of mental health services, according to a World Journal of Psychiatry review of 452 studies.

Virtual visits can also save patients money, because they might not need to travel, take time off work, or pay for child care, said Jay Shore, MD, MPH, chairperson of the American Psychiatric Association’s telepsychiatry committee and a psychiatrist at the University of Colorado.

Dr. Shore started examining the potential of video conferencing to reach rural patients in the late ’90s and concluded that patients and providers can virtually build rapport, which he said is fundamental for effective therapy and medicine management.

But before the pandemic, almost 64% of psychiatrists had never used telehealth, according to the psychiatric association. Amid widespread skepticism, providers then had to do “10 years of implementations in 10 days,” said Dr. Shore, who has consulted with Dr. Dempsey and other providers.

Dr. Dempsey and colleagues faced a steep learning curve. She said she recently held a video therapy session with a mother who “seemed very out of it” before disappearing from the screen while her baby was crying.

She wondered if the patient’s exit was related to the stress of new motherhood or “something more concerning,” like addiction. She thinks she might have better understood the woman’s condition had they been in the same room. The patient called Dr. Dempsey’s team that night and told them she had relapsed into drug use and been taken to the emergency room. The mental health providers directed her to a treatment program, Dr. Dempsey said.

“We spent a lot of time reviewing what happened with that case and thinking about what we need to do differently,” Dr. Dempsey said.

Providers now routinely ask for the name of someone to call if they lose a connection and can no longer reach the patient.

In another session, Dr. Dempsey noticed that a patient seemed guarded and saw her partner hovering in the background. She said she worried about the possibility of domestic violence or “some other form of controlling behavior.”

In such cases, Dr. Dempsey called after the appointments or sent the patients secure messages to their online health portal. She asked if they felt safe and suggested they talk in person.

Such inability to maintain privacy remains a concern.

In a Walmart parking lot recently, psychologist Kristy Keefe, PsyD, of Western Illinois University, Macomb, heard a patient talking with her therapist from her car. Dr. Keefe said she wondered if the patient “had no other safe place to go to.”

To avoid that scenario, Dr. Keefe does 30-minute consultations with patients before their first telehealth appointment. She asks if they have space to talk where no one can overhear them and makes sure they have sufficient internet access and know how to use video conferencing.

To ensure that she, too, was prepared, Dr. Keefe upgraded her WiFi router, purchased two white-noise machines to drown out her conversations, and placed a stop sign on her door during appointments so her 5-year-old son knew she was seeing patients.

Dr. Keefe concluded that audio alone sometimes works better than video, which often lags. Over the phone, she and her psychology students “got really sensitive to tone fluctuations” in a patient’s voice and were better able to “pick up the emotion” than with video conferencing.

With those telehealth visits, her 20% no-show rate evaporated.

Kate Barnes, a 29-year-old middle school teacher in Fayetteville, Ark., who struggles with anxiety and depression, also has found visits easier by phone than by Zoom, because she doesn’t feel like a spotlight is on her.

“I can focus more on what I want to say,” she said.

In one of Dr. Keefe’s video sessions, though, a patient reached out, touched the camera and started to cry as she said how appreciative she was that someone was there, Dr. Keefe recalled.

“I am so very thankful that they had something in this terrible time of loss and trauma and isolation,” said Dr. Keefe.

Demand for mental health services will likely continue even after the lifting of all COVID restrictions. About 41% of adults were suffering from anxiety or depression in January, compared with about 11% 2 years before, according to data from the U.S. Census Bureau and the National Health Interview Survey.

“That is not going to go away with snapping our fingers,” Dr. Dempsey said.

After the pandemic, Dr. Shore said, providers should review data from the past year and determine when virtual care or in-person care is more effective. He also said the health care industry needs to work to bridge the digital divide that exists because of lack of access to devices and broadband internet.

Even though Ms. Barnes said she did not see teletherapy as less effective than in-person therapy, she would like to return to seeing her therapist in person.

“When you are in person with someone, you can pick up on their body language better,” she said. “It’s a lot harder over a video call to do that.”

KHN  (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at  KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

When the COVID-19 pandemic forced behavioral health providers to stop seeing patients in person and instead hold therapy sessions remotely, the switch produced an unintended, positive consequence: Fewer patients skipped appointments.

RichLegg/E+

That had long been a problem in mental health care. Some outpatient programs previously had no-show rates as high as 60%, according to several studies.

Only 9% of psychiatrists reported that all patients kept their appointments before the pandemic, according to an American Psychiatric Association report. Once providers switched to telepsychiatry, that number increased to 32%.

Not only that, but providers and patients say teletherapy has largely been an effective lifeline for people struggling with anxiety, depression, and other psychological issues during an extraordinarily difficult time, even though it created a new set of challenges.

Many providers say they plan to continue offering teletherapy after the pandemic. Some states are making permanent the temporary pandemic rules that allow providers to be reimbursed at the same rates as for in-person visits, which is welcome news to practitioners who take patients’ insurance.

“We are in a mental health crisis right now, so more people are struggling and may be more open to accessing services,” said psychologist Allison Dempsey, PhD, associate professor at University of Colorado at Denver, Aurora. “It’s much easier to connect from your living room.”

The problem for patients who didn’t show up was often as simple as a canceled ride, said Jody Long, a clinical social worker who studied the 60% rate of no-shows or late cancellations at the University of Tennessee Health Science Center psychiatric clinic in Memphis.

But sometimes it was the health problem itself. Mr. Long remembers seeing a first-time patient drive around the parking lot and then exit. The patient later called and told Mr. Long, “I just could not get out of the car; please forgive me and reschedule me.”

Mr. Long, now an assistant professor at Jacksonville (Ala.) State University, said that incident changed his perspective. “I realized when you’re having panic attacks or anxiety attacks or suffering from major depressive disorder, it’s hard,” he said. “It’s like you have built up these walls for protection and then all of a sudden you’re having to let these walls down.”

Absences strain providers whose bosses set billing and productivity expectations and those in private practice who lose billable hours, said Dr. Dempsey, who directs a program to provide mental health care for families of babies with serious medical complications. Psychotherapists often overbooked patients with the expectation that some would not show up.

Now Dr. Dempsey and colleagues no longer need to overbook. When patients don’t show up, staffers can sometimes contact a patient right away and hold the session. Other times, they can reschedule them for later that day or a different day.

And telepsychiatry performs as well as, if not better than, face-to-face delivery of mental health services, according to a World Journal of Psychiatry review of 452 studies.

Virtual visits can also save patients money, because they might not need to travel, take time off work, or pay for child care, said Jay Shore, MD, MPH, chairperson of the American Psychiatric Association’s telepsychiatry committee and a psychiatrist at the University of Colorado.

Dr. Shore started examining the potential of video conferencing to reach rural patients in the late ’90s and concluded that patients and providers can virtually build rapport, which he said is fundamental for effective therapy and medicine management.

But before the pandemic, almost 64% of psychiatrists had never used telehealth, according to the psychiatric association. Amid widespread skepticism, providers then had to do “10 years of implementations in 10 days,” said Dr. Shore, who has consulted with Dr. Dempsey and other providers.

Dr. Dempsey and colleagues faced a steep learning curve. She said she recently held a video therapy session with a mother who “seemed very out of it” before disappearing from the screen while her baby was crying.

She wondered if the patient’s exit was related to the stress of new motherhood or “something more concerning,” like addiction. She thinks she might have better understood the woman’s condition had they been in the same room. The patient called Dr. Dempsey’s team that night and told them she had relapsed into drug use and been taken to the emergency room. The mental health providers directed her to a treatment program, Dr. Dempsey said.

“We spent a lot of time reviewing what happened with that case and thinking about what we need to do differently,” Dr. Dempsey said.

Providers now routinely ask for the name of someone to call if they lose a connection and can no longer reach the patient.

In another session, Dr. Dempsey noticed that a patient seemed guarded and saw her partner hovering in the background. She said she worried about the possibility of domestic violence or “some other form of controlling behavior.”

In such cases, Dr. Dempsey called after the appointments or sent the patients secure messages to their online health portal. She asked if they felt safe and suggested they talk in person.

Such inability to maintain privacy remains a concern.

In a Walmart parking lot recently, psychologist Kristy Keefe, PsyD, of Western Illinois University, Macomb, heard a patient talking with her therapist from her car. Dr. Keefe said she wondered if the patient “had no other safe place to go to.”

To avoid that scenario, Dr. Keefe does 30-minute consultations with patients before their first telehealth appointment. She asks if they have space to talk where no one can overhear them and makes sure they have sufficient internet access and know how to use video conferencing.

To ensure that she, too, was prepared, Dr. Keefe upgraded her WiFi router, purchased two white-noise machines to drown out her conversations, and placed a stop sign on her door during appointments so her 5-year-old son knew she was seeing patients.

Dr. Keefe concluded that audio alone sometimes works better than video, which often lags. Over the phone, she and her psychology students “got really sensitive to tone fluctuations” in a patient’s voice and were better able to “pick up the emotion” than with video conferencing.

With those telehealth visits, her 20% no-show rate evaporated.

Kate Barnes, a 29-year-old middle school teacher in Fayetteville, Ark., who struggles with anxiety and depression, also has found visits easier by phone than by Zoom, because she doesn’t feel like a spotlight is on her.

“I can focus more on what I want to say,” she said.

In one of Dr. Keefe’s video sessions, though, a patient reached out, touched the camera and started to cry as she said how appreciative she was that someone was there, Dr. Keefe recalled.

“I am so very thankful that they had something in this terrible time of loss and trauma and isolation,” said Dr. Keefe.

Demand for mental health services will likely continue even after the lifting of all COVID restrictions. About 41% of adults were suffering from anxiety or depression in January, compared with about 11% 2 years before, according to data from the U.S. Census Bureau and the National Health Interview Survey.

“That is not going to go away with snapping our fingers,” Dr. Dempsey said.

After the pandemic, Dr. Shore said, providers should review data from the past year and determine when virtual care or in-person care is more effective. He also said the health care industry needs to work to bridge the digital divide that exists because of lack of access to devices and broadband internet.

Even though Ms. Barnes said she did not see teletherapy as less effective than in-person therapy, she would like to return to seeing her therapist in person.

“When you are in person with someone, you can pick up on their body language better,” she said. “It’s a lot harder over a video call to do that.”

KHN  (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at  KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Look ma, I’m writing with no hands

Imagine being able to type every thought you had without using your hands, the words just magically appearing on the screen as fast as you can think of writing them down. Well, with the help of a new brain-computer interface (BCI), you can.

In a recent paper published in Nature, a team of researchers described how they developed a whole new way of communicating that blows previous BCIs, which used a method of pointing and clicking on letters, out of the water as far as accuracy and speed are concerned.

Developed for individuals with medical conditions or other disabilities that prevent them from communicating verbally or manually, the technology involves placing tiny sensors on the brain in the areas that control hand and arm movements. All the individual has to do is think of the process of writing and the system does the rest.

©Thinkstock

Chicken noodle salmonella

Chickens and ducks sure are cute, especially babies, but humans should be extra careful around these animals for risk of salmonella. This isn’t a new thing to loyal readers of Livin’ on the MDedge.

As more people keep such creatures at home – Emily Shoop of Penn State University told the N.Y. Times that raising poultry was “the fastest-growing animal-related hobby in the United States” – the ducks and chickens are being treated more like house pets, which is sweet but not safe.

In the latest outbreak, more than 160 people, mostly children under 5 years old, have fallen ill from salmonella poisoning and more than 30 have been hospitalized across 43 states, and the Centers for Disease Control and Prevention suspects the numbers could be higher because many did not get tested and recovered on their own.

JasonJiron/Thinkstock

This kidney research rocks!

When kids pick teams on the playground, someone is going to get their feelings hurt by being chosen last. There’s no way around it. Someone has to be last.

It’s the same way with research teams. When scientists are trying to cure diseases or pioneer new surgical techniques, they get a team together. And who always gets picked last? That’s right, the geologist, because who needs a geologist when you’re studying brain-computer interfaces?

Turns out, though, that there was a research team that needed a geologist: The one studying kidney stones.

Illinois geology professor Bruce Fouke explains: “The process of kidney stone formation is part of the natural process of the stone formation seen throughout nature. We are bringing together geology, biology, and medicine to map the entire process of kidney stone formation, step by step.”

Mayandi Sivaguru

Gene therapy: What is it good for? Absolutely nothing!

Gene therapy has the potential to permanently cure all sorts of terrible diseases, and one would assume that this would be something we all could agree on. Yes, no more cancer or diabetes or anything like that, no sane person could possibly be against this, right?

Oh, you poor naive fool.

To be fair, the report written by Goldman Sachs does lay out many potential applications for gene therapy, and all the markets it can expand into. But then the writers ask the question that they’re not supposed to say out loud: Is curing patients a sustainable business model?

Pogonic/Getty Images

Look ma, I’m writing with no hands

Imagine being able to type every thought you had without using your hands, the words just magically appearing on the screen as fast as you can think of writing them down. Well, with the help of a new brain-computer interface (BCI), you can.

In a recent paper published in Nature, a team of researchers described how they developed a whole new way of communicating that blows previous BCIs, which used a method of pointing and clicking on letters, out of the water as far as accuracy and speed are concerned.

Developed for individuals with medical conditions or other disabilities that prevent them from communicating verbally or manually, the technology involves placing tiny sensors on the brain in the areas that control hand and arm movements. All the individual has to do is think of the process of writing and the system does the rest.

©Thinkstock

Chicken noodle salmonella

Chickens and ducks sure are cute, especially babies, but humans should be extra careful around these animals for risk of salmonella. This isn’t a new thing to loyal readers of Livin’ on the MDedge.

As more people keep such creatures at home – Emily Shoop of Penn State University told the N.Y. Times that raising poultry was “the fastest-growing animal-related hobby in the United States” – the ducks and chickens are being treated more like house pets, which is sweet but not safe.

In the latest outbreak, more than 160 people, mostly children under 5 years old, have fallen ill from salmonella poisoning and more than 30 have been hospitalized across 43 states, and the Centers for Disease Control and Prevention suspects the numbers could be higher because many did not get tested and recovered on their own.

JasonJiron/Thinkstock

This kidney research rocks!

When kids pick teams on the playground, someone is going to get their feelings hurt by being chosen last. There’s no way around it. Someone has to be last.

It’s the same way with research teams. When scientists are trying to cure diseases or pioneer new surgical techniques, they get a team together. And who always gets picked last? That’s right, the geologist, because who needs a geologist when you’re studying brain-computer interfaces?

Turns out, though, that there was a research team that needed a geologist: The one studying kidney stones.

Illinois geology professor Bruce Fouke explains: “The process of kidney stone formation is part of the natural process of the stone formation seen throughout nature. We are bringing together geology, biology, and medicine to map the entire process of kidney stone formation, step by step.”

Mayandi Sivaguru

Gene therapy: What is it good for? Absolutely nothing!

Gene therapy has the potential to permanently cure all sorts of terrible diseases, and one would assume that this would be something we all could agree on. Yes, no more cancer or diabetes or anything like that, no sane person could possibly be against this, right?

Oh, you poor naive fool.

To be fair, the report written by Goldman Sachs does lay out many potential applications for gene therapy, and all the markets it can expand into. But then the writers ask the question that they’re not supposed to say out loud: Is curing patients a sustainable business model?

Pogonic/Getty Images

Look ma, I’m writing with no hands

Imagine being able to type every thought you had without using your hands, the words just magically appearing on the screen as fast as you can think of writing them down. Well, with the help of a new brain-computer interface (BCI), you can.

In a recent paper published in Nature, a team of researchers described how they developed a whole new way of communicating that blows previous BCIs, which used a method of pointing and clicking on letters, out of the water as far as accuracy and speed are concerned.

Developed for individuals with medical conditions or other disabilities that prevent them from communicating verbally or manually, the technology involves placing tiny sensors on the brain in the areas that control hand and arm movements. All the individual has to do is think of the process of writing and the system does the rest.

©Thinkstock

Chicken noodle salmonella

Chickens and ducks sure are cute, especially babies, but humans should be extra careful around these animals for risk of salmonella. This isn’t a new thing to loyal readers of Livin’ on the MDedge.

As more people keep such creatures at home – Emily Shoop of Penn State University told the N.Y. Times that raising poultry was “the fastest-growing animal-related hobby in the United States” – the ducks and chickens are being treated more like house pets, which is sweet but not safe.

In the latest outbreak, more than 160 people, mostly children under 5 years old, have fallen ill from salmonella poisoning and more than 30 have been hospitalized across 43 states, and the Centers for Disease Control and Prevention suspects the numbers could be higher because many did not get tested and recovered on their own.

JasonJiron/Thinkstock

This kidney research rocks!

When kids pick teams on the playground, someone is going to get their feelings hurt by being chosen last. There’s no way around it. Someone has to be last.

It’s the same way with research teams. When scientists are trying to cure diseases or pioneer new surgical techniques, they get a team together. And who always gets picked last? That’s right, the geologist, because who needs a geologist when you’re studying brain-computer interfaces?

Turns out, though, that there was a research team that needed a geologist: The one studying kidney stones.

Illinois geology professor Bruce Fouke explains: “The process of kidney stone formation is part of the natural process of the stone formation seen throughout nature. We are bringing together geology, biology, and medicine to map the entire process of kidney stone formation, step by step.”

Mayandi Sivaguru

Gene therapy: What is it good for? Absolutely nothing!

Gene therapy has the potential to permanently cure all sorts of terrible diseases, and one would assume that this would be something we all could agree on. Yes, no more cancer or diabetes or anything like that, no sane person could possibly be against this, right?

Oh, you poor naive fool.

To be fair, the report written by Goldman Sachs does lay out many potential applications for gene therapy, and all the markets it can expand into. But then the writers ask the question that they’re not supposed to say out loud: Is curing patients a sustainable business model?

Pogonic/Getty Images

Despite the shutdowns and plummeting patient volumes early in the COVID-19 pandemic, gastroenterologists’ earnings were just 3.1% lower in 2020 than in 2019, according to new survey results from Medscape.

That drop, from $419,000 to $406,000, was larger, however, than the average for all specialists, which slipped just 0.6% in 2020.

“Most gastroenterologists who saw a drop in income cited COVID-19–related issues, such as job loss, fewer hours, and fewer patients,” Keith L. Martin wrote in the 2021 Medscape Gastroenterologist Compensation Report.

Specialties with larger declines than gastroenterology included dermatology (–4%), pediatrics (–5%), and otolaryngology (–9%). Conversely, plastic surgeons saw the largest increases last year, with their average compensation rising 10% over 2019. Oncologists (+7%) and cardiologists (+5%) also did well, the Medscape data show.

For the physicians who did encounter financial hardships, relief came in several forms.

Many turned to “the federal Paycheck Protection Program to help keep themselves afloat; some were able to renegotiate their lease contracts; a large percentage reduced their staff, which reduced their expenses; and those in capitated plans were still getting paid even though they weren’t seeing as many patients,” Michael Belkin, JD, divisional vice president at Merritt Hawkins and Associates in Dallas, said in an interview.

One complication on the road to recovery was the furloughs experienced by some gastroenterologists, but work hours for the specialty have largely recovered. The prepandemic average was 53 hours per week, compared with 52 hours for this year’s gastroenterologist respondents, who represented about 2% of the 17,903 Medscape member physicians who completed the survey.

Among the gastroenterologists surveyed who did experience negative financial or practice-related effects from the pandemic, about one-third estimated that it would take 2-3 years for their income to return to the pre-COVID level, and 14% believe that it will never return to those levels. It is worth noting, however, that 45% of physicians overall reported no such harms last year.

Despite the drop in their incomes last year, more gastroenterologists said that they felt fairly compensated in 2020 than indicated as such in 2019 (55% vs. 52%). This year’s higher figure, though, is on the low end of the scale: of the 29 specialties included, only 4 were lower, and 19 were higher. Five others were the same, according to Medscape’s findings.

In other matters covered by the survey, gastroenterologists found themselves closer to the top. When asked if they would choose medicine again, 81% said yes. Only 8 of the 29 specialties were higher; 93% of gastroenterologists said they would choose gastroenterology again. Only four specialties were higher.

The survey was conducted from Oct. 6, 2020, to Feb. 11, 2021, and had a sampling error of ±0.73%. The salary figures were calculated using data for full-time physicians only.

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

Despite the shutdowns and plummeting patient volumes early in the COVID-19 pandemic, gastroenterologists’ earnings were just 3.1% lower in 2020 than in 2019, according to new survey results from Medscape.

That drop, from $419,000 to $406,000, was larger, however, than the average for all specialists, which slipped just 0.6% in 2020.

“Most gastroenterologists who saw a drop in income cited COVID-19–related issues, such as job loss, fewer hours, and fewer patients,” Keith L. Martin wrote in the 2021 Medscape Gastroenterologist Compensation Report.

Specialties with larger declines than gastroenterology included dermatology (–4%), pediatrics (–5%), and otolaryngology (–9%). Conversely, plastic surgeons saw the largest increases last year, with their average compensation rising 10% over 2019. Oncologists (+7%) and cardiologists (+5%) also did well, the Medscape data show.

For the physicians who did encounter financial hardships, relief came in several forms.

Many turned to “the federal Paycheck Protection Program to help keep themselves afloat; some were able to renegotiate their lease contracts; a large percentage reduced their staff, which reduced their expenses; and those in capitated plans were still getting paid even though they weren’t seeing as many patients,” Michael Belkin, JD, divisional vice president at Merritt Hawkins and Associates in Dallas, said in an interview.

One complication on the road to recovery was the furloughs experienced by some gastroenterologists, but work hours for the specialty have largely recovered. The prepandemic average was 53 hours per week, compared with 52 hours for this year’s gastroenterologist respondents, who represented about 2% of the 17,903 Medscape member physicians who completed the survey.

Among the gastroenterologists surveyed who did experience negative financial or practice-related effects from the pandemic, about one-third estimated that it would take 2-3 years for their income to return to the pre-COVID level, and 14% believe that it will never return to those levels. It is worth noting, however, that 45% of physicians overall reported no such harms last year.

Despite the drop in their incomes last year, more gastroenterologists said that they felt fairly compensated in 2020 than indicated as such in 2019 (55% vs. 52%). This year’s higher figure, though, is on the low end of the scale: of the 29 specialties included, only 4 were lower, and 19 were higher. Five others were the same, according to Medscape’s findings.

In other matters covered by the survey, gastroenterologists found themselves closer to the top. When asked if they would choose medicine again, 81% said yes. Only 8 of the 29 specialties were higher; 93% of gastroenterologists said they would choose gastroenterology again. Only four specialties were higher.

The survey was conducted from Oct. 6, 2020, to Feb. 11, 2021, and had a sampling error of ±0.73%. The salary figures were calculated using data for full-time physicians only.

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

Despite the shutdowns and plummeting patient volumes early in the COVID-19 pandemic, gastroenterologists’ earnings were just 3.1% lower in 2020 than in 2019, according to new survey results from Medscape.

That drop, from $419,000 to $406,000, was larger, however, than the average for all specialists, which slipped just 0.6% in 2020.

“Most gastroenterologists who saw a drop in income cited COVID-19–related issues, such as job loss, fewer hours, and fewer patients,” Keith L. Martin wrote in the 2021 Medscape Gastroenterologist Compensation Report.

Specialties with larger declines than gastroenterology included dermatology (–4%), pediatrics (–5%), and otolaryngology (–9%). Conversely, plastic surgeons saw the largest increases last year, with their average compensation rising 10% over 2019. Oncologists (+7%) and cardiologists (+5%) also did well, the Medscape data show.

For the physicians who did encounter financial hardships, relief came in several forms.

Many turned to “the federal Paycheck Protection Program to help keep themselves afloat; some were able to renegotiate their lease contracts; a large percentage reduced their staff, which reduced their expenses; and those in capitated plans were still getting paid even though they weren’t seeing as many patients,” Michael Belkin, JD, divisional vice president at Merritt Hawkins and Associates in Dallas, said in an interview.

One complication on the road to recovery was the furloughs experienced by some gastroenterologists, but work hours for the specialty have largely recovered. The prepandemic average was 53 hours per week, compared with 52 hours for this year’s gastroenterologist respondents, who represented about 2% of the 17,903 Medscape member physicians who completed the survey.

Among the gastroenterologists surveyed who did experience negative financial or practice-related effects from the pandemic, about one-third estimated that it would take 2-3 years for their income to return to the pre-COVID level, and 14% believe that it will never return to those levels. It is worth noting, however, that 45% of physicians overall reported no such harms last year.

Despite the drop in their incomes last year, more gastroenterologists said that they felt fairly compensated in 2020 than indicated as such in 2019 (55% vs. 52%). This year’s higher figure, though, is on the low end of the scale: of the 29 specialties included, only 4 were lower, and 19 were higher. Five others were the same, according to Medscape’s findings.

In other matters covered by the survey, gastroenterologists found themselves closer to the top. When asked if they would choose medicine again, 81% said yes. Only 8 of the 29 specialties were higher; 93% of gastroenterologists said they would choose gastroenterology again. Only four specialties were higher.

The survey was conducted from Oct. 6, 2020, to Feb. 11, 2021, and had a sampling error of ±0.73%. The salary figures were calculated using data for full-time physicians only.

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

Overuse of basal insulin rather than adding therapies that target mealtime glucose levels is a common problem in primary care management of type 2 diabetes that impedes achievement of optimal glycemic control, new research suggests.

Such ‘overbasalization,’ defined as a hemoglobin A1c of greater than 8% despite use of more than 0.5 units/kg per day of basal insulin, was identified in about 40% of patients seen in a Florida primary care clinic during 2015-2018. The findings were published in the April 2021 issue of Clinical Diabetes by Kevin Cowart, PharmD, a diabetes care and education specialist at the University of South Florida, Tampa, and colleagues.

The literature suggests that once people with type 2 diabetes start basal insulin, the chance that they’ll achieve a given hemoglobin A1c target, i.e., less than 7%, diminishes significantly if that goal isn’t achieved within the first year of starting insulin, Dr. Cowart said in an interview.

“Our analysis suggests that overbasalization plays a role in patients with type 2 diabetes on basal insulin not achieving optimal glycemic control. Basal insulin is not designed to address postprandial hyperglycemia. I think there’s a clear need to address hesitancy in therapeutic progression beyond basal insulin. A lot of factors underlie the delays, with therapeutic inertia being one of them. It’s complex,” he said.
 

Overbasalization seen in large proportion of patients

The study comprised 655 adults diagnosed with type 2 diabetes for at least a year who received a prescription for a basal insulin (glargine U-100, glargine U-300, detemir, degludec U-100, degludec U-200, regular U-500, or NPH insulin).

The patients had a mean hemoglobin A1c of 8.4% and a mean basal insulin dose 0.4 units/kg per day. The prevalence of overbasalization was 38.1% for those with hemoglobin A1c above 8%, 42.7% for those with A1c of 9% or above, and 42% with A1c of 10% or greater.

Patient characteristics independently associated with overbasalization were age 35-54 years (odds ratio 1.89), age 65-80 years (0.44), A1c 9% or greater (13.97), and A1c 10% or greater (6.04). Having a prescription for insulin glargine U-100 was associated with a lower overbasalization risk (0.62). In multivariate analysis, only an A1c of 9% or greater remained significant.

Rozalina G. McCoy, MD, an endocrinologist and primary care clinician at the Mayo Clinic, Rochester, Minn., said in an interview that she sees [overbasalization] frequently in patients who are referred to her. “It’s kind of that wall that patients with type 2 diabetes hit because their A1c is high but their fasting blood sugars are normal. Sometimes it’s assumed that there’s a discrepancy, because people don’t always think about postprandial hyperglycemia.”

She also noted that there has been a push in recent years to simplify regimens, particularly in older patients.

“We really want to avoid rapid-acting insulin in older patients because we’re afraid of hypoglycemia, so we start them on basal and keep the noninsulins like metformin and sulfonylureas around. Initially those control the postprandial blood sugar but over time they’re no longer enough.”
 

Options exist for addressing postmeal blood sugar highs while minimizing lows

While in the past adding premeal insulin was the only option, today there are alternatives for addressing postmeal hyperglycemia, at least in the short term.

Dr. Cowart advised that the first step is to have patients self-monitor their blood glucose and titrate their basal insulin to address fasting hyperglycemia first. Once that appropriate dose is reached, if the patient’s hemoglobin A1c is still above target, the next step is to evaluate the need for postmeal control.

For patients who are at high cardiovascular risk, the next step might involve adding a sodium-glucose cotransporter 2 inhibitor (SGLT2i) or a glucagon-like peptide 1 receptor agonist (GLP-1RA) instead of premeal insulin. But for patients in whom overbasalization is the main concern, a GLP-1RA might be the better choice since it will have a greater impact on postprandial glucose levels, while an SGLT2i will have more effect on fasting blood sugar, he said.

Another option is to use a fixed-dose combination of basal insulin and a glucagon-like peptide 1 receptor agonist (GLP-1RA), provided there aren’t cost or formulary barriers. “We want to use the right combination of drugs and not use too much of one to lead to hypoglycemia,” Dr. Cowart said.

Dr. McCoy doesn’t use fixed-dose combinations because they don’t allow as much flexibility in dosing. To correct overbasalization, she also recommends adding either a GLP-1RA or SGLT2i instead of premeal insulin. However, she cautions, “you still have to monitor those patients because after a few years it still won’t be enough and you’ll have to add mealtime insulin.”

If cost or lack of coverage prevents a patient’s use of SLGT2i/GLP-1RAs, Dr. McCoy said that adding just one premeal injection of rapid-acting insulin before the largest meal of the day is one option. Another is to use twice-daily NPH insulin instead of analog basal insulin, since that does offer some postprandial coverage.

Dr. Cowart said his approach in cost barrier situations is to try to use patient assistance programs and to look into the patient’s formulary to see if there is step therapy or tier considerations, and maybe have a discussion with the insurance company. “We often have to navigate that, and it does take a significant amount of time and could potentially delay patients getting the right therapy when it’s warranted. That is an area where there is a particular role for pharmacists in helping to overcome that and get patients on the right drugs,” he explained.
 

Problem may be even more common; testing is key

Dr. McCoy said that the A1c cutoff of 8% used to define overbasalization in the study probably resulted in an underestimation of the problem, since many patients are experiencing nighttime hypoglycemia from the basal insulin. The lows bring down their A1c level, but they’re still experiencing postmeal highs.

“I think they’re missing a lot of people, to be honest. I see a lot of patients with A1cs that aren’t that bad, say 7.5%, and their fasting blood sugars are okay, but if you were to put a [continuous glucose monitor] on those patients, invariably there’s hypoglycemia at night that no one knew about.”

Of course, for insurance reasons, most people with type 2 diabetes don’t currently have access to continuous glucose monitors. And often those who are not taking multiple daily injections are limited to one fingerstick test strip a day.

Dr. McCoy says that if hypoglycemia is a concern she will write a prior authorization justifying more test strips.

“I state explicitly in my notes why I recommend frequent monitoring. If they’re on a sulfonylurea, they should be able to check more frequently because they can have hypoglycemia. Same thing with basal insulin.”

Dr. McCoy advises that patients test their blood sugar 2 hours after the largest meal on one day, and at other times on different days. “Blood glucose after a meal shouldn’t be more than 200 [mg/dL]. If it is, that’s not a failure of basal insulin. It’s doing its job. You just need a different agent.”

Dr. Cowart has no disclosures. Dr. McCoy receives funding from the National Institutes of Health.

Overuse of basal insulin rather than adding therapies that target mealtime glucose levels is a common problem in primary care management of type 2 diabetes that impedes achievement of optimal glycemic control, new research suggests.

Such ‘overbasalization,’ defined as a hemoglobin A1c of greater than 8% despite use of more than 0.5 units/kg per day of basal insulin, was identified in about 40% of patients seen in a Florida primary care clinic during 2015-2018. The findings were published in the April 2021 issue of Clinical Diabetes by Kevin Cowart, PharmD, a diabetes care and education specialist at the University of South Florida, Tampa, and colleagues.

The literature suggests that once people with type 2 diabetes start basal insulin, the chance that they’ll achieve a given hemoglobin A1c target, i.e., less than 7%, diminishes significantly if that goal isn’t achieved within the first year of starting insulin, Dr. Cowart said in an interview.

“Our analysis suggests that overbasalization plays a role in patients with type 2 diabetes on basal insulin not achieving optimal glycemic control. Basal insulin is not designed to address postprandial hyperglycemia. I think there’s a clear need to address hesitancy in therapeutic progression beyond basal insulin. A lot of factors underlie the delays, with therapeutic inertia being one of them. It’s complex,” he said.
 

Overbasalization seen in large proportion of patients

The study comprised 655 adults diagnosed with type 2 diabetes for at least a year who received a prescription for a basal insulin (glargine U-100, glargine U-300, detemir, degludec U-100, degludec U-200, regular U-500, or NPH insulin).

The patients had a mean hemoglobin A1c of 8.4% and a mean basal insulin dose 0.4 units/kg per day. The prevalence of overbasalization was 38.1% for those with hemoglobin A1c above 8%, 42.7% for those with A1c of 9% or above, and 42% with A1c of 10% or greater.

Patient characteristics independently associated with overbasalization were age 35-54 years (odds ratio 1.89), age 65-80 years (0.44), A1c 9% or greater (13.97), and A1c 10% or greater (6.04). Having a prescription for insulin glargine U-100 was associated with a lower overbasalization risk (0.62). In multivariate analysis, only an A1c of 9% or greater remained significant.

Rozalina G. McCoy, MD, an endocrinologist and primary care clinician at the Mayo Clinic, Rochester, Minn., said in an interview that she sees [overbasalization] frequently in patients who are referred to her. “It’s kind of that wall that patients with type 2 diabetes hit because their A1c is high but their fasting blood sugars are normal. Sometimes it’s assumed that there’s a discrepancy, because people don’t always think about postprandial hyperglycemia.”

She also noted that there has been a push in recent years to simplify regimens, particularly in older patients.

“We really want to avoid rapid-acting insulin in older patients because we’re afraid of hypoglycemia, so we start them on basal and keep the noninsulins like metformin and sulfonylureas around. Initially those control the postprandial blood sugar but over time they’re no longer enough.”
 

Options exist for addressing postmeal blood sugar highs while minimizing lows

While in the past adding premeal insulin was the only option, today there are alternatives for addressing postmeal hyperglycemia, at least in the short term.

Dr. Cowart advised that the first step is to have patients self-monitor their blood glucose and titrate their basal insulin to address fasting hyperglycemia first. Once that appropriate dose is reached, if the patient’s hemoglobin A1c is still above target, the next step is to evaluate the need for postmeal control.

For patients who are at high cardiovascular risk, the next step might involve adding a sodium-glucose cotransporter 2 inhibitor (SGLT2i) or a glucagon-like peptide 1 receptor agonist (GLP-1RA) instead of premeal insulin. But for patients in whom overbasalization is the main concern, a GLP-1RA might be the better choice since it will have a greater impact on postprandial glucose levels, while an SGLT2i will have more effect on fasting blood sugar, he said.

Another option is to use a fixed-dose combination of basal insulin and a glucagon-like peptide 1 receptor agonist (GLP-1RA), provided there aren’t cost or formulary barriers. “We want to use the right combination of drugs and not use too much of one to lead to hypoglycemia,” Dr. Cowart said.

Dr. McCoy doesn’t use fixed-dose combinations because they don’t allow as much flexibility in dosing. To correct overbasalization, she also recommends adding either a GLP-1RA or SGLT2i instead of premeal insulin. However, she cautions, “you still have to monitor those patients because after a few years it still won’t be enough and you’ll have to add mealtime insulin.”

If cost or lack of coverage prevents a patient’s use of SLGT2i/GLP-1RAs, Dr. McCoy said that adding just one premeal injection of rapid-acting insulin before the largest meal of the day is one option. Another is to use twice-daily NPH insulin instead of analog basal insulin, since that does offer some postprandial coverage.

Dr. Cowart said his approach in cost barrier situations is to try to use patient assistance programs and to look into the patient’s formulary to see if there is step therapy or tier considerations, and maybe have a discussion with the insurance company. “We often have to navigate that, and it does take a significant amount of time and could potentially delay patients getting the right therapy when it’s warranted. That is an area where there is a particular role for pharmacists in helping to overcome that and get patients on the right drugs,” he explained.
 

Problem may be even more common; testing is key

Dr. McCoy said that the A1c cutoff of 8% used to define overbasalization in the study probably resulted in an underestimation of the problem, since many patients are experiencing nighttime hypoglycemia from the basal insulin. The lows bring down their A1c level, but they’re still experiencing postmeal highs.

“I think they’re missing a lot of people, to be honest. I see a lot of patients with A1cs that aren’t that bad, say 7.5%, and their fasting blood sugars are okay, but if you were to put a [continuous glucose monitor] on those patients, invariably there’s hypoglycemia at night that no one knew about.”

Of course, for insurance reasons, most people with type 2 diabetes don’t currently have access to continuous glucose monitors. And often those who are not taking multiple daily injections are limited to one fingerstick test strip a day.

Dr. McCoy says that if hypoglycemia is a concern she will write a prior authorization justifying more test strips.

“I state explicitly in my notes why I recommend frequent monitoring. If they’re on a sulfonylurea, they should be able to check more frequently because they can have hypoglycemia. Same thing with basal insulin.”

Dr. McCoy advises that patients test their blood sugar 2 hours after the largest meal on one day, and at other times on different days. “Blood glucose after a meal shouldn’t be more than 200 [mg/dL]. If it is, that’s not a failure of basal insulin. It’s doing its job. You just need a different agent.”

Dr. Cowart has no disclosures. Dr. McCoy receives funding from the National Institutes of Health.

Overuse of basal insulin rather than adding therapies that target mealtime glucose levels is a common problem in primary care management of type 2 diabetes that impedes achievement of optimal glycemic control, new research suggests.

Such ‘overbasalization,’ defined as a hemoglobin A1c of greater than 8% despite use of more than 0.5 units/kg per day of basal insulin, was identified in about 40% of patients seen in a Florida primary care clinic during 2015-2018. The findings were published in the April 2021 issue of Clinical Diabetes by Kevin Cowart, PharmD, a diabetes care and education specialist at the University of South Florida, Tampa, and colleagues.

The literature suggests that once people with type 2 diabetes start basal insulin, the chance that they’ll achieve a given hemoglobin A1c target, i.e., less than 7%, diminishes significantly if that goal isn’t achieved within the first year of starting insulin, Dr. Cowart said in an interview.

“Our analysis suggests that overbasalization plays a role in patients with type 2 diabetes on basal insulin not achieving optimal glycemic control. Basal insulin is not designed to address postprandial hyperglycemia. I think there’s a clear need to address hesitancy in therapeutic progression beyond basal insulin. A lot of factors underlie the delays, with therapeutic inertia being one of them. It’s complex,” he said.
 

Overbasalization seen in large proportion of patients

The study comprised 655 adults diagnosed with type 2 diabetes for at least a year who received a prescription for a basal insulin (glargine U-100, glargine U-300, detemir, degludec U-100, degludec U-200, regular U-500, or NPH insulin).

The patients had a mean hemoglobin A1c of 8.4% and a mean basal insulin dose 0.4 units/kg per day. The prevalence of overbasalization was 38.1% for those with hemoglobin A1c above 8%, 42.7% for those with A1c of 9% or above, and 42% with A1c of 10% or greater.

Patient characteristics independently associated with overbasalization were age 35-54 years (odds ratio 1.89), age 65-80 years (0.44), A1c 9% or greater (13.97), and A1c 10% or greater (6.04). Having a prescription for insulin glargine U-100 was associated with a lower overbasalization risk (0.62). In multivariate analysis, only an A1c of 9% or greater remained significant.

Rozalina G. McCoy, MD, an endocrinologist and primary care clinician at the Mayo Clinic, Rochester, Minn., said in an interview that she sees [overbasalization] frequently in patients who are referred to her. “It’s kind of that wall that patients with type 2 diabetes hit because their A1c is high but their fasting blood sugars are normal. Sometimes it’s assumed that there’s a discrepancy, because people don’t always think about postprandial hyperglycemia.”

She also noted that there has been a push in recent years to simplify regimens, particularly in older patients.

“We really want to avoid rapid-acting insulin in older patients because we’re afraid of hypoglycemia, so we start them on basal and keep the noninsulins like metformin and sulfonylureas around. Initially those control the postprandial blood sugar but over time they’re no longer enough.”
 

Options exist for addressing postmeal blood sugar highs while minimizing lows

While in the past adding premeal insulin was the only option, today there are alternatives for addressing postmeal hyperglycemia, at least in the short term.

Dr. Cowart advised that the first step is to have patients self-monitor their blood glucose and titrate their basal insulin to address fasting hyperglycemia first. Once that appropriate dose is reached, if the patient’s hemoglobin A1c is still above target, the next step is to evaluate the need for postmeal control.

For patients who are at high cardiovascular risk, the next step might involve adding a sodium-glucose cotransporter 2 inhibitor (SGLT2i) or a glucagon-like peptide 1 receptor agonist (GLP-1RA) instead of premeal insulin. But for patients in whom overbasalization is the main concern, a GLP-1RA might be the better choice since it will have a greater impact on postprandial glucose levels, while an SGLT2i will have more effect on fasting blood sugar, he said.

Another option is to use a fixed-dose combination of basal insulin and a glucagon-like peptide 1 receptor agonist (GLP-1RA), provided there aren’t cost or formulary barriers. “We want to use the right combination of drugs and not use too much of one to lead to hypoglycemia,” Dr. Cowart said.

Dr. McCoy doesn’t use fixed-dose combinations because they don’t allow as much flexibility in dosing. To correct overbasalization, she also recommends adding either a GLP-1RA or SGLT2i instead of premeal insulin. However, she cautions, “you still have to monitor those patients because after a few years it still won’t be enough and you’ll have to add mealtime insulin.”

If cost or lack of coverage prevents a patient’s use of SLGT2i/GLP-1RAs, Dr. McCoy said that adding just one premeal injection of rapid-acting insulin before the largest meal of the day is one option. Another is to use twice-daily NPH insulin instead of analog basal insulin, since that does offer some postprandial coverage.

Dr. Cowart said his approach in cost barrier situations is to try to use patient assistance programs and to look into the patient’s formulary to see if there is step therapy or tier considerations, and maybe have a discussion with the insurance company. “We often have to navigate that, and it does take a significant amount of time and could potentially delay patients getting the right therapy when it’s warranted. That is an area where there is a particular role for pharmacists in helping to overcome that and get patients on the right drugs,” he explained.
 

Problem may be even more common; testing is key

Dr. McCoy said that the A1c cutoff of 8% used to define overbasalization in the study probably resulted in an underestimation of the problem, since many patients are experiencing nighttime hypoglycemia from the basal insulin. The lows bring down their A1c level, but they’re still experiencing postmeal highs.

“I think they’re missing a lot of people, to be honest. I see a lot of patients with A1cs that aren’t that bad, say 7.5%, and their fasting blood sugars are okay, but if you were to put a [continuous glucose monitor] on those patients, invariably there’s hypoglycemia at night that no one knew about.”

Of course, for insurance reasons, most people with type 2 diabetes don’t currently have access to continuous glucose monitors. And often those who are not taking multiple daily injections are limited to one fingerstick test strip a day.

Dr. McCoy says that if hypoglycemia is a concern she will write a prior authorization justifying more test strips.

“I state explicitly in my notes why I recommend frequent monitoring. If they’re on a sulfonylurea, they should be able to check more frequently because they can have hypoglycemia. Same thing with basal insulin.”

Dr. McCoy advises that patients test their blood sugar 2 hours after the largest meal on one day, and at other times on different days. “Blood glucose after a meal shouldn’t be more than 200 [mg/dL]. If it is, that’s not a failure of basal insulin. It’s doing its job. You just need a different agent.”

Dr. Cowart has no disclosures. Dr. McCoy receives funding from the National Institutes of Health.