From the Journals

New recommendations from the WikiGuidelines Group offer strategies for the prevention, diagnosis, and management of urinary tract infections (UTIs) in children and adults.

While the guideline covers a range of clinical topics, including prophylaxis and antimicrobial stewardship, many key clinical questions remain unanswered because of a lack of high-quality evidence, according to lead author Zachary Nelson, PharmD, MPH, of HealthPartners and Park Nicollet Health Services, St. Louis Park, Minnesota, and colleagues.

“This guideline fills a critical gap by providing pragmatic, broadly applicable recommendations tailored for generalist care and systems-based practice,” Nelson and colleagues wrote in JAMA Network Open. “Our guidance is rooted in the best available evidence and is designed for clinicians from various backgrounds and healthcare environments. It emphasizes a patient-centered approach to the diagnosis, prevention, and treatment of UTIs and related genitourinary infections.”

The guideline panelists, including 54 experts from 12 countries, developed the document in accordance with Standards for Quality Improvement Reporting Excellence and the WikiGuidelines charter. The latter requires that “clear recommendations” are based on data from at least two concordant randomized clinical trials (RCTs), or one RCT plus one concordant prospective observational study.

This approach allowed the panel to provide clear recommendations for 6 out of 37 unique questions, while 3 other questions were partially answered. In other words, 75% of the questions lacked sufficient evidence for answers.

“These guidelines are important because they illuminate the clinical data and lack of data we have for approaching diagnosis and treatment of this common infection that leads to a wide array of morbidity and sometimes mortality, as well as significant cost burden to the healthcare system,” said coauthor Sarah Kurz, MD, clinical assistant professor of internal medicine at Michigan Medicine, Ann Arbor, in a written comment.

Jessica Hammett, MD, a urologist at Emory Healthcare, Atlanta, Georgia, who was not an author of the study, suggested that the guideline is additionally impactful because of the panel’s geographic diversity.

“It is an international collaboration that takes into account regional and international practice patterns and differences,” Hammett said in a written comment.

The key guideline recommendations are briefly summarized below.

Preventive Strategies for UTI

The guideline endorses cranberry products as preventive for UTI-prone women, children, and post-intervention patients, though data are insufficient to recommend them for older adults, those with bladder issues, or pregnant women.

Topical estrogen is recommended for postmenopausal women with recurrent UTIs, as it helps restore the vaginal microbiome with minimal systemic absorption. It may also benefit patients with breast cancer when nonhormonal alternatives fail.

For those with intact bladder anatomy, methenamine hippurate is suggested as a noninferior alternative to low-dose antibiotics for preventing recurrent UTIs.

“These findings confirm the best practice of starting postmenopausal women on vaginal estrogen to prevent UTIs, which is a treatment option that should be implemented more commonly,” Hammett said. “Interestingly as compared to the AUA guidelines, this paper recommends the use of cranberry supplementation and methenamine as antibiotic alternatives for preventing UTIs.”

 

Empirical Treatment Recommendations

According to the guideline, empirical treatment for UTIs should focus on antimicrobials with high urinary tract concentration and local pathogen efficacy.

Nitrofurantoin is recommended for uncomplicated cystitis, while trimethoprim/sulfamethoxazole (TMP/SMX) and first-generation cephalosporins are advised for pyelonephritis.

For intravenous therapy, ceftriaxone is preferred unless there are risk factors for multidrug resistance.

Recommended treatment durations include 5 days for nitrofurantoin, 3 days for TMP/SMX and fluoroquinolones, and a single dose for fosfomycin in acute cystitis cases. For acute pyelonephritis, fluoroquinolones are advised for 5-7 days, with dose-optimized beta-lactams for 7 days. Gram-negative bacteremia from urinary sources warrants a 7-day course.

 

Stewardship and Clinical Management

The guideline emphasizes antimicrobial stewardship, with support for antibiotic de-escalation and oral regimens where feasible, to reduce adverse effects and hospital stays. Although evidence is limited, the authors suggest thorough allergy assessment and selective reporting of susceptibility results to enhance antibiotic selection.

While data were insufficient to make clear recommendations about the treatment of asymptomatic bacteriuria, Nelson and colleagues suggested that this practice “risks side effects without benefit” while threatening antimicrobial sustainability.

Hammett agreed, noting that “[this] serves as an important reminder not to treat asymptomatic bacteriuria, as it increases side effects and bacterial resistance without any improvement as compared to placebo.”

 

Special Considerations for Urologic Procedures

Finally, patients undergoing urologic procedures, routine cystoscopy, and urodynamic studies generally do not require prophylactic antibiotics, according to the guideline. Single-dose antibiotic prophylaxis is recommended for low-risk nephrolithotomy patients, though high-risk individuals, such as those who are pregnant or post kidney transplant, may require extended prophylaxis.

Kurz suggested that the guideline consolidates and supports the foundation of evidence driving common practices.

“I don’t think these guidelines offer any strikingly new strategies, which is unsurprising, as they were created after a deep dive into existing literature,” Kurz said. “But more importantly, what I think they do is to highlight where and what the evidence is for many of the clinical strategies that are commonly employed. For example, in terms of prevention, it is common for primary care physicians, urologists, and infectious diseases doctors to recommend cranberry and hydration and to use methenamine. These guidelines highlight that there is sufficient quality and quantity of evidence to support these interventions.”

She also noted how the guidelines emphasize the need for symptoms to make a UTI diagnosis and advise against routine testing of asymptomatic individuals.

“Despite this not being new information, typical clinical practice is often out of step here, and this [guideline] reemphasizes the important factors when considering UTI diagnosis,” Kurz said.

Finally, she expressed frustration for the numerous knowledge gaps remaining in this area, which may be traced back to barriers ranging from the semantic to the more systemic.

“Some of the difficulty is lack of clear definitions and precise terminology regarding UTIs,” Kurz said, noting the unclear distinction between complicated and uncomplicated UTIs. “I would also argue that UTIs are a disease that predominantly affects women, and like many other diseases where this is the case, [they] tend to be less studied. Hopefully, this guideline’s spotlight on all that we do not know can inspire high-quality research to address these gaps, leading to optimal patient care along with decreased burden on the system as a whole in terms of cost and antimicrobial resistance.”

The study was funded by Merck. The WikiGuidelines Group that established this guideline is entirely voluntary and unpaid; the group intends to establish a nonprofit organization to support the development of other guidelines using this novel methodology and eventually intends to trademark the name WikiGuidelines. The authors disclosed relationships with Pfizer, Eumedica, GSK, and others.

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

New recommendations from the WikiGuidelines Group offer strategies for the prevention, diagnosis, and management of urinary tract infections (UTIs) in children and adults.

While the guideline covers a range of clinical topics, including prophylaxis and antimicrobial stewardship, many key clinical questions remain unanswered because of a lack of high-quality evidence, according to lead author Zachary Nelson, PharmD, MPH, of HealthPartners and Park Nicollet Health Services, St. Louis Park, Minnesota, and colleagues.

“This guideline fills a critical gap by providing pragmatic, broadly applicable recommendations tailored for generalist care and systems-based practice,” Nelson and colleagues wrote in JAMA Network Open. “Our guidance is rooted in the best available evidence and is designed for clinicians from various backgrounds and healthcare environments. It emphasizes a patient-centered approach to the diagnosis, prevention, and treatment of UTIs and related genitourinary infections.”

The guideline panelists, including 54 experts from 12 countries, developed the document in accordance with Standards for Quality Improvement Reporting Excellence and the WikiGuidelines charter. The latter requires that “clear recommendations” are based on data from at least two concordant randomized clinical trials (RCTs), or one RCT plus one concordant prospective observational study.

This approach allowed the panel to provide clear recommendations for 6 out of 37 unique questions, while 3 other questions were partially answered. In other words, 75% of the questions lacked sufficient evidence for answers.

“These guidelines are important because they illuminate the clinical data and lack of data we have for approaching diagnosis and treatment of this common infection that leads to a wide array of morbidity and sometimes mortality, as well as significant cost burden to the healthcare system,” said coauthor Sarah Kurz, MD, clinical assistant professor of internal medicine at Michigan Medicine, Ann Arbor, in a written comment.

Jessica Hammett, MD, a urologist at Emory Healthcare, Atlanta, Georgia, who was not an author of the study, suggested that the guideline is additionally impactful because of the panel’s geographic diversity.

“It is an international collaboration that takes into account regional and international practice patterns and differences,” Hammett said in a written comment.

The key guideline recommendations are briefly summarized below.

Preventive Strategies for UTI

The guideline endorses cranberry products as preventive for UTI-prone women, children, and post-intervention patients, though data are insufficient to recommend them for older adults, those with bladder issues, or pregnant women.

Topical estrogen is recommended for postmenopausal women with recurrent UTIs, as it helps restore the vaginal microbiome with minimal systemic absorption. It may also benefit patients with breast cancer when nonhormonal alternatives fail.

For those with intact bladder anatomy, methenamine hippurate is suggested as a noninferior alternative to low-dose antibiotics for preventing recurrent UTIs.

“These findings confirm the best practice of starting postmenopausal women on vaginal estrogen to prevent UTIs, which is a treatment option that should be implemented more commonly,” Hammett said. “Interestingly as compared to the AUA guidelines, this paper recommends the use of cranberry supplementation and methenamine as antibiotic alternatives for preventing UTIs.”

 

Empirical Treatment Recommendations

According to the guideline, empirical treatment for UTIs should focus on antimicrobials with high urinary tract concentration and local pathogen efficacy.

Nitrofurantoin is recommended for uncomplicated cystitis, while trimethoprim/sulfamethoxazole (TMP/SMX) and first-generation cephalosporins are advised for pyelonephritis.

For intravenous therapy, ceftriaxone is preferred unless there are risk factors for multidrug resistance.

Recommended treatment durations include 5 days for nitrofurantoin, 3 days for TMP/SMX and fluoroquinolones, and a single dose for fosfomycin in acute cystitis cases. For acute pyelonephritis, fluoroquinolones are advised for 5-7 days, with dose-optimized beta-lactams for 7 days. Gram-negative bacteremia from urinary sources warrants a 7-day course.

 

Stewardship and Clinical Management

The guideline emphasizes antimicrobial stewardship, with support for antibiotic de-escalation and oral regimens where feasible, to reduce adverse effects and hospital stays. Although evidence is limited, the authors suggest thorough allergy assessment and selective reporting of susceptibility results to enhance antibiotic selection.

While data were insufficient to make clear recommendations about the treatment of asymptomatic bacteriuria, Nelson and colleagues suggested that this practice “risks side effects without benefit” while threatening antimicrobial sustainability.

Hammett agreed, noting that “[this] serves as an important reminder not to treat asymptomatic bacteriuria, as it increases side effects and bacterial resistance without any improvement as compared to placebo.”

 

Special Considerations for Urologic Procedures

Finally, patients undergoing urologic procedures, routine cystoscopy, and urodynamic studies generally do not require prophylactic antibiotics, according to the guideline. Single-dose antibiotic prophylaxis is recommended for low-risk nephrolithotomy patients, though high-risk individuals, such as those who are pregnant or post kidney transplant, may require extended prophylaxis.

Kurz suggested that the guideline consolidates and supports the foundation of evidence driving common practices.

“I don’t think these guidelines offer any strikingly new strategies, which is unsurprising, as they were created after a deep dive into existing literature,” Kurz said. “But more importantly, what I think they do is to highlight where and what the evidence is for many of the clinical strategies that are commonly employed. For example, in terms of prevention, it is common for primary care physicians, urologists, and infectious diseases doctors to recommend cranberry and hydration and to use methenamine. These guidelines highlight that there is sufficient quality and quantity of evidence to support these interventions.”

She also noted how the guidelines emphasize the need for symptoms to make a UTI diagnosis and advise against routine testing of asymptomatic individuals.

“Despite this not being new information, typical clinical practice is often out of step here, and this [guideline] reemphasizes the important factors when considering UTI diagnosis,” Kurz said.

Finally, she expressed frustration for the numerous knowledge gaps remaining in this area, which may be traced back to barriers ranging from the semantic to the more systemic.

“Some of the difficulty is lack of clear definitions and precise terminology regarding UTIs,” Kurz said, noting the unclear distinction between complicated and uncomplicated UTIs. “I would also argue that UTIs are a disease that predominantly affects women, and like many other diseases where this is the case, [they] tend to be less studied. Hopefully, this guideline’s spotlight on all that we do not know can inspire high-quality research to address these gaps, leading to optimal patient care along with decreased burden on the system as a whole in terms of cost and antimicrobial resistance.”

The study was funded by Merck. The WikiGuidelines Group that established this guideline is entirely voluntary and unpaid; the group intends to establish a nonprofit organization to support the development of other guidelines using this novel methodology and eventually intends to trademark the name WikiGuidelines. The authors disclosed relationships with Pfizer, Eumedica, GSK, and others.

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

New recommendations from the WikiGuidelines Group offer strategies for the prevention, diagnosis, and management of urinary tract infections (UTIs) in children and adults.

While the guideline covers a range of clinical topics, including prophylaxis and antimicrobial stewardship, many key clinical questions remain unanswered because of a lack of high-quality evidence, according to lead author Zachary Nelson, PharmD, MPH, of HealthPartners and Park Nicollet Health Services, St. Louis Park, Minnesota, and colleagues.

“This guideline fills a critical gap by providing pragmatic, broadly applicable recommendations tailored for generalist care and systems-based practice,” Nelson and colleagues wrote in JAMA Network Open. “Our guidance is rooted in the best available evidence and is designed for clinicians from various backgrounds and healthcare environments. It emphasizes a patient-centered approach to the diagnosis, prevention, and treatment of UTIs and related genitourinary infections.”

The guideline panelists, including 54 experts from 12 countries, developed the document in accordance with Standards for Quality Improvement Reporting Excellence and the WikiGuidelines charter. The latter requires that “clear recommendations” are based on data from at least two concordant randomized clinical trials (RCTs), or one RCT plus one concordant prospective observational study.

This approach allowed the panel to provide clear recommendations for 6 out of 37 unique questions, while 3 other questions were partially answered. In other words, 75% of the questions lacked sufficient evidence for answers.

“These guidelines are important because they illuminate the clinical data and lack of data we have for approaching diagnosis and treatment of this common infection that leads to a wide array of morbidity and sometimes mortality, as well as significant cost burden to the healthcare system,” said coauthor Sarah Kurz, MD, clinical assistant professor of internal medicine at Michigan Medicine, Ann Arbor, in a written comment.

Jessica Hammett, MD, a urologist at Emory Healthcare, Atlanta, Georgia, who was not an author of the study, suggested that the guideline is additionally impactful because of the panel’s geographic diversity.

“It is an international collaboration that takes into account regional and international practice patterns and differences,” Hammett said in a written comment.

The key guideline recommendations are briefly summarized below.

Preventive Strategies for UTI

The guideline endorses cranberry products as preventive for UTI-prone women, children, and post-intervention patients, though data are insufficient to recommend them for older adults, those with bladder issues, or pregnant women.

Topical estrogen is recommended for postmenopausal women with recurrent UTIs, as it helps restore the vaginal microbiome with minimal systemic absorption. It may also benefit patients with breast cancer when nonhormonal alternatives fail.

For those with intact bladder anatomy, methenamine hippurate is suggested as a noninferior alternative to low-dose antibiotics for preventing recurrent UTIs.

“These findings confirm the best practice of starting postmenopausal women on vaginal estrogen to prevent UTIs, which is a treatment option that should be implemented more commonly,” Hammett said. “Interestingly as compared to the AUA guidelines, this paper recommends the use of cranberry supplementation and methenamine as antibiotic alternatives for preventing UTIs.”

 

Empirical Treatment Recommendations

According to the guideline, empirical treatment for UTIs should focus on antimicrobials with high urinary tract concentration and local pathogen efficacy.

Nitrofurantoin is recommended for uncomplicated cystitis, while trimethoprim/sulfamethoxazole (TMP/SMX) and first-generation cephalosporins are advised for pyelonephritis.

For intravenous therapy, ceftriaxone is preferred unless there are risk factors for multidrug resistance.

Recommended treatment durations include 5 days for nitrofurantoin, 3 days for TMP/SMX and fluoroquinolones, and a single dose for fosfomycin in acute cystitis cases. For acute pyelonephritis, fluoroquinolones are advised for 5-7 days, with dose-optimized beta-lactams for 7 days. Gram-negative bacteremia from urinary sources warrants a 7-day course.

 

Stewardship and Clinical Management

The guideline emphasizes antimicrobial stewardship, with support for antibiotic de-escalation and oral regimens where feasible, to reduce adverse effects and hospital stays. Although evidence is limited, the authors suggest thorough allergy assessment and selective reporting of susceptibility results to enhance antibiotic selection.

While data were insufficient to make clear recommendations about the treatment of asymptomatic bacteriuria, Nelson and colleagues suggested that this practice “risks side effects without benefit” while threatening antimicrobial sustainability.

Hammett agreed, noting that “[this] serves as an important reminder not to treat asymptomatic bacteriuria, as it increases side effects and bacterial resistance without any improvement as compared to placebo.”

 

Special Considerations for Urologic Procedures

Finally, patients undergoing urologic procedures, routine cystoscopy, and urodynamic studies generally do not require prophylactic antibiotics, according to the guideline. Single-dose antibiotic prophylaxis is recommended for low-risk nephrolithotomy patients, though high-risk individuals, such as those who are pregnant or post kidney transplant, may require extended prophylaxis.

Kurz suggested that the guideline consolidates and supports the foundation of evidence driving common practices.

“I don’t think these guidelines offer any strikingly new strategies, which is unsurprising, as they were created after a deep dive into existing literature,” Kurz said. “But more importantly, what I think they do is to highlight where and what the evidence is for many of the clinical strategies that are commonly employed. For example, in terms of prevention, it is common for primary care physicians, urologists, and infectious diseases doctors to recommend cranberry and hydration and to use methenamine. These guidelines highlight that there is sufficient quality and quantity of evidence to support these interventions.”

She also noted how the guidelines emphasize the need for symptoms to make a UTI diagnosis and advise against routine testing of asymptomatic individuals.

“Despite this not being new information, typical clinical practice is often out of step here, and this [guideline] reemphasizes the important factors when considering UTI diagnosis,” Kurz said.

Finally, she expressed frustration for the numerous knowledge gaps remaining in this area, which may be traced back to barriers ranging from the semantic to the more systemic.

“Some of the difficulty is lack of clear definitions and precise terminology regarding UTIs,” Kurz said, noting the unclear distinction between complicated and uncomplicated UTIs. “I would also argue that UTIs are a disease that predominantly affects women, and like many other diseases where this is the case, [they] tend to be less studied. Hopefully, this guideline’s spotlight on all that we do not know can inspire high-quality research to address these gaps, leading to optimal patient care along with decreased burden on the system as a whole in terms of cost and antimicrobial resistance.”

The study was funded by Merck. The WikiGuidelines Group that established this guideline is entirely voluntary and unpaid; the group intends to establish a nonprofit organization to support the development of other guidelines using this novel methodology and eventually intends to trademark the name WikiGuidelines. The authors disclosed relationships with Pfizer, Eumedica, GSK, and others.

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

TOPLINE:

Long-term treatment with TransCon parathyroid hormone (PTH), a replacement therapy for hypoparathyroidism, demonstrates sustained efficacy and safety in patients with hypoparathyroidism over 52 weeks, with 95% of participants able to discontinue conventional therapy.

METHODOLOGY:

• Conventional therapy for hypoparathyroidism (active vitamin D and elemental calcium) alleviates symptoms of hypocalcemia, but it does not improve insufficient PTH levels and is linked to long-term complications, such as nephrocalcinosis, nephrolithiasis, and renal dysfunction.
• This phase 3 (PaTHway) trial aimed to investigate the long-term efficacy, safety, and tolerability of TransCon PTH (palopegteriparatide) in adults with hypoparathyroidism.
• Overall, 82 patients with chronic hypoparathyroidism (mean age, 48.6 years; 78% women; 93% White) were randomly assigned to receive TransCon PTH or placebo, both coadministered with conventional therapy for 26 weeks.
• At the 26-week visit, patients who completed the blinded treatment (n = 79) were assigned to receive only TransCon PTH with conventional therapy in an ongoing 156-week open-label extension.
• For this analysis at week 52, the main efficacy endpoint was the proportion of patients (n = 78) with normal serum calcium levels (8.3-10.6 mg/dL) and independence from conventional therapy (active vitamin D and therapeutic doses of calcium); safety assessments included serum chemistries, 24-hour urine calcium excretion, and treatment-emergent adverse events.

TAKEAWAY:

• At week 52, the majority of the patients receiving TransCon PTH achieved normal serum calcium levels within the normal range (86%) and independence from conventional therapy (95%). None required active vitamin D.
• In secondary endpoints, patients receiving TransCon PTH showed sustained improvement in Hypoparathyroidism Patient Experience Scale scores, reflecting better symptom management, enhanced functioning, and overall well-being through week 52.
• At week 52, the mean 24-hour urine calcium excretion in patients first randomized to TransCon PTH was 185.1 mg/d, remaining well below the upper limit of normal (≤ 250 mg/d), while the placebo group mean fell to 223.1 mg/d during the open-label extension of TransCon PTH.
• TransCon PTH was well-tolerated, with most treatment-emergent adverse events being mild or moderate and none leading to treatment discontinuation.

IN PRACTICE:

“These results suggest that TransCon PTH may improve outcomes and advance the standard of care for adults living with hypoparathyroidism,” the authors wrote.

SOURCE:

The study was led by Bart L. Clarke, MD, Mayo Clinic, Rochester, Minnesota. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s limitations included the open-label design during the extension period, which may have introduced bias in patient-reported outcomes. Additionally, the study population was predominantly women and White, which may have limited the generalizability of the findings. Further research is needed to assess the long-term effects of TransCon PTH on renal complications. One patient died of fatal cardiac arrest deemed unrelated to the study drug.

DISCLOSURES:

The study was funded by Ascendis Pharma A/S. Seven authors declared being current or former employees of Ascendis Pharma. The other authors declared receiving grants, research funding, honoraria, serving as consultants, advisory board members, study investigators, and other ties with Ascendis Pharma and multiple other pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Long-term treatment with TransCon parathyroid hormone (PTH), a replacement therapy for hypoparathyroidism, demonstrates sustained efficacy and safety in patients with hypoparathyroidism over 52 weeks, with 95% of participants able to discontinue conventional therapy.

METHODOLOGY:

• Conventional therapy for hypoparathyroidism (active vitamin D and elemental calcium) alleviates symptoms of hypocalcemia, but it does not improve insufficient PTH levels and is linked to long-term complications, such as nephrocalcinosis, nephrolithiasis, and renal dysfunction.
• This phase 3 (PaTHway) trial aimed to investigate the long-term efficacy, safety, and tolerability of TransCon PTH (palopegteriparatide) in adults with hypoparathyroidism.
• Overall, 82 patients with chronic hypoparathyroidism (mean age, 48.6 years; 78% women; 93% White) were randomly assigned to receive TransCon PTH or placebo, both coadministered with conventional therapy for 26 weeks.
• At the 26-week visit, patients who completed the blinded treatment (n = 79) were assigned to receive only TransCon PTH with conventional therapy in an ongoing 156-week open-label extension.
• For this analysis at week 52, the main efficacy endpoint was the proportion of patients (n = 78) with normal serum calcium levels (8.3-10.6 mg/dL) and independence from conventional therapy (active vitamin D and therapeutic doses of calcium); safety assessments included serum chemistries, 24-hour urine calcium excretion, and treatment-emergent adverse events.

TAKEAWAY:

• At week 52, the majority of the patients receiving TransCon PTH achieved normal serum calcium levels within the normal range (86%) and independence from conventional therapy (95%). None required active vitamin D.
• In secondary endpoints, patients receiving TransCon PTH showed sustained improvement in Hypoparathyroidism Patient Experience Scale scores, reflecting better symptom management, enhanced functioning, and overall well-being through week 52.
• At week 52, the mean 24-hour urine calcium excretion in patients first randomized to TransCon PTH was 185.1 mg/d, remaining well below the upper limit of normal (≤ 250 mg/d), while the placebo group mean fell to 223.1 mg/d during the open-label extension of TransCon PTH.
• TransCon PTH was well-tolerated, with most treatment-emergent adverse events being mild or moderate and none leading to treatment discontinuation.

IN PRACTICE:

“These results suggest that TransCon PTH may improve outcomes and advance the standard of care for adults living with hypoparathyroidism,” the authors wrote.

SOURCE:

The study was led by Bart L. Clarke, MD, Mayo Clinic, Rochester, Minnesota. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s limitations included the open-label design during the extension period, which may have introduced bias in patient-reported outcomes. Additionally, the study population was predominantly women and White, which may have limited the generalizability of the findings. Further research is needed to assess the long-term effects of TransCon PTH on renal complications. One patient died of fatal cardiac arrest deemed unrelated to the study drug.

DISCLOSURES:

The study was funded by Ascendis Pharma A/S. Seven authors declared being current or former employees of Ascendis Pharma. The other authors declared receiving grants, research funding, honoraria, serving as consultants, advisory board members, study investigators, and other ties with Ascendis Pharma and multiple other pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Long-term treatment with TransCon parathyroid hormone (PTH), a replacement therapy for hypoparathyroidism, demonstrates sustained efficacy and safety in patients with hypoparathyroidism over 52 weeks, with 95% of participants able to discontinue conventional therapy.

METHODOLOGY:

• Conventional therapy for hypoparathyroidism (active vitamin D and elemental calcium) alleviates symptoms of hypocalcemia, but it does not improve insufficient PTH levels and is linked to long-term complications, such as nephrocalcinosis, nephrolithiasis, and renal dysfunction.
• This phase 3 (PaTHway) trial aimed to investigate the long-term efficacy, safety, and tolerability of TransCon PTH (palopegteriparatide) in adults with hypoparathyroidism.
• Overall, 82 patients with chronic hypoparathyroidism (mean age, 48.6 years; 78% women; 93% White) were randomly assigned to receive TransCon PTH or placebo, both coadministered with conventional therapy for 26 weeks.
• At the 26-week visit, patients who completed the blinded treatment (n = 79) were assigned to receive only TransCon PTH with conventional therapy in an ongoing 156-week open-label extension.
• For this analysis at week 52, the main efficacy endpoint was the proportion of patients (n = 78) with normal serum calcium levels (8.3-10.6 mg/dL) and independence from conventional therapy (active vitamin D and therapeutic doses of calcium); safety assessments included serum chemistries, 24-hour urine calcium excretion, and treatment-emergent adverse events.

TAKEAWAY:

• At week 52, the majority of the patients receiving TransCon PTH achieved normal serum calcium levels within the normal range (86%) and independence from conventional therapy (95%). None required active vitamin D.
• In secondary endpoints, patients receiving TransCon PTH showed sustained improvement in Hypoparathyroidism Patient Experience Scale scores, reflecting better symptom management, enhanced functioning, and overall well-being through week 52.
• At week 52, the mean 24-hour urine calcium excretion in patients first randomized to TransCon PTH was 185.1 mg/d, remaining well below the upper limit of normal (≤ 250 mg/d), while the placebo group mean fell to 223.1 mg/d during the open-label extension of TransCon PTH.
• TransCon PTH was well-tolerated, with most treatment-emergent adverse events being mild or moderate and none leading to treatment discontinuation.

IN PRACTICE:

“These results suggest that TransCon PTH may improve outcomes and advance the standard of care for adults living with hypoparathyroidism,” the authors wrote.

SOURCE:

The study was led by Bart L. Clarke, MD, Mayo Clinic, Rochester, Minnesota. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s limitations included the open-label design during the extension period, which may have introduced bias in patient-reported outcomes. Additionally, the study population was predominantly women and White, which may have limited the generalizability of the findings. Further research is needed to assess the long-term effects of TransCon PTH on renal complications. One patient died of fatal cardiac arrest deemed unrelated to the study drug.

DISCLOSURES:

The study was funded by Ascendis Pharma A/S. Seven authors declared being current or former employees of Ascendis Pharma. The other authors declared receiving grants, research funding, honoraria, serving as consultants, advisory board members, study investigators, and other ties with Ascendis Pharma and multiple other pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Signs of frailty may signal future dementia more than a decade before cognitive symptoms occur, in new findings that may provide a potential opportunity to identify high-risk populations for targeted enrollment in clinical trials of dementia prevention and treatment.

Results of an international study assessing frailty trajectories showed frailty levels notably increased in the 4-9 years before dementia diagnosis. Even among study participants whose baseline frailty measurement was taken prior to that acceleration period, frailty was still positively associated with dementia risk, the investigators noted.

“We found that with every four to five additional health problems, there is on average a 40% higher risk of developing dementia, while the risk is lower for people who are more physically fit,” said study investigator David Ward, PhD, of the Centre for Health Services Research, The University of Queensland, Brisbane, Australia.

The findings were published online in JAMA Neurology.

 

A Promising Biomarker

An accessible biomarker for both biologic age and dementia risk is essential for advancing dementia prevention and treatment strategies, the investigators noted, adding that growing evidence suggests frailty may be a promising candidate for this role.

To learn more about the association between frailty and dementia, Ward and his team analyzed data on 29,849 participants aged 60 years or above (mean age, 71.6 years; 62% women) who participated in four cohort studies: the English Longitudinal Study of Ageing (ELSA; n = 6771), the Health and Retirement Study (HRS; n = 9045), the Rush Memory and Aging Project (MAP; n = 1451), and the National Alzheimer’s Coordinating Center (NACC; n = 12,582).

The primary outcome was all-cause dementia. Depending on the cohort, dementia diagnoses were determined through cognitive testing, self- or family report of physician diagnosis, or a diagnosis by the study physician. Participants were excluded if they had cognitive impairment at baseline.

Investigators retrospectively determined frailty index scores by gathering information on health and functional outcomes for participants from each cohort. Only participants with frailty data on at least 30 deficits were included.

Commonly included deficits included high blood pressure, cancer, and chronic pain, as well as functional problems such as hearing impairment, difficulty with mobility, and challenges managing finances.

Investigators conducted follow-up visits with participants until they developed dementia or until the study ended, with follow-up periods varying across cohorts.

After adjustment for potential confounders, frailty scores were modeled using backward time scales.

Among participants who developed incident dementia (n = 3154), covariate-adjusted expected frailty index scores were, on average, higher in women than in men by 18.5% in ELSA, 20.9% in HRS, and 16.2% in MAP. There were no differences in frailty scores between sexes in the NACC cohort.

When measured on a timeline, as compared with those who didn’t develop dementia, frailty scores were significantly and consistently higher in the dementia groups 8-20 before dementia onset (20 years in HRS; 13 in MAP; 12 in ELSA; 8 in NACC).

Increases in the rates of frailty index scores began accelerating 4-9 years before dementia onset for the various cohorts, investigators noted.

In all four cohorts, each 0.1 increase in frailty scores was positively associated with increased dementia risk.

Adjusted hazard ratios [aHRs] ranged from 1.18 in the HRS cohort to 1.73 in the NACC cohort, which showed the strongest association.

In participants whose baseline frailty measurement was conducted before the predementia acceleration period began, the association of frailty scores and dementia risk was positive. These aHRs ranged from 1.18 in the HRS cohort to 1.43 in the NACC cohort.

 

The ‘Four Pillars’ of Prevention

The good news, investigators said, is that the long trajectory of frailty symptoms preceding dementia onset provides plenty of opportunity for intervention.

To slow the development of frailty, Ward suggested adhering to the “four pillars of frailty prevention and management,” which include good nutrition with plenty of protein, exercise, optimizing medications for chronic conditions, and maintaining a strong social network.

Ward suggested neurologists track frailty in their patients and pointed to a recent article focused on helping neurologists use frailty measures to influence care planning.

Study limitations include the possibility of reverse causality and the fact that investigators could not adjust for genetic risk for dementia.

 

Unclear Pathway

Commenting on the findings, Lycia Neumann, PhD, senior director of Health Services Research at the Alzheimer’s Association, noted that many studies over the years have shown a link between frailty and dementia. However, she cautioned that a link does not imply causation.

The pathway from frailty to dementia is not 100% clear, and both are complex conditions, said Neumann, who was not part of the study.

“Adopting healthy lifestyle behaviors early and consistently can help decrease the risk of — or postpone the onset of — both frailty and cognitive decline,” she said. Neumann added that physical activity, a healthy diet, social engagement, and controlling diabetes and blood pressure can also reduce the risk for dementia as well as cardiovascular disease.

The study was funded in part by the Deep Dementia Phenotyping Network through the Frailty and Dementia Special Interest Group. Ward and Neumann reported no relevant financial relationships.

 

A version of this article appeared on Medscape.com.

Signs of frailty may signal future dementia more than a decade before cognitive symptoms occur, in new findings that may provide a potential opportunity to identify high-risk populations for targeted enrollment in clinical trials of dementia prevention and treatment.

Results of an international study assessing frailty trajectories showed frailty levels notably increased in the 4-9 years before dementia diagnosis. Even among study participants whose baseline frailty measurement was taken prior to that acceleration period, frailty was still positively associated with dementia risk, the investigators noted.

“We found that with every four to five additional health problems, there is on average a 40% higher risk of developing dementia, while the risk is lower for people who are more physically fit,” said study investigator David Ward, PhD, of the Centre for Health Services Research, The University of Queensland, Brisbane, Australia.

The findings were published online in JAMA Neurology.

 

A Promising Biomarker

An accessible biomarker for both biologic age and dementia risk is essential for advancing dementia prevention and treatment strategies, the investigators noted, adding that growing evidence suggests frailty may be a promising candidate for this role.

To learn more about the association between frailty and dementia, Ward and his team analyzed data on 29,849 participants aged 60 years or above (mean age, 71.6 years; 62% women) who participated in four cohort studies: the English Longitudinal Study of Ageing (ELSA; n = 6771), the Health and Retirement Study (HRS; n = 9045), the Rush Memory and Aging Project (MAP; n = 1451), and the National Alzheimer’s Coordinating Center (NACC; n = 12,582).

The primary outcome was all-cause dementia. Depending on the cohort, dementia diagnoses were determined through cognitive testing, self- or family report of physician diagnosis, or a diagnosis by the study physician. Participants were excluded if they had cognitive impairment at baseline.

Investigators retrospectively determined frailty index scores by gathering information on health and functional outcomes for participants from each cohort. Only participants with frailty data on at least 30 deficits were included.

Commonly included deficits included high blood pressure, cancer, and chronic pain, as well as functional problems such as hearing impairment, difficulty with mobility, and challenges managing finances.

Investigators conducted follow-up visits with participants until they developed dementia or until the study ended, with follow-up periods varying across cohorts.

After adjustment for potential confounders, frailty scores were modeled using backward time scales.

Among participants who developed incident dementia (n = 3154), covariate-adjusted expected frailty index scores were, on average, higher in women than in men by 18.5% in ELSA, 20.9% in HRS, and 16.2% in MAP. There were no differences in frailty scores between sexes in the NACC cohort.

When measured on a timeline, as compared with those who didn’t develop dementia, frailty scores were significantly and consistently higher in the dementia groups 8-20 before dementia onset (20 years in HRS; 13 in MAP; 12 in ELSA; 8 in NACC).

Increases in the rates of frailty index scores began accelerating 4-9 years before dementia onset for the various cohorts, investigators noted.

In all four cohorts, each 0.1 increase in frailty scores was positively associated with increased dementia risk.

Adjusted hazard ratios [aHRs] ranged from 1.18 in the HRS cohort to 1.73 in the NACC cohort, which showed the strongest association.

In participants whose baseline frailty measurement was conducted before the predementia acceleration period began, the association of frailty scores and dementia risk was positive. These aHRs ranged from 1.18 in the HRS cohort to 1.43 in the NACC cohort.

 

The ‘Four Pillars’ of Prevention

The good news, investigators said, is that the long trajectory of frailty symptoms preceding dementia onset provides plenty of opportunity for intervention.

To slow the development of frailty, Ward suggested adhering to the “four pillars of frailty prevention and management,” which include good nutrition with plenty of protein, exercise, optimizing medications for chronic conditions, and maintaining a strong social network.

Ward suggested neurologists track frailty in their patients and pointed to a recent article focused on helping neurologists use frailty measures to influence care planning.

Study limitations include the possibility of reverse causality and the fact that investigators could not adjust for genetic risk for dementia.

 

Unclear Pathway

Commenting on the findings, Lycia Neumann, PhD, senior director of Health Services Research at the Alzheimer’s Association, noted that many studies over the years have shown a link between frailty and dementia. However, she cautioned that a link does not imply causation.

The pathway from frailty to dementia is not 100% clear, and both are complex conditions, said Neumann, who was not part of the study.

“Adopting healthy lifestyle behaviors early and consistently can help decrease the risk of — or postpone the onset of — both frailty and cognitive decline,” she said. Neumann added that physical activity, a healthy diet, social engagement, and controlling diabetes and blood pressure can also reduce the risk for dementia as well as cardiovascular disease.

The study was funded in part by the Deep Dementia Phenotyping Network through the Frailty and Dementia Special Interest Group. Ward and Neumann reported no relevant financial relationships.

 

A version of this article appeared on Medscape.com.

Signs of frailty may signal future dementia more than a decade before cognitive symptoms occur, in new findings that may provide a potential opportunity to identify high-risk populations for targeted enrollment in clinical trials of dementia prevention and treatment.

Results of an international study assessing frailty trajectories showed frailty levels notably increased in the 4-9 years before dementia diagnosis. Even among study participants whose baseline frailty measurement was taken prior to that acceleration period, frailty was still positively associated with dementia risk, the investigators noted.

“We found that with every four to five additional health problems, there is on average a 40% higher risk of developing dementia, while the risk is lower for people who are more physically fit,” said study investigator David Ward, PhD, of the Centre for Health Services Research, The University of Queensland, Brisbane, Australia.

The findings were published online in JAMA Neurology.

 

A Promising Biomarker

An accessible biomarker for both biologic age and dementia risk is essential for advancing dementia prevention and treatment strategies, the investigators noted, adding that growing evidence suggests frailty may be a promising candidate for this role.

To learn more about the association between frailty and dementia, Ward and his team analyzed data on 29,849 participants aged 60 years or above (mean age, 71.6 years; 62% women) who participated in four cohort studies: the English Longitudinal Study of Ageing (ELSA; n = 6771), the Health and Retirement Study (HRS; n = 9045), the Rush Memory and Aging Project (MAP; n = 1451), and the National Alzheimer’s Coordinating Center (NACC; n = 12,582).

The primary outcome was all-cause dementia. Depending on the cohort, dementia diagnoses were determined through cognitive testing, self- or family report of physician diagnosis, or a diagnosis by the study physician. Participants were excluded if they had cognitive impairment at baseline.

Investigators retrospectively determined frailty index scores by gathering information on health and functional outcomes for participants from each cohort. Only participants with frailty data on at least 30 deficits were included.

Commonly included deficits included high blood pressure, cancer, and chronic pain, as well as functional problems such as hearing impairment, difficulty with mobility, and challenges managing finances.

Investigators conducted follow-up visits with participants until they developed dementia or until the study ended, with follow-up periods varying across cohorts.

After adjustment for potential confounders, frailty scores were modeled using backward time scales.

Among participants who developed incident dementia (n = 3154), covariate-adjusted expected frailty index scores were, on average, higher in women than in men by 18.5% in ELSA, 20.9% in HRS, and 16.2% in MAP. There were no differences in frailty scores between sexes in the NACC cohort.

When measured on a timeline, as compared with those who didn’t develop dementia, frailty scores were significantly and consistently higher in the dementia groups 8-20 before dementia onset (20 years in HRS; 13 in MAP; 12 in ELSA; 8 in NACC).

Increases in the rates of frailty index scores began accelerating 4-9 years before dementia onset for the various cohorts, investigators noted.

In all four cohorts, each 0.1 increase in frailty scores was positively associated with increased dementia risk.

Adjusted hazard ratios [aHRs] ranged from 1.18 in the HRS cohort to 1.73 in the NACC cohort, which showed the strongest association.

In participants whose baseline frailty measurement was conducted before the predementia acceleration period began, the association of frailty scores and dementia risk was positive. These aHRs ranged from 1.18 in the HRS cohort to 1.43 in the NACC cohort.

 

The ‘Four Pillars’ of Prevention

The good news, investigators said, is that the long trajectory of frailty symptoms preceding dementia onset provides plenty of opportunity for intervention.

To slow the development of frailty, Ward suggested adhering to the “four pillars of frailty prevention and management,” which include good nutrition with plenty of protein, exercise, optimizing medications for chronic conditions, and maintaining a strong social network.

Ward suggested neurologists track frailty in their patients and pointed to a recent article focused on helping neurologists use frailty measures to influence care planning.

Study limitations include the possibility of reverse causality and the fact that investigators could not adjust for genetic risk for dementia.

 

Unclear Pathway

Commenting on the findings, Lycia Neumann, PhD, senior director of Health Services Research at the Alzheimer’s Association, noted that many studies over the years have shown a link between frailty and dementia. However, she cautioned that a link does not imply causation.

The pathway from frailty to dementia is not 100% clear, and both are complex conditions, said Neumann, who was not part of the study.

“Adopting healthy lifestyle behaviors early and consistently can help decrease the risk of — or postpone the onset of — both frailty and cognitive decline,” she said. Neumann added that physical activity, a healthy diet, social engagement, and controlling diabetes and blood pressure can also reduce the risk for dementia as well as cardiovascular disease.

The study was funded in part by the Deep Dementia Phenotyping Network through the Frailty and Dementia Special Interest Group. Ward and Neumann reported no relevant financial relationships.

 

A version of this article appeared on Medscape.com.

Canada’s National Guideline for the Clinical Management of Opioid Use Disorder (OUD) has been updated to reflect the latest literature. The new document recommends buprenorphine and methadone as first-line treatments for OUD.

Opioid use and OUD remain the leading causes of drug-related death worldwide. In Canada, the number of apparent opioid-related deaths increased from 2831 in 2016 to 8049 in 2023. Despite the expansion of treatment options, including the lifting of restrictions on methadone prescribing in 2018, there has been a substantial surge in opioid-related harms, the authors wrote.

“OUD and opioid-related harms have devastating outcomes for our communities across Canada,” author Ginette Poulin, MD, a family physician at the University of Manitoba in Winnipeg, Manitoba, Canada, said in a statement. “With the growing dangers associated with the illicit market, we need to ensure we are sharing the most relevant therapeutic tools and up-to-date knowledge to help providers and communities address this complex issue.”

The 2024 update, which was drafted by the Canadian Research Initiative in Substance Matters (CRISM), was published  in CMAJ.

 

Expanding Access

The COVID-19 pandemic marked an increase in opioid-related harms, senior author Julie Bruneau, MD, Canada research chair in addiction medicine and professor of family and emergency medicine at the Université de Montréal, in Quebec, Canada, told this news organization. Access to essential services and support for people with OUD became restricted, and the drug supply became toxic and volatile.

“In March 2018, CRISM published the first Canadian national clinical practice guideline to assist clinicians in making informed decisions regarding the clinical management of OUD, and recommendations were made in light of existing evidence on prioritizing available treatments,” said Bruneau.

“This guideline is intended for use by healthcare providers, including physicians, nurse practitioners, pharmacists, clinical psychologists, social workers, medical educators, and clinical care case managers with or without specialized experience in addiction treatment. We hope it will help expand access to evidence-based interventions for people with OUD beyond tertiary care,” she said.

Bruneau added that integrating first-line opioid agonist treatment into primary care could reduce stigma, increase early screening and patient retention, and help reduce Canada’s opioid crisis.

The CRISM guideline development team carried out a comprehensive systematic review of the literature published from January 1, 2017, to September 14, 2023. The team, which included patients with OUD, drafted and graded their recommendations using the Grading of Recommendations, Assessment, Development and Evaluation approach.

“First, OUD management should be based on a patient-centered approach, which includes respect for the patient’s rights, preferences, and dignity,” said Bruneau.

Highlights of the guideline include the following recommendations:

• Buprenorphine, with or without naloxone, and methadone can be used as standard first-line treatment options.
• Opioid agonist treatment with slow-release oral morphine should be made available and offered as a second-line option.
• Patients with OUD should not be offered withdrawal management as stand-alone treatment because it is associated with increased rates of relapse, morbidity, and mortality.
• Psychosocial treatment, interventions, and supports can be offered as adjunct treatments but should not be a mandatory component of standard treatment for OUD and should not prevent access to opioid agonist therapy.
• Harm reduction strategies should be offered as part of the continuum of care for patients with OUD.
• Pregnant people can be offered buprenorphine or methadone as treatment options.

Treating More Patients

“Too many people die from untreated opioid addiction in Canada,” coauthor Peter Selby, MD, director of medical education at the Centre for Addiction and Mental Health, said in a statement. “We have medicines that help people stop using, but too few patients are treated due to stigma and lack of prescribers knowing what to do. These national guidelines help them use proven medications to not only prevent death but also help people recover.”

“That both buprenorphine and methadone are now to be considered first-line therapy for the management of OUD is an important change to the guideline,” said Abhimanyu Sud, MD, PhD, research chair in primary care and population health systems at Humber River Health and assistant professor of family and community medicine at the University of Toronto. He did not participate in drafting the guidelines.

“There is a lot of good evidence that these agents are effective for the management of OUD. We had this idea that methadone was harder or somehow more unsafe than buprenorphine, and that buprenorphine was therefore a safer therapy that should be used more widely. Now we have very high-potency opioids that are circulating, and methadone, as a strong opioid agonist, has an important role to play. Clinical experience has borne that out, and this is reflected in the guidelines,” said Sud. 

“When we treat patients who are using fentanyl, for example, or fentanyl analogs, or they’re not sure what they are using because the drug supply has been so contaminated, you sometimes need another agent. Also, a lot of patients do not respond very well to buprenorphine, so for many people, a full agonist like methadone is needed,” he added.

Giving higher priority to slow-release morphine is a good move, and the drug’s use is likely to be safe when administered by a skilled clinician, said Akash Goel, MD, staff physician in the Department of Anesthesiology and Pain Medicine at St. Michael’s Hospital and assistant professor of anesthesiology and pain medicine at the University of Toronto. Goel was not involved in drafting the guideline. 

The updated document will empower patients to make informed decisions about their care, he said. “Buprenorphine, for example, may not be the right selection for all patients. The updated guideline recognizes this. So, for patients who are at risk of failing OUD therapy and going back to using, buprenorphine may not be the best option. The new guideline gives patients the opportunity to have a conversation with their healthcare providers and then decide what’s the best way forward for them.” 

The guideline was supported by Health Canada and the Canadian Institutes of Health Research (CIHR) via CRISM. Poulin reported receiving honoraria for presentations from the Master Clinician Alliance and Indivior outside this work. Bruneau reported receiving a CIHR research grant and a grant from Health Canada’s Substance Use and Addictions Program. Outside this work, Bruneau received a National Institutes of Health research grant and consulting fees for Gilead Sciences and AbbVie.

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

Canada’s National Guideline for the Clinical Management of Opioid Use Disorder (OUD) has been updated to reflect the latest literature. The new document recommends buprenorphine and methadone as first-line treatments for OUD.

Opioid use and OUD remain the leading causes of drug-related death worldwide. In Canada, the number of apparent opioid-related deaths increased from 2831 in 2016 to 8049 in 2023. Despite the expansion of treatment options, including the lifting of restrictions on methadone prescribing in 2018, there has been a substantial surge in opioid-related harms, the authors wrote.

“OUD and opioid-related harms have devastating outcomes for our communities across Canada,” author Ginette Poulin, MD, a family physician at the University of Manitoba in Winnipeg, Manitoba, Canada, said in a statement. “With the growing dangers associated with the illicit market, we need to ensure we are sharing the most relevant therapeutic tools and up-to-date knowledge to help providers and communities address this complex issue.”

The 2024 update, which was drafted by the Canadian Research Initiative in Substance Matters (CRISM), was published  in CMAJ.

 

Expanding Access

The COVID-19 pandemic marked an increase in opioid-related harms, senior author Julie Bruneau, MD, Canada research chair in addiction medicine and professor of family and emergency medicine at the Université de Montréal, in Quebec, Canada, told this news organization. Access to essential services and support for people with OUD became restricted, and the drug supply became toxic and volatile.

“In March 2018, CRISM published the first Canadian national clinical practice guideline to assist clinicians in making informed decisions regarding the clinical management of OUD, and recommendations were made in light of existing evidence on prioritizing available treatments,” said Bruneau.

“This guideline is intended for use by healthcare providers, including physicians, nurse practitioners, pharmacists, clinical psychologists, social workers, medical educators, and clinical care case managers with or without specialized experience in addiction treatment. We hope it will help expand access to evidence-based interventions for people with OUD beyond tertiary care,” she said.

Bruneau added that integrating first-line opioid agonist treatment into primary care could reduce stigma, increase early screening and patient retention, and help reduce Canada’s opioid crisis.

The CRISM guideline development team carried out a comprehensive systematic review of the literature published from January 1, 2017, to September 14, 2023. The team, which included patients with OUD, drafted and graded their recommendations using the Grading of Recommendations, Assessment, Development and Evaluation approach.

“First, OUD management should be based on a patient-centered approach, which includes respect for the patient’s rights, preferences, and dignity,” said Bruneau.

Highlights of the guideline include the following recommendations:

• Buprenorphine, with or without naloxone, and methadone can be used as standard first-line treatment options.
• Opioid agonist treatment with slow-release oral morphine should be made available and offered as a second-line option.
• Patients with OUD should not be offered withdrawal management as stand-alone treatment because it is associated with increased rates of relapse, morbidity, and mortality.
• Psychosocial treatment, interventions, and supports can be offered as adjunct treatments but should not be a mandatory component of standard treatment for OUD and should not prevent access to opioid agonist therapy.
• Harm reduction strategies should be offered as part of the continuum of care for patients with OUD.
• Pregnant people can be offered buprenorphine or methadone as treatment options.

Treating More Patients

“Too many people die from untreated opioid addiction in Canada,” coauthor Peter Selby, MD, director of medical education at the Centre for Addiction and Mental Health, said in a statement. “We have medicines that help people stop using, but too few patients are treated due to stigma and lack of prescribers knowing what to do. These national guidelines help them use proven medications to not only prevent death but also help people recover.”

“That both buprenorphine and methadone are now to be considered first-line therapy for the management of OUD is an important change to the guideline,” said Abhimanyu Sud, MD, PhD, research chair in primary care and population health systems at Humber River Health and assistant professor of family and community medicine at the University of Toronto. He did not participate in drafting the guidelines.

“There is a lot of good evidence that these agents are effective for the management of OUD. We had this idea that methadone was harder or somehow more unsafe than buprenorphine, and that buprenorphine was therefore a safer therapy that should be used more widely. Now we have very high-potency opioids that are circulating, and methadone, as a strong opioid agonist, has an important role to play. Clinical experience has borne that out, and this is reflected in the guidelines,” said Sud. 

“When we treat patients who are using fentanyl, for example, or fentanyl analogs, or they’re not sure what they are using because the drug supply has been so contaminated, you sometimes need another agent. Also, a lot of patients do not respond very well to buprenorphine, so for many people, a full agonist like methadone is needed,” he added.

Giving higher priority to slow-release morphine is a good move, and the drug’s use is likely to be safe when administered by a skilled clinician, said Akash Goel, MD, staff physician in the Department of Anesthesiology and Pain Medicine at St. Michael’s Hospital and assistant professor of anesthesiology and pain medicine at the University of Toronto. Goel was not involved in drafting the guideline. 

The updated document will empower patients to make informed decisions about their care, he said. “Buprenorphine, for example, may not be the right selection for all patients. The updated guideline recognizes this. So, for patients who are at risk of failing OUD therapy and going back to using, buprenorphine may not be the best option. The new guideline gives patients the opportunity to have a conversation with their healthcare providers and then decide what’s the best way forward for them.” 

The guideline was supported by Health Canada and the Canadian Institutes of Health Research (CIHR) via CRISM. Poulin reported receiving honoraria for presentations from the Master Clinician Alliance and Indivior outside this work. Bruneau reported receiving a CIHR research grant and a grant from Health Canada’s Substance Use and Addictions Program. Outside this work, Bruneau received a National Institutes of Health research grant and consulting fees for Gilead Sciences and AbbVie.

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

Canada’s National Guideline for the Clinical Management of Opioid Use Disorder (OUD) has been updated to reflect the latest literature. The new document recommends buprenorphine and methadone as first-line treatments for OUD.

Opioid use and OUD remain the leading causes of drug-related death worldwide. In Canada, the number of apparent opioid-related deaths increased from 2831 in 2016 to 8049 in 2023. Despite the expansion of treatment options, including the lifting of restrictions on methadone prescribing in 2018, there has been a substantial surge in opioid-related harms, the authors wrote.

“OUD and opioid-related harms have devastating outcomes for our communities across Canada,” author Ginette Poulin, MD, a family physician at the University of Manitoba in Winnipeg, Manitoba, Canada, said in a statement. “With the growing dangers associated with the illicit market, we need to ensure we are sharing the most relevant therapeutic tools and up-to-date knowledge to help providers and communities address this complex issue.”

The 2024 update, which was drafted by the Canadian Research Initiative in Substance Matters (CRISM), was published  in CMAJ.

 

Expanding Access

The COVID-19 pandemic marked an increase in opioid-related harms, senior author Julie Bruneau, MD, Canada research chair in addiction medicine and professor of family and emergency medicine at the Université de Montréal, in Quebec, Canada, told this news organization. Access to essential services and support for people with OUD became restricted, and the drug supply became toxic and volatile.

“In March 2018, CRISM published the first Canadian national clinical practice guideline to assist clinicians in making informed decisions regarding the clinical management of OUD, and recommendations were made in light of existing evidence on prioritizing available treatments,” said Bruneau.

“This guideline is intended for use by healthcare providers, including physicians, nurse practitioners, pharmacists, clinical psychologists, social workers, medical educators, and clinical care case managers with or without specialized experience in addiction treatment. We hope it will help expand access to evidence-based interventions for people with OUD beyond tertiary care,” she said.

Bruneau added that integrating first-line opioid agonist treatment into primary care could reduce stigma, increase early screening and patient retention, and help reduce Canada’s opioid crisis.

The CRISM guideline development team carried out a comprehensive systematic review of the literature published from January 1, 2017, to September 14, 2023. The team, which included patients with OUD, drafted and graded their recommendations using the Grading of Recommendations, Assessment, Development and Evaluation approach.

“First, OUD management should be based on a patient-centered approach, which includes respect for the patient’s rights, preferences, and dignity,” said Bruneau.

Highlights of the guideline include the following recommendations:

• Buprenorphine, with or without naloxone, and methadone can be used as standard first-line treatment options.
• Opioid agonist treatment with slow-release oral morphine should be made available and offered as a second-line option.
• Patients with OUD should not be offered withdrawal management as stand-alone treatment because it is associated with increased rates of relapse, morbidity, and mortality.
• Psychosocial treatment, interventions, and supports can be offered as adjunct treatments but should not be a mandatory component of standard treatment for OUD and should not prevent access to opioid agonist therapy.
• Harm reduction strategies should be offered as part of the continuum of care for patients with OUD.
• Pregnant people can be offered buprenorphine or methadone as treatment options.

Treating More Patients

“Too many people die from untreated opioid addiction in Canada,” coauthor Peter Selby, MD, director of medical education at the Centre for Addiction and Mental Health, said in a statement. “We have medicines that help people stop using, but too few patients are treated due to stigma and lack of prescribers knowing what to do. These national guidelines help them use proven medications to not only prevent death but also help people recover.”

“That both buprenorphine and methadone are now to be considered first-line therapy for the management of OUD is an important change to the guideline,” said Abhimanyu Sud, MD, PhD, research chair in primary care and population health systems at Humber River Health and assistant professor of family and community medicine at the University of Toronto. He did not participate in drafting the guidelines.

“There is a lot of good evidence that these agents are effective for the management of OUD. We had this idea that methadone was harder or somehow more unsafe than buprenorphine, and that buprenorphine was therefore a safer therapy that should be used more widely. Now we have very high-potency opioids that are circulating, and methadone, as a strong opioid agonist, has an important role to play. Clinical experience has borne that out, and this is reflected in the guidelines,” said Sud. 

“When we treat patients who are using fentanyl, for example, or fentanyl analogs, or they’re not sure what they are using because the drug supply has been so contaminated, you sometimes need another agent. Also, a lot of patients do not respond very well to buprenorphine, so for many people, a full agonist like methadone is needed,” he added.

Giving higher priority to slow-release morphine is a good move, and the drug’s use is likely to be safe when administered by a skilled clinician, said Akash Goel, MD, staff physician in the Department of Anesthesiology and Pain Medicine at St. Michael’s Hospital and assistant professor of anesthesiology and pain medicine at the University of Toronto. Goel was not involved in drafting the guideline. 

The updated document will empower patients to make informed decisions about their care, he said. “Buprenorphine, for example, may not be the right selection for all patients. The updated guideline recognizes this. So, for patients who are at risk of failing OUD therapy and going back to using, buprenorphine may not be the best option. The new guideline gives patients the opportunity to have a conversation with their healthcare providers and then decide what’s the best way forward for them.” 

The guideline was supported by Health Canada and the Canadian Institutes of Health Research (CIHR) via CRISM. Poulin reported receiving honoraria for presentations from the Master Clinician Alliance and Indivior outside this work. Bruneau reported receiving a CIHR research grant and a grant from Health Canada’s Substance Use and Addictions Program. Outside this work, Bruneau received a National Institutes of Health research grant and consulting fees for Gilead Sciences and AbbVie.

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

TOPLINE:

Atrial arrhythmias were found in 26% of patients with sickle cell disease (SCD), with a significant association with stroke history. Early detection and treatment of atrial arrhythmias may help prevent strokes in this population.

METHODOLOGY:

• A total of 130 adult patients with SCD were included in the DREPACOEUR prospective registry from November 2018 to November 2022.
• The patients underwent a comprehensive cardiac evaluation, including 24-hour electrocardiogram monitoring, echocardiography, and laboratory tests.
• The primary endpoint was the occurrence of atrial arrhythmias, defined by excessive supraventricular ectopic activity or any recent history of atrial fibrillation.
• Patients with a history of stroke or transient ischemic attack were also included in the PCDREP prospective registry for further assessment.
• Written informed consent was collected from all participating patients, and the study was approved by the ethics committee.
•  

TAKEAWAY:

• Atrial arrhythmias were found in 26% of patients with SCD, with a significant association with stroke history (P = .001).
• Age and left atrial volume were independently associated with atrial arrhythmias, with optimal cutoffs of 47 years and 55 mL/m², respectively.
• Patients with atrial arrhythmias had higher diastolic blood pressure, worse kidney function, and higher NT pro-BNP levels than those without arrhythmias.
• Atrial arrhythmias were associated with an increased risk for stroke unrelated to cerebral vasculopathy or other defined causes (odds ratio, 6.6; P = .009).
•  

“Atrial arrhythmias were found in 26% of patients with sickle cell anemia, with a significant association with stroke history,” wrote the authors of the study. In a commentary published concurrently, Jonathan Uniat, MD, of Children’s Hospital Los Angeles in California, wrote, “Early detection and treatment of atrial arrhythmias may help prevent strokes in this population.”

 

SOURCE:

The study was led by Thomas d’Humières, Henri Mondor Hospital in Créteil, France. It was published online on November 12 in Blood Advances.

 

LIMITATIONS:

This study was a pilot prospective study and was underpowered with atrial arrhythmias occurring in only 34 patients. The population was relatively old for sickle cell anemia (45 years), and the study was biased because patients were selected based on clinical criteria indicative of underlying cardiovascular abnormalities. The population was heterogeneous in terms of antiarrhythmic therapy, and overall, at an advanced stage of the disease with frequent organ complications.

 

DISCLOSURES:

The study was supported by grants from FHU-SENEC. Pablo Bartolucci received grants from Addmedica, the Fabre Foundation, Novartis, and Bluebird in the past 36 months; received consulting fees from Addmedica, Novartis, Roche, GBT, Bluebird, Emmaus, Hemanext, and Agios; received honoraria for lectures from Novartis, Addmedica, and Jazz Pharmaceuticals; and reported being a member of the Novartis steering committee and cofounder of Innovhem. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Atrial arrhythmias were found in 26% of patients with sickle cell disease (SCD), with a significant association with stroke history. Early detection and treatment of atrial arrhythmias may help prevent strokes in this population.

METHODOLOGY:

• A total of 130 adult patients with SCD were included in the DREPACOEUR prospective registry from November 2018 to November 2022.
• The patients underwent a comprehensive cardiac evaluation, including 24-hour electrocardiogram monitoring, echocardiography, and laboratory tests.
• The primary endpoint was the occurrence of atrial arrhythmias, defined by excessive supraventricular ectopic activity or any recent history of atrial fibrillation.
• Patients with a history of stroke or transient ischemic attack were also included in the PCDREP prospective registry for further assessment.
• Written informed consent was collected from all participating patients, and the study was approved by the ethics committee.
•  

TAKEAWAY:

• Atrial arrhythmias were found in 26% of patients with SCD, with a significant association with stroke history (P = .001).
• Age and left atrial volume were independently associated with atrial arrhythmias, with optimal cutoffs of 47 years and 55 mL/m², respectively.
• Patients with atrial arrhythmias had higher diastolic blood pressure, worse kidney function, and higher NT pro-BNP levels than those without arrhythmias.
• Atrial arrhythmias were associated with an increased risk for stroke unrelated to cerebral vasculopathy or other defined causes (odds ratio, 6.6; P = .009).
•  

“Atrial arrhythmias were found in 26% of patients with sickle cell anemia, with a significant association with stroke history,” wrote the authors of the study. In a commentary published concurrently, Jonathan Uniat, MD, of Children’s Hospital Los Angeles in California, wrote, “Early detection and treatment of atrial arrhythmias may help prevent strokes in this population.”

 

SOURCE:

The study was led by Thomas d’Humières, Henri Mondor Hospital in Créteil, France. It was published online on November 12 in Blood Advances.

 

LIMITATIONS:

This study was a pilot prospective study and was underpowered with atrial arrhythmias occurring in only 34 patients. The population was relatively old for sickle cell anemia (45 years), and the study was biased because patients were selected based on clinical criteria indicative of underlying cardiovascular abnormalities. The population was heterogeneous in terms of antiarrhythmic therapy, and overall, at an advanced stage of the disease with frequent organ complications.

 

DISCLOSURES:

The study was supported by grants from FHU-SENEC. Pablo Bartolucci received grants from Addmedica, the Fabre Foundation, Novartis, and Bluebird in the past 36 months; received consulting fees from Addmedica, Novartis, Roche, GBT, Bluebird, Emmaus, Hemanext, and Agios; received honoraria for lectures from Novartis, Addmedica, and Jazz Pharmaceuticals; and reported being a member of the Novartis steering committee and cofounder of Innovhem. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Atrial arrhythmias were found in 26% of patients with sickle cell disease (SCD), with a significant association with stroke history. Early detection and treatment of atrial arrhythmias may help prevent strokes in this population.

METHODOLOGY:

• A total of 130 adult patients with SCD were included in the DREPACOEUR prospective registry from November 2018 to November 2022.
• The patients underwent a comprehensive cardiac evaluation, including 24-hour electrocardiogram monitoring, echocardiography, and laboratory tests.
• The primary endpoint was the occurrence of atrial arrhythmias, defined by excessive supraventricular ectopic activity or any recent history of atrial fibrillation.
• Patients with a history of stroke or transient ischemic attack were also included in the PCDREP prospective registry for further assessment.
• Written informed consent was collected from all participating patients, and the study was approved by the ethics committee.
•  

TAKEAWAY:

• Atrial arrhythmias were found in 26% of patients with SCD, with a significant association with stroke history (P = .001).
• Age and left atrial volume were independently associated with atrial arrhythmias, with optimal cutoffs of 47 years and 55 mL/m², respectively.
• Patients with atrial arrhythmias had higher diastolic blood pressure, worse kidney function, and higher NT pro-BNP levels than those without arrhythmias.
• Atrial arrhythmias were associated with an increased risk for stroke unrelated to cerebral vasculopathy or other defined causes (odds ratio, 6.6; P = .009).
•  

“Atrial arrhythmias were found in 26% of patients with sickle cell anemia, with a significant association with stroke history,” wrote the authors of the study. In a commentary published concurrently, Jonathan Uniat, MD, of Children’s Hospital Los Angeles in California, wrote, “Early detection and treatment of atrial arrhythmias may help prevent strokes in this population.”

 

SOURCE:

The study was led by Thomas d’Humières, Henri Mondor Hospital in Créteil, France. It was published online on November 12 in Blood Advances.

 

LIMITATIONS:

This study was a pilot prospective study and was underpowered with atrial arrhythmias occurring in only 34 patients. The population was relatively old for sickle cell anemia (45 years), and the study was biased because patients were selected based on clinical criteria indicative of underlying cardiovascular abnormalities. The population was heterogeneous in terms of antiarrhythmic therapy, and overall, at an advanced stage of the disease with frequent organ complications.

 

DISCLOSURES:

The study was supported by grants from FHU-SENEC. Pablo Bartolucci received grants from Addmedica, the Fabre Foundation, Novartis, and Bluebird in the past 36 months; received consulting fees from Addmedica, Novartis, Roche, GBT, Bluebird, Emmaus, Hemanext, and Agios; received honoraria for lectures from Novartis, Addmedica, and Jazz Pharmaceuticals; and reported being a member of the Novartis steering committee and cofounder of Innovhem. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Vitamin K supplementation significantly reduced the frequency, intensity, and duration of nocturnal leg cramps in older adults. No adverse events related to vitamin K were identified.

METHODOLOGY:

• Researchers conducted a multicenter, double-blind, placebo-controlled randomized clinical trial in China from September 2022 to December 2023.
• A total of 199 participants aged ≥ 65 years with at least two documented episodes of nocturnal leg cramps during a 2-week screening period were included.
• Participants were randomized in a 1:1 ratio to receive either 180 μg of vitamin K (menaquinone 7) or a placebo daily for 8 weeks.
• The primary outcome was the mean number of nocturnal leg cramps per week, while secondary outcomes were the duration and severity of muscle cramps.
• The ethics committees of Third People’s Hospital of Chengdu and Affiliated Hospital of North Sichuan Medical College approved the study, and all participants provided written informed consent.

TAKEAWAY:

• Vitamin K group experienced a significant reduction in the mean weekly frequency of cramps (mean difference, 2.60 [SD, 0.81] to 0.96 [SD, 1.41]) compared with the placebo group, which maintained a mean weekly frequency of 3.63 (SD, 2.20) (P < .001).
• The severity of nocturnal leg cramps decreased more in the vitamin K group (mean difference, −2.55 [SD, 2.12] points) than in the placebo group (mean difference, −1.24 [SD, 1.16] points).
• The duration of nocturnal leg cramps also decreased more in the vitamin K group (mean difference, −0.90 [SD, 0.88] minutes) than in the placebo group (mean difference, −0.32 [SD, 0.78] minutes).
• No adverse events related to vitamin K use were identified, indicating a good safety profile for the supplementation.

IN PRACTICE:

“Given the generally benign characteristics of NLCs, treatment modality must be both effective and safe, thus minimizing the risk of iatrogenic harm,” the study authors wrote.

SOURCE:

This study was led by Jing Tan, MD, the Third People’s Hospital of Chengdu in Chengdu, China. It was published online on October 28 in JAMA Internal Medicine.

LIMITATIONS: 

This study did not investigate the quality of life or sleep, which could have provided additional insights into the impact of vitamin K on nocturnal leg cramps. The relatively mild nature of nocturnal leg cramps experienced by the participants may limit the generalizability of the findings to populations with more severe symptoms.

DISCLOSURES:

This study was supported by grants from China Health Promotion Foundation and the Third People’s Hospital of Chengdu Scientific Research Project. Tan disclosed receiving personal fees from BeiGene, AbbVie, Pfizer, Xian Janssen Pharmaceutical, and Takeda Pharmaceutical outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Vitamin K supplementation significantly reduced the frequency, intensity, and duration of nocturnal leg cramps in older adults. No adverse events related to vitamin K were identified.

METHODOLOGY:

• Researchers conducted a multicenter, double-blind, placebo-controlled randomized clinical trial in China from September 2022 to December 2023.
• A total of 199 participants aged ≥ 65 years with at least two documented episodes of nocturnal leg cramps during a 2-week screening period were included.
• Participants were randomized in a 1:1 ratio to receive either 180 μg of vitamin K (menaquinone 7) or a placebo daily for 8 weeks.
• The primary outcome was the mean number of nocturnal leg cramps per week, while secondary outcomes were the duration and severity of muscle cramps.
• The ethics committees of Third People’s Hospital of Chengdu and Affiliated Hospital of North Sichuan Medical College approved the study, and all participants provided written informed consent.

TAKEAWAY:

• Vitamin K group experienced a significant reduction in the mean weekly frequency of cramps (mean difference, 2.60 [SD, 0.81] to 0.96 [SD, 1.41]) compared with the placebo group, which maintained a mean weekly frequency of 3.63 (SD, 2.20) (P < .001).
• The severity of nocturnal leg cramps decreased more in the vitamin K group (mean difference, −2.55 [SD, 2.12] points) than in the placebo group (mean difference, −1.24 [SD, 1.16] points).
• The duration of nocturnal leg cramps also decreased more in the vitamin K group (mean difference, −0.90 [SD, 0.88] minutes) than in the placebo group (mean difference, −0.32 [SD, 0.78] minutes).
• No adverse events related to vitamin K use were identified, indicating a good safety profile for the supplementation.

IN PRACTICE:

“Given the generally benign characteristics of NLCs, treatment modality must be both effective and safe, thus minimizing the risk of iatrogenic harm,” the study authors wrote.

SOURCE:

This study was led by Jing Tan, MD, the Third People’s Hospital of Chengdu in Chengdu, China. It was published online on October 28 in JAMA Internal Medicine.

LIMITATIONS: 

This study did not investigate the quality of life or sleep, which could have provided additional insights into the impact of vitamin K on nocturnal leg cramps. The relatively mild nature of nocturnal leg cramps experienced by the participants may limit the generalizability of the findings to populations with more severe symptoms.

DISCLOSURES:

This study was supported by grants from China Health Promotion Foundation and the Third People’s Hospital of Chengdu Scientific Research Project. Tan disclosed receiving personal fees from BeiGene, AbbVie, Pfizer, Xian Janssen Pharmaceutical, and Takeda Pharmaceutical outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Vitamin K supplementation significantly reduced the frequency, intensity, and duration of nocturnal leg cramps in older adults. No adverse events related to vitamin K were identified.

METHODOLOGY:

• Researchers conducted a multicenter, double-blind, placebo-controlled randomized clinical trial in China from September 2022 to December 2023.
• A total of 199 participants aged ≥ 65 years with at least two documented episodes of nocturnal leg cramps during a 2-week screening period were included.
• Participants were randomized in a 1:1 ratio to receive either 180 μg of vitamin K (menaquinone 7) or a placebo daily for 8 weeks.
• The primary outcome was the mean number of nocturnal leg cramps per week, while secondary outcomes were the duration and severity of muscle cramps.
• The ethics committees of Third People’s Hospital of Chengdu and Affiliated Hospital of North Sichuan Medical College approved the study, and all participants provided written informed consent.

TAKEAWAY:

• Vitamin K group experienced a significant reduction in the mean weekly frequency of cramps (mean difference, 2.60 [SD, 0.81] to 0.96 [SD, 1.41]) compared with the placebo group, which maintained a mean weekly frequency of 3.63 (SD, 2.20) (P < .001).
• The severity of nocturnal leg cramps decreased more in the vitamin K group (mean difference, −2.55 [SD, 2.12] points) than in the placebo group (mean difference, −1.24 [SD, 1.16] points).
• The duration of nocturnal leg cramps also decreased more in the vitamin K group (mean difference, −0.90 [SD, 0.88] minutes) than in the placebo group (mean difference, −0.32 [SD, 0.78] minutes).
• No adverse events related to vitamin K use were identified, indicating a good safety profile for the supplementation.

IN PRACTICE:

“Given the generally benign characteristics of NLCs, treatment modality must be both effective and safe, thus minimizing the risk of iatrogenic harm,” the study authors wrote.

SOURCE:

This study was led by Jing Tan, MD, the Third People’s Hospital of Chengdu in Chengdu, China. It was published online on October 28 in JAMA Internal Medicine.

LIMITATIONS: 

This study did not investigate the quality of life or sleep, which could have provided additional insights into the impact of vitamin K on nocturnal leg cramps. The relatively mild nature of nocturnal leg cramps experienced by the participants may limit the generalizability of the findings to populations with more severe symptoms.

DISCLOSURES:

This study was supported by grants from China Health Promotion Foundation and the Third People’s Hospital of Chengdu Scientific Research Project. Tan disclosed receiving personal fees from BeiGene, AbbVie, Pfizer, Xian Janssen Pharmaceutical, and Takeda Pharmaceutical outside the submitted work.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.