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How Can Kidney Cancer Patients Benefit From New Combination Therapy?
Michael Serzan, MD, who works in the Lank Center for Genitourinary Oncology at the institute, stated this at the 2024 National Comprehensive Cancer Network Annual Conference, during a presentation.
A systematic review and meta-analysis published in 2022 in European Urology Open Science summarized six randomized controlled trials with a total of 5121 adult patients. In the review, the researchers found that immune checkpoint inhibitors plus vascular endothelial growth factor tyrosine kinase inhibitors (VEGF TKI) were associated with consistent improvements across all risk groups for metastatic renal cell carcinoma.
Additional newer research supports the use of immunotherapy combinations or other immunotherapy plus tyrosine kinase inhibitors as first-line or adjuvant treatments for renal cell carcinoma, Dr. Serzan said during an interview. However, more genomic and histology-directed therapies are needed, he noted.
Tips for Evaluating Risk When Treating Renal Cell Carcinoma?
For patients with localized clear cell renal cell carcinoma who have undergone partial or radical nephrectomy, there are several models that estimate the risk of recurrence based on pathologic tumor stage, grade, histology, invasion, and the extent of necrosis, Dr. Serzan said. These models can help guide selection of patients who may be at high risk of recurrence and, therefore, may benefit from adjuvant therapy.
For patients with metastatic clear cell renal cell carcinoma, the IMDC and MSKCC prognostic models stratify patients to favorable, intermediate, and poor risk groups based on clinical and lab factors. The IMDC risk stratification model is used as a prognostic model to stratify patients diagnosed with metastatic kidney cancer, Dr. Serzan said.
What Research Supports Treatments for Clear Cell and Non–Clear Cell Renal Cell Carcinoma?
The US Food and Drug Administration (FDA) approved pembrolizumab in 2021 for the adjuvant treatment of renal cell carcinoma (RCC) in patients with intermediate-risk or high-risk of recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions.
Pembrolizumab is the first adjuvant therapy shown to significantly improve overall survival in these patients, Dr. Serzan said. In the KEYNOTE-564 study, published in 2024 in the Journal of Clinical Oncology, pembrolizumab demonstrated an improvement in disease free survival as well as overall survival when compared with placebo.
Several similar studies of adjuvant immune checkpoint inhibitors for renal cell carcinoma involving atezolizumab vs. placebo, nivolumab plus ipilimumab vs. placebo, and nivolumab vs. observation have not shown significant benefits in terms of disease-free survival, Dr. Serzan noted.
The current NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer (Version: 3.2024), which were updated this year, support the use of adjuvant pembrolizumab for patients with stage II, III, or IV clear cell renal cell carcinoma after partial or radical nephrectomy, he said.
Looking ahead, biomarkers are needed to understand the risk of recurrence, and which patients benefit from adjuvant pembrolizumab, Dr. Serzan added.
Where Do VEGF-TKIs Fit In?
VEGF is a treatment target for renal cancer, and angiogenesis inhibition with VEGF TKIs continues to be a subject for study, Dr. Serzan said. In the CABOSUN study, published in the Journal of Clinical Oncology in 2017, patients were randomized to cabozantinib or sunitinib. Progression-free survival was significantly greater in the cabozantinib group, but overall survival was similar between the groups.
In another randomized trial, the CheckMate 214 study, patients received either sunitinib or a combination of nivolumab plus ipilimumab in four doses given every 3 weeks, followed by nivolumab alone every 2 weeks, and these patients were stratified by risk, Dr. Serzan noted.
The median progression-free survival was 12.4 months in the combination group vs. 8.5 months in the sunitinib group for patients at intermediate or poor risk of recurrence. The median progression-free survival was significantly greater in sunitinib patients with favorable risk vs. combination patients with favorable risk (28.9 months vs. 12.4 months).
Overall survival was higher for all patients with combination therapy vs. sunitinib regardless of risk stratification.
Dr. Serzan reviewed the pros of VEGF/PD1 (programmed death-ligand 1) combinations as including a high response rate (generally 52%-72%) and a low rate of primary progressive disease (5%-12%), as well as favorable progression-free and overall survival and low rates of immune-related adverse events.
However, cons of this treatment include lack of data on treatment-free survival as well as the decrease in progression-free survival and overall survival hazard ratios over time and potential chronic VEGF/TKI toxicities, he said.
What Treatments Are Recommended for Metastatic Clear Cell Renal Cell Carcinoma Now?
Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of kidney cancer, accounting for 70%-75% of cases, and these patients are prone to metastasis, recurrence, and resistance to radiotherapy and chemotherapy, according to authors of a recent review published in Frontiers in Oncology.
Dr. Serzan shared his preferred protocol for treatment-naive metastatic ccRCC patients, based on the NCCN guidelines for Kidney Cancer (Version: 3.2024) that had been updated in 2024.
For those with sarcomatoid features, he favors the use of nivolumab/ipilimumab combination, while those without sarcomatoid features, if highly symptomatic, may be treated with any of several combinations: nivolumab/ipilimumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.
For asymptomatic patients without sarcomatoid features, treatment depends on eligibility for immune checkpoint inhibitors or ipilimumab, Dr. Serzan said. His first choice for those eligible is nivolumab/ipilimumab; those not eligible for ipilimumab could receive nivolumab, pembrolizumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.
For patients not eligible for ICIs because of uncontrolled autoimmune disease, or high-dose glucocorticoids, Dr. Serzan recommended treatment with cabozantinib, lenvatinib/everolimus, pazopanib, or sunitinib.
What are Some Takeaway Points About Immunotherapy and Renal Cell Carcinoma?
“Immunotherapy has revolutionized treatment for renal cell carcinoma, with significant increases in overall survival, and a small but consistent cure fraction that was unimaginable 10 years ago,” Eric Jonasch, MD, of The University of Texas MD Anderson Cancer Center and vice-chair of the NCCN Guidelines Panel for Kidney Cancer, said in an interview.
However, challenges to implementing new treatments in clinical practice are ongoing, he said. The major challenges facing clinicians, patients, and their families include the cost of therapy, logistics of treatment administration, and managing toxicities, Dr. Jonasch said.
Patient selection is key to optimize outcomes with immunotherapy, and shared decision-making is essential to ensure that choice of therapy matches patient expectations and needs — and to maintain clear and open channels of communication while patients are on therapy, Dr. Jonasch said. “In my clinic, we empower patients to take treatment breaks to manage side effects, thereby optimizing quality of life while maintaining treatment efficacy,” he said.
Although significant progress has been made in managing renal cell carcinoma, more research is needed to increase the proportion of patients cured, said Dr. Jonasch. “A clearer understanding of the determinants of response and resistance, which will be driven by information rich clinical trials, will help move us in that direction,” he said.
Dr. Serzan had no financial conflicts to disclose. Dr. Jonasch disclosed research support from AbbVie, Arrowhead, Aveo, BMS, Corvus, Merck, NiKang, ProfoundBio, and Telix, as well as honoraria from Aveo, Eisai, Exelixis, GlaxoSmithKline, Ipsen, Merck, Novartis, NiKang, and Takeda.
Michael Serzan, MD, who works in the Lank Center for Genitourinary Oncology at the institute, stated this at the 2024 National Comprehensive Cancer Network Annual Conference, during a presentation.
A systematic review and meta-analysis published in 2022 in European Urology Open Science summarized six randomized controlled trials with a total of 5121 adult patients. In the review, the researchers found that immune checkpoint inhibitors plus vascular endothelial growth factor tyrosine kinase inhibitors (VEGF TKI) were associated with consistent improvements across all risk groups for metastatic renal cell carcinoma.
Additional newer research supports the use of immunotherapy combinations or other immunotherapy plus tyrosine kinase inhibitors as first-line or adjuvant treatments for renal cell carcinoma, Dr. Serzan said during an interview. However, more genomic and histology-directed therapies are needed, he noted.
Tips for Evaluating Risk When Treating Renal Cell Carcinoma?
For patients with localized clear cell renal cell carcinoma who have undergone partial or radical nephrectomy, there are several models that estimate the risk of recurrence based on pathologic tumor stage, grade, histology, invasion, and the extent of necrosis, Dr. Serzan said. These models can help guide selection of patients who may be at high risk of recurrence and, therefore, may benefit from adjuvant therapy.
For patients with metastatic clear cell renal cell carcinoma, the IMDC and MSKCC prognostic models stratify patients to favorable, intermediate, and poor risk groups based on clinical and lab factors. The IMDC risk stratification model is used as a prognostic model to stratify patients diagnosed with metastatic kidney cancer, Dr. Serzan said.
What Research Supports Treatments for Clear Cell and Non–Clear Cell Renal Cell Carcinoma?
The US Food and Drug Administration (FDA) approved pembrolizumab in 2021 for the adjuvant treatment of renal cell carcinoma (RCC) in patients with intermediate-risk or high-risk of recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions.
Pembrolizumab is the first adjuvant therapy shown to significantly improve overall survival in these patients, Dr. Serzan said. In the KEYNOTE-564 study, published in 2024 in the Journal of Clinical Oncology, pembrolizumab demonstrated an improvement in disease free survival as well as overall survival when compared with placebo.
Several similar studies of adjuvant immune checkpoint inhibitors for renal cell carcinoma involving atezolizumab vs. placebo, nivolumab plus ipilimumab vs. placebo, and nivolumab vs. observation have not shown significant benefits in terms of disease-free survival, Dr. Serzan noted.
The current NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer (Version: 3.2024), which were updated this year, support the use of adjuvant pembrolizumab for patients with stage II, III, or IV clear cell renal cell carcinoma after partial or radical nephrectomy, he said.
Looking ahead, biomarkers are needed to understand the risk of recurrence, and which patients benefit from adjuvant pembrolizumab, Dr. Serzan added.
Where Do VEGF-TKIs Fit In?
VEGF is a treatment target for renal cancer, and angiogenesis inhibition with VEGF TKIs continues to be a subject for study, Dr. Serzan said. In the CABOSUN study, published in the Journal of Clinical Oncology in 2017, patients were randomized to cabozantinib or sunitinib. Progression-free survival was significantly greater in the cabozantinib group, but overall survival was similar between the groups.
In another randomized trial, the CheckMate 214 study, patients received either sunitinib or a combination of nivolumab plus ipilimumab in four doses given every 3 weeks, followed by nivolumab alone every 2 weeks, and these patients were stratified by risk, Dr. Serzan noted.
The median progression-free survival was 12.4 months in the combination group vs. 8.5 months in the sunitinib group for patients at intermediate or poor risk of recurrence. The median progression-free survival was significantly greater in sunitinib patients with favorable risk vs. combination patients with favorable risk (28.9 months vs. 12.4 months).
Overall survival was higher for all patients with combination therapy vs. sunitinib regardless of risk stratification.
Dr. Serzan reviewed the pros of VEGF/PD1 (programmed death-ligand 1) combinations as including a high response rate (generally 52%-72%) and a low rate of primary progressive disease (5%-12%), as well as favorable progression-free and overall survival and low rates of immune-related adverse events.
However, cons of this treatment include lack of data on treatment-free survival as well as the decrease in progression-free survival and overall survival hazard ratios over time and potential chronic VEGF/TKI toxicities, he said.
What Treatments Are Recommended for Metastatic Clear Cell Renal Cell Carcinoma Now?
Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of kidney cancer, accounting for 70%-75% of cases, and these patients are prone to metastasis, recurrence, and resistance to radiotherapy and chemotherapy, according to authors of a recent review published in Frontiers in Oncology.
Dr. Serzan shared his preferred protocol for treatment-naive metastatic ccRCC patients, based on the NCCN guidelines for Kidney Cancer (Version: 3.2024) that had been updated in 2024.
For those with sarcomatoid features, he favors the use of nivolumab/ipilimumab combination, while those without sarcomatoid features, if highly symptomatic, may be treated with any of several combinations: nivolumab/ipilimumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.
For asymptomatic patients without sarcomatoid features, treatment depends on eligibility for immune checkpoint inhibitors or ipilimumab, Dr. Serzan said. His first choice for those eligible is nivolumab/ipilimumab; those not eligible for ipilimumab could receive nivolumab, pembrolizumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.
For patients not eligible for ICIs because of uncontrolled autoimmune disease, or high-dose glucocorticoids, Dr. Serzan recommended treatment with cabozantinib, lenvatinib/everolimus, pazopanib, or sunitinib.
What are Some Takeaway Points About Immunotherapy and Renal Cell Carcinoma?
“Immunotherapy has revolutionized treatment for renal cell carcinoma, with significant increases in overall survival, and a small but consistent cure fraction that was unimaginable 10 years ago,” Eric Jonasch, MD, of The University of Texas MD Anderson Cancer Center and vice-chair of the NCCN Guidelines Panel for Kidney Cancer, said in an interview.
However, challenges to implementing new treatments in clinical practice are ongoing, he said. The major challenges facing clinicians, patients, and their families include the cost of therapy, logistics of treatment administration, and managing toxicities, Dr. Jonasch said.
Patient selection is key to optimize outcomes with immunotherapy, and shared decision-making is essential to ensure that choice of therapy matches patient expectations and needs — and to maintain clear and open channels of communication while patients are on therapy, Dr. Jonasch said. “In my clinic, we empower patients to take treatment breaks to manage side effects, thereby optimizing quality of life while maintaining treatment efficacy,” he said.
Although significant progress has been made in managing renal cell carcinoma, more research is needed to increase the proportion of patients cured, said Dr. Jonasch. “A clearer understanding of the determinants of response and resistance, which will be driven by information rich clinical trials, will help move us in that direction,” he said.
Dr. Serzan had no financial conflicts to disclose. Dr. Jonasch disclosed research support from AbbVie, Arrowhead, Aveo, BMS, Corvus, Merck, NiKang, ProfoundBio, and Telix, as well as honoraria from Aveo, Eisai, Exelixis, GlaxoSmithKline, Ipsen, Merck, Novartis, NiKang, and Takeda.
Michael Serzan, MD, who works in the Lank Center for Genitourinary Oncology at the institute, stated this at the 2024 National Comprehensive Cancer Network Annual Conference, during a presentation.
A systematic review and meta-analysis published in 2022 in European Urology Open Science summarized six randomized controlled trials with a total of 5121 adult patients. In the review, the researchers found that immune checkpoint inhibitors plus vascular endothelial growth factor tyrosine kinase inhibitors (VEGF TKI) were associated with consistent improvements across all risk groups for metastatic renal cell carcinoma.
Additional newer research supports the use of immunotherapy combinations or other immunotherapy plus tyrosine kinase inhibitors as first-line or adjuvant treatments for renal cell carcinoma, Dr. Serzan said during an interview. However, more genomic and histology-directed therapies are needed, he noted.
Tips for Evaluating Risk When Treating Renal Cell Carcinoma?
For patients with localized clear cell renal cell carcinoma who have undergone partial or radical nephrectomy, there are several models that estimate the risk of recurrence based on pathologic tumor stage, grade, histology, invasion, and the extent of necrosis, Dr. Serzan said. These models can help guide selection of patients who may be at high risk of recurrence and, therefore, may benefit from adjuvant therapy.
For patients with metastatic clear cell renal cell carcinoma, the IMDC and MSKCC prognostic models stratify patients to favorable, intermediate, and poor risk groups based on clinical and lab factors. The IMDC risk stratification model is used as a prognostic model to stratify patients diagnosed with metastatic kidney cancer, Dr. Serzan said.
What Research Supports Treatments for Clear Cell and Non–Clear Cell Renal Cell Carcinoma?
The US Food and Drug Administration (FDA) approved pembrolizumab in 2021 for the adjuvant treatment of renal cell carcinoma (RCC) in patients with intermediate-risk or high-risk of recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions.
Pembrolizumab is the first adjuvant therapy shown to significantly improve overall survival in these patients, Dr. Serzan said. In the KEYNOTE-564 study, published in 2024 in the Journal of Clinical Oncology, pembrolizumab demonstrated an improvement in disease free survival as well as overall survival when compared with placebo.
Several similar studies of adjuvant immune checkpoint inhibitors for renal cell carcinoma involving atezolizumab vs. placebo, nivolumab plus ipilimumab vs. placebo, and nivolumab vs. observation have not shown significant benefits in terms of disease-free survival, Dr. Serzan noted.
The current NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer (Version: 3.2024), which were updated this year, support the use of adjuvant pembrolizumab for patients with stage II, III, or IV clear cell renal cell carcinoma after partial or radical nephrectomy, he said.
Looking ahead, biomarkers are needed to understand the risk of recurrence, and which patients benefit from adjuvant pembrolizumab, Dr. Serzan added.
Where Do VEGF-TKIs Fit In?
VEGF is a treatment target for renal cancer, and angiogenesis inhibition with VEGF TKIs continues to be a subject for study, Dr. Serzan said. In the CABOSUN study, published in the Journal of Clinical Oncology in 2017, patients were randomized to cabozantinib or sunitinib. Progression-free survival was significantly greater in the cabozantinib group, but overall survival was similar between the groups.
In another randomized trial, the CheckMate 214 study, patients received either sunitinib or a combination of nivolumab plus ipilimumab in four doses given every 3 weeks, followed by nivolumab alone every 2 weeks, and these patients were stratified by risk, Dr. Serzan noted.
The median progression-free survival was 12.4 months in the combination group vs. 8.5 months in the sunitinib group for patients at intermediate or poor risk of recurrence. The median progression-free survival was significantly greater in sunitinib patients with favorable risk vs. combination patients with favorable risk (28.9 months vs. 12.4 months).
Overall survival was higher for all patients with combination therapy vs. sunitinib regardless of risk stratification.
Dr. Serzan reviewed the pros of VEGF/PD1 (programmed death-ligand 1) combinations as including a high response rate (generally 52%-72%) and a low rate of primary progressive disease (5%-12%), as well as favorable progression-free and overall survival and low rates of immune-related adverse events.
However, cons of this treatment include lack of data on treatment-free survival as well as the decrease in progression-free survival and overall survival hazard ratios over time and potential chronic VEGF/TKI toxicities, he said.
What Treatments Are Recommended for Metastatic Clear Cell Renal Cell Carcinoma Now?
Clear cell renal cell carcinoma (ccRCC) is the most prevalent histological subtype of kidney cancer, accounting for 70%-75% of cases, and these patients are prone to metastasis, recurrence, and resistance to radiotherapy and chemotherapy, according to authors of a recent review published in Frontiers in Oncology.
Dr. Serzan shared his preferred protocol for treatment-naive metastatic ccRCC patients, based on the NCCN guidelines for Kidney Cancer (Version: 3.2024) that had been updated in 2024.
For those with sarcomatoid features, he favors the use of nivolumab/ipilimumab combination, while those without sarcomatoid features, if highly symptomatic, may be treated with any of several combinations: nivolumab/ipilimumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.
For asymptomatic patients without sarcomatoid features, treatment depends on eligibility for immune checkpoint inhibitors or ipilimumab, Dr. Serzan said. His first choice for those eligible is nivolumab/ipilimumab; those not eligible for ipilimumab could receive nivolumab, pembrolizumab, axitinib/pembrolizumab, cabozantinib/nivolumab, or lenvatinib/pembrolizumab.
For patients not eligible for ICIs because of uncontrolled autoimmune disease, or high-dose glucocorticoids, Dr. Serzan recommended treatment with cabozantinib, lenvatinib/everolimus, pazopanib, or sunitinib.
What are Some Takeaway Points About Immunotherapy and Renal Cell Carcinoma?
“Immunotherapy has revolutionized treatment for renal cell carcinoma, with significant increases in overall survival, and a small but consistent cure fraction that was unimaginable 10 years ago,” Eric Jonasch, MD, of The University of Texas MD Anderson Cancer Center and vice-chair of the NCCN Guidelines Panel for Kidney Cancer, said in an interview.
However, challenges to implementing new treatments in clinical practice are ongoing, he said. The major challenges facing clinicians, patients, and their families include the cost of therapy, logistics of treatment administration, and managing toxicities, Dr. Jonasch said.
Patient selection is key to optimize outcomes with immunotherapy, and shared decision-making is essential to ensure that choice of therapy matches patient expectations and needs — and to maintain clear and open channels of communication while patients are on therapy, Dr. Jonasch said. “In my clinic, we empower patients to take treatment breaks to manage side effects, thereby optimizing quality of life while maintaining treatment efficacy,” he said.
Although significant progress has been made in managing renal cell carcinoma, more research is needed to increase the proportion of patients cured, said Dr. Jonasch. “A clearer understanding of the determinants of response and resistance, which will be driven by information rich clinical trials, will help move us in that direction,” he said.
Dr. Serzan had no financial conflicts to disclose. Dr. Jonasch disclosed research support from AbbVie, Arrowhead, Aveo, BMS, Corvus, Merck, NiKang, ProfoundBio, and Telix, as well as honoraria from Aveo, Eisai, Exelixis, GlaxoSmithKline, Ipsen, Merck, Novartis, NiKang, and Takeda.
FROM NCCN 2024
Which Probiotics Are Effective in Irritable Bowel Syndrome?
PARIS — Irritable bowel syndrome (IBS) is a common brain-gut axis disorder, and patients are often dissatisfied with conventional treatments.
The role of the microbiota in IBS is now well established, and patients frequently take probiotics on their own initiative or on the advice of a physician or pharmacist. However, not all probiotics have equal efficacy, so which ones should be recommended?
Jean-Marc Sabaté, MD, PhD, a gastroenterologist at Avicenne Hospital in Bobigny, France, shared insights about probiotics at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.
IBS, according to the Rome IV symptom-based classification, is a “disorder of brain-gut axis interactions” with a prevalence of about 4% in the adult population. In France, during an average care pathway of about 8 years, patients try an average of five therapeutic strategies (and as many as 11), including antispasmodics (85%), diets (78%), and probiotics. In addition, 66.4% of patients had either taken or were taking probiotics at the time of a recent survey.
While the 2022 recommendations from the American College of Gastroenterology on the diagnosis and management of IBS do not support the use of probiotics for overall symptom relief — a recommendation for which they cite a low level of evidence — “there is nevertheless a rationale for prescribing probiotics in IBS due to the significant role of the microbiota (or dysbiosis) in this condition,” said Dr. Sabaté.
Microbiota in IBS
Evidence indicating that antibiotics exacerbate IBS symptoms and revealing chronic bacterial overgrowth in the small intestine of patients with IBS supports the role of the microbiota. Studies using a molecular approach (16s rRNA) have settled the debate, confirming differences in the intestinal flora between patients with IBS and healthy subjects. Data also indicate differences in flora between patient subtypes, such as an increased Firmicutes to Bacteroidetes ratio. However, one subgroup, which can represent as much as a third of patients, seems to harbor a “normal” microbiota.
Nonetheless, the microbiota plays a significant role in IBS. A Swedish study highlighted the influence of bacterial enterotypes on transit type associated with IBS and symptom severity, independent of diet composition or medication use.
This dysbiosis could play a significant role as it interacts with other mechanisms involved in IBS, including changes in intestinal motility related to diet (related to fermentable carbohydrates, for example). Moreover, the microbiota seems to induce a low level of immune activation in patients with IBS, leading to microinflammation and increased intestinal permeability, especially after an infection.
Furthermore, alterations in the regulation of bile acid deconjugation by the microbiota partly explain the frequency and consistency of stools in diarrhea-predominant IBS patients.
In addition, colonic gas production is higher in these patients. Those complaining of flatulence have poor tolerance to intestinal gases after a flatulent meal, associated with microbiota instability.
Data regarding the interaction between the microbiota and central mechanisms mainly come from animal studies. In rodents, microbiota constituents seem to affect brain development, function, and morphology. Emotional and physical traumas during childhood appear to be risk factors. Moreover, even brief exposure to broad-spectrum antibiotics in neonates could cause subsequent visceral hypersensitivity.
Lastly, the role of the microbiota in changes in medullary pain control after visceral stimulation (eg, rectal distension) has still not been demonstrated in humans.
Recent Guideline
In its February 2023 Global Guideline “Probiotics and Prebiotics” for IBS, the World Gastroenterology Organization looked at the level of evidence for probiotics.
Three strains, as well as a combination of several strains, were supported by level 2 evidence, meaning at least two randomized studies with converging results. These are Bifidobacterium bifidum MIMBb75, which improves overall symptoms and quality of life; Lactobacillus plantarum 299v (DSM 9843), which acts on the severity of abdominal pain and bloating; and B infantis 35624 (new name: B longum 35624), which improves the overall assessment of IBS symptoms, as does the multistrain product containing L rhamnosus GG, L rhamnosus LC705, Propionibacterium freudenreichii ssp shermanii JS DSM 7067, and B animalis ssp lactis B012 DSM 15954.
Efficacy and Availability
Probiotics belonging to the category of dietary supplements or medical devices are not required to provide evidence for a mechanism of action or even efficacy to be marketed. Thus, for most probiotics sold, there are no human or even animal studies available.
Dr. Sabaté proposed a choice of probiotics based on the literature and the presence of at least one randomized placebo-controlled trial conducted in patients with IBS showing positive results.
“,” he emphasized. The parameters that can be improved include symptom severity, quality of life, abdominal pain, and bloating.
Effective Probiotics
B longum 35624, which was developed with researchers from University College Cork in Ireland, is probably the most studied in animals and humans. Research has encompassed the mechanistic, clinical, and safety aspects of the probiotic. It has shown good results on the IBS-Symptom Severity Score (SSS), quality of life, abdominal pain, bowel disturbances, and bloating. The treatment duration in studies is 4-8 weeks.
L plantarum 299v (DSM 9843) affects the frequency of abdominal pain and pain score. The treatment duration in studies is 4 weeks.
The multistrain product that includes L plantarum CECT 7484/L plantarum CECT 7485/ Pediococcus acidilactici CECT 7483 allows for an improvement in quality of life and anxiety related to digestive symptoms. No positive effect has been described on digestive symptoms, especially diarrhea. The treatment duration is 6 weeks.
B bifidum MIMBb75 (both normal and heat-inactivated forms) is beneficial for pain, the composite IBS-SSS score, and quality of life. The treatment duration is 4-8 weeks.
“Except for the multistrain combination, which is more suited to patients with diarrhea-predominant IBS, the other three probiotics can be prescribed regardless of the IBS subtype,” said Dr. Sabaté. “Treatment durations are typically 4 weeks, but it is possible to continue up to 8 weeks, which is the maximum duration of these studies. In practice, there are no tolerance issues with probiotics prescribed for IBS based on the literature. These should be tested under the conditions and for the duration of the published studies and should only be continued if there is individual benefit on symptoms or quality of life.”
Note that microbiota analyses conducted for individual purposes are of no help in choosing probiotics.
Mechanisms of Action
In a murine model, but not in humans, some strains, especially L acidophilus NCFM, have shown an antinociceptive effect by inducing opioid and cannabinoid receptors.
Only in animals to date, L farciminis and B lactis CNCM I-2494 have shown prevention of induced hypersensitivity (ie, inhibition of the cytoskeleton contraction of colon epithelial cells and subsequent opening of tight junctions).
B infantis 35624 has an anti-inflammatory action by modifying the IL-10 and IL-12 cytokine ratio in animals and humans. It has an immunomodulatory action by increasing dendritic cells in the mucosa and decreasing Th1 and Th7 helper T cells.
B infantis 35624 and L farciminis are two strains that decrease visceral sensitivity in mice.
Escherichia coli Nissle 1917 acts on lipopeptide production with an antinociceptive effect, as observed in mice, by decreasing visceral sensitivity through calcium nociceptor flux blockade (action on GABA type B receptor).
Acting on dysbiosis by modifying fecal microbiota during probiotic intake is possible but depends on the probiotics, like B infantis 35624. In humans, B longum NCC 3001 could modify brain activations.
Dr. Sabaté disclosed financial relationships with Mayoly Spindler, Kyowa Kirin, Tillotts, Servier, Norgine, Biocodex, Merck, Viatris, Abivax, and Inventiva.
This story was translated from the Medscape French edition 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.
PARIS — Irritable bowel syndrome (IBS) is a common brain-gut axis disorder, and patients are often dissatisfied with conventional treatments.
The role of the microbiota in IBS is now well established, and patients frequently take probiotics on their own initiative or on the advice of a physician or pharmacist. However, not all probiotics have equal efficacy, so which ones should be recommended?
Jean-Marc Sabaté, MD, PhD, a gastroenterologist at Avicenne Hospital in Bobigny, France, shared insights about probiotics at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.
IBS, according to the Rome IV symptom-based classification, is a “disorder of brain-gut axis interactions” with a prevalence of about 4% in the adult population. In France, during an average care pathway of about 8 years, patients try an average of five therapeutic strategies (and as many as 11), including antispasmodics (85%), diets (78%), and probiotics. In addition, 66.4% of patients had either taken or were taking probiotics at the time of a recent survey.
While the 2022 recommendations from the American College of Gastroenterology on the diagnosis and management of IBS do not support the use of probiotics for overall symptom relief — a recommendation for which they cite a low level of evidence — “there is nevertheless a rationale for prescribing probiotics in IBS due to the significant role of the microbiota (or dysbiosis) in this condition,” said Dr. Sabaté.
Microbiota in IBS
Evidence indicating that antibiotics exacerbate IBS symptoms and revealing chronic bacterial overgrowth in the small intestine of patients with IBS supports the role of the microbiota. Studies using a molecular approach (16s rRNA) have settled the debate, confirming differences in the intestinal flora between patients with IBS and healthy subjects. Data also indicate differences in flora between patient subtypes, such as an increased Firmicutes to Bacteroidetes ratio. However, one subgroup, which can represent as much as a third of patients, seems to harbor a “normal” microbiota.
Nonetheless, the microbiota plays a significant role in IBS. A Swedish study highlighted the influence of bacterial enterotypes on transit type associated with IBS and symptom severity, independent of diet composition or medication use.
This dysbiosis could play a significant role as it interacts with other mechanisms involved in IBS, including changes in intestinal motility related to diet (related to fermentable carbohydrates, for example). Moreover, the microbiota seems to induce a low level of immune activation in patients with IBS, leading to microinflammation and increased intestinal permeability, especially after an infection.
Furthermore, alterations in the regulation of bile acid deconjugation by the microbiota partly explain the frequency and consistency of stools in diarrhea-predominant IBS patients.
In addition, colonic gas production is higher in these patients. Those complaining of flatulence have poor tolerance to intestinal gases after a flatulent meal, associated with microbiota instability.
Data regarding the interaction between the microbiota and central mechanisms mainly come from animal studies. In rodents, microbiota constituents seem to affect brain development, function, and morphology. Emotional and physical traumas during childhood appear to be risk factors. Moreover, even brief exposure to broad-spectrum antibiotics in neonates could cause subsequent visceral hypersensitivity.
Lastly, the role of the microbiota in changes in medullary pain control after visceral stimulation (eg, rectal distension) has still not been demonstrated in humans.
Recent Guideline
In its February 2023 Global Guideline “Probiotics and Prebiotics” for IBS, the World Gastroenterology Organization looked at the level of evidence for probiotics.
Three strains, as well as a combination of several strains, were supported by level 2 evidence, meaning at least two randomized studies with converging results. These are Bifidobacterium bifidum MIMBb75, which improves overall symptoms and quality of life; Lactobacillus plantarum 299v (DSM 9843), which acts on the severity of abdominal pain and bloating; and B infantis 35624 (new name: B longum 35624), which improves the overall assessment of IBS symptoms, as does the multistrain product containing L rhamnosus GG, L rhamnosus LC705, Propionibacterium freudenreichii ssp shermanii JS DSM 7067, and B animalis ssp lactis B012 DSM 15954.
Efficacy and Availability
Probiotics belonging to the category of dietary supplements or medical devices are not required to provide evidence for a mechanism of action or even efficacy to be marketed. Thus, for most probiotics sold, there are no human or even animal studies available.
Dr. Sabaté proposed a choice of probiotics based on the literature and the presence of at least one randomized placebo-controlled trial conducted in patients with IBS showing positive results.
“,” he emphasized. The parameters that can be improved include symptom severity, quality of life, abdominal pain, and bloating.
Effective Probiotics
B longum 35624, which was developed with researchers from University College Cork in Ireland, is probably the most studied in animals and humans. Research has encompassed the mechanistic, clinical, and safety aspects of the probiotic. It has shown good results on the IBS-Symptom Severity Score (SSS), quality of life, abdominal pain, bowel disturbances, and bloating. The treatment duration in studies is 4-8 weeks.
L plantarum 299v (DSM 9843) affects the frequency of abdominal pain and pain score. The treatment duration in studies is 4 weeks.
The multistrain product that includes L plantarum CECT 7484/L plantarum CECT 7485/ Pediococcus acidilactici CECT 7483 allows for an improvement in quality of life and anxiety related to digestive symptoms. No positive effect has been described on digestive symptoms, especially diarrhea. The treatment duration is 6 weeks.
B bifidum MIMBb75 (both normal and heat-inactivated forms) is beneficial for pain, the composite IBS-SSS score, and quality of life. The treatment duration is 4-8 weeks.
“Except for the multistrain combination, which is more suited to patients with diarrhea-predominant IBS, the other three probiotics can be prescribed regardless of the IBS subtype,” said Dr. Sabaté. “Treatment durations are typically 4 weeks, but it is possible to continue up to 8 weeks, which is the maximum duration of these studies. In practice, there are no tolerance issues with probiotics prescribed for IBS based on the literature. These should be tested under the conditions and for the duration of the published studies and should only be continued if there is individual benefit on symptoms or quality of life.”
Note that microbiota analyses conducted for individual purposes are of no help in choosing probiotics.
Mechanisms of Action
In a murine model, but not in humans, some strains, especially L acidophilus NCFM, have shown an antinociceptive effect by inducing opioid and cannabinoid receptors.
Only in animals to date, L farciminis and B lactis CNCM I-2494 have shown prevention of induced hypersensitivity (ie, inhibition of the cytoskeleton contraction of colon epithelial cells and subsequent opening of tight junctions).
B infantis 35624 has an anti-inflammatory action by modifying the IL-10 and IL-12 cytokine ratio in animals and humans. It has an immunomodulatory action by increasing dendritic cells in the mucosa and decreasing Th1 and Th7 helper T cells.
B infantis 35624 and L farciminis are two strains that decrease visceral sensitivity in mice.
Escherichia coli Nissle 1917 acts on lipopeptide production with an antinociceptive effect, as observed in mice, by decreasing visceral sensitivity through calcium nociceptor flux blockade (action on GABA type B receptor).
Acting on dysbiosis by modifying fecal microbiota during probiotic intake is possible but depends on the probiotics, like B infantis 35624. In humans, B longum NCC 3001 could modify brain activations.
Dr. Sabaté disclosed financial relationships with Mayoly Spindler, Kyowa Kirin, Tillotts, Servier, Norgine, Biocodex, Merck, Viatris, Abivax, and Inventiva.
This story was translated from the Medscape French edition 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.
PARIS — Irritable bowel syndrome (IBS) is a common brain-gut axis disorder, and patients are often dissatisfied with conventional treatments.
The role of the microbiota in IBS is now well established, and patients frequently take probiotics on their own initiative or on the advice of a physician or pharmacist. However, not all probiotics have equal efficacy, so which ones should be recommended?
Jean-Marc Sabaté, MD, PhD, a gastroenterologist at Avicenne Hospital in Bobigny, France, shared insights about probiotics at the Francophone Days of Hepatology, Gastroenterology, and Digestive Oncology.
IBS, according to the Rome IV symptom-based classification, is a “disorder of brain-gut axis interactions” with a prevalence of about 4% in the adult population. In France, during an average care pathway of about 8 years, patients try an average of five therapeutic strategies (and as many as 11), including antispasmodics (85%), diets (78%), and probiotics. In addition, 66.4% of patients had either taken or were taking probiotics at the time of a recent survey.
While the 2022 recommendations from the American College of Gastroenterology on the diagnosis and management of IBS do not support the use of probiotics for overall symptom relief — a recommendation for which they cite a low level of evidence — “there is nevertheless a rationale for prescribing probiotics in IBS due to the significant role of the microbiota (or dysbiosis) in this condition,” said Dr. Sabaté.
Microbiota in IBS
Evidence indicating that antibiotics exacerbate IBS symptoms and revealing chronic bacterial overgrowth in the small intestine of patients with IBS supports the role of the microbiota. Studies using a molecular approach (16s rRNA) have settled the debate, confirming differences in the intestinal flora between patients with IBS and healthy subjects. Data also indicate differences in flora between patient subtypes, such as an increased Firmicutes to Bacteroidetes ratio. However, one subgroup, which can represent as much as a third of patients, seems to harbor a “normal” microbiota.
Nonetheless, the microbiota plays a significant role in IBS. A Swedish study highlighted the influence of bacterial enterotypes on transit type associated with IBS and symptom severity, independent of diet composition or medication use.
This dysbiosis could play a significant role as it interacts with other mechanisms involved in IBS, including changes in intestinal motility related to diet (related to fermentable carbohydrates, for example). Moreover, the microbiota seems to induce a low level of immune activation in patients with IBS, leading to microinflammation and increased intestinal permeability, especially after an infection.
Furthermore, alterations in the regulation of bile acid deconjugation by the microbiota partly explain the frequency and consistency of stools in diarrhea-predominant IBS patients.
In addition, colonic gas production is higher in these patients. Those complaining of flatulence have poor tolerance to intestinal gases after a flatulent meal, associated with microbiota instability.
Data regarding the interaction between the microbiota and central mechanisms mainly come from animal studies. In rodents, microbiota constituents seem to affect brain development, function, and morphology. Emotional and physical traumas during childhood appear to be risk factors. Moreover, even brief exposure to broad-spectrum antibiotics in neonates could cause subsequent visceral hypersensitivity.
Lastly, the role of the microbiota in changes in medullary pain control after visceral stimulation (eg, rectal distension) has still not been demonstrated in humans.
Recent Guideline
In its February 2023 Global Guideline “Probiotics and Prebiotics” for IBS, the World Gastroenterology Organization looked at the level of evidence for probiotics.
Three strains, as well as a combination of several strains, were supported by level 2 evidence, meaning at least two randomized studies with converging results. These are Bifidobacterium bifidum MIMBb75, which improves overall symptoms and quality of life; Lactobacillus plantarum 299v (DSM 9843), which acts on the severity of abdominal pain and bloating; and B infantis 35624 (new name: B longum 35624), which improves the overall assessment of IBS symptoms, as does the multistrain product containing L rhamnosus GG, L rhamnosus LC705, Propionibacterium freudenreichii ssp shermanii JS DSM 7067, and B animalis ssp lactis B012 DSM 15954.
Efficacy and Availability
Probiotics belonging to the category of dietary supplements or medical devices are not required to provide evidence for a mechanism of action or even efficacy to be marketed. Thus, for most probiotics sold, there are no human or even animal studies available.
Dr. Sabaté proposed a choice of probiotics based on the literature and the presence of at least one randomized placebo-controlled trial conducted in patients with IBS showing positive results.
“,” he emphasized. The parameters that can be improved include symptom severity, quality of life, abdominal pain, and bloating.
Effective Probiotics
B longum 35624, which was developed with researchers from University College Cork in Ireland, is probably the most studied in animals and humans. Research has encompassed the mechanistic, clinical, and safety aspects of the probiotic. It has shown good results on the IBS-Symptom Severity Score (SSS), quality of life, abdominal pain, bowel disturbances, and bloating. The treatment duration in studies is 4-8 weeks.
L plantarum 299v (DSM 9843) affects the frequency of abdominal pain and pain score. The treatment duration in studies is 4 weeks.
The multistrain product that includes L plantarum CECT 7484/L plantarum CECT 7485/ Pediococcus acidilactici CECT 7483 allows for an improvement in quality of life and anxiety related to digestive symptoms. No positive effect has been described on digestive symptoms, especially diarrhea. The treatment duration is 6 weeks.
B bifidum MIMBb75 (both normal and heat-inactivated forms) is beneficial for pain, the composite IBS-SSS score, and quality of life. The treatment duration is 4-8 weeks.
“Except for the multistrain combination, which is more suited to patients with diarrhea-predominant IBS, the other three probiotics can be prescribed regardless of the IBS subtype,” said Dr. Sabaté. “Treatment durations are typically 4 weeks, but it is possible to continue up to 8 weeks, which is the maximum duration of these studies. In practice, there are no tolerance issues with probiotics prescribed for IBS based on the literature. These should be tested under the conditions and for the duration of the published studies and should only be continued if there is individual benefit on symptoms or quality of life.”
Note that microbiota analyses conducted for individual purposes are of no help in choosing probiotics.
Mechanisms of Action
In a murine model, but not in humans, some strains, especially L acidophilus NCFM, have shown an antinociceptive effect by inducing opioid and cannabinoid receptors.
Only in animals to date, L farciminis and B lactis CNCM I-2494 have shown prevention of induced hypersensitivity (ie, inhibition of the cytoskeleton contraction of colon epithelial cells and subsequent opening of tight junctions).
B infantis 35624 has an anti-inflammatory action by modifying the IL-10 and IL-12 cytokine ratio in animals and humans. It has an immunomodulatory action by increasing dendritic cells in the mucosa and decreasing Th1 and Th7 helper T cells.
B infantis 35624 and L farciminis are two strains that decrease visceral sensitivity in mice.
Escherichia coli Nissle 1917 acts on lipopeptide production with an antinociceptive effect, as observed in mice, by decreasing visceral sensitivity through calcium nociceptor flux blockade (action on GABA type B receptor).
Acting on dysbiosis by modifying fecal microbiota during probiotic intake is possible but depends on the probiotics, like B infantis 35624. In humans, B longum NCC 3001 could modify brain activations.
Dr. Sabaté disclosed financial relationships with Mayoly Spindler, Kyowa Kirin, Tillotts, Servier, Norgine, Biocodex, Merck, Viatris, Abivax, and Inventiva.
This story was translated from the Medscape French edition 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.
How Long Should Active Surveillance Last?
Previous studies have shown that active surveillance continued for 15 years is appropriate to identify men who progress and need treatment, but now data out to 25 years “suggest that meticulous follow-up is needed over a longer time if the chance for cure is not to be missed,” said Emmeli Palmstedt, PhD, a research student in the Department of Urology at the Sahlgrenska Academy at the University of Gothenburg, Sweden. “These data are crucial, given the long current life expectancy” of men in otherwise good health.
Dr. Palmstedt presented the findings at the 2024 annual meeting of the European Association of Urology.
At many centers, active surveillance is a standard of care for men with low-risk prostate cancer based on a benefit-to-risk ratio that favors delayed intervention, according to Palmstedt. Several studies, including the Göteburg-1 active surveillance trial initiated at her institution, have supported follow-up for 15 years. A new set of data from Göteborg now extends to 25 years.
Long-Life Expectancy Justifies Extended Surveillance
The prospective Göteborg study began enrolling men with very low- or low-risk (78%) or intermediate-risk (22%) prostate cancer in 1995. In the active surveillance program, prostate-specific antigen (PSA) was measured routinely with biopsies ordered for PSA levels ≥ 2.5 ng/mL.
In an analysis published in 2016 when 202 (43%) of 474 patients managed with active surveillance had discontinued surveillance to start treatment, the median follow-up period was 8 years. The rate of mortality associated with prostate cancer at 15 years was estimated to be 0% for men in the very low-risk group, 4% for men in the low-risk group, and 10% for those with intermediate-risk tumors. The estimates for failure-free survival at 15 years were 88%, 77%, and 40% for the very low-, low-, and intermediate-risk groups, respectively.
In the most recent follow-up, when the median age in the Göteburg-1 study was 80 years (the median age at diagnosis was 66 years), the median follow-up period was 15.1 years with a range of up to 28.1 years. In this analysis, which focused on patients with low-risk prostate cancer at baseline, discontinuations from active surveillance had climbed to 47%. Most of these men discontinued to initiate treatment, but 79 (16%) had failed acute surveillance, meaning their progression was not caught in time for curative-intent treatment, and 2% had died from prostate cancer.
Treatment-Free Survival Falls to 31%
The rate of treatment-free survival, which was estimated to be 65% in the 15-year analysis published in 2016, had declined to 31%. The rate of failure-free survival was 59%, and prostate cancer-specific survival was 92%, according to the researchers.
While Dr. Palmstedt did not separate out her data for very low- and low-risk patients, she noted that deaths from prostate cancer among all low-risk patients climbed fourfold (8% vs 2%) since the 2016 figures were published. The proportion of men no longer failure-free climbed from 10% to more than 40%.
“These are non-negligible numbers,” said Dr. Palmstedt, who added that overall survival fell from 69% at 15 years to 37% at 25 years.
Although some men between the 15-year and 25-year timepoints were switched to watchful waiting, these data have not yet been analyzed.
The low rate of deaths from prostate cancer over the extended period is reassuring, Dr. Palmstedt said, but the main message from the new study is that active surveillance permits curative-intent treatment to be offered even after late follow-up. She emphasized that patients without progression by 15 years cannot be considered “safe.”
Based on these data, “men with a long remaining life expectancy should be informed that active surveillance is still viable after 15 years,” Dr. Palmstedt said.
Active Surveillance Now More Common
Over the past decade, the proportion of men with prostate cancer managed with active surveillance has been rising steadily, according to Matthew R. Cooperberg, MD, MPH, professor of urology at the University of California, San Francisco. In a study published last year in JAMA Network Open, Dr. Cooperberg and his colleagues reported that rates of active surveillance rose from 26.5% in 2014 to 59.6% in 2021. However, given the value of the approach for avoiding overtreatment of men with low-risk prostate cancers, even that increase is not enough, he said.
“The window of opportunity for cure is typically very wide,” Dr. Cooperberg said. Although many men “will never need treatment ... long-term surveillance is definitely important” for those that do, he said. The data from trials like Göteborg-1 support the principle that this strategy still preserves the option of treatment when it is needed.
“Treatment for cure at age 70 is generally far preferable to treatment at 55, and surveillance should absolutely be preferred treatment for the vast majority of men with low-grade disease at diagnosis,” he explained.
Dr. Palmstedt reported no potential conflicts of interest. Dr. Cooperberg reported financial relationships with Astellas, AstraZeneca, Bayer, Dendreon, Exact Sciences, Janssen, Merck, Pfizer, and Verana Health.
A version of this article appeared on Medscape.com.
Previous studies have shown that active surveillance continued for 15 years is appropriate to identify men who progress and need treatment, but now data out to 25 years “suggest that meticulous follow-up is needed over a longer time if the chance for cure is not to be missed,” said Emmeli Palmstedt, PhD, a research student in the Department of Urology at the Sahlgrenska Academy at the University of Gothenburg, Sweden. “These data are crucial, given the long current life expectancy” of men in otherwise good health.
Dr. Palmstedt presented the findings at the 2024 annual meeting of the European Association of Urology.
At many centers, active surveillance is a standard of care for men with low-risk prostate cancer based on a benefit-to-risk ratio that favors delayed intervention, according to Palmstedt. Several studies, including the Göteburg-1 active surveillance trial initiated at her institution, have supported follow-up for 15 years. A new set of data from Göteborg now extends to 25 years.
Long-Life Expectancy Justifies Extended Surveillance
The prospective Göteborg study began enrolling men with very low- or low-risk (78%) or intermediate-risk (22%) prostate cancer in 1995. In the active surveillance program, prostate-specific antigen (PSA) was measured routinely with biopsies ordered for PSA levels ≥ 2.5 ng/mL.
In an analysis published in 2016 when 202 (43%) of 474 patients managed with active surveillance had discontinued surveillance to start treatment, the median follow-up period was 8 years. The rate of mortality associated with prostate cancer at 15 years was estimated to be 0% for men in the very low-risk group, 4% for men in the low-risk group, and 10% for those with intermediate-risk tumors. The estimates for failure-free survival at 15 years were 88%, 77%, and 40% for the very low-, low-, and intermediate-risk groups, respectively.
In the most recent follow-up, when the median age in the Göteburg-1 study was 80 years (the median age at diagnosis was 66 years), the median follow-up period was 15.1 years with a range of up to 28.1 years. In this analysis, which focused on patients with low-risk prostate cancer at baseline, discontinuations from active surveillance had climbed to 47%. Most of these men discontinued to initiate treatment, but 79 (16%) had failed acute surveillance, meaning their progression was not caught in time for curative-intent treatment, and 2% had died from prostate cancer.
Treatment-Free Survival Falls to 31%
The rate of treatment-free survival, which was estimated to be 65% in the 15-year analysis published in 2016, had declined to 31%. The rate of failure-free survival was 59%, and prostate cancer-specific survival was 92%, according to the researchers.
While Dr. Palmstedt did not separate out her data for very low- and low-risk patients, she noted that deaths from prostate cancer among all low-risk patients climbed fourfold (8% vs 2%) since the 2016 figures were published. The proportion of men no longer failure-free climbed from 10% to more than 40%.
“These are non-negligible numbers,” said Dr. Palmstedt, who added that overall survival fell from 69% at 15 years to 37% at 25 years.
Although some men between the 15-year and 25-year timepoints were switched to watchful waiting, these data have not yet been analyzed.
The low rate of deaths from prostate cancer over the extended period is reassuring, Dr. Palmstedt said, but the main message from the new study is that active surveillance permits curative-intent treatment to be offered even after late follow-up. She emphasized that patients without progression by 15 years cannot be considered “safe.”
Based on these data, “men with a long remaining life expectancy should be informed that active surveillance is still viable after 15 years,” Dr. Palmstedt said.
Active Surveillance Now More Common
Over the past decade, the proportion of men with prostate cancer managed with active surveillance has been rising steadily, according to Matthew R. Cooperberg, MD, MPH, professor of urology at the University of California, San Francisco. In a study published last year in JAMA Network Open, Dr. Cooperberg and his colleagues reported that rates of active surveillance rose from 26.5% in 2014 to 59.6% in 2021. However, given the value of the approach for avoiding overtreatment of men with low-risk prostate cancers, even that increase is not enough, he said.
“The window of opportunity for cure is typically very wide,” Dr. Cooperberg said. Although many men “will never need treatment ... long-term surveillance is definitely important” for those that do, he said. The data from trials like Göteborg-1 support the principle that this strategy still preserves the option of treatment when it is needed.
“Treatment for cure at age 70 is generally far preferable to treatment at 55, and surveillance should absolutely be preferred treatment for the vast majority of men with low-grade disease at diagnosis,” he explained.
Dr. Palmstedt reported no potential conflicts of interest. Dr. Cooperberg reported financial relationships with Astellas, AstraZeneca, Bayer, Dendreon, Exact Sciences, Janssen, Merck, Pfizer, and Verana Health.
A version of this article appeared on Medscape.com.
Previous studies have shown that active surveillance continued for 15 years is appropriate to identify men who progress and need treatment, but now data out to 25 years “suggest that meticulous follow-up is needed over a longer time if the chance for cure is not to be missed,” said Emmeli Palmstedt, PhD, a research student in the Department of Urology at the Sahlgrenska Academy at the University of Gothenburg, Sweden. “These data are crucial, given the long current life expectancy” of men in otherwise good health.
Dr. Palmstedt presented the findings at the 2024 annual meeting of the European Association of Urology.
At many centers, active surveillance is a standard of care for men with low-risk prostate cancer based on a benefit-to-risk ratio that favors delayed intervention, according to Palmstedt. Several studies, including the Göteburg-1 active surveillance trial initiated at her institution, have supported follow-up for 15 years. A new set of data from Göteborg now extends to 25 years.
Long-Life Expectancy Justifies Extended Surveillance
The prospective Göteborg study began enrolling men with very low- or low-risk (78%) or intermediate-risk (22%) prostate cancer in 1995. In the active surveillance program, prostate-specific antigen (PSA) was measured routinely with biopsies ordered for PSA levels ≥ 2.5 ng/mL.
In an analysis published in 2016 when 202 (43%) of 474 patients managed with active surveillance had discontinued surveillance to start treatment, the median follow-up period was 8 years. The rate of mortality associated with prostate cancer at 15 years was estimated to be 0% for men in the very low-risk group, 4% for men in the low-risk group, and 10% for those with intermediate-risk tumors. The estimates for failure-free survival at 15 years were 88%, 77%, and 40% for the very low-, low-, and intermediate-risk groups, respectively.
In the most recent follow-up, when the median age in the Göteburg-1 study was 80 years (the median age at diagnosis was 66 years), the median follow-up period was 15.1 years with a range of up to 28.1 years. In this analysis, which focused on patients with low-risk prostate cancer at baseline, discontinuations from active surveillance had climbed to 47%. Most of these men discontinued to initiate treatment, but 79 (16%) had failed acute surveillance, meaning their progression was not caught in time for curative-intent treatment, and 2% had died from prostate cancer.
Treatment-Free Survival Falls to 31%
The rate of treatment-free survival, which was estimated to be 65% in the 15-year analysis published in 2016, had declined to 31%. The rate of failure-free survival was 59%, and prostate cancer-specific survival was 92%, according to the researchers.
While Dr. Palmstedt did not separate out her data for very low- and low-risk patients, she noted that deaths from prostate cancer among all low-risk patients climbed fourfold (8% vs 2%) since the 2016 figures were published. The proportion of men no longer failure-free climbed from 10% to more than 40%.
“These are non-negligible numbers,” said Dr. Palmstedt, who added that overall survival fell from 69% at 15 years to 37% at 25 years.
Although some men between the 15-year and 25-year timepoints were switched to watchful waiting, these data have not yet been analyzed.
The low rate of deaths from prostate cancer over the extended period is reassuring, Dr. Palmstedt said, but the main message from the new study is that active surveillance permits curative-intent treatment to be offered even after late follow-up. She emphasized that patients without progression by 15 years cannot be considered “safe.”
Based on these data, “men with a long remaining life expectancy should be informed that active surveillance is still viable after 15 years,” Dr. Palmstedt said.
Active Surveillance Now More Common
Over the past decade, the proportion of men with prostate cancer managed with active surveillance has been rising steadily, according to Matthew R. Cooperberg, MD, MPH, professor of urology at the University of California, San Francisco. In a study published last year in JAMA Network Open, Dr. Cooperberg and his colleagues reported that rates of active surveillance rose from 26.5% in 2014 to 59.6% in 2021. However, given the value of the approach for avoiding overtreatment of men with low-risk prostate cancers, even that increase is not enough, he said.
“The window of opportunity for cure is typically very wide,” Dr. Cooperberg said. Although many men “will never need treatment ... long-term surveillance is definitely important” for those that do, he said. The data from trials like Göteborg-1 support the principle that this strategy still preserves the option of treatment when it is needed.
“Treatment for cure at age 70 is generally far preferable to treatment at 55, and surveillance should absolutely be preferred treatment for the vast majority of men with low-grade disease at diagnosis,” he explained.
Dr. Palmstedt reported no potential conflicts of interest. Dr. Cooperberg reported financial relationships with Astellas, AstraZeneca, Bayer, Dendreon, Exact Sciences, Janssen, Merck, Pfizer, and Verana Health.
A version of this article appeared on Medscape.com.
Why Lung Cancer Screening Is Not for Everyone
Why does this happen? Could it also occur in Italy?
Reasons in Favor
The authors of the study, which was published in Annals of Family Medicine interviewed 40 former military personnel with a significant history of smoking. Though the patients presented with various comorbidities and had a limited life expectancy, the Veterans Health Administration had offered them lung cancer screening.
Of the 40 respondents, 26 had accepted the screening test. When asked why they had done so, they responded, “to take care of my health and achieve my life goals,” “because screening is an opportunity to identify potential issues,” “because it was recommended by a doctor I trust,” and “because I don’t want to regret not accepting it.” Strangely, when deciding about lung cancer screening, the respondents did not consider their poor health or life expectancy.
Potential Harms
The screening was also welcomed because low-dose computed tomography (LDCT) is a noninvasive test. However, many participants were unaware that the screening needed to be repeated annually and that further imaging or other types of tests could follow LDCT, such as biopsies and bronchoscopies.
Many did not recall discussing with the doctor the potential harms of screening, including overdiagnosis, stress due to false positives, and complications and risks associated with investigations and treatments. Informed about this, several patients stated that they would not necessarily undergo further tests or antitumor treatments, especially if intensive or invasive.
The authors of the article emphasized the importance of shared decision-making with patients who have a marginal expected benefit from screening. But is it correct to offer screening under these conditions? Guidelines advise against screening individuals with limited life expectancy and multiple comorbidities because the risk-benefit ratio is not favorable.
Screening in Italy
Italy has no organized public program for lung screening. However, in 2022, the Rete Italiana Screening Polmonare (RISP) program for early lung cancer diagnosis was launched. Supported by European funds, it is coordinated by the National Cancer Institute (INT) in Milan and aims to recruit 10,000 high-risk candidates for free screening at 18 hospitals across Italy.
Optimizing participant selection is important in any screening, but in a program like RISP, it is essential, said Alessandro Pardolesi, MD, a thoracic surgeon at INT. “Subjects with multiple comorbidities would create a limit to the study, because there would be too many confounding factors. By maintaining correct inclusion criteria, we can build a reproducible model to demonstrate that screening has a clear social and economic impact. Only after proving its effectiveness can we consider extending it to patients with pre-existing issues or who are very elderly,” he said. The RISP project is limited to participants aged 55-75 years. Participants must be smokers or have quit smoking no more than 15 years ago, with an average consumption of 20 cigarettes per day for 30 years.
Participant selection for the RISP program is also dictated by the costs to be incurred. “If something emerges from the CT scan, whether oncologic or not, it needs to be investigated, triggering mechanisms that consume time, space, and resources,” said Dr. Pardolesi. The economic aspect is crucial for determining the effectiveness of screening. “We need to demonstrate that in addition to increasing the patient’s life expectancy, healthcare costs are reduced. By anticipating the diagnosis, the intervention is less expensive, the patient is discharged in three days, and there’s no need for therapy, so there’s a saving. This is important, given the increasingly evident economic problems of the Italian public health system,” said Dr. Pardolesi.
This story was translated from Univadis Italy, which is part of the Medscape professional network, 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.
Why does this happen? Could it also occur in Italy?
Reasons in Favor
The authors of the study, which was published in Annals of Family Medicine interviewed 40 former military personnel with a significant history of smoking. Though the patients presented with various comorbidities and had a limited life expectancy, the Veterans Health Administration had offered them lung cancer screening.
Of the 40 respondents, 26 had accepted the screening test. When asked why they had done so, they responded, “to take care of my health and achieve my life goals,” “because screening is an opportunity to identify potential issues,” “because it was recommended by a doctor I trust,” and “because I don’t want to regret not accepting it.” Strangely, when deciding about lung cancer screening, the respondents did not consider their poor health or life expectancy.
Potential Harms
The screening was also welcomed because low-dose computed tomography (LDCT) is a noninvasive test. However, many participants were unaware that the screening needed to be repeated annually and that further imaging or other types of tests could follow LDCT, such as biopsies and bronchoscopies.
Many did not recall discussing with the doctor the potential harms of screening, including overdiagnosis, stress due to false positives, and complications and risks associated with investigations and treatments. Informed about this, several patients stated that they would not necessarily undergo further tests or antitumor treatments, especially if intensive or invasive.
The authors of the article emphasized the importance of shared decision-making with patients who have a marginal expected benefit from screening. But is it correct to offer screening under these conditions? Guidelines advise against screening individuals with limited life expectancy and multiple comorbidities because the risk-benefit ratio is not favorable.
Screening in Italy
Italy has no organized public program for lung screening. However, in 2022, the Rete Italiana Screening Polmonare (RISP) program for early lung cancer diagnosis was launched. Supported by European funds, it is coordinated by the National Cancer Institute (INT) in Milan and aims to recruit 10,000 high-risk candidates for free screening at 18 hospitals across Italy.
Optimizing participant selection is important in any screening, but in a program like RISP, it is essential, said Alessandro Pardolesi, MD, a thoracic surgeon at INT. “Subjects with multiple comorbidities would create a limit to the study, because there would be too many confounding factors. By maintaining correct inclusion criteria, we can build a reproducible model to demonstrate that screening has a clear social and economic impact. Only after proving its effectiveness can we consider extending it to patients with pre-existing issues or who are very elderly,” he said. The RISP project is limited to participants aged 55-75 years. Participants must be smokers or have quit smoking no more than 15 years ago, with an average consumption of 20 cigarettes per day for 30 years.
Participant selection for the RISP program is also dictated by the costs to be incurred. “If something emerges from the CT scan, whether oncologic or not, it needs to be investigated, triggering mechanisms that consume time, space, and resources,” said Dr. Pardolesi. The economic aspect is crucial for determining the effectiveness of screening. “We need to demonstrate that in addition to increasing the patient’s life expectancy, healthcare costs are reduced. By anticipating the diagnosis, the intervention is less expensive, the patient is discharged in three days, and there’s no need for therapy, so there’s a saving. This is important, given the increasingly evident economic problems of the Italian public health system,” said Dr. Pardolesi.
This story was translated from Univadis Italy, which is part of the Medscape professional network, 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.
Why does this happen? Could it also occur in Italy?
Reasons in Favor
The authors of the study, which was published in Annals of Family Medicine interviewed 40 former military personnel with a significant history of smoking. Though the patients presented with various comorbidities and had a limited life expectancy, the Veterans Health Administration had offered them lung cancer screening.
Of the 40 respondents, 26 had accepted the screening test. When asked why they had done so, they responded, “to take care of my health and achieve my life goals,” “because screening is an opportunity to identify potential issues,” “because it was recommended by a doctor I trust,” and “because I don’t want to regret not accepting it.” Strangely, when deciding about lung cancer screening, the respondents did not consider their poor health or life expectancy.
Potential Harms
The screening was also welcomed because low-dose computed tomography (LDCT) is a noninvasive test. However, many participants were unaware that the screening needed to be repeated annually and that further imaging or other types of tests could follow LDCT, such as biopsies and bronchoscopies.
Many did not recall discussing with the doctor the potential harms of screening, including overdiagnosis, stress due to false positives, and complications and risks associated with investigations and treatments. Informed about this, several patients stated that they would not necessarily undergo further tests or antitumor treatments, especially if intensive or invasive.
The authors of the article emphasized the importance of shared decision-making with patients who have a marginal expected benefit from screening. But is it correct to offer screening under these conditions? Guidelines advise against screening individuals with limited life expectancy and multiple comorbidities because the risk-benefit ratio is not favorable.
Screening in Italy
Italy has no organized public program for lung screening. However, in 2022, the Rete Italiana Screening Polmonare (RISP) program for early lung cancer diagnosis was launched. Supported by European funds, it is coordinated by the National Cancer Institute (INT) in Milan and aims to recruit 10,000 high-risk candidates for free screening at 18 hospitals across Italy.
Optimizing participant selection is important in any screening, but in a program like RISP, it is essential, said Alessandro Pardolesi, MD, a thoracic surgeon at INT. “Subjects with multiple comorbidities would create a limit to the study, because there would be too many confounding factors. By maintaining correct inclusion criteria, we can build a reproducible model to demonstrate that screening has a clear social and economic impact. Only after proving its effectiveness can we consider extending it to patients with pre-existing issues or who are very elderly,” he said. The RISP project is limited to participants aged 55-75 years. Participants must be smokers or have quit smoking no more than 15 years ago, with an average consumption of 20 cigarettes per day for 30 years.
Participant selection for the RISP program is also dictated by the costs to be incurred. “If something emerges from the CT scan, whether oncologic or not, it needs to be investigated, triggering mechanisms that consume time, space, and resources,” said Dr. Pardolesi. The economic aspect is crucial for determining the effectiveness of screening. “We need to demonstrate that in addition to increasing the patient’s life expectancy, healthcare costs are reduced. By anticipating the diagnosis, the intervention is less expensive, the patient is discharged in three days, and there’s no need for therapy, so there’s a saving. This is important, given the increasingly evident economic problems of the Italian public health system,” said Dr. Pardolesi.
This story was translated from Univadis Italy, which is part of the Medscape professional network, 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.
Eli Lilly to Ask FDA to Approve Weight Loss Drug for Sleep Apnea
Results from a preliminary clinical trial demonstrated the obesity drug, tirzepatide, effectively treated obstructive sleep apnea (OSA), according to information sent to investors of the pharmaceutical company, Eli Lilly.
Indiana-based Eli Lilly sells tirzepatide under the brand name Zepbound, which was approved by the FDA in November to treat overweight and obesity. Tirzepatide is also marketed under the name Mounjaro to treat diabetes, and it’s among the same class of drugs as other well-known weight loss and diabetes drugs like Ozempic and Wegovy.
The newly announced results came from a pair of studies that followed people with moderate to severe OSA who also had obesity. People in the study took tirzepatide, which is given by injection, for one year. About 70% of people in the studies were men.
The findings have not yet been published in a peer-reviewed medical journal, and the preliminary results were announced by Eli Lilly because of reporting requirements related to information that could affect stock prices. The company indicated that detailed results will be presented at a conference of the American Diabetes Association in June and will be submitted to a peer-reviewed journal for consideration of publication. The company also plans to submit the information to the FDA for approval consideration mid-year, the investor news release stated.
People in the study taking tirzepatide on average experienced 63% fewer instances of reduced oxygen due to breathing changes, or events when breathing entirely stopped, Eli Lilly reported.
A sleep expert from Washington University in St. Louis told The New York Times the initial findings were extremely positive and noted that tirzepatide works to treat the underlying cause of sleep apnea, rather than current treatments that just address symptoms.
Tirzepatide “is a great alternative for people who are obese and can’t use CPAP or are on CPAP and want to improve the effect,” Eric Landsness, MD, PhD, told The New York Times.
Eli Lilly indicated the most commonly reported adverse events in the studies were diarrhea, nausea, vomiting, and constipation.
An estimated 39 million people have OSA and about 33 million people use CPAP machines, according to The National Council on Aging. The condition has been increasingly diagnosed in recent years and becomes more likely to affect people as they get older.
A version of this article appeared on WebMD.com.
Results from a preliminary clinical trial demonstrated the obesity drug, tirzepatide, effectively treated obstructive sleep apnea (OSA), according to information sent to investors of the pharmaceutical company, Eli Lilly.
Indiana-based Eli Lilly sells tirzepatide under the brand name Zepbound, which was approved by the FDA in November to treat overweight and obesity. Tirzepatide is also marketed under the name Mounjaro to treat diabetes, and it’s among the same class of drugs as other well-known weight loss and diabetes drugs like Ozempic and Wegovy.
The newly announced results came from a pair of studies that followed people with moderate to severe OSA who also had obesity. People in the study took tirzepatide, which is given by injection, for one year. About 70% of people in the studies were men.
The findings have not yet been published in a peer-reviewed medical journal, and the preliminary results were announced by Eli Lilly because of reporting requirements related to information that could affect stock prices. The company indicated that detailed results will be presented at a conference of the American Diabetes Association in June and will be submitted to a peer-reviewed journal for consideration of publication. The company also plans to submit the information to the FDA for approval consideration mid-year, the investor news release stated.
People in the study taking tirzepatide on average experienced 63% fewer instances of reduced oxygen due to breathing changes, or events when breathing entirely stopped, Eli Lilly reported.
A sleep expert from Washington University in St. Louis told The New York Times the initial findings were extremely positive and noted that tirzepatide works to treat the underlying cause of sleep apnea, rather than current treatments that just address symptoms.
Tirzepatide “is a great alternative for people who are obese and can’t use CPAP or are on CPAP and want to improve the effect,” Eric Landsness, MD, PhD, told The New York Times.
Eli Lilly indicated the most commonly reported adverse events in the studies were diarrhea, nausea, vomiting, and constipation.
An estimated 39 million people have OSA and about 33 million people use CPAP machines, according to The National Council on Aging. The condition has been increasingly diagnosed in recent years and becomes more likely to affect people as they get older.
A version of this article appeared on WebMD.com.
Results from a preliminary clinical trial demonstrated the obesity drug, tirzepatide, effectively treated obstructive sleep apnea (OSA), according to information sent to investors of the pharmaceutical company, Eli Lilly.
Indiana-based Eli Lilly sells tirzepatide under the brand name Zepbound, which was approved by the FDA in November to treat overweight and obesity. Tirzepatide is also marketed under the name Mounjaro to treat diabetes, and it’s among the same class of drugs as other well-known weight loss and diabetes drugs like Ozempic and Wegovy.
The newly announced results came from a pair of studies that followed people with moderate to severe OSA who also had obesity. People in the study took tirzepatide, which is given by injection, for one year. About 70% of people in the studies were men.
The findings have not yet been published in a peer-reviewed medical journal, and the preliminary results were announced by Eli Lilly because of reporting requirements related to information that could affect stock prices. The company indicated that detailed results will be presented at a conference of the American Diabetes Association in June and will be submitted to a peer-reviewed journal for consideration of publication. The company also plans to submit the information to the FDA for approval consideration mid-year, the investor news release stated.
People in the study taking tirzepatide on average experienced 63% fewer instances of reduced oxygen due to breathing changes, or events when breathing entirely stopped, Eli Lilly reported.
A sleep expert from Washington University in St. Louis told The New York Times the initial findings were extremely positive and noted that tirzepatide works to treat the underlying cause of sleep apnea, rather than current treatments that just address symptoms.
Tirzepatide “is a great alternative for people who are obese and can’t use CPAP or are on CPAP and want to improve the effect,” Eric Landsness, MD, PhD, told The New York Times.
Eli Lilly indicated the most commonly reported adverse events in the studies were diarrhea, nausea, vomiting, and constipation.
An estimated 39 million people have OSA and about 33 million people use CPAP machines, according to The National Council on Aging. The condition has been increasingly diagnosed in recent years and becomes more likely to affect people as they get older.
A version of this article appeared on WebMD.com.
Early Evidence Supports Ketogenic Diet for Mental Illness
The ketogenic diet shows promise in reducing the symptoms of bipolar disorder and schizophrenia and reversing metabolic syndrome, results of a new pilot study show.
Participants who adhered to the high-fat, low-carb diet experienced a 30% reduction in psychiatric symptoms and an average 10% reduction in weight.
“We’re seeing huge changes,” first author Shebani Sethi, MD, of Stanford University in Stanford, California said in a press release. “Even if you’re on antipsychotic drugs, we can still reverse the obesity, the metabolic syndrome, and the insulin resistance. I think that’s very encouraging for patients.”
The findings were published online in Psychiatric Research.
Neuroprotective Effect?
The pilot study included 21 participants with schizophrenia (n = 5) or bipolar disorder (n = 16) who were aged 18-75 years. All were currently taking psychotropic medications. Participants were overweight (body mass index [BMI] ≥ 25) and had gained more than 5% of their body mass while taking psychotropic medication, or they had at least one metabolic abnormality, such as insulin resistance or dyslipidemia.
At baseline, participants received a physical and psychiatric evaluation and 1 hour of instruction on how to implement the keto diet, which included 10% carbohydrate, 30% protein, and 60% fat.
Investigators monitored blood ketone levels at least once a week and defined participants as keto-adherent if their levels were 0.5-5 mM for 80%-100% of the times they were measured.
Health coaches checked in with participants for about 5-10 minutes each week to answer diet-related questions.
Psychiatric assessments, which included mood rating and global functioning scales, were completed at baseline, 2 months, and at the end of the 4-month study.
The research team tracked participants’ adherence to the diet by weekly measurement of blood ketone levels.
By the end of the trial, 14 patients had been fully adherent with the diet, six had been semi-adherent, and only one had been nonadherent. Higher ketone levels, suggesting greater adherence, correlated with better metabolic health.
As measured by the Clinical Global Impression-Schizophrenia and Clinical Global Impression for Bipolar Disorder–Overall Severity, participants experienced a 31% reduction in symptom severity (P < .001). Overall, 43% (P < .02) of participants achieved recovery as defined by the Clinical Mood Monitoring Form criteria: 50% of the adherent group and 33% of those who were semi-adherent.
Metabolic Benefits
Initially, 29% of participants had metabolic syndrome and more than 85% had co-occurring medical conditions such as obesity, hyperlipidemia, or prediabetes. By the end of the study, none met criteria for metabolic syndrome.
On average, participants experienced a 10% reduction in weight and BMI. Waist circumference was reduced by 11%, fat mass index dropped by 17%, and systolic blood pressure decreased by 6%. In addition, metabolic markers including visceral fat, inflammation, A1c, and insulin resistance also improved. All outcomes were significant at P < .001 except for systolic blood pressure, at P < .005.
There was also a 20% reduction in triglycerides and a 21% increase in low-density lipoprotein cholesterol (both at P < .02).
The study’s limitations include its small sample size, the lack of control arm, and short duration.
“Mental health and physical health are interconnected and addressing metabolic issues can complement psychiatric treatment to enhance overall well-being. Understanding the
mechanisms and potential synergies between psychiatric treatment and metabolic improvements can also inform the development of more effective interventions,” the researchers wrote.
The study was funded by the Baszucki Group, Kuen Lau Fund, and the Obesity Treatment Foundation. The authors declare no competing interests.
A version of this article appeared on Medscape.com.
The ketogenic diet shows promise in reducing the symptoms of bipolar disorder and schizophrenia and reversing metabolic syndrome, results of a new pilot study show.
Participants who adhered to the high-fat, low-carb diet experienced a 30% reduction in psychiatric symptoms and an average 10% reduction in weight.
“We’re seeing huge changes,” first author Shebani Sethi, MD, of Stanford University in Stanford, California said in a press release. “Even if you’re on antipsychotic drugs, we can still reverse the obesity, the metabolic syndrome, and the insulin resistance. I think that’s very encouraging for patients.”
The findings were published online in Psychiatric Research.
Neuroprotective Effect?
The pilot study included 21 participants with schizophrenia (n = 5) or bipolar disorder (n = 16) who were aged 18-75 years. All were currently taking psychotropic medications. Participants were overweight (body mass index [BMI] ≥ 25) and had gained more than 5% of their body mass while taking psychotropic medication, or they had at least one metabolic abnormality, such as insulin resistance or dyslipidemia.
At baseline, participants received a physical and psychiatric evaluation and 1 hour of instruction on how to implement the keto diet, which included 10% carbohydrate, 30% protein, and 60% fat.
Investigators monitored blood ketone levels at least once a week and defined participants as keto-adherent if their levels were 0.5-5 mM for 80%-100% of the times they were measured.
Health coaches checked in with participants for about 5-10 minutes each week to answer diet-related questions.
Psychiatric assessments, which included mood rating and global functioning scales, were completed at baseline, 2 months, and at the end of the 4-month study.
The research team tracked participants’ adherence to the diet by weekly measurement of blood ketone levels.
By the end of the trial, 14 patients had been fully adherent with the diet, six had been semi-adherent, and only one had been nonadherent. Higher ketone levels, suggesting greater adherence, correlated with better metabolic health.
As measured by the Clinical Global Impression-Schizophrenia and Clinical Global Impression for Bipolar Disorder–Overall Severity, participants experienced a 31% reduction in symptom severity (P < .001). Overall, 43% (P < .02) of participants achieved recovery as defined by the Clinical Mood Monitoring Form criteria: 50% of the adherent group and 33% of those who were semi-adherent.
Metabolic Benefits
Initially, 29% of participants had metabolic syndrome and more than 85% had co-occurring medical conditions such as obesity, hyperlipidemia, or prediabetes. By the end of the study, none met criteria for metabolic syndrome.
On average, participants experienced a 10% reduction in weight and BMI. Waist circumference was reduced by 11%, fat mass index dropped by 17%, and systolic blood pressure decreased by 6%. In addition, metabolic markers including visceral fat, inflammation, A1c, and insulin resistance also improved. All outcomes were significant at P < .001 except for systolic blood pressure, at P < .005.
There was also a 20% reduction in triglycerides and a 21% increase in low-density lipoprotein cholesterol (both at P < .02).
The study’s limitations include its small sample size, the lack of control arm, and short duration.
“Mental health and physical health are interconnected and addressing metabolic issues can complement psychiatric treatment to enhance overall well-being. Understanding the
mechanisms and potential synergies between psychiatric treatment and metabolic improvements can also inform the development of more effective interventions,” the researchers wrote.
The study was funded by the Baszucki Group, Kuen Lau Fund, and the Obesity Treatment Foundation. The authors declare no competing interests.
A version of this article appeared on Medscape.com.
The ketogenic diet shows promise in reducing the symptoms of bipolar disorder and schizophrenia and reversing metabolic syndrome, results of a new pilot study show.
Participants who adhered to the high-fat, low-carb diet experienced a 30% reduction in psychiatric symptoms and an average 10% reduction in weight.
“We’re seeing huge changes,” first author Shebani Sethi, MD, of Stanford University in Stanford, California said in a press release. “Even if you’re on antipsychotic drugs, we can still reverse the obesity, the metabolic syndrome, and the insulin resistance. I think that’s very encouraging for patients.”
The findings were published online in Psychiatric Research.
Neuroprotective Effect?
The pilot study included 21 participants with schizophrenia (n = 5) or bipolar disorder (n = 16) who were aged 18-75 years. All were currently taking psychotropic medications. Participants were overweight (body mass index [BMI] ≥ 25) and had gained more than 5% of their body mass while taking psychotropic medication, or they had at least one metabolic abnormality, such as insulin resistance or dyslipidemia.
At baseline, participants received a physical and psychiatric evaluation and 1 hour of instruction on how to implement the keto diet, which included 10% carbohydrate, 30% protein, and 60% fat.
Investigators monitored blood ketone levels at least once a week and defined participants as keto-adherent if their levels were 0.5-5 mM for 80%-100% of the times they were measured.
Health coaches checked in with participants for about 5-10 minutes each week to answer diet-related questions.
Psychiatric assessments, which included mood rating and global functioning scales, were completed at baseline, 2 months, and at the end of the 4-month study.
The research team tracked participants’ adherence to the diet by weekly measurement of blood ketone levels.
By the end of the trial, 14 patients had been fully adherent with the diet, six had been semi-adherent, and only one had been nonadherent. Higher ketone levels, suggesting greater adherence, correlated with better metabolic health.
As measured by the Clinical Global Impression-Schizophrenia and Clinical Global Impression for Bipolar Disorder–Overall Severity, participants experienced a 31% reduction in symptom severity (P < .001). Overall, 43% (P < .02) of participants achieved recovery as defined by the Clinical Mood Monitoring Form criteria: 50% of the adherent group and 33% of those who were semi-adherent.
Metabolic Benefits
Initially, 29% of participants had metabolic syndrome and more than 85% had co-occurring medical conditions such as obesity, hyperlipidemia, or prediabetes. By the end of the study, none met criteria for metabolic syndrome.
On average, participants experienced a 10% reduction in weight and BMI. Waist circumference was reduced by 11%, fat mass index dropped by 17%, and systolic blood pressure decreased by 6%. In addition, metabolic markers including visceral fat, inflammation, A1c, and insulin resistance also improved. All outcomes were significant at P < .001 except for systolic blood pressure, at P < .005.
There was also a 20% reduction in triglycerides and a 21% increase in low-density lipoprotein cholesterol (both at P < .02).
The study’s limitations include its small sample size, the lack of control arm, and short duration.
“Mental health and physical health are interconnected and addressing metabolic issues can complement psychiatric treatment to enhance overall well-being. Understanding the
mechanisms and potential synergies between psychiatric treatment and metabolic improvements can also inform the development of more effective interventions,” the researchers wrote.
The study was funded by the Baszucki Group, Kuen Lau Fund, and the Obesity Treatment Foundation. The authors declare no competing interests.
A version of this article appeared on Medscape.com.
FROM PSYCHIATRIC RESEARCH
Antipsychotics for Dementia Pose Wide-Ranging Health Risks
Antipsychotic use in older adults with dementia is associated with a significant increased risk for stroke, myocardial infarction, heart failure, pneumonia, fracture, acute kidney injury, and a range of other health problems compared with nonuse, new research showed.
The adverse events are far broader and pose more severe health risks than previously reported, investigators noted, and suggested greater caution is needed when prescribing antipsychotics to treat psychological symptoms of dementia.
The matched cohort study used patient registry data on nearly 174,000 people with dementia and compared those who were prescribed an antipsychotic on or after their dementia diagnosis with those who had not received a prescription for the drugs.
Any antipsychotic use was associated with double the risk for pneumonia, a 1.7-fold increased risk for acute kidney injury, and 1.6-fold higher odds of venous thromboembolism compared to nonuse.
Investigators found an increased risk for all outcomes studied, except for ventricular arrythmia, and risk was highest for most within the first week of treatment.
“Any potential benefits of antipsychotic treatment therefore need to be weighed against the risk of serious harm across multiple outcomes. Although there may be times when an antipsychotic prescription is the least bad option, clinicians should actively consider the risks, considering patients’ pre-existing comorbidities and living support,” lead investigator Pearl Mok, research fellow at the Centre for Pharmacoepidemiology and Drug Safety, The University of Manchester, Manchester, England, and colleagues wrote.
The findings were published online in The BMJ.
High Risk
Depression, aggression, anxiety, psychosis, and other behavioral and psychological symptoms are common in people with dementia. Despite earlier reports of increased risk for stroke and mortality with antipsychotic use, the drugs are frequently prescribed to treat these symptoms.
While some preliminary studies identified other adverse outcomes from antipsychotic use, results are limited and inconsistent.
Investigators used primary and secondary care data from the Clinical Practice Research Datalink in England. A total of 173,910 adults (63% women) had a dementia diagnosis between January 1998 and May 2018.
Of the total cohort, 35,339 patients were prescribed an antipsychotic on, or after, a dementia diagnosis. Each was matched with up to 15 patients with dementia with no history of antipsychotic use following diagnosis.
Almost 80% of antipsychotic prescriptions were for risperidone, quetiapine, haloperidol, and olanzapine.
Any antipsychotic use was associated with significantly higher risks for pneumonia (hazard ratio [HR], 2.03; 95% CI, 1.96-2.10), acute kidney injury (HR, 1.57; 95% CI, 1.48-1.66), stroke (HR, 1.54; 95% CI, 1.46-1.63), venous thromboembolism (HR, 1.52; 95% CI, 1.38-1.67), fracture (HR, 1.36; 95% CI, 1.30-1.44), myocardial infarction (HR, 1.22; 95% CI, 1.12-1.34), and heart failure (HR, 1.16; 95% CI, 1.09-1.24).
The risk for all conditions was highest within the first 3 months of treatment, with a cumulative incidence of pneumonia among antipsychotic users of 4.48% vs 1.49% among nonusers. At 1 year, this increased to 10.41% for users vs 5.63% for nonusers.
“Given the higher risks of adverse events in the early days after drug initiation, clinical examinations should be taken before, and clinical reviews conducted shortly after, the start of treatment,” the authors wrote. “Our study reaffirms that these drugs should only be prescribed for the shortest period possible.”
‘Serious Harms’
In an accompanying editorial, Raya Elfadel Kheirbek, MD, and Cristina LaFont, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, said the findings “highlight the need for careful justification of antipsychotic use in dementia care, including a comprehensive assessment of the benefits weighed against a broader range of serious harms than previously acknowledged.”
“Using antipsychotics for the management of dementia-related behaviors requires nuanced decision-making after careful assessment, informed by a personalized approach,” they continued. “Dr. Mok and colleagues call for a critical re-evaluation of antipsychotic use in this clinical setting.”
While the findings add to and expand what was already known, “we need to be clear that they don’t show antipsychotics cause all the adverse outcomes reported,” Masud Husain, DPhil, professor of neurology, University of Oxford, England, said in a statement.
While investigators attempted to use matched controls with dementia who had not received antipsychotics, “the people who were prescribed the drugs may simply have been more vulnerable to some of the conditions that occurred more frequently in them, such as pneumonia and cardiovascular disorders,” said Dr. Husain, who was not part of the research.
Although the study was not designed to explore reverse causality, the findings are important for clinicians who prescribe antipsychotics for patients with dementia, Robert Howard, professor of old age psychiatry, at the University of College London, London, England said in a statement.
“Initiation of these drugs in people with dementia should only ever be under specialist supervision, with involvement of patients and family members in informed discussion and review,” said Dr. Howard, who was not involved in the study.
The study was funded by the National Institute for Health and Care Research. Dr. Mok reported no relevant conflicts. Other authors’ disclosures are included in the original article. Dr. Hussain, Dr. Howard, Dr. Kheirbek, and Dr. LeFon reported no relevant conflicts.
A version of this article appeared on Medscape.com.
Antipsychotic use in older adults with dementia is associated with a significant increased risk for stroke, myocardial infarction, heart failure, pneumonia, fracture, acute kidney injury, and a range of other health problems compared with nonuse, new research showed.
The adverse events are far broader and pose more severe health risks than previously reported, investigators noted, and suggested greater caution is needed when prescribing antipsychotics to treat psychological symptoms of dementia.
The matched cohort study used patient registry data on nearly 174,000 people with dementia and compared those who were prescribed an antipsychotic on or after their dementia diagnosis with those who had not received a prescription for the drugs.
Any antipsychotic use was associated with double the risk for pneumonia, a 1.7-fold increased risk for acute kidney injury, and 1.6-fold higher odds of venous thromboembolism compared to nonuse.
Investigators found an increased risk for all outcomes studied, except for ventricular arrythmia, and risk was highest for most within the first week of treatment.
“Any potential benefits of antipsychotic treatment therefore need to be weighed against the risk of serious harm across multiple outcomes. Although there may be times when an antipsychotic prescription is the least bad option, clinicians should actively consider the risks, considering patients’ pre-existing comorbidities and living support,” lead investigator Pearl Mok, research fellow at the Centre for Pharmacoepidemiology and Drug Safety, The University of Manchester, Manchester, England, and colleagues wrote.
The findings were published online in The BMJ.
High Risk
Depression, aggression, anxiety, psychosis, and other behavioral and psychological symptoms are common in people with dementia. Despite earlier reports of increased risk for stroke and mortality with antipsychotic use, the drugs are frequently prescribed to treat these symptoms.
While some preliminary studies identified other adverse outcomes from antipsychotic use, results are limited and inconsistent.
Investigators used primary and secondary care data from the Clinical Practice Research Datalink in England. A total of 173,910 adults (63% women) had a dementia diagnosis between January 1998 and May 2018.
Of the total cohort, 35,339 patients were prescribed an antipsychotic on, or after, a dementia diagnosis. Each was matched with up to 15 patients with dementia with no history of antipsychotic use following diagnosis.
Almost 80% of antipsychotic prescriptions were for risperidone, quetiapine, haloperidol, and olanzapine.
Any antipsychotic use was associated with significantly higher risks for pneumonia (hazard ratio [HR], 2.03; 95% CI, 1.96-2.10), acute kidney injury (HR, 1.57; 95% CI, 1.48-1.66), stroke (HR, 1.54; 95% CI, 1.46-1.63), venous thromboembolism (HR, 1.52; 95% CI, 1.38-1.67), fracture (HR, 1.36; 95% CI, 1.30-1.44), myocardial infarction (HR, 1.22; 95% CI, 1.12-1.34), and heart failure (HR, 1.16; 95% CI, 1.09-1.24).
The risk for all conditions was highest within the first 3 months of treatment, with a cumulative incidence of pneumonia among antipsychotic users of 4.48% vs 1.49% among nonusers. At 1 year, this increased to 10.41% for users vs 5.63% for nonusers.
“Given the higher risks of adverse events in the early days after drug initiation, clinical examinations should be taken before, and clinical reviews conducted shortly after, the start of treatment,” the authors wrote. “Our study reaffirms that these drugs should only be prescribed for the shortest period possible.”
‘Serious Harms’
In an accompanying editorial, Raya Elfadel Kheirbek, MD, and Cristina LaFont, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, said the findings “highlight the need for careful justification of antipsychotic use in dementia care, including a comprehensive assessment of the benefits weighed against a broader range of serious harms than previously acknowledged.”
“Using antipsychotics for the management of dementia-related behaviors requires nuanced decision-making after careful assessment, informed by a personalized approach,” they continued. “Dr. Mok and colleagues call for a critical re-evaluation of antipsychotic use in this clinical setting.”
While the findings add to and expand what was already known, “we need to be clear that they don’t show antipsychotics cause all the adverse outcomes reported,” Masud Husain, DPhil, professor of neurology, University of Oxford, England, said in a statement.
While investigators attempted to use matched controls with dementia who had not received antipsychotics, “the people who were prescribed the drugs may simply have been more vulnerable to some of the conditions that occurred more frequently in them, such as pneumonia and cardiovascular disorders,” said Dr. Husain, who was not part of the research.
Although the study was not designed to explore reverse causality, the findings are important for clinicians who prescribe antipsychotics for patients with dementia, Robert Howard, professor of old age psychiatry, at the University of College London, London, England said in a statement.
“Initiation of these drugs in people with dementia should only ever be under specialist supervision, with involvement of patients and family members in informed discussion and review,” said Dr. Howard, who was not involved in the study.
The study was funded by the National Institute for Health and Care Research. Dr. Mok reported no relevant conflicts. Other authors’ disclosures are included in the original article. Dr. Hussain, Dr. Howard, Dr. Kheirbek, and Dr. LeFon reported no relevant conflicts.
A version of this article appeared on Medscape.com.
Antipsychotic use in older adults with dementia is associated with a significant increased risk for stroke, myocardial infarction, heart failure, pneumonia, fracture, acute kidney injury, and a range of other health problems compared with nonuse, new research showed.
The adverse events are far broader and pose more severe health risks than previously reported, investigators noted, and suggested greater caution is needed when prescribing antipsychotics to treat psychological symptoms of dementia.
The matched cohort study used patient registry data on nearly 174,000 people with dementia and compared those who were prescribed an antipsychotic on or after their dementia diagnosis with those who had not received a prescription for the drugs.
Any antipsychotic use was associated with double the risk for pneumonia, a 1.7-fold increased risk for acute kidney injury, and 1.6-fold higher odds of venous thromboembolism compared to nonuse.
Investigators found an increased risk for all outcomes studied, except for ventricular arrythmia, and risk was highest for most within the first week of treatment.
“Any potential benefits of antipsychotic treatment therefore need to be weighed against the risk of serious harm across multiple outcomes. Although there may be times when an antipsychotic prescription is the least bad option, clinicians should actively consider the risks, considering patients’ pre-existing comorbidities and living support,” lead investigator Pearl Mok, research fellow at the Centre for Pharmacoepidemiology and Drug Safety, The University of Manchester, Manchester, England, and colleagues wrote.
The findings were published online in The BMJ.
High Risk
Depression, aggression, anxiety, psychosis, and other behavioral and psychological symptoms are common in people with dementia. Despite earlier reports of increased risk for stroke and mortality with antipsychotic use, the drugs are frequently prescribed to treat these symptoms.
While some preliminary studies identified other adverse outcomes from antipsychotic use, results are limited and inconsistent.
Investigators used primary and secondary care data from the Clinical Practice Research Datalink in England. A total of 173,910 adults (63% women) had a dementia diagnosis between January 1998 and May 2018.
Of the total cohort, 35,339 patients were prescribed an antipsychotic on, or after, a dementia diagnosis. Each was matched with up to 15 patients with dementia with no history of antipsychotic use following diagnosis.
Almost 80% of antipsychotic prescriptions were for risperidone, quetiapine, haloperidol, and olanzapine.
Any antipsychotic use was associated with significantly higher risks for pneumonia (hazard ratio [HR], 2.03; 95% CI, 1.96-2.10), acute kidney injury (HR, 1.57; 95% CI, 1.48-1.66), stroke (HR, 1.54; 95% CI, 1.46-1.63), venous thromboembolism (HR, 1.52; 95% CI, 1.38-1.67), fracture (HR, 1.36; 95% CI, 1.30-1.44), myocardial infarction (HR, 1.22; 95% CI, 1.12-1.34), and heart failure (HR, 1.16; 95% CI, 1.09-1.24).
The risk for all conditions was highest within the first 3 months of treatment, with a cumulative incidence of pneumonia among antipsychotic users of 4.48% vs 1.49% among nonusers. At 1 year, this increased to 10.41% for users vs 5.63% for nonusers.
“Given the higher risks of adverse events in the early days after drug initiation, clinical examinations should be taken before, and clinical reviews conducted shortly after, the start of treatment,” the authors wrote. “Our study reaffirms that these drugs should only be prescribed for the shortest period possible.”
‘Serious Harms’
In an accompanying editorial, Raya Elfadel Kheirbek, MD, and Cristina LaFont, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, said the findings “highlight the need for careful justification of antipsychotic use in dementia care, including a comprehensive assessment of the benefits weighed against a broader range of serious harms than previously acknowledged.”
“Using antipsychotics for the management of dementia-related behaviors requires nuanced decision-making after careful assessment, informed by a personalized approach,” they continued. “Dr. Mok and colleagues call for a critical re-evaluation of antipsychotic use in this clinical setting.”
While the findings add to and expand what was already known, “we need to be clear that they don’t show antipsychotics cause all the adverse outcomes reported,” Masud Husain, DPhil, professor of neurology, University of Oxford, England, said in a statement.
While investigators attempted to use matched controls with dementia who had not received antipsychotics, “the people who were prescribed the drugs may simply have been more vulnerable to some of the conditions that occurred more frequently in them, such as pneumonia and cardiovascular disorders,” said Dr. Husain, who was not part of the research.
Although the study was not designed to explore reverse causality, the findings are important for clinicians who prescribe antipsychotics for patients with dementia, Robert Howard, professor of old age psychiatry, at the University of College London, London, England said in a statement.
“Initiation of these drugs in people with dementia should only ever be under specialist supervision, with involvement of patients and family members in informed discussion and review,” said Dr. Howard, who was not involved in the study.
The study was funded by the National Institute for Health and Care Research. Dr. Mok reported no relevant conflicts. Other authors’ disclosures are included in the original article. Dr. Hussain, Dr. Howard, Dr. Kheirbek, and Dr. LeFon reported no relevant conflicts.
A version of this article appeared on Medscape.com.
FROM THE BMJ
Vaporized Cannabis for Acute Migraine Yields Rapid, Sustained Relief
DENVER — , new research suggests.
“In this single-center randomized controlled trial across 247 treated migraine attacks, four puffs of vaporized THC-CBD mix were efficacious for acute migraine treatment,” said study investigator Nathaniel Marc Schuster, MD, with University of California San Diego Center for Pain Medicine.
The superiority of THC-CBD over placebo was “unlikely explained by unmasking given that in our blinding analysis most patients who got THC actually did not think they got some THC,” Dr. Schuster said.
He presented the results at the 2024 annual meeting of the American Academy of Neurology.
Sustained Pain Relief
Preclinical and retrospective studies point to antimigraine effects of cannabinoids, yet strong evidence of efficacy from a randomized controlled trial has been lacking.
The researchers tested the efficacy of cannabis for acute migraine in what they report is the first randomized, double-blind, placebo-controlled, crossover trial of adults with migraine.
Participants treated up to four separate moderate to severe migraine attacks, each with one of four different treatments. The four treatments were: 6% THC, 11% CBD, a mix of 6% THC and 11% CBD, or placebo flower from the National Institute on Drug Abuse that has a similar taste and smell to the other products.
The four treatments were vaporized in a randomized order, with at least 1 week washout between treatments. The primary endpoint was pain relief at 2 hours from vaporization. Secondary endpoints were freedom from pain and most bothersome symptom (MBS) at 2 hours from vaporization.
Of the 92 enrolled patients (mean age 41 years, 83% women), 19 treated zero migraine attacks thus leaving 73 patients who treated a total of 247 migraine attacks over the 1-year study.
The THC-CBD mix was superior to placebo at achieving pain relief (67.2% vs 46.6%; P = .016), pain freedom (34.5% vs 15.5%; P = .017), and MBS freedom (60.3% vs 34.5%; P = .005) at 2 hours.
The THC-CBD mix was also superior to placebo for sustained pain freedom at 24 hours and sustained MBS freedom at 24 and 48 hours.
There were no serious adverse events. The THC-CBD mix was better tolerated than THC-only was, with lower rates of euphoria and cognitive impairment and lower subjective highness, Dr. Schuster said.
Adverse events were more common with THC only (vs THC-CBD) “and this is really expected because CBD is known to bring down the side effects of THC,” Dr. Schuster noted.
Summing up his presentation, Dr. Schuster said, “This is one single-center study, and, of course, we need more data. We need to study the rates of medication overuse headache and the rates of cannabis use disorder that may develop with the use of cannabis for migraine.”
Cautious Optimism
Reached for comment, Hsiangkuo (Scott) Yuan, MD, PhD, Department of Neurology, Thomas Jefferson University, and director of clinical research, Jefferson Headache Center, Philadelphia, Pennsylvania, noted that the “statistically significant” differences between THC-CBD versus placebo on 2-hour pain relief, pain freedom and MBS freedom are “certainly very exciting, especially when no serious adverse event was reported.”
“Since THC has a narrow therapeutic window for analgesia (too high causes psychoactive side effects and may even worsen the pain), its dosing needs to be carefully controlled. The study was wisely designed to ensure uniform dosing from the vaporizer, which is usually safer than smoking or a vape pen and has a quicker onset than ingestion for acute usage,” said Dr. Yuan, who was not involved in the study.
“However, the optimal THC-CBD ratio and potency (percent THC) for acute migraine remain to be studied. Perhaps there is an individualized dose that can be obtained by titration. We also don’t know if the effect changes after repeated use,” Dr. Yuan cautioned.
He also noted that cannabis use was associated with medication overuse headache in a retrospective study, “although the causality remains to be determined.”
“While there was no serious adverse event, it is not completely risk-free, especially when cannabis is used repeatedly for a short duration. Since the physician does not have direct control over what happens at the dispensary, we need to counsel our patients more carefully when recommending cannabis/cannabinoids,” Dr. Yuan said.
Overall, he said he is “cautiously optimistic about cannabis use for acute migraine.”
This was an investigator-initiated study, with no commercial funding. Dr. Schuster has disclosed relationships with Schedule 1 Therapeutics, Averitas, Lundbeck, Eli Lilly, ShiraTronics, and Syneos. In the past 24 months, Dr. Yuan has served as a site investigator for Teva, AbbVie, Ipsen, Parema; received advisory/consultant fees from Salvia, Pfizer, AbbVie, Cerenovus; and royalties from Cambridge University Press and MedLink.
A version of this article appeared on Medscape.com.
DENVER — , new research suggests.
“In this single-center randomized controlled trial across 247 treated migraine attacks, four puffs of vaporized THC-CBD mix were efficacious for acute migraine treatment,” said study investigator Nathaniel Marc Schuster, MD, with University of California San Diego Center for Pain Medicine.
The superiority of THC-CBD over placebo was “unlikely explained by unmasking given that in our blinding analysis most patients who got THC actually did not think they got some THC,” Dr. Schuster said.
He presented the results at the 2024 annual meeting of the American Academy of Neurology.
Sustained Pain Relief
Preclinical and retrospective studies point to antimigraine effects of cannabinoids, yet strong evidence of efficacy from a randomized controlled trial has been lacking.
The researchers tested the efficacy of cannabis for acute migraine in what they report is the first randomized, double-blind, placebo-controlled, crossover trial of adults with migraine.
Participants treated up to four separate moderate to severe migraine attacks, each with one of four different treatments. The four treatments were: 6% THC, 11% CBD, a mix of 6% THC and 11% CBD, or placebo flower from the National Institute on Drug Abuse that has a similar taste and smell to the other products.
The four treatments were vaporized in a randomized order, with at least 1 week washout between treatments. The primary endpoint was pain relief at 2 hours from vaporization. Secondary endpoints were freedom from pain and most bothersome symptom (MBS) at 2 hours from vaporization.
Of the 92 enrolled patients (mean age 41 years, 83% women), 19 treated zero migraine attacks thus leaving 73 patients who treated a total of 247 migraine attacks over the 1-year study.
The THC-CBD mix was superior to placebo at achieving pain relief (67.2% vs 46.6%; P = .016), pain freedom (34.5% vs 15.5%; P = .017), and MBS freedom (60.3% vs 34.5%; P = .005) at 2 hours.
The THC-CBD mix was also superior to placebo for sustained pain freedom at 24 hours and sustained MBS freedom at 24 and 48 hours.
There were no serious adverse events. The THC-CBD mix was better tolerated than THC-only was, with lower rates of euphoria and cognitive impairment and lower subjective highness, Dr. Schuster said.
Adverse events were more common with THC only (vs THC-CBD) “and this is really expected because CBD is known to bring down the side effects of THC,” Dr. Schuster noted.
Summing up his presentation, Dr. Schuster said, “This is one single-center study, and, of course, we need more data. We need to study the rates of medication overuse headache and the rates of cannabis use disorder that may develop with the use of cannabis for migraine.”
Cautious Optimism
Reached for comment, Hsiangkuo (Scott) Yuan, MD, PhD, Department of Neurology, Thomas Jefferson University, and director of clinical research, Jefferson Headache Center, Philadelphia, Pennsylvania, noted that the “statistically significant” differences between THC-CBD versus placebo on 2-hour pain relief, pain freedom and MBS freedom are “certainly very exciting, especially when no serious adverse event was reported.”
“Since THC has a narrow therapeutic window for analgesia (too high causes psychoactive side effects and may even worsen the pain), its dosing needs to be carefully controlled. The study was wisely designed to ensure uniform dosing from the vaporizer, which is usually safer than smoking or a vape pen and has a quicker onset than ingestion for acute usage,” said Dr. Yuan, who was not involved in the study.
“However, the optimal THC-CBD ratio and potency (percent THC) for acute migraine remain to be studied. Perhaps there is an individualized dose that can be obtained by titration. We also don’t know if the effect changes after repeated use,” Dr. Yuan cautioned.
He also noted that cannabis use was associated with medication overuse headache in a retrospective study, “although the causality remains to be determined.”
“While there was no serious adverse event, it is not completely risk-free, especially when cannabis is used repeatedly for a short duration. Since the physician does not have direct control over what happens at the dispensary, we need to counsel our patients more carefully when recommending cannabis/cannabinoids,” Dr. Yuan said.
Overall, he said he is “cautiously optimistic about cannabis use for acute migraine.”
This was an investigator-initiated study, with no commercial funding. Dr. Schuster has disclosed relationships with Schedule 1 Therapeutics, Averitas, Lundbeck, Eli Lilly, ShiraTronics, and Syneos. In the past 24 months, Dr. Yuan has served as a site investigator for Teva, AbbVie, Ipsen, Parema; received advisory/consultant fees from Salvia, Pfizer, AbbVie, Cerenovus; and royalties from Cambridge University Press and MedLink.
A version of this article appeared on Medscape.com.
DENVER — , new research suggests.
“In this single-center randomized controlled trial across 247 treated migraine attacks, four puffs of vaporized THC-CBD mix were efficacious for acute migraine treatment,” said study investigator Nathaniel Marc Schuster, MD, with University of California San Diego Center for Pain Medicine.
The superiority of THC-CBD over placebo was “unlikely explained by unmasking given that in our blinding analysis most patients who got THC actually did not think they got some THC,” Dr. Schuster said.
He presented the results at the 2024 annual meeting of the American Academy of Neurology.
Sustained Pain Relief
Preclinical and retrospective studies point to antimigraine effects of cannabinoids, yet strong evidence of efficacy from a randomized controlled trial has been lacking.
The researchers tested the efficacy of cannabis for acute migraine in what they report is the first randomized, double-blind, placebo-controlled, crossover trial of adults with migraine.
Participants treated up to four separate moderate to severe migraine attacks, each with one of four different treatments. The four treatments were: 6% THC, 11% CBD, a mix of 6% THC and 11% CBD, or placebo flower from the National Institute on Drug Abuse that has a similar taste and smell to the other products.
The four treatments were vaporized in a randomized order, with at least 1 week washout between treatments. The primary endpoint was pain relief at 2 hours from vaporization. Secondary endpoints were freedom from pain and most bothersome symptom (MBS) at 2 hours from vaporization.
Of the 92 enrolled patients (mean age 41 years, 83% women), 19 treated zero migraine attacks thus leaving 73 patients who treated a total of 247 migraine attacks over the 1-year study.
The THC-CBD mix was superior to placebo at achieving pain relief (67.2% vs 46.6%; P = .016), pain freedom (34.5% vs 15.5%; P = .017), and MBS freedom (60.3% vs 34.5%; P = .005) at 2 hours.
The THC-CBD mix was also superior to placebo for sustained pain freedom at 24 hours and sustained MBS freedom at 24 and 48 hours.
There were no serious adverse events. The THC-CBD mix was better tolerated than THC-only was, with lower rates of euphoria and cognitive impairment and lower subjective highness, Dr. Schuster said.
Adverse events were more common with THC only (vs THC-CBD) “and this is really expected because CBD is known to bring down the side effects of THC,” Dr. Schuster noted.
Summing up his presentation, Dr. Schuster said, “This is one single-center study, and, of course, we need more data. We need to study the rates of medication overuse headache and the rates of cannabis use disorder that may develop with the use of cannabis for migraine.”
Cautious Optimism
Reached for comment, Hsiangkuo (Scott) Yuan, MD, PhD, Department of Neurology, Thomas Jefferson University, and director of clinical research, Jefferson Headache Center, Philadelphia, Pennsylvania, noted that the “statistically significant” differences between THC-CBD versus placebo on 2-hour pain relief, pain freedom and MBS freedom are “certainly very exciting, especially when no serious adverse event was reported.”
“Since THC has a narrow therapeutic window for analgesia (too high causes psychoactive side effects and may even worsen the pain), its dosing needs to be carefully controlled. The study was wisely designed to ensure uniform dosing from the vaporizer, which is usually safer than smoking or a vape pen and has a quicker onset than ingestion for acute usage,” said Dr. Yuan, who was not involved in the study.
“However, the optimal THC-CBD ratio and potency (percent THC) for acute migraine remain to be studied. Perhaps there is an individualized dose that can be obtained by titration. We also don’t know if the effect changes after repeated use,” Dr. Yuan cautioned.
He also noted that cannabis use was associated with medication overuse headache in a retrospective study, “although the causality remains to be determined.”
“While there was no serious adverse event, it is not completely risk-free, especially when cannabis is used repeatedly for a short duration. Since the physician does not have direct control over what happens at the dispensary, we need to counsel our patients more carefully when recommending cannabis/cannabinoids,” Dr. Yuan said.
Overall, he said he is “cautiously optimistic about cannabis use for acute migraine.”
This was an investigator-initiated study, with no commercial funding. Dr. Schuster has disclosed relationships with Schedule 1 Therapeutics, Averitas, Lundbeck, Eli Lilly, ShiraTronics, and Syneos. In the past 24 months, Dr. Yuan has served as a site investigator for Teva, AbbVie, Ipsen, Parema; received advisory/consultant fees from Salvia, Pfizer, AbbVie, Cerenovus; and royalties from Cambridge University Press and MedLink.
A version of this article appeared on Medscape.com.
FROM AAN 2024
Ocular Microbiome May Be Dry Eye Culprit
A mix of microbes may help explain why some people develop dry eye disease, new research showed.
This finding suggests that bacteria may cause dry eye and could someday point to new treatments for the condition and related disorders, which affect an estimated 27 million Americans, according to researchers.
Current treatments aim to preserve and enhance tears and tear production to ease the grittiness and itchiness that accompany dry eye disease.
To examine the role of the ocular microbiome in dry eye disease, scientists in Texas analyzed swab samples from 30 men and women, nine of whom had dry eye.
They found Streptococcus and Pedobacter species were the most common bacteria in healthy eyes.
In people with dry eye, however, more Acinetobacter species were detected.
“We think the metabolites produced by these bacteria are responsible for dry eye conditions,” study coauthor Pallavi Sharma said in a news release about the findings.
Sharma, a graduate student at Stephen F. Austin State University in Nacogdoches, Texas, presented this research last month at the annual meeting of the American Society for Biochemistry and Molecular Biology. The research team was led by Alexandra Van Kley, PhD, a professor of biology at the university.
“Once we understand the eye microbiota properly, it will improve disease diagnosis at an early stage,” Van Kley predicted in the news release. “This knowledge can also serve as a catalyst for developing innovative therapies aimed at preventing and treating ocular disease as well as those that affect the central microbiome site: The gut.”
Investigators in Australia have conducted similar experiments in patients with meibomian gland dysfunction, a condition marked by underproduction of key oils in the eye.
One group reported in August 2023 the finding of “detectable differences in the bacterial richness, diversity, and community structure of the conjunctiva and eyelid margin between individuals with meibomian gland dysfunction with and without lacrimal dysfunction, as well as to healthy controls.”
More research is needed to confirm and understand the findings, though, and “to determine if manipulating the microbiome could be a potential treatment for the condition,” they wrote.
A version of this article appeared on Medscape.com.
A mix of microbes may help explain why some people develop dry eye disease, new research showed.
This finding suggests that bacteria may cause dry eye and could someday point to new treatments for the condition and related disorders, which affect an estimated 27 million Americans, according to researchers.
Current treatments aim to preserve and enhance tears and tear production to ease the grittiness and itchiness that accompany dry eye disease.
To examine the role of the ocular microbiome in dry eye disease, scientists in Texas analyzed swab samples from 30 men and women, nine of whom had dry eye.
They found Streptococcus and Pedobacter species were the most common bacteria in healthy eyes.
In people with dry eye, however, more Acinetobacter species were detected.
“We think the metabolites produced by these bacteria are responsible for dry eye conditions,” study coauthor Pallavi Sharma said in a news release about the findings.
Sharma, a graduate student at Stephen F. Austin State University in Nacogdoches, Texas, presented this research last month at the annual meeting of the American Society for Biochemistry and Molecular Biology. The research team was led by Alexandra Van Kley, PhD, a professor of biology at the university.
“Once we understand the eye microbiota properly, it will improve disease diagnosis at an early stage,” Van Kley predicted in the news release. “This knowledge can also serve as a catalyst for developing innovative therapies aimed at preventing and treating ocular disease as well as those that affect the central microbiome site: The gut.”
Investigators in Australia have conducted similar experiments in patients with meibomian gland dysfunction, a condition marked by underproduction of key oils in the eye.
One group reported in August 2023 the finding of “detectable differences in the bacterial richness, diversity, and community structure of the conjunctiva and eyelid margin between individuals with meibomian gland dysfunction with and without lacrimal dysfunction, as well as to healthy controls.”
More research is needed to confirm and understand the findings, though, and “to determine if manipulating the microbiome could be a potential treatment for the condition,” they wrote.
A version of this article appeared on Medscape.com.
A mix of microbes may help explain why some people develop dry eye disease, new research showed.
This finding suggests that bacteria may cause dry eye and could someday point to new treatments for the condition and related disorders, which affect an estimated 27 million Americans, according to researchers.
Current treatments aim to preserve and enhance tears and tear production to ease the grittiness and itchiness that accompany dry eye disease.
To examine the role of the ocular microbiome in dry eye disease, scientists in Texas analyzed swab samples from 30 men and women, nine of whom had dry eye.
They found Streptococcus and Pedobacter species were the most common bacteria in healthy eyes.
In people with dry eye, however, more Acinetobacter species were detected.
“We think the metabolites produced by these bacteria are responsible for dry eye conditions,” study coauthor Pallavi Sharma said in a news release about the findings.
Sharma, a graduate student at Stephen F. Austin State University in Nacogdoches, Texas, presented this research last month at the annual meeting of the American Society for Biochemistry and Molecular Biology. The research team was led by Alexandra Van Kley, PhD, a professor of biology at the university.
“Once we understand the eye microbiota properly, it will improve disease diagnosis at an early stage,” Van Kley predicted in the news release. “This knowledge can also serve as a catalyst for developing innovative therapies aimed at preventing and treating ocular disease as well as those that affect the central microbiome site: The gut.”
Investigators in Australia have conducted similar experiments in patients with meibomian gland dysfunction, a condition marked by underproduction of key oils in the eye.
One group reported in August 2023 the finding of “detectable differences in the bacterial richness, diversity, and community structure of the conjunctiva and eyelid margin between individuals with meibomian gland dysfunction with and without lacrimal dysfunction, as well as to healthy controls.”
More research is needed to confirm and understand the findings, though, and “to determine if manipulating the microbiome could be a potential treatment for the condition,” they wrote.
A version of this article appeared on Medscape.com.
Heart Failure the Most Common Complication of Atrial Fibrillation, Not Stroke
FROM BMJ
The lifetime risk of atrial fibrillation (AF) increased from 2000 to 2022 from one in four to one in three, a Danish population-based study of temporal trends found.
Heart failure was the most frequent complication linked to this arrhythmia, with a lifetime risk of two in five, twice that of stroke, according to investigators led by Nicklas Vinter, MD, PhD, a postdoctoral researcher at the Danish Center for Health Service Research in the Department of Clinical Medicine at Aalborg University, Denmark.
Published in BMJ, the study found the lifetime risks of post-AF stroke, ischemic stroke, and myocardial infarction improved only modestly over time and remained high, with virtually no improvement in the lifetime risk of heart failure.
“Our work provides novel lifetime risk estimates that are instrumental in facilitating effective risk communication between patients and their physicians,” Dr. Vinter said in an interview. “The knowledge of risks from a lifelong perspective may serve as a motivator for patients to commence or intensify preventive efforts.” AF patients could, for example, adopt healthier lifestyles or adhere to prescribed medications, Dr. Vinter explained.
“The substantial lifetime risk of heart failure following atrial fibrillation necessitates heightened attention to its prevention and early detection,” Dr. Vinter said. “Furthermore, the high lifetime risk of stroke remains a critical complication, which highlights the importance of continuous attention to the initiation and maintenance of oral anticoagulation therapy.”
The Study
The cohort consisted of 3.5 million individuals (51.7% women) who did not have AF as of age 45 or older. These individuals were followed until incident AF, migration, death, or end of follow-up, whichever came first.
All 362,721 individuals with incident AF (53.6% men) but no prevalent complication were further followed over two time periods (2000-2010 and 2011-2020) until incident heart failure, stroke, or myocardial infarction.
Among the findings:
- Lifetime AF risk increased from 24.2% in 2000-2010 to 30.9% in 2011-2022, for a difference of 6.7% (95% confidence interval [CI], 6.5%-6.8%).
- Lifetime AF risk rose across all subgroups over time, with a larger increase in men and individuals with heart failure, myocardial infarction, stroke, diabetes, and chronic kidney disease.
- Lifetime risk of heart failure was 42.9% in 2000-2010 and 42.1% in 2011-2022, for a difference of −0.8% (95% CI, −3.8% to 2.2%).
- The lifetime risks of post-AF stroke and of myocardial infarction decreased slightly between the two periods, from 22.4% to 19.9% for stroke (difference −2.5%, 95% CI, −4.2% to −0.7%) and from 13.7% to 9.8% for myocardial infarction (−3.9%, 95% CI, −5.3% to −2.4%). No differential decrease between men and women emerged.
“Our novel quantification of the long-term downstream consequences of atrial fibrillation highlights the critical need for treatments to further decrease stroke risk as well as for heart failure prevention strategies among patients with atrial fibrillation,” the Danish researchers wrote.
Offering an outsider’s perspective, John P. Higgins, MD, MBA, MPhil, a sports cardiologist at McGovern Medical School at The University of Texas Health Science Center at Houston, said, “Think of atrial fibrillation as a barometer of underlying stress on the heart. When blood pressure is high, or a patient has underlying asymptomatic coronary artery disease or heart failure, they are more likely to have episodes of atrial fibrillation.”
According to Dr. Higgins, risk factors for AF are underappreciated in the United States and elsewhere, and primary care doctors need to be aware of them. “We should try to identify these risk factors and do primary prevention to improve risk factors to reduce the progression to heart failure and myocardial infarction and stroke. But lifelong prevention is even better, he added. “Doing things to prevent actually getting risk factors in the first place. So a healthy lifestyle including exercise, diet, hydration, sleep, relaxation, social contact, and a little sunlight might be the long-term keys and starting them at a young age, too.”
In an accompanying editorial, Jianhua Wu, PhD, a professor of biostatistics and health data science with the Wolfson Institute of Population Health at Queen Mary University of London, and a colleague, cited the study’s robust observational research and called the analysis noteworthy for its quantification of the long-term risks of post-AF sequelae. They cautioned, however, that its grouping into two 10-year periods (2000-2010 and 2011-2020) came at the cost of losing temporal resolution. They also called out the lack of reporting on the ethnic composition of the study population, a factor that influences lifetime AF risk, and the absence of subgroup analysis by socioeconomic status, which affects incidence and outcomes.
The editorialists noted that while interventions to prevent stroke dominated AF research and guidelines during the study time period, no evidence suggests these interventions can prevent incident heart failure. “Alignment of both randomised clinical trials and guidelines to better reflect the needs of the real-world population with atrial fibrillation is necessary because further improvements to patient prognosis are likely to require a broader perspective on atrial fibrillation management beyond prevention of stroke,” they wrote.
In the meantime this study “challenges research priorities and guideline design, and raises critical questions for the research and clinical communities about how the growing burden of atrial fibrillation can be stopped,” they wrote.
This work was supported by the Danish Cardiovascular Academy, which is funded by the Novo Nordisk Foundation, and The Danish Heart Foundation. Dr. Vinter has been an advisory board member and consultant for AstraZeneca and has an institutional research grant from BMS/Pfizer unrelated to the current study. He reported personal consulting fees from BMS and Pfizer. Other coauthors disclosed research support from and/or consulting work for private industry, as well as grants from not-for-profit research-funding organizations. Dr. Higgins had no competing interest to declare. The editorial writers had no relevant financial interests to declare. Dr. Wu is supported by Barts Charity.
FROM BMJ
The lifetime risk of atrial fibrillation (AF) increased from 2000 to 2022 from one in four to one in three, a Danish population-based study of temporal trends found.
Heart failure was the most frequent complication linked to this arrhythmia, with a lifetime risk of two in five, twice that of stroke, according to investigators led by Nicklas Vinter, MD, PhD, a postdoctoral researcher at the Danish Center for Health Service Research in the Department of Clinical Medicine at Aalborg University, Denmark.
Published in BMJ, the study found the lifetime risks of post-AF stroke, ischemic stroke, and myocardial infarction improved only modestly over time and remained high, with virtually no improvement in the lifetime risk of heart failure.
“Our work provides novel lifetime risk estimates that are instrumental in facilitating effective risk communication between patients and their physicians,” Dr. Vinter said in an interview. “The knowledge of risks from a lifelong perspective may serve as a motivator for patients to commence or intensify preventive efforts.” AF patients could, for example, adopt healthier lifestyles or adhere to prescribed medications, Dr. Vinter explained.
“The substantial lifetime risk of heart failure following atrial fibrillation necessitates heightened attention to its prevention and early detection,” Dr. Vinter said. “Furthermore, the high lifetime risk of stroke remains a critical complication, which highlights the importance of continuous attention to the initiation and maintenance of oral anticoagulation therapy.”
The Study
The cohort consisted of 3.5 million individuals (51.7% women) who did not have AF as of age 45 or older. These individuals were followed until incident AF, migration, death, or end of follow-up, whichever came first.
All 362,721 individuals with incident AF (53.6% men) but no prevalent complication were further followed over two time periods (2000-2010 and 2011-2020) until incident heart failure, stroke, or myocardial infarction.
Among the findings:
- Lifetime AF risk increased from 24.2% in 2000-2010 to 30.9% in 2011-2022, for a difference of 6.7% (95% confidence interval [CI], 6.5%-6.8%).
- Lifetime AF risk rose across all subgroups over time, with a larger increase in men and individuals with heart failure, myocardial infarction, stroke, diabetes, and chronic kidney disease.
- Lifetime risk of heart failure was 42.9% in 2000-2010 and 42.1% in 2011-2022, for a difference of −0.8% (95% CI, −3.8% to 2.2%).
- The lifetime risks of post-AF stroke and of myocardial infarction decreased slightly between the two periods, from 22.4% to 19.9% for stroke (difference −2.5%, 95% CI, −4.2% to −0.7%) and from 13.7% to 9.8% for myocardial infarction (−3.9%, 95% CI, −5.3% to −2.4%). No differential decrease between men and women emerged.
“Our novel quantification of the long-term downstream consequences of atrial fibrillation highlights the critical need for treatments to further decrease stroke risk as well as for heart failure prevention strategies among patients with atrial fibrillation,” the Danish researchers wrote.
Offering an outsider’s perspective, John P. Higgins, MD, MBA, MPhil, a sports cardiologist at McGovern Medical School at The University of Texas Health Science Center at Houston, said, “Think of atrial fibrillation as a barometer of underlying stress on the heart. When blood pressure is high, or a patient has underlying asymptomatic coronary artery disease or heart failure, they are more likely to have episodes of atrial fibrillation.”
According to Dr. Higgins, risk factors for AF are underappreciated in the United States and elsewhere, and primary care doctors need to be aware of them. “We should try to identify these risk factors and do primary prevention to improve risk factors to reduce the progression to heart failure and myocardial infarction and stroke. But lifelong prevention is even better, he added. “Doing things to prevent actually getting risk factors in the first place. So a healthy lifestyle including exercise, diet, hydration, sleep, relaxation, social contact, and a little sunlight might be the long-term keys and starting them at a young age, too.”
In an accompanying editorial, Jianhua Wu, PhD, a professor of biostatistics and health data science with the Wolfson Institute of Population Health at Queen Mary University of London, and a colleague, cited the study’s robust observational research and called the analysis noteworthy for its quantification of the long-term risks of post-AF sequelae. They cautioned, however, that its grouping into two 10-year periods (2000-2010 and 2011-2020) came at the cost of losing temporal resolution. They also called out the lack of reporting on the ethnic composition of the study population, a factor that influences lifetime AF risk, and the absence of subgroup analysis by socioeconomic status, which affects incidence and outcomes.
The editorialists noted that while interventions to prevent stroke dominated AF research and guidelines during the study time period, no evidence suggests these interventions can prevent incident heart failure. “Alignment of both randomised clinical trials and guidelines to better reflect the needs of the real-world population with atrial fibrillation is necessary because further improvements to patient prognosis are likely to require a broader perspective on atrial fibrillation management beyond prevention of stroke,” they wrote.
In the meantime this study “challenges research priorities and guideline design, and raises critical questions for the research and clinical communities about how the growing burden of atrial fibrillation can be stopped,” they wrote.
This work was supported by the Danish Cardiovascular Academy, which is funded by the Novo Nordisk Foundation, and The Danish Heart Foundation. Dr. Vinter has been an advisory board member and consultant for AstraZeneca and has an institutional research grant from BMS/Pfizer unrelated to the current study. He reported personal consulting fees from BMS and Pfizer. Other coauthors disclosed research support from and/or consulting work for private industry, as well as grants from not-for-profit research-funding organizations. Dr. Higgins had no competing interest to declare. The editorial writers had no relevant financial interests to declare. Dr. Wu is supported by Barts Charity.
FROM BMJ
The lifetime risk of atrial fibrillation (AF) increased from 2000 to 2022 from one in four to one in three, a Danish population-based study of temporal trends found.
Heart failure was the most frequent complication linked to this arrhythmia, with a lifetime risk of two in five, twice that of stroke, according to investigators led by Nicklas Vinter, MD, PhD, a postdoctoral researcher at the Danish Center for Health Service Research in the Department of Clinical Medicine at Aalborg University, Denmark.
Published in BMJ, the study found the lifetime risks of post-AF stroke, ischemic stroke, and myocardial infarction improved only modestly over time and remained high, with virtually no improvement in the lifetime risk of heart failure.
“Our work provides novel lifetime risk estimates that are instrumental in facilitating effective risk communication between patients and their physicians,” Dr. Vinter said in an interview. “The knowledge of risks from a lifelong perspective may serve as a motivator for patients to commence or intensify preventive efforts.” AF patients could, for example, adopt healthier lifestyles or adhere to prescribed medications, Dr. Vinter explained.
“The substantial lifetime risk of heart failure following atrial fibrillation necessitates heightened attention to its prevention and early detection,” Dr. Vinter said. “Furthermore, the high lifetime risk of stroke remains a critical complication, which highlights the importance of continuous attention to the initiation and maintenance of oral anticoagulation therapy.”
The Study
The cohort consisted of 3.5 million individuals (51.7% women) who did not have AF as of age 45 or older. These individuals were followed until incident AF, migration, death, or end of follow-up, whichever came first.
All 362,721 individuals with incident AF (53.6% men) but no prevalent complication were further followed over two time periods (2000-2010 and 2011-2020) until incident heart failure, stroke, or myocardial infarction.
Among the findings:
- Lifetime AF risk increased from 24.2% in 2000-2010 to 30.9% in 2011-2022, for a difference of 6.7% (95% confidence interval [CI], 6.5%-6.8%).
- Lifetime AF risk rose across all subgroups over time, with a larger increase in men and individuals with heart failure, myocardial infarction, stroke, diabetes, and chronic kidney disease.
- Lifetime risk of heart failure was 42.9% in 2000-2010 and 42.1% in 2011-2022, for a difference of −0.8% (95% CI, −3.8% to 2.2%).
- The lifetime risks of post-AF stroke and of myocardial infarction decreased slightly between the two periods, from 22.4% to 19.9% for stroke (difference −2.5%, 95% CI, −4.2% to −0.7%) and from 13.7% to 9.8% for myocardial infarction (−3.9%, 95% CI, −5.3% to −2.4%). No differential decrease between men and women emerged.
“Our novel quantification of the long-term downstream consequences of atrial fibrillation highlights the critical need for treatments to further decrease stroke risk as well as for heart failure prevention strategies among patients with atrial fibrillation,” the Danish researchers wrote.
Offering an outsider’s perspective, John P. Higgins, MD, MBA, MPhil, a sports cardiologist at McGovern Medical School at The University of Texas Health Science Center at Houston, said, “Think of atrial fibrillation as a barometer of underlying stress on the heart. When blood pressure is high, or a patient has underlying asymptomatic coronary artery disease or heart failure, they are more likely to have episodes of atrial fibrillation.”
According to Dr. Higgins, risk factors for AF are underappreciated in the United States and elsewhere, and primary care doctors need to be aware of them. “We should try to identify these risk factors and do primary prevention to improve risk factors to reduce the progression to heart failure and myocardial infarction and stroke. But lifelong prevention is even better, he added. “Doing things to prevent actually getting risk factors in the first place. So a healthy lifestyle including exercise, diet, hydration, sleep, relaxation, social contact, and a little sunlight might be the long-term keys and starting them at a young age, too.”
In an accompanying editorial, Jianhua Wu, PhD, a professor of biostatistics and health data science with the Wolfson Institute of Population Health at Queen Mary University of London, and a colleague, cited the study’s robust observational research and called the analysis noteworthy for its quantification of the long-term risks of post-AF sequelae. They cautioned, however, that its grouping into two 10-year periods (2000-2010 and 2011-2020) came at the cost of losing temporal resolution. They also called out the lack of reporting on the ethnic composition of the study population, a factor that influences lifetime AF risk, and the absence of subgroup analysis by socioeconomic status, which affects incidence and outcomes.
The editorialists noted that while interventions to prevent stroke dominated AF research and guidelines during the study time period, no evidence suggests these interventions can prevent incident heart failure. “Alignment of both randomised clinical trials and guidelines to better reflect the needs of the real-world population with atrial fibrillation is necessary because further improvements to patient prognosis are likely to require a broader perspective on atrial fibrillation management beyond prevention of stroke,” they wrote.
In the meantime this study “challenges research priorities and guideline design, and raises critical questions for the research and clinical communities about how the growing burden of atrial fibrillation can be stopped,” they wrote.
This work was supported by the Danish Cardiovascular Academy, which is funded by the Novo Nordisk Foundation, and The Danish Heart Foundation. Dr. Vinter has been an advisory board member and consultant for AstraZeneca and has an institutional research grant from BMS/Pfizer unrelated to the current study. He reported personal consulting fees from BMS and Pfizer. Other coauthors disclosed research support from and/or consulting work for private industry, as well as grants from not-for-profit research-funding organizations. Dr. Higgins had no competing interest to declare. The editorial writers had no relevant financial interests to declare. Dr. Wu is supported by Barts Charity.