New UTI Guideline Offers Treatment Clarity, Reveals Gaps in Knowledge

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Wed, 11/27/2024 - 04:07

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

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

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

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

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

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

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

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

The key guideline recommendations are briefly summarized below.

Preventive Strategies for UTI

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

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

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

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

 

Empirical Treatment Recommendations

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

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

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

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

 

Stewardship and Clinical Management

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

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

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

 

Special Considerations for Urologic Procedures

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The key guideline recommendations are briefly summarized below.

Preventive Strategies for UTI

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

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

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

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

 

Empirical Treatment Recommendations

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

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

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

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

 

Stewardship and Clinical Management

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

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

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

 

Special Considerations for Urologic Procedures

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The key guideline recommendations are briefly summarized below.

Preventive Strategies for UTI

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

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

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

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

 

Empirical Treatment Recommendations

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

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

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

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

 

Stewardship and Clinical Management

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

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

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

 

Special Considerations for Urologic Procedures

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

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

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

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

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

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

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

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

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

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PRECISE-DAPT Score Predicts GI Bleeding Risk Among Post-PCI Patients

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— Gastrointestinal (GI) bleeding after percutaneous coronary intervention (PCI) among patients on dual antiplatelet therapy (DAPT) remains risky in terms of morbidity and mortality, but the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score could help predict that risk, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

In a predominantly Hispanic population in Texas, 2.5% of post-PCI patients on DAPT had GI bleeding in the first year. The PRECISE-DAPT score helped to predict GI bleeding among high-risk and moderate-risk patients.

“Our study established that the PRECISE-DAPT score possesses a moderate predictive accuracy not only for overall bleeding risk but also specifically for gastrointestinal bleeding,” said lead author Jesus Guzman, MD, a gastroenterology fellow at the Texas Tech University Health Sciences Center El Paso.

Current guidelines from the American College of Cardiology and American Heart Association recommend DAPT for 6-12 months post-PCI, with consideration for shorter durations in patients with lower ischemic risks but higher bleeding risks.

“Interestingly, some of these patients were on DAPT for more than 2 years, which goes beyond the guidelines,” he said. “In this patient population, this has to do with them being lost to follow-up and getting reestablished, and they kept refilling their prescriptions.”

Guzman and colleagues conducted a retrospective cohort study of patients receiving DAPT after PCI from 2014 to 2021. They looked for GI bleeding rates at 1 year and across the duration of the study period, as well as endoscopic indications, findings, concurrent antiplatelet therapy, and the primary cause of bleeding.

In addition, the research team evaluated the predictive value of the PRECISE-DAPT score, which categorizes patients based on low risk (≤ 17), moderate risk (18-24), and high risk (≥ 25) for bleeding. The score aims to optimize the balance between bleeding and ischemic risks, Guzman said, by incorporating five factors: Age, creatinine clearance, hemoglobin, white blood cell count, and history of spontaneous bleeding.

Among 1067 patients, 563 (57.9%) received clopidogrel and 409 (42%) received ticagrelor. The overall cohort was 66.6% men, 77.1% Hispanic, and had a mean age of 62 years.

The GI bleeding rate was 2.5% at 1-year post-PCI among 27 patients and 3.7% for the study duration among 39 patients, with a median follow-up of 2.2 years.

Among the 39 GI bleeds, 41% were lower GI bleeds, 28% were upper GI bleeds, 15% were small bowel bleeds, and 15% were undetermined. The most frequent etiology was colon cancer, accounting for 18% of bleeds, followed by 15% for gastric ulcers, 10% for diverticular bleeds, and 10% for hemorrhoidal bleeds.

In general, analyses indicated no significant differences in GI bleeding between patients on clopidogrel (21.2%) and those on ticagrelor (19.2%).

However, the odds of GI bleeding were significantly higher in patients with high-risk PRECISE-DAPT scores (odds ratio [OR], 2.5) and moderate-risk scores (OR, 2.8) than in those with low-risk scores. The majority of patients without GI bleeding had scores < 17, whereas the majority of patients with GI bleeding had scores > 24. An optimal threshold for the PRECISE-DAPT score was identified as ≥ 19.

“When patients on DAPT present with GI bleeding, it can be a clinical conundrum for gastroenterologists and cardiologists, especially when it can be a life-or-death event, and stopping DAPT can increase risk of thrombosis,” said Jeff Taclob, MD, a hepatology fellow at The University of Tennessee Health Science Center in Memphis. Taclob, who wasn’t involved with the study, attended the conference session.

“In this population in El Paso, in particular, many patients don’t have adequate healthcare, may be lost to follow-up, and get their prescriptions filled elsewhere, such as Juárez, Mexico,” he said. “Then they come in with this life-threatening bleed, so we need to focus more on their risks.”

Paying attention to specific patient populations, cultures, and values remains important for patient communication and clinical decision-making, Taclob noted.

“In this population of older men, there’s often a macho persona where they don’t want to seek help,” he said. “DAPT criteria could differ in other populations, but here, the PRECISE-DAPT score appeared to help.”

The study was awarded the ACG Outstanding Research Award in the GI Bleeding Category (Trainee). Guzman and Taclob reported no relevant disclosures.

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

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— Gastrointestinal (GI) bleeding after percutaneous coronary intervention (PCI) among patients on dual antiplatelet therapy (DAPT) remains risky in terms of morbidity and mortality, but the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score could help predict that risk, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

In a predominantly Hispanic population in Texas, 2.5% of post-PCI patients on DAPT had GI bleeding in the first year. The PRECISE-DAPT score helped to predict GI bleeding among high-risk and moderate-risk patients.

“Our study established that the PRECISE-DAPT score possesses a moderate predictive accuracy not only for overall bleeding risk but also specifically for gastrointestinal bleeding,” said lead author Jesus Guzman, MD, a gastroenterology fellow at the Texas Tech University Health Sciences Center El Paso.

Current guidelines from the American College of Cardiology and American Heart Association recommend DAPT for 6-12 months post-PCI, with consideration for shorter durations in patients with lower ischemic risks but higher bleeding risks.

“Interestingly, some of these patients were on DAPT for more than 2 years, which goes beyond the guidelines,” he said. “In this patient population, this has to do with them being lost to follow-up and getting reestablished, and they kept refilling their prescriptions.”

Guzman and colleagues conducted a retrospective cohort study of patients receiving DAPT after PCI from 2014 to 2021. They looked for GI bleeding rates at 1 year and across the duration of the study period, as well as endoscopic indications, findings, concurrent antiplatelet therapy, and the primary cause of bleeding.

In addition, the research team evaluated the predictive value of the PRECISE-DAPT score, which categorizes patients based on low risk (≤ 17), moderate risk (18-24), and high risk (≥ 25) for bleeding. The score aims to optimize the balance between bleeding and ischemic risks, Guzman said, by incorporating five factors: Age, creatinine clearance, hemoglobin, white blood cell count, and history of spontaneous bleeding.

Among 1067 patients, 563 (57.9%) received clopidogrel and 409 (42%) received ticagrelor. The overall cohort was 66.6% men, 77.1% Hispanic, and had a mean age of 62 years.

The GI bleeding rate was 2.5% at 1-year post-PCI among 27 patients and 3.7% for the study duration among 39 patients, with a median follow-up of 2.2 years.

Among the 39 GI bleeds, 41% were lower GI bleeds, 28% were upper GI bleeds, 15% were small bowel bleeds, and 15% were undetermined. The most frequent etiology was colon cancer, accounting for 18% of bleeds, followed by 15% for gastric ulcers, 10% for diverticular bleeds, and 10% for hemorrhoidal bleeds.

In general, analyses indicated no significant differences in GI bleeding between patients on clopidogrel (21.2%) and those on ticagrelor (19.2%).

However, the odds of GI bleeding were significantly higher in patients with high-risk PRECISE-DAPT scores (odds ratio [OR], 2.5) and moderate-risk scores (OR, 2.8) than in those with low-risk scores. The majority of patients without GI bleeding had scores < 17, whereas the majority of patients with GI bleeding had scores > 24. An optimal threshold for the PRECISE-DAPT score was identified as ≥ 19.

“When patients on DAPT present with GI bleeding, it can be a clinical conundrum for gastroenterologists and cardiologists, especially when it can be a life-or-death event, and stopping DAPT can increase risk of thrombosis,” said Jeff Taclob, MD, a hepatology fellow at The University of Tennessee Health Science Center in Memphis. Taclob, who wasn’t involved with the study, attended the conference session.

“In this population in El Paso, in particular, many patients don’t have adequate healthcare, may be lost to follow-up, and get their prescriptions filled elsewhere, such as Juárez, Mexico,” he said. “Then they come in with this life-threatening bleed, so we need to focus more on their risks.”

Paying attention to specific patient populations, cultures, and values remains important for patient communication and clinical decision-making, Taclob noted.

“In this population of older men, there’s often a macho persona where they don’t want to seek help,” he said. “DAPT criteria could differ in other populations, but here, the PRECISE-DAPT score appeared to help.”

The study was awarded the ACG Outstanding Research Award in the GI Bleeding Category (Trainee). Guzman and Taclob reported no relevant disclosures.

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

— Gastrointestinal (GI) bleeding after percutaneous coronary intervention (PCI) among patients on dual antiplatelet therapy (DAPT) remains risky in terms of morbidity and mortality, but the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score could help predict that risk, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

In a predominantly Hispanic population in Texas, 2.5% of post-PCI patients on DAPT had GI bleeding in the first year. The PRECISE-DAPT score helped to predict GI bleeding among high-risk and moderate-risk patients.

“Our study established that the PRECISE-DAPT score possesses a moderate predictive accuracy not only for overall bleeding risk but also specifically for gastrointestinal bleeding,” said lead author Jesus Guzman, MD, a gastroenterology fellow at the Texas Tech University Health Sciences Center El Paso.

Current guidelines from the American College of Cardiology and American Heart Association recommend DAPT for 6-12 months post-PCI, with consideration for shorter durations in patients with lower ischemic risks but higher bleeding risks.

“Interestingly, some of these patients were on DAPT for more than 2 years, which goes beyond the guidelines,” he said. “In this patient population, this has to do with them being lost to follow-up and getting reestablished, and they kept refilling their prescriptions.”

Guzman and colleagues conducted a retrospective cohort study of patients receiving DAPT after PCI from 2014 to 2021. They looked for GI bleeding rates at 1 year and across the duration of the study period, as well as endoscopic indications, findings, concurrent antiplatelet therapy, and the primary cause of bleeding.

In addition, the research team evaluated the predictive value of the PRECISE-DAPT score, which categorizes patients based on low risk (≤ 17), moderate risk (18-24), and high risk (≥ 25) for bleeding. The score aims to optimize the balance between bleeding and ischemic risks, Guzman said, by incorporating five factors: Age, creatinine clearance, hemoglobin, white blood cell count, and history of spontaneous bleeding.

Among 1067 patients, 563 (57.9%) received clopidogrel and 409 (42%) received ticagrelor. The overall cohort was 66.6% men, 77.1% Hispanic, and had a mean age of 62 years.

The GI bleeding rate was 2.5% at 1-year post-PCI among 27 patients and 3.7% for the study duration among 39 patients, with a median follow-up of 2.2 years.

Among the 39 GI bleeds, 41% were lower GI bleeds, 28% were upper GI bleeds, 15% were small bowel bleeds, and 15% were undetermined. The most frequent etiology was colon cancer, accounting for 18% of bleeds, followed by 15% for gastric ulcers, 10% for diverticular bleeds, and 10% for hemorrhoidal bleeds.

In general, analyses indicated no significant differences in GI bleeding between patients on clopidogrel (21.2%) and those on ticagrelor (19.2%).

However, the odds of GI bleeding were significantly higher in patients with high-risk PRECISE-DAPT scores (odds ratio [OR], 2.5) and moderate-risk scores (OR, 2.8) than in those with low-risk scores. The majority of patients without GI bleeding had scores < 17, whereas the majority of patients with GI bleeding had scores > 24. An optimal threshold for the PRECISE-DAPT score was identified as ≥ 19.

“When patients on DAPT present with GI bleeding, it can be a clinical conundrum for gastroenterologists and cardiologists, especially when it can be a life-or-death event, and stopping DAPT can increase risk of thrombosis,” said Jeff Taclob, MD, a hepatology fellow at The University of Tennessee Health Science Center in Memphis. Taclob, who wasn’t involved with the study, attended the conference session.

“In this population in El Paso, in particular, many patients don’t have adequate healthcare, may be lost to follow-up, and get their prescriptions filled elsewhere, such as Juárez, Mexico,” he said. “Then they come in with this life-threatening bleed, so we need to focus more on their risks.”

Paying attention to specific patient populations, cultures, and values remains important for patient communication and clinical decision-making, Taclob noted.

“In this population of older men, there’s often a macho persona where they don’t want to seek help,” he said. “DAPT criteria could differ in other populations, but here, the PRECISE-DAPT score appeared to help.”

The study was awarded the ACG Outstanding Research Award in the GI Bleeding Category (Trainee). Guzman and Taclob reported no relevant disclosures.

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

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Periodontitis Management: GPs Should Play a Role

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Periodontitis is a chronic inflammatory disease that triggers a local immuno-inflammatory response, potentially leading to periodontal tissue destruction and tooth loss. Affecting 1.1 billion people worldwide, periodontitis is recognized as a significant public health issue. It is also linked to a number of other conditions, such as diabetes, cardiovascular disease, and respiratory disorders. The European Federation of Periodontology recently published a consensus report recommending that the optimal management of periodontitis should involve a collaboration between general practitioners (GPs) and oral health professionals.

Diabetes and Periodontitis

A bidirectional association exists between diabetes and periodontitis. Hyperglycemia accelerates periodontitis progression by promoting inflammation and hindering the healing process, while periodontitis is associated with higher hemoglobin A1c levels in patients with diabetes and an increased risk for diabetes development in others. Intervention studies have demonstrated the positive effect of glycemic control on periodontitis and vice versa, with periodontal treatment improving A1c levels.

GPs can raise awareness of the links between these conditions as well as emphasize the benefits of addressing both metabolic and periodontal abnormalities. They should refer patients with diabetes to oral health specialists and look for signs of periodontitis, such as bleeding gums and loose teeth, in patients with diabetes and those with prediabetes.

 

Cardiovascular Diseases and Periodontitis

Cardiovascular diseases and periodontitis are linked by their epidemiological associations and common biologic mechanisms. This connection can be explained by some of their shared risk factors, such as smoking and systemic inflammatory pathways. Although no intervention studies have shown a direct reduction in cardiovascular risk from periodontal care, two studies have demonstrated improvements in surrogate markers such as blood pressure and arterial stiffness. GPs should inquire about symptoms of periodontitis in cardiovascular patients and, if necessary, refer them to oral health specialists. Periodontal treatments, whether surgical or nonsurgical, pose no risk for patients receiving well-managed secondary preventive treatments.

 

Respiratory Diseases and Periodontitis

The primary evidence linking periodontitis with chronic respiratory diseases concerns chronic obstructive pulmonary disease (COPD). Individuals with periodontitis have a 33% higher risk of developing COPD, and patients with COPD and periodontitis may experience a greater decline in lung function. An established association also exists between periodontitis and obstructive sleep apnea, although the data remain inconclusive regarding a link with asthma. GPs should encourage patients with COPD to quit smoking, as it benefits both respiratory and oral health.

Finally, based on meta-analyses of COVID-19, experts note significant associations between periodontitis and the need for assisted ventilation or the risk for death during a COVID-19 infection.

This story was translated from Univadis France 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.

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Periodontitis is a chronic inflammatory disease that triggers a local immuno-inflammatory response, potentially leading to periodontal tissue destruction and tooth loss. Affecting 1.1 billion people worldwide, periodontitis is recognized as a significant public health issue. It is also linked to a number of other conditions, such as diabetes, cardiovascular disease, and respiratory disorders. The European Federation of Periodontology recently published a consensus report recommending that the optimal management of periodontitis should involve a collaboration between general practitioners (GPs) and oral health professionals.

Diabetes and Periodontitis

A bidirectional association exists between diabetes and periodontitis. Hyperglycemia accelerates periodontitis progression by promoting inflammation and hindering the healing process, while periodontitis is associated with higher hemoglobin A1c levels in patients with diabetes and an increased risk for diabetes development in others. Intervention studies have demonstrated the positive effect of glycemic control on periodontitis and vice versa, with periodontal treatment improving A1c levels.

GPs can raise awareness of the links between these conditions as well as emphasize the benefits of addressing both metabolic and periodontal abnormalities. They should refer patients with diabetes to oral health specialists and look for signs of periodontitis, such as bleeding gums and loose teeth, in patients with diabetes and those with prediabetes.

 

Cardiovascular Diseases and Periodontitis

Cardiovascular diseases and periodontitis are linked by their epidemiological associations and common biologic mechanisms. This connection can be explained by some of their shared risk factors, such as smoking and systemic inflammatory pathways. Although no intervention studies have shown a direct reduction in cardiovascular risk from periodontal care, two studies have demonstrated improvements in surrogate markers such as blood pressure and arterial stiffness. GPs should inquire about symptoms of periodontitis in cardiovascular patients and, if necessary, refer them to oral health specialists. Periodontal treatments, whether surgical or nonsurgical, pose no risk for patients receiving well-managed secondary preventive treatments.

 

Respiratory Diseases and Periodontitis

The primary evidence linking periodontitis with chronic respiratory diseases concerns chronic obstructive pulmonary disease (COPD). Individuals with periodontitis have a 33% higher risk of developing COPD, and patients with COPD and periodontitis may experience a greater decline in lung function. An established association also exists between periodontitis and obstructive sleep apnea, although the data remain inconclusive regarding a link with asthma. GPs should encourage patients with COPD to quit smoking, as it benefits both respiratory and oral health.

Finally, based on meta-analyses of COVID-19, experts note significant associations between periodontitis and the need for assisted ventilation or the risk for death during a COVID-19 infection.

This story was translated from Univadis France 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.

Periodontitis is a chronic inflammatory disease that triggers a local immuno-inflammatory response, potentially leading to periodontal tissue destruction and tooth loss. Affecting 1.1 billion people worldwide, periodontitis is recognized as a significant public health issue. It is also linked to a number of other conditions, such as diabetes, cardiovascular disease, and respiratory disorders. The European Federation of Periodontology recently published a consensus report recommending that the optimal management of periodontitis should involve a collaboration between general practitioners (GPs) and oral health professionals.

Diabetes and Periodontitis

A bidirectional association exists between diabetes and periodontitis. Hyperglycemia accelerates periodontitis progression by promoting inflammation and hindering the healing process, while periodontitis is associated with higher hemoglobin A1c levels in patients with diabetes and an increased risk for diabetes development in others. Intervention studies have demonstrated the positive effect of glycemic control on periodontitis and vice versa, with periodontal treatment improving A1c levels.

GPs can raise awareness of the links between these conditions as well as emphasize the benefits of addressing both metabolic and periodontal abnormalities. They should refer patients with diabetes to oral health specialists and look for signs of periodontitis, such as bleeding gums and loose teeth, in patients with diabetes and those with prediabetes.

 

Cardiovascular Diseases and Periodontitis

Cardiovascular diseases and periodontitis are linked by their epidemiological associations and common biologic mechanisms. This connection can be explained by some of their shared risk factors, such as smoking and systemic inflammatory pathways. Although no intervention studies have shown a direct reduction in cardiovascular risk from periodontal care, two studies have demonstrated improvements in surrogate markers such as blood pressure and arterial stiffness. GPs should inquire about symptoms of periodontitis in cardiovascular patients and, if necessary, refer them to oral health specialists. Periodontal treatments, whether surgical or nonsurgical, pose no risk for patients receiving well-managed secondary preventive treatments.

 

Respiratory Diseases and Periodontitis

The primary evidence linking periodontitis with chronic respiratory diseases concerns chronic obstructive pulmonary disease (COPD). Individuals with periodontitis have a 33% higher risk of developing COPD, and patients with COPD and periodontitis may experience a greater decline in lung function. An established association also exists between periodontitis and obstructive sleep apnea, although the data remain inconclusive regarding a link with asthma. GPs should encourage patients with COPD to quit smoking, as it benefits both respiratory and oral health.

Finally, based on meta-analyses of COVID-19, experts note significant associations between periodontitis and the need for assisted ventilation or the risk for death during a COVID-19 infection.

This story was translated from Univadis France 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.

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Building an AI Army of Digital Twins to Fight Cancer

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A patient has cancer. It’s decision time.

Clinician and patient alike face, really, the ultimate challenge when making those decisions. They have to consider the patient’s individual circumstances, available treatment options, potential side effects, relevant clinical data such as the patient’s genetic profile and cancer specifics, and more.

“That’s a lot of information to hold,” said Uzma Asghar, PhD, MRCP, a British consultant medical oncologist at The Royal Marsden Hospital and a chief scientific officer at Concr LTD.

What if there were a way to test — quickly and accurately — all the potential paths forward?

That’s the goal of digital twins. An artificial intelligence (AI)–based program uses all the known data on patients and their types of illness and creates a “twin” that can be used over and over to simulate disease progression, test treatments, and predict individual responses to therapies.

“What the [digital twin] model can do for the clinician is to hold all that information and process it really quickly, within a couple of minutes,” Asghar noted.

A digital twin is more than just a computer model or simulation because it copies a real-world person and relies on real-world data. Some digital twin programs also integrate new information as it becomes available. This technology holds promise for personalized medicine, drug discovery, developing screening strategies, and better understanding diseases.
 

How to Deliver a Twin

To create a digital twin, experts develop a computer model with data to hone its expertise in an area of medicine, such as cancer types and treatments. Then “you train the model on information it’s seen, and then introduce a patient and patient’s information,” said Asghar.

Asghar is currently working with colleagues to develop digital twins that could eventually help solve the aforementioned cancer scenario — a doctor and patient decide the best course of cancer treatment. But their applications are manifold, particularly in clinical research.

Digital twins often include a machine learning component, which would fall under the umbrella term of AI, said Asghar, but it’s not like ChatGPT or other generative AI modules many people are now familiar with.

“The difference here is the model is not there to replace the clinician or to replace clinical trials,” Asghar noted. Instead, digital twins help make decisions faster in a way that can be more affordable.
 

Digital Twins to Predict Cancer Outcomes

Asghar is currently involved in UK clinical trials enrolling patients with cancer to test the accuracy of digital twin programs.

At this point, these studies do not yet use digital twins to guide the course of treatment, which is something they hope to do eventually. For now, they are still at the validation phase — the digital twin program makes predictions about the treatments and then the researchers later evaluate how accurate the predictions turned out to be based on real information from the enrolled patients.

Their current model gives predictions for RECIST (response evaluation criteria in solid tumor), treatment response, and survival. In addition to collecting data from ongoing clinical trials, they’ve used retrospective data, such as from the Cancer Tumor Atlas, to test the model.

“We’ve clinically validated it now in over 9000 patients,” said Asghar, who noted that they are constantly testing it on new patients. Their data include 30 chemotherapies and 23 cancer types, but they are focusing on four: Triple-negative breast cancer, cancer of unknown primary, pancreatic cancer, and colorectal cancer.

“The reason for choosing those four cancer types is that they are aggressive, their response to chemotherapy isn’t as great, and the outcome for those patient populations, there’s significant room for improvement,” Asghar explained.

Currently, Asghar said, the model is around 80%-90% correct in predicting what the actual clinical outcomes turn out to be.

The final stage of their work, before it becomes widely available to clinicians, will be to integrate it into a clinical trial in which some clinicians use the model to make decisions about treatment vs some who don’t use the model. By studying patient outcomes in both groups, they will be able to determine the value of the digital twin program they created.
 

 

 

What Else Can a Twin Do? A Lot

While a model that helps clinicians make decisions about cancer treatments may be among the first digital twin programs that become widely available, there are many other kinds of digital twins in the works.

For example, a digital twin could be used as a benchmark for a patient to determine how their cancer might have progressed without treatment. Say a patient’s tumor grew during treatment, it might seem like the treatment failed, but a digital twin might show that if left untreated, the tumor would have grown five times as fast, said Paul Macklin, PhD, professor in the Department of Intelligent Systems Engineering at Indiana University Bloomington.

Alternatively, if the virtual patient’s tumor is around the same size as the real patient’s tumor, “that means that treatment has lost its efficacy. It’s time to do something new,” said Macklin. And a digital twin could help with not only choosing a therapy but also choosing a dosing schedule, he noted.

The models can also be updated as new treatments come out, which could help clinicians virtually explore how they might affect a patient before having that patient switch treatments.

Digital twins could also assist in decision-making based on a patient’s priorities and real-life circumstances. “Maybe your priority is not necessarily to shrink this [tumor] at all costs ... maybe your priority is some mix of that and also quality of life,” Macklin said, referring to potential side effects. Or if someone lives 3 hours from the nearest cancer center, a digital twin could help determine whether less frequent treatments could still be effective.

And while much of the activity around digital twins in biomedical research has been focused on cancer, Asghar said the technology has the potential to be applied to other diseases as well. A digital twin for cardiovascular disease could help doctors choose the best treatment. It could also integrate new information from a smartwatch or glucose monitor to make better predictions and help doctors adjust the treatment plan.
 

Faster, More Effective Research With Twins

Because digital twin programs can quickly analyze large datasets, they can also make real-world studies more effective and efficient.

Though digital twins would not fully replace real clinical trials, they could help run through preliminary scenarios before starting a full clinical trial, which would “save everybody some money, time and pain and risk,” said Macklin.

It’s also possible to use digital twins to design better screening strategies for early cancer detection and monitoring, said Ioannis Zervantonakis, PhD, a bioengineering professor at the University of Pittsburgh.

Zervantonakis is tapping digital twin technology for research that homes in on understanding tumors. In this case, the digital twin is a virtual representation of a real tumor, complete with its complex network of cells and the surrounding tissue.

Zervantonakis’ lab is using the technology to study cell-cell interactions in the tumor microenvironment, with a focus on human epidermal growth factor receptor 2–targeted therapy resistance in breast cancer. The digital twin they developed will simulate tumor growth, predict drug response, analyze cellular interactions, and optimize treatment strategies.
 

 

 

The Long Push Forward

One big hurdle to making digital twins more widely available is that regulation for the technology is still in progress.

“We’re developing the technology, and what’s also happening is the regulatory framework is being developed in parallel. So we’re almost developing things blindly on the basis that we think this is what the regulators would want,” explained Asghar.

“It’s really important that these technologies are regulated properly, just like drugs, and that’s what we’re pushing and advocating for,” said Asghar, noting that people need to know that like drugs, a digital twin has strengths and limitations.

And while a digital twin can be a cost-saving approach in the long run, it does require funding to get a program built, and finding funds can be difficult because not everyone knows about the technology. More funding means more trials.

With more data, Asghar is hopeful that within a few years, a digital twin model could be available for clinicians to use to help inform treatment decisions. This could lead to more effective treatments and, ultimately, better patient outcomes.
 

A version of this article appeared on Medscape.com.

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A patient has cancer. It’s decision time.

Clinician and patient alike face, really, the ultimate challenge when making those decisions. They have to consider the patient’s individual circumstances, available treatment options, potential side effects, relevant clinical data such as the patient’s genetic profile and cancer specifics, and more.

“That’s a lot of information to hold,” said Uzma Asghar, PhD, MRCP, a British consultant medical oncologist at The Royal Marsden Hospital and a chief scientific officer at Concr LTD.

What if there were a way to test — quickly and accurately — all the potential paths forward?

That’s the goal of digital twins. An artificial intelligence (AI)–based program uses all the known data on patients and their types of illness and creates a “twin” that can be used over and over to simulate disease progression, test treatments, and predict individual responses to therapies.

“What the [digital twin] model can do for the clinician is to hold all that information and process it really quickly, within a couple of minutes,” Asghar noted.

A digital twin is more than just a computer model or simulation because it copies a real-world person and relies on real-world data. Some digital twin programs also integrate new information as it becomes available. This technology holds promise for personalized medicine, drug discovery, developing screening strategies, and better understanding diseases.
 

How to Deliver a Twin

To create a digital twin, experts develop a computer model with data to hone its expertise in an area of medicine, such as cancer types and treatments. Then “you train the model on information it’s seen, and then introduce a patient and patient’s information,” said Asghar.

Asghar is currently working with colleagues to develop digital twins that could eventually help solve the aforementioned cancer scenario — a doctor and patient decide the best course of cancer treatment. But their applications are manifold, particularly in clinical research.

Digital twins often include a machine learning component, which would fall under the umbrella term of AI, said Asghar, but it’s not like ChatGPT or other generative AI modules many people are now familiar with.

“The difference here is the model is not there to replace the clinician or to replace clinical trials,” Asghar noted. Instead, digital twins help make decisions faster in a way that can be more affordable.
 

Digital Twins to Predict Cancer Outcomes

Asghar is currently involved in UK clinical trials enrolling patients with cancer to test the accuracy of digital twin programs.

At this point, these studies do not yet use digital twins to guide the course of treatment, which is something they hope to do eventually. For now, they are still at the validation phase — the digital twin program makes predictions about the treatments and then the researchers later evaluate how accurate the predictions turned out to be based on real information from the enrolled patients.

Their current model gives predictions for RECIST (response evaluation criteria in solid tumor), treatment response, and survival. In addition to collecting data from ongoing clinical trials, they’ve used retrospective data, such as from the Cancer Tumor Atlas, to test the model.

“We’ve clinically validated it now in over 9000 patients,” said Asghar, who noted that they are constantly testing it on new patients. Their data include 30 chemotherapies and 23 cancer types, but they are focusing on four: Triple-negative breast cancer, cancer of unknown primary, pancreatic cancer, and colorectal cancer.

“The reason for choosing those four cancer types is that they are aggressive, their response to chemotherapy isn’t as great, and the outcome for those patient populations, there’s significant room for improvement,” Asghar explained.

Currently, Asghar said, the model is around 80%-90% correct in predicting what the actual clinical outcomes turn out to be.

The final stage of their work, before it becomes widely available to clinicians, will be to integrate it into a clinical trial in which some clinicians use the model to make decisions about treatment vs some who don’t use the model. By studying patient outcomes in both groups, they will be able to determine the value of the digital twin program they created.
 

 

 

What Else Can a Twin Do? A Lot

While a model that helps clinicians make decisions about cancer treatments may be among the first digital twin programs that become widely available, there are many other kinds of digital twins in the works.

For example, a digital twin could be used as a benchmark for a patient to determine how their cancer might have progressed without treatment. Say a patient’s tumor grew during treatment, it might seem like the treatment failed, but a digital twin might show that if left untreated, the tumor would have grown five times as fast, said Paul Macklin, PhD, professor in the Department of Intelligent Systems Engineering at Indiana University Bloomington.

Alternatively, if the virtual patient’s tumor is around the same size as the real patient’s tumor, “that means that treatment has lost its efficacy. It’s time to do something new,” said Macklin. And a digital twin could help with not only choosing a therapy but also choosing a dosing schedule, he noted.

The models can also be updated as new treatments come out, which could help clinicians virtually explore how they might affect a patient before having that patient switch treatments.

Digital twins could also assist in decision-making based on a patient’s priorities and real-life circumstances. “Maybe your priority is not necessarily to shrink this [tumor] at all costs ... maybe your priority is some mix of that and also quality of life,” Macklin said, referring to potential side effects. Or if someone lives 3 hours from the nearest cancer center, a digital twin could help determine whether less frequent treatments could still be effective.

And while much of the activity around digital twins in biomedical research has been focused on cancer, Asghar said the technology has the potential to be applied to other diseases as well. A digital twin for cardiovascular disease could help doctors choose the best treatment. It could also integrate new information from a smartwatch or glucose monitor to make better predictions and help doctors adjust the treatment plan.
 

Faster, More Effective Research With Twins

Because digital twin programs can quickly analyze large datasets, they can also make real-world studies more effective and efficient.

Though digital twins would not fully replace real clinical trials, they could help run through preliminary scenarios before starting a full clinical trial, which would “save everybody some money, time and pain and risk,” said Macklin.

It’s also possible to use digital twins to design better screening strategies for early cancer detection and monitoring, said Ioannis Zervantonakis, PhD, a bioengineering professor at the University of Pittsburgh.

Zervantonakis is tapping digital twin technology for research that homes in on understanding tumors. In this case, the digital twin is a virtual representation of a real tumor, complete with its complex network of cells and the surrounding tissue.

Zervantonakis’ lab is using the technology to study cell-cell interactions in the tumor microenvironment, with a focus on human epidermal growth factor receptor 2–targeted therapy resistance in breast cancer. The digital twin they developed will simulate tumor growth, predict drug response, analyze cellular interactions, and optimize treatment strategies.
 

 

 

The Long Push Forward

One big hurdle to making digital twins more widely available is that regulation for the technology is still in progress.

“We’re developing the technology, and what’s also happening is the regulatory framework is being developed in parallel. So we’re almost developing things blindly on the basis that we think this is what the regulators would want,” explained Asghar.

“It’s really important that these technologies are regulated properly, just like drugs, and that’s what we’re pushing and advocating for,” said Asghar, noting that people need to know that like drugs, a digital twin has strengths and limitations.

And while a digital twin can be a cost-saving approach in the long run, it does require funding to get a program built, and finding funds can be difficult because not everyone knows about the technology. More funding means more trials.

With more data, Asghar is hopeful that within a few years, a digital twin model could be available for clinicians to use to help inform treatment decisions. This could lead to more effective treatments and, ultimately, better patient outcomes.
 

A version of this article appeared on Medscape.com.

A patient has cancer. It’s decision time.

Clinician and patient alike face, really, the ultimate challenge when making those decisions. They have to consider the patient’s individual circumstances, available treatment options, potential side effects, relevant clinical data such as the patient’s genetic profile and cancer specifics, and more.

“That’s a lot of information to hold,” said Uzma Asghar, PhD, MRCP, a British consultant medical oncologist at The Royal Marsden Hospital and a chief scientific officer at Concr LTD.

What if there were a way to test — quickly and accurately — all the potential paths forward?

That’s the goal of digital twins. An artificial intelligence (AI)–based program uses all the known data on patients and their types of illness and creates a “twin” that can be used over and over to simulate disease progression, test treatments, and predict individual responses to therapies.

“What the [digital twin] model can do for the clinician is to hold all that information and process it really quickly, within a couple of minutes,” Asghar noted.

A digital twin is more than just a computer model or simulation because it copies a real-world person and relies on real-world data. Some digital twin programs also integrate new information as it becomes available. This technology holds promise for personalized medicine, drug discovery, developing screening strategies, and better understanding diseases.
 

How to Deliver a Twin

To create a digital twin, experts develop a computer model with data to hone its expertise in an area of medicine, such as cancer types and treatments. Then “you train the model on information it’s seen, and then introduce a patient and patient’s information,” said Asghar.

Asghar is currently working with colleagues to develop digital twins that could eventually help solve the aforementioned cancer scenario — a doctor and patient decide the best course of cancer treatment. But their applications are manifold, particularly in clinical research.

Digital twins often include a machine learning component, which would fall under the umbrella term of AI, said Asghar, but it’s not like ChatGPT or other generative AI modules many people are now familiar with.

“The difference here is the model is not there to replace the clinician or to replace clinical trials,” Asghar noted. Instead, digital twins help make decisions faster in a way that can be more affordable.
 

Digital Twins to Predict Cancer Outcomes

Asghar is currently involved in UK clinical trials enrolling patients with cancer to test the accuracy of digital twin programs.

At this point, these studies do not yet use digital twins to guide the course of treatment, which is something they hope to do eventually. For now, they are still at the validation phase — the digital twin program makes predictions about the treatments and then the researchers later evaluate how accurate the predictions turned out to be based on real information from the enrolled patients.

Their current model gives predictions for RECIST (response evaluation criteria in solid tumor), treatment response, and survival. In addition to collecting data from ongoing clinical trials, they’ve used retrospective data, such as from the Cancer Tumor Atlas, to test the model.

“We’ve clinically validated it now in over 9000 patients,” said Asghar, who noted that they are constantly testing it on new patients. Their data include 30 chemotherapies and 23 cancer types, but they are focusing on four: Triple-negative breast cancer, cancer of unknown primary, pancreatic cancer, and colorectal cancer.

“The reason for choosing those four cancer types is that they are aggressive, their response to chemotherapy isn’t as great, and the outcome for those patient populations, there’s significant room for improvement,” Asghar explained.

Currently, Asghar said, the model is around 80%-90% correct in predicting what the actual clinical outcomes turn out to be.

The final stage of their work, before it becomes widely available to clinicians, will be to integrate it into a clinical trial in which some clinicians use the model to make decisions about treatment vs some who don’t use the model. By studying patient outcomes in both groups, they will be able to determine the value of the digital twin program they created.
 

 

 

What Else Can a Twin Do? A Lot

While a model that helps clinicians make decisions about cancer treatments may be among the first digital twin programs that become widely available, there are many other kinds of digital twins in the works.

For example, a digital twin could be used as a benchmark for a patient to determine how their cancer might have progressed without treatment. Say a patient’s tumor grew during treatment, it might seem like the treatment failed, but a digital twin might show that if left untreated, the tumor would have grown five times as fast, said Paul Macklin, PhD, professor in the Department of Intelligent Systems Engineering at Indiana University Bloomington.

Alternatively, if the virtual patient’s tumor is around the same size as the real patient’s tumor, “that means that treatment has lost its efficacy. It’s time to do something new,” said Macklin. And a digital twin could help with not only choosing a therapy but also choosing a dosing schedule, he noted.

The models can also be updated as new treatments come out, which could help clinicians virtually explore how they might affect a patient before having that patient switch treatments.

Digital twins could also assist in decision-making based on a patient’s priorities and real-life circumstances. “Maybe your priority is not necessarily to shrink this [tumor] at all costs ... maybe your priority is some mix of that and also quality of life,” Macklin said, referring to potential side effects. Or if someone lives 3 hours from the nearest cancer center, a digital twin could help determine whether less frequent treatments could still be effective.

And while much of the activity around digital twins in biomedical research has been focused on cancer, Asghar said the technology has the potential to be applied to other diseases as well. A digital twin for cardiovascular disease could help doctors choose the best treatment. It could also integrate new information from a smartwatch or glucose monitor to make better predictions and help doctors adjust the treatment plan.
 

Faster, More Effective Research With Twins

Because digital twin programs can quickly analyze large datasets, they can also make real-world studies more effective and efficient.

Though digital twins would not fully replace real clinical trials, they could help run through preliminary scenarios before starting a full clinical trial, which would “save everybody some money, time and pain and risk,” said Macklin.

It’s also possible to use digital twins to design better screening strategies for early cancer detection and monitoring, said Ioannis Zervantonakis, PhD, a bioengineering professor at the University of Pittsburgh.

Zervantonakis is tapping digital twin technology for research that homes in on understanding tumors. In this case, the digital twin is a virtual representation of a real tumor, complete with its complex network of cells and the surrounding tissue.

Zervantonakis’ lab is using the technology to study cell-cell interactions in the tumor microenvironment, with a focus on human epidermal growth factor receptor 2–targeted therapy resistance in breast cancer. The digital twin they developed will simulate tumor growth, predict drug response, analyze cellular interactions, and optimize treatment strategies.
 

 

 

The Long Push Forward

One big hurdle to making digital twins more widely available is that regulation for the technology is still in progress.

“We’re developing the technology, and what’s also happening is the regulatory framework is being developed in parallel. So we’re almost developing things blindly on the basis that we think this is what the regulators would want,” explained Asghar.

“It’s really important that these technologies are regulated properly, just like drugs, and that’s what we’re pushing and advocating for,” said Asghar, noting that people need to know that like drugs, a digital twin has strengths and limitations.

And while a digital twin can be a cost-saving approach in the long run, it does require funding to get a program built, and finding funds can be difficult because not everyone knows about the technology. More funding means more trials.

With more data, Asghar is hopeful that within a few years, a digital twin model could be available for clinicians to use to help inform treatment decisions. This could lead to more effective treatments and, ultimately, better patient outcomes.
 

A version of this article appeared on Medscape.com.

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Smokeless Tobacco, Areca Nut Chewing Behind 1 in 3 Oral Cancers: IARC Report

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Globally, nearly one in three cases of oral cancer can be attributed to use of smokeless tobacco and areca nut products, according to a new study from the International Agency for Research on Cancer (IARC), a part of the World Health Organization (WHO).

“Smokeless tobacco and areca nut products are available to consumers in many different forms across the world, but consuming smokeless tobacco and areca nut is linked to multiple diseases, including oral cancer,” Harriet Rumgay, PhD, a scientist in the Cancer Surveillance Branch at IARC and first author of the study in Lancet Oncology, said in a news release.

Worldwide, about 300 million people use smokeless tobacco and 600 million people use areca (also called betel) nut, one of the most popular psychoactive substances in the world after nicotine, alcohol, and caffeine. Smokeless tobacco products are consumed without burning and can be chewed, sucked, inhaled, applied locally, or ingested. Areca nut is the seed of the areca palm and can be consumed in various forms.

“Our estimates highlight the burden these products pose on health care and the importance of prevention strategies to reduce consumption of smokeless tobacco and areca nut,” Rumgay said.

According to the new report, in 2022, an estimated 120,200 of the 389,800 (30.8%) global cases of oral cancer were attributable to these products.

More than three quarters (77%) of attributable cases were among men and about one quarter (23%) among women.

The vast majority (96%) of all oral cancer cases caused by smokeless tobacco and areca nut use occurred in low- and middle-income countries.

Regions with the highest burden of oral cancers from these products were Southcentral Asia — with 105,500 of 120,200 cases (nearly 88%), including 83,400 in India, 9700 in Bangladesh, 8900 in Pakistan, and 1300 in Sri Lanka — followed by Southeastern Asia with a total of 3900 cases (1600 in Myanmar, 990 in Indonesia, and 785 in Thailand) and East Asia with 3300 cases (3200 in China).
 

Limitations and Action Points

The authors noted a limitation of the analysis is not accounting for the potential synergistic effects of combined use of smokeless tobacco or areca nut products with other risk factors for oral cancer, such as smoking tobacco or drinking alcohol.

The researchers explained that combined consumption of smokeless tobacco or areca nut, smoked tobacco, and alcohol has a “multiplicative effect” on oral cancer risk, with reported odds ratios increasing from 2.7 for smokeless tobacco only, 7.0 for smoked tobacco only, and 1.6 for alcohol only to 16.2 for all three exposures (vs no use).

However, the proportion of people who chewed tobacco and also smoked in countries with high smokeless tobacco or areca nut use was small. In India, for example, 6% of men and 0.5% of women in 2016-2017 were dual users of both smoked and smokeless tobacco, compared with 23% of men and 12% of women who only used smokeless tobacco.

Overall, curbing or preventing smokeless tobacco and areca nut use could help avoid many instances of oral cancer.

Despite “encouraging trends” in control of tobacco smoking in many regions of the world over the past two decades, progress in reducing the prevalence of smokeless tobacco consumption has stalled in many countries that are major consumers, the authors said.

Compounding the problem, areca nut does not fall within the WHO framework of tobacco control and there are very few areca nut control policies worldwide.

Smokeless tobacco control must be “prioritized” and a framework on areca nut control should be developed with guidelines to incorporate areca nut prevention into cancer control programs, the authors concluded.

Funding for the study was provided by the French National Cancer Institute. The authors had no relevant disclosures.

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

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Globally, nearly one in three cases of oral cancer can be attributed to use of smokeless tobacco and areca nut products, according to a new study from the International Agency for Research on Cancer (IARC), a part of the World Health Organization (WHO).

“Smokeless tobacco and areca nut products are available to consumers in many different forms across the world, but consuming smokeless tobacco and areca nut is linked to multiple diseases, including oral cancer,” Harriet Rumgay, PhD, a scientist in the Cancer Surveillance Branch at IARC and first author of the study in Lancet Oncology, said in a news release.

Worldwide, about 300 million people use smokeless tobacco and 600 million people use areca (also called betel) nut, one of the most popular psychoactive substances in the world after nicotine, alcohol, and caffeine. Smokeless tobacco products are consumed without burning and can be chewed, sucked, inhaled, applied locally, or ingested. Areca nut is the seed of the areca palm and can be consumed in various forms.

“Our estimates highlight the burden these products pose on health care and the importance of prevention strategies to reduce consumption of smokeless tobacco and areca nut,” Rumgay said.

According to the new report, in 2022, an estimated 120,200 of the 389,800 (30.8%) global cases of oral cancer were attributable to these products.

More than three quarters (77%) of attributable cases were among men and about one quarter (23%) among women.

The vast majority (96%) of all oral cancer cases caused by smokeless tobacco and areca nut use occurred in low- and middle-income countries.

Regions with the highest burden of oral cancers from these products were Southcentral Asia — with 105,500 of 120,200 cases (nearly 88%), including 83,400 in India, 9700 in Bangladesh, 8900 in Pakistan, and 1300 in Sri Lanka — followed by Southeastern Asia with a total of 3900 cases (1600 in Myanmar, 990 in Indonesia, and 785 in Thailand) and East Asia with 3300 cases (3200 in China).
 

Limitations and Action Points

The authors noted a limitation of the analysis is not accounting for the potential synergistic effects of combined use of smokeless tobacco or areca nut products with other risk factors for oral cancer, such as smoking tobacco or drinking alcohol.

The researchers explained that combined consumption of smokeless tobacco or areca nut, smoked tobacco, and alcohol has a “multiplicative effect” on oral cancer risk, with reported odds ratios increasing from 2.7 for smokeless tobacco only, 7.0 for smoked tobacco only, and 1.6 for alcohol only to 16.2 for all three exposures (vs no use).

However, the proportion of people who chewed tobacco and also smoked in countries with high smokeless tobacco or areca nut use was small. In India, for example, 6% of men and 0.5% of women in 2016-2017 were dual users of both smoked and smokeless tobacco, compared with 23% of men and 12% of women who only used smokeless tobacco.

Overall, curbing or preventing smokeless tobacco and areca nut use could help avoid many instances of oral cancer.

Despite “encouraging trends” in control of tobacco smoking in many regions of the world over the past two decades, progress in reducing the prevalence of smokeless tobacco consumption has stalled in many countries that are major consumers, the authors said.

Compounding the problem, areca nut does not fall within the WHO framework of tobacco control and there are very few areca nut control policies worldwide.

Smokeless tobacco control must be “prioritized” and a framework on areca nut control should be developed with guidelines to incorporate areca nut prevention into cancer control programs, the authors concluded.

Funding for the study was provided by the French National Cancer Institute. The authors had no relevant disclosures.

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

Globally, nearly one in three cases of oral cancer can be attributed to use of smokeless tobacco and areca nut products, according to a new study from the International Agency for Research on Cancer (IARC), a part of the World Health Organization (WHO).

“Smokeless tobacco and areca nut products are available to consumers in many different forms across the world, but consuming smokeless tobacco and areca nut is linked to multiple diseases, including oral cancer,” Harriet Rumgay, PhD, a scientist in the Cancer Surveillance Branch at IARC and first author of the study in Lancet Oncology, said in a news release.

Worldwide, about 300 million people use smokeless tobacco and 600 million people use areca (also called betel) nut, one of the most popular psychoactive substances in the world after nicotine, alcohol, and caffeine. Smokeless tobacco products are consumed without burning and can be chewed, sucked, inhaled, applied locally, or ingested. Areca nut is the seed of the areca palm and can be consumed in various forms.

“Our estimates highlight the burden these products pose on health care and the importance of prevention strategies to reduce consumption of smokeless tobacco and areca nut,” Rumgay said.

According to the new report, in 2022, an estimated 120,200 of the 389,800 (30.8%) global cases of oral cancer were attributable to these products.

More than three quarters (77%) of attributable cases were among men and about one quarter (23%) among women.

The vast majority (96%) of all oral cancer cases caused by smokeless tobacco and areca nut use occurred in low- and middle-income countries.

Regions with the highest burden of oral cancers from these products were Southcentral Asia — with 105,500 of 120,200 cases (nearly 88%), including 83,400 in India, 9700 in Bangladesh, 8900 in Pakistan, and 1300 in Sri Lanka — followed by Southeastern Asia with a total of 3900 cases (1600 in Myanmar, 990 in Indonesia, and 785 in Thailand) and East Asia with 3300 cases (3200 in China).
 

Limitations and Action Points

The authors noted a limitation of the analysis is not accounting for the potential synergistic effects of combined use of smokeless tobacco or areca nut products with other risk factors for oral cancer, such as smoking tobacco or drinking alcohol.

The researchers explained that combined consumption of smokeless tobacco or areca nut, smoked tobacco, and alcohol has a “multiplicative effect” on oral cancer risk, with reported odds ratios increasing from 2.7 for smokeless tobacco only, 7.0 for smoked tobacco only, and 1.6 for alcohol only to 16.2 for all three exposures (vs no use).

However, the proportion of people who chewed tobacco and also smoked in countries with high smokeless tobacco or areca nut use was small. In India, for example, 6% of men and 0.5% of women in 2016-2017 were dual users of both smoked and smokeless tobacco, compared with 23% of men and 12% of women who only used smokeless tobacco.

Overall, curbing or preventing smokeless tobacco and areca nut use could help avoid many instances of oral cancer.

Despite “encouraging trends” in control of tobacco smoking in many regions of the world over the past two decades, progress in reducing the prevalence of smokeless tobacco consumption has stalled in many countries that are major consumers, the authors said.

Compounding the problem, areca nut does not fall within the WHO framework of tobacco control and there are very few areca nut control policies worldwide.

Smokeless tobacco control must be “prioritized” and a framework on areca nut control should be developed with guidelines to incorporate areca nut prevention into cancer control programs, the authors concluded.

Funding for the study was provided by the French National Cancer Institute. The authors had no relevant disclosures.

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

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Many Patients With Cancer Visit EDs Before Diagnosis

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More than one third of patients with cancer visited an emergency department (ED) in the 90 days before their diagnosis, according to a study of medical records from Ontario, Canada.

Researchers examined Institute for Clinical Evaluative Sciences (ICES) data that had been gathered from January 1, 2014, to December 31, 2021. The study focused on patients aged 18 years or older with confirmed primary cancer diagnoses.

Factors associated with an increased likelihood of an ED visit ahead of diagnosis included having certain cancers, living in rural areas, and having less access to primary care, according to study author Keerat Grewal, MD, an emergency physician and clinician scientist at the Schwartz/Reisman Emergency Medicine Institute at Sinai Health in Toronto, Ontario, Canada, and coauthors.

“The ED is a distressing environment for patients to receive a possible cancer diagnosis,” the authors wrote. “Moreover, it is frequently ill equipped to provide ongoing continuity of care, which can lead patients down a poorly defined diagnostic pathway before receiving a confirmed diagnosis based on tissue and a subsequent treatment plan.”

The findings were published online on November 4 in CMAJ).
 

Neurologic Cancers Prominent

In an interview, Grewal said in an interview that the study reflects her desire as an emergency room physician to understand why so many patients with cancer get the initial reports about their disease from clinicians whom they often have just met for the first time.

Among patients with an ED visit before cancer diagnosis, 51.4% were admitted to hospital from the most recent visit.

Compared with patients with a family physician on whom they could rely for routine care, those who had no outpatient visits (odds ratio [OR], 2.09) or fewer than three outpatient visits (OR, 1.41) in the 6-30 months before cancer diagnosis were more likely to have an ED visit before their cancer diagnosis.

Other factors associated with increased odds of ED use before cancer diagnosis included rurality (OR, 1.15), residence in northern Ontario (northeast region: OR, 1.14 and northwest region: OR, 1.27 vs Toronto region), and living in the most marginalized areas (material resource deprivation: OR, 1.37 and housing stability: OR, 1.09 vs least marginalized area).

The researchers also found that patients with certain cancers were more likely to have sought care in the ED. They compared these cancers with breast cancer, which is often detected through screening.

“Patients with neurologic cancers had extremely high odds of ED use before cancer diagnosis,” the authors wrote. “This is likely because of the emergent nature of presentation, with acute neurologic symptoms such as weakness, confusion, or seizures, which require urgent assessment.” On the other hand, pancreatic, liver, or thoracic cancer can trigger nonspecific symptoms that may be ignored until they reach a crisis level that prompts an ED visit.

The limitations of the study included its inability to identify cancer-related ED visits and its narrow focus on patients in Ontario, according to the researchers. But the use of the ICES databases also allowed researchers access to a broader pool of data than are available in many other cases.

The findings in the new paper echo those of previous research, the authors noted. Research in the United Kingdom found that 24%-31% of cancer diagnoses involved the ED. In addition, a study of people enrolled in the US Medicare program, which serves patients aged 65 years or older, found that 23% were seen in the ED in the 30 days before diagnosis.
 

 

 

‘Unpacking the Data’

The current findings also are consistent with those of an International Cancer Benchmarking Partnership study that was published in 2022 in The Lancet Oncology, said Erika Nicholson, MHS, vice president of cancer systems and innovation at the Canadian Partnership Against Cancer. The latter study analyzed cancer registration and linked hospital admissions data from 14 jurisdictions in Australia, Canada, Denmark, New Zealand, Norway, and the United Kingdom.

“We see similar trends in terms of people visiting EDs and being diagnosed through EDs internationally,” Nicholson said. “We’re working with partners to put in place different strategies to address the challenges” that this phenomenon presents in terms of improving screening and follow-up care.

“Cancer is not one disease, but many diseases,” she said. “They present differently. We’re focused on really unpacking the data and understanding them.”

All this research highlights the need for more services and personnel to address cancer, including people who are trained to help patients cope after getting concerning news through emergency care, she said.

“That means having a system that fully supports you and helps you navigate through that diagnostic process,” Nicholson said. Addressing the added challenges for patients who don’t have secure housing is a special need, she added.

This study was supported by the Canadian Institutes of Health Research (CIHR). Grewal reported receiving grants from CIHR and the Canadian Association of Emergency Physicians. Nicholson reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

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More than one third of patients with cancer visited an emergency department (ED) in the 90 days before their diagnosis, according to a study of medical records from Ontario, Canada.

Researchers examined Institute for Clinical Evaluative Sciences (ICES) data that had been gathered from January 1, 2014, to December 31, 2021. The study focused on patients aged 18 years or older with confirmed primary cancer diagnoses.

Factors associated with an increased likelihood of an ED visit ahead of diagnosis included having certain cancers, living in rural areas, and having less access to primary care, according to study author Keerat Grewal, MD, an emergency physician and clinician scientist at the Schwartz/Reisman Emergency Medicine Institute at Sinai Health in Toronto, Ontario, Canada, and coauthors.

“The ED is a distressing environment for patients to receive a possible cancer diagnosis,” the authors wrote. “Moreover, it is frequently ill equipped to provide ongoing continuity of care, which can lead patients down a poorly defined diagnostic pathway before receiving a confirmed diagnosis based on tissue and a subsequent treatment plan.”

The findings were published online on November 4 in CMAJ).
 

Neurologic Cancers Prominent

In an interview, Grewal said in an interview that the study reflects her desire as an emergency room physician to understand why so many patients with cancer get the initial reports about their disease from clinicians whom they often have just met for the first time.

Among patients with an ED visit before cancer diagnosis, 51.4% were admitted to hospital from the most recent visit.

Compared with patients with a family physician on whom they could rely for routine care, those who had no outpatient visits (odds ratio [OR], 2.09) or fewer than three outpatient visits (OR, 1.41) in the 6-30 months before cancer diagnosis were more likely to have an ED visit before their cancer diagnosis.

Other factors associated with increased odds of ED use before cancer diagnosis included rurality (OR, 1.15), residence in northern Ontario (northeast region: OR, 1.14 and northwest region: OR, 1.27 vs Toronto region), and living in the most marginalized areas (material resource deprivation: OR, 1.37 and housing stability: OR, 1.09 vs least marginalized area).

The researchers also found that patients with certain cancers were more likely to have sought care in the ED. They compared these cancers with breast cancer, which is often detected through screening.

“Patients with neurologic cancers had extremely high odds of ED use before cancer diagnosis,” the authors wrote. “This is likely because of the emergent nature of presentation, with acute neurologic symptoms such as weakness, confusion, or seizures, which require urgent assessment.” On the other hand, pancreatic, liver, or thoracic cancer can trigger nonspecific symptoms that may be ignored until they reach a crisis level that prompts an ED visit.

The limitations of the study included its inability to identify cancer-related ED visits and its narrow focus on patients in Ontario, according to the researchers. But the use of the ICES databases also allowed researchers access to a broader pool of data than are available in many other cases.

The findings in the new paper echo those of previous research, the authors noted. Research in the United Kingdom found that 24%-31% of cancer diagnoses involved the ED. In addition, a study of people enrolled in the US Medicare program, which serves patients aged 65 years or older, found that 23% were seen in the ED in the 30 days before diagnosis.
 

 

 

‘Unpacking the Data’

The current findings also are consistent with those of an International Cancer Benchmarking Partnership study that was published in 2022 in The Lancet Oncology, said Erika Nicholson, MHS, vice president of cancer systems and innovation at the Canadian Partnership Against Cancer. The latter study analyzed cancer registration and linked hospital admissions data from 14 jurisdictions in Australia, Canada, Denmark, New Zealand, Norway, and the United Kingdom.

“We see similar trends in terms of people visiting EDs and being diagnosed through EDs internationally,” Nicholson said. “We’re working with partners to put in place different strategies to address the challenges” that this phenomenon presents in terms of improving screening and follow-up care.

“Cancer is not one disease, but many diseases,” she said. “They present differently. We’re focused on really unpacking the data and understanding them.”

All this research highlights the need for more services and personnel to address cancer, including people who are trained to help patients cope after getting concerning news through emergency care, she said.

“That means having a system that fully supports you and helps you navigate through that diagnostic process,” Nicholson said. Addressing the added challenges for patients who don’t have secure housing is a special need, she added.

This study was supported by the Canadian Institutes of Health Research (CIHR). Grewal reported receiving grants from CIHR and the Canadian Association of Emergency Physicians. Nicholson reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

More than one third of patients with cancer visited an emergency department (ED) in the 90 days before their diagnosis, according to a study of medical records from Ontario, Canada.

Researchers examined Institute for Clinical Evaluative Sciences (ICES) data that had been gathered from January 1, 2014, to December 31, 2021. The study focused on patients aged 18 years or older with confirmed primary cancer diagnoses.

Factors associated with an increased likelihood of an ED visit ahead of diagnosis included having certain cancers, living in rural areas, and having less access to primary care, according to study author Keerat Grewal, MD, an emergency physician and clinician scientist at the Schwartz/Reisman Emergency Medicine Institute at Sinai Health in Toronto, Ontario, Canada, and coauthors.

“The ED is a distressing environment for patients to receive a possible cancer diagnosis,” the authors wrote. “Moreover, it is frequently ill equipped to provide ongoing continuity of care, which can lead patients down a poorly defined diagnostic pathway before receiving a confirmed diagnosis based on tissue and a subsequent treatment plan.”

The findings were published online on November 4 in CMAJ).
 

Neurologic Cancers Prominent

In an interview, Grewal said in an interview that the study reflects her desire as an emergency room physician to understand why so many patients with cancer get the initial reports about their disease from clinicians whom they often have just met for the first time.

Among patients with an ED visit before cancer diagnosis, 51.4% were admitted to hospital from the most recent visit.

Compared with patients with a family physician on whom they could rely for routine care, those who had no outpatient visits (odds ratio [OR], 2.09) or fewer than three outpatient visits (OR, 1.41) in the 6-30 months before cancer diagnosis were more likely to have an ED visit before their cancer diagnosis.

Other factors associated with increased odds of ED use before cancer diagnosis included rurality (OR, 1.15), residence in northern Ontario (northeast region: OR, 1.14 and northwest region: OR, 1.27 vs Toronto region), and living in the most marginalized areas (material resource deprivation: OR, 1.37 and housing stability: OR, 1.09 vs least marginalized area).

The researchers also found that patients with certain cancers were more likely to have sought care in the ED. They compared these cancers with breast cancer, which is often detected through screening.

“Patients with neurologic cancers had extremely high odds of ED use before cancer diagnosis,” the authors wrote. “This is likely because of the emergent nature of presentation, with acute neurologic symptoms such as weakness, confusion, or seizures, which require urgent assessment.” On the other hand, pancreatic, liver, or thoracic cancer can trigger nonspecific symptoms that may be ignored until they reach a crisis level that prompts an ED visit.

The limitations of the study included its inability to identify cancer-related ED visits and its narrow focus on patients in Ontario, according to the researchers. But the use of the ICES databases also allowed researchers access to a broader pool of data than are available in many other cases.

The findings in the new paper echo those of previous research, the authors noted. Research in the United Kingdom found that 24%-31% of cancer diagnoses involved the ED. In addition, a study of people enrolled in the US Medicare program, which serves patients aged 65 years or older, found that 23% were seen in the ED in the 30 days before diagnosis.
 

 

 

‘Unpacking the Data’

The current findings also are consistent with those of an International Cancer Benchmarking Partnership study that was published in 2022 in The Lancet Oncology, said Erika Nicholson, MHS, vice president of cancer systems and innovation at the Canadian Partnership Against Cancer. The latter study analyzed cancer registration and linked hospital admissions data from 14 jurisdictions in Australia, Canada, Denmark, New Zealand, Norway, and the United Kingdom.

“We see similar trends in terms of people visiting EDs and being diagnosed through EDs internationally,” Nicholson said. “We’re working with partners to put in place different strategies to address the challenges” that this phenomenon presents in terms of improving screening and follow-up care.

“Cancer is not one disease, but many diseases,” she said. “They present differently. We’re focused on really unpacking the data and understanding them.”

All this research highlights the need for more services and personnel to address cancer, including people who are trained to help patients cope after getting concerning news through emergency care, she said.

“That means having a system that fully supports you and helps you navigate through that diagnostic process,” Nicholson said. Addressing the added challenges for patients who don’t have secure housing is a special need, she added.

This study was supported by the Canadian Institutes of Health Research (CIHR). Grewal reported receiving grants from CIHR and the Canadian Association of Emergency Physicians. Nicholson reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

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Plasma Omega-6 and Omega-3 Fatty Acids Inversely Associated With Cancer

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TOPLINE:

Higher plasma levels of omega-6 and omega-3 fatty acids are associated with a lower incidence of cancer. However, omega-3 fatty acids are linked to an increased risk for prostate cancer, specifically.

METHODOLOGY:

  • Researchers looked for associations of plasma omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) with the incidence of cancer overall and 19 site-specific cancers in the large population-based prospective UK Biobank cohort.
  • They included 253,138 participants aged 37-73 years who were followed for an average of 12.9 years, with 29,838 diagnosed with cancer.
  • Plasma levels of omega-3 and omega-6 fatty acids were measured using nuclear magnetic resonance and expressed as percentages of total fatty acids.
  • Participants with cancer diagnoses at baseline, those who withdrew from the study, and those with missing data on plasma PUFAs were excluded.
  • The study adjusted for multiple covariates, including age, sex, ethnicity, socioeconomic status, lifestyle behaviors, and family history of diseases.

TAKEAWAY:

  • Higher plasma levels of omega-6 and omega-3 fatty acids were associated with a 2% and 1% reduction in overall cancer risk per SD increase, respectively (P = .001 and P = .03).
  • Omega-6 fatty acids were inversely associated with 14 site-specific cancers, whereas omega-3 fatty acids were inversely associated with five site-specific cancers.
  • Prostate cancer was positively associated with omega-3 fatty acids, with a 3% increased risk per SD increase (P = .049).
  • A higher omega-6/omega-3 ratio was associated with an increased risk for overall cancer, and three site-specific cancers showed positive associations with the ratio. “Each standard deviation increase, corresponding to a 13.13 increase in the omega ratio, was associated with a 2% increase in the risk of rectum cancer,” for example, the authors wrote.

IN PRACTICE:

“Overall, our findings provide support for possible small net protective roles of omega-3 and omega-6 PUFAs in the development of new cancer incidence. Our study also suggests that the usage of circulating blood biomarkers captures different aspects of dietary intake, reduces measurement errors, and thus enhances statistical power. The differential effects of omega-6% and omega-3% in age and sex subgroups warrant future investigation,” wrote the authors of the study.

SOURCE:

The study was led by Yuchen Zhang of the University of Georgia in Athens, Georgia. It was published online in the International Journal of Cancer.

LIMITATIONS:

The study’s potential for selective bias persists due to the participant sample skewing heavily toward European ancestry and White ethnicity. The number of events was small for some specific cancer sites, which may have limited the statistical power. The study focused on total omega-3 and omega-6 PUFAs, with only two individual fatty acids measured. Future studies are needed to examine the roles of other individual PUFAs and specific genetic variants. 

DISCLOSURES:

This study was supported by grants from the National Institute of General Medical Sciences of the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.
 

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

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TOPLINE:

Higher plasma levels of omega-6 and omega-3 fatty acids are associated with a lower incidence of cancer. However, omega-3 fatty acids are linked to an increased risk for prostate cancer, specifically.

METHODOLOGY:

  • Researchers looked for associations of plasma omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) with the incidence of cancer overall and 19 site-specific cancers in the large population-based prospective UK Biobank cohort.
  • They included 253,138 participants aged 37-73 years who were followed for an average of 12.9 years, with 29,838 diagnosed with cancer.
  • Plasma levels of omega-3 and omega-6 fatty acids were measured using nuclear magnetic resonance and expressed as percentages of total fatty acids.
  • Participants with cancer diagnoses at baseline, those who withdrew from the study, and those with missing data on plasma PUFAs were excluded.
  • The study adjusted for multiple covariates, including age, sex, ethnicity, socioeconomic status, lifestyle behaviors, and family history of diseases.

TAKEAWAY:

  • Higher plasma levels of omega-6 and omega-3 fatty acids were associated with a 2% and 1% reduction in overall cancer risk per SD increase, respectively (P = .001 and P = .03).
  • Omega-6 fatty acids were inversely associated with 14 site-specific cancers, whereas omega-3 fatty acids were inversely associated with five site-specific cancers.
  • Prostate cancer was positively associated with omega-3 fatty acids, with a 3% increased risk per SD increase (P = .049).
  • A higher omega-6/omega-3 ratio was associated with an increased risk for overall cancer, and three site-specific cancers showed positive associations with the ratio. “Each standard deviation increase, corresponding to a 13.13 increase in the omega ratio, was associated with a 2% increase in the risk of rectum cancer,” for example, the authors wrote.

IN PRACTICE:

“Overall, our findings provide support for possible small net protective roles of omega-3 and omega-6 PUFAs in the development of new cancer incidence. Our study also suggests that the usage of circulating blood biomarkers captures different aspects of dietary intake, reduces measurement errors, and thus enhances statistical power. The differential effects of omega-6% and omega-3% in age and sex subgroups warrant future investigation,” wrote the authors of the study.

SOURCE:

The study was led by Yuchen Zhang of the University of Georgia in Athens, Georgia. It was published online in the International Journal of Cancer.

LIMITATIONS:

The study’s potential for selective bias persists due to the participant sample skewing heavily toward European ancestry and White ethnicity. The number of events was small for some specific cancer sites, which may have limited the statistical power. The study focused on total omega-3 and omega-6 PUFAs, with only two individual fatty acids measured. Future studies are needed to examine the roles of other individual PUFAs and specific genetic variants. 

DISCLOSURES:

This study was supported by grants from the National Institute of General Medical Sciences of the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.
 

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

 

TOPLINE:

Higher plasma levels of omega-6 and omega-3 fatty acids are associated with a lower incidence of cancer. However, omega-3 fatty acids are linked to an increased risk for prostate cancer, specifically.

METHODOLOGY:

  • Researchers looked for associations of plasma omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) with the incidence of cancer overall and 19 site-specific cancers in the large population-based prospective UK Biobank cohort.
  • They included 253,138 participants aged 37-73 years who were followed for an average of 12.9 years, with 29,838 diagnosed with cancer.
  • Plasma levels of omega-3 and omega-6 fatty acids were measured using nuclear magnetic resonance and expressed as percentages of total fatty acids.
  • Participants with cancer diagnoses at baseline, those who withdrew from the study, and those with missing data on plasma PUFAs were excluded.
  • The study adjusted for multiple covariates, including age, sex, ethnicity, socioeconomic status, lifestyle behaviors, and family history of diseases.

TAKEAWAY:

  • Higher plasma levels of omega-6 and omega-3 fatty acids were associated with a 2% and 1% reduction in overall cancer risk per SD increase, respectively (P = .001 and P = .03).
  • Omega-6 fatty acids were inversely associated with 14 site-specific cancers, whereas omega-3 fatty acids were inversely associated with five site-specific cancers.
  • Prostate cancer was positively associated with omega-3 fatty acids, with a 3% increased risk per SD increase (P = .049).
  • A higher omega-6/omega-3 ratio was associated with an increased risk for overall cancer, and three site-specific cancers showed positive associations with the ratio. “Each standard deviation increase, corresponding to a 13.13 increase in the omega ratio, was associated with a 2% increase in the risk of rectum cancer,” for example, the authors wrote.

IN PRACTICE:

“Overall, our findings provide support for possible small net protective roles of omega-3 and omega-6 PUFAs in the development of new cancer incidence. Our study also suggests that the usage of circulating blood biomarkers captures different aspects of dietary intake, reduces measurement errors, and thus enhances statistical power. The differential effects of omega-6% and omega-3% in age and sex subgroups warrant future investigation,” wrote the authors of the study.

SOURCE:

The study was led by Yuchen Zhang of the University of Georgia in Athens, Georgia. It was published online in the International Journal of Cancer.

LIMITATIONS:

The study’s potential for selective bias persists due to the participant sample skewing heavily toward European ancestry and White ethnicity. The number of events was small for some specific cancer sites, which may have limited the statistical power. The study focused on total omega-3 and omega-6 PUFAs, with only two individual fatty acids measured. Future studies are needed to examine the roles of other individual PUFAs and specific genetic variants. 

DISCLOSURES:

This study was supported by grants from the National Institute of General Medical Sciences of the National Institutes of Health. No relevant conflicts of interest were disclosed by the authors.
 

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

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Prostate Cancer Treatment Associated With More Complications

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TOPLINE:

Patients treated for prostate cancer had higher rates of complications, including urinary and sexual issues, than a control group of men. Radiotherapy increases the risk for bladder cancer and radiation-specific complications, according to the new cohort study.
 

METHODOLOGY:

  • Researchers conducted a cohort study to try to characterize long-term treatment-related adverse effects and complications in patients treated for prostate cancer, compared with a general population of older males.
  • They used data from the Prostate Cancer Prevention Trial and the Selenium and Vitamin E Cancer Prevention Trial, linked with Medicare claims. A total of 29,196 participants were included in the study’s control group. Of 3946 patients diagnosed with prostate cancer, 655 were treated with prostatectomy, and 1056 were treated with radiotherapy.
  • Participants were followed for a median of 10.2 years, with specific follow-up durations being 10.5 years and 8.5 years for the prostatectomy and radiotherapy groups, respectively.
  • The study analyzed ten potential treatment-related complications using Medicare claims data, including urinary incontinenceerectile dysfunction, and secondary cancers. 
  • Multivariable Cox regression was used to adjust for age, race, and year of time-at-risk initiation, with stratification by study and intervention arm. 

TAKEAWAY:

  • At 12 years, there was a 7.23 increase in hazard risk for urinary or sexual complications for patients who had prostatectomy, compared with controls (P < .001).
  • Radiotherapy-treated patients had a nearly three times greater hazard risk for bladder cancer and a 100-fold increased hazard risk for radiation-specific complications, such as radiation cystitis and radiation proctitis (P < .001).
  • The incidence of any treatment-related complication per 1000 person-years was 124.26 for prostatectomy, 62.15 for radiotherapy, and 23.61 for untreated participants.
  • The authors stated that these findings highlight the importance of patient counseling before prostate cancer screening and treatment.

IN PRACTICE:

“We found that, after accounting for baseline population rates, most patients with PCA undergoing treatment experience complications associated with worse quality of life and/or new health risks. The magnitude of these risks, compared with the relatively small benefit found by randomized clinical trials of PCA screening and treatment, should be explicitly reflected in national cancer screening and treatment guidelines and be integral to shared decision-making with patients before initiation of PSA screening, biopsy, or PCA treatment,” wrote the authors of the study.
 

SOURCE:

The study was led by Joseph M. Unger, PhD, SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Center in Seattle, Washington. It was published online on November 7, 2024, in JAMA Oncology.
 

LIMITATIONS:

The study did not account for multiple comparisons, which may affect the statistical significance of some findings. Claims data are subject to misclassification and may underreport complications that are not reported to a physician. The study did not differentiate among strategies of prostatectomy or radiotherapy, which may result in different patterns of complications. The cohort comprised men enrolled in large, randomized prevention trials, which may limit the generalizability of the incidence estimates. Confounding by unknown factors cannot be ruled out, affecting the attribution of risks to prostate cancer treatment alone.
 

DISCLOSURES:

Unger disclosed consulting fees from AstraZeneca and Loxo/Lilly outside the submitted work. One coauthor reported grants from the US National Cancer Institute during the conduct of the study. Another coauthor reported employment with Flatiron Health at the time of manuscript submission and review. Additional disclosures are noted in the original article.

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

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TOPLINE:

Patients treated for prostate cancer had higher rates of complications, including urinary and sexual issues, than a control group of men. Radiotherapy increases the risk for bladder cancer and radiation-specific complications, according to the new cohort study.
 

METHODOLOGY:

  • Researchers conducted a cohort study to try to characterize long-term treatment-related adverse effects and complications in patients treated for prostate cancer, compared with a general population of older males.
  • They used data from the Prostate Cancer Prevention Trial and the Selenium and Vitamin E Cancer Prevention Trial, linked with Medicare claims. A total of 29,196 participants were included in the study’s control group. Of 3946 patients diagnosed with prostate cancer, 655 were treated with prostatectomy, and 1056 were treated with radiotherapy.
  • Participants were followed for a median of 10.2 years, with specific follow-up durations being 10.5 years and 8.5 years for the prostatectomy and radiotherapy groups, respectively.
  • The study analyzed ten potential treatment-related complications using Medicare claims data, including urinary incontinenceerectile dysfunction, and secondary cancers. 
  • Multivariable Cox regression was used to adjust for age, race, and year of time-at-risk initiation, with stratification by study and intervention arm. 

TAKEAWAY:

  • At 12 years, there was a 7.23 increase in hazard risk for urinary or sexual complications for patients who had prostatectomy, compared with controls (P < .001).
  • Radiotherapy-treated patients had a nearly three times greater hazard risk for bladder cancer and a 100-fold increased hazard risk for radiation-specific complications, such as radiation cystitis and radiation proctitis (P < .001).
  • The incidence of any treatment-related complication per 1000 person-years was 124.26 for prostatectomy, 62.15 for radiotherapy, and 23.61 for untreated participants.
  • The authors stated that these findings highlight the importance of patient counseling before prostate cancer screening and treatment.

IN PRACTICE:

“We found that, after accounting for baseline population rates, most patients with PCA undergoing treatment experience complications associated with worse quality of life and/or new health risks. The magnitude of these risks, compared with the relatively small benefit found by randomized clinical trials of PCA screening and treatment, should be explicitly reflected in national cancer screening and treatment guidelines and be integral to shared decision-making with patients before initiation of PSA screening, biopsy, or PCA treatment,” wrote the authors of the study.
 

SOURCE:

The study was led by Joseph M. Unger, PhD, SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Center in Seattle, Washington. It was published online on November 7, 2024, in JAMA Oncology.
 

LIMITATIONS:

The study did not account for multiple comparisons, which may affect the statistical significance of some findings. Claims data are subject to misclassification and may underreport complications that are not reported to a physician. The study did not differentiate among strategies of prostatectomy or radiotherapy, which may result in different patterns of complications. The cohort comprised men enrolled in large, randomized prevention trials, which may limit the generalizability of the incidence estimates. Confounding by unknown factors cannot be ruled out, affecting the attribution of risks to prostate cancer treatment alone.
 

DISCLOSURES:

Unger disclosed consulting fees from AstraZeneca and Loxo/Lilly outside the submitted work. One coauthor reported grants from the US National Cancer Institute during the conduct of the study. Another coauthor reported employment with Flatiron Health at the time of manuscript submission and review. Additional disclosures are noted in the original article.

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

 

TOPLINE:

Patients treated for prostate cancer had higher rates of complications, including urinary and sexual issues, than a control group of men. Radiotherapy increases the risk for bladder cancer and radiation-specific complications, according to the new cohort study.
 

METHODOLOGY:

  • Researchers conducted a cohort study to try to characterize long-term treatment-related adverse effects and complications in patients treated for prostate cancer, compared with a general population of older males.
  • They used data from the Prostate Cancer Prevention Trial and the Selenium and Vitamin E Cancer Prevention Trial, linked with Medicare claims. A total of 29,196 participants were included in the study’s control group. Of 3946 patients diagnosed with prostate cancer, 655 were treated with prostatectomy, and 1056 were treated with radiotherapy.
  • Participants were followed for a median of 10.2 years, with specific follow-up durations being 10.5 years and 8.5 years for the prostatectomy and radiotherapy groups, respectively.
  • The study analyzed ten potential treatment-related complications using Medicare claims data, including urinary incontinenceerectile dysfunction, and secondary cancers. 
  • Multivariable Cox regression was used to adjust for age, race, and year of time-at-risk initiation, with stratification by study and intervention arm. 

TAKEAWAY:

  • At 12 years, there was a 7.23 increase in hazard risk for urinary or sexual complications for patients who had prostatectomy, compared with controls (P < .001).
  • Radiotherapy-treated patients had a nearly three times greater hazard risk for bladder cancer and a 100-fold increased hazard risk for radiation-specific complications, such as radiation cystitis and radiation proctitis (P < .001).
  • The incidence of any treatment-related complication per 1000 person-years was 124.26 for prostatectomy, 62.15 for radiotherapy, and 23.61 for untreated participants.
  • The authors stated that these findings highlight the importance of patient counseling before prostate cancer screening and treatment.

IN PRACTICE:

“We found that, after accounting for baseline population rates, most patients with PCA undergoing treatment experience complications associated with worse quality of life and/or new health risks. The magnitude of these risks, compared with the relatively small benefit found by randomized clinical trials of PCA screening and treatment, should be explicitly reflected in national cancer screening and treatment guidelines and be integral to shared decision-making with patients before initiation of PSA screening, biopsy, or PCA treatment,” wrote the authors of the study.
 

SOURCE:

The study was led by Joseph M. Unger, PhD, SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Center in Seattle, Washington. It was published online on November 7, 2024, in JAMA Oncology.
 

LIMITATIONS:

The study did not account for multiple comparisons, which may affect the statistical significance of some findings. Claims data are subject to misclassification and may underreport complications that are not reported to a physician. The study did not differentiate among strategies of prostatectomy or radiotherapy, which may result in different patterns of complications. The cohort comprised men enrolled in large, randomized prevention trials, which may limit the generalizability of the incidence estimates. Confounding by unknown factors cannot be ruled out, affecting the attribution of risks to prostate cancer treatment alone.
 

DISCLOSURES:

Unger disclosed consulting fees from AstraZeneca and Loxo/Lilly outside the submitted work. One coauthor reported grants from the US National Cancer Institute during the conduct of the study. Another coauthor reported employment with Flatiron Health at the time of manuscript submission and review. Additional disclosures are noted in the original article.

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

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How Extreme Rainfall Amplifies Health Risks

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Climate change is intensifying the variability of precipitation caused by extreme daily and overall rainfall events. Awareness of the effects of these events is crucial for understanding the complex health consequences of climate change. The connections between health and climate have been recognized by physicians and patients even when climatology did not have the status of an exact science. Physicians have often advised their patients to move to a better climate, and when they did, the recommendation was rarely based on precise scientific knowledge. However, the benefits of changing environments were often so evident that they were indisputable.

Today, advanced models, satellite imagery, and biological approaches such as environmental epigenetics are enhancing our understanding of health risks related to climate change.
 

Extreme Rainfall and Health

The increase in precipitation variability is linked to climate warming, which leads to higher atmospheric humidity and extreme rainfall events. These manifestations can cause rapid weather changes, increasing interactions with harmful aerosols and raising the risk for various cardiovascular and respiratory conditions. However, a full understanding of the association between rain and health has been hindered by conflicting results and methodological issues (limited geographical locations and short observation durations) in studies.

The association between rainfall intensity and health effects is likely nonlinear. Moderate precipitation can mitigate summer heat and help reduce air pollution, an effect that may lower some environmental health risks. Conversely, intense, low-frequency, short-duration rainfall events can have particularly harmful effects on health, as such events can trigger rapid weather changes, increased proliferation of pathogens, and a rise in the risk of various pollutants, potentially exacerbating health conditions.
 

Rain and Mortality

Using an intensity-duration-frequency model of three rainfall indices (high intensity, low frequency, short duration), a study published in October 2024 combined these with mortality data from 34 countries or regions. Researchers estimated associations between mortality (all cause, cardiovascular, and respiratory) and rainfall events with different return periods (the average time expected before an extreme event of a certain magnitude occurs again) and crucial effect modifiers, including climatic, socioeconomic, and urban environmental conditions.

The analysis included 109,954,744 deaths from all causes; 31,164,161 cardiovascular deaths; and 11,817,278 respiratory deaths. During the study period, from 1980 to 2020, a total of 50,913 rainfall events with a 1-year return period, 8362 events with a 2-year return period, and 3301 events with a 5-year return period were identified.

The most significant finding was a global positive association between all-cause mortality and extreme rainfall events with a 5-year return period. One day of extreme rainfall with a 5-year return period was associated with a cumulative relative risk (RRc) of 1.08 (95% CI, 1.05-1.11) for daily mortality from all causes. Rainfall events with a 2-year return period were associated with increased daily respiratory mortality (RRc, 1.14), while no significant effect was observed for cardiovascular mortality during the same period. Rainfall events with a 5-year return period were associated with an increased risk for both cardiovascular mortality (RRc, 1.05) and respiratory mortality (RRc, 1.29), with the respiratory mortality being significantly higher.
 

Points of Concern

According to the authors, moderate to high rainfall can exert protective effects through two main mechanisms: Improving air quality (rainfall can reduce the concentration of particulate matter 2.5 cm in diameter or less in the atmosphere) and behavioral changes in people (more time spent in enclosed environments, reducing direct exposure to outdoor air pollution and nonoptimal temperatures). As rainfall intensity increases, the initial protective effects may be overshadowed by a cascade of negative impacts including:

  • Critical resource disruptions: Intense rainfall can cause severe disruptions to access to healthcare, infrastructure damage including power outages, and compromised water and food quality.
  • Physiological effects: Increased humidity levels facilitate the growth of airborne pathogens, potentially triggering allergic reactions and respiratory issues, particularly in vulnerable individuals. Rapid shifts in atmospheric pressure and temperature fluctuations can lead to cardiovascular and respiratory complications.
  • Indirect effects: Extreme rainfall can have profound effects on mental health, inducing stress and anxiety that may exacerbate pre-existing mental health conditions and indirectly contribute to increased overall mortality from nonexternal causes.

The intensity-response curves for the health effects of heavy rainfall showed a nonlinear trend, transitioning from a protective effect at moderate levels of rainfall to a risk for severe harm when rainfall intensity became extreme. Additionally, the significant effects of extreme events were modified by various types of climate and were more pronounced in areas characterized by low variability in precipitation or sparse vegetation cover.

The study demonstrated that various local factors, such as climatic conditions, climate type, and vegetation cover, can potentially influence cardiovascular and respiratory mortality and all-cause mortality related to precipitation. The findings may help physicians convey to their patients the impact of climate change on their health.

This story was translated from Univadis Italy 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.

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Climate change is intensifying the variability of precipitation caused by extreme daily and overall rainfall events. Awareness of the effects of these events is crucial for understanding the complex health consequences of climate change. The connections between health and climate have been recognized by physicians and patients even when climatology did not have the status of an exact science. Physicians have often advised their patients to move to a better climate, and when they did, the recommendation was rarely based on precise scientific knowledge. However, the benefits of changing environments were often so evident that they were indisputable.

Today, advanced models, satellite imagery, and biological approaches such as environmental epigenetics are enhancing our understanding of health risks related to climate change.
 

Extreme Rainfall and Health

The increase in precipitation variability is linked to climate warming, which leads to higher atmospheric humidity and extreme rainfall events. These manifestations can cause rapid weather changes, increasing interactions with harmful aerosols and raising the risk for various cardiovascular and respiratory conditions. However, a full understanding of the association between rain and health has been hindered by conflicting results and methodological issues (limited geographical locations and short observation durations) in studies.

The association between rainfall intensity and health effects is likely nonlinear. Moderate precipitation can mitigate summer heat and help reduce air pollution, an effect that may lower some environmental health risks. Conversely, intense, low-frequency, short-duration rainfall events can have particularly harmful effects on health, as such events can trigger rapid weather changes, increased proliferation of pathogens, and a rise in the risk of various pollutants, potentially exacerbating health conditions.
 

Rain and Mortality

Using an intensity-duration-frequency model of three rainfall indices (high intensity, low frequency, short duration), a study published in October 2024 combined these with mortality data from 34 countries or regions. Researchers estimated associations between mortality (all cause, cardiovascular, and respiratory) and rainfall events with different return periods (the average time expected before an extreme event of a certain magnitude occurs again) and crucial effect modifiers, including climatic, socioeconomic, and urban environmental conditions.

The analysis included 109,954,744 deaths from all causes; 31,164,161 cardiovascular deaths; and 11,817,278 respiratory deaths. During the study period, from 1980 to 2020, a total of 50,913 rainfall events with a 1-year return period, 8362 events with a 2-year return period, and 3301 events with a 5-year return period were identified.

The most significant finding was a global positive association between all-cause mortality and extreme rainfall events with a 5-year return period. One day of extreme rainfall with a 5-year return period was associated with a cumulative relative risk (RRc) of 1.08 (95% CI, 1.05-1.11) for daily mortality from all causes. Rainfall events with a 2-year return period were associated with increased daily respiratory mortality (RRc, 1.14), while no significant effect was observed for cardiovascular mortality during the same period. Rainfall events with a 5-year return period were associated with an increased risk for both cardiovascular mortality (RRc, 1.05) and respiratory mortality (RRc, 1.29), with the respiratory mortality being significantly higher.
 

Points of Concern

According to the authors, moderate to high rainfall can exert protective effects through two main mechanisms: Improving air quality (rainfall can reduce the concentration of particulate matter 2.5 cm in diameter or less in the atmosphere) and behavioral changes in people (more time spent in enclosed environments, reducing direct exposure to outdoor air pollution and nonoptimal temperatures). As rainfall intensity increases, the initial protective effects may be overshadowed by a cascade of negative impacts including:

  • Critical resource disruptions: Intense rainfall can cause severe disruptions to access to healthcare, infrastructure damage including power outages, and compromised water and food quality.
  • Physiological effects: Increased humidity levels facilitate the growth of airborne pathogens, potentially triggering allergic reactions and respiratory issues, particularly in vulnerable individuals. Rapid shifts in atmospheric pressure and temperature fluctuations can lead to cardiovascular and respiratory complications.
  • Indirect effects: Extreme rainfall can have profound effects on mental health, inducing stress and anxiety that may exacerbate pre-existing mental health conditions and indirectly contribute to increased overall mortality from nonexternal causes.

The intensity-response curves for the health effects of heavy rainfall showed a nonlinear trend, transitioning from a protective effect at moderate levels of rainfall to a risk for severe harm when rainfall intensity became extreme. Additionally, the significant effects of extreme events were modified by various types of climate and were more pronounced in areas characterized by low variability in precipitation or sparse vegetation cover.

The study demonstrated that various local factors, such as climatic conditions, climate type, and vegetation cover, can potentially influence cardiovascular and respiratory mortality and all-cause mortality related to precipitation. The findings may help physicians convey to their patients the impact of climate change on their health.

This story was translated from Univadis Italy 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.

Climate change is intensifying the variability of precipitation caused by extreme daily and overall rainfall events. Awareness of the effects of these events is crucial for understanding the complex health consequences of climate change. The connections between health and climate have been recognized by physicians and patients even when climatology did not have the status of an exact science. Physicians have often advised their patients to move to a better climate, and when they did, the recommendation was rarely based on precise scientific knowledge. However, the benefits of changing environments were often so evident that they were indisputable.

Today, advanced models, satellite imagery, and biological approaches such as environmental epigenetics are enhancing our understanding of health risks related to climate change.
 

Extreme Rainfall and Health

The increase in precipitation variability is linked to climate warming, which leads to higher atmospheric humidity and extreme rainfall events. These manifestations can cause rapid weather changes, increasing interactions with harmful aerosols and raising the risk for various cardiovascular and respiratory conditions. However, a full understanding of the association between rain and health has been hindered by conflicting results and methodological issues (limited geographical locations and short observation durations) in studies.

The association between rainfall intensity and health effects is likely nonlinear. Moderate precipitation can mitigate summer heat and help reduce air pollution, an effect that may lower some environmental health risks. Conversely, intense, low-frequency, short-duration rainfall events can have particularly harmful effects on health, as such events can trigger rapid weather changes, increased proliferation of pathogens, and a rise in the risk of various pollutants, potentially exacerbating health conditions.
 

Rain and Mortality

Using an intensity-duration-frequency model of three rainfall indices (high intensity, low frequency, short duration), a study published in October 2024 combined these with mortality data from 34 countries or regions. Researchers estimated associations between mortality (all cause, cardiovascular, and respiratory) and rainfall events with different return periods (the average time expected before an extreme event of a certain magnitude occurs again) and crucial effect modifiers, including climatic, socioeconomic, and urban environmental conditions.

The analysis included 109,954,744 deaths from all causes; 31,164,161 cardiovascular deaths; and 11,817,278 respiratory deaths. During the study period, from 1980 to 2020, a total of 50,913 rainfall events with a 1-year return period, 8362 events with a 2-year return period, and 3301 events with a 5-year return period were identified.

The most significant finding was a global positive association between all-cause mortality and extreme rainfall events with a 5-year return period. One day of extreme rainfall with a 5-year return period was associated with a cumulative relative risk (RRc) of 1.08 (95% CI, 1.05-1.11) for daily mortality from all causes. Rainfall events with a 2-year return period were associated with increased daily respiratory mortality (RRc, 1.14), while no significant effect was observed for cardiovascular mortality during the same period. Rainfall events with a 5-year return period were associated with an increased risk for both cardiovascular mortality (RRc, 1.05) and respiratory mortality (RRc, 1.29), with the respiratory mortality being significantly higher.
 

Points of Concern

According to the authors, moderate to high rainfall can exert protective effects through two main mechanisms: Improving air quality (rainfall can reduce the concentration of particulate matter 2.5 cm in diameter or less in the atmosphere) and behavioral changes in people (more time spent in enclosed environments, reducing direct exposure to outdoor air pollution and nonoptimal temperatures). As rainfall intensity increases, the initial protective effects may be overshadowed by a cascade of negative impacts including:

  • Critical resource disruptions: Intense rainfall can cause severe disruptions to access to healthcare, infrastructure damage including power outages, and compromised water and food quality.
  • Physiological effects: Increased humidity levels facilitate the growth of airborne pathogens, potentially triggering allergic reactions and respiratory issues, particularly in vulnerable individuals. Rapid shifts in atmospheric pressure and temperature fluctuations can lead to cardiovascular and respiratory complications.
  • Indirect effects: Extreme rainfall can have profound effects on mental health, inducing stress and anxiety that may exacerbate pre-existing mental health conditions and indirectly contribute to increased overall mortality from nonexternal causes.

The intensity-response curves for the health effects of heavy rainfall showed a nonlinear trend, transitioning from a protective effect at moderate levels of rainfall to a risk for severe harm when rainfall intensity became extreme. Additionally, the significant effects of extreme events were modified by various types of climate and were more pronounced in areas characterized by low variability in precipitation or sparse vegetation cover.

The study demonstrated that various local factors, such as climatic conditions, climate type, and vegetation cover, can potentially influence cardiovascular and respiratory mortality and all-cause mortality related to precipitation. The findings may help physicians convey to their patients the impact of climate change on their health.

This story was translated from Univadis Italy 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.

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America’s PCPs: Take a Bow

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Hi, everyone. I’m Dr. Kenny Lin. I am a family physician and associate director of the Lancaster General Hospital Family Medicine Residency, and I blog at Common Sense Family Doctor.

For the past 4 years, primary care clinicians have labored under a seemingly endless onslaught of bad news. A recent report estimated that there were over 1.3 million excess deaths in the United States from March 2020 to May 2023, including nearly half a million Americans younger than age 65. Social isolation and an ailing economy accelerated preexisting rises in drug overdoses and obesity, while teenage vaping threatened to hook a new generation on tobacco products even as adult smoking plummeted. Meanwhile, more than half of the nation’s physicians now report feelings of burnout, pay for family doctors appears to be stagnating, and our interactions with an increasing number of patients are fraught with suspicions about the value of vaccines— not just against COVID-19 but against flu and other viruses, too — and the medical system as a whole, doctors included. 

Now, for the good news.

A year and a half since the end of the pandemic emergency, we are seeing gains on several fronts, and physicians deserve much of the credit. Preliminary data from the Centers for Disease Control and Prevention show that 10,000 fewer people died from drug overdoses than in the previous year. Although multiple factors contributed to this change, the elimination of the X-waiver, which had previously been required for physicians to prescribe buprenorphine for opioid use disorder, in January 2023 has improved access to medications for addiction treatment. In addition, the expansion of state requirements to check prescription drug monitoring programs when opioids or benzodiazepines are prescribed, and to prescribe naloxone to patients taking more than a certain number of morphine milligram equivalents per day, has probably reduced the harms of hazardous drug use.

On the obesity front, recent data from the National Health and Nutrition Examination Survey found that the prevalence of obesity in adults fell for the first time in more than a decade, from 41.9% to 40.3%. To be sure, obesity remains far too common, and this finding could be the result of statistical chance rather than representing a true decline. But the widespread prescribing of GLP-1 receptor agonists by primary care physicians, in particular, could have played a role in the encouraging trend.

Although more research is needed to prove causality, one analysis suggests that these drugs could easily have lowered the body mass index (BMI) of more than enough patients to account for the observed decline. What’s more, the rise in prevalence of BMIs above 40 (from 7.7% to 9.7%) could be explained by the mortality benefit of the drugs: More people remained in this severe obesity category because they didn’t die from complications of their weight. Whether future studies support keeping people on GLP-1s for life or eventually “off-ramping” them to other weight control strategies, family physicians are well positioned to help.

Finally, with little fanfare, the youth smoking rate has fallen precipitously. In 2023, 1.9% of high school students and 1.1% of middle-schoolers reported smoking cigarettes in the past 30 days. And they didn’t simply swap one form of nicotine delivery device for another. The 30-day prevalence of vaping among high school students fell from 27.5% in 2019 to 7.8% this year. Changing social norms and stricter federal regulation of tobacco products are probably more responsible for this positive trend than medical care, though the US Preventive Services Task Force recommends education or brief counseling to prevent initiation of tobacco use among school-aged children and adolescents. Should tobacco use in youth remain at these historically low levels, millions of premature deaths from lung cancer and heart disease will have been prevented.

America’s doctors have earned the right to take a bow. We have much more work to do, but our efforts are making a meaningful difference in three seemingly intractable health problems.

Dr. Lin, Associate Director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania, has disclosed no relevant financial relationships.

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

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Hi, everyone. I’m Dr. Kenny Lin. I am a family physician and associate director of the Lancaster General Hospital Family Medicine Residency, and I blog at Common Sense Family Doctor.

For the past 4 years, primary care clinicians have labored under a seemingly endless onslaught of bad news. A recent report estimated that there were over 1.3 million excess deaths in the United States from March 2020 to May 2023, including nearly half a million Americans younger than age 65. Social isolation and an ailing economy accelerated preexisting rises in drug overdoses and obesity, while teenage vaping threatened to hook a new generation on tobacco products even as adult smoking plummeted. Meanwhile, more than half of the nation’s physicians now report feelings of burnout, pay for family doctors appears to be stagnating, and our interactions with an increasing number of patients are fraught with suspicions about the value of vaccines— not just against COVID-19 but against flu and other viruses, too — and the medical system as a whole, doctors included. 

Now, for the good news.

A year and a half since the end of the pandemic emergency, we are seeing gains on several fronts, and physicians deserve much of the credit. Preliminary data from the Centers for Disease Control and Prevention show that 10,000 fewer people died from drug overdoses than in the previous year. Although multiple factors contributed to this change, the elimination of the X-waiver, which had previously been required for physicians to prescribe buprenorphine for opioid use disorder, in January 2023 has improved access to medications for addiction treatment. In addition, the expansion of state requirements to check prescription drug monitoring programs when opioids or benzodiazepines are prescribed, and to prescribe naloxone to patients taking more than a certain number of morphine milligram equivalents per day, has probably reduced the harms of hazardous drug use.

On the obesity front, recent data from the National Health and Nutrition Examination Survey found that the prevalence of obesity in adults fell for the first time in more than a decade, from 41.9% to 40.3%. To be sure, obesity remains far too common, and this finding could be the result of statistical chance rather than representing a true decline. But the widespread prescribing of GLP-1 receptor agonists by primary care physicians, in particular, could have played a role in the encouraging trend.

Although more research is needed to prove causality, one analysis suggests that these drugs could easily have lowered the body mass index (BMI) of more than enough patients to account for the observed decline. What’s more, the rise in prevalence of BMIs above 40 (from 7.7% to 9.7%) could be explained by the mortality benefit of the drugs: More people remained in this severe obesity category because they didn’t die from complications of their weight. Whether future studies support keeping people on GLP-1s for life or eventually “off-ramping” them to other weight control strategies, family physicians are well positioned to help.

Finally, with little fanfare, the youth smoking rate has fallen precipitously. In 2023, 1.9% of high school students and 1.1% of middle-schoolers reported smoking cigarettes in the past 30 days. And they didn’t simply swap one form of nicotine delivery device for another. The 30-day prevalence of vaping among high school students fell from 27.5% in 2019 to 7.8% this year. Changing social norms and stricter federal regulation of tobacco products are probably more responsible for this positive trend than medical care, though the US Preventive Services Task Force recommends education or brief counseling to prevent initiation of tobacco use among school-aged children and adolescents. Should tobacco use in youth remain at these historically low levels, millions of premature deaths from lung cancer and heart disease will have been prevented.

America’s doctors have earned the right to take a bow. We have much more work to do, but our efforts are making a meaningful difference in three seemingly intractable health problems.

Dr. Lin, Associate Director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania, has disclosed no relevant financial relationships.

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

Hi, everyone. I’m Dr. Kenny Lin. I am a family physician and associate director of the Lancaster General Hospital Family Medicine Residency, and I blog at Common Sense Family Doctor.

For the past 4 years, primary care clinicians have labored under a seemingly endless onslaught of bad news. A recent report estimated that there were over 1.3 million excess deaths in the United States from March 2020 to May 2023, including nearly half a million Americans younger than age 65. Social isolation and an ailing economy accelerated preexisting rises in drug overdoses and obesity, while teenage vaping threatened to hook a new generation on tobacco products even as adult smoking plummeted. Meanwhile, more than half of the nation’s physicians now report feelings of burnout, pay for family doctors appears to be stagnating, and our interactions with an increasing number of patients are fraught with suspicions about the value of vaccines— not just against COVID-19 but against flu and other viruses, too — and the medical system as a whole, doctors included. 

Now, for the good news.

A year and a half since the end of the pandemic emergency, we are seeing gains on several fronts, and physicians deserve much of the credit. Preliminary data from the Centers for Disease Control and Prevention show that 10,000 fewer people died from drug overdoses than in the previous year. Although multiple factors contributed to this change, the elimination of the X-waiver, which had previously been required for physicians to prescribe buprenorphine for opioid use disorder, in January 2023 has improved access to medications for addiction treatment. In addition, the expansion of state requirements to check prescription drug monitoring programs when opioids or benzodiazepines are prescribed, and to prescribe naloxone to patients taking more than a certain number of morphine milligram equivalents per day, has probably reduced the harms of hazardous drug use.

On the obesity front, recent data from the National Health and Nutrition Examination Survey found that the prevalence of obesity in adults fell for the first time in more than a decade, from 41.9% to 40.3%. To be sure, obesity remains far too common, and this finding could be the result of statistical chance rather than representing a true decline. But the widespread prescribing of GLP-1 receptor agonists by primary care physicians, in particular, could have played a role in the encouraging trend.

Although more research is needed to prove causality, one analysis suggests that these drugs could easily have lowered the body mass index (BMI) of more than enough patients to account for the observed decline. What’s more, the rise in prevalence of BMIs above 40 (from 7.7% to 9.7%) could be explained by the mortality benefit of the drugs: More people remained in this severe obesity category because they didn’t die from complications of their weight. Whether future studies support keeping people on GLP-1s for life or eventually “off-ramping” them to other weight control strategies, family physicians are well positioned to help.

Finally, with little fanfare, the youth smoking rate has fallen precipitously. In 2023, 1.9% of high school students and 1.1% of middle-schoolers reported smoking cigarettes in the past 30 days. And they didn’t simply swap one form of nicotine delivery device for another. The 30-day prevalence of vaping among high school students fell from 27.5% in 2019 to 7.8% this year. Changing social norms and stricter federal regulation of tobacco products are probably more responsible for this positive trend than medical care, though the US Preventive Services Task Force recommends education or brief counseling to prevent initiation of tobacco use among school-aged children and adolescents. Should tobacco use in youth remain at these historically low levels, millions of premature deaths from lung cancer and heart disease will have been prevented.

America’s doctors have earned the right to take a bow. We have much more work to do, but our efforts are making a meaningful difference in three seemingly intractable health problems.

Dr. Lin, Associate Director, Family Medicine Residency Program, Lancaster General Hospital, Lancaster, Pennsylvania, has disclosed no relevant financial relationships.

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

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