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Systematic Review: Effects of ACE inhibitors and ARBs on kidney and cardiovascular outcomes in diabetic patients – Cochrane Library

4 May, 2024 | 13:32h | UTC

Study Design and Population:

This systematic review and meta-analysis evaluated the effectiveness of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) in managing cardiovascular and kidney outcomes in adults with diabetes and kidney disease. It included data from 109 randomized controlled trials totaling 28,341 participants, comparing the impact of ACEi and ARBs, either alone or in combination, against each other, placebo, or no treatment.

 

Main Findings:

The analysis revealed that ACEi may reduce the risk of kidney failure (RR 0.61, 95% CI 0.39 to 0.94) but generally has little effect on all-cause mortality and cardiovascular death compared to placebo, with low certainty of evidence. Similarly, ARBs showed potential in preventing kidney failure (RR 0.82, 95% CI 0.72 to 0.94) and the progression from microalbuminuria to macroalbuminuria. The effects on cardiovascular outcomes remained uncertain and showed minimal difference compared to placebo or no treatment.

 

Implications for Practice:

While ACEi and ARBs may aid in preventing kidney failure in patients with diabetic kidney disease, their broader impacts on mortality and cardiovascular health remain uncertain. This underscores the necessity for further rigorous research to verify these findings and better determine the optimal therapeutic strategies. Clinicians should weigh these results against individual patient profiles considering the overall low certainty of the evidence.

 

Reference (link to abstract – $ for full-text):

Natale, P. et al. (2024). Comparative Efficacy of ACE Inhibitors and ARB on Kidney and Cardiovascular Outcomes in Diabetic Kidney Disease. Cochrane Database of Systematic Reviews. DOI: 10.1002/14651858.CD006257.pub2.

 


Systematic Review: Comparing antibiotic treatment vs. appendectomy for the initial treatment of uncomplicated appendicitis – Cochrane Library

4 May, 2024 | 13:09h | UTC

Study Design and Population:

This Cochrane review analyzed 13 randomized controlled trials involving 3,358 participants to compare the efficacy of antibiotic treatment versus appendectomy in managing uncomplicated acute appendicitis. The included studies predominantly involved adult participants and utilized broad-spectrum antibiotics, with interventions ranging from open to predominantly laparoscopic appendectomy. Data collection spanned from hospital admission to up to seven years, with studies conducted across various global regions, including Asia, Europe, and North America.

 

Main Findings:

The primary outcomes revealed that antibiotic treatment might slightly increase the risk of unsuccessful treatment with 76 additional unsuccessful cases per 1,000 individuals compared to surgery, though these results did not reach clinical significance. Antibiotics reduced wound infections but possibly increased the average hospital stay by half a day. About 30.7% of participants treated with antibiotics required an appendectomy within one year. Secondary outcomes showed very uncertain evidence on antibiotics’ effect on intra-abdominal abscess or reoperation rates, and a slight increase in negative appendectomy rates was observed.

 

Implications for Practice:

The findings suggest that while antibiotics could serve as an initial treatment to avoid surgery in two-thirds of cases annually, a significant portion may still require surgical intervention. This information is crucial for clinicians in making informed treatment decisions, particularly considering patient preferences and the risk of surgery. Further research is needed to explore long-term outcomes and identify patient subgroups that may benefit most from either treatment.

 

Reference (link to abstract – $ for full-text):

Doleman B, Fonnes S, Lund JN, et al. (2024). Appendectomy versus antibiotic treatment for acute appendicitis. Cochrane Database of Systematic Reviews, (April 29), CD015038.pub2. DOI: https://doi.org/10.1002/14651858.CD015038.pub2.

 


RCT: Acute impact of provoked anger on endothelial health in healthy adults – J Am Heart Assoc

4 May, 2024 | 13:00h | UTC

This study explored the immediate effects of negative emotions on vascular endothelial health in a sample of 280 healthy adults. Participants were assigned to recall tasks that induced feelings of anger, anxiety, sadness, or a neutral emotional state, followed by assessments of endothelial health. The primary measure, endothelium-dependent vasodilation (reactive hyperemia index), significantly deteriorated in the anger group compared to the neutral condition (mean change: 0.20±0.67 vs. 0.50±0.60; P=0.007). Anxiety and sadness did not significantly affect this measure. Additionally, there were no significant changes in endothelial cell-derived microparticles or endothelial progenitor cells across all conditions. The findings indicate that short-term anger provocation can impair endothelial function, suggesting a specific pathway by which anger could increase cardiovascular disease risk.

 

Reference (link to free full-text):

Daichi Shimbo et al. (2024). Translational Research of the Acute Effects of Negative Emotions on Vascular Endothelial Health: Findings From a Randomized Controlled Study. Journal of the American Heart Association, 0:e032698. DOI: https://doi.org/10.1161/JAHA.123.032698

 


M-A: Psilocybin significantly reduces depression symptoms across diverse populations – The BMJ

4 May, 2024 | 12:51h | UTC

Study Design and Population:

This systematic review and meta-analysis synthesized data from randomized trials assessing the efficacy of psilocybin as a treatment for depression in adults. Researchers utilized five electronic databases for published literature and four databases for unpublished and international studies. The analysis included 436 participants, aged 36 to 60 years, from seven randomized trials, with both genders represented and varying comorbidities such as cancer.

 

Main Findings:

The meta-analysis revealed a significant reduction in depression scores among participants treated with psilocybin, with a Hedges’ g value of 1.64, indicating a large effect size. Notably, the improvement was more pronounced among those with secondary depression and those assessed using self-report depression scales. Subgroup analyses and metaregression also highlighted that older age and previous use of psychedelics correlated with greater symptom improvement. Despite the robust findings, high heterogeneity and a risk of small study bias led to a low certainty of evidence.

 

Implications for Practice:

The findings support psilocybin’s potential as an effective antidepressant, particularly among specific subgroups such as those with secondary depression. However, the presence of high heterogeneity and small study biases suggests that further research is needed to explore the impact of expectancy effects, moderating factors, and treatment modalities. Clinicians should consider these elements when discussing psilocybin as a treatment option with patients, and further high-quality studies are necessary to solidify its role in clinical practice.

 

Reference (link to free full-text):

Reference: Metaxa, A.-M. et al. (2024). Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis. BMJ, 385. DOI: https://doi.org/10.1136/bmj-2023-078084.

 


ACP Guidelines for the pharmacologic management of type 2 diabetes in adults – Ann Intern Med

3 May, 2024 | 14:05h | UTC

The American College of Physicians (ACP) has issued an updated guideline focusing on the pharmacological management of type 2 diabetes. This guideline reviews the efficacy and safety of new medications, including GLP-1 agonists, SGLT-2 inhibitors, and others, emphasizing a systematic evaluation using the GRADE methodology. Key recommendations advise the integration of SGLT-2 inhibitors or GLP-1 agonists with metformin and lifestyle changes for better glycemic control and reduction in mortality and major cardiovascular events. Conversely, the use of DPP-4 inhibitors in similar therapeutic contexts is not recommended due to insufficient evidence of benefit. This guideline targets healthcare providers managing nonpregnant adults with type 2 diabetes.

 

Reference (link to free full-text):

Qaseem et al. (2024). Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Clinical Guideline From the American College of Physicians. Annals of Internal Medicine. DOI:10.7326/M23-2788.

 


ACP cost-effectiveness analysis: Newer antidiabetic medications in type 2 diabetes – Ann Intern Med

3 May, 2024 | 13:57h | UTC

This systematic review evaluates the cost-effectiveness of newer antidiabetic medications for type 2 diabetes from U.S. clinical and economic perspectives. Analyzing non-industry funded cost-effectiveness analyses (CEAs) using GRADE and Drummond criteria, the study identifies varying cost per quality-adjusted life-year (QALY) values for medications such as GLP1a and SGLT2i. It concludes that while GLP1a and SGLT2i offer low value as primary therapies due to high costs, they may present intermediate value as adjunct treatments to metformin. The study highlights the methodological variability in CEAs and the influence of drug cost and effectiveness assumptions on outcomes. The results suggest cautious interpretation in clinical decision-making due to varied evidence quality and cost-effectiveness profiles among the reviewed medications.

 

Reference (link to free full-text):

Schousboe, J. T et al. Cost-Effectiveness of Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review of Cost-Effectiveness Studies for the American College of Physicians. Annals of Internal Medicine. DOI: [10.7326/M23-1492].

 


ACP Meta-Analysis: Comparative efficacy of newer antidiabetic agents in type 2 diabetes management – Ann Intern Med

3 May, 2024 | 13:49h | UTC

This systematic review and network meta-analysis evaluates the effectiveness and safety of modern antidiabetic drugs in managing type 2 diabetes mellitus. The study analyzed 130 publications from 84 randomized controlled trials, using GRADE criteria for evidence assessment. Sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP1) agonists demonstrated significant reductions in all-cause mortality and major adverse cardiovascular events when compared to usual care, with SGLT2 inhibitors also showing benefits in reducing chronic kidney disease progression and hospitalizations due to heart failure. In contrast, dipeptidyl peptidase-4 (DPP4) inhibitors, insulin, and tirzepatide showed no significant mortality benefits. The study identified limitations including sparse direct drug comparisons and inadequate data for certain patient subgroups. Overall, SGLT2 inhibitors and GLP1 agonists were associated with fewer serious adverse events and severe hypoglycemia compared to insulin and sulfonylureas.

 

Reference (link to free full-text):

Drake, T. et al. (2023). Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review and Network Meta-analysis for the American College of Physicians. Annals of Internal Medicine. DOI: 10.7326/M23-1490.

 


Review: Key findings from the Women’s Health Initiative studies on postmenopausal interventions – JAMA

3 May, 2024 | 13:34h | UTC

The Women’s Health Initiative (WHI) studied the impact of various interventions on postmenopausal women aged 50-79, using data from 161,808 participants between 1993 and 2018. The findings suggest that hormone therapy, specifically with conjugated equine estrogens and medroxyprogesterone acetate, does not reduce the risk of cardiovascular diseases, dementia, or other chronic conditions in postmenopausal women. It is, however, effective for managing severe menopausal symptoms when initiated before age 60 in women without contraindications. The trials also concluded that universal supplementation of calcium and vitamin D does not effectively prevent fractures and should be limited to those not meeting dietary intake recommendations. Furthermore, a low-fat diet rich in fruits, vegetables, and grains did not reduce the incidence of breast or colorectal cancer, though it may decrease breast cancer mortality rates, indicating the need for further investigation.

 

Reference (link to free full-text for a limited period):

Manson JE et al. (2024). The Women’s Health Initiative Randomized Trials and Clinical Practice: A Review. JAMA, Published online May 1, 2024. DOI: 10.1001/jama.2024.6542.

 


Guideline: Management of age-related hearing loss – Otolaryngol Head Neck Surg

2 May, 2024 | 23:22h | UTC

This guideline by the American Academy of Otolaryngology–Head and Neck Surgery Foundation offers a comprehensive approach for the detection and management of age-related hearing loss (ARHL) in adults aged 50 and older. It stresses the importance of early identification and appropriate intervention to mitigate the effects of ARHL, which is commonly underdiagnosed despite being the most prevalent sensory deficit in the elderly. The guideline includes eleven Key Action Statements that guide clinicians in screening, diagnosis, and management strategies, emphasizing the use of audiograms, otoscopy, and hearing aids, as well as the importance of addressing sociodemographic factors affecting healthcare access. It also highlights the necessity of patient and family education on the impacts of hearing loss and communication strategies. This structured approach aims to enhance healthcare delivery and improve the quality of life for those affected by hearing loss.

 

Reference (link to free-full-text):

Tsai Do. et al. (2024). Clinical Practice Guideline: Age-Related Hearing Loss. Otolaryngology–Head and Neck Surgery. DOI: 10.1002/ohn.750

 


USPSTF Guideline: Biennial screening mammography recommended for women aged 40-74 to reduce breast cancer morbidity and mortality

1 May, 2024 | 21:45h | UTC

Study Design and Population:

The US Preventive Services Task Force (USPSTF) performed a systematic review and collaborated on modeling studies to evaluate the effectiveness of various mammography-based breast cancer screening strategies. This assessment included factors such as age of initiation and cessation of screening, screening intervals, modalities, and the use of supplemental imaging. The population studied consisted of cisgender women and all other persons assigned female at birth who are 40 years or older and at average risk of breast cancer.

 

Main Findings:

The USPSTF concludes with moderate certainty that biennial screening mammography for women aged 40 to 74 years provides a moderate net benefit in reducing the incidence of and progression to advanced breast cancer, as well as in decreasing breast cancer morbidity and mortality. However, the evidence is insufficient to assess the benefits and harms of mammography screening in women aged 75 and older, as well as the use of supplemental screening with ultrasound or MRI in women with dense breasts.

 

Implications for Practice:

Based on these findings, the USPSTF recommends biennial screening mammography for women aged 40 to 74 years. This recommendation aims to optimize breast cancer outcomes while considering the balance of benefits and harms of screening. There is a need for further research to clarify the benefits and risks associated with mammography in women older than 75 and for those with dense breasts considering supplemental screening.

 

Commentary on X (thread – click for more)

 

Reference (link to free full-text):

Screening for Breast Cancer US Preventive Services Task Force Recommendation Statement. JAMA. Published online April 30, 2024. doi:10.1001/jama.2024.5534

 


RCT: Beta-blockers post myocardial infarction showed no benefit in patients with preserved ejection fraction

30 Apr, 2024 | 13:40h | UTC

This randomized, open-label clinical trial conducted across 45 centers in Sweden, Estonia, and New Zealand examined the impact of long-term beta-blocker treatment in patients with acute myocardial infarction (AMI) who had undergone coronary angiography and had a preserved left ventricular ejection fraction (LVEF ≥ 50%). The study involved 5020 patients, predominantly from Sweden, with a median follow-up of 3.5 years. Participants were randomly assigned to receive either a beta-blocker (metoprolol or bisoprolol) or no beta-blocker. The primary endpoint was a composite of death from any cause or new myocardial infarction. The results showed no significant difference in the primary endpoint between the beta-blocker group (7.9%) and the no–beta-blocker group (8.3%) with a hazard ratio of 0.96 (95% CI, 0.79 to 1.16; P=0.64). Additionally, no significant differences were observed in secondary endpoints such as death from cardiovascular causes, myocardial infarction, or hospitalizations for atrial fibrillation and heart failure. Safety endpoints were also comparable between the groups. Overall, long-term beta-blocker treatment did not confer a reduction in risk for the primary composite endpoint or improve secondary outcomes in this patient population.

 

Commentary on X:

 

Reference (link to abstract – $ for full-text):

Troels Yndigegn et al. (2024). Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction. N Engl J Med, 390(15), 1372-1381. DOI: 10.1056/NEJMoa2401479.

 


RCT: Post-1 month ticagrelor monotherapy vs. dual antiplatelet therapy significantly reduces bleeding events in acute coronary syndromes

30 Apr, 2024 | 13:26h | UTC

In this randomized, placebo-controlled, double-blind clinical trial, 3400 patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI) were assessed to compare the effects of ticagrelor alone versus ticagrelor plus aspirin from 1 to 12 months post-PCI. The study aimed to determine if ticagrelor alone could reduce bleeding without increasing major adverse cardiovascular or cerebrovascular events (MACCE). The primary findings indicated that ticagrelor alone resulted in significantly lower clinically relevant bleeding (2.1% vs. 4.6%, p<0.0001) and demonstrated non-inferiority in MACCE rates compared to the dual therapy group (3.6% vs. 3.7%, pnon-inferiority<0.0001). These outcomes suggest that ticagrelor monotherapy, starting one month post-PCI, may be an effective alternative to standard dual antiplatelet therapy in reducing bleeding risks without compromising safety.

 

Commentary on X:

 

Reference (link to abstract – $ for full-text):

Ge Z. et al. (2024). Ticagrelor alone versus ticagrelor plus aspirin from month 1 to month 12 after percutaneous coronary intervention in patients with acute coronary syndromes (ULTIMATE-DAPT): a randomised, placebo-controlled, double-blind clinical trial. The Lancet, 404(10102), 1173-1182. DOI: https://doi.org/10.1016/S0140-6736(24)00473-2.

 


Phase 2 RCT: Lixisenatide slows progression of motor disability in early Parkinson’s disease, but with notable gastrointestinal side effects

30 Apr, 2024 | 13:00h | UTC

In a phase 2, double-blind, randomized, placebo-controlled trial, the effect of lixisenatide, a glucagon-like peptide-1 receptor agonist, was evaluated for its potential to slow the progression of motor disability in patients with early Parkinson’s disease. A total of 156 patients, diagnosed within the past three years and stable on symptom-managing medications, were enrolled and equally divided into lixisenatide and placebo groups. After 12 months, the lixisenatide group showed a slight improvement in motor disability (−0.04 point change) compared to a worsening in the placebo group (3.04 point change) on the Movement Disorder Society–Unified Parkinson’s Disease Rating Scale part III. This difference was statistically significant (p=0.007). However, after a 2-month washout period, improvements were less distinct. Notably, 46% of lixisenatide-treated patients experienced nausea, and 13% reported vomiting. These findings suggest potential benefits of lixisenatide for motor symptoms in Parkinson’s disease, though further research is necessary to fully assess its efficacy and tolerability.

 

Commentary on X:

 

Reference (link to abstract – $ for full-text):

Wassilios G. Meissner et al. (2024). Trial of Lixisenatide in Early Parkinson’s Disease. N Engl J Med, 390(15), 1176-1185. DOI: 10.1056/NEJMoa2312323

 


RCT: Empagliflozin does not reduce heart failure hospitalization or death post-myocardial infarction

29 Apr, 2024 | 12:39h | UTC

This randomized, placebo-controlled trial assessed empagliflozin in preventing heart failure or death in patients recently hospitalized for acute myocardial infarction. Among 6,522 patients divided evenly into empagliflozin and placebo groups, there was no significant difference in the primary outcome—a composite of heart failure hospitalization or death—after 17.9 months. The empagliflozin group saw 8.2% experiencing the primary outcome versus 9.1% in the placebo group, yielding a non-significant hazard ratio of 0.90 (95% CI, 0.76 to 1.06; P=0.21). The results indicate that empagliflozin does not effectively reduce the risk of heart failure or mortality compared to placebo in this setting.

 

Reference (link to abstract – $ for full-text):

Butler, J. et al. (2024). Empagliflozin after Acute Myocardial Infarction. N Engl J Med, 390(16), 1455-1466. DOI: 10.1056/NEJMoa2314051

 


RCT: Semaglutide significantly improves symptoms and weight loss in HFpEF and type 2 diabetes patients

29 Apr, 2024 | 12:36h | UTC

This randomized clinical trial evaluated the effects of semaglutide on 616 patients with obesity-related heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes. Patients received weekly doses of 2.4 mg semaglutide or a placebo for 52 weeks. The study’s primary findings included a significant improvement in heart failure–related symptoms, as measured by the Kansas City Cardiomyopathy Questionnaire clinical summary score (average increase of 13.7 points in the semaglutide group versus 6.4 points in the placebo group). Additionally, semaglutide treatment resulted in a mean 9.8% reduction in body weight compared to 3.4% with placebo. Secondary outcomes also favored semaglutide, showing enhancements in 6-minute walk distance and reductions in C-reactive protein levels. Notably, semaglutide was associated with fewer serious adverse events compared to placebo.

 

Reference (link to abstract – $ for full-text):

Mikhail N. Kosiborod et al. (2024). Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes. N Engl J Med, 390(15), 1394-1407. DOI: 10.1056/NEJMoa2313917

 


Cohort Study: No increased risk of autism, ADHD, or intellectual disability from acetaminophen use in pregnancy

29 Apr, 2024 | 12:34h | UTC

This cohort study investigated the association between acetaminophen use during pregnancy and the risk of autism, ADHD, and intellectual disability in children. The study utilized a population-based sample of nearly 2.5 million Swedish children born between 1995 and 2019, with data analyzed up to 2021. Initial findings without sibling controls suggested a marginal increase in the risks of autism and ADHD. However, sibling control analyses, which help adjust for familial confounding, showed no significant associations (HR for autism and ADHD at 0.98, and intellectual disability at 1.01). These results imply that earlier observed risks might be due to unaccounted familial factors, not acetaminophen exposure.

 

Reference (link to abstract – $ for full-text):

Viktor H. Ahlqvist et al. (2024). Acetaminophen Use During Pregnancy and Children’s Risk of Autism, ADHD, and Intellectual Disability. JAMA, 331(14), 1205-1214. DOI: 10.1001/jama.2024.3172

 


Meta-Analysis: Efficacy of MRI in prostate cancer screening for reducing unnecessary biopsies

28 Apr, 2024 | 20:13h | UTC

This meta-analysis evaluated the effectiveness of incorporating magnetic resonance imaging (MRI) into prostate cancer screening pathways, compared to prostate-specific antigen (PSA)–only screening strategies. Analyzing data from 80,114 men across 12 studies, the findings demonstrate that MRI-based screening, particularly when using a sequential approach and a PI-RADS score ≥3 cutoff for biopsy, significantly increases the odds of detecting clinically significant prostate cancers (OR, 4.15) while reducing unnecessary biopsies (OR, 0.28) and detection of clinically insignificant cancers (OR, 0.34). Implementing a higher PI-RADS score of ≥4 further decreased the detection of insignificant cancers and biopsies performed, without impacting the detection rate of significant cancers. These results support the integration of MRI into screening programs to enhance diagnostic precision and reduce patient harm.

 

Reference (link to abstract – $ for full-text):

Tamás Fazekas et al. (2024). Magnetic Resonance Imaging in Prostate Cancer Screening:  A Systematic Review and Meta-Analysis. JAMA Oncol, Published online April 5, 2024. DOI: 10.1001/jamaoncol.2024.0734

 


Pooled Analysis: Semaglutide improves symptoms and reduces weight in obesity-related heart failure with preserved ejection fraction

28 Apr, 2024 | 16:33h | UTC

This pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomized trials assessed the efficacy of semaglutide in 1,145 participants with obesity-related heart failure and preserved ejection fraction, across 129 research sites globally. Participants, who had a BMI of at least 30 kg/m2 and varied cardiovascular conditions, were administered 2.4 mg of semaglutide weekly for 52 weeks. Semaglutide significantly improved heart failure-related symptoms (7.5 points increase in KCCQ-CSS), reduced body weight by 8.4%, and increased the 6-min walk distance by 17.1 meters, compared to placebo. The treatment also demonstrated safety, with fewer serious adverse events than the placebo group. These benefits were consistent across various subgroups, confirming semaglutide’s potential as a treatment in this patient population.

 

Reference (link to abstract – $ for full-text):

Reference: Prof Javed Butler et al. (2024). Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials. The Lancet, (Volume and Issue Pending), Pages. DOI: https://doi.org/10.1016/S0140-6736(24)00469-0.

 


Diagnostic Study: Enhanced prediction of TB progression with IGRAs compared to tuberculin skin test

27 Apr, 2024 | 18:53h | UTC

Study Design and Population:

This prospective diagnostic study analyzed the predictive accuracy of tuberculosis (TB) tests among 22,020 high-risk participants across 10 US sites from 2012 to 2020. Participants included individuals with close contacts to infectious TB cases, those born in or travelers to high-incidence countries, individuals living with HIV, or belonging to locally prevalent high-risk groups. Testing included two interferon-γ release assays (IGRAs), QuantiFERON-TB Gold In-Tube (QFT-GIT) and SPOT.TB (TSPOT), alongside the traditional tuberculin skin test (TST).

 

Main Findings:

The study found that both IGRAs, TSPOT and QFT-GIT, showed significantly superior positive predictive value (PPV) for predicting TB disease progression compared to the TST, with PPV ratios of 1.65 (95% CI, 1.35-2.02) and 1.47 (95% CI, 1.22-1.77) respectively. Additionally, when considering a positive TST result, further positive results from either IGRA significantly increased the PPV, emphasizing the enhanced predictive capability of IGRAs over TST alone.

 

Implications for Practice:

The superior predictive performance of Interferon-γ Release Assays (IGRAs) suggests they should be considered in clinical settings for high-risk populations, if available and feasible, to better identify individuals at increased risk of progressing to active tuberculosis (TB). This enhanced detection capability could guide more targeted preventive treatments, ultimately supporting global efforts toward TB elimination. Clinicians should assess the accessibility and cost-effectiveness of IGRAs to refine decision-making processes in TB prevention strategies, ensuring that the benefits of these advanced diagnostics are balanced against their costs.

 

Reference (free full-text):

Ayers, T. et al. (2024). Comparison of Tuberculin Skin Testing and Interferon-γ Release Assays in Predicting Tuberculosis Disease. JAMA Network Open, 7(4), e244769. DOI: https://doi.org/10.1001/jamanetworkopen.2024.4769.


Cohort Study: Metabolic biomarkers and long-term risk of psychiatric disorders in over 200,000 individuals

27 Apr, 2024 | 18:29h | UTC

Study Design and Population:

This population-based cohort study assessed 211,200 participants from the Apolipoprotein-Related Mortality Risk (AMORIS) cohort, who underwent occupational health screening primarily in the Stockholm region of Sweden from 1985 to 1996. Participants were followed longitudinally, with statistical analysis performed between 2022 and 2023. The study included extensive biomarker measurements such as glucose, triglycerides, and high-density lipoprotein.

 

Main Findings:

The study found significant associations between certain metabolic biomarkers and the risk of developing psychiatric disorders such as depression, anxiety, and stress-related disorders. Specifically, high levels of glucose (HR, 1.30) and triglycerides (HR, 1.15) were linked to an increased risk of these disorders, while high levels of high-density lipoprotein (HR, 0.88) were associated with a reduced risk. These findings held true across both genders and all disorders tested, with nested case-control analyses confirming these trends.

 

Implications for Practice:

The study suggests that metabolic dysregulation, as indicated by specific biomarkers, may either increase the risk or be a marker of increased risk for the development of common psychiatric disorders. These findings support the potential for closer monitoring and follow-up of individuals with abnormal metabolic profiles to aid in the prevention and early diagnosis of psychiatric conditions.

 

Reference (free full-text):

Chourpiliadis, C. et al. (2024). Metabolic Profile and Long-Term Risk of Depression, Anxiety, and Stress-Related Disorders. JAMA Network Open, 7(4), e244525. DOI: 10.1001/jamanetworkopen.2024.4525


Observational Study: Synergistic effects of early menopause and vascular risk on cognitive decline in postmenopausal women

27 Apr, 2024 | 18:20h | UTC

Study Design and Population:
This study analyzed data from 8,360 postmenopausal women and an equal number of age-matched male participants from the Canadian Longitudinal Study on Aging. Researchers assessed the independent and combined effects of age at menopause, vascular risk factors, and history of hormone therapy on cognitive outcomes. Participants’ cognitive function was measured using a global cognitive composite at baseline and again at a 3-year follow-up.

 

Main Findings:
The study found a synergistic interaction between early menopause (ages 35-48) and high vascular risk, significantly associated with lower cognitive scores at follow-up. Specifically, earlier menopause combined with higher vascular risk resulted in greater cognitive decline, compared to their individual effects. Notably, hormone therapy did not modify this association. This pattern was not observed in female participants with average or later menopause ages, nor in the age-matched male cohort.

 

Implications for Practice:
The findings underscore the importance of considering both endocrine and vascular health as predictive markers in dementia prevention strategies, particularly for women. These results suggest that women with early menopause and vascular risk factors should be closely monitored to mitigate their higher risk of cognitive impairment.

 

Reference (link to abstract – $ for full-text):

Alexander, M.W. et al. (2024). Associations Between Age at Menopause, Vascular Risk, and 3-Year Cognitive Change in the Canadian Longitudinal Study on Aging. Neurology, 102(9), 1-12. DOI: https://doi.org/10.1212/WNL.0000000000209298.


Retrospective Cohort Study: Delirium associated with increased risk of subsequent dementia and higher mortality in older adults

27 Apr, 2024 | 15:54h | UTC

Study Design and Population:

This retrospective cohort study utilized hospital administrative data from both public and private hospitals in New South Wales, Australia, spanning from July 2001 to March 2020. The study examined data from 650,590 patients aged 65 years or older, who did not have dementia at baseline. Diagnoses of dementia and delirium were identified using ICD-10 codes. The cohort was carefully matched into 55,211 pairs based on personal and clinical characteristics, focusing on those who developed delirium and their outcomes over a follow-up period exceeding five years.

 

Main Findings:

The analysis found that patients who experienced delirium had a 39% increased risk of mortality (hazard ratio: 1.39, 95% CI: 1.37-1.41) and a threefold increase in the risk of developing dementia (subdistribution hazard ratio: 3.00, 95% CI: 2.91-3.10) compared to those without delirium. The risk associated with dementia was notably stronger among men. Furthermore, each additional episode of delirium was linked to a 20% increased risk of subsequent dementia (subdistribution hazard ratio: 1.20, 95% CI: 1.18-1.23).

 

Implications for Practice:

The strong association between delirium and increased risks of death and incident dementia in older adults highlights the importance of delirium as a clinical marker that warrants significant attention. These findings suggest that enhanced monitoring and management of delirium in hospital settings could be crucial for identifying patients at higher risk of adverse outcomes, including dementia. Efforts to improve delirium management might not only address immediate clinical needs but also assist in stratifying risk and tailoring post-discharge care plans to better support the long-term health of these patients. Further research is needed to explore effective strategies for delirium intervention and to determine how these approaches can impact long-term cognitive outcomes and overall mortality.

 

Reference (free full-text):

Reference: Gordon, E. H., Ward, D. D., Xiong, H., Berkovsky, S., & Hubbard, R. E. (2024). Delirium Associated with Increased Risk of Death and Incident Dementia in Older Adults. BMJ, 384, e077634. DOI: https://doi.org/10.1136/bmj-2023-077634.


M-A Proportional increase in new-onset diabetes with different intensities of statin therapy

27 Apr, 2024 | 15:41h | UTC

Study Design and Population:

This research is a meta-analysis of individual participant data from large, long-term, randomized, double-blind controlled trials involving statins. The study encompasses 19 trials comparing statin use to placebo and four trials comparing varying intensities of statin therapy, involving a total of 154,664 participants over periods ranging from 4.3 to 4.9 years. Participants were adults enrolled in statin trials with a scheduled duration of at least two years and a participant count of at least 1000.

 

Main Findings:

The study revealed a dose-dependent increase in the incidence of new-onset diabetes when using statins. Participants receiving low to moderate-intensity statin therapy showed a 10% increase in new-onset diabetes annually compared to placebo, while those on high-intensity statin therapy exhibited a 36% increase. The absolute increases in new-onset diabetes were significantly influenced by the extent of HbA1c measurement. Notably, a large portion of new-onset diabetes cases occurred among participants with baseline glycaemic levels nearing the diabetes diagnostic threshold. Furthermore, the study found a moderate rise in mean glucose levels and HbA1c among those without baseline diabetes, and a significant worsening of glycemia among those with existing diabetes.

 

Implications for Practice:

The findings highlight a moderate, dose-dependent risk of new-onset diabetes associated with statin therapy, especially in individuals close to the diagnostic threshold for diabetes. These results should be considered in the clinical management of statin therapy, balancing the small increases in glycemia against the substantial benefits of statins in reducing cardiovascular risk. Healthcare providers should monitor glycaemic control in patients on statin therapy, particularly those prescribed high-intensity doses.

 

Reference (free full-text):

Cholesterol Treatment Trialists’ (CTT) Collaboration. (2024). Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: an individual participant data meta-analysis. Lancet Diabetes & Endocrinology, (Online First), 1-12. DOI: https://doi.org/10.1016/S2213-8587(24)00040-8


Cohort Study: Higher serious bleeding rates linked to diltiazem in elderly atrial fibrillation patients on anticoagulation

26 Apr, 2024 | 12:35h | UTC

Study Design and Population:
This retrospective cohort study analyzed data from 204,155 Medicare beneficiaries aged 65 years or older diagnosed with atrial fibrillation. The study focused on new users of the anticoagulants apixaban or rivaroxaban who commenced treatment with either diltiazem or metoprolol between January 2012 and November 2020, with follow-up extending up to 365 days.

 

Main Findings:
Patients treated with diltiazem exhibited a significantly increased risk of serious bleeding, including bleeding-related hospitalization and death, compared to those treated with metoprolol. The hazard ratio (HR) for serious bleeding events was 1.21, with a rate difference (RD) of 10.6 per 1000 person-years. Notably, the risk escalated with diltiazem doses exceeding 120 mg/day, indicating a dose-response relationship. Secondary outcomes, such as ischemic stroke or systemic embolism, did not show significant differences between the treatment groups.

 

Implications for Practice:
The findings suggest that in older adults with atrial fibrillation treated with apixaban or rivaroxaban, diltiazem increases the risk of serious bleeding, especially at higher doses. These results underscore the importance of cautious medication management and might influence clinical decisions regarding the choice of ventricular rate control in this population.

 

Reference (link to abstract – $ for full-text):

Ray, W. A., Chung, C. P., Stein, C. M., et al. (2024). Serious Bleeding in Patients With Atrial Fibrillation Using Diltiazem With Apixaban or Rivaroxaban. JAMA, Published online April 15, 2024. doi:10.1001/jama.2024.3867


Cohort Study: Increased fracture risk linked with initiation of antihypertensive medication in older veterans

26 Apr, 2024 | 12:29h | UTC

Study Design and Population:
This retrospective cohort study evaluated the association between antihypertensive medication initiation and fracture risk among older long-term care nursing home residents within the Veterans Health Administration. Conducted from 2006 to 2019 with data analysis spanning 2021 to 2023, the study utilized target trial emulation techniques and included 29,648 residents. A 1:4 propensity score-matched method was employed to compare medication initiators with non-initiators.

 

Main Findings:
Out of the matched cohort of 64,710 residents, those who initiated antihypertensive medication showed a higher incidence of fractures (5.4 per 100 person-years) compared to controls (2.2 per 100 person-years). The adjusted hazard ratio for fractures was 2.42. Notably, higher risks were observed in subgroups with dementia or elevated blood pressure thresholds (systolic ≥140 mm Hg or diastolic ≥80 mm Hg). Risks for severe falls and syncope were also elevated in the medication-initiating group.

 

Implications for Practice:
The study indicates a significant association between the initiation of antihypertensive medications and increased fracture risks among older, frail nursing home residents. Given these findings, clinicians should exercise caution and consider enhanced monitoring and preventive strategies when prescribing these medications to this vulnerable population.

 

Reference (link to abstract – $ for full-text):
Dave, C. V. et al. (2024). Antihypertensive Medication and Fracture Risk in Older Veterans Health Administration Nursing Home Residents. JAMA Intern Med, Published online April 22, 2024. DOI:10.1001/jamainternmed.2024.0507.


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