Family Medicine
USPSTF Guideline: Biennial screening mammography recommended for women aged 40-74 to reduce breast cancer morbidity and mortality
1 May, 2024 | 21:45h | UTCStudy 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)
🧵 Just published: USPSTF recommends all women undergo routine #breastcancer screening every other year beginning at age 40, an update from the 2016 recommendation to start at age 50.
https://t.co/xDPK4qu7JH pic.twitter.com/3zVBMWeuKb— JAMA (@JAMA_current) April 30, 2024
Reference (link to free full-text):
RCT: Beta-blockers post myocardial infarction showed no benefit in patients with preserved ejection fraction
30 Apr, 2024 | 13:40h | UTCThis 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:
Original Article: Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction (REDUCE-AMI trial) https://t.co/z1NNeAK9Mm
Editorial: Routine Beta-Blockers in Secondary Prevention — On Injured Reserve https://t.co/NzlExH0LZm #ACC24 pic.twitter.com/8Jqpj2dM6E
— NEJM (@NEJM) April 17, 2024
Reference (link to abstract – $ for full-text):
RCT: Semaglutide significantly improves symptoms and weight loss in HFpEF and type 2 diabetes patients
29 Apr, 2024 | 12:36h | UTCThis 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):
Cohort Study: No increased risk of autism, ADHD, or intellectual disability from acetaminophen use in pregnancy
29 Apr, 2024 | 12:34h | UTCThis 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):
Meta-Analysis: Efficacy of MRI in prostate cancer screening for reducing unnecessary biopsies
28 Apr, 2024 | 20:13h | UTCThis 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):
Systematic Review: Diagnostic accuracy of clinical examination for dislocated hips in infants
28 Apr, 2024 | 16:52h | UTCThis systematic review assesses the diagnostic accuracy of clinical examinations in identifying dislocated hips in infants, using data from nine studies that compared clinical examinations to diagnostic ultrasound as the reference. The study involved 37,859 hips with a dislocation prevalence of 0.94%. The Barlow and Ortolani maneuvers showed a sensitivity of 46% and a specificity of 99.1%, with a positive likelihood ratio of 52, highlighting their effectiveness in predicting hip dislocation. Other methods such as limited hip abduction and a clicking sound were found to have minimal diagnostic utility. This evidence supports the clinical utility of specific maneuvers in early detection to prevent long-term complications.
Reference (link to abstract – $ for full-text):
Pooled Analysis: Semaglutide improves symptoms and reduces weight in obesity-related heart failure with preserved ejection fraction
28 Apr, 2024 | 16:33h | UTCThis 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):
Diagnostic Study: Enhanced prediction of TB progression with IGRAs compared to tuberculin skin test
27 Apr, 2024 | 18:53h | UTCStudy 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):
Cohort Study: Metabolic biomarkers and long-term risk of psychiatric disorders in over 200,000 individuals
27 Apr, 2024 | 18:29h | UTCStudy 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):
Observational Study: Synergistic effects of early menopause and vascular risk on cognitive decline in postmenopausal women
27 Apr, 2024 | 18:20h | UTCStudy 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):
Retrospective Cohort Study: Delirium associated with increased risk of subsequent dementia and higher mortality in older adults
27 Apr, 2024 | 15:54h | UTCStudy 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):
M-A Proportional increase in new-onset diabetes with different intensities of statin therapy
27 Apr, 2024 | 15:41h | UTCStudy 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):
Cohort Study: Higher serious bleeding rates linked to diltiazem in elderly atrial fibrillation patients on anticoagulation
26 Apr, 2024 | 12:35h | UTCStudy 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):
Cohort Study: Increased fracture risk linked with initiation of antihypertensive medication in older veterans
26 Apr, 2024 | 12:29h | UTCStudy 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.
M-A: Reduced risk of infective endocarditis following dental procedures with antibiotic prophylaxis in high-risk individuals
26 Apr, 2024 | 12:07h | UTCStudy Design and Population:
This systematic review and meta-analysis evaluated the impact of antibiotic prophylaxis on the incidence of infective endocarditis following invasive dental procedures. Researchers analyzed data from 1,152,345 cases sourced from PubMed, Cochrane-CENTRAL, Scopus, and other databases up to May 2023. The study included various research designs, such as case-control, cohort, and time-trend studies, assessing the effectiveness of antibiotic prophylaxis across different risk groups.
Main Findings:
The meta-analysis revealed that antibiotic prophylaxis significantly lowers the risk of infective endocarditis among individuals at high risk (pooled relative risk, 0.41; 95% CI, 0.29-0.57), with consistent findings across studies of good quality. However, the effectiveness of prophylaxis in individuals at moderate or low/unknown risk remains unsupported by sufficient evidence. Time-trend studies provided mixed results, with some indicating no change or an increase in infective endocarditis incidence post-guideline changes in 2007.
Implications for Practice:
The findings support the continued use of antibiotic prophylaxis for high-risk individuals undergoing invasive dental procedures, aligning with current guidelines from the American Heart Association and European Society of Cardiology. The lack of clear benefits in moderate and low-risk groups suggests a need for further research to optimize prophylaxis guidelines and ensure effective risk stratification in clinical practice.
Reference (link to abstract – $ for full-text):
RCT: Lack of significant effect of Paxlovid (nirmatrelvir–ritonavir) on symptom alleviation in Covid-19
26 Apr, 2024 | 11:49h | UTCStudy Design and Population:
This phase 2–3 randomized clinical trial investigated the efficacy of nirmatrelvir in combination with ritonavir for treating mild-to-moderate Covid-19 in adults. Participants, both vaccinated and unvaccinated, were enrolled based on their risk factors for severe Covid-19. The study included 1296 adults who had confirmed Covid-19 with symptom onset within the past 5 days. They were randomly assigned to receive either nirmatrelvir–ritonavir or placebo every 12 hours for 5 days.
Main Findings:
The primary endpoint was the time to sustained alleviation of all targeted Covid-19 signs and symptoms. Results showed that the median time to alleviation was 12 days for the treatment group and 13 days for the placebo group, a difference that was not statistically significant (P=0.60). Hospitalizations and deaths were slightly lower in the treatment group (0.8%) compared to the placebo group (1.6%), but this difference was also not statistically significant. Adverse events were similar across both groups, with dysgeusia and diarrhea being the most common in the treatment group.
Implications for Practice:
The findings indicate that nirmatrelvir–ritonavir treatment does not significantly reduce the time to symptom alleviation for Covid-19 compared to placebo among vaccinated or unvaccinated adults. These results suggest that further research is needed to explore the potential benefits of this treatment in specific subpopulations or in combination with other interventions.
Reference (free full-text):
Pragmatic Cluster-Randomised Trial: Efficacy of a Fixed-Dose Polypill in Reducing Cardiovascular Disease Risk in Rural Iran
21 Apr, 2024 | 21:05h | UTCStudy Design and Population: The PolyPars Study was structured as a two-arm pragmatic cluster-randomised trial within the larger PARS cohort study. It targeted residents aged over 50 in a district in southern Iran, dividing 91 villages into two groups: one receiving a once-daily polypill (containing two antihypertensives, a statin, and aspirin) alongside non-pharmacological interventions, and the other receiving only the non-pharmacological interventions. The trial included 4,415 participants aged 50-75 years, with the primary endpoint being the first occurrence of major cardiovascular events.
Main Findings: Over a median follow-up of 4.6 years, adherence to the polypill was high at 86%. The intervention arm showed a significant reduction in the incidence of the primary outcome, with only 4.0% (88 participants) experiencing major cardiovascular events compared to 8.0% (176 participants) in the control arm. This translates to a hazard ratio of 0.50, indicating a 50% reduction in risk, and an absolute risk reduction of 4.0%.
Implications for Practice: The study demonstrates the significant potential of fixed-dose combination therapy with the polypill to halve the risk of major cardiovascular diseases in a population-level intervention. This finding supports the polypill as a safe and effective strategy for both primary and secondary prevention of cardiovascular diseases, particularly in settings where access to individual medications and consistent medical supervision might be limited.
Nested Case-Control Study: Increased risk of major bleeding in atrial fibrillation patients with concomitant SSRI and oral anticoagulant use
23 Mar, 2024 | 20:48h | UTCStudy Design and Population
This nested case-control study investigated the association between the concomitant use of selective serotonin reuptake inhibitors (SSRIs) and oral anticoagulants (OACs) on the risk of major bleeding among patients with atrial fibrillation. Conducted within the UK’s Clinical Practice Research Datalink, the study included 42,190 cases of major bleeding matched to 1,156,641 controls based on age, sex, cohort entry date, and follow-up duration. Patients initiating OACs between January 2, 1998, and March 29, 2021, were included, with risk-set sampling utilized for control selection.
Main Findings
The study found that concomitant use of SSRIs and OACs was associated with a 33% increased risk of major bleeding compared to OAC use alone, with the highest risk observed within the first 30 days of concurrent use. The increased risk was consistent across different ages, sexes, and patient histories, including those with chronic kidney disease or previous bleeding events. Notably, the elevated risk of bleeding extended up to 6 months of concomitant use but did not vary significantly with the potency of SSRIs or the type of OAC used (direct OACs or vitamin K antagonists).
Implications for Practice
These findings underscore the need for healthcare professionals to closely monitor patients with atrial fibrillation who are prescribed SSRIs in addition to OACs, particularly during the initial months of treatment. This study highlights the importance of managing bleeding risk factors and suggests reconsidering the necessity and duration of concomitant SSRI and OAC use. Future research should focus on strategies to mitigate this bleeding risk and explore alternative treatments for managing depression in patients requiring anticoagulation.
Reference
RCT: Clarithromycin improves early clinical and inflammatory responses in hospitalized community-acquired pneumonia patients
23 Mar, 2024 | 20:25h | UTCStudy Design and Population: The ACCESS trial was a phase 3, prospective, double-blind, randomized controlled trial conducted in 18 Greek hospitals, involving adults hospitalized with community-acquired pneumonia who displayed systemic inflammatory response syndrome, had a Sequential Organ Failure Assessment (SOFA) score of 2 or more, and procalcitonin levels of 0.25 ng/mL or more. Participants were randomly assigned to receive either standard of care with intravenous cephalosporins or β-lactam/β-lactamase inhibitor combinations plus oral clarithromycin (500 mg twice daily for 7 days) or placebo. The trial aimed to evaluate the impact of clarithromycin on early clinical and inflammatory responses.
Main Findings: Among 278 participants allocated to clarithromycin (n=139) or placebo (n=139), the primary composite endpoint—indicating early clinical response and inflammatory burden reduction within 72 hours—was met by 68% of patients in the clarithromycin group compared to 38% in the placebo group, showcasing a significant difference (29.6%, odds ratio 3.40, p<0.0001). Serious treatment-emergent adverse events were slightly lower in the clarithromycin group than in the placebo group, although not statistically significant.
Implications for Practice: The addition of clarithromycin to the standard of care for hospitalized patients with community-acquired pneumonia significantly improves early clinical response and reduces inflammatory burden, potentially through modulation of the immune response. These results support the use of clarithromycin alongside β-lactam antibiotics in the treatment of community-acquired pneumonia, highlighting its role in enhancing patient outcomes by targeting early clinical and inflammatory indicators.
Reference
Prof Evangelos J Giamarellos-Bourboulis, MD et al. (2024). Clarithromycin for early anti-inflammatory responses in community-acquired pneumonia in Greece (ACCESS): a randomised, double-blind, placebo-controlled trial. The Lancet Respiratory Medicine, Volume(Issue), Pages. DOI: https://doi.org/10.1016/S2213-2600(23)00412-5. Access the study here: Link
Observational Study: Association of antiarrhythmic drug use with increased risk of pacemaker implantation and syncope in new-onset atrial fibrillation patients
23 Mar, 2024 | 20:08h | UTCStudy Design and Population
This observational study utilized data from the Korean National Health Insurance Service to evaluate the impact of antiarrhythmic drugs (AADs) on the risk of pacemaker implantation or syncope in patients diagnosed with new-onset atrial fibrillation (AF) between 2013 and 2019. A total of 770,977 new-onset AF cases were identified, with 142,141 patients prescribed AADs within one year of diagnosis. The study compared the risk of these outcomes between AAD users and nonusers.
Main Findings
The study found that the use of AADs was associated with a significantly increased risk of pacemaker implantation or syncope, with adjusted risks being 3.5 times higher for either outcome, 2.0 times higher for syncope alone, and 5.0 times higher for pacemaker implantation. These associations were consistent across various patient subgroups, and propensity score-matched analysis supported these findings. Notably, women were found to be more susceptible to the adverse effects of AADs than men.
Implications for Practice
The findings suggest a need for careful evaluation of the risks associated with AAD use in patients with new-onset AF, particularly regarding the potential for pacemaker implantation or syncope. These results highlight the importance of individualized patient assessment before prescribing AADs to mitigate these risks effectively. Further research is needed to explore the mechanisms behind these associations and to develop strategies to minimize adverse outcomes in this patient population.
Reference
Cohort Study: The impact of rare kidney diseases on kidney failure and survival rates in the UK’s RaDaR cohort
22 Mar, 2024 | 11:29h | UTCStudy Design and Population: This cohort study utilized data from the UK National Registry of Rare Kidney Diseases (RaDaR), encompassing 27,285 participants aged 0-96 years with 28 types of rare kidney diseases, recruited from 108 renal care facilities across the UK. The primary outcomes assessed were the cumulative incidence of mortality and kidney failure, compared with those of a general population with chronic kidney disease (CKD).
Main Findings: Over a median follow-up of 9.6 years, participants with rare kidney diseases exhibited a significantly higher 5-year cumulative incidence of kidney failure (28%) compared to the broader UK CKD population (1%, p<0.0001). However, they also showed better survival rates, with a standardized mortality ratio of 0.42. There was considerable variability in median ages at kidney failure and death, time from dialysis start to death, and time from diagnosis to reaching specific eGFR thresholds among different rare diseases.
Implications for Practice: This study highlights the distinct trajectory of rare kidney diseases compared to more common forms of CKD, with higher rates of kidney failure but improved survival outcomes. These findings emphasize the over-representation of patients with rare kidney diseases in kidney replacement therapy cohorts and underscore the urgent need for targeted therapeutic interventions. Addressing this unmet need could significantly reduce the demand for long-term kidney replacement therapy, benefiting patients and easing healthcare system burdens.
Reference
Wong K, Pitcher D, Braddon F, Downward L, Steenkamp R, Annear N, et al. (2024). Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort. The Lancet, 395(10223), P1234-P1245. DOI: https://doi.org/10.1016/S0140-6736(23)02843-X. Access the study here: Link
M-A: Cardiovascular benefits of SGLT2 inhibitors in patients without diabetes
22 Mar, 2024 | 11:07h | UTCStudy Design and Population: This meta-analysis investigated the cardiovascular (CV) outcomes associated with sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients without diabetes mellitus (DM). By systematically reviewing online databases, the authors identified and included six randomized controlled trials (RCTs) in their analysis. These trials compared SGLT2i with placebo/control in a total of 12,984 participants, who were followed for an average duration of 17.7 months. The study population comprised mainly patients with heart failure (HF), chronic kidney disease, or myocardial infarction, with a mean age of 64 years, where 72% were men and the mean hemoglobin A1C level was 5.7%.
Main Findings: The use of SGLT2i was associated with a significant reduction in composite CV death or hospitalization for HF, with an odds ratio (OR) of 0.77 (95% confidence interval [CI], 0.68 to 0.87, p < 0.0001), primarily due to a decrease in hospitalization for HF (OR 0.70, 95% CI 0.60 to 0.81, p < 0.00001). No significant differences were observed in CV death, all-cause death, or major adverse CV events when comparing SGLT2i to placebo. Notably, serious adverse events were lower with the use of empagliflozin compared to placebo.
Implications for Practice: This meta-analysis highlights the significant CV benefits of SGLT2i treatment in reducing CV death or hospitalization for HF in patients without DM, compared with placebo. These findings suggest the potential for broader use of SGLT2i in populations without diabetes to improve cardiovascular outcomes.
Reference: Sahib Singh et al. (2024). Cardiovascular Outcomes With Empagliflozin and Dapagliflozin in Patients Without Diabetes. The American Journal of Cardiology, Published: February 29, 2024. DOI: https://doi.org/10.1016/j.amjcard.2024.02.039. Access the study here: [Link]
Cohort Study: Elevated autism spectrum disorder risk in children exposed to valproate during pregnancy
21 Mar, 2024 | 13:16h | UTCStudy Design and Population: This cohort study utilized two health care utilization databases in the United States, covering the period from 2000 to 2020, to investigate the association between prenatal exposure to antiseizure medications and the risk of autism spectrum disorder (ASD) in children. The study compared children exposed to topiramate, valproate, or lamotrigine during the second half of pregnancy to those unexposed to any antiseizure medication, specifically focusing on a population-based cohort of pregnant women and their offspring.
Main Findings: The cumulative incidence of ASD at 8 years of age was found to be higher in children exposed to these medications compared to the general population. Notably, the incidence was 6.2% for children exposed to topiramate, 10.5% for valproate, and 4.1% for lamotrigine among children born to mothers with epilepsy. However, after adjusting for potential confounders, the increased risk of ASD remained significant only for valproate exposure, with a hazard ratio of 2.67, indicating a substantial risk compared to unexposed children. Topiramate and lamotrigine showed no significant increase in risk after adjustment.
Implications for Practice: The findings underscore the importance of carefully considering the risks and benefits of using antiseizure medications during pregnancy. Specifically, valproate should be used with caution, if at all, given its significant association with an increased risk of ASD in offspring. This study supports the need for targeted counseling and monitoring of pregnant women with epilepsy and highlights the necessity for further research to fully understand the neurodevelopmental impact of prenatal exposure to antiseizure medications.
Reference: Sonia Hernández-Díaz et al. (2024). Cohort Study: Assessing Autism Spectrum Disorder Risk in Children Exposed to Antiseizure Medications During Pregnancy. N Engl J Med, 390(13), 1069-1079. DOI: 10.1056/NEJMoa2309359. Access the study here: [Link]
Systematic Analysis: Global Burden and Trends of Nervous System Disorders, 1990–2021
21 Mar, 2024 | 11:10h | UTCStudy Design and Population
This study, a systematic analysis conducted by the Global Burden of Disease Study 2021, aimed to estimate the global, regional, and national health loss attributable to 37 unique nervous system conditions from 1990 to 2021. The researchers estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life years (DALYs) across 204 countries. The analysis included morbidity and deaths directly resulting from damage to the central or peripheral nervous system, as well as neurological health loss from conditions where nervous system morbidity is a secondary outcome.
Main Findings
The collective global burden of these nervous system conditions emerged as the leading cause of DALYs in 2021, affecting approximately 3.40 billion individuals (43.1% of the global population) and resulting in 443 million DALYs. Although global DALY counts for these conditions increased by 18.2% from 1990 to 2021, there was a notable decrease in the age-standardised rates of deaths and DALYs by 33.6% and 27.0%, respectively. The conditions contributing most significantly to the age-standardised DALYs were stroke, neonatal encephalopathy, migraine, and Alzheimer’s disease among others.
Implications for Practice
This analysis underscores the critical need for effective prevention, treatment, and rehabilitation strategies for nervous system disorders, which now lead the global disease burden. Highlighting an 18.2% increase in DALY counts over the study period, it calls for heightened public health attention and resource allocation towards these conditions. The findings support the prioritization of nervous system health on the global health agenda and stress the importance of further research into modifiable risk factors and equitable access to care.
Reference
GBD 2021 Nervous System Disorders Collaborators (2024). Systematic Analysis: Global Burden and Trends of Nervous System Disorders, 1990–2021. The Lancet Neurology, Volume(issue), Pages. DOI: https://doi.org/10.1016/S1474-4422(24)00038-3. Access the study here: Link
Meta-Analysis: Effectiveness of therapist-guided remote vs. in-person cognitive behavioral therapy
20 Mar, 2024 | 19:32h | UTCStudy Design and Population: This systematic review and meta-analysis investigated the efficacy of therapist-guided remote cognitive behavioral therapy (CBT) compared to traditional in-person CBT. The authors conducted a comprehensive search across several databases, including MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials, up to July 4, 2023. A total of 54 randomized controlled trials (RCTs) were included, encompassing 5463 adult patients presenting with various clinical conditions. The study meticulously assessed the risk of bias and extracted data using a standardized approach, and outcomes were analyzed using a random-effects model.
Main Findings: The primary analysis focused on patient-important outcomes, comparing the effectiveness of remote and in-person CBT across diverse conditions such as anxiety and related disorders, depressive symptoms, insomnia, chronic pain or fatigue syndromes, body image or eating disorders, tinnitus, alcohol use disorder, and mood and anxiety disorders. The meta-analysis, based on moderate-certainty evidence, found little to no difference in effectiveness between remote and in-person CBT (standardized mean difference [SMD] −0.02, 95% confidence interval −0.12 to 0.07), suggesting that both delivery methods are comparably effective across a range of disorders.
Implications for Practice: The findings indicate that therapist-guided remote CBT is nearly as effective as in-person CBT for treating a variety of mental health and somatic disorders. This supports the potential for remote CBT to significantly increase access to evidence-based care, especially in settings where in-person therapy is not feasible or is limited by geographic, economic, or social barriers. Future research should explore optimizing remote CBT delivery methods to further enhance accessibility and efficacy.
Reference: Zandieh, S. et al (2024). Therapist-guided remote versus in-person cognitive behavioural therapy: a systematic review and meta-analysis of randomized controlled trials. CMAJ, 196(10), E327-E340. [Link]