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Daily Archives: April 27, 2024

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.


The Lancet Commission: Global projections and recommendations for managing the increasing burden of prostate cancer

27 Apr, 2024 | 18:42h | UTC

The Lancet Commission’s report on prostate cancer highlights the expected doubling of annual cases from 1.4 million in 2020 to 2.9 million by 2040, driven by demographic changes and increased life expectancy. This comprehensive analysis divides the issue into epidemiology, diagnostics, management of localized and advanced disease, emphasizing disparities between high-income countries (HICs) and low- and middle-income countries (LMICs). Key findings indicate that late diagnoses are common, particularly in LMICs, leading to worse outcomes. The Commission advocates for significant changes in the diagnostic pathways and increased use of current technologies tailored to available resources to improve outcomes. Education and awareness programs are recommended to facilitate early detection and shift the treatment paradigm from palliative to curative, focusing on surgery and radiotherapy. Without decisive action, the global mortality from prostate cancer is set to rise, highlighting the need for urgent interventions across all countries, with a special focus on underserved populations.

 

Reference:

James, N.D., Tannock, I., N’Dow, J., Feng, F., Gillessen, S., Ali, S.A., et al. (2024). The Lancet Commission on prostate cancer: planning for the surge in cases. The Lancet, 404(10052), 1-29. DOI: https://doi.org/10.1016/S0140-6736(24)00651-2.


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.


Cohort Study: Validation of a risk score for severe acute kidney injury in cisplatin treatment

27 Apr, 2024 | 16:24h | UTC

Study Design and Population:
This multicenter cohort study aimed to develop and validate a risk prediction model for severe cisplatin-associated acute kidney injury (CP-AKI). Conducted across six major academic cancer centers in the U.S., it included 24,717 adult participants (≥18 years) who received their first dose of intravenous cisplatin from 2006 to 2022. The study population was split into a derivation cohort of 11,766 and a validation cohort of 12,951.

 

Main Findings:
The study reported an incidence of CP-AKI of 5.2% in the derivation cohort and 3.3% in the validation cohort. Factors independently associated with CP-AKI included age, hypertension, diabetes, and baseline serum levels of creatinine, magnesium, and other relevant biomarkers. A novel, simple risk score was developed using nine covariates, demonstrating significant predictive capability for CP-AKI. The highest risk category had up to 24.00-fold increased odds of CP-AKI compared to the lowest risk category, with the primary model showing superior discrimination (C statistic 0.75) over previous models.

 

Implications for Practice:
The validated risk score offers a practical tool for clinicians to estimate the risk of severe CP-AKI in patients undergoing cisplatin chemotherapy. Its use could enhance monitoring strategies and potentially guide therapeutic decision-making to mitigate the risk of kidney injury and associated mortality.

 

Reference (free full-text):
Gupta et al. (2024). Derivation and external validation of a simple risk score for predicting severe acute kidney injury after intravenous cisplatin: cohort study. BMJ, 384, e077169. DOI: https://doi.org/10.1136/bmj-2023-077169


WHO report on HIV drug resistance – Rising dolutegravir resistance and implications for global care standards

27 Apr, 2024 | 16:08h | UTC

The World Health Organization’s latest HIV Drug Resistance Report highlights both the effectiveness and emerging challenges with dolutegravir (DTG)-based therapies. While there is significant suppression of HIV viral loads in populations treated with DTG, data reveals increasing resistance levels, particularly among those with high viral loads and prior treatment experiences. The report calls for enhanced surveillance and management strategies to address these resistance patterns and maintain treatment efficacy. It also underscores the necessity of robust data systems and proactive healthcare policies to improve the overall quality of HIV treatment and prevent the transmission of resistant HIV strains, aligning with global efforts to combat antimicrobial resistance.

 

Source:

New report documents increase in HIV drug resistance to dolutegravir – World Health Organization


Pooled Analysis: Changes in prevalence of underweight and obesity from 1990 to 2022 in 200 countries

27 Apr, 2024 | 16:02h | UTC

Study Design and Population:
This pooled analysis utilized data from 3,663 population-representative studies involving 222 million participants to assess trends in underweight, thinness, and obesity. The study separated its analysis between adults (aged ≥20 years) and school-aged children and adolescents (aged 5–19 years) across 200 countries from 1990 to 2022. Bayesian hierarchical models were employed to estimate trends in different BMI categories.

 

Main Findings:
The findings indicate significant geographical and demographic variations in the prevalence of underweight and obesity. While the combined prevalence of underweight and obesity decreased in a minority of countries, it increased significantly in the majority, particularly in island nations, the Middle East, and North Africa. The study also found that obesity rates have surpassed underweight rates in the vast majority of countries by 2022.

 

Implications for Practice:
The increasing prevalence of obesity alongside persistent underweight and thinness issues underscores the need for a dual-focused public health approach. Strategies should prioritize not only the reduction of obesity through healthy eating and physical activity but also address undernutrition by improving access to nutritious foods, especially in regions like south Asia and parts of Africa where underweight remains prevalent.

 

Reference (free full-text):
NCD Risk Factor Collaboration (NCD-RisC) (2024). Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults. The Lancet, 403(10387), e14-e26. DOI: https://doi.org/10.1016/S0140-6736(23)02750-2


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


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