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Long-term outcomes following alternative second-line oral glucose-lowering treatments: Results from the real-world progression in type 2 diabetes mellitus United Kingdom (RAPIDS-UK) model.
Get PDFAIMS: To compare long-term complications for people with type 2 diabetes mellitus (T2DM) following second-line treatment in routine practice with sulphonylureas (SU), dipeptidyl peptidase-4 inhibitors (DPP4i), or sodium-glucose co-transporter-2 inhibitors (SGLT2i) added to metformin. MATERIALS AND METHODS: We used the RAPIDS microsimulation model to predict diabetes complications over 5 years after second-line treatment initiation. We combined information on 'real-world' treatment duration in England from the Clinical Practice Research Datalink with evidence on treatment effectiveness from Randomised Controlled Trials (RCTs). We estimated between-treatment differences in the probabilities of end-stage kidney disease (ESKD), heart failure hospitalisation (HF), diabetic eye disease, myocardial infarction (MI), and lower-extremity amputation (LEA). RESULTS: The predicted probabilities of complications within 5 years were lower following second-line treatment with SGLT2i compared to SU and DPP4i. The mean (95% CI) difference (reduction) in the predicted probability of ESKD following SGLT2i versus SU was -0.81% (-0.89, -0.73), and for SGLT2i versus DPP4i the corresponding difference was -0.87% (-0.95, -0.79). The reduction in the probability of HF following SGLT2i versus SU was -0.90% (-1.01, -0.80), and for SGLT2i versus DPP4i it was -0.95% (-1.06, -0.84). The corresponding differences in the probabilities of diabetic eye disease following SGLT2i versus SU were -1.41% (-1.57, -1.26), and for SGLT2i versus DPP4i was -0.44% (-0.59, -0.29). The predicted probabilities of LEA were similar across treatments. Pre-existing CVD did not modify the predicted probabilities of complications. CONCLUSIONS: For a general T2DM population, second-line treatment with SGLT2i rather than SU or DPP4i can reduce the probability of complications within 5 years
Physical Activity and Cancer Incidence and Mortality: Current Evidence and Biological Mechanisms.
Get PDFObjectives: There is strong evidence that not enough physical activity is among the most critical risk factors for cancer disease and premature mortality. The literature on the benefits of regular physical activity regarding cancer disease has grown in the last decades. This review aimed to present the current findings on the effect of prediagnosis physical activity on cancer incidence and mortality published between January 2019 and October 2024; this study summarizes the previous evidence, as well as the literature underlying biological mechanisms operating in the exercise-cancer relationship. The review also highlights gaps in the existing research and identifies future research directions. Methods: Medline/PubMed, ScienceDirect, and Google Scholar were searched with the search terms "physical activity" and "physical exercise" in conjunction with the MeSH terms for "cancer" and "carcinoma". Primary, review, and meta-analysis studies published in English were included if they reported a measure of the effect size of prediagnosis physical activity on cancer incidence and/or cancer mortality. Results: Evidence from 37 observational studies and 10 reviews were included in this systematic review; 22 studies reported the effect of physical activity on cancer incidence, and 15 studies on cancer mortality. Of the 37 included observational studies, 19 confirmed the previous evidence that physical activity significantly decreased all-cancer-combined and cancer-specific site incidences, and 10 studies focused on cancer mortality. However, the molecular mechanisms involved in this process require future studies. The most convincing evidence maintains the effects of physical activity on body weight and fat, insulin resistance, sex hormones, regulation of redox homeostasis, enhancing the antioxidant defense system, and reducing oxidative stress. Conclusions: These data demonstrate substantial prevention against several cancer incidences and mortality among patients who performed regular physical activity, of which dose meets at least the WHO's guidelines. Further prospective cohort studies and long-term RCT studies are warranted to address a safe and personalized activity dose for cancer-site prevention, identify more precisely the biological mechanisms operating in the physical activity-cancer relationship, and promote the benefits of being physically active
The Association Between Cultural Tightness and COVID-19 Vaccine Confidence From 28 Countries: Cross-Sectional Study.
Get PDFBACKGROUND: Social norms provided a framework for understanding a variety of behaviors. Cultural tightness was introduced to measure the level of adherence to social norms and tolerance of deviant behavior. OBJECTIVE: We aimed to explore the association between cultural tightness and COVID-19 vaccine hesitancy. METHODS: A total of 44,339 participants aged 18 years and older were enrolled from 28 different countries between 2020 and 2022. We used the Vaccine Confidence Index (3 items related to evaluation of importance, effectiveness, and safety) with a 5-point Likert scale to collect COVID-19 vaccine confidence. Demographic information at the individual-level was obtained through the survey, while national-level data were sourced from the World Bank and Hofstede insights. Multilevel linear regressions with random effects for country were used to examine the association between cultural tightness and COVID-19 vaccine confidence. RESULTS: Of the participants, 21,968 (50.2%) were male and 18,957 (43.3%) had an education level of university or above. Vietnam exhibited the highest level of confidence (mean 13.31, SD 1.71) on COVID-19 vaccine and Slovakia had the lowest level (mean 9.52, SD 0.14). The higher levels of cultural tightness were positively linked to greater vaccine confidence (β=1.94, 95% CI 1.72-2.15; P<.001) after controlling individual- and national- level variables. Individuals who were younger in age, female, had lower levels of educational level, or belonged to minority religious groups demonstrated a positive association with lower vaccine confidence. Hofstede's 5 cultural dimensions were not significantly associated with vaccine confidence. The level of vaccine confidence in 2021 (β=-0.54, 95% CI -0.67 to -0.37; P<.001) and 2022 (β=-0.23, 95% CI -0.34 to -0.10; P<.001) was lower than that observed in 2020. CONCLUSIONS: Lower level of cultural tightness might be positively associated with low vaccine confidence. Our findings offered the insight for designing tailor interventions to vaccine hesitancy in different cultural tightness context
Drug use and acute kidney injury: a Drug-Wide Association Study (DWAS) in Denmark and Sweden.
Get PDFBACKGROUND: Knowledge of which medications may lead to acute kidney injury (AKI) is limited, relying mostly on spontaneous reporting in pharmacovigilance systems. We here conducted an exploratory drug-wide association study (DWAS) to screen for associations between dispensed drugs and AKI risk. METHODS: Using two large Danish and Swedish data linkages, we identified AKI hospitalizations occurring between April 1997 and December 2021 in Denmark and between March 2007 and December 2021 in Sweden. We used a case-time control design comparing drug dispensing in the 3 months prior to the AKI with earlier periods for the same patient. Odds ratios (ORs) for the association between each drug and AKI were estimated using conditional logistic regression and adjusting for the presence of comorbidities. We sought replication of signals in both health systems and explored the plausibility of findings through pharmacovigilance system analysis in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, appearance in the RESCUE list of medications that report AKI as a side effect, PubMed evidence review and causality assessment through direct acyclic graphs. RESULTS: We included 20 622 adults in Denmark and 13 852 in Sweden hospitalized for AKI. In total, 16 unique medications were identified in both cohorts as associated to increased AKI occurrence. Of these, 10 medications had higher reporting ORs in the FAERS database, 9 were listed by RESCUE, and 7 appearing in PubMed. This analysis identified some medications with known AKI risks (i.e. likely true positives such as furosemide, penicillin, spironolactone and omeprazole), medications that may have initiated in response to conditions that lead to AKI (i.e. false positives like metoclopramide provided to treat nausea/vomiting) and other candidates (e.g. opioids) that warrant further evaluation in subsequent studies. CONCLUSIONS: This hypothesis-generating study identifies medications with potential involvement in AKI that require confirmation and validation
Insulin resistance and beta-cell dysfunction in adults with different patterns of diet: a cross-sectional study in north-western Tanzania.
Get PDFBACKGROUND: The diabetes burden in sub-Saharan Africa is rising, but there is little African data on associations between diet, insulin resistance, and beta-cell dysfunction. OBJECTIVE: We investigated the association between dietary patterns and insulin resistance and beta-cell dysfunction among adults in Mwanza, Tanzania. METHODS: In a cross-sectional study involving adults with or without HIV, insulin resistance and beta-cell dysfunction were calculated from plasma insulin and glucose measures during an oral glucose tolerance test. Diet data were collected using a validated food frequency questionnaire and dietary patterns were derived by principal component analysis and reduced rank regression. Logistic regression analysis was used to assess the association between exposure variables (dietary patterns terciles) with outcome variables (insulin resistance and beta-cell dysfunction), adjusting for HIV status, age, sex, body mass index, alcohol consumption, and smoking. RESULTS: Of 462 participants, the mean age was 42 (±12) years, 58% were females, and 60% were HIV-infected. Carbohydrate-dense patterns were associated with more insulin resistance by HOMA-IR (aOR 2.7, 95% CI 1.5; 4.8) and Matsuda index (aOR 3.7, 95% CI 2.0; 6.7), but not with either HOMA-β, insulinogenic index or oral disposition index. The level of adherence to either the vegetable-rich or vegetable-poor pattern was not associated with any of the markers of insulin resistance or beta-cell dysfunction. HIV infection did not affect the association between patterns of diet and glucose metabolism outcomes. CONCLUSION: The lack of association between either vegetable-rich or vegetable-poor patterns with insulin resistance or beta cell dysfunction requires further research
Development and Validation of a Brief Measure of Sexual Wellbeing for Population Surveys: The Natsal Sexual Wellbeing Measure (Natsal-SW).
Get PDFSexual wellbeing is an important aspect of population health. Addressing and monitoring it as a distinct issue requires valid measures. Our previous conceptual work identified seven domains of sexual wellbeing: security; respect; self-esteem; resilience; forgiveness; self-determination; and comfort. Here, we describe the development and validation of a measure of sexual wellbeing reflecting these domains. Based on the analysis of 40 semi-structured interviews, we operationalized domains into items, and refined them via cognitive interviews, workshops, and expert review. We tested the items via two web-based surveys (n = 590; n = 814). Using data from the first survey, we carried out exploratory factor analysis to assess and eliminate poor performing items. Using data from the second survey, we carried out confirmatory factor analysis to examine model fit and associations between the item reduced measure and external variables hypothesized to correlate with sexual wellbeing (external validity). A sub-sample (n = 113) repeated the second survey after 2 weeks to evaluate test-retest reliability. Confirmatory factor analysis indicated that a "general specific model" had best fit (RMSEA: 0.064; CFI: 0.975, TLI: 0.962), and functioned equivalently across age group, gender, sexual orientation, and relationship status. The final Natsal-SW measure comprised 13 items (from an initial set of 25). It was associated with external variables in the directions hypothesized (all p < .001), including mental wellbeing (0.454), self-esteem (0.564), body image (0.232), depression (-0.384), anxiety (-0.340), sexual satisfaction (0.680) and sexual distress (-0.615), and demonstrated good test-retest reliability (ICC = 0.78). The measure enables sexual wellbeing to be quantified and understood within and across populations
Estimated timing of the first menstrual period and dietary and nutritional correlates of menarche among urban school-going adolescents in four sub-Saharan African sites.
Get PDFCharacterizing the timing of menarche and the factors that are associated with it is important for understanding a population's reproductive health needs and long-term health trajectories. We estimated the age at the menstrual onset among adolescent girls and the association between dietary and nutritional factors and menarche in four sub-Saharan African urban sites. We used cross-sectional school-based data from 2307 female adolescents aged 10-14 years collected by the Africa Research, Implementation Science, and Education (ARISE) Network in Ouagadougou, Burkina Faso; Addis Ababa, Ethiopia; Khartoum, Sudan; and Dar es Salaam, Tanzania. Logit models were used to estimate the median age at menarche at each site. Associations between menarche and BMI-for-age, stunting, dietary quality and food insecurity across settings were assessed using Poisson regression models adjusted for country and school levels. The estimated median age at menarche was 13.1 years (95% confidence interval: 12.7, 13.5) in Ouagadougou; 12.9 (12.6, 13.2) in Addis Ababa; 13.3 (12.7, 13.6) in Khartoum; and 13.2 (12.3, 14.0) in Dar es Salaam. Between 18% and 49% of the girls in each setting had already menstruated. Based on the pooled multivariable models, underweight participants were 42% less likely (adjusted prevalence ratio [PR] 0.58 [0.44, 0.77]) to have experienced menarche in comparison to normal-weight individuals. The likelihood of experiencing menarche increased for overweight [PR 1.47 (1.30,1.66)] and obese [PR 1.57 (1.35,1.82)] in comparison to normal-weight girls. Those stunted were 47% less likely to have experienced menarche [PR 0.53 (0.41, 0.69)] than their nonstunted counterparts. A lower likelihood of menarche among those experiencing moderate/severe hunger when compared to those with no/little hunger was also observed (PR 0.78 [0.63,0.96]). No evidence of association with dietary quality was found. Further research is needed to strengthen the body of evidence and inform evidence-based initiatives in low- and middle-income settings
"It's Their Little Red Bible": Exploring Immigration and Immunization Journeys Through Nigerian Mother Relationships with Child Health Records in London.
Get PDFDrawing on an ethnography of Nigerian migrant motherhood in London, we explore how the original design of children's health records, known as the Red Book, to log routine vaccinations has been transformed to document family proof of residency amidst Britain's "hostile environment." Nigerian migrant mothers use the Red Book as evidence of raising British children and to overcome their precarity. By resolutely documenting their children's immunizations, Nigerian mothers pursue both biological and political immunity while on a simultaneous immunization and citizenship journey
The effectiveness of heat prevention plans in reducing heat-related mortality across Europe.
Get PDFHeat-health warning systems and action plans, referred to as heat prevention plans (HPPs), are key public health interventions aimed at reducing heat-related mortality. Despite their importance, prior assessments of their effectiveness have yielded inconsistent results. The objective of this study is to systematically assess the effectiveness of HPPs in reducing heat-related mortality risk across Europe. We analysed daily mortality and mean temperature data from 102 locations in 14 European countries between 1990 and 2019. Using data from national experts, we identified the year of HPP implementation and categorised their development class. A three-stage analysis was conducted: (1) quasi-Poisson time series models were used to estimate location-specific warm-season exposure-response functions in 3 year subperiods; (2) mixed-effect meta-regression models with multilevel longitudinal structures were employed to quantify changes in pooled exposure-response functions due to HPP implementation, adjusted for long-term trends in heat-related mortality risks; and (3) the heat-related excess mortality due to HPP was calculated by comparing factual (with HPP) and counterfactual (without HPP) scenarios. Estimates are reported by country, region, and HPP class. HPP implementation was associated with a 25.2% [95% CI: 19.8% to 31.9%] reduction in excess deaths attributable to extreme heat, corresponding to 1.8 [95% CI: 1.3-2.4] avoided deaths annually per 100 000 inhabitants. This equates to an estimated 14 551 [95% CI: 10 118-19 072] total deaths avoided across all study locations following HPP implementation. No significant differences in HPP effectiveness were observed by European region or HPP class. Our findings provide robust evidence that HPPs substantially reduce heat-related mortality across Europe, accounting for temporal changes and geographical differences in risks. These results emphasise the importance of monitoring and evaluating HPPs to enhance adaptation to a warming climate
Liposomal antimicrobials in the fight against bacterial and fungal pathogens: Clinical successes and development challenges.
No full textBacterial, fungal, and protozoan infections pose a rapidly escalating threat to global health, exacerbated by the rise in antimicrobial resistance. Current therapies against microbial pathogens are limited by high systemic toxicity and poor drug solubility. Liposomal formulations (spherical vesicles composed of lipid bilayers) have demonstrated remarkable clinical potential in addressing these concerns, as evidenced by the marketed products AmBisome® and Arikayce®. These products, which deliver amphotericin B via parenteral injection and amikacin via inhalation, exemplify how liposomes effectively mitigate drug-associated toxicity, enhance therapeutic efficacy, and overcome the biological barriers inherent to infection sites, including complex microbial biofilms, mucosal interfaces, or the blood-brain barrier. Complementary insights from anticancer research indicate that strategic manipulation of liposomal composition and structure can enhance their therapeutic potential. Adjustments in lipid charge, fluidity, and PEGylation, in particular, highlight their versatility and broad applicability for antimicrobial drug delivery. Liposomal antimicrobials can modulate pharmacokinetic profiles, achieve targeted release at sites of infection, and increase local drug concentrations, which are key advantages over conventional treatments. Despite these therapeutic advances, successful clinical translation and widespread adoption of liposomal antimicrobials remain highly dependent on overcoming existing technological and manufacturing challenges. This review emphasises the need for a paradigm shift within liposomal antimicrobial development, encouraging progression from initial research and development toward scalable, reproducible, and economically viable commercial manufacturing platforms. This transition is essential not only for ensuring the global accessibility and affordability of existing therapies but also for expanding the development of clinically relevant liposomal antimicrobial nanomedicines