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Deprivation and limitations in daily life in new onset kidney disease: a population study.
Get PDFBACKGROUND: Existing population research has evaluated inequities in health outcomes for people in deprived communities who have early kidney disease, but not the differences in their self-reported overall health and ability to manage daily life activities when they first present, or the additional burden for people of working age. Using their responses to the national Census in Scotland, we studied the self-reported overall health and impact on day-to-day life of people in deprived and affluent households who newly presented with evidence of kidney disease.
METHODS: Of 458 897 adult North Scotland residents, we included all 24 775 individuals who presented with new onset kidney disease (eGFR <60 ml/min/1.72 m2) in 2011-2014. We measured deprivation based on household (Census) and resident neighbourhood (index of multiple deprivation). We fitted proportional odds regression models that accounted for age, sex, comorbidities, and additional impairments (e.g. vision, hearing, learning difficulties). We further adjusted for self-reported mental health and living alone as potential mediators, and tested for interactions with working age (18-65 years), sex, and mental health.
RESULTS: Of 24 775 people newly presenting with kidney disease, already 11 115 (45%) reported limitations in their daily lives. People in the most deprived (vs least) neighbourhoods and households experienced 2-fold greater odds of worse self-reported health (adjusted odds ratio, OR 2.05, 1.81-2.32 neighbourhood; OR 1.93, 1.64-2.26 household); and greater limitation in day-to-day activities (OR 1.70, 1.49-1.95 neighbourhood; OR 1.65, 1.39-1.96 household). This pattern of inequity was even more pronounced (3-fold) among those of working age (interaction P < .0001).
CONCLUSION: The association of deprivation with health and daily life represents an additional dimension of health inequity that is substantial, and evident from the earliest stages for people with kidney disease
Current burden and future projections of glaucoma in the United Kingdom.
Get PDFBACKGROUND/AIMS: Up-to-date, stratified estimates of the number of individuals affected by glaucoma in the UK are lacking. This study aimed to estimate the current and future glaucoma burden in the UK population.
METHODS: The most recent UK census data were used to obtain population counts stratified by age, sex and ethnicity. Age and sex-specific glaucoma prevalence estimates for individuals of European ancestry were sourced from a recent individual participant data meta-analysis of the European Eye Epidemiology Consortium. For non-European ethnic groups, prevalence was estimated by applying relative risks from a Bayesian global meta-analysis to the European baseline. Population projections from the UK's Office for National Statistics were used to estimate future disease burden.
RESULTS: Among 34 million UK adults aged ≥40 years, an estimated 1 019 629 individuals (95% CI 691 042 to 1 428 594) are currently living with glaucoma. Estimated age-specific case numbers increase from approximately 10 000 at ages 40-44 to nearly 173 000 in those ≥85 years. Although non-European groups represent only 5.8% of the UK population aged ≥65, they account for an estimated 8.1% of current glaucoma cases. By 2060, the number of affected individuals is projected to rise to 1.61 million (95% CI 1.11 million to 2.22 million), corresponding to a 60% rise in cases despite only a 28% population increase, driven by demographic ageing and the growth of higher-risk ethnic populations.
CONCLUSION: The UK glaucoma burden is substantially higher than previously estimated and is expected to rise further by 2060, underscoring the need for targeted resource allocation and strategic healthcare planning
Estimating the effect of hepatitis C infection on multidrug-resistant tuberculosis treatment outcomes under hypothetical interventions on regimen composition and adherence.
No full textHepatitis C virus (HCV) infection is associated with unfavorable multidrug- and rifampicin-resistant (MDR/RR) tuberculosis (TB) outcomes. We examined whether this association would decrease in settings where no participants were lost-to-follow-up or where all adhered to regimens comprised of priority TB drugs. We analyzed data from 1530 participants with HCV testing in the endTB observational cohort (NCT03259269). We estimated the relative risk of death, treatment failure, and loss-to-follow-up comparing participants with and without HCV, using inverse probability weighting to adjust for confounding. We then estimated relative risks of HCV on death and failure in weighted pseudopopulations representing hypothetical interventions eliminating loss-to-follow-up and ensuring adherence to strong MDR/RR-TB regimens. The unadjusted risk difference comparing participants with and without HCV was 14.1% (95% confidence interval [CI] 8.0%, 20.1%), decreasing to 11.0% (95%CI, 3.0%, 19.1%) after weighting. In pseudopopulations without loss-to-follow-up or with adequate adherence to strong regimens, the risk differences were 7.7% (95% CI, 0.8%, 16.2%) and 7.0% (95% CI, -1.6%, 17.3%), respectively. Adjustment for baseline confounders attenuated the association between HCV and unfavorable outcomes, suggesting these factors partly explain the disparity. Further attenuation after eliminating loss-to-follow-up suggests that improving treatment retention in MDR/RR-TB care may reduce outcome disparities among patients with HCV
Sociodemographic Factors and Childhood Growth: Associations with Environmental Sanitation Phases.
Get PDFBACKGROUND: Early childhood growth trajectories can influence the risk of chronic diseases in adulthood. Improvements in environmental sanitation may affect child development in low-resource settings. OBJECTIVE: to examine the associations among socioeconomic factors with nutrition indicators, and trajectories of anthropometric indicators across three epidemiological cohorts that reflect different phases of environmental sanitation implementation. METHODS: A longitudinal study was conducted in Salvador, Brazil, from 1997 to 2013. A total of 1429 children were recruited across three epidemiological cohorts, corresponding to the phases of a sanitation program: pre-intervention (n = 299), intervention (n = 1007), and post-intervention (n = 123). Height-for-age (HAZ) and BMI-for-age (BAZ) z-scores were assessed at four time points. Multilevel linear models were used to adjust for socioeconomic factors. RESULTS: A total of 992 children (68.7%) completed follow-up. Post-intervention children showed improved HAZ trajectories, with sex-specific patterns that varied across cohorts. Birth weight is positively associated with HAZ across all cohorts (0.34-0.49 kg increase per z-score). Household overcrowding (>2 persons/room) is consistently associated with lower HAZ (-0.34 to -0.63 z-score reduction). Children who were never exclusively breastfed in the post-intervention phase had a higher BAZ (0.76 z-score increase). Caesarean delivery is associated with higher BAZ in the pre-intervention (0.23) and intervention (0.27) cohorts. CONCLUSIONS: Children born in later time periods showed better growth trajectories, which may reflect the combined effects of sanitation improvements, economic development, and other societal changes in Brazil during this period. Further research using experimental or quasi-experimental designs is needed to isolate the specific contribution of sanitation to child growth
Incidence and prevalence of obstructive sleep apnoea and narcolepsy in the UK: a population-based descriptive study.
Get PDFBACKGROUND: Obstructive sleep apnoea (OSA) and narcolepsy are estimated to affect approximately 4.8% and 0.047% of the UK population, respectively. We do not know how many people have been diagnosed or how this varies over time and by demographic factors. METHODS: We, therefore, conducted a historical population-based descriptive study estimating prevalence and incidence of diagnosed OSA and narcolepsy in England from 2000 to 2019 stratified by demographic factors, and compared estimates to Scotland, Wales and Northern Ireland. Data were from Clinical Practice Research Datalink (CPRD) primary care records linked to Hospital Episode Statistics (HES) admissions. The study population included people with ≥90 days follow-up between 1 January 2000 and 31 December 2019, no prior record of primary or central sleep apnoea, and aged ≥18 years (OSA only). Diagnoses were defined using the first coded record for each condition in CPRD or HES data. Annual prevalence was estimated at mid-year and directly age/sex-standardised to the national population. Incidence was estimated by dividing new diagnoses by total person-time at risk. RESULTS: In England, 2019 adult standardised diagnosed OSA prevalence was 1.40% (95% CI 1.40% to 1.41%) representing approximately 622 528 people; standardised narcolepsy prevalence was 0.020% (95% CI 0.019% to 0.021%) representing approximately 11 307 people. Despite increases over time, diagnosed incidence and prevalence remained substantially lower than published estimates of symptomatic frequency. Rates varied by age, sex, ethnicity and UK nation for both conditions, and urban-rural living, area-based deprivation and practice size for OSA. CONCLUSION: Our results call for high-quality research to drive initiatives that increase diagnosis rates and address variation
Developing a new albuminuria-free risk prediction equation for kidney failure in patients with chronic kidney disease: retrospective cohort study.
Get PDFOBJECTIVE: To develop new risk prediction equations for kidney failure in patients with chronic kidney disease who do not require data for the urine albumin to creatinine ratio.
DESIGN: Retrospective cohort study.
SETTING: Stockholm Creatinine Measurements (SCREAM) database of routinely collected electronic healthcare records in primary and outpatient care from the region of Stockholm, Sweden.
PARTICIPANTS: 116 158 adults with chronic kidney disease stages 3-4, defined by two estimated glomerular filtration rate (eGFR) results of <60 to ≥15 mL/min/1.73 m², at least 90 days apart, with no intermediate eGFR value ≥60 mL/min/1.73 m², between 1 January 2010 to 31 December 2018.
MAIN OUTCOME MEASURE: Kidney failure, defined as starting kidney replacement therapy, recorded within five years of the index date.
RESULTS: Based on temporal split sample validation, development and validation cohorts included 85 012 patients (736 kidney replacement therapy events) and 28 338 patients (114 kidney replacement therapy events), respectively. After Cox regression with automated backwards selection, the final model included 10 predictors (in order of significance): eGFR, age, diabetes, sex, atrial fibrillation, antihypertensive drugs, peripheral artery disease, reduction in eGFR slope, acute kidney injury, and hypertension. Model discrimination was excellent in both the development cohort (C statistic 0.941, 95% confidence interval (CI) 0.932 to 0.951) and validation cohort (C statistic 0.944, 0.923 to 0.965). In 26 229 patients with data for the urine albumin to creatinine ratio, the four variable kidney failure risk equation (KFRE) showed marginal improvement in discrimination over our new equation (C statistic 0.950, 95% CI 0.942 to 0.958 for KFRE v 0.926, 0.915 to 0.936, for the new equation). KFRE under-estimated the risk in the study cohort, however, with an observed-expected event probability ratio of 2.11, suggesting that recalibration is required.
CONCLUSIONS: The findings of the study indicate that predicting the risk of kidney failure with high accuracy in a general population of patients with chronic kidney disease is possible based on data that are routinely available, without requiring data for the urine albumin to creatinine ratio
Unsuppressed viraemia and lower CD4 count associated with faster telomere attrition in African children with perinatal HIV on long-term antiretroviral therapy.
No full textBACKGROUND: HIV leads to reduced telomere length (TL), a biomarker of immune ageing. We investigated relationships between HIV viral load (VL) and CD4 count with TL and its rate of attrition in children with HIV (CWH) from Zambia and Zimbabwe.
METHODS: Buffy coat was obtained at baseline and 48 weeks from children aged 11-19 years with perinatally-acquired HIV taking combination antiretroviral therapy (cART) for >6 months recruited into the VITALITY trial [Trial registration no: PACTR202009897660297]. Relative TL was measured using monochrome multiplex qPCR, standardising units for analysis. Cross-sectional analyses used multivariable linear regression adjusting for age, sex and study site; longitudinal analysis additionally adjusted for baseline TL.
RESULTS: Among participants at baseline (N=842, mean±SD age 15.5±2.6 years, 53.2% female), 678(80.5%) had HIV VL1000 copies/mL. The CD4 count was 584±243 cells/μL. Compared to participants with VL1000 copies/mL had shorter TL (β[95%CI]=-0.239[-0.451, -0.026], P=0.028) whereas those with 60-1000 copies/mL did not (P=0.836). Lower CD4 cell count was associated with shorter TL (β[95%CI]=-0.038[-0.009, -0.066] per 100 CD4 cells/μL, P=0.009). In longitudinal analysis (N=783) after 336±6 days, those with HIV VL>1000 copies/mL at both timepoints had an accelerated telomere attrition rate (β[95%CI]=-0.276[-0.546, -0.005], P=0.046) compared with participants with VL<1000 copies/mL. Lower baseline CD4 count was associated with faster telomere attrition rate (β[95%CI]=-0.033[-0.008, -0.057], P=0.009).
CONCLUSIONS: HIV VL>1000 copies/mL among CWH on cART in Africa is associated with a degradation of immune age within one year, which may increase risk of co-morbidities later in life
Estimating the global burden of viable Mycobacterium tuberculosis infection: A mathematical modelling study.
Get PDFBACKGROUND: Estimating the proportion of individuals currently infected with Mycobacterium tuberculosis (Mtb) is key for informing global health policies. Although a substantial portion of the global population exhibit tuberculous immunoreactivity, not all have a viable Mtb infection. Moreover, individuals with recent infections are at a higher risk of developing tuberculosis (TB). Here, we present estimates of the global burden of viable Mtb infection, using new insights into the natural history of TB. METHODS AND FINDINGS: We constructed country-specific trends in annual risk of infection considering estimates of TB burden, immunoreactivity reversion, and age-specific mixing. We applied these trends to a deterministic mathematical model incorporating reinfection and self-clearance to estimate recent (within 2 years) and total viable Mtb infections. Empirical data on self-clearance are limited, so rates were informed by modelling estimates. In 2022, we estimated that 133.7 million people (95% uncertainty interval [UI]: 104.0, 171.1) had a recent Mtb infection, representing 1.7% (95% UI: 1.3, 2.2) of the global population. In total, 288.9 million people (95% UI: 242.2, 342.7)-or 3.7% (95% UI: 3.1, 4.3) globally-were estimated to harbour a viable Mtb infection. Among those recently infected, 12.0% (95% UI: 11.4, 12.7) were children under 15 years of age. Most recent infections were found in the World Health Organization regions of South-East Asia (49.0%; 95% UI: 37.2, 62.4), the Western Pacific (19.7%; 95% UI: 12.6, 30.5), and Africa (17.9%; 95% UI: 12.9, 24.1). India, Indonesia, and China had the highest burden, with 39.1 million (95% UI: 18.0, 73.6), 12.0 million (95% UI: 5.8, 22.9), and 11.2 million (95% UI: 5.0, 25.5) people, respectively, recently infected with Mtb. Sensitivity analyses of varying self-clearance scenarios showed significant changes in global estimates of viable Mtb infection, particularly in total burden, with lower self-clearance rates. Overall uncertainty in the estimates was considerable, reflecting limitations in the underlying data informing key model parameters. CONCLUSIONS: Our findings offer global burden estimates of viable Mtb infection and reveal a sizable population recently infected with Mtb and at high risk of progression to disease. New diagnostic tools that can detect individuals with viable Mtb-particularly those who would benefit from TB preventive therapy-are urgently needed
KidneyGenAfrica multi-cohort Genome-wide association study and polygenic prediction of kidney function in 110,000 Africans.
No full textKidney disease disproportionately affects populations of African ancestry, yet most genetic studies have focused on Europeans. Here, we present a three-stage genome-wide association study meta-analysis of estimated glomerular filtration rate in ~26,000 individuals across Eastern, Western, and Southern Africa and ~81,000 African-ancestry individuals in the diaspora. Continental African meta-analysis identifies four independent genome-wide significant loci, including two previously unreported loci. Pan-African meta-analysis identifies 19 independent loci, including three previously unreported loci. Fine-mapping reveals four loci with high causality probability, and phenome-wide analyses demonstrate pleiotropic effects on cardiometabolic and immunological traits. Notably, APOL1 high-risk variants strongly associated with kidney disease in African Americans show markedly lower frequency and attenuated effects in continental Africa, indicating potential distinct genetic architectures. Polygenic scores from genetically similar populations significantly outperformed those from distant cohorts. These findings demonstrate the necessity of conducting genomic research across diverse African populations to enable equitable health outcomes
Enhancing evidence-based care using trial emulation in electronic health records: real-world effects of empagliflozin in people with type 2 diabetes.
Get PDFBACKGROUND: There is growing interest in widening the use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) to all people with type 2 diabetes mellitus (T2DM). However, pivotal randomized controlled trials (RCTs) evaluated these drugs only in highly selected populations, often lacking generalizability to real-world populations. Understanding the effects of SGLT2i in populations where RCT evidence may be lacking is essential to help inform guideline development. To address this, we estimated the effect of empagliflozin in real-world users, many of whom would not have been eligible for the pivotal EMPA-REG RCT. METHODS: We designed a trial emulation in UK primary care data, based on the EMPA-REG RCT, to assess the effect of empagliflozin in a more clinically relevant population. Adults with T2DM initiating empagliflozin (intervention) or dipeptidyl peptidase-4 inhibitors (active control) between January 1, 2014 and December 31, 2022 were included. Eligibility was extended to both RCT-eligible and RCT-ineligible individuals. The effect of empagliflozin on all-cause mortality was estimated using an adjusted Cox proportional hazards model, with stratified analyses by RCT eligibility. FINDINGS: The majority of people prescribed empagliflozin would not have met the EMPA-REG RCT eligibility criteria (11,011/13,239, 83.2% RCT-ineligible). During follow-up, all-cause mortality occurred in 551 out of 13,239 (4.2%) in the empagliflozin group and 6,589 out of 49,264 (13.4%) in the active control group (adjusted HR 0.76, 95% CI 0.69 to 0.83). There was no evidence of differential treatment effect by RCT eligibility status (p-interaction=0.27). INTERPRETATION: Patients prescribed empagliflozin in real-world settings differ substantially from those enrolled in the EMPA-REG RCT. Using electronic health records, we demonstrate that the mortality benefit observed in EMPA-REG extends to a broader, more diverse real-world population, including those excluded from the original RCT. These findings provide a novel source of real-world evidence supporting the wider use of empagliflozin in routine clinical practice