Predicting short- to medium-term care home admission risk in older adults: a systematic review of externally validated models.

INTRODUCTION: Predicting risk of care home admission could identify older adults for early intervention to support independent living but require external validation in a different dataset before clinical use. We systematically reviewed external validations of care home admission risk prediction models in older adults. METHODS: We searched Medline, Embase and Cochrane Library until 14 August 2023 for external validations of prediction models for care home admission risk in adults aged ≥65 years with up to 3 years of follow-up. We extracted and narratively synthesised data on study design, model characteristics, and model discrimination and calibration (accuracy of predictions). We assessed risk of bias and applicability using Prediction model Risk Of Bias Assessment Tool. RESULTS: Five studies reporting validations of nine unique models were included. Model applicability was fair but risk of bias was mostly high due to not reporting model calibration. Morbidities were used as predictors in four models, most commonly neurological or psychiatric diseases. Physical function was also included in four models. For 1-year prediction, three of the six models had acceptable discrimination (area under the receiver operating characteristic curve (AUC)/c statistic 0.70-0.79) and the remaining three had poor discrimination (AUC < 0.70). No model accounted for competing mortality risk. The only study examining model calibration (but ignoring competing mortality) concluded that it was excellent. CONCLUSIONS: The reporting of models was incomplete. Model discrimination was at best acceptable, and calibration was rarely examined (and ignored competing mortality risk when examined). There is a need to derive better models that account for competing mortality risk and report calibration as well as discrimination.

Uneasy bedfellows: Public-Private partnerships for malaria control.

It is argued that reducing poverty is likely to alleviate malaria transmission and that the way to do this is by reducing inequality. The present capitalist system (as opposed to a straightforward market) tends to erode equality and promote profit over product. This may extend to the manufacture of bednets, bought by agencies rather than individual consumers, whose products may suffer from built in obsolescence. It is argued that better quality nets that can be re-impregnated locally are both desired and required. Derek Charlwood (aka Mzshensy#1) started his career as a medical entomologist in 1974 as a Research Assistant in the laboratory of the legendary Mick Gillies. By 2012 he had risen to become a Senior Research Assistant working for the Liverpool School of Tropical Medicine and so he is definitely ascending the career ladder. He has worked in numerous malaria endemic countries including Brazil, Papua New Guinea, Tanzania, Cambodia, São Tomé and Príncipe, Mozambique and Eritrea.

Multimorbidity analysis with low condition counts: a robust Bayesian approach for small but important subgroups.

BACKGROUND: Robustly examining associations between long-term conditions may be important in identifying opportunities for intervention in multimorbidity but is challenging when evidence is limited. We have developed a Bayesian inference framework that is robust to sparse data and used it to quantify morbidity associations in the oldest old, a population with limited available data. METHODS: We conducted a retrospective cross-sectional study of a representative dataset of primary care patients in Scotland as of March 2007. We included 40 long-term conditions and studied their associations in 12,009 individuals aged 90 and older, stratified by sex (3039 men, 8970 women). We analysed associations obtained with Relative Risk (RR), a standard measure in the literature, and compared them with our proposed measure, Associations Beyond Chance (ABC). To enable a broad exploration of interactions between long-term conditions, we built networks of association and assessed differences in their analysis when associations are estimated by RR or ABC. FINDINGS: Our Bayesian framework was appropriately more cautious in attributing association when evidence is lacking, particularly in uncommon conditions. This caution in reporting association was also present in reporting differences in associations between sex and affected the aggregated measures of multimorbidity and network representations. INTERPRETATION: Incorporating uncertainty into multimorbidity research is crucial to avoid misleading findings when evidence is limited, a problem that particularly affects small but important subgroups. Our proposed framework improves the reliability of estimations of associations and, more in general, of research into disease mechanisms and multimorbidity. FUNDING: National Institute for Health and Care Research.

Performance of models for predicting 1-year to 3-year mortality in older adults: a systematic review of externally validated models.

Mortality prediction models support identifying older adults with short life expectancy for whom clinical care might need modifications. We systematically reviewed external validations of mortality prediction models in older adults (ie, aged 65 years and older) with up to 3 years of follow-up. In March, 2023, we conducted a literature search resulting in 36 studies reporting 74 validations of 64 unique models. Model applicability was fair but validation risk of bias was mostly high, with 50 (68%) of 74 validations not reporting calibration. Morbidities (most commonly cardiovascular diseases) were used as predictors by 45 (70%) of 64 of models. For 1-year prediction, 31 (67%) of 46 models had acceptable discrimination, but only one had excellent performance. Models with more than 20 predictors were more likely to have acceptable discrimination (risk ratio [RR] vs <10 predictors 1·68, 95% CI 1·06-2·66), as were models including sex (RR 1·75, 95% CI 1·12-2·73) or predicting risk during comprehensive geriatric assessment (RR 1·86, 95% CI 1·12-3·07). Development and validation of better-performing mortality prediction models in older people are needed.

The HIV capsid mimics karyopherin engagement of FG-nucleoporins.

HIV can infect non-dividing cells because the viral capsid can overcome the selective barrier of the nuclear pore complex and deliver the genome directly into the nucleus1,2. Remarkably, the intact HIV capsid is more than 1,000 times larger than the size limit prescribed by the diffusion barrier of the nuclear pore3. This barrier in the central channel of the nuclear pore is composed of intrinsically disordered nucleoporin domains enriched in phenylalanine-glycine (FG) dipeptides. Through multivalent FG interactions, cellular karyopherins and their bound cargoes solubilize in this phase to drive nucleocytoplasmic transport4. By performing an in vitro dissection of the nuclear pore complex, we show that a pocket on the surface of the HIV capsid similarly interacts with FG motifs from multiple nucleoporins and that this interaction licences capsids to penetrate FG-nucleoporin condensates. This karyopherin mimicry model addresses a key conceptual challenge for the role of the HIV capsid in nuclear entry and offers an explanation as to how an exogenous entity much larger than any known cellular cargo may be able to non-destructively breach the nuclear envelope.

Évaluation de la structure factorielle et des qualités psychométriques de l'Échelle de Fatigue Pandémique parmi la population adulte québécoise: Evaluation of the factorial structure and psychometric qualities of the Pandemic Fatigue Scale among Quebec adult population.

OBJECTIVE: The objective of the study is to evaluate the factorial structure and the psychometric qualities of the Pandemic Fatigue Scale among the Quebec adult population. METHOD: The data analyzed come from a web survey conducted in October 2021 among 10 368 adults residing in Quebec. The scale's factor structure and invariance by gender, age and language used to complete the questionnaire were tested using confirmatory factor analyses. Convergent and divergent validity were also assessed. Finally, the reliability of the scale was estimated from the alpha and omega coefficients. RESULTS: The analyzes suggest the presence of a bidimensional structure in the sample of Quebec adults with informational fatigue and behavioral fatigue. The invariance of the measure is noted for sex, for age subgroups and for the language used for the questionnaire. The results of convergent and divergent validity provide additional evidence for the validity of the scale. Finally, the reliability of the scale scores is excellent. CONCLUSION: The results support the presence of a bidimensional structure as in the initial work of Lilleholt et al. They also confirm that the scale has good psychometric qualities and that it can be used among the adult population of Quebec.

The Early HOSPITAL Score to Predict 30-Day Readmission Soon After Hospitalization: a Prospective Multicenter Study.

BACKGROUND: The simplified HOSPITAL score is an easy-to-use prediction model to identify patients at high risk of 30-day readmission before hospital discharge. An earlier stratification of this risk would allow more preparation time for transitional care interventions. OBJECTIVE: To assess whether the simplified HOSPITAL score would perform similarly by using hemoglobin and sodium level at the time of admission instead of discharge. DESIGN: Prospective national multicentric cohort study. PARTICIPANTS: In total, 934 consecutively discharged medical inpatients from internal general services. MAIN MEASURES: We measured the composite of the first unplanned readmission or death within 30 days after discharge of index admission and compared the performance of the simplified score with lab at discharge (simplified HOSPITAL score) and lab at admission (early HOSPITAL score) according to their discriminatory power (Area Under the Receiver Operating characteristic Curve (AUROC)) and the Net Reclassification Improvement (NRI). KEY RESULTS: During the study period, a total of 3239 patients were screened and 934 included. In total, 122 (13.2%) of them had a 30-day unplanned readmission or death. The simplified and the early versions of the HOSPITAL score both showed very good accuracy (Brier score 0.11, 95%CI 0.10-0.13). Their AUROC were 0.66 (95%CI 0.60-0.71), and 0.66 (95%CI 0.61-0.71), respectively, without a statistical difference (p value 0.79). Compared with the model at discharge, the model with lab at admission showed improvement in classification based on the continuous NRI (0.28; 95%CI 0.08 to 0.48; p value 0.004). CONCLUSION: The early HOSPITAL score performs, at least similarly, in identifying patients at high risk for 30-day unplanned readmission and allows a readmission risk stratification early during the hospital stay. Therefore, this new version offers a timely preparation of transition care interventions to the patients who may benefit the most.

Mucosal response of inactivated and recombinant COVID-19 vaccines in Congolese individuals.

BACKGROUND: The efficacy of immunization against an airborne pathogen depends in part on its ability to induce antibodies at the major entry site of the virus, the mucosa. Recent studies have revealed that mucosal immunity is poorly activated after vaccination with messenger RNA vaccines, thus failing in blocking virus acquisition upon its site of initial exposure. Little information is available about the induction of mucosal immunity by inactivated and recombinant coronavirus disease 2019 (COVID-19) vaccines. This study aims to investigate this topic. METHODS: Saliva and plasma samples from 440 healthy Congolese were collected including (1) fully vaccinated 2 month postvaccination with either an inactivated or a recombinant COVID-19 vaccine and (2) nonvaccinated control group. Total anti-severe acute respiratory syndrome coronavirus 2 receptor-binding domain IgG and IgA antibodies were assessed using in-house enzyme-linked immunosorbent assays for both specimens. FINDINGS: Altogether, the positivity of IgG was significantly higher in plasma than in saliva samples both in vaccinated and nonvaccinated control groups. Inversely, IgA positivity was slightly higher in saliva than in plasma of vaccinated group. The overall IgG and IgA levels were respectively over 103 and 14 times lower in saliva than in plasma samples. We found a strong positive correlation between IgG in saliva and plasma also between IgA in both specimens (r = .70 for IgG and r = .52 for IgA). Interestingly, contrary to IgG, the level of salivary IgA was not different between seropositive control group and seropositive vaccinated group. No significant difference was observed between recombinant and inactivated COVID-19 vaccines in total IgG and IgA antibody concentration release 2 months postvaccination both in plasma and saliva. CONCLUSION: Inactivated and recombinant COVID-19 vaccines in use in the Republic of Congo poorly activated mucosal IgA-mediated antibody response 2 months postvaccination.

Oxycodone Self-Administration in Female Rats is Enhanced by ∆9-tetrahydrocannabinol, but not by Cannabidiol, in a Progressive Ratio Procedure.

Epidemiological evidence suggests that the legalization of cannabis may reduce opioid-related harms. Preclinical evidence of neuropharmacological interactions of endogenous cannabinoid and opioid systems prompts further investigation of cannabinoids as potential therapeutics for the non-medical use of opioids. In these studies female rats, previously trained to self-administer oxycodone (0.15 mg/kg/infusion) intravenously in 6 h sessions, were allowed to self-administer oxycodone after exposure to cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) by vapor inhalation and THC by injection (5.0-20 mg/kg, i.p.). Self-administration was characterized under Progressive Ratio (PR) and Fixed Ratio (FR) 1 schedules of reinforcement in 3 h sessions. THC decreased IVSA of oxycodone in a FR procedure but increased reward seeking in a PR procedure. CBD decreased the IVSA of oxycodone in the FR but not the PR procedure. The results are consistent with an anti-reward effect of CBD but suggest THC acts to increase the reinforcing efficacy of oxycodone in this procedure.

Nicotine, THC, and Dolutegravir Modulate E-Cigarette-Induced Changes in Addiction- and Inflammation-Associated Genes in Rat Brains and Astrocytes.

E-cigarette use has been marketed as a safer alternative to traditional cigarettes, as a means of smoking cessation, and are used at a higher rate than the general population in people with HIV (PWH). Early growth receptor 2 (EGR2) and Activity-Regulated Cytoskeleton-Associated Protein (ARC) have a role in addiction, synaptic plasticity, inflammation, and neurodegeneration. This study showed that 10 days of exposure to e-cigarette vapor altered gene expression in the brains of 6-month-old, male, Sprague Dawley rats. Specifically, the e-cigarette solvent vapor propylene glycol (PG) downregulated EGR2 and ARC mRNA expression in frontal cortex, an effect which was reversed by nicotine (NIC) and THC, suggesting that PG could have a protective role against NIC and cannabis dependence. However, in vitro, PG upregulated EGR2 and ARC mRNA expression at 18 h in cultured C6 rat astrocytes suggesting that PG may have neuroinflammatory effects. PG-induced upregulation of EGR2 and ARC mRNA was reversed by NIC but not THC. The HIV antiretroviral DTG reversed the effect NIC had on decreasing PG-induced upregulation of EGR2, which is concerning because EGR2 has been implicated in HIV latency reversal, T-cell apoptosis, and neuroinflammation, a process that underlies the development of HIV-associated neurocognitive disorders.

Adult consequences of repeated nicotine vapor inhalation in adolescent rats.

INTRODUCTION: There has been a resurgence in nicotine inhalation in adolescents due to the popularity and availability of Electronic Nicotine Delivery Systems (ENDS). Almost five times as many US high-school seniors inhale nicotine vapor daily compared with those who smoke tobacco. This study was conducted to determine the impact of repeated adolescent vapor inhalation of nicotine on behavior in adulthood. METHODS: Male and female Sprague-Dawley rats were exposed to 30-minute sessions of ENDS vapor inhalation, twice daily, from Post-Natal Day (PND) 31 to PND 40. Conditions included vapor from the propylene glycol (PG) vehicle or nicotine (30 mg/mL in the PG). Animals were assessed for effects of nicotine on open field (PND 74-105) and wheel activity (PND 126-180) and for volitional exposure to nicotine vapor (PND 285-395). Plasma nicotine and cotinine were assessed in separate groups of male and female Wistar and Sprague-Dawley rats after a single nicotine inhalation session. RESULTS: Group mean plasma nicotine ranged from 39 to 59 ng/mL post-session with minimal strain differences detected. Adolescent nicotine exposure enhanced sensitivity to the locomotor stimulating effects of nicotine (0.1-0.8 mg/kg, s.c.) in an open field in female rats, but didn't change effects of nicotine on wheel activity. Female rats exposed to nicotine (30 mg/mL) vapor as adolescents responded more vigorously than PG exposed females for nicotine vapor in a FR5 challenge. CONCLUSIONS: Repeated adolescent nicotine vapor inhalation leads to enhanced liability for volitional exposure to nicotine vapor in adulthood in female rats, but minimal change in spontaneous locomotor behavior. IMPLICATIONS: These results show that adolescent vaping of nicotine can lead to lasting sensitization to the effects of nicotine in adulthood, including volitional responding for nicotine vapor. Demonstration of this in a controlled animal model establishes causality in a manner not possible from longitudinal evidence in human populations. These findings further highlight the importance of decreasing adolescent nicotine exposure by e-cigarettes to reduce consumption in adulthood.

Effectiveness of piperonyl butoxide and pyrethroid-treated long-lasting insecticidal nets (LLINs) versus pyrethroid-only LLINs with and without indoor residual spray against malaria infection: third year results of a cluster, randomised controlled, two-by-two factorial design trial in Tanzania.

BACKGROUND: After decades of success in reducing malaria through the scale-up of pyrethroid long-lasting insecticidal nets (LLINs), the decline in the malaria burden has stalled, coinciding with the rapid spread of pyrethroid resistance. In a previously reported study, nets treated with a pyrethroid and a synergist, piperonyl butoxide (PBO), demonstrated superior efficacy compared to standard pyrethroid LLINs (std-LLINs) against malaria. Evidence was used to support the public health recommendation of PBO-Pyrethroid-LLIN by the World Health Organization in 2018. This study looks at the third year of rollout of these nets in Muleba district, Tanzania to inform whether policy guidelines need to be updated. METHODS: A four-group cluster randomized trial (CRT) using a two-by-two factorial design was carried out between January 2014 and December 2017. A total of 48 clusters, were randomized in a 1:1:1:1 ratio to the following treatment groups, each intervention being provided once in 2015: 1/std-LLIN; 2/PBO-pyrethroid LLIN; 3/std-LLIN + Indoor Residual Spraying (IRS) and 4/PBO-Pyrethroid-LLIN + IRS. During the third year follow-up, malaria infection prevalence in 80 children per cluster, aged 6 months to 14 years, was measured at 28- and 33-months post-intervention and analysed as intention-to-treat (ITT) and per protocol (PP). Mosquito collections were performed monthly in all clusters, using CDC light traps in 7 randomly selected houses per cluster. RESULTS: At 28 and 33 months, study net usage among household participants was only 47% and 31%, respectively. In ITT analysis, after 28 months malaria infection prevalence among 7471 children was 80.9% in the two std-LLIN groups compared to 69.3% in the two PBO-Pyrethroid-LLIN (Odds Ratio: 0.45, 95% Confidence Interval: 0.21-0.95, p-value: 0.0364). After 33 months the effect was weaker in the ITT analysis (prevalence 59.6% versus 49.9%, OR: 0.60, 95%CI:0.32-1.13, p-value: 0.1131) but still evident in the PP analysis (57.2% versus 44.2%, OR: 0.34, 95%CI: 0.16-0.71, p-value: 0.0051). Mean number of Anopheles per night collected per house was similar between PBO-Pyrethroid-LLIN groups (5.48) and std-LLIN groups (5.24) during the third year. CONCLUSIONS: Despite low usage of PBO- Pyrethroid LLIN, a small impact of those nets on malaria infection prevalence was still observed in the 3rd year with the most protection offered to children still using them. To maximize impact, it is essential that net re-distribution cycles are aligned with this LLIN lifespan to maintain maximum coverage. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov (registration number NCT02288637).

Factors associated with one-year mortality after hospital discharge: A multicenter prospective cohort study.

OBJECTIVES: 1) To identify predictors of one-year mortality in hospitalized medical patients using factors available during their hospital stay. 2) To evaluate whether healthcare system use within 30 days of hospital discharge is associated with one-year mortality. STUDY DESIGN AND SETTING: This prospective, observational study included adult patients from four mid-sized hospital general internal medicine units. During index hospitalization, we retrieved patient characteristics, including demographic and socioeconomic indicators, diagnoses, and early simplified HOSPITAL scores from electronic health records and patient interviews. Data on healthcare system use was collected using telephone interviews 30 days after discharge. Survival status at one year was collected by telephone and from health records. We used a univariable analysis including variables available from the hospitalization and 30-day post-discharge periods. We then performed multivariable analyses with one model using index hospitalization data and one using 30-day post-discharge data. RESULTS: Of 934 patients, 123 (13.2%; 95% CI 11.0-15.4%) were readmitted or died within 30 days. Of 814 patients whose primary outcome was available, 108 died (13.3%) within one year. Using factors obtained during hospitalization, the early simplified HOSPITAL score (OR 1.50; 95% CI 1.31-1.71; P < 0.001) and not living at home (OR 4.0; 95% CI 1.8-8.3; P < 0.001) were predictors of one-year mortality. Using 30-day post-discharge predictors, hospital readmission was significantly associated with one-year mortality (OR 4.81; 95% CI 2.77-8.33; P < 0.001). SIGNIFICANCE: Factors predicting one-year mortality were a high early simplified HOSPITAL score, not living at home, and a 30-day unplanned readmission.

Time series analysis of survival and oviposition cycle duration of Anopheles funestus (Giles) in Mozambique.

Background: Survival and gonotrophic cycle duration are important determinants of the vectorial capacity of malaria vectors but there are a limited number of approaches to estimate these quantities from field data. Time-series of observations of mosquitoes at different stages in the life-cycle are under-used. Methods: Anopheles funestus mosquitoes were caught using various methods over a 7.6-year period in Furvela, Mozambique. Survival and oviposition cycle duration were estimated using (i) an existing time-series approach for analysing dissections of mosquitoes caught in light-traps, extended to allow for variability in the duration of the cycle; (ii) an established approach for estimating cycle duration from resting collection data; (iii) a novel time-series approach fitted to numbers and categories of mosquitoes caught in exit-traps. Results: Data were available from 7,396, 6,041 and 1,527 trap-nights for exit-traps, light-traps and resting collections respectively. Estimates of cycle duration varied considerably between the different methods. The estimated proportion of female mosquitoes surviving each day of 0.740 (95% credible interval [0.650-0.815]) derived from light-trap data was much lower than the estimated daily survival of male mosquitoes from the model fitted to exit-trap data (0.881, 95% credible interval [0.747-0.987]). There was no tendency for the oviposition cycle to become shorter at higher temperature while the odds of survival of females through the cycle was estimated to be multiplied by 1.021 for every degree of mean weekly temperature increase (95% credible interval [0.991-1.051]). There was negligible temperature dependence and little inter-annual variation in male survival. Discussion: The time-series approach fitted to the exit-traps suggests that male An. funestus have higher survival than do females, and that male survival was temperature independent and unaffected by the introduction of long-lasting insecticidal nets (LLINs). The patterns of temperature dependence in females are at variance with results of laboratory studies. Time series approaches have the advantage for estimating survival that they do not depend on representative sampling of mosquitoes over the whole year. However, the estimates of oviposition cycle duration were associated with considerable uncertainty, which appears to be due to variability between insects in the duration of the resting period, and the estimates based on exit-trap data are sensitive to assumptions about relative trapping efficiencies.

Improvements in Hypertension Control in the Rural Longitudinal HAALSI Cohort of South African Adults Aged 40 and Older, From 2014 to 2019.

BACKGROUND: Over half of the South African adults aged 45 years and older have hypertension but its effective management along the treatment cascade (awareness, treatment, and control) remains poorly understood. METHODS: We compared the prevalence of all stages of the hypertension treatment cascade in the rural HAALSI cohort of older adults at baseline and after four years of follow-up using household surveys and blood pressure data. Hypertension was a mean systolic blood pressure >140 mm Hg or diastolic pressure >90 mm Hg, or current use of anti-hypertension medication. Control was a mean blood pressure <140/90 mm Hg. The effects of sex and age on the treatment cascade at follow-up were assessed. Multivariate Poisson regression models were used to estimate prevalence ratios along the treatment cascade at follow-up. RESULTS: Prevalence along the treatment cascade increased from baseline (B) to follow-up (F): awareness (64.4% vs. 83.6%), treatment (49.7% vs. 73.9%), and control (22.8% vs. 41.3%). At both time points, women had higher levels of awareness (B: 70.5% vs. 56.3%; F: 88.1% vs. 76.7%), treatment (B: 55.9% vs. 41.55; F: 79.9% vs. 64.7%), and control (B: 26.5% vs. 17.9%; F: 44.8% vs. 35.7%). Prevalence along the cascade increased linearly with age for everyone. Predictors of awareness included being female, elderly, or visiting a primary health clinic three times in the previous 3 months, and the latter two also predicted hypertension control. CONCLUSIONS: There were significant improvements in awareness, treatment, and control of hypertension from baseline to follow-up and women fared better at all stages, at both time points.

Development of prediction models for one-year brain tumour survival using machine learning: a comparison of accuracy and interpretability.

BACKGROUND AND OBJECTIVE: Prediction of survival in patients diagnosed with a brain tumour is challenging because of heterogeneous tumour behaviours and treatment response. Advances in machine learning have led to the development of clinical prognostic models, but due to the lack of model interpretability, integration into clinical practice is almost non-existent. In this retrospective study, we compare five classification models with varying degrees of interpretability for the prediction of brain tumour survival greater than one year following diagnosis. METHODS: 1028 patients aged ≥16 years with a brain tumour diagnosis between April 2012 and April 2020 were included in our study. Three intrinsically interpretable 'glass box' classifiers (Bayesian Rule Lists [BRL], Explainable Boosting Machine [EBM], and Logistic Regression [LR]), and two 'black box' classifiers (Random Forest [RF] and Support Vector Machine [SVM]) were trained on electronic patients records for the prediction of one-year survival. All models were evaluated using balanced accuracy (BAC), F1-score, sensitivity, specificity, and receiver operating characteristics. Black box model interpretability and misclassified predictions were quantified using SHapley Additive exPlanations (SHAP) values and model feature importance was evaluated by clinical experts. RESULTS: The RF model achieved the highest BAC of 78.9%, closely followed by SVM (77.7%), LR (77.5%) and EBM (77.1%). Across all models, age, diagnosis (tumour type), functional features, and first treatment were top contributors to the prediction of one year survival. We used EBM and SHAP to explain model misclassifications and investigated the role of feature interactions in prognosis. CONCLUSION: Interpretable models are a natural choice for the domain of predictive medicine. Intrinsically interpretable models, such as EBMs, may provide an advantage over traditional clinical assessment of brain tumour prognosis by weighting potential risk factors and their interactions that may be unknown to clinicians. An agreement between model predictions and clinical knowledge is essential for establishing trust in the models decision making process, as well as trust that the model will make accurate predictions when applied to new data.

Impact of diabetes on longevity and disability-free life expectancy among older South African adults: A prospective longitudinal analysis.

AIMS: We seek to understand the coexisting effects of population aging and a rising burden of diabetes on healthy longevity in South Africa. METHODS: We used longitudinal data from the 2015 and 2018 waves of the "Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa" (HAALSI) study to explore life expectancy (LE) and disability-free life expectancy (DFLE) of adults aged 45 and older with and without diabetes in rural South Africa. We estimated LE and DFLE by diabetes status using Markov-based microsimulation. RESULTS: We find a clear gradient in remaining LE and DFLE based on diabetes status. At age 45, a man without diabetes could expect to live 7.4 [95% CI 3.4 - 11.7] more years than a man with diabetes, and a woman without diabetes could expect to live 3.9 [95% CI: 0.8 - 6.9] more years than a woman with diabetes. Individuals with diabetes lived proportionately more years subject to disability than individuals without diabetes. CONCLUSIONS: We find large and important decrements in disability-free aging for people with diabetes in South Africa. This finding should motivate efforts to strengthen prevention and treatment efforts for diabetes and its complications for older adults in this setting.

Rapidly shifting immunologic landscape and severity of SARS-CoV-2 in the Omicron era in South Africa.

South Africa was among the first countries to detect the SARS-CoV-2 Omicron variant. However, the size of its Omicron BA.1 and BA.2 subvariants (BA.1/2) wave remains poorly understood. We analyzed sequential serum samples collected through a prospective cohort study before, during, and after the Omicron BA.1/2 wave to infer infection rates and monitor changes in the immune histories of participants over time. We found that the Omicron BA.1/2 wave infected more than half of the cohort population, with reinfections and vaccine breakthroughs accounting for > 60% of all infections in both rural and urban sites. After the Omicron BA.1/2 wave, we found few (< 6%) remained naïve to SARS-CoV-2 and the population immunologic landscape is fragmented with diverse infection/immunization histories. Prior infection with the ancestral strain, Beta, and Delta variants provided 13%, 34%, and 51% protection against Omicron BA.1/2 infection, respectively. Hybrid immunity and repeated prior infections reduced the risks of Omicron BA.1/2 infection by 60% and 85% respectively. Our study sheds light on a rapidly shifting landscape of population immunity in the Omicron era and provides context for anticipating the long-term circulation of SARS-CoV-2 in populations no longer naïve to the virus.

Estimating population level 24-h sodium excretion using spot urine samples in older adults in rural South Africa.

BACKGROUND: South Africa has introduced regulations to reduce sodium in processed foods. Assessing salt consumption with 24-h urine collection is logistically challenging and expensive. We assess the accuracy of using spot urine samples to estimate 24-h urine sodium (24hrUNa) excretion at the population level in a cohort of older adults in rural South Africa. METHODS: 24hrUNa excretion was measured and compared to that estimated from matched spot urine samples in 399 individuals, aged 40-75 years, from rural Mpumalanga, South Africa. We used the Tanaka, Kawasaki, International Study of Sodium, Potassium, and Blood Pressure (INTERSALT), and Population Mean Volume (PMV) method to predict 24hrUNa at the individual and population level. RESULTS: The population median 24hrUNa excretion from our samples collected in 2017 was 2.6 g (interquartile range: 1.53-4.21) equal to an average daily salt intake of 6.6 g, whereas 65.4% of participants had a salt excretion above the WHO recommended 5 g/day. Estimated population median 24hrUNa derived from the INTERSALT, both with and without potassium, showed a nonsignificant difference of 0.25 g (P = 0.59) and 0.21 g (P = 0.67), respectively. In contrast, the Tanaka, Kawasaki, and PMV formulas were markedly higher than the measured 24hrUNa, with a median difference of 0.51 g (P = 0.004), 0.99 g (P = 0.00), and 1.05 g (P = 0.00) respectively. All formulas however performed poorly when predicting an individual's 24hrUNa. CONCLUSION: In this population, the INTERSALT formulas are a well suited and cost-effective alternative to 24-h urine collection for the evaluation of population median 24hrUNa excretion. This could play an important role for governments and public health agencies in evaluating local salt regulations and identifying at-risk populations.