Predicting all-cause unplanned readmission within 30 days of discharge using electronic medical record data: A multi-centre study.

OBJECTIVE: To develop a predictive model for identifying patients at high risk of all-cause unplanned readmission within 30 days after discharge, using administrative data available before discharge. MATERIALS AND METHODS: Hospital administrative data of all adult admissions in three tertiary metropolitan hospitals in Australia between July 01, 2015, and July 31, 2016, were extracted. Predictive performance of four mixed-effect multivariable logistic regression models was compared and validated using a split-sample design. Diagnostic details (Charlson Comorbidity Index CCI, components of CCI, and primary diagnosis categorised into International Classification of Diseases chapters) were added gradually in the clinically simplified model with socio-demographic, index admission, and prior hospital utilisation variables. RESULTS: Of the total 99 470 patients admitted, 5796 (5.8%) were re-admitted through the emergency department of three hospitals within 30 days after discharge. The clinically simplified model was as discriminative (C-statistic 0.694, 95% CI [0.681-0.706]) as other models and showed excellent calibration. Models with diagnostic details did not exhibit any substantial improvement in predicting 30-days unplanned readmission. CONCLUSION: We propose a 10-item predictive model to flag high-risk patients in a diverse population before discharge using readily available hospital administrative data which can easily be integrated into the hospital information system.

Comparing indigenous mortality across urban, rural and very remote areas: a systematic review and meta-analysis.

Background: It remains unclear how indigenous mortality varies between residential areas. We conducted a systematic review and meta-analysis on mortality patterns in urban, rural and very remote areas for the adult and infant indigenous populations of Australia, Canada, New Zealand and the USA. Methods: A literature search was performed using major online electronic publication repositories. Studies presenting indigenous mortality or disease incidence/prevalence in urban, rural or very remote areas were included. Indigenous mortality and disease incidence/prevalence in both urban and very remote areas were compared with those in rural areas. Studies that reported number of deaths or disease incidences along with population were included in the meta-analysis. Results: Thirty-one studies were included with data from Australia (n=19), Canada (n=3), New Zealand (n=1) and the USA (n=8). Indigenous adult all-cause mortality, cervical cancer mortality, trauma mortality and incidence of myocardial infarction were all significantly lower in urban areas compared with rural areas. Likewise, indigenous adult cardiovascular mortality and renal disease mortality were significantly lower in very remote areas compared with rural areas, while indigenous infant all-cause mortality showed no significant difference in urban, rural or very remote areas. Conclusions: Urban areas consistently experienced lower adult indigenous mortality compared with rural areas, as did some very remote areas. Indigenous infants, however, experience similar mortality rates across all residential areas.

Effect of APOE ε4 allele on survival and fertility in an adverse environment.

BACKGROUND: The apolipoprotein-ε4 allele (APOE-ε4) is strongly associated with detrimental outcomes in affluent populations including atherosclerotic disease, Alzheimer's disease, and reduced lifespan. Despite these detrimental outcomes, population frequencies of APOE-ε4 are high. We hypothesize that the high frequency of APOE-ε4 was maintained because of beneficial effects during evolution when infectious pathogens were more prevalent and a major cause of mortality. We examined a rural Ghanaian population with a high pathogen exposure for selective advantages of APOE-ε4, to survival and or fertility. METHODS AND FINDINGS: This rural Ghanaian population (n = 4311) has high levels of mortality from widespread infectious diseases which are the main cause of death. We examined whether APOE-ε4 was associated with survival (total follow-up time was 30,262 years) and fertility after stratifying by exposure to high or low pathogen levels. Households drawing water from open wells and rivers were classified as exposed to high pathogen levels while low pathogen exposure was classified as those drawing water from borehole wells. We found a non-significant, but positive survival benefit, i.e. the hazard ratio per APOE-ε4 allele was 0.80 (95% confidence interval: 0.69 to 1.05), adjusted for sex, tribe, and socioeconomic status. Among women aged 40 years and older (n = 842), APOE-ε4 was not associated with the lifetime number of children. However, APOE-ε4 was associated with higher fertility in women exposed to high pathogen levels. Compared with women not carrying an APOE-ε4 allele, those carrying one APOE-ε4 allele had on average one more child and those carrying two APOE-ε4 alleles had 3.5 more children (p = 0.018). CONCLUSIONS: Contrary to affluent modern-day populations, APOE-ε4 did not carry a survival disadvantage in this rural Ghanaian population. Moreover, APOE-ε4 promotes fertility in highly infectious environments. Our findings suggest that APOE-ε4 may be considered as evolutionarily adaptive. Its adverse associations in affluent modern populations with later onset diseases of aging further characterize APOE-ε4 as an example of antagonistic pleiotropy.

Current factors of fragility and delirium in vascular surgery.

BACKGROUND: Vascular surgery patients are frequently deemed to be in a frail clinical condition and at risk for delirium. Therefore, we evaluated the incidence and independent perioperative risk factors for delirium. In addition, we describe factors on frailty in the various vascular disease groups in current practice. METHODS: This observational longitudinal study included 206 selected patients who were referred to a vascular surgery ward of a large-sized teaching hospital (Amphia Hospital, Breda, The Netherlands) for critical limb ischemia (n = 80), diabetic foot ulcers (n = 27), abdominal aortic aneurysm (AAA) (n = 62), and carotid surgery (n = 37) between April 2013 and December 2013. Data on factors that characterize frailty were collected. Delirium was scored using the Delirium Observation Screening Scale. Multivariable logistic regression analysis was performed to find independent risk factors for delirium. RESULTS: Delirium was present in 24% of the critical limb ischemia patients, in 19% of the patients with a diabetic foot ulcer, in 7% of the patients with an AAA, and in 8% of the patients undergoing carotid surgery (P > 0.05). Of the patients with critical limb ischemia and a delirium, 53% were octogenarians. Multivariable stepwise logistic regression analysis revealed that history of delirium and nurse help at patient's home were independently associated with delirium. Patients with critical limb ischemia scored worse on factors related to frailty compared with the other disease groups in our current clinical practice on vascular surgery. CONCLUSIONS: Delirium is a frequent complication in vascular surgery clinical practice, especially in the elderly. Nurse visits at patients' homes and the Amphia Risk Score for delirium were independent risk factors for delirium in our study population. In this study, we identified patients with critical limb ischemia as the most frail and vulnerable.

Variants of the IL-10 gene associate with muscle strength in elderly from rural Africa: a candidate gene study.

Recently, it has been shown that the capacity of the innate immune system to produce cytokines relates to skeletal muscle mass and strength in older persons. The interleukin-10 (IL-10) gene regulates the production capacities of IL-10 and tumour necrosis factor-α (TNF-α). In rural Ghana, IL-10 gene variants associated with different production capacities of IL-10 and TNF-α are enriched compared with Caucasian populations. In this setting, we explored the association between these gene variants and muscle strength. Among 554 Ghanaians aged 50 years and older, we determined 20 single nucleotide polymorphisms in the IL-10 gene, production capacities of IL-10 and TNF-α in whole blood upon stimulation with lipopolysaccharide (LPS) and handgrip strength as a proxy for skeletal muscle strength. We distinguished pro-inflammatory haplotypes associated with low IL-10 production capacity and anti-inflammatory haplotypes with high IL-10 production capacity. We found that distinct haplotypes of the IL-10 gene associated with handgrip strength. A pro-inflammatory haplotype with a population frequency of 43.2% was associated with higher handgrip strength (P = 0.015). An anti-inflammatory haplotype with a population frequency of 7.9% was associated with lower handgrip strength (P = 0.006). In conclusion, variants of the IL-10 gene contributing to a pro-inflammatory cytokine response associate with higher muscle strength, whereas those with anti-inflammatory response associate with lower muscle strength. Future research needs to elucidate whether these effects of variation in the IL-10 gene are exerted directly through its role in the repair of muscle tissue or indirectly through its role in the defence against infectious diseases.

Common CFTR gene variants influence body composition and survival in rural Ghana.

Various studies in mice have found support for the hypothesis that heterozygous carriers of cystic fibrosis transmembrane conductance regulator (CFTR) mutations have an increased resistance to fatal infection compared to both homozygous mutation carriers and non-carriers, while in humans such evidence is scarce. In this study, we assessed the CFTR heterozygotes survival advantage hypothesis in a contemporary rural population that lives under adverse environmental conditions in the Upper-East region of Ghana. We genotyped 30 SNPs throughout the CFTR gene in 4,230 participants and tested their influence on survival and on body composition in the population at large. With a sliding-window haplotype analysis, we identified a set of six common haplotypes that influenced survival probabilities (global p = 6.00 x 10(-05)). Individual haplotype analyses revealed two haplotypes of specific interest. One of these haplotypes was enriched (p = 0.003), whereas the other was depleted (p = 0.041) among people of old age (> or = 65 years) compared to young study participants (< or = 5 years). In addition, children (n = 474) carrying the latter haplotype had lower body weight (p (trend) = 0.020) and height (p (trend) = 0.010) compared to non-carriers. For all these analyses, similar associations for heterozygous and homozygous CFTR haplotype carriers were observed, revealing an additive effect of haplotype alleles. In conclusion, we identified common haplotypes in the CFTR gene that influence survival and body composition in the population at large with no evidence for heterozygote advantage.

Selection for genetic variation inducing pro-inflammatory responses under adverse environmental conditions in a Ghanaian population.

BACKGROUND: Chronic inflammation is involved in the pathogenesis of chronic age-associated, degenerative diseases. Pro-inflammatory host responses that are deleterious later in life may originate from evolutionary selection for genetic variation mediating resistance to infectious diseases under adverse environmental conditions. METHODOLOGY/PRINCIPAL FINDINGS: In the Upper-East region of Ghana where infection has remained the leading cause of death, we studied the effect on survival of genetic variations at the IL10 gene locus that have been associated with chronic diseases. Here we show that an IL10 haplotype that associated with a pro-inflammatory innate immune response, characterised by low IL-10 (p = 0.028) and high TNF-alpha levels (p = 1.39 x 10(-3)), was enriched among Ghanaian elders (p = 2.46 x 10(-6)). Furthermore, in an environment where the source of drinking water (wells/rivers vs. boreholes) influences mortality risks (HR 1.28, 95% CI [1.09-1.50]), we observed that carriers of the pro-inflammatory haplotype have a survival advantage when drinking from wells/rivers but a disadvantage when drinking from boreholes (p(interaction) = 0.013). Resequencing the IL10 gene region did not uncover any additional common variants in the pro-inflammatory haplotype to those SNPs that were initially genotyped. CONCLUSIONS/SIGNIFICANCE: Altogether, these data lend strong arguments for the selection of pro-inflammatory host responses to overcome fatal infection and promote survival in adverse environments.