Clustering of physical health multimorbidity in people with severe mental illness: An accumulated prevalence analysis of United Kingdom primary care data

BACKGROUND: People with severe mental illness (SMI) have higher rates of a range of physical health conditions, yet little is known regarding the clustering of physical health conditions in this population. We aimed to investigate the prevalence and clustering of chronic physical health conditions in people with SMI, compared to people without SMI. METHODS AND FINDINGS: We performed a cohort-nested accumulated prevalence study, using primary care data from the Clinical Practice Research Datalink (CPRD), which holds details of 39 million patients in the United Kingdom. We identified 68,783 adults with a primary care diagnosis of SMI (schizophrenia, bipolar disorder, or other psychoses) from 2000 to 2018, matched up to 1:4 to 274,684 patients without an SMI diagnosis, on age, sex, primary care practice, and year of registration at the practice. Patients had a median of 28.85 (IQR: 19.10 to 41.37) years of primary care observations. Patients with SMI had higher prevalence of smoking (27.65% versus 46.08%), obesity (24.91% versus 38.09%), alcohol misuse (3.66% versus 13.47%), and drug misuse (2.08% versus 12.84%) than comparators. We defined 24 physical health conditions derived from the Elixhauser and Charlson comorbidity indices and used logistic regression to investigate individual conditions and multimorbidity. We controlled for age, sex, region, and ethnicity and then additionally for health risk factors: smoking status, alcohol misuse, drug misuse, and body mass index (BMI). We defined multimorbidity clusters using multiple correspondence analysis (MCA) and K-means cluster analysis and described them based on the observed/expected ratio. Patients with SMI had higher odds of 19 of 24 conditions and a higher prevalence of multimorbidity (odds ratio (OR): 1.84; 95% confidence interval [CI]: 1.80 to 1.88, p < 0.001) compared to those without SMI, particularly in younger age groups (males aged 30 to 39: OR: 2.49; 95% CI: 2.27 to 2.73; p < 0.001; females aged 18 to 30: OR: 2.69; 95% CI: 2.36 to 3.07; p < 0.001). Adjusting for health risk factors reduced the OR of all conditions. We identified 7 multimorbidity clusters in those with SMI and 7 in those without SMI. A total of 4 clusters were common to those with and without SMI; 1, heart disease, appeared as one cluster in those with SMI and 3 distinct clusters in comparators; and 2 small clusters were unique to the SMI cohort. Limitations to this study include missing data, which may have led to residual confounding, and an inability to investigate the temporal associations between SMI and physical health conditions. CONCLUSIONS: In this study, we observed that physical health conditions cluster similarly in people with and without SMI, although patients with SMI had higher burden of multimorbidity, particularly in younger age groups. While interventions aimed at the general population may also be appropriate for those with SMI, there is a need for interventions aimed at better management of younger-age multimorbidity, and preventative measures focusing on diseases of younger age, and reduction of health risk factors

Bone gain following loading is site-specifically enhanced by prior and concurrent disuse in aged male mice

The primary aim of osteoanabolic therapies is to strategically increase bone mass in skeletal regions likely to experience high strains. In the young healthy skeleton, this is primarily achieved by bone's adaptation to loading. This adaptation appears to fail with age, resulting in osteoporosis and fractures. We previously demonstrated that prior and concurrent disuse enhances bone gain following loading in old female mice. Here, we applied site specificity micro-computed tomography analysis to map regional differences in bone anabolic responses to axial loading of the tibia between young (19-week-old) and aged (19-month-old), male and female mice. Loading increased bone mass specifically in the proximal tibia in both sexes and ages. Young female mice gained more cortical bone than young males in specific regions of the tibia. However, these site-specific sex differences were lost with age such that bone gain following loading was not significantly different between old males and females. To test whether disuse enhances functional adaption in old male mice as it does in females, old males were subjected to sciatic neurectomy or sham surgery, and loading was initiated four days after surgery. Disuse augmented tibial cortical bone gain in response to loading in old males, but only in regions which were load-responsive in the young. Prior and concurrent disuse also increased loading-induced trabecular thickening in the proximal tibia of old males. Understanding how diminished background loading rejuvenates the osteogenic loading response in the old may improve osteogenic exercise regimes and lead to novel osteoanabolic therapies

Individual correlates of podoconiosis in areas of varying endemicity: a case-control study

BACKGROUND Podoconiosis is a non-filarial form of elephantiasis resulting in lymphedema of the lower legs. Previous studies have suggested that podoconiosis arises from the interplay of individual and environmental factors. Here, our aim was to understand the individual-level correlates of podoconiosis by comparing 460 podoconiosis-affected individuals and 707 unaffected controls. METHODS/PRINCIPAL FINDINGS This was a case-control study carried out in six kebeles (the lowest governmental administrative unit) in northern Ethiopia. Each kebele was classified into one of three endemicity levels: 'low' (prevalence 5%). A total of 142 (30.7%) households had two or more cases of podoconiosis. Compared to controls, the majority of the cases, especially women, were less educated (OR = 1.7, 95% CI = 1.3 to 2.2), were unmarried (OR = 3.4, 95% CI = 2.6-4.6) and had lower income (t = -4.4, p<0.0001). On average, cases started wearing shoes ten years later than controls. Among cases, age of first wearing shoes was positively correlated with age of onset of podoconiosis (r = 0.6, t = 12.5, p<0.0001). Among all study participants average duration of shoe wearing was less than 30 years. Between both cases and controls, people in 'high' and 'medium' endemicity kebeles were less likely than people in 'low' endemicity areas to 'ever' have owned shoes (OR = 0.5, 95% CI = 0.4-0.7). CONCLUSIONS Late use of shoes, usually after the onset of podoconiosis, and inequalities in education, income and marriage were found among cases, particularly among females. There were clustering of cases within households, thus interventions against podoconiosis will benefit from household-targeted case tracing. Most importantly, we identified a secular increase in shoe-wearing over recent years, which may give opportunities to promote shoe-wearing without increasing stigma among those at high risk of podoconiosis

Quantification of Alterations in Cortical Bone Geometry Using Site Specificity Software in Mouse models of Aging and the Responses to Ovariectomy and Altered Loading.

Investigations into the effect of (re)modeling stimuli on cortical bone in rodents normally rely on analysis of changes in bone mass and architecture at a narrow cross-sectional site. However, it is well established that the effects of axial loading produce site-specific changes throughout bones' structure. Non-mechanical influences (e.g., hormones) can be additional to or oppose locally controlled adaptive responses and may have more generalized effects. Tools currently available to study site-specific cortical bone adaptation are limited. Here, we applied novel site specificity software to measure bone mass and architecture at each 1% site along the length of the mouse tibia from standard micro-computed tomography (μCT) images. Resulting measures are directly comparable to those obtained through μCT analysis (R (2) > 0.96). Site Specificity analysis was used to compare a number of parameters in tibiae from young adult (19-week-old) versus aged (19-month-old) mice; ovariectomized and entire mice; limbs subjected to short periods of axial loading or disuse induced by sciatic neurectomy. Age was associated with uniformly reduced cortical thickness and site-specific decreases in cortical area most apparent in the proximal tibia. Mechanical loading site-specifically increased cortical area and thickness in the proximal tibia. Disuse uniformly decreased cortical thickness and decreased cortical area in the proximal tibia. Ovariectomy uniformly reduced cortical area without altering cortical thickness. Differences in polar moment of inertia between experimental groups were only observed in the proximal tibia. Aging and ovariectomy also altered eccentricity in the distal tibia. In summary, site specificity analysis provides a valuable tool for measuring changes in cortical bone mass and architecture along the entire length of a bone. Changes in the (re)modeling response determined at a single site may not reflect the response at different locations within the same bone

Личные интересы участников российского уголовного процесса: Автореф. дис.... канд. юрид. наук: 12.00.09

Background Rigorous estimates for clearance rates of untreated chlamydia infections are important for understanding chlamydia epidemiology and designing control interventions, but were previously only available for women. Methods We used data from published studies of chlamydia-infected men who were retested at a later date without having received treatment. Our analysis allowed new infections to take one of 1, 2, or 3 courses, each clearing at a different rate. We determined which of these 3 models had the most empirical support. Results The best-fitting model had 2 courses of infection in men, as was previously found for women: “slow-clearing” and “fast-clearing.” Only 68% (57%–78%) (posterior median and 95% credible interval [CrI]) of incident infections in men were slow-clearing, vs 77% (69%–84%) in women. The slow clearance rate in men (based on 6 months’ follow-up) was 0.35 (.05–1.15) year-1 (posterior median and 95% CrI), corresponding to mean infection duration 2.84 (.87–18.79) years. This compares to 1.35 (1.13–1.63) years in women. Conclusions Our estimated clearance rate is slower than previously assumed. Fewer infections become established in men than women but once established, they clear more slowly. This study provides an improved description of chlamydia’s natural history to inform public health decision making. We describe how further data collection could reduce uncertainty in estimates

The incidence rate of planned and emergency physical health hospital admissions in people diagnosed with severe mental illness: a cohort study

BACKGROUND: People with severe mental illness (SMI) have more physical health conditions than the general population, resulting in higher rates of hospitalisations and mortality. In this study, we aimed to determine the rate of emergency and planned physical health hospitalisations in those with SMI, compared to matched comparators, and to investigate how these rates differ by SMI diagnosis. METHODS: We used Clinical Practice Research DataLink Gold and Aurum databases to identify 20,668 patients in England diagnosed with SMI between January 2000 and March 2016, with linked hospital records in Hospital Episode Statistics. Patients were matched with up to four patients without SMI. Primary outcomes were emergency and planned physical health admissions. Avoidable (ambulatory care sensitive) admissions and emergency admissions for accidents, injuries and substance misuse were secondary outcomes. We performed negative binomial regression, adjusted for clinical and demographic variables, stratified by SMI diagnosis. RESULTS: Emergency physical health (aIRR:2.33; 95% CI 2.22-2.46) and avoidable (aIRR:2.88; 95% CI 2.60-3.19) admissions were higher in patients with SMI than comparators. Emergency admission rates did not differ by SMI diagnosis. Planned physical health admissions were lower in schizophrenia (aIRR:0.80; 95% CI 0.72-0.90) and higher in bipolar disorder (aIRR:1.33; 95% CI 1.24-1.43). Accident, injury and substance misuse emergency admissions were particularly high in the year after SMI diagnosis (aIRR: 6.18; 95% CI 5.46-6.98). CONCLUSION: We found twice the incidence of emergency physical health admissions in patients with SMI compared to those without SMI. Avoidable admissions were particularly elevated, suggesting interventions in community settings could reduce hospitalisations. Importantly, we found underutilisation of planned inpatient care in patients with schizophrenia. Interventions are required to ensure appropriate healthcare use, and optimal diagnosis and treatment of physical health conditions in people with SMI, to reduce the mortality gap due to physical illness

Podoconiosis and soil-transmitted helminths (STHs): double burden of neglected tropical diseases in Wolaita zone, rural southern Ethiopia

Background Both podoconiosis and soil-transmitted helminth (STH) infections occur among barefoot people in areas of extreme poverty; however, their co-morbidity has not previously been investigated. We explored the overlap of STH infection and podoconiosis in Southern Ethiopia and quantified their separate and combined effects on prevalent anemia and hemoglobin levels in podoconiosis patients and health controls from the same area. Methods and Principal Findings A two-part comparative cross-sectional study was conducted in Wolaita zone, southern Ethiopia. Data were collected from adult patients presenting with clinically confirmed podoconiosis, and unmatched adult neighborhood controls living in the same administrative area. Information on demographic and selected lifestyle factors was collected using interviewer-administered questionnaires. Stool samples were collected and examined qualitatively using the modified formalin-ether sedimentation method. Hemoglobin level was determined using two different methods: hemoglobinometer and automated hematology analyzer. A total of 913 study subjects (677 podoconiosis patients and 236 controls) participated. The prevalence of any STH infection was 47.6% among patients and 33.1% among controls (p<0.001). The prevalence of both hookworm and Trichuris trichiura infections was significantly higher in podoconiosis patients than in controls (AOR 1.74, 95% CI 1.25 to2.42, AOR 6.53, 95% CI 2.34 to 18.22, respectively). Not wearing shoes and being a farmer remained significant independent predictors of infection with any STH. There was a significant interaction between STH infection and podoconiosis on reduction of hemoglobin level (interaction p value = 0.002). Conclusions Prevalence of any STH and hookworm infection was higher among podoconiosis patients than among controls. A significant reduction in hemoglobin level was observed among podoconiosis patients co-infected with hookworm and ‘non-hookworm STH’. Promotion of consistent shoe-wearing practices may have double advantages in controlling both podoconiosis and hookworm infection in the study area

The impact of comorbid severe mental illness and common chronic physical health conditions on hospitalisation: A systematic review and meta-analysis

BACKGROUND: People with severe mental illness (SMI) are at higher risk of physical health conditions compared to the general population, however, the impact of specific underlying health conditions on the use of secondary care by people with SMI is unknown. We investigated hospital use in people managed in the community with SMI and five common physical long-term conditions: cardiovascular diseases, COPD, cancers, diabetes and liver disease. METHODS: We performed a systematic review and meta-analysis (Prospero: CRD42020176251) using terms for SMI, physical health conditions and hospitalisation. We included observational studies in adults under the age of 75 with a diagnosis of SMI who were managed in the community and had one of the physical conditions of interest. The primary outcomes were hospital use for all causes, physical health causes and related to the physical condition under study. We performed random-effects meta-analyses, stratified by physical condition. RESULTS: We identified 5,129 studies, of which 50 were included: focusing on diabetes (n = 21), cardiovascular disease (n = 19), COPD (n = 4), cancer (n = 3), liver disease (n = 1), and multiple physical health conditions (n = 2). The pooled odds ratio (pOR) of any hospital use in patients with diabetes and SMI was 1.28 (95%CI:1.15-1.44) compared to patients with diabetes alone and pooled hazard ratio was 1.19 (95%CI:1.08-1.31). The risk of 30-day readmissions was raised in patients with SMI and diabetes (pOR: 1.18, 95%CI:1.08-1.29), SMI and cardiovascular disease (pOR: 1.27, 95%CI:1.06-1.53) and SMI and COPD (pOR:1.18, 95%CI: 1.14-1.22) compared to patients with those conditions but no SMI. CONCLUSION: People with SMI and five physical conditions are at higher risk of hospitalisation compared to people with that physical condition alone. Further research is warranted into the combined effects of SMI and physical conditions on longer-term hospital use to better target interventions aimed at reducing inappropriate hospital use and improving disease management and outcomes

Common evidence gaps in point-of-care diagnostic test evaluation: a review of horizon scan reports

Objective: Since 2008, the Oxford Diagnostic Horizon Scan Programme has been identifying and summarising evidence on new and emerging diagnostic technologies relevant to primary care. We used these reports to determine the sequence and timing of evidence for new point-of-care diagnostic tests and to identify common evidence gaps in this process. Design: Systematic overview of diagnostic horizon scan reports. Primary outcome measures: We obtained the primary studies referenced in each horizon scan report (n=40) and extracted details of the study size, clinical setting and design characteristics. In particular, we assessed whether each study evaluated test accuracy, test impact or cost-effectiveness. The evidence for each point-of-care test was mapped against the Horvath framework for diagnostic test evaluation. Results: We extracted data from 500 primary studies. Most diagnostic technologies underwent clinical performance (ie, ability to detect a clinical condition) assessment (71.2%), with very few progressing to comparative clinical effectiveness (10.0%) and a cost-effectiveness evaluation (8.6%), even in the more established and frequently reported clinical domains, such as cardiovascular disease. The median time to complete an evaluation cycle was 9 years (IQR 5.5–12.5 years). The sequence of evidence generation was typically haphazard and some diagnostic tests appear to be implemented in routine care without completing essential evaluation stages such as clinical effectiveness. Conclusions: Evidence generation for new point-of-care diagnostic tests is slow and tends to focus on accuracy, and overlooks other test attributes such as impact, implementation and cost-effectiveness. Evaluation of this dynamic cycle and feeding back data from clinical effectiveness to refine analytical and clinical performance are key to improve the efficiency of point-of-care diagnostic test development and impact on clinically relevant outcomes. While the ‘road map’ for the steps needed to generate evidence are reasonably well delineated, we provide evidence on the complexity, length and variability of the actual process that many diagnostic technologies undergo