Reference values and clinical predictors of bone strength for HR-pQCT-based distal radius and tibia strength assessments in women and men.

Reference values for radius and tibia strength using multiple-stack high-resolution peripheral quantitative computed tomography (HR-pQCT) with homogenized finite element analysis are presented in order to derive critical values improving risk prediction models of osteoporosis. Gender and femoral neck areal bone mineral density (aBMD) were independent predictors of bone strength. INTRODUCTION The purpose was to obtain reference values for radius and tibia bone strength computed by using the homogenized finite element analysis (hFE) using multiple stacks with a HR-pQCT. METHODS Male and female healthy participants aged 20-39 years were recruited at the University Hospital of Bern. They underwent interview and clinical examination including hand grip, gait speed and DXA of the hip. The nondominant forearm and tibia were scanned with a double and a triple-stack protocol, respectively, using HR-pQCT (XCT II, SCANCO Medical AG). Bone strength was estimated by using the hFE analysis, and reference values were calculated using quantile regression. Multivariable analyses were performed to identify clinical predictors of bone strength. RESULTS Overall, 46 women and 41 men were recruited with mean ages of 25.1 (sd 5.0) and 26.2 (sd 5.2) years. Sex-specific reference values for bone strength were established. Men had significantly higher strength for radius (mean (sd) 6640 (1800) N vs. 4110 (1200) N; p < 0.001) and tibia (18,200 (4220) N vs. 11,970 (3150) N; p < 0.001) than women. In the two multivariable regression models with and without total hip aBMD, the addition of neck hip aBMD significantly improved the model (p < 0.001). No clinical predictors of bone strength other than gender and aBMD were identified. CONCLUSION Reference values for radius and tibia strength using multiple HR-pQCT stacks with hFE analysis are presented and provide the basis to help refining accurate risk prediction models. Femoral neck aBMD and gender were significant predictors of bone strength

Non-Hodgkin lymphoma risk in adults living with HIV across five continents: a multicohort study

OBJECTIVE: To compare non-Hodgkin lymphoma (NHL) incidence rates in adults who started antiretroviral therapy (ART) across the Asia-Pacific, South Africa, Europe, Latin, and North America. METHODS: We included cohort data of adults living with HIV who started ART after 1995 within the framework of the International epidemiology Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE). We used flexible parametric survival models to compare regional NHL rates at 2 years after ART start and to identify risk factors for NHL. RESULTS: We included 210,898 adults with 1.1 million person-years (pys) of follow-up and 1,552 incident NHL cases (raw overall incidence rate 142/100,000 pys). After adjusting for age at ART start, first-line ART regimen, calendar period of ART start, and especially current CD4 cell count, NHL rates were similar across regions for most population groups. However, South African women remained at increased risk of developing NHL compared with their European counterparts (adjusted hazard ratio [aHR] 1.79, 95% CI 1.19-2.70). In Europe, Latin and North America, NHL risk was highest in men who have sex with men (MSM, aHR 1.30, 95% CI 1.14-1.48), followed by heterosexual men (referent), and women (aHR 0.66, 95% CI 0.57-0.78). CONCLUSIONS: The risk of developing NHL is higher in women in South Africa than in Europe and higher in MSM compared with heterosexual men and women. Reasons for these differences remain unclear. Early ART access and regular patient monitoring to avert low CD4 cell counts remain key for NHL prevention

Forecasting future crop suitability with microclimate data

This is the final version. Available on open access from Elsevier via the DOI in this recordContext: Against a background of unprecedented climate change, humanity faces the challenge of how to increase global food production without compromising the natural environment. Crop suitability models can indicate the best locations to grow different crops and, in doing so, support efficient use of land to leave space for, or share space with, nature. However, challenges in downscaling the climate data needed to drive these models to make predictions for the future has meant that they are often run using national or regional climate projections. At finer spatial scales, variation in climate conditions can have a substantial influence on yield and so the continued use of coarse resolution climate data risks maladaptive agricultural decisions. Opportunities to grow novel crops, for which knowledge of local variation in microclimate may be critical, may be missed. Objective: We demonstrate how microclimate information can be acquired for a region and used to run a mechanistic crop suitability model under present day and possible future climate scenarios. Methods: We use microclimate modelling techniques to generate 100 m spatial resolution climate datasets for the south-west of the UK for present day (2012–2017) and predicted future (2042–2047) time periods. We use these data to run the mechanistic crop model WOrld FOod STudies (WOFOST) for 56 crop varieties, which returns information on maximum crop yields for each planting month. Results and conclusions: Over short distances, we find that the highest attainable yields vary substantially and discuss how these differences mean that field-level assessments of climate suitability could support land-use decisions, enabling food production whilst protecting biodiversity. Significance: We provide code for running WOFOST in the WofostR R package, thus enabling integration with microclimate models and meaning that our methodology could be applied anywhere in the world. As such, we make available to anyone the tools to predict climate suitability for crops at high spatial resolution for both present day and possible future climate scenarios.Natural Environment Research Council (NERC)European Regional Development Fund (ERDF)Cornwall CouncilCouncil for the Isles of Scill

Effectiveness of Transition Care Intervention Targeted to High-Risk Patients to Reduce Readmissions: Study Protocol for the TARGET-READ Multicenter Randomized-Controlled Trial.

Hospital readmissions within 30 days represent a burden for the patients and the entire health care system. Improving the care around hospital discharge period could decrease the risk of avoidable readmissions. We describe the methods of a trial that aims to evaluate the effect of a structured multimodal transitional care intervention targeted to higher-risk medical patients on 30-day unplanned readmissions and death. The TARGET-READ study is an investigator-initiated, pragmatic single-blinded randomized multicenter controlled trial with two parallel groups. We include all adult patients at risk of hospital readmission based on a simplified HOSPITAL score of ≥4 who are discharged home or nursing home after a hospital stay of one day or more in the department of medicine of the four participating hospitals. The patients randomized to the intervention group will receive a pre-discharge intervention by a study nurse with patient education, medication reconciliation, and follow-up appointment with their referring physician. They will receive short follow-up phone calls at 3 and 14 days after discharge to ensure medication adherence and follow-up by the ambulatory care physician. A blind study nurse will collect outcomes at 1 month by phone call interview. The control group will receive usual care. The TARGET-READ study aims to increase the knowledge about the efficacy of a bundled intervention aimed at reducing 30-day hospital readmission or death in higher-risk medical patients

Cohort profile: the South African HIV Cancer Match (SAM) study, a national population-based cohort

Purpose The South African HIV Cancer Match (SAM) Study is a national cohort of people living with HIV (PLWH). It was created using probabilistic record linkages of routine laboratory records of PLWH retrieved by National Health Laboratory Services (NHLS) and cancer data from the National Cancer Registry. The SAM Study aims to assess the spectrum and risk of cancer in PLWH in the context of the evolving South African HIV epidemic. The SAM Study's overarching goal is to inform cancer prevention and control programmes in PLWH in the era of antiretroviral treatment in South Africa. Participants PLWH (both adults and children) who accessed HIV care in public sector facilities and had HIV diagnostic or monitoring laboratory tests from NHLS. Findings to date The SAM cohort currently includes 5 248 648 PLWH for the period 2004 to 2014; 69% of these are women. The median age at cohort entry was 33.0 years (IQR: 26.2-40.9). The overall cancer incidence in males and females was 235.9 (95% CI: 231.5 to 240.5) and 183.7 (181.2-186.2) per 100 000 person-years, respectively. Using data from the SAM Study, we examined national cancer incidence in PLWH and the association of different cancers with immunodeficiency. Cancers with the highest incidence rates were Kaposi sarcoma, cervix, breast, non-Hodgkin's lymphoma and eye cancer. Future plans The SAM Study is a unique, evolving resource for research and surveillance of malignancies in PLWH. The SAM Study will be regularly updated. We plan to enrich the SAM Study through record linkages with other laboratory data within the NHLS (eg, tuberculosis, diabetes and lipid profile data), mortality data and socioeconomic data to facilitate comprehensive epidemiological research of comorbidities among PLWH

Cervical cancer screening cascade for women living with HIV: a cohort study from Zimbabwe

Countries with high HIV prevalence, predominantly in sub-Sahahran Africa, have the highest cervical cancer rates globally. HIV care cascades successfully facilitated the scale-up of antiretroviral therapy. A cascade approach could similarly succeed to scale-up cervical cancer screening, supporting WHO's goal to eliminate cervical cancer. We defined a Cervical Cancer Screening Cascade for women living with HIV (WLHIV), evaluating the continuum of cervical cancer screening integrated into an HIV clinic in Zimbabwe. We included WLHIV aged ≥18 years enrolled at Newlands Clinic in Harare from June 2012-2017 and followed them until June 2018. We used a cascade approach to evaluate the full continuum of secondary prevention from screening to treatment of pre-cancer and follow-up. We report percentages, median time to reach cascade stages, and cumulative incidence at two years with 95% confidence intervals (CI). We used univariable Cox proportional hazard regressions to calculate cause-specific hazard ratios with 95% CIs for factors associated with completing the cascade stages. We included 1624 WLHIV in the study. The cumulative incidence of cervical screening was 85.4% (95% CI 83.5-87.1) at two years. Among the 396 WLHIV who received screen-positive tests in the study, the cumulative incidence of treatment after a positive screening test was 79.5% (95% CI 75.1-83.2) at two years. The cumulative incidence of testing negative at re-screening after treatment was 36.1% (95% CI 31.2-40.7) at two years. Using a cascade approach to evaluate the full continuum of cervical cancer screening, we found less-than 80% of WLHIV received treatment after screen-positive tests and less-than 40% were screen-negative at follow-up. Interventions to improve linkage to treatment for screen-positive WLHIV and studies to understand the clinical significance of screen-positive tests at follow-up among WLHIV are needed. These gaps in the continuum of care must be addressed in order to prevent cervical cancer

Effect of biomechanical footwear on knee pain in people with knee osteoarthritis : the BIOTOK randomized clinical trial

Importance: Individually calibrated biomechanical footwear therapy may improve pain and physical function in people with symptomatic knee osteoarthritis, but the benefits of this therapy are unclear. Objective: To assess the effect of a biomechanical footwear therapy vs control footwear over 24 weeks of follow-up. Design, Setting, and Participants: Randomized clinical trial conducted at a Swiss university hospital. Participants (N = 220) with symptomatic, radiologically confirmed knee osteoarthritis were recruited between April 20, 2015, and January 10, 2017. The last participant visit occurred on August 15, 2017. Interventions: Participants were randomized to biomechanical footwear involving shoes with individually adjustable external convex pods attached to the outsole (n = 111) or to control footwear (n = 109) that had visible outsole pods that were not adjustable and did not create a convex walking surface. Main Outcomes and Measures: The primary outcome was knee pain at 24 weeks of follow-up assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscore standardized to range from 0 (no symptoms) to 10 (extreme symptoms). The secondary outcomes included WOMAC physical function and stiffness subscores and the WOMAC global score, all ranging from 0 (no symptoms) to 10 (extreme symptoms) at 24 weeks of follow-up, and serious adverse events. Results: Among the 220 randomized participants (mean age, 65.2 years [SD, 9.3 years]; 104 women [47.3%]), 219 received the allocated treatment and 213 (96.8%) completed follow-up. At 24 weeks of follow-up, the mean standardized WOMAC pain subscore improved from 4.3 to 1.3 in the biomechanical footwear group and from 4.0 to 2.6 in the control footwear group (between-group difference in scores at 24 weeks of follow-up, -1.3 [95% CI, -1.8 to -0.9]; P < .001). The results were consistent for WOMAC physical function subscore (between-group difference, -1.1 [95% CI, -1.5 to -0.7]), WOMAC stiffness subscore (between-group difference, -1.4 [95% CI, -1.9 to -0.9]), and WOMAC global score (between-group difference, -1.2 [95% CI, -1.6 to -0.8]) at 24 weeks of follow-up. Three serious adverse events occurred in the biomechanical footwear group compared with 9 in the control footwear group (2.7% vs 8.3%, respectively); none were related to treatment. Conclusions and Relevance: Among participants with knee pain from osteoarthritis, use of biomechanical footwear compared with control footwear resulted in an improvement in pain at 24 weeks of follow-up that was statistically significant but of uncertain clinical importance. Further research would be needed to assess long-term efficacy and safety, as well as replication, before reaching conclusions about the clinical value of this device

Intra-hospital differences in antibiotic use correlate with antimicrobial resistance rate in <i>Escherichia coli</i> and <i>Klebsiella pneumoniae</i>: a retrospective observational study.

Monitoring antimicrobial use and resistance in hospitals are important tools of antimicrobial stewardship programs. We aimed to determine the association between the use of frequently prescribed antibiotics and the corresponding resistance rates in &lt;i&gt;Escherichia coli&lt;/i&gt; and &lt;i&gt;Klebsiella pneumoniae&lt;/i&gt; among the clinical departments of a tertiary care hospital. We performed a retrospective observational study to analyse the use of nine frequently prescribed antibiotics and the corresponding antimicrobial resistance rates in hospital acquired &lt;i&gt;E. coli&lt;/i&gt; and &lt;i&gt;K. pneumoniae&lt;/i&gt; isolates from 18 departments of our institution over 9 years (2008-2016). The main cross-sectional analysis assessed the hypothetical influence of antibiotic consumption on resistance by mixed logistic regression models. We found an association between antibiotic use and resistance rates in &lt;i&gt;E. coli&lt;/i&gt; for amoxicillin-clavulanic acid (OR per each step of 5 defined daily dose/100 bed-days 1.07, 95% CI 1.02-1.12; &lt;i&gt;p&lt;/i&gt;  = 0.004), piperacillin-tazobactam (OR 2.11, 95% CI 1.45-3.07; &lt;i&gt;p&lt;/i&gt;  &lt; 0.001), quinolones (OR 1.52, 95% CI 1.25-1.86; &lt;i&gt;p&lt;/i&gt;  &lt; 0.001) and trimethoprim-sulfamethoxazole (OR 1.59, 95% CI 1.19-2.13; &lt;i&gt;p&lt;/i&gt;  = 0.002). Additionally, we found a significant association when all nine antibiotics were combined in one analysis. The association between consumption and resistance rates was stronger for nosocomial than for community strains. In &lt;i&gt;K. pneumoniae,&lt;/i&gt; we found an association for amoxicillin-clavulanic acid (OR 1.07, 95% CI 1.01-1.14; &lt;i&gt;p&lt;/i&gt;  = 0.025) and for trimethoprim-sulfamethoxazole (OR 2.02, 95% CI 1.44-2.84; &lt;i&gt;p&lt;/i&gt;  &lt; 0.001). The combined analysis did not show an association between consumption and resistance (OR 1.06, 95% CI 0.99-1.14; &lt;i&gt;p&lt;/i&gt;  = 0.07). We documented an association between antibiotic use and resistance rate for amoxicillin-clavulanic acid, piperacillin-tazobactam, quinolones and trimethoprim-sulfamethoxazole in &lt;i&gt;E. coli&lt;/i&gt; and for amoxicillin-clavulanic acid and trimethoprim-sulfamethoxazole in &lt;i&gt;K. pneumoniae&lt;/i&gt; across different hospital departments. Our data will support stewardship interventions to optimize antibiotic prescribing at a department level

Comparison of codes assessing galactic cosmic radiation exposure of aircraft crew

The assessment of the exposure to cosmic radiation onboard aircraft is one of the preoccupations of bodies responsible for radiation protection. Cosmic particle flux is significantly higher onboard aircraft than at ground level and its intensity depends on the solar activity. The dose is usually estimated using codes validated by the experimental data. In this paper, a comparison of various codes is presented, some of them are used routinely, to assess the dose received by the aircraft crew caused by the galactic cosmic radiation. Results are provided for periods close to solar maximum and minimum and for selected flights covering major commercial routes in the world. The overall agreement between the codes, particularly for those routinely used for aircraft crew dosimetry, was better than ±20 % from the median in all but two cases. The agreement within the codes is considered to be fully satisfactory for radiation protection purpose

Major Surface Glycoproteins of Insect Forms of Trypanosoma brucei Are Not Essential for Cyclical Transmission by Tsetse

Procyclic forms of Trypanosoma brucei reside in the midgut of tsetse flies where they are covered by several million copies of glycosylphosphatidylinositol-anchored proteins known as procyclins. It has been proposed that procyclins protect parasites against proteases and/or participate in tropism, directing them from the midgut to the salivary glands. There are four different procyclin genes, each subject to elaborate levels of regulation. To determine if procyclins are essential for survival and transmission of T. brucei, all four genes were deleted and parasite fitness was compared in vitro and in vivo. When co-cultured in vitro, the null mutant and wild type trypanosomes (tagged with cyan fluorescent protein) maintained a near-constant equilibrium. In contrast, when flies were infected with the same mixture, the null mutant was rapidly overgrown in the midgut, reflecting a reduction in fitness in vivo. Although the null mutant is patently defective in competition with procyclin-positive parasites, on its own it can complete the life cycle and generate infectious metacyclic forms. The procyclic form of T. brucei thus differs strikingly from the bloodstream form, which does not tolerate any perturbation of its variant surface glycoprotein coat, and from other parasites such as Plasmodium berghei, which requires the circumsporozoite protein for successful transmission to a new host