Short-term and long-term cardiovascular risk, metabolic syndrome and HIV in Tanzania.

OBJECTIVE: To compare short-term and long-term cardiovascular disease (CVD) risk scores and prevalence of metabolic syndrome in HIV-infected adults receiving and not receiving antiretroviral therapy (ART) to HIV-negative controls. METHODS: A cross-sectional study including 151 HIV-infected, ART-naive, 150 HIV-infected on ART and 153 HIV-negative adults. Traditional cardiovascular risk factors were determined by standard investigations. The primary outcome was American College of Cardiology/American Heart Association Atherosclerotic CVD (ASCVD) Risk Estimator lifetime CVD risk score. Secondary outcomes were ASCVD 10-year risk, Framingham risk scores, statin indication and metabolic syndrome. RESULTS: Compared with HIV-negative controls, more HIV-infected adults on ART were classified as high lifetime CVD risk (34.7% vs 17.0%, p<0.001) although 10-year risk scores were similar, a trend which was similar across multiple CVD risk models. In addition, HIV-infected adults on ART had a higher prevalence of metabolic syndrome versus HIV-negative controls (21.3% vs 7.8%, p=0.008), with two common clusters of risk factors. More than one-quarter (28.7%) of HIV-infected Tanzanian adults on ART meet criteria for statin initiation. CONCLUSIONS: HIV-infected ART-treated individuals have high lifetime cardiovascular risk, and this risk seems to develop rapidly in the first 3-4 years of ART as does the development of clusters of metabolic syndrome criteria. These data identify a new subgroup of low short-term/high-lifetime risk HIV-infected individuals on ART who do not currently meet criteria for CVD risk factor modification but require further study

Oesophageal varices, schistosomiasis, and mortality among patients admitted with haematemesis in Mwanza, Tanzania: a prospective cohort study.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a common cause of hospital admissions worldwide. Aetiologies vary by sociodemographics and geography. Retrospective studies of endoscopies in much of Africa have documented oesophageal varices as a leading cause of UGIB. Prospective studies describing outcomes and associations with clinical factors are lacking. METHODS: We conducted a prospective cohort study at a referral hospital in Mwanza, Tanzania where schistosomiasis is endemic. Adults admitted with haematemesis underwent laboratory workup, schistosomiasis antigen testing and elective endoscopy, and were followed for two months for death or re-bleeding. We assessed predictors of endoscopic findings using logistic regression models, and determined prediction rules that maximised sensitivity and positive predictive value (PPV). RESULTS: Of 124 enrolled patients, 13 died within two months (10%); active schistosomiasis prevalence was 48%. 64/91(70%) patients had oesophageal varices. We found strong associations between varices and numerous demographic or clinical findings, permitting construction of simple, high-fidelity prediction rules for oesophageal varices applicable even in rural settings. Portal vein diameter ≥ 13 mm or water sourced from the lake yielded sensitivity, specificity, PPV and NPV >90% for oesophageal varices; presence of splenomegaly or water sourced from the lake maintained sensitivity and PPV >90%. CONCLUSIONS: Our results guide identification of patients, via ultrasound and clinical examination, likely to have varices for whom referral for endoscopy may be life-saving. Furthermore, they support empiric anti-schistosome treatment for patients with UGIB in schistosome-endemic regions. These interventions have potential to reduce UGIB-related morbidity and mortality in Africa

Local Instrumental Variable Methods to Address Confounding and Heterogeneity when Using Electronic Health Records: An Application to Emergency Surgery

BACKGROUND: Electronic health records (EHRs) offer opportunities for comparative effectiveness research to inform decision making. However, to provide useful evidence, these studies must address confounding and treatment effect heterogeneity according to unmeasured prognostic factors. Local instrumental variable (LIV) methods can help studies address these challenges, but have yet to be applied to EHR data. This article critically examines a LIV approach to evaluate the cost-effectiveness of emergency surgery (ES) for common acute conditions from EHRs. METHODS: This article uses hospital episodes statistics (HES) data for emergency hospital admissions with acute appendicitis, diverticular disease, and abdominal wall hernia to 175 acute hospitals in England from 2010 to 2019. For each emergency admission, the instrumental variable for ES receipt was each hospital's ES rate in the year preceding the emergency admission. The LIV approach provided individual-level estimates of the incremental quality-adjusted life-years, costs and net monetary benefit of ES, which were aggregated to the overall population and subpopulations of interest, and contrasted with those from traditional IV and risk-adjustment approaches. RESULTS: The study included 268,144 (appendicitis), 138,869 (diverticular disease), and 106,432 (hernia) patients. The instrument was found to be strong and to minimize covariate imbalance. For diverticular disease, the results differed by method; although the traditional approaches reported that, overall, ES was not cost-effective, the LIV approach reported that ES was cost-effective but with wide statistical uncertainty. For all 3 conditions, the LIV approach found heterogeneity in the cost-effectiveness estimates across population subgroups: in particular, ES was not cost-effective for patients with severe levels of frailty. CONCLUSIONS: EHRs can be combined with LIV methods to provide evidence on the cost-effectiveness of routinely provided interventions, while fully recognizing heterogeneity. HIGHLIGHTS: This article addresses the confounding and heterogeneity that arise when assessing the comparative effectiveness from electronic health records (EHR) data, by applying a local instrumental variable (LIV) approach to evaluate the cost-effectiveness of emergency surgery (ES) versus alternative strategies, for patients with common acute conditions (appendicitis, diverticular disease, and abdominal wall hernia).The instrumental variable, the hospital's tendency to operate, was found to be strongly associated with ES receipt and to minimize imbalances in baseline characteristics between the comparison groups.The LIV approach found that, for each condition, there was heterogeneity in the estimates of cost-effectiveness according to baseline characteristics.The study illustrates how an LIV approach can be applied to EHR data to provide cost-effectiveness estimates that recognize heterogeneity and can be used to inform decision making as well as to generate hypotheses for further research

AnemoCheck-LRS: An optimized, color-based point-of-care test to identify severe anemia in limited-resource settings

BACKGROUND: Severe anemia is common and frequently fatal for hospitalized patients in limited-resource settings. Lack of access to low-cost, accurate, and rapid diagnosis of anemia impedes the delivery of life-saving care and appropriate use of the limited blood supply. The WHO Haemoglobin Colour Scale (HCS) is a simple low-cost test but frequently inaccurate. AnemoCheck-LRS (limited-resource settings) is a rapid, inexpensive, color-based point-of-care (POC) test optimized to diagnose severe anemia. METHODS: Deidentified whole blood samples were diluted with plasma to create variable hemoglobin (Hb) concentrations, with most in the severe (≤ 7 g/dL) or profound (≤ 5 g/dL) anemia range. Each sample was tested with AnemoCheck-LRS and WHO HCS independently by three readers and compared to Hb measured by an electronic POC test (HemoCue 201 RESULTS: For 570 evaluations within the limits of detection of AnemoCheck-LRS (Hb ≤ 8 g/dL), the average difference between AnemoCheck-LRS and measured Hb was 0.5 ± 0.4 g/dL. In contrast, the WHO HCS overestimated Hb with an absolute difference of 4.9 ± 1.3 g/dL for samples within its detection range (Hb 4-14 g/dL, n = 405). AnemoCheck-LRS was much more sensitive (92%) for the diagnosis of profound anemia than WHO HCS (22%). CONCLUSIONS: AnemoCheck-LRS is a rapid, inexpensive, and accurate POC test for anemia. AnemoCheck-LRS is more accurate than WHO HCS for detection of low Hb levels, severe anemia that may require blood transfusion. AnemoCheck-LRS should be tested prospectively in limited-resource settings where severe anemia is common, to determine its utility as a screening tool to identify patients who may require transfusion

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Elevated <scp>CO₂</scp> interacts with nutrient inputs to restructure plant communities in phosphorus‐limited grasslands

AbstractGlobally pervasive increases in atmospheric CO2 and nitrogen (N) deposition could have substantial effects on plant communities, either directly or mediated by their interactions with soil nutrient limitation. While the direct consequences of N enrichment on plant communities are well documented, potential interactions with rising CO2 and globally widespread phosphorus (P) limitation remain poorly understood. We investigated the consequences of simultaneous elevated CO2 (eCO2) and N and P additions on grassland biodiversity, community and functional composition in P‐limited grasslands. We exposed soil‐turf monoliths from limestone and acidic grasslands that have received &gt;25 years of N additions (3.5 and 14 g m−2 year−1) and 11 (limestone) or 25 (acidic) years of P additions (3.5 g m−2 year−1) to eCO2 (600 ppm) for 3 years. Across both grasslands, eCO2, N and P additions significantly changed community composition. Limestone communities were more responsive to eCO2 and saw significant functional shifts resulting from eCO2–nutrient interactions. Here, legume cover tripled in response to combined eCO2 and P additions, and combined eCO2 and N treatments shifted functional dominance from grasses to sedges. We suggest that eCO2 may disproportionately benefit P acquisition by sedges by subsidising the carbon cost of locally intense root exudation at the expense of co‐occurring grasses. In contrast, the functional composition of the acidic grassland was insensitive to eCO2 and its interactions with nutrient additions. Greater diversity of P‐acquisition strategies in the limestone grassland, combined with a more functionally even and diverse community, may contribute to the stronger responses compared to the acidic grassland. Our work suggests we may see large changes in the composition and biodiversity of P‐limited grasslands in response to eCO2 and its interactions with nutrient loading, particularly where these contain a high diversity of P‐acquisition strategies or developmentally young soils with sufficient bioavailable mineral P.</jats:p

Care in the time of catastrophe: citizenship, community and the ecological imagination

Published without an abstract

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial

Background Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. Methods In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. Findings Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18–45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference −1·4%, 95% CI −7·0 to 4·3; hazard ratio 0·96, 0·68–1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3–4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). Interpretation Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia