Metformin for the prevention of diabetes among people with HIV and either impaired fasting glucose or impaired glucose tolerance (prediabetes) in Tanzania: a Phase II randomised placebo-controlled trial.

AIMS/HYPOTHESIS: In sub-Saharan Africa (SSA), 5% of adults are living with type 2 diabetes and this is rising sharply, with a greater increase among people with HIV. Evidence on the efficacy of prevention strategies in this cohort is scarce. We conducted a Phase II double-blind placebo-controlled trial that aimed to determine the impact of metformin on blood glucose levels among people with prediabetes (defined as impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT]) and HIV in SSA. METHODS: Adults (≥18 years old) who were stable in HIV care and found to have prediabetes (IFG and/or IGT) and who were attending hospitals in Dar es Salaam, Tanzania, were randomised to receive sustained-release metformin, 2000 mg daily, or matching placebo between 4 November 2019 and 21 July 2020. Randomisation used permuted blocks. Allocation was concealed in the trial database and made visible only to the Chief Pharmacist after consent was taken. All participants, research and clinical staff remained blinded to the allocation. Participants were provided with information on diet and lifestyle and had access to various health information following the start of the coronavirus disease 2019 (COVID-19) pandemic. Participants were followed up for 12 months. The primary outcome measure was capillary blood glucose measured 2 h following a 75 g glucose load. Analyses were by intention-to-treat. RESULTS: In total, 364 participants (182 in each arm) were randomised to the metformin or placebo group. At enrolment, in the metformin and placebo arms, mean fasting glucose was 6.37 mmol/l (95% CI 6.23, 6.50) and 6.26 mmol/l (95% CI 6.15, 6.36), respectively, and mean 2 h glucose levels following a 75 g oral glucose load were 8.39 mmol/l (95% CI 8.22, 8.56) and 8.24 mmol/l (95% CI 8.07, 8.41), respectively. At the final assessment at 12 months, 145/182 (79.7%) individuals randomised to metformin compared with 158/182 (86.8%) randomised to placebo indicated that they had taken >95% of their medicines in the previous 28 days (p=0.068). At this visit, in the metformin and placebo arms, mean fasting glucose levels were 6.17 mmol/l (95% CI 6.03, 6.30) and 6.30 mmol/l (95% CI 6.18, 6.42), respectively, and mean 2 h glucose levels following a 75 g oral glucose load were 7.88 mmol/l (95% CI 7.65, 8.12) and 7.71 mmol/l (95% CI 7.49, 7.94), respectively. Using a linear mixed model controlling for respective baseline values, the mean difference between the metformin and placebo group (metformin-placebo) was -0.08 mmol/l (95% CI -0.37, 0.20) for fasting glucose and 0.20 mmol/l (95% CI -0.17, 0.58) for glucose levels 2 h post a 75 g glucose load. Weight was significantly lower in the metformin arm than in the placebo arm: using the linear mixed model adjusting for baseline values, the mean difference in weight was -1.47 kg (95% CI -2.58, -0.35). In total, 16/182 (8.8%) individuals had a serious adverse event (Grade 3 or Grade 4 in the Division of Acquired Immunodeficiency Syndrome [DAIDS] adverse event grading table) or died in the metformin arm compared with 18/182 (9.9%) in the placebo arm; these events were either unrelated to or unlikely to be related to the study drugs. CONCLUSIONS/INTERPRETATION: Blood glucose decreased over time in both the metformin and placebo arms during the trial but did not differ significantly between the arms at 12 months of follow up. Metformin therapy was found to be safe for use in individuals with HIV and prediabetes. A larger trial with longer follow up is needed to establish if metformin can be safely used for the prevention of diabetes in people who have HIV. TRIAL REGISTRATION: The trial is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry ( www.isrctn.com/ ), registration number: ISCRTN76157257. FUNDING: This research was funded by the National Institute for Health Research using UK aid from the UK Government to support global health research.

Retention in care for type 2 diabetes management in Sub-Saharan Africa: A systematic review.

OBJECTIVE: Diabetes prevalence has risen rapidly in Sub-Saharan Africa, but rates of retention in diabetes care are poorly understood. We conducted a systematic review and meta-analysis to determine rates of retention in care of persons with type 2 diabetes. METHODS: We searched MEDLINE, Global Health and CINAHL online databases for cohort studies and randomised control trials (RCTs) published up to 12 October 2021, that reported retention in or attrition from care for patients with type 2 diabetes in Sub-Saharan Africa. Retention was defined as persons diagnosed with diabetes who were alive and in care or with a known outcome, while attrition was defined as loss from care. RESULTS: From 6559 articles identified, after title and abstract screening, 209 articles underwent full text review. Forty six papers met the inclusion criteria, comprising 22,610 participants. Twenty one articles were of RCTs of which 8 trials had 1 year or more of follow-up and 25 articles were of non-randomised studies of which 19 had 12 months or more of follow-up. A total of 11 studies (5 RCTs and 6 non-randomised) were assessed to be of good quality. Sixteen RCTs were done in secondary or tertiary care settings. Their pooled retention rate (95% CI) was 80% (77%, 84%) in the control arm. Four RCTs had been done in primary care settings and their pooled retention rate (95% CI) was 53% (45%, 62%) in the control arm. The setting of one trial was unclear. For non-randomised studies, retention rates (95% CI) were 68% (62%, 75%) among 19 studies done in secondary and tertiary care settings, and 40% (33%, 49%) among the 6 studies done in primary care settings. CONCLUSION: Rates of retention in care of people living with diabetes are poor in primary care research settings.

Marked Increase in Avidity of SARS-CoV-2 Antibodies 7-8 Months After Infection Is Not Diminished in Old Age.

The kinetics of immunoglobulin G (IgG) avidity maturation during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection obtained from 217 participants of the Ischgl cohort, Austria, was studied 0.5-1.5 months (baseline) and 7-8 months (follow-up) after infection. The IgG avidity assay, using a modified IgG enzyme-linked immunosorbent assay (ELISA) and 5.5 M urea, revealed that old age does not diminish the increase in avidity, detected in all participants positive at both time points, from 18% to 42%. High avidity was associated with a marked residual neutralization capacity in 97.2.% of participants (211/217), which was even higher in the older age group, revealing an important role of avidity assays as easy and cheap surrogate tests for assessing the maturation of the immune system conveying potential protection against further SARS-CoV-2 infections without necessitating expensive and laborious neutralization assays.

Pharmacological management of modifiable cardiovascular risk factors (blood pressure and lipids) following diagnosis of myocardial infarction, stroke and diabetes: comparison between population-based studies in Russia and Norway.

BACKGROUND: Cardiovascular disease (CVD) mortality is substantially higher in Russia than in neighbouring Norway. We aimed to compare blood pressure- and lipid-lowering medication use and proportion meeting treatment targets between general population samples in the two countries in those with CVD and diabetes. METHODS: The study population was adults aged 40-69 years reporting a diagnosis of myocardial infarction (MI), stroke and/or diabetes participating in cross-sectional population-based studies in Russia (Know Your Heart (KYH) 2015-18 N = 626) and Norway (The Tromsø Study 2015-16 (Tromsø 7) N = 1353). Reported medications were coded according to the 2016 WHO Anatomical Therapeutic Chemical Classification system. Treatment targets were defined using the Joint European Societies guidelines for CVD prevention in clinical practice (2016). RESULTS: Age- and sex-standardized prevalence of use of lipid-lowering medications was higher in Tromsø 7 for all three conditions with a disproportionately large difference in those reporting MI (+ 48% (95% CI 39, 57%)). Proportion meeting treatment targets for LDL cholesterol was poor in both studies (age- and sex-standardized prevalence of control KYH vs Tromsø 7: MI 5.1% vs 10.1%; stroke 11.6% vs 5.8%; diabetes 24.9% vs 23.3%). Use of antihypertensive medication was higher in KYH for stroke (+ 40% (95% CI 30, 50%)) and diabetes (+ 27% (95% CI 19, 34%)) groups but approximately equal for the MI group (- 1% (95% CI -1, 1%)). Proportion meeting blood pressure targets was lower in KYH vs Tromsø 7 (MI 51.8% vs 76.3%; stroke 49.5% vs 69.6%; diabetes 51.9% vs 63.9%). CONCLUSIONS: We identified different patterns of medication use in people with CVD and diabetes. However despite higher use of lipid-lowering medication in the Norwegian study treatment to target for total cholesterol was poor in both Russian and Norwegian studies. In contrast we found higher levels of use of antihypertensive medications in the Russian study but also that less participants met treatment targets for blood pressure. Further work should investigate what factors are responsible for this seeming paradox and how management of modifiable risk factors for secondary prevention could be improved.

Impacts of rapid mass vaccination against SARS-CoV2 in an early variant of concern hotspot.

We study the real-life effect of an unprecedented rapid mass vaccination campaign. Following a large outbreak of the Beta variant in the district of Schwaz/Austria, 100,000 doses of BNT162b2 (Pfizer/BioNTech) were procured to mass vaccinate the entire adult population of the district between the 11th and 16th of March 2021. This made the district the first widely inoculated region in Europe. We examine the effect of this campaign on the number of infections, cases of variants of concern, hospital and ICU admissions. We compare Schwaz with (i) a control group of highly similar districts, and (ii) with populations residing in municipalities along the border of Schwaz which were just excluded from the campaign. We find large and significant decreases for all outcomes after the campaign. Our results suggest that rapid mass vaccination is an effective tool to curb the spread of SARS-CoV-2.

Impact of aortic root repair or replacement in severe destructive aortic valve endocarditis with paravalvular abscesses on long-term survival.

OBJECTIVES: Surgical treatment of destructive infective endocarditis consists of extensive debridement followed by root repair or replacement. However, it remains unknown whether 1 is superior to the other. We aimed to analyse whether long-term results were better after root repair or replacement in patients with root endocarditis. METHODS: A total of 148 consecutive patients with root endocarditis treated with surgery from 1997 to 2020 at our department were included. Patients were divided into 2 groups: aortic root repair (n = 85) or root replacement using xenografts or homografts (n = 63). RESULTS: Patients receiving aortic root repair showed significantly better long-term survival compared to patients receiving aortic root replacement (log-rank: P = 0.037). There was no difference in terms of freedom from valvular reoperations among both treatment groups (log-rank: P = 0.58). Patients with aortic root repair showed higher freedom from recurrent endocarditis compared to patients with aortic root replacement (log-rank: P = 0.022). Patients with aortic root repair exhibited higher event-free survival (defined as a combination end point of freedom from death, valvular reoperation or recurrent endocarditis) compared to patients receiving aortic root replacement (log-rank: P = 0.022). Age increased the risk of mortality with 1.7% per year. Multi-variable adjusted statistical analysis revealed improved long-term event-free survival after aortic root repair (hazards ratio: 0.57, 95% confidence interval: 0.39-0.95; P = 0.031). CONCLUSIONS: Aortic root repair and replacement are feasible options for the surgical treatment of root endocarditis and are complementary methods, depending on the extent of infection. Patients with less advanced infection have a more favourable prognosis. CLINICAL TRIAL REGISTRATION: UN4232 382/3.1 (retrospective study).

Hypofractionated and single-fraction radiosurgery for brain metastases with sex as a key predictor of overall survival.

Overall survival (OS) of patients with brain metastases treated with hypofractionated (HFSRT) or single-fraction (SRS) radiosurgery depends on several prognostic factors. The aim of this study was to investigate the potential of sex as an independent predictor of OS and evaluate the predictive accuracy of common prognostic scores. Retrospective analysis of 281 consecutive patients receiving radiosurgery of brain metastases was performed. Kaplan-Meier survival curves and Cox proportional hazards models were used to compare OS between SRS and HFSRT and by sex, before and after propensity-score matching (PSM) on key baseline prognostic covariates. Prognostic scores were evaluated using Harrell's concordance index. Median OS was 11 months after both SRS and HFSRT. After PSM, median OS was 12 months after SRS (95% CI: 7.5-16.5) and 9 months after HFSRT (95% CI: 5.0-13.0; p = 0.77). Independent prognostic factors were sex, primary tumor, KPI, and systemic disease status. Median OS was 16 months for women and 7 months for male patients (p < 0.001). After excluding sex specific tumors, PSM revealed a median OS of 16 months for women and 8 months for male patients (p < 0.01). Evaluation of prognostic indices showed BSBM to be the most accurate (Harrell's C = 0.68), followed by SIR (0.61), GPA (0.60), RPA (0.58), and Rades et al. (0.57). OS after HFSRT and SRS did not differ, although PSM revealed a non-significant advantage for SRS. Female sex was found to be a major independent positive prognostic factor for survival, and thus should be considered in the personalized decision-making of brain metastases treatment.

Persistence of immunity to SARS-CoV-2 over time in the ski resort Ischgl.

Background In early March 2020, a SARS-CoV-2 outbreak in the ski resort Ischgl in Austria triggered the spread of SARS-CoV-2 throughout Austria and Northern Europe. In a previous study, we found that the seroprevalence in the adult population of Ischgl had reached 45% by the end of April, representing an exceptionally high level of local seropositivity in Europe. We performed a follow-up study in Ischgl, which is the first to show persistence of immunity and protection against SARS-CoV-2 and some of its variants at a community level. Methods Of the 1259 adults that participated in the baseline study, 801 have been included in the follow-up in November 2020. The study involved the analysis of binding and neutralizing antibodies and T cell responses. In addition, the incidence of SARS-CoV-2 and its variants in Ischgl was compared to the incidence in similar municipalities in Tyrol until April 2021. Findings For the 801 individuals that participated in both studies, the seroprevalence declined from 51.4% (95% confidence interval (CI) 47.9-54.9) to 45.4% (95% CI 42.0-49.0). Median antibody concentrations dropped considerably (5.345, 95% CI 4.833 - 6.123 to 2.298, 95% CI 2.141 - 2.527) but antibody avidity increased (17.02, 95% CI 16.49 - 17.94 to 42.46, 95% CI 41.06 - 46.26). Only one person had lost detectable antibodies and T cell responses. In parallel to this persistent immunity, we observed that Ischgl was relatively spared, compared to similar municipalities, from the prominent second COVID-19 wave that hit Austria in November 2020. In addition, we used sequencing data to show that the local immunity acquired from wild-type infections also helped to curb infections from variants of SARS-CoV-2 which spread in Austria since January 2021. Interpretation The relatively high level of seroprevalence (40-45%) in Ischgl persisted and might have been associated with the observed protection of Ischgl residents against virus infection during the second COVID-19 wave as well as against variant spread in 2021. Funding Funding was provided by the government of Tyrol and the FWF Austrian Science Fund.

High SARS-CoV-2 seroprevalence in children and adults in the Austrian ski resort of Ischgl.

BACKGROUND: In early March 2020, a SARS-CoV-2 outbreak in the ski resort Ischgl in Austria initiated the spread of SARS-CoV-2 throughout Austria and Northern Europe. METHODS: Between April 21st and 27th 2020, a cross-sectional epidemiologic study targeting the full population of Ischgl (n = 1867), of which 79% could be included (n = 1473, incl. 214 children), was performed. For each individual, the study involved a SARS-CoV-2 PCR, antibody testing and structured questionnaires. A mathematical model was used to help understand the influence of the determined seroprevalence on virus transmission. RESULTS: The seroprevalence was 42.4% (95% confidence interval (CI) 39.8-44.7). Individuals under 18 showed a significantly lower seroprevalence of 27.1% (95% CI 21.3-33.6) than adults (45%; 95% CI 42.2-47.7; OR of 0.455, 95% CI 0.356-0.682, p < 0.001). Of the seropositive individuals, 83.7% had not been diagnosed to have had SARS-CoV-2 infection previously. The clinical course was generally mild. Over the previous two months, two COVID-19-related deaths had been recorded, corresponding to an infection fatality rate of 0.25% (95% CI 0.03-0.91). Only 8 (0.5 %) individuals were newly diagnosed to be infected with SARS-CoV-2 during this study. CONCLUSIONS: Ischgl was hit early and hard by SARS-CoV-2 leading to a high local seroprevalence of 42.4%, which was lower in individuals below the age of 18 than in adults. Mathematical modeling suggests that a drastic decline of newly infected individuals in Ischgl by the end of April occurred due to the dual impact from the non-pharmacological interventions and a high immunization of the Ischgl population.

Quality improvement in hospitals in the Russian Federation, 2000-2016: a systematic review.

We reviewed published evidence on quality improvement in hospitals in the Russian Federation since 2000. We used three data sources: MEDLINE, 'Rossiiskaia Meditsina' (Central Scientific Medical Library), and elibrary.ru using specific search terms. No language or study design restrictions were imposed. In total, 1717 articles were identified; 51 met the inclusion criteria and were thematically analysed. Russian legislation, government acts and grey literature were sourced to contextualise identified themes. Since 2010, the Federal Ministry of Health has increasingly sought to improve quality of care, providing additional resources and new initiatives across the health system. These include clinical practice guidelines, pay for performance schemes, electronic medical records, more specialist care, paraclinical care, and quality control systems. Quality of care, increasingly a concern of the Russian government, is said to be improving. Yet most initiatives have rarely been evaluated. This reflects the limited capacity for health services research in Russia. It seems likely that the full potential for improvements in quality of care in Russia is still to be realised.

Cardiac catherization in Austria : Results from the Austrian National Cardiac Catheterization Laboratory Registry (ANCALAR) 2012-2018.

BACKGROUND: Cardiac catheterization is one of the most widely performed cardiac interventional procedures worldwide. The Austrian National Catheterization Laboratory Registry (ANCALAR), started in 1992, collects annual data on cardiac catheterization in Austria. The registry enables in-depth understanding of the dynamics of cardiac catheterization procedures and their use across 34 cardiac catheterization laboratories in Austria. METHODS: Data from ANCALAR on cardiac catheterization including the latest data for 2017, voluntarily provided by centers with cardiac catheterization laboratories, were analyzed. Where possible, international comparisons in therapeutic and interventional cardiac procedures are made with Switzerland and Germany. RESULTS: Internationally, Austria ranks alongside the top countries in Europe. Whilst the number of people undergoing routine percutaneous coronary interventions (PCI) remains stable, complex and acute interventions are increasing year by year in Austria. CONCLUSION: Evidence from ANCALAR revealed that Austria is another example of the difficulties of weighing current guidelines with new emerging evidence and resulting real-life clinical practice in the dynamic world of interventional cardiology.

Management of patients with acute ST-segment elevation myocardial infarction in Russian hospitals adheres to international guidelines.

Objective: Russia has one of the highest cardiovascular mortality rates. Modernisation of the Russian health system has been accompanied by a substantial increase in uptake of percutaneous coronary intervention (PCI), which substantially reduces the risk of mortality in patients with acute ST-elevation myocardial infarction (STEMI). This paper aims to describe contemporary Hospital treatment of acute STEMI among patients in a range of hospitals in the Russian Federation. Methods: This study used data from a prospective observational cohort of 1128 suspected patients with myocardial infarction recruited in both PCI and non-PCI hospitals across 13 regions and multiple levels of the health system in Russia. The primary objective was to examine the use of reperfusion strategies in patients with STEMI. Results: Among patients reaching PCI centres within 12 hours of symptom onset, the vast majority received angiography and PCI, regardless of age, sex and comorbidity, in line with current European Society of Cardiology guidelines. Conclusion: Patients reaching Russian hospitals are very likely to receive appropriate treatment, although performance varies. The best hospitals can serve as beacons of good practice as PCI facilities continue to expand across Russia where geography allows.

Positive family history of cardiovascular disease and long-term outcomes after coronary artery bypass grafting: a genetic paradox?

OBJECTIVES: Parental cardiovascular disease (CVD) is a known risk factor for premature CVD. It is unknown whether a positive family history (PFH) affects outcomes after coronary artery bypass grafting (CABG). METHODS: Data come from a retrospective longitudinal study of CABG patients consecutively recruited from 2001 to 2018 (n = 5389). From this study, 2535 patients with premature CVD undergoing CABG under the age of 60 years and information on parental CVD were identified. The Framingham offspring study criteria were used to identify PFH of CVD. Multivariable Cox proportional hazards regression models were used to assess the effect of PFH on overall and major adverse cardiovascular and cerebrovascular event-free survival. RESULTS: A total of 273 deaths and 428 major adverse cardiovascular and cerebrovascular events occurred during follow-up. PFH of CVD was found in 54.2% of patients (n = 1375). Within these patients, 66.1% had a father who experienced a premature cardiovascular event (n = 909), 27.8% a mother (n = 382) and 6.1% both a mother and a father (n = 84). In the majority of cases, the patient's parent had experienced a cardiac event (85.9%, n = 1181) and 14.1% of patients with PFH reported parental stroke (n = 194). Following CABG, PFH was associated with improved overall [adjusted hazards ratio (HR) 0.67, 95% confidence interval (CI) 0.50-0.90; P = 0.008] and major adverse cardiovascular and cerebrovascular event-free survival (adjusted HR 0.73, 95% CI 0.68-0.89; P = 0.01). Among the covariates adjusted for age, diabetes, renal insufficiency, peripheral arterial disease, ejection fraction, previous cerebrovascular events and previous mediastinal radiation were all associated with poorer outcomes. CONCLUSIONS: Although it is well established that a PFH increases the risk of requiring CABG at younger ages, this study shows that, paradoxically, PFH is also protective regarding long-term outcomes. REGISTRATION NUMBER LOCAL IRB: UN4232 297/4.3 (retrospective study).

Endocarditis-related stroke is not a contraindication for early cardiac surgery: an investigation among 440 patients with left-sided endocarditis.

OBJECTIVES: A treatment dilemma arises when surgery is indicated in patients with infective endocarditis (IE) complicated by stroke. Neurologists recommend surgery to be postponed for at least 1 month. This study aims to investigate the neurological complication rate and neurological recovery potential in patients with IE-related stroke. METHODS: A total of 440 consecutive patients with left-sided IE undergoing surgery were investigated. During follow-up, neurological recovery was assessed using the modified Rankin scale and the Barthel index. Mortality was assessed with regression models adjusting for age. RESULTS: The median follow-up time was 9.0 years. Patients with previous strokes were more likely to suffer from mitral valve endocarditis (29.5% vs 47.4%, P < 0.001). Symptomatic stroke was found in 135 (30.7%) patients; of them, 42 patients presented with complicated stroke (additional meningitis, haemorrhagic stroke or intracranial abscess). Driven by symptomatic stroke, the age-adjusted hospital mortality risk was 1.4-fold [95% confidence interval (CI) 0.74-2.57; P = 0.31] higher and the long-term mortality risk was 1.4-fold higher (95% CI 1.003-2.001; P = 0.048). Hospital mortality was higher in patients with complicated stroke (21.4% vs 9.7%; P = 0.06) only; however, mortality rates were similar comparing uncomplicated stroke versus no stroke. Among patients with complicated ischaemic strokes, the observed risk for intraoperative cerebral haemorrhage was 2.3% only and the increased hospital mortality was not driven by cerebral complications. In the long-term follow-up, full neurological recovery was observed in 84 out of 118 survivors (71.2%), and partial recovery was observed in 32 (27.1%) patients. Neurological recovery was lower in patients with complete middle cerebral artery stroke compared to other localization (52.9% vs 77.6%; P = 0.003). CONCLUSIONS: Contrary to current clinical practice and neurological recommendations, early surgery in IE is safe and neurological recovery is excellent among patients with IE-related stroke. CLINICAL REGISTRATION NUMBER LOCAL IRB: UN4232 382/3.1 (retrospective study).

Organ-Sparing Surgery in Testicular Tumor: Is This the Right Approach for Lesions ≤ 20 mm?

Background: This study was conducted in order to analyze factors predicting malignancy in patients undergoing organ-sparing surgery (OSS) for small testicular lesions. Methods: Patients with small (£20 mm) marker-negative clinical stage I testicular tumors were managed by OSS with tumor enucleation and frozen section examination (FSE) for the past 15 years at our institution. Benign and malignant cases were compared, focusing on preoperative and postoperative lesion sizes. Results: Eighty-nine patients were enrolled in this retrospective study. Ten (11.2%) of them were treated for synchronous bilateral tumors. Sixty-seven (67.7%) of ninety-nine lesions were benign, confirming a high concordance rate (98%) between FSE and final histology. Patients with benign tumors were significantly older than patients with malignant tumors (p = 0.026), and benign tumors were detected more frequently during urologic work-up of hormone disorders (p = 0.001). Preoperative tumor size was a strong predictor of malignancy (area under the curve (AUC) = 0.726; p < 0.001). According to the Youden index, the best cutoff to predict tumor dignity was 13.5 mm, resulting in a sensitivity and specificity of 53% and 85%, respectively. No cases of local recurrence or distant metastasis were confirmed after a median follow-up of 42 months. Conclusion: Our findings are consistent with previous reports, supporting an OSS approach in small testicular tumors whenever possible. Most tumors ≤ 20 mm were benign, and in the case of malignancy, OSS with FSE and consecutive orchiectomy is oncologically safe due to the high concordance rate of FSE and final histology, thus preventing a two-stage procedure.

Understanding the role of physicians within the managerial structure of Russian hospitals.

This article examines the role of physicians within the managerial structure of Russian hospitals. A comparative qualitative methodology with a structured assessment framework is used to conduct case studies that allow for international comparison. The research is exploratory in nature and comprises 63 individual interviews and 49 focus groups with key informants in 15 hospitals, complemented by document analysis. The material was collected between February and April 2017 in five different regions of the Russian Federation. The results reveal three major problems of hospital management in the Russian Federation. First, hospitals exhibit a leaky system of coordination with a lack of structures for horizontal exchange of information within the hospitals (meso-level). Second, at the macro-level, the governance system includes implementation gaps, lacking mechanisms for coordination between hospitals that may reinforce existing inequalities in service provision. Third, there is little evidence of a learning culture, and consequently, a risk that the same mistakes could be made repeatedly. We argue for a new approach to governing hospitals that can guide implementation of structures and processes that allow systematic and coherent coordination within and among Russian hospitals, based on modern approaches to accountability and organisational learning.

Binding nucleophiles to [Fe4Y4Cl4](2-) (Y = S or Se) can increase or suppress the rate of proton transfer to the cluster.

In the proton transfer reactions between [Fe 4Y 4Cl 4] (2-) (Y = S or Se) and [pyrH] (+) (pyr = pyrrolidine) in the presence of a variety of nucleophiles (L = I (-), Br (-), PhS (-), EtS (-) or ButNC), initial binding of the nucleophile can occur to generate [Fe 4Y 4Cl 4(L)] ( n- ). The subsequent rate of proton transfer depends markedly on the nature of L. Stopped-flow kinetic studies show that proton transfer from [pyrH] (+) to [Fe 4Y 4Cl 4] (2-) { (S) k 4 = (2.1 +/- 0.5) x 10 (4) dm (3) mol (-1) s (-1); (Se) k 4 = (8.0 +/- 0.5) x 10 (3) dm (3) mol (-1) s (-1)} is increased by prior binding of L = PhS (-) or Bu ( t )NC to form [Fe 4Y 4Cl 4(L)] (n-) ( (S) k 7 (L) approximately 1 x 10 (6) dm (3) mol (-1) s (-1)), but prior binding of L = I (-), Br (-), or EtS (-) to the clusters inhibits the rate of proton transfer {e.g. (S) k 7 (I) = (6.0 +/- 0.8) x 10 (2) dm (3) mol (-1) s (-1); (Se) k 7 (I) = (4.5 +/- 0.5) x 10 (2) dm (3) mol (-1) s (-1)}. This behavior is correlated with the bonding characteristics of L and the effect this has on bond length reorganization within the cluster upon proton transfer.

Double burden or double counting of child malnutrition? The methodological and theoretical implications of stuntingoverweight in low and middle income countries.

BACKGROUND: There is increasing concern at research and policy levels about the double burden of child malnutrition (DBCM)-with stunting and overweight found across different groups of children. Despite some case studies suggesting that stunting and overweight can occur concurrently in children, here known as 'stuntingoverweight', and major drives to reduce all forms of malnutrition in low and middle income countries (LMICs), stuntingoverweight is continually overlooked. This research evidences the prevalence of stuntingoverweight across LMICs, exploring the theoretical and methodological implications of failing to acknowledge this form of malnutrition. METHODS: Prevalence estimates of stuntingoverweight are constructed from 79 LMICs with nationally representative anthropometric survey data. Stunting and overweight estimates are amended to exclude stuntedoverweight children. These estimates are compared with those published in the Joint Child Malnutrition Estimates (JMEs)-evidencing overestimation and double counting of stuntedoverweight children. RESULTS: Children can be concurrently stunted and overweight. Stuntedoverweight children are found in all LMICs, from 0.3% to 11.7% of under-fives and are included in both stunting and overweight rates. Analysed together, this leads to double counting of stuntedoverweight children. This artificial inflation of stunting and overweight rates can give a false impression of a DBCM, obscuring the true diversity of malnutrition present. Over 10 million children are stuntedoverweight in the world. CONCLUSIONS: Stuntingoverweight is a newly recognised, understudied phenomenon. Affected children are included in both stunting and overweight prevalence estimates, introducing unobserved heterogeneity to both individual-level and population-level research and double counting to population-level research. Overlooking stuntedoverweight children has great implications for methodology, theory, policies, programmes and the health of affected children.