Effects of hypoglycaemic agents on reducing surrogate metabolic parameters for the prevention of cardiovascular events and death in patients with type 2 diabetes: A systematic review and meta-analysis.

AIMS: To investigate the impact of glucose-lowering therapy-induced glycated haemoglobin (HbA1c) reduction on the risk of major clinical events according to body weight change and, as a secondary objective, to evaluate the impact of concomitant reductions in HbA1c and body weight on major clinical events. MATERIALS AND METHODS: We searched the MEDLINE and EMBASE databases up to June 30, 2022, for large-scale studies on glucose-lowering therapies in which more than 1000 patient-years of follow-up in each randomized group were completed. The primary outcome was all-cause mortality. The study was registered in PROSPERO (CRD42022355479). RESULTS: Thirty-four trials involving 227 220 patients with type 2 diabetes were meta-analysed using a random-effects model. Each 1% reduction in HbA1c was associated with a different risk of mortality depending on the ability of glucose-lowering therapies to induce body weight loss or gain. When glucose-lowering therapies were associated with weight gain, the risk of mortality increased by 8% (hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.00-1.16) for each 1% reduction in HbA1c. When glucose-lowering therapies were associated with weight loss, the risk of mortality was reduced by 22% (HR 0.78, 95% CI 0.72-0.85) for each 1% reduction in HbA1c. In addition, concomitant reductions in HbA1c and body weight were associated with a significantly lower risk of mortality and vascular events. CONCLUSIONS: In patients with type 2 diabetes, concomitant reductions in HbA1c and body weight might be more effective in preventing the risk of vascular events and mortality.

Co-existence of depression and post-concussion syndrome one month after mild traumatic brain injury.

BACKGROUND: Previous studies suggest an association between Post-concussion syndrome (PCS) and depression, both highly prevalent after mTBI. OBJECTIVE: To assess the prevalence and risk-factors of depression among patients with PCS 1 month after mTBI. METHODS: We prospectively screened 372 mTBI patients admitted in two academic Emergency Departments between 2017 and 2019. One month after mTBI, we administered the Rivermead Post-concussion symptoms Questionnaire (RPQ) and the Patient Health Questionnaire (PHQ-9) questionnaires over the telephone. PCS and depression were defined by RPQ ≥ 12 and PHQ-9 ≥ 10. Multivariate multinomial regression identified baseline factors associated with PCS and depression. RESULTS: Two hundred and eight completed RPQ and PHQ-9. Forty-seven patients (22.5%) met criteria for PCS, among which 22 (46.8%) met criteria for depression (PCS+D+). Patients with PCS but without depression were less likely to present with an associated injury (Coefficient = -1.6, p = 0.047) and to report initial sadness (Coefficient = -2.5, p = 0.03). Initial sadness (Coefficient = -1.3, p = 0.047), associated injury (Coefficient = -1.9, p = 0.008), as well as initial nausea (Coefficient = -1.8, p = 0.002), and male sex (Coefficient = 1.8, p = 0.002), were associated with the absence of depression and PCS in comparison with PCS+D+ patients. CONCLUSION: Among patients with PCS 1 month after mTBI, those with depression are more likely to present with initial sadness and with an associated injury.

Larger effect size in composite kidney outcomes than in major cardiovascular events associated with sodium-glucose cotransporter-2 (SGLT2) inhibitors compared with glucagon-like peptide-1 receptor agonists (GLP-1RAs): A pooled analysis of type 2 diabetes trials.

AIM: To compare treatment effect sizes between a composite kidney outcome (CKO) and three-point major adverse cardiovascular event (MACE-3) outcomes with use of sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs), and to investigate the relationship between treatment effects on CKO and MACE-3 in patients with type 2 diabetes (T2D). MATERIALS AND METHODS: We performed a MEDLINE database search up to December 31, 2021 to identify all placebo-controlled Phase 3 trials which investigated the efficacy of glucose-lowering interventions, and selected those reporting results for CKO and MACE-3. Hazard ratios (HRs) with 95% confidence intervals (CIs) for both outcomes were extracted for each trial, and we evaluated differences in treatment effect sizes by using a ratio of HRs (rHR): the HR for CKO to the HR for MACE-3. A random-effects meta-analysis was used to obtain the overall rHR across trials and according to subgroup. We investigated the relationship between treatment effects on CKO and MACE-3 using the coefficient of determination (R2 ) with weighted meta-regression. The study protocol was registered on PROSPERO (CRD42022299690). RESULTS: A total of 12 studies fulfilled the prespecified criteria, and comprised a total of 104 987 patients with T2D. On average, treatment effect sizes were 17% greater for CKO than for MACE-3 (rHR 0.83, 95% CI 0.74 to 0.92; I2  = 50%; P = 0.03; τ2  = 0.0161), especially for trials of SGLT2 inhibitors compared with GLP-1RAs. For secondary outcomes, treatment effect size was 22%, 21%, 16% and 9% greater for CKO than for myocardial infarction, stroke, death from cardiovascular causes, and hospitalization for heart disease, respectively. MACE-3 and CKO were moderately correlated (ρ = 0.40; P = 0.21), and only 11% (95% CI 1% to 54%) of the variability in the MACE-3 effect could be explained by the variability in the CKO effect. CONCLUSION: In T2D patients, treatment effect sizes were greater for kidney than for macrovascular (MACE-3) outcomes, with important differences according to the drugs considered. CKO and MACE-3 are independent. Caution must be taken when interpreting CKO in the absence of MACE-3 data.

Development of SARAhome , a New Video-Based Tool for the Assessment of Ataxia at Home.

BACKGROUND: Clinical scales such as the Scale for the Assessment and Rating of Ataxia (SARA) cannot be used to study ataxia at home or to assess daily fluctuations. The objective of the current study was to develop a video-based instrument, SARAhome , for measuring ataxia severity easily and independently at home. METHODS: Based on feasibility of self-application, we selected 5 SARA items (gait, stance, speech, nose-finger test, fast alternating hand movements) for SARAhome (range, 0-28). We compared SARAhome items with total SARA scores in 526 patients with spinocerebellar ataxia types 1, 2, 3, and 6 from the EUROSCA natural history study. To prospectively validate the SARAhome , we directly compared the self-applied SARAhome and the conventional SARA in 50 ataxia patients. To demonstrate feasibility of independent home recordings in a pilot study, 12 ataxia patients were instructed to obtain a video each morning and evening over a period of 14 days. All videos were rated offline by a trained rater. RESULTS: SARAhome extracted from the EUROSCA baseline data was highly correlated with conventional SARA (r = 0.9854, P < 0.0001). In the prospective validation study, the SARAhome was highly correlated with the conventional SARA (r = 0.9254, P < 0.0001). Five of 12 participants of the pilot study obtained a complete set of 28 evaluable videos. Seven participants obtained 13-27 videos. The intraindividual differences between the lowest and highest SARAhome scores ranged from 1 to 5.5. CONCLUSION: The SARAhome and the conventional SARA are highly correlated. Application at home is feasible. There was a considerable degree of intraindividual variability of the SARAhome scores. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Different profiles of body mass index variation among patients with multidrug-resistant tuberculosis: a retrospective cohort study.

BACKGROUND: Despite the predictive role of body weight variation in treatment outcome in multidrug-resistant tuberculosis (MDR-TB), few corroborating data are available. We studied weight variation in patients with MDR-TB to identify groups of weight change and to determine factors that influence these changes. METHODS: We analyzed patients with rifampicin resistance who were treated with an MDR-TB treatment regimen between June 07, 2016 and June 22, 2018 at three major drug-resistant TB centers in Guinea. Patients were seen monthly until the end of treatment. Clinical outcome was the body mass index (BMI). We used a linear mixed model to analyze trajectories of BMI and a latent class mixed model to identify groups of BMI trajectories. RESULTS: Of 232 patients treated for MDR-TB during the study period, 165 were analyzed. These patients had a total of 1387 visits, with a median of 5 visits (interquartile range, 3-8 visits). Monthly BMI increase was 0.24 (SE 0.02) per kg/m2. Factors associated with faster BMI progression were success of MDR-TB treatment (0.24 [SE 0.09] per kg/m2; p = 0.0205) and absence of lung cavities on X-ray (0.18 [0.06] per kg/m2; p = 0.0068). Two groups of BMI change were identified: rapid BMI increase (n = 121; 85%) and slow BMI increase (n = 22; 15%). Patients in the slow BMI increase group were mostly female (68%) had no history of TB treatment (41%), had a positive HIV infection (59%), and had a more severe clinical condition at baseline, characterized by a higher frequency of symptoms including depression (18%), dyspnea (68%), poor adherence to MDR-TB treatment (64%), lower platelet count, and higher SGOT. These patients also had a longer time to initial culture conversion (log-rank test: p = 0.0218). CONCLUSION: Quantitative BMI data on patients with MDR-TB treated with a short regimen allowed the identification of subgroups of patients with different trajectories of BMI and emphasized the usefulness of BMI as a biomarker for the monitoring of MDR-TB treatment outcome.

Prediction of Survival With Long-Term Disease Progression in Most Common Spinocerebellar Ataxia.

BACKGROUND: Spinocerebellar ataxias are rare dominantly inherited neurodegenerative diseases that lead to severe disability and premature death. OBJECTIVE: To quantify the impact of disease progression measured by the Scale for the Assessment and Rating of Ataxia on survival, and to identify different profiles of disease progression and survival. METHODS: Four hundred sixty-two spinocerebellar ataxia patients from the EUROSCA prospective cohort study, suffering from spinocerebellar ataxia type 1, spinocerebellar ataxia type 2, spinocerebellar ataxia type 3, and spinocerebellar ataxia type 6, and who had at least two measurements of Scale for the Assessment and Rating of Ataxia score, were analyzed. Outcomes were change over time in Scale for the Assessment and Rating of Ataxia score and time to death. Joint model was used to analyze disease progression and survival. RESULTS: Disease progression was the strongest predictor for death in all genotypes: An increase of 1 standard deviation in total Scale for the Assessment and Rating of Ataxia score increased the risk of death by 1.28 times (95% confidence interval: 1.18-1.38) for patients with spinocerebellar ataxia type 1; 1.19 times (1.12-1.26) for spinocerebellar ataxia type 2; 1.30 times (1.19-1.42) for spinocerebellar ataxia type 3; and 1.26 times (1.11-1.43) for spinocerebellar ataxia type 6. Three subgroups of disease progression and survival were identified for patients with spinocerebellar ataxia type 1: "severe" (n = 13; 12%), "intermediate" (n = 31; 29%), and "moderate" (n = 62; 58%). Patients in the severe group were more severely affected at baseline with higher Scale for the Assessment and Rating of Ataxia scores and frequency of nonataxia signs compared to those in the other groups. CONCLUSION: Rapid ataxia progression is associated with poor survival of the most common spinocerebellar ataxia. Theses current results have implications for the design of future interventional studies of spinocerebellar ataxia. © 2019 International Parkinson and Movement Disorder Society.

Phase II Trial of Bevacizumab in Combination With Temozolomide as First-Line Treatment in Patients With Metastatic Uveal Melanoma.

BACKGROUND: In experimental models, bevacizumab suppressed in vitro growth and in vivo hepatic metastasis of ocular melanoma cells. Additional preclinical data suggested a potential benefit when combining bevacizumab with dacarbazine. METHODS: This noncomparative phase II study evaluated a combination of bevacizumab (10 mg/kg on days 8 and 22) with temozolomide (150 mg/m(2) on days 1-7 and 15-21) in 36 patients with metastatic uveal melanoma (MUM). The primary endpoint was the progression-free rate (PFR) at 6 months. Using a modified 2-step Fleming plan, at least 10 of 35 patients were required to support a predefined PFR at 6 months of 40%. Secondary objectives were progression-free survival (PFS), overall survival (OS), and safety; liver perfusion computed tomography (CT) for response imaging; and impact of VEGF-A gene polymorphisms on bevacizumab pharmacodynamics. RESULTS: First- and second-step analyses revealed nonprogression at 6 months in 3 of 17 and 8 of 35 patients, respectively. Finally, the 6-month PFR was 23% (95% confidence interval [CI]: 10-39), with long-lasting stable disease in 5 patients (14%). Median PFS and OS were 12 weeks and 10 months, respectively. No unexpected toxicity occurred. Liver perfusion CT imaging was not useful in assessing tumor response, and VEGF-A gene polymorphisms were not correlated with toxicity or survival. CONCLUSION: In patients with MUM, a combination of bevacizumab plus temozolomide achieved a 6-month PFR of 23%.

Traumatic Life Events, Violence, and Obesity: A Cross-Sectional Study from 408 Patients Enrolled in a Bariatric Surgery Program.

INTRODUCTION: Obesity is a chronic disease that increases cardiovascular and metabolic morbidity and mortality, decreases quality of life, and increases health care costs. While the role of lifestyle behavioral factors in the development of obesity is well established, the role of traumatic life events, including violence, is unclear. The purpose of this study was to describe situations of traumatic life events reported by patients undergoing a bariatric surgery program, with a particular focus on sexual violence and its clinical correlates. METHODS: In this cross-sectional study, patients with grade II or III obesity, admitted to our digestive surgery department for bariatric surgery from August 01, 2019, to December 31, 2020, underwent a structured interview by a trained psychologist to describe the history of traumatic life events self-reported by the patients. The primary endpoint was the presence of a history of sexual violence (SV). Multivariate logistic regressions were applied to identify independent risk factors for SV. RESULTS: Of the 408 patients interviewed, 87.1% reported at least one traumatic life event and 33.1% reported having had an SV in the past. Female gender (aOR = 7.44, 95% confidence interval: 3.85-15.73; p < 0.001) and higher body mass index (1.05, 1.02-1.08; p = 0.002) were associated with an increased risk of SV. Male gender was associated with a higher risk of difficulties including sports cessation, depression, and work-related distress. CONCLUSION: In the context of obesity, psychosocial trauma is characterized by a high frequency and several gender specificities that must be taken into account in the management of these patients.

Prevalence and factors associated with maternal and neonatal sepsis in sub-Saharan Africa: a systematic review and meta-analysis.

Objectives: This study aimed to determine the prevalence and factors associated with maternal and neonatal sepsis in sub-Saharan Africa. Methods: This systematic review and meta-analysis used the PRISMA guideline on sepsis data in sub-Saharan Africa. The bibliographic search was carried out on the following databases: Medline/PubMed, Cochrane Library, African Index Medicus, and Google Scholar. Additionally, the reference lists of the included studies were screened for potentially relevant studies. The last search was conducted on 15 October 2022. The Joanna Briggs Institute quality assessment checklist was applied for critical appraisal. Estimates of the prevalence of maternal and neonatal sepsis were pooled using a random-effects meta-analysis model. Heterogeneity between studies was estimated using the Q statistic and the I2 statistic. The funnel plot and Egger's regression test were used to assess the publication bias. Results: A total of 39 studies were included in our review: 32 studies on neonatal sepsis and 7 studies on maternal sepsis. The overall pooled prevalence of maternal and neonatal sepsis in Sub-Saharan Africa was 19.21% (95% CI, 11.46-26.97) and 36.02% (CI: 26.68-45.36), respectively. The meta-analyses revealed that Apgar score < 7 (OR: 2.4, 95% CI: 1.6-3.5), meconium in the amniotic fluid (OR: 2.9, 95% CI: 1.8-4.5), prolonged rupture of membranes >12 h (OR: 2.8, 95% CI: 1.9-4.1), male sex (OR: 1.2, 95% CI: 1.1-1.4), intrapartum fever (OR: 2.4, 95% CI: 1.5-3.7), and history of urinary tract infection in the mother (OR: 2.7, 95% CI: 1.4-5.2) are factors associated with neonatal sepsis. Rural residence (OR: 2.3, 95% CI: 1.01-10.9), parity (OR: 0.5, 95% CI: 0.3-0.7), prolonged labor (OR: 3.4, 95% CI: 1.6-6.9), and multiple digital vaginal examinations (OR: 4.4, 95% CI: 1.3-14.3) were significantly associated with maternal sepsis. Conclusion: The prevalence of maternal and neonatal sepsis was high in sub-Saharan Africa. Multiple factors associated with neonatal and maternal sepsis were identified. These factors could help in the prevention and development of strategies to combat maternal and neonatal sepsis. Given the high risk of bias and high heterogeneity, further high-quality research is needed in the sub-Saharan African context, including a meta-analysis of individual data.Systematic review registration: PROSPERO (ID: CRD42022382050).

Blood pressure-lowering effects of SGLT2 inhibitors and GLP-1 receptor agonists for preventing of cardiovascular events and death in type 2 diabetes: a systematic review and meta-analysis.

AIMS: To investigate the lowering BP effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) on the risk of major cardiovascular event stratified by glucose-lowering drugs, baseline BP, glycated hemoglobin (HbA1c), and history of cardiovascular disease in patients with type 2 diabetes. METHODS: We performed a systematic review of the MEDLINE and EMBASE databases search up to December 31, 2022, (PROSPERO, CRD42023400899) to identify all large-scale cardiovascular outcomes (CVO) trials of SGLT2i and GLP-1 RAs in which more than 1,000 patient-years of follow-up in each randomized group. Outcomes included all-cause mortality, major adverse cardiovascular event (MACE) and its component (cardiovascular death, myocardial infarction [MI], and stroke), heart failure, and renal failure. A random-effects meta-analyses were used to pool the estimates. RESULTS: Eighteen CVOTs (ten for SGLT2i and eight for GLP-1 RAs) with 127,606 patients with type 2 diabetes were included. Over 2.5 years median follow-up, the average reduction of systolic BP was 2.2 mmHg (mean difference [MD] - 2.2; 95% CI - 2.7 to - 1.7) with more important reduction (Pinteraction = 0.001) with SGLT2 inhibitors (- 2.9; - 3.4 to - 2.5) than with GLP-1 RAs (- 1.4; - 1.8 to - 1). With SGLT2i, every 5-mmHg reduction in systolic BP was associated with a significantly lower risk of mortality (hazard ratio[HR], 0.77; 95% CI 0.65-0.90), MACE (HR 0.81 [0.74-0.89]), cardiovascular death (HR 0.72 [0.59-0.88]), MI (HR 0.82 [0.71-0.95]), heart failure (HR 0.49 [0.42-0.57]), and renal failure (HR 0.46 [0.38-0.55]), while the association was not significant for stroke (HR 0.91 [0.69-1.19]). The corresponding effects for every 5-mmHg reduction in SBP with GLP-1 RAs were 0.65 (0.51-0.84) for all-cause mortality, 0.65 (0.56-0.76) for MACE, 0.62 (0.45-0.85) for CV death, 0.71 (0.52-0.76) for MI, 0.49 (0.35-0.69) for stroke, and 0.49 (0.35-0.66) for renal failure, while the association was not significant for heart failure (HR 0.82 [0.63-1.08]). CONCLUSION: In patients with type 2 diabetes, the hypotensive effects of SGLT2i and GLP-1 RAs were significantly associated with a reduction in mortality and cardiorenal events. These findings suggest that the lowering BP effect could be seen as an additive indicator of cardiovascular protection by SGLT2i and GLP-1 RAs drugs.

Perceptions of bariatric surgery in patients with type 2 diabetes: data from a self-administered questionnaire.

BACKGROUND: Although bariatric surgery (BS) is recommended for patients with type 2 diabetes (T2D) and moderate to severe obesity, only approximately 2% of patients undergo surgery. OBJECTIVE: To compare the knowledge and perception of BS with that of other treatments for diabetes among patients with diabetes. SETTING: French social media platforms. METHODS: A self-administered questionnaire was distributed from May 13 to June 3, 2020, via different French social media, including patients with T2D (main target), and patients with type 1 diabetes (control population). Different profiles of reluctance to BS were identified using a factorial analysis. RESULTS: Of the 4481 responders (50.4% women, 33.9% aged over 65), 60% had T2D. Of the 1736 patients who had heard of BS (38.7%), 1493 declared they never addressed it with their physician. Among T2D patients, BS is the treatment that elicits the most negative response, with more than 10% showing reluctance. Four reluctance profiles were identified: (1) cluster 1 (43.4%), fear of consequences on their eating habits and irreversibility of the procedure; (2) cluster 2 (34.9%), fear of poorer diabetes control; (3) cluster 3 (9.3%), fear of surgical risk; and (4) cluster 4 (12.4%), fear of side effects. In all clusters, the opinion of their physician would be the most important factor to change their mind. CONCLUSION: Bariatric surgery for T2D is rarely addressed in routine medical visits. Fear of operative risks and irreversibility of the procedure largely explains the reluctance to BS. Information and education campaigns on the benefit of metabolic surgery for patients with T2D remain necessary.

Age, sex, race, BMI, and duration of diabetes differences in cardiovascular outcomes with glucose lowering drugs in type 2 diabetes: A systematic review and meta-analysis.

Background: Summarized data of cardiovascular outcomes trials (CVOTs) of sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have shown a reduction in major adverse cardiovascular event (MACE), whether these benefits are extended in certain risk groups (elderly or obese patients or those with a longer duration of diabetes) or certain minorities (Black participants) are not clearly established. We aimed to provide overall hazard ratios (HRs) estimates for MACE of SGLT2i and GLP-1 RAs stratified by age (< 65 years vs. ≥ 65 years and < 75 years vs. ≥ 75 years), sex (male vs. female), race (Black vs. White, Black vs. Asian, and White vs. Asian), body mass index (BMI: < 30 kg/m2 vs. ≥ 30 kg/m2), and duration of diabetes (< 10 years vs. ≥ 10 years). Methods: We performed a MEDLINE database search from inception up to July 31, 2022 to identify all placebo-controlled phase 3 CVOTs that evaluated the efficacy of SGLT2i and GLP-1 RAs on vascular events at least 1-year after randomisation in participants with type 2 diabetes, and we selected those reporting hazard ratios (HRs) for the specific risk groups for MACE. Differences on MACE in risk groups were examined using a random-effect meta-analysis. The study protocol was registered on PROSPERO (CRD42022347901). Findings: A total of 11 studies fulfilled the prespecified criteria, comprising 96,580 patients with T2D were included. Of these patients, 61,975 (64.2%) were male, 34,605 (35.8%) were female, and race groups included 74,982 (77.6%) White, 7760 (8.0%) Asian, and 4023 (4.2%) Black. In two SGLT2i trials, the HR (95% CI) for long-term diabetes duration more than10 years versus short duration was 0.84 (0.77-0.93) vs. 1.02 (0.89-1.16), respectively (P interaction = 0.03). In four SGLT2i trials, the MACE benefit was similar by sex (P interaction = 0.13), age (P interaction = 0.36), BMI (P interaction = 0.69), and race groups (P interaction = 0.86 between Black and White, P interaction = 0.98 between Black and Asian, and P interaction = 0.69 between White and Asian). For GLP-1 RAs, the MACE benefit from the seven trials tended to be greater for Asian (0.71, [0.58-0.87]) than for White (0.87, [0.81-0.94]), (P interaction = 0.07). In two GLP-1 RAs trials, the MACE outcome was reduced by 22% (0.78, 0.63-0.95) in elderly patients (≥ 75 years) while no difference was observed in those < 75 years (0.87; 0.75-1.01), (P interaction = 0.37). In the remaining risk groups, the MACE benefit was similar by sex (P interaction = 0.37), age < 65 years (P interaction = 0.80), duration of diabetes (P interaction = 0.70), and race (P interaction = 0.57 between Black and White, and P interaction = 0.15 between Black and Asian), BMI (P interaction = 0.78). Risk of bias was lower, and overall heterogeneity was high for sex with SGLT2i, and moderate to low for the remaining comparisons, with a I2 values ranging from 0% to 54%. Interpretation: In patients with type 2 diabetes at highest risk of cardiovascular disease or established cardiovascular disease, a greater benefit on MACE was found for elderly patients and for Asian individuals compared with White individuals with GLP-1 RAs, and those with a long duration of diabetes with SGLT2i. These findings could help in providing guidance for treatment prescription and facilitate selection and stratification of patients for future CVOTs. Furthermore, pooled individual patient-level data are urgently needed to support our conclusions, and to derive definitive evidence. Funding: None.

Efficacy of approved vaccines to prevent COVID-19: a systematic review and network meta-analysis of reconstructed individual patient data from randomized trials.

Aim: To optimize vaccination strategy, evidence on vaccine efficacy against COVID-19 is needed. Method: The present network meta-analysis uses reconstructed individual patient data from phase III trials on vaccine efficacy (VE), identified through MEDLINE, EMBASE, and Cochrane library (CENTRAL) peer-reviewed and published in English before August 31, 2021. The primary outcome was the VE against confirmed COVID-19 at any time after the first dose as defined in each study. VE was re-estimated using the two-stage approach. Poisson regression models were applied to each trial at the first stage, and the incidence risk ratio (IRR) and their 95% CI were aggregated to allow random-effects network meta-analysis (NMA) at the second stage. VE was expressed as: (1-IRR) × 100. The study protocol is registered in PROSPERO (CRD42020200012). Results: A total of eight studies, evaluating nine different vaccines were identified and analyzed. Between April 23, 2020 and January 05, 2021, 210,418 participants were recruited in 354 sites worldwide. During a median (IQR) follow-up duration of 69.8 (69.7-70.3) days, 2131 confirmed COVID-19 cases occurred (604; 26.0 per 1000 person-years in vaccine recipients and 1527; 85.9 per 1000 person-years in the control group). The mRNA-1273 vaccine was the most effective (P-score 0.99); at any time after dose 1, incidence reduction for mRNA-1273 ranged from 78% to 98% compared to the other vaccines. Conclusion: Our results provide evidence for the short-term superiority of mRNA vaccines, especially the mRNA-1273 vaccine in prevention of COVID-19 in different populations. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-022-01707-1.

Assessment of Predictor Factors Associated with Multiple Emergency Department Attendance with Asthma Attack: A Qualitative and Multicentric Prospective Observational Study.

Purpose: Identified factors associated with multiple emergency department (ED) visits (≥) for asthma, which is associated with death. Patients and Methods: We first conducted a qualitative study. We invited French-speaking adults (≥18 years old) with a diagnosis of asthma for more than 6 months. The identified concepts were transcribed into items. A Delphi method allowed for selecting items for a self-reported questionnaire. In an observational multicentric cross-sectional quantitative study, the resulting 20-item questionnaire and 12-item General Health Questionnaire, exploring psychological distress, were administered to adults visiting an ED for asthma exacerbation. Multivariable logistic regression was used to assess factors associated with ED visits. Results: Data saturation was obtained after 8 patient interviews. Patients who came to the ED seemed unfamiliar with their illness or treatments but were concerned by the disease. The questionnaire was administered to 182 patients. On multivariable logistic regression, multiple and systematic ED visits were associated with asthma exacerbation (adjusted odds ratio (aOR) = 6.89, 95% confidence interval [CI]: 2.25-21.09), asthma perceived as a handicap (aOR=3.19, 95% CI: 1.55-6.57) and reported atopy (OR=2.09, 95% CI: 1.03-4.26). High educational level and lack of maintenance inhaled corticosteroids were protective for multiple ED visits. Conclusion: Inadequate medical care is frequent in patients attending the ED for an asthma exacerbation, associated with strong psychological impact. Questioning the reasons for consulting the ED may help quickly identify patients requiring asthma education and improve their referral.

Long-term outcome following blunt cerebrovascular injuries: occurrence of ischemic complications, treatment, and outcome.

PURPOSE: Blunt cerebrovascular injuries (BCVI) are a rare but serious complication after trauma. Among patients with BCVI, neurological status is altered in 30% of cases and the prognosis seems to be associated with ischemic complications. The aim of this study was to assess the long-term outcome of BCVI-associated ischemic events. METHODS: This retrospective cohort study (2011-2017) included all patients admitted for severe trauma with identified BCVI in two level-1 trauma centers. Patients were considered to have a poor neurological outcome with a GOS-E between 2 and 5 and a good neurological outcome with GOS-E between 6 and 8. A multivariate logistic regression identified risk factors for poor neurological outcome at 1 year. RESULTS: Of the 6,294 patients admitted in both trauma centers between 2011 and 2017, 81 patients presenting BCVI were identified (incidence of 1.3%). The median age was 35 years (24-44) with a median Injury Severity Score of 28 (17-41). 29 patients (50%) had a good neurological prognosis, while 25 patients (43%) had a poor neurological prognosis at 1 year. Ischemic stroke occurred in 11 patients (13.6%) within a median time of 2 days (2-2.5). No ischemic stroke occurred in the first year after ICU discharge in both groups. In our study, good prognosis at 1 year was not associated with ischemic complications [3 (10) vs 3 (12) p = 1]. CONCLUSION: Ischemic complications after BCVI are rare, occur within the first week and do not seem to impact independently the 1-year neurological prognosis.

Natural history of most common spinocerebellar ataxia: a systematic review and meta-analysis.

BACKGROUND: Spinocerebellar ataxias (SCAs) are rare dominantly inherited neurodegenerative disorders that lead to severe disability and premature death. OBJECTIVE: To better characterize the natural history of the most common SCAs, SCA1, SCA2, SCA3 and SCA6, we performed a meta-analysis of literature to determine disease progression, provide data for sample-sizes calculations for interventional trials and study the impact of geographical locations and study follow-up on disease progression. METHODS: A systematic literature search from MEDLINE and EMBASE databases for longitudinal natural history studies of SCA patients was conducted. Studies using the Scale for the Assessment and Rating Ataxia (SARA) as outcome measure were considered. Random-effect (RE) meta-analysis was applied to estimate pooled disease progression. RESULTS: Six studies with 1215 SCA patients enrolled between 2005 and 2016 were finally selected. Annual pooled SARA score increase was 1.83 (1.46-2.20) in patients with SCA1, 1.40 (1.19-1.61) in patients with SCA2, 1.41 (0.97-1.84) in patients with SCA3, and 0.81 (0.66-0.97) in patients with SCA6. For patients with SCA3, disease progression was faster in studies located in Asia and Europe than in the US. Two-arm interventional trials of 1-year duration to achieve 80% power and α level of 5% would require 92 patients per group with SCA1, 97 with SCA2, 115 with SCA3, and 430 with SCA6 to detect a 50% reduction in disease progression. CONCLUSION: This meta-analysis provides quantitative data on the progression of the most common spinocerebellar ataxias based on patient numbers that exceed those of previous studies and confirms that disease progression is faster in SCA1, intermediate in SCA2 and SCA3 and slower in SCA6, with similar rates of disease progression in SCA2 and SCA3 between different populations, suggesting a possibility of international collaborative studies. Nevertheless, individual-patient data meta-analysis is needed to better understand the risk factors that influence disease progression and improve patient stratification in interventional trials.

An updated systematic review and network meta-analysis of 25 randomized trials assessing the efficacy and safety of treatments in COVID-19 disease.

To date, there is no definite effective treatment for the COVID- 19 pandemic. We performed an update network meta-analysis to compare and rank COVID-19 treatments according to their efficacy and safety. Literature search was performed from MEDLINE and CENTRAL databases from inception to September 5, 2020. Randomized clinical trials (RCTs) which compared the effect of any pharmacological drugs versus standard care or placebo 28-day after hospitalization in adult patients with COVID-19 disease were included. Risk ratio (RR) and 95% CI were calculated for 28-day all-cause mortality, clinical improvement, any adverse event (AEs), and viral clearance. A total of 25 RCTs, evaluating 17 different treatments, and 11,597 participants were analyzed. Remdesivir for 10- day compared to standard care (RR 0.69, 95% CI [0.48-0.99]), and a low dose compared to a high dose of HCQ (0.38, [0.17-0.89]) were associated with a lower risk of death. A total of 2,766 patients experienced clinical improvement, a 5-day course of remdesivir was associated with a higher frequency of clinical improvement compared to standard care (RR 1.21, 95% CI [1.00-1.47]). Compared to standard care, remdesivir for both 5 and 10 days, lopinavir/ritonavir, and dexamethasone reduced the risk of any severe AEs by 52% (0.48, 0.34-0.67), 24% (0.77, 0.63-0.92), 40% (0.60, 0.37-0.98), and 50% (0.50, 0.25-0.98) respectively. In this study of hospitalized patients with COVID-19, administration of remdesivir for 10-day compared to standard care was associated with lower 28-day all-cause mortality and serious AEs, and higher clinical improvement rate.

[Profile and quality of life of patients with rheumatoid arthritis in Guinea Conakry and Cameroon]. / Profil et qualité de vie de patients atteints de polyarthrite rhumatoïde en Guinée Conakry et au Cameroun.

INTRODUCTION: rheumatoid arthritis (RA) dramatically affects the quality of life of patients. The objective of our study was to study the link between the activity of the disease and the quality of life of Guinean (Conakry) and Cameroonian patients with RA. METHODS: pilot multicentric cross-sectional study (Ignace Dean National Hospital of Conakry in Guinea and Efoulan Yaoundé District Hospital in Cameroon) for 15 months (1st October 2016 to 30th January 2018). The diagnosis of RA was based on the criteria of the ACR/EULAR. Disease activity was assessed by DAS 28. The EMIR questionnaire and the Steinbrocker score were used to assess quality of life. RESULTS: fifty-two patients, 82% of whom were women. The total EMIR score was 5.06±0.50 as a relatively impaired quality of life. Alteration of quality of life was more marked on psychic components (6.78±0.99) and pain (5.37±0.99). The work component was the least affected (4.03±0.98). DAS28 was significantly related to psychic components (p=0.036, R=0.29), pain (p=0.076, R=0.25), physical (p=0.0029, R=0.41), and at the overall quality of life (total EMIR) (p=0.027, R=0.31). CONCLUSION: the most significant of RA on quality of life was related to pain (EVA-pain) and RA activity (DAS 28). The results of this pilot study will have to be confirmed by a largest study.