[Covid-19: how the pandemic revealed gender inequalities]. / Covid-19 : dans le genre on peut faire mieux !

The SARS-CoV-2 pandemic has revealed inequalities between men and women and has deepened some existing disparities. While in Switzerland, more women than men have been infected, men have been at greater risk of developing complications and dying. A weaker immune response and more co-morbidities help to explain this poorer prognosis. Socially and economically, women have become more precarious as a result of less stable employment and greater involvement in domestic work. Domestic violence has increased and women's access to sexual and reproductive health services has become more difficult. Finally, women have been under-represented as research authors but also among experts in task forces and media.

La pandémie liée au SARS-CoV-2 a révélé des inégalités entre les hommes et les femmes et a creusé certaines disparités existantes. Si en Suisse les femmes sont plus nombreuses à avoir été infectées que les hommes, ces derniers ont eu un plus grand risque de décéder. Une réponse immunitaire moins performante et davantage de comorbidités contribuent à expliquer ce pronostic défavorable. Sur le plan social et économique, les femmes ont été davantage précarisées du fait d'emplois moins stables et d'une plus grande implication dans les tâches domestiques. La violence domestique a augmenté et l'accès des femmes aux services de santé sexuelle et reproductive a été plus difficile. Finalement, les femmes ont été sous-représentées comme autrices dans la recherche mais également parmi les expert·e·s dans les task forces et les médias.

Early experimental COVID-19 therapies: associations with length of hospital stay, mortality and related costs.

AIMS OF THE STUDY: Hydroxychloroquine and lopinavir/ritonavir have been used as experimental therapies to treat COVID-19 during the first wave of the pandemic. Randomised controlled trials have recently shown that there are no meaningful benefits of these two therapies in hospitalised patients. Uncertainty remains regarding the potential harmful impact of these therapies as very early treatments and their burden to the health care system. The present study investigated the length of hospital stay (LOS), mortality, and costs of hydroxychloroquine, lopinavir/ritonavir or their combination in comparison with standard of care among patients hospitalised for coronavirus disease 2019 (COVID-19). METHODS: This retrospective observational cohort study took place in the Geneva University Hospitals, Geneva, Switzerland (n = 840) between 26 February and 31 May 2020. Demographics, treatment regimens, comorbidities, the modified National Early Warning Score (mNEWS) on admission, and contraindications to COVID-19 treatment options were assessed. Outcomes included LOS, in-hospital mortality, and drug and LOS costs. RESULTS: After successful propensity score matching, patients treated with (1) hydroxychloroquine, (2) lopinavir/ritonavir or (3) their combination had on average 3.75 additional hospitalisation days (95% confidence interval [CI] 1.37–6.12, p = 0.002), 1.23 additional hospitalisation days (95% CI −1.24 – 3.51, p = 0.319), and 4.19 additional hospitalisation days (95% CI 1.52–5.31, p <0.001), respectively, compared with patients treated with the standard of care. Neither experimental therapy was significantly associated with mortality. These additional hospital days amounted to 1010.77 additional days for hydroxychloroquine and hydroxychloroquine combined with lopinavir/ritonavir, resulting in an additional cost of US$ 2,492,214 (95%CI US$ 916,839–3,450,619). CONCLUSIONS: Prescribing experimental therapies for COVID-19 was not associated with a reduced LOS and might have increased the pressure put on healthcare systems.

Access to unauthorized hepatitis C generics: Perception and knowledge of physicians, pharmacists, patients and non-healthcare professionals.

OBJECTIVES: Hepatitis C virus (HCV) causes both acute and chronic infection, which can potentially develop into cirrhosis and liver cancer. Healthcare systems are struggling to finance costly direct-acting antiviral agents through public funding for uninsured patients, despite the unprecedented high cure rates of these agents. Vulnerable populations are at higher risk of HCV infection. The personal importation scheme is based on the legal right to import any unauthorized generics for personal use. This study was designed to assess the knowledge and perceptions of stakeholders on unauthorized generics. METHODS: We conducted an anonymous online survey based on the fictitious situation of a patient diagnosed with HCV who lacked mandatory health insurance and personal financial resources. RESULTS: We obtained a sample of 781 respondents: 445 physicians, 77 pharmacists, 51 patients and 207 non-healthcare professionals. We found that only 36% and 58% of respondents believe that the quality and efficacy, respectively, of unauthorized generics are equivalent to their corresponding brand. An overwhelming majority (98%) favoured quality control upon arrival, and 31% felt they could recognize fraudulent websites. A total of 79% expressed support for financial assistance for vulnerable patients, and support among physicians was 83%. CONCLUSIONS: Overall, the limited knowledge of the efficacy and quality of unauthorized generics, despite evidence in peer-reviewed literature, contrasts with the overwhelmingly positive attitudes toward financial assistance for personal import. This finding emphasizes the need for clearer information on imported generics and the potential safety provided by buyers' club schemes to complete the WHO agenda of eradicating viral hepatitis by 2030 within otherwise excluded vulnerable populations.

Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage: a meta-analysis of individual patient-level data from 40 138 bleeding patients.

BACKGROUND: Antifibrinolytics reduce death from bleeding in trauma and post-partum haemorrhage. We examined the effect of treatment delay on the effectiveness of antifibrinolytics. METHODS: We did an individual patient-level data meta-analysis of randomised trials done with more than 1000 patients that assessed antifibrinolytics in acute severe bleeding. We identified trials done between Jan 1, 1946, and April 7, 2017, from MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, PubMed, Popline, and the WHO International Clinical Trials Registry Platform. The primary measure of treatment benefit was absence of death from bleeding. We examined the effect of treatment delay on treatment effectiveness using logistic regression models. We investigated the effect of measurement error (misclassification) in sensitivity analyses. This study is registered with PROSPERO, number 42016052155. FINDINGS: We obtained data for 40 138 patients from two randomised trials of tranexamic acid in acute severe bleeding (traumatic and post-partum haemorrhage). Overall, there were 3558 deaths, of which 1408 (40%) were from bleeding. Most (884 [63%] of 1408) bleeding deaths occurred within 12 h of onset. Deaths from post-partum haemorrhage peaked 2-3 h after childbirth. Tranexamic acid significantly increased overall survival from bleeding (odds ratio [OR] 1·20, 95% CI 1·08-1·33; p=0·001), with no heterogeneity by site of bleeding (interaction p=0·7243). Treatment delay reduced the treatment benefit (p<0·0001). Immediate treatment improved survival by more than 70% (OR 1·72, 95% CI 1·42-2·10; p<0·0001). Thereafter, the survival benefit decreased by 10% for every 15 min of treatment delay until 3 h, after which there was no benefit. There was no increase in vascular occlusive events with tranexamic acid, with no heterogeneity by site of bleeding (p=0·5956). Treatment delay did not modify the effect of tranexamic acid on vascular occlusive events. INTERPRETATION: Death from bleeding occurs soon after onset and even a short delay in treatment reduces the benefit of tranexamic acid administration. Patients must be treated immediately. Further research is needed to deepen our understanding of the mechanism of action of tranexamic acid. FUNDING: UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation (CRASH-2 trial). London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation (WOMAN trial).

Acute necrotising gingivitis in young children from villages with and without noma in Niger and its association with sociodemographic factors, nutritional status and oral hygiene practices: results of a population-based survey.

BACKGROUND: Previous studies have suggested that acute necrotising gingivitis precedes noma disease and that noma clusters in some villages in certain regions of low- and middle-income countries. We sought to assess the prevalence of gingivitis with bleeding in young children from villages with or without a history of noma and to analyse epidemiological differences related to sociodemographic characteristics, nutritional status and oral hygiene practices. METHODS: We conducted a cross-sectional study in 440 children aged between 2 and 6 years from four villages in the Zinder region of southeast Niger in Africa. In two villages, cases of noma have repeatedly been detected; in the other two, noma has never been identified. We randomly selected 110 participants from each village. RESULTS: The prevalence of acute necrotising gingivitis was significantly higher in the noma villages compared with the non-noma villages (6.8% vs 0.9%; p=0.001). We found differences between the four villages regarding socioeconomic factors, stunting, undernourishment and oral hygiene practices. The type of oral hygiene procedures influenced the amount of dental plaque and gingival inflammation. Children using sand, coal or other abrasive products instead of a toothbrush had a significantly increased likelihood to be diagnosed with acute necrotising gingivitis (p=0.041). CONCLUSIONS: Our data suggest that efforts to prevent noma should focus on populations with a high prevalence of acute necrotising gingivitis and include nutritional support and attempts to introduce safe and efficient oral hygiene practices to improve gingival health.

How do researchers determine the difference to be detected in superiority trials? Results of a survey from a panel of researchers.

BACKGROUND: There is currently no guidance for selecting a specific difference to be detected in a superiority trial. We explored 3 factors that in our opinion should influence the difference to be detected (type of outcome, patient age group, and presence of treatment side-effects), and 3 that should not (baseline level of risk, logistical difficulties, and cost of treatment). METHODS: We conducted an experimental survey using a factorial design among 380 corresponding authors of randomized controlled trials indexed in Medline. Two hypothetical vignettes were submitted to participants: one described a trial of a new analgesic in mild trauma injuries, the other described a trial of a new chemotherapy among cancer patients. The first vignette tested the baseline level of risk, patient age-group, patient recruitment difficulties, and treatment side-effects. The second tested the baseline level of risk, patient age-group, type of outcome, and cost of treatment. The respondents were asked to select the smallest gain of effectiveness that should be detected by the trial. RESULTS: In vignette 1, respondents selected a median difference to be detected corresponding to an improvement of 7.0 % in pain control with the new treatment. In vignette 2, they selected a median difference to be detected corresponding to a reduction of 5.0 % in mortality or cancer recurrence with the new chemotherapy. In both vignettes, the difference to be detected decreased significantly with the baseline risk. The other factor influencing difference to be detected was the age group, but the impact of this factor was smaller. Cost, side-effects, outcome severity, or mention of logistical difficulties did not significantly impact the difference to be detected selected by participants. CONCLUSIONS: Three of the anticipated effects conformed to our expectations (the effect of patient age, and absence of effect of the cost of treatment and of patient recruitment difficulties) and the other three did not. These findings can guide future research in determining differences to be detected in trials that can translate to meaningful clinical decision-making.

Global implementation of WHO's multimodal strategy for improvement of hand hygiene: a quasi-experimental study.

BACKGROUND: Health-care-associated infections are a major threat to patient safety worldwide. Transmission is mainly via the hands of health-care workers, but compliance with recommendations is usually low and effective improvement strategies are needed. We assessed the effect of WHO's strategy for improvement of hand hygiene in five countries. METHODS: We did a quasi-experimental study between December, 2006, and December, 2008, at six pilot sites (55 departments in 43 hospitals) in Costa Rica, Italy, Mali, Pakistan, and Saudi Arabia. A step-wise approach in four 3-6 month phases was used to implement WHO's strategy and we assessed the hand-hygiene compliance of health-care workers and their knowledge, by questionnaire, of microbial transmission and hand-hygiene principles. We expressed compliance as the proportion of predefined opportunities met by hand-hygiene actions (ie, handwashing or hand rubbing). We assessed long-term sustainability of core strategy activities in April, 2010. FINDINGS: We noted 21,884 hand-hygiene opportunities during 1423 sessions before the intervention and 23,746 opportunities during 1784 sessions after. Overall compliance increased from 51.0% before the intervention (95% CI 45.1-56.9) to 67.2% after (61.8-72.2). Compliance was independently associated with gross national income per head, with a greater effect of the intervention in low-income and middle-income countries (odds ratio [OR] 4.67, 95% CI 3.16-6.89; p<0.0001) than in high-income countries (2.19, 2.03-2.37; p<0.0001). Implementation had a major effect on compliance of health-care workers across all sites after adjustment for main confounders (OR 2.15, 1.99-2.32). Health-care-workers' knowledge improved at all sites with an increase in the average score from 18.7 (95% CI 17.8-19.7) to 24.7 (23.7-25.6) after educational sessions. 2 years after the intervention, all sites reported ongoing hand-hygiene activities with sustained or further improvement, including national scale-up. INTERPRETATION: Implementation of WHO's hand-hygiene strategy is feasible and sustainable across a range of settings in different countries and leads to significant compliance and knowledge improvement in health-care workers, supporting recommendation for use worldwide. FUNDING: WHO, University of Geneva Hospitals, the Swiss National Science Foundation, Swiss Society of Public Health Administration and Hospital Pharmacists.

Self-rated health: analysis of distances and transitions between response options.

PURPOSE: We explored health differences between population groups who describe their health as excellent, very good, good, fair, or poor. METHODS: We used data from a population-based survey which included self-rated health (SRH) and three global measures of health: the SF36 general health score (computed from the 4 items other than SRH), the EQ-5D health utility, and a visual analogue health thermometer. We compared health characteristics of respondents across the five health ratings. RESULTS: Survey respondents (N = 1.844, 49.2 % response) rated their health as excellent (12.2 %), very good (39.1 %), good (41.9 %), fair (6.0 %), or poor (0.9 %). The means of global health assessments were not equidistant across these five groups, for example, means of the health thermometer were 95.8 (SRH excellent), 88.8 (SRH very good), 76.6 (SRH good), 49.7 (SRH fair), and 33.5 (SRH poor, p < 0.001). Recoding the SRH to reflect these mean values substantially improved the variance explained by the SRH, for example, the linear r (2) increased from 0.50 to 0.56 for the health thermometer if the SRH was coded as poor = 1, fair = 2, good = 3.7, very good = 4.5, and excellent = 5. Furthermore, transitions between response options were not explained by the same health-related characteristics of the respondents. CONCLUSIONS: The adjectival SRH is not an evenly spaced interval scale. However, it can be turned into an interval variable if the ratings are recoded in proportion to the underlying construct of health. Possible improvements include the addition of a rating option between good and fair or the use of a numerical scale instead of the classic adjectival scale.

CD4-guided scheduled treatment interruptions compared with continuous therapy for patients infected with HIV-1: results of the Staccato randomised trial.

BACKGROUND: Stopping antiretroviral therapy in patients with HIV-1 infection can reduce costs and side-effects, but carries the risk of increased immune suppression and emergence of resistance. METHODS: 430 patients with CD4-positive T-lymphocyte (CD4) counts greater than 350 cells per muL, and viral load less than 50 copies per mL were randomised to continued therapy (n=146) or scheduled treatment interruptions (n=284). Median time on randomised treatment was 21.9 months (range 16.4-25.3). Primary endpoints were proportion of patients with viral load less than 50 copies per mL at the end of the trial, and amount of drugs used. Analysis was intention-to-treat. This study is registered at ClinicalTrials.gov with the identifier NCT00113126. FINDINGS: Drug savings in the scheduled treatment interruption group, compared with continuous treatment, amounted to 61.5%. 257 of 284 (90.5%) patients in the scheduled treatment interruption group reached a viral load less than 50 copies per mL, compared with 134 of 146 (91.8%) in the continued treatment group (difference 1.3%, 95% CI-4.3 to 6.9, p=0.90). No AIDS-defining events occurred. Diarrhoea and neuropathy were more frequent with continuous treatment; candidiasis was more frequent with scheduled treatment interruption. Ten patients (2.3%) had resistance mutations, with no significant differences between groups. INTERPRETATION: Drug savings with scheduled treatment interruption were substantial, and no evidence of increased treatment resistance emerged. Treatment-related adverse events were more frequent with continuous treatment, but low CD4 counts and minor manifestations of HIV infection were more frequent with scheduled treatment interruption.