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Potential interactions between medications for rate control and direct oral anticoagulants: Population-based cohort and case-crossover study.
Get PDFBACKGROUND: Direct oral anticoagulants (DOACs) are commonly co-prescribed with amiodarone/diltiazem/verapamil, but whether there is a drug interaction between these drugs is unclear. OBJECTIVE: The purpose of this study was to investigate the risk of clinical outcomes associated with concomitant use of DOACs and amiodarone/diltiazem/verapamil. METHODS: We identified DOAC users in the Clinical Practice Research Datalink Aurum from January 1, 2011, to December 31, 2019. We used a cohort design to estimate hazard ratios for ischemic stroke, myocardial infarction, venous thromboembolism, intracranial bleeding, gastrointestinal bleeding, other bleeding, cardiovascular mortality, and all-cause mortality, comparing DOACs + amiodarone/diltiazem/verapamil users and DOACs + beta-blocker users. A case-crossover design comparing odds of exposure to different drug initiation patterns for all outcomes in hazard window vs referent window within an individual also was conducted. RESULTS: Of 397,459 DOAC users, we included 9075 co-prescribed amiodarone, 9612 co-prescribed diltiazem, and 2907 co-prescribed verapamil. There was no difference in risk of any outcomes between DOACs + amiodarone/diltiazem/verapamil users vs DOACs + beta-blocker users in the cohort design. However, in the case-crossover design, we observed an odds ratio (OR) of 2.09 (99% confidence interval [CI] 1.37-3.18) for all-cause mortality associated with initiation of a DOAC while taking amiodarone, which was greater than that observed for DOAC monotherapy (OR 1.30; 99% CI 1.25-1.35). Similar findings were observed for cardiovascular mortality and all-cause mortality respectively with diltiazem. CONCLUSION: Our study showed no evidence of higher bleeding or cardiovascular risk associated with co-prescribed DOACs and amiodarone, diltiazem, or verapamil. Elevated risks of cardiovascular and all-cause mortality were only observed during DOAC initiation when diltiazem/amiodarone were being taken
Antibiotics for treatment of leptospirosis.
Get PDFBACKGROUND: Leptospirosis is a disease transmitted from animals to humans through water, soil, or food contaminated with the urine of infected animals, caused by pathogenic Leptospira species. Antibiotics are commonly prescribed for the management of leptospirosis. Despite the widespread use of antibiotic treatment for leptospirosis, there seems to be insufficient evidence to determine its effectiveness or to recommend antibiotic use as a standard practice. This updated systematic review evaluated the available evidence regarding the use of antibiotics in treating leptospirosis, building upon a previously published Cochrane review. OBJECTIVES: To evaluate the benefits and harms of antibiotics versus placebo, no intervention, or another antibiotic for the treatment of people with leptospirosis. SEARCH METHODS: We identified randomised clinical trials following standard Cochrane procedures. The date of the last search was 27 March 2023. SELECTION CRITERIA: We searched for randomised clinical trials of various designs that examined the use of antibiotics for treating leptospirosis. We did not impose any restrictions based on the age, sex, occupation, or comorbidities of the participants involved in the trials. Our search encompassed trials that evaluated antibiotics, regardless of the method of administration, dosage, and schedule, and compared them with placebo or no intervention, or compared different antibiotics. We included trials regardless of the outcomes reported. DATA COLLECTION AND ANALYSIS: During the preparation of this review, we adhered to the Cochrane methodology and used Review Manager. The primary outcomes were all-cause mortality and serious adverse events (nosocomial infection). Our secondary outcomes were quality of life, proportion of people with adverse events considered non-serious, and days of hospitalisation. To assess the risk of bias of the included trials, we used the RoB 2 tool, and for evaluating the certainty of evidence we used GRADEpro GDT software. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD), both accompanied by their corresponding 95% confidence intervals (CI). We used the random-effects model for all our main analyses and the fixed-effect model for sensitivity analyses. For our primary outcome analyses, we included trial data from the longest follow-up period. MAIN RESULTS: We identified nine randomised clinical trials comprising 1019 participants. Seven trials compared two intervention groups and two trials compared three intervention groups. Amongst the trials comparing antibiotics versus placebos, four trials assessed penicillin and one trial assessed doxycycline. In the trials comparing different antibiotics, one trial evaluated doxycycline versus azithromycin, one trial assessed penicillin versus doxycycline versus cefotaxime, and one trial evaluated ceftriaxone versus penicillin. One trial assessed penicillin with chloramphenicol and no intervention. Apart from two trials that recruited military personnel stationed in endemic areas or military personnel returning from training courses in endemic areas, the remaining trials recruited people from the general population presenting to the hospital with fever in an endemic area. The participants' ages in the included trials was 13 to 92 years. The treatment duration was seven days for penicillin, doxycycline, and cephalosporins; five days for chloramphenicol; and three days for azithromycin. The follow-up durations varied across trials, with three trials not specifying their follow-up periods. Three trials were excluded from quantitative synthesis; one reported zero events for a prespecified outcome, and two did not provide data for any prespecified outcomes. Antibiotics versus placebo or no intervention The evidence is very uncertain about the effect of penicillin versus placebo on all-cause mortality (RR 1.57, 95% CI 0.65 to 3.79; I2 = 8%; 3 trials, 367 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin or chloramphenicol versus placebo on adverse events considered non-serious (RR 1.05, 95% CI 0.35 to 3.17; I2 = 0%; 2 trials, 162 participants; very low-certainty evidence). None of the included trials assessed serious adverse events. Antibiotics versus another antibiotic The evidence is very uncertain about the effect of penicillin versus cephalosporin on all-cause mortality (RR 1.38, 95% CI 0.47 to 4.04; I2 = 0%; 2 trials, 348 participants; very low-certainty evidence), or versus doxycycline (RR 0.93, 95% CI 0.13 to 6.46; 1 trial, 168 participants; very low-certainty evidence). The evidence is very uncertain about the effect of cefotaxime versus doxycycline on all-cause mortality (RR 0.18, 95% CI 0.01 to 3.78; 1 trial, 169 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus doxycycline on serious adverse events (nosocomial infection) (RR 0.62, 95% CI 0.11 to 3.62; 1 trial, 168 participants; very low-certainty evidence) or versus cefotaxime (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of doxycycline versus cefotaxime on serious adverse events (nosocomial infection) (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus cefotaxime (RR 3.03, 95% CI 0.13 to 73.47; 1 trial, 175 participants; very low-certainty evidence), versus doxycycline (RR 2.80, 95% CI 0.12 to 67.66; 1 trial, 175 participants; very low-certainty evidence), or versus chloramphenicol on adverse events considered non-serious (RR 0.74, 95% CI 0.15 to 3.67; 1 trial, 52 participants; very low-certainty evidence). Funding Six of the nine trials included statements disclosing their funding/supporting sources and three trials did not mention funding source. Four of the six trials mentioning sources received funds from public or governmental sources or from international charitable sources, and the remaining two, in addition to public or governmental sources, received support in the form of trial drug supply directly from pharmaceutical companies. AUTHORS' CONCLUSIONS: As the certainty of evidence is very low, we do not know if antibiotics provide little to no effect on all-cause mortality, serious adverse events, or adverse events considered non-serious. There is a lack of definitive rigorous data from randomised trials to support the use of antibiotics for treating leptospirosis infection, and the absence of trials reporting data on clinically relevant outcomes further adds to this limitation
Cognitive decline related to chronic kidney disease as an exclusion factor from kidney transplantation: results from an international survey.
Get PDFBACKGROUND AND HYPOTHESIS: There seems to be a lack of consensus on the necessity and the modality of psychological and specifically cognitive assessment of candidates for kidney transplantation. Both points are often delegated to individual hospitals/centres, whereas international guidelines are inconsistent. We think it is essential to investigate professionals' opinions to advance towards a consistent clinical practice. METHODS: This paper presents the results of an international survey among clinical professionals, mainly nephrologists from the CONNECT (Cognitive decline in Nephro-Neurology: European Cooperative Target) network and beyond (i.e. from personal contacts of CONNECT members). The survey investigated their opinions about the question of whether cognitive decline in patients with chronic kidney disease may affect their eligibility for kidney transplantation. RESULTS: Our results show that most clinicians working with patients affected by chronic kidney disease think that cognitive decline may challenge their eligibility for transplantation despite data that suggest that, in some patients, cognitive problems improve after kidney transplantation. CONCLUSION: We conclude that three needs emerge as particularly pressing: defining agreed-on standards for a multifaceted and multifactorial assessment (i.e. including both clinical/medical and psychosocial factors) of candidates with chronic kidney disease to kidney transplantation; further investigating empirically the causal connection between chronic kidney disease and cognition; and further investigating empirically the possible partial reversibility of cognitive decline after kidney transplantation
The first BILGENSA Research Network workshop in Zambia: identifying research priorities, challenges and needs in genital bilharzia in Southern Africa [version 1; peer review: 1 approved, 3 approved with reservations]
Get PDFFemale genital schistosomiasis (FGS) and male genital schistosomiasis (MGS) are gender-specific manifestations of urogenital schistosomiasis. Morbidity is a consequence of prolonged inflammation in the human genital tract caused by the entrapped eggs of the waterborne parasite, Schistosoma (S.) haematobium. Both diseases affect the sexual and reproductive health (SRH) of millions of people globally, especially in sub-Sahara Africa (SSA). Awareness and knowledge of these diseases is largely absent among affected communities and healthcare workers in endemic countries. Accurate burden of FGS and MGS disease estimates, single and combined, are absent, mostly due to the absence of standardized methods for individual or population-based screening and diagnosis. In addition, there are disparities in country-specific FGS and MGS knowledge, research and implementation approaches, and diagnosis and treatment. There are currently no WHO guidelines to inform practice. The BILGENSA (Genital Bilharzia in Southern Africa) Research Network aimed to create a collaborative multidisciplinary network to advance clinical research of FGS and MGS across Southern African endemic countries. The workshop was held in Lusaka, Zambia over two days in November 2022. Over 150 researchers and stakeholders from different schistosomiasis endemic settings attended. Attendees identified challenges and research priorities around FGS and MGS from their respective countries. Key research themes identified acrosssettings included: 1) To increase the knowledge about the local burden of FGS and MGS; 2) To raise awareness among local communities and healthcare workers; 3) To develop effective and scalable guidelines for disease diagnosis and management; 4) To understand the effect of treatment interventions on disease progression, and 5) To integrate FGS and MGS within other existing sexual and reproductive health (SRH) services. In its first meeting, the BILGENSA Network set forth a common research agenda across S. haematobium endemic countries for the control of FGS and MG
Aligning rhetoric with reality: a qualitative analysis of multistakeholder initiatives in the global food system.
Get PDFGlobal food system governance increasingly relies on multistakeholder initiatives (MSIs) that aim to include those who are affected by and/or affected by an issue. Multistakeholderism's perceived legitimacy is premised on both its outcomes (output legitimacy) and processes (input legitimacy), the latter in turn based on four key rationales: inclusiveness, procedural fairness, consensual orientation and transparency. To date, evidence on the ineffectiveness of MSI's outcomes undermines its claims to output legitimacy. While individual case study assessments have also raised concerns over their processes, documenting instances of power asymmetries and corporate capture, there has hitherto been no comprehensive assessment of the input legitimacy of multistakeholderism. This work addresses that gap through interviews with 31 participants working either in or on MSIs. Participants noted significant challenges related to input legitimacy, including that (i) inclusion was often based on pre-existing networks of an MSI's founders-most of whom were based in the global North-and risked excluding less well-resourced or marginalized actors; (ii) pre-existing power imbalances, both internal and external to the MSI, considerably influenced its processes and structures; (iii) goal-setting was complicated by conflicts of interest and (iv) reliance on informal processes limited transparency. The similarities in challenges across MSIs indicate that these are not attributable to shortcomings of individual MSIs but are instead indicative of wider system constraints. Rather than rely on multistakeholderism as a 'good' governance norm, our findings add to evidence that MSIs do not meet output legitimacy and signal that the legitimacy of MSIs in their current form should be questioned
A retrospective cohort study of monthly rifampicin, ofloxacin and minocycline in the management of leprosy at the Hospital for Tropical Diseases, London, United Kingdom.
Get PDFINTRODUCTION: The World Health Organization (WHO) recommends rifampicin, dapsone and clofazimine multi-drug therapy (MDT) for the treatment of leprosy. Severe adverse effects include dapsone hypersensitivity syndrome, skin pigmentation, haemolytic anaemia, and hepatitis. At the Hospital for Tropical Diseases (HTD), London, United Kingdom monthly rifampicin, ofloxacin and minocycline (mROM) is used as first line treatment for leprosy. OBJECTIVES: To determine the clinical outcomes and experiences of individuals treated with mROM. METHODS: A retrospective study of individuals with leprosy who were prescribed mROM at HTD was conducted. Demographic and clinical data were collected on outcomes including relapses, leprosy reactions, bacterial index (BI) and adverse effects. Individuals were interviewed using a semi-structured questionnaire to understand their experiences of mROM. RESULTS: 29 individuals were identified and 20 interviewed. 26 (89.7%) individuals completed monthly mROM. 9 (31%) had switched from WHO MDT to mROM (five of whom (55.6%) were interviewed). BI reduced significantly following mROM treatment (p = 0.04). 17 individuals (58.6%) experienced a leprosy reaction. One of the 29 (3.4%) relapsed. The relapse rate was 9.5/1000 person years. 49 reports of adverse effects were either mild or moderate. The most frequent adverse effect (14/49) reported was orange discolouration of urine. No adverse effect required hospitalisation or discontinuation of mROM. Most individuals reported that skin lesions improved by the time they had completed mROM. CONCLUSIONS: In this small study in a non-endemic setting mROM was safe, effective and acceptable. mROM therapy is associated with improvement in skin lesions, decline in bacterial index and acceptable adverse effects. Larger, prospective, randomised studies are needed to determine whether relapse rates with mROM are equivalent or better than WHO MDT and to provide robust data on the seemingly better adverse effect profile of mROM
Application of geospatial analysis in health research: A systematic review of methodological aspects of studies on violence against children and young people.
Get PDFBackground Geographical variation exists in violence experienced by children and young people; however, there is limited research applying geospatial techniques to study this variation, and the methodological quality of this body of work is unclear. Objective This study aimed to review the application of geospatial analysis in research on violence against children (VAC) and evaluate how essential methodological aspects are reported. Methods Twelve databases were searched for studies on VAC using geospatial techniques. Two independent reviewers screened the papers for eligibility. Findings were narratively synthesised. Results Sixty studies were included. Six studies estimated the prevalence of VAC and 54 investigated the associations between VAC and covariates. Most studies were conducted in the US (68 %), and the broad definition of 'child maltreatment' (53 %) was the most common form of violence explored. Most studies (83 %) used administrative data, whereas 23 % used an ecological study design to estimate the associations between risk factors and official reports of VAC. Frequentist modelling approaches were used in 54 % of the studies, and 47 % investigated VAC at census tract level. Model fit metrics were reported in 69 % of studies. Conclusions Current knowledge of the geographical distribution of VAC is severely limited because of the reliance on administrative data, which vastly underestimates the prevalence of VAC compared with self-reports and poor reporting of quality characteristics. There is a huge opportunity for applying geospatial methods in VAC research in diverse geographic contexts. Future research must adopt rigorous and standardised approaches to model fitting and validation and make better use of self-reported data
Political dimensions of misinformation, trust, and vaccine confidence in a digital age.
Get PDFGlobal health leaders often dismiss politics as antithetical to the aims of public health, but Luisa Enria and colleagues argue that political analysis can offer new ways to build trust in vaccination in the context of growing online misinformation
A better integration of health and economic impact assessments of climate change.
Get PDFClimate change could lead to high economic burden for individuals (i.e. low income and high prices). While economic conditions are important determinants of climate change vulnerability, environmental epidemiological studies focus primarily on the direct impact of temperature on morbidity and mortality without accounting for climate-induced impacts on the economy. More integrated approaches are needed to provide comprehensive assessments of climate-induced direct and indirect impacts on health. This paper provides some perspectives on how epidemiological and economic impact assessments could be better integrated. We argue that accounting for the economic repercussions of climate change on people's health and, vice versa, the consequences of health effects on the economy could provide more realistic scenario projections and could be more useful for adaptation policy
Factors associated with hookworm and Schistosoma mansoni infections among school-aged children in Mayuge district, Uganda.
Get PDFBACKGROUND: Hookworm infection and schistosomiasis are two of sub-Saharan Africa's most common neglected tropical diseases. An annual mass drug administration (MDA) program against schistosomiasis and soil-transmitted helminths (STHs), including hookworm, has been implemented in Mayuge district, Uganda, since 2003 to date. However, hookworm and schistosomiasis remain prevalent in Mayuge district. Understanding the factors that predispose children to these infections in the context of MDA could inform interventions to reduce prevalence in Uganda and similar settings. METHOD: This cross-sectional study took place in 33 randomly selected primary schools in the Mayuge district from January to February 2022. Children in primary classes 4 or 5, in the selected schools provided single stool samples and completed questionnaires. Stool specimens were examined using the Kato-Katz method to determine the prevalence of hookworm and schistosomiasis. We performed univariable and multivariable logistic regression to assess the associations of each infection with potential risk factors. RESULT: A total of 1,617 students (mean age 12.1 years, 50.1% male) were enrolled. The prevalence of hookworm infection and schistosomiasis was 21.8% (95% confidence interval (CI): 19.8-23.9%) and 18.7% (95% CI: 16.8-20.7%), respectively. In multivariable analysis, longer water fetching time (over 30 min versus less than 30 min) and working daily in the soil were associated with increased odds of hookworm infection (adjusted odds ratio (AOR): 1.49, 95% CI: 1.13-1.96 and 1.37, 95% CI: 1.03-1.82, respectively). Higher odds of schistosomiasis were linked to proximity to water bodies within a one-hour walking distance (AOR: 1.84, 95% CI: 1.35-2.50), and not always washing hands before eating (AOR: 2.00, 95% CI: 1.50-2.67). Swimming, bathing, or washing in water bodies twice a week, compared to never, also increased schistosomiasis odds (AOR: 2.91, 95% CI: 1.66-5.13). CONCLUSION: Consistent with the mechanisms of acquisition, hookworm infection increased with exposure to soil, and schistosomiasis increased with exposure to unclean water. Our findings highlight the importance of Water, Sanitation, and Hygiene programs and strategies aimed at reducing exposure within the framework of Neglected Tropical Disease elimination programs