Greater human mobility, largely driven by air travel, is leading to an increase in the frequency and reach of infectious disease epidemics. Air travel can rapidly connect any two points on the planet, and this has the potential to cause swift and broad dissemination of emerging and re-emerging infectious diseases that may pose a threat to global health security. Investments to strengthen surveillance, build robust early-warning systems, improve predictive models, and coordinate public health responses may help to prevent, detect, and respond to new infectious disease epidemics.
Due to worldwide increased human mobility, air-transportation data and mathematical models have been widely used to measure risks of global dispersal of pathogens. However, the seasonal and interannual risks of pathogens importation and onward transmission from endemic countries have rarely been quantified and validated. We constructed a modelling framework, integrating air travel, epidemiological, demographical, entomological and meteorological data, to measure the seasonal probability of dengue introduction from endemic countries. This framework has been applied retrospectively to elucidate spatiotemporal patterns and increasing seasonal risk of dengue importation from South-East Asia into China via air travel in multiple populations, Chinese travelers and local residents, over a decade of 2005–15. We found that the volume of airline travelers from South-East Asia into China has quadrupled from 2005 to 2015 with Chinese travelers increased rapidly. Following the growth of air traffic, the probability of dengue importation from South-East Asia into China has increased dramatically from 2005 to 2015. This study also revealed seasonal asymmetries of transmission routes: Sri Lanka and Maldives have emerged as origins; neglected cities at central and coastal China have been increasingly vulnerable to dengue importation and onward transmission. Compared to the monthly occurrence of dengue reported in China, our model performed robustly for importation and onward transmission risk estimates. The approach and evidence could facilitate to understand and mitigate the changing seasonal threat of arbovirus from endemic regions.
Background Recent years have seen unprecedented growth in international travel. Travellers are at high risk for acquiring infections while abroad and potentially bringing these infections back to their home country. There are many ways to mitigate this risk by seeking pre-travel advice (PTA), including receiving recommended vaccinations and chemoprophylaxis, however many travellers do not seek or adhere to PTA. We conducted a systematic review to further understand PTA-seeking behaviour with an ultimate aim to implement interventions that improve adherence to PTA and reduce morbidity and mortality in travellers. Methods We conducted a systematic review of published medical literature selecting studies that examined reasons for not seeking PTA and non-adherence to PTA over the last ten years. 4484 articles were screened of which 56 studies met our search criteria after full text review. Results The major reason for not seeking or non-adherence to PTA was perceived low risk of infection while travelling. Side effects played a significant role for lack of adherence specific to malaria prophylaxis. Conclusions These data may help clinicians and public health providers to better understand reasons for non-adherence to PTA and target interventions to improve travellers understanding of potential and modifiable risks. Additionally, we discuss specific recommendations to increase public health education that may enable travellers to seek PTA.
BackgroundThe objective of this study is to evaluate ‘near miss’ and mortality in women with postpartum infections.MethodsWe performed a retrospective review of all patients referred to the University Teaching Hospital of Kigali (CHUK) between January 2012 and December 2013. We identified 117 patients with postpartum infections. Demographic data, length of admission, location of referral, initial surgery and subsequent treatment modalities including antibiotic administration and secondary surgery were recorded. The primary outcome of interest was a composite of maternal mortality and “near miss” defined as more than one laparotomy with/without hysterectomy and prolonged hospitalization.ResultsDiagnoses at CHUK were: pelvic peritonitis (56 %), deep surgical site infection including fasciitis (17 %), and endometritis (15 %). The primary procedures performed prior to transfer were: cesarean section (81 %), septic abortion management (12 %), and vaginal delivery (7 %). Antibiotics were initiated prior to transfer in 66 % of women. Surgery was required in 73 % of patients. Hysterectomies were performed in 22 % of patients. Maternal death occurred in 5 % of the patient population. The primary outcome of severe maternal morbidity and mortality occurred in 90 patients (77 %).ConclusionPeritonitis—primarily as a result of cesarean deliveries—is associated with significant morbidity and mortality in our population.
Background In non-inferiority trials, there is a concern that intention-to-treat (ITT) analysis, by including participants who did not receive the planned interventions, may bias towards making the treatment and control arms look similar and lead to mistaken claims of non-inferiority. In contrast, per protocol (PP) analysis is viewed as less likely to make this mistake and therefore preferable in non-inferiority trials. In a systematic review of antibiotic non-inferiority trials, we compared ITT and PP analyses to determine which analysis was more conservative. Methods In a secondary analysis of a systematic review, we included non-inferiority trials that compared different antibiotic regimens, used absolute risk reduction (ARR) as the main outcome and reported both ITT and PP analyses. All estimates and confidence intervals (CIs) were oriented so that a negative ARR favored the control arm, and a positive ARR favored the treatment arm. We compared ITT to PP analyses results. The more conservative analysis between ITT and PP analyses was defined as the one having a more negative lower CI limit. Results The analysis included 164 comparisons from 154 studies. In terms of the ARR, ITT analysis yielded the more conservative point estimate and lower CI limit in 83 (50.6%) and 92 (56.1%) comparisons respectively. The lower CI limits in ITT analysis favored the control arm more than in PP analysis (median of − 7.5% vs. -6.9%, p = 0.0402). CIs were slightly wider in ITT analyses than in PP analyses (median of 13.3% vs. 12.4%, p < 0.0001). The median success rate was 89% (interquartile range IQR 82 to 93%) in the PP population and 44% (IQR 23 to 60%) in the patients who were included in the ITT population but excluded from the PP population (p < 0.0001). Conclusions Contrary to common belief, ITT analysis was more conservative than PP analysis in the majority of antibiotic non-inferiority trials. The lower treatment success rate in the ITT analysis led to a larger variance and wider CI, resulting in a more conservative lower CI limit. ITT analysis should be mandatory and considered as either the primary or co-primary analysis for non-inferiority trials. Trial registration PROSPERO registration number CRD42020165040.
Background Antibiotic non-inferiority randomized controlled trials (RCTs) are used for approval of new antibiotics and making changes to antibiotic prescribing in clinical practice. We conducted a systematic review to assess the methodological and reporting quality of antibiotic non-inferiority RCTs. Methods We searched MEDLINE, Embase, the Cochrane Database of Systematic Reviews and the FDA drug database from inception until Nov 22, 2019 for non-inferiority RCTs comparing different systemic antibiotic therapies. Comparisons between antibiotic types, doses, administration routes or durations were included. Methodological and reporting quality indicators were based on the CONSORT reporting guidelines. Two independent reviewers extracted the data. Results The systematic review included 227 studies. Of these, 135 (59.5%) studies were supported by pharmaceutical industry. Only 83 (36.6%) studies provided a justification for the non-inferiority margin. Reporting of both intention-to-treat (ITT) and per-protocol (PP) analyses were done in 165 (72.7%) studies. The conclusion was misleading in 34 (15.0%) studies. The studies funded by pharmaceutical industry were less likely to be stopped early due to logistical reasons (3.0% vs. 19.1%, OR=0.13 95% CI 0.04-0.37) and to show inconclusive results (11.1% vs. 42.9%, OR=0.17 95% CI 0.08-0.33). The quality of studies decreased over time with respect to blinding, early stopping, reporting of ITT with PP analysis and having misleading conclusions. Conclusions There is room for improvement in the methodology and reporting of antibiotic non-inferiority trials. Quality can be improved across the entire spectrum from investigators, funding agencies, as well as during the peer-review process.
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