Magnitude and determinants of antibiotic dispensing without prescription in Spain: a simulated patient study

Objectives: Excessive and inappropriate use of antibiotics increases antimicrobial resistance. The aim of this study was to determine the magnitude and determinants of antibiotic dispensing without prescription in Spain by the simulated patient technique. Methods: A cross-sectional study was conducted with all the pharmacies in a region of north-west Spain (n = 977), between December 2016 and January 2017. Four actors visited the pharmacies simulating a respiratory infection. Four incremental levels of pressure were used to obtain an antibiotic. The education and sex of the person who was dispensing and the area where the pharmacy was located were recorded. The effect of these independent variables on the dispensing of an antibiotic without prescription (1 = yes, 0 = no) was modelled by logistic regression. Results: An antibiotic was obtained in 18.83% (95% CI = 16.5%-21.41%) of the visits. The area influenced the dispensing of antibiotics without a medical prescription, with a greater likelihood of dispensing in rural (OR = 1.79; 95% CI = 1.20-2.68) or semi-rural (OR = 1.66; 95% CI = 1.13-2.44) areas than in urban areas. No association was found with the sex or the training of the person who dispensed the antibiotic. In the pharmacies in urban areas, a lower level of pressure was needed to obtain the antibiotic. Conclusions: This study shows that one-fifth of the pharmacies still dispense antibiotics without prescription, especially under patient pressure. A rural setting has been identified as a risk factor for dispensing without prescription, so it must be taken into account for future interventions

Estimating spatiotemporally varying malaria reproduction numbers in a near elimination setting

In 2016 the World Health Organization identified 21 countries that could eliminate malaria by 2020. Monitoring progress towards this goal requires tracking ongoing transmission. Here we develop methods that estimate individual reproduction numbers and their variation through time and space. Individual reproduction numbers, Rc, describe the state of transmission at a point in time and differ from mean reproduction numbers, which are averages of the number of people infected by a typical case. We assess elimination progress in El Salvador using data for confirmed cases of malaria from 2010 to 2016. Our results demonstrate that whilst the average number of secondary malaria cases was below one (0.61, 95% CI 0.55–0.65), individual reproduction numbers often exceeded one. We estimate a decline in Rc between 2010 and 2016. However we also show that if importation is maintained at the same rate, the country may not achieve malaria elimination by 2020

Short-term effectiveness of a mobile phone app for increasing physical activity and adherence to the mediterranean diet in primary care: A randomized controlled trial (EVIDENT II study)

Background: The use of mobile phone apps for improving lifestyles has become generalized in the population, although little is still known about their effectiveness in improving health. Objective: We evaluate the effect of adding an app to standard counseling on increased physical activity (PA) and adherence to the Mediterranean diet, 3 months after implementation. Methods: A randomized, multicenter clinical trial was carried out. A total of 833 participants were recruited in six primary care centers in Spain through random sampling: 415 in the app+counseling group and 418 in the counseling only group. Counseling on PA and the Mediterranean diet was given to both groups. The app+counseling participants additionally received training in the use of an app designed to promote PA and the Mediterranean diet over a 3-month period. PA was measured with the 7-day Physical Activity Recall (PAR) questionnaire and an accelerometer; adherence to the Mediterranean diet was assessed using the Mediterranean Diet Adherence Screener questionnaire. Results: Participants were predominantly female in both the app+counseling (249/415, 60.0%) and counseling only (268/418, 64.1%) groups, with a mean age of 51.4 (SD 12.1) and 52.3 (SD 12.0) years, respectively. Leisure-time moderate-to-vigorous physical activity (MVPA) by 7-day PAR increased in the app+counseling (mean 29, 95% CI 5-53 min/week; P=.02) but not in the counseling only group (mean 17.4, 95% CI ''18 to 53 min/week; P=.38). No differences in increase of activity were found between the two groups. The accelerometer recorded a decrease in PA after 3 months in both groups: MVPA mean ''55.3 (95% CI ''75.8 to ''34.9) min/week in app+counseling group and mean ''30.1 (95% CI ''51.8 to ''8.4) min/week in counseling only group. Adherence to the Mediterranean diet increased in both groups (8.4% in app+counseling and 10.4% in counseling only group), with an increase in score of 0.42 and 0.53 points, respectively (P<.001), but no difference between groups (P=.86). Conclusions: Leisure-time MVPA increased more in the app+counseling than counseling only group, although no difference was found when comparing the increase between the two groups. Counseling accompanied by printed materials appears to be effective in improving adherence to the Mediterranean diet, although the app does not increase adherence

Factors Associated with the Rapid and Durable Decline in Malaria Incidence in El Salvador, 1980-2017

A decade after the Global Malaria Eradication Program, El Salvador had the highest burden of malaria in Mesoamerica, with approximately 20% due to Plasmodium falciparum. A resurgence of malaria in the 1970s led El Salvador to alter its national malaria control strategy. By 1995, El Salvador recorded its last autochthonous P. falciparum case with fewer than 20 Plasmodium vivax cases annually since 2011. By contrast, its immediate neighbors continue to have the highest incidences of malaria in the region. We reviewed and evaluated the policies and interventions implemented by the Salvadoran National Malaria Program that likely contributed to this progress toward malaria elimination. Decentralization of the malaria program, early regional stratification by risk, and data-driven stratum-specific actions resulted in the timely and targeted allocation of resources for vector control, surveillance, case detection, and treatment. Weekly reporting by health workers and volunteer collaborators-distributed throughout the country by strata and informed via the national surveillance system-enabled local malaria teams to provide rapid, adaptive, and focalized program actions. Sustained investments in surveillance and response have led to a dramatic reduction in local transmission, with most current malaria cases in El Salvador due to importation from neighboring countries. Additional support for systematic elimination efforts in neighboring countries would benefit the region and may be needed for El Salvador to achieve and maintain malaria elimination. El Salvador's experience provides a relevant case study that can guide the application of similar strategies in other countries committed to malaria elimination

Evaluating the impact of programmatic mass drug administration for malaria in Zambia using routine incidence data.

BACKGROUND NlmCategory: BACKGROUND content: In 2016, the Zambian National Malaria Elimination Centre started programmatic mass drug administration (pMDA) campaigns with dihydroartemisinin-piperaquine as a malaria elimination tool in Southern Province. Two rounds were administered, two months apart (coverage 70% and 57% respectively). We evaluated the impact of one year of pMDA on malaria incidence using routine data. - Label: METHODS NlmCategory: METHODS content: We conducted an interrupted time series with comparison group analysis on monthly incidence data collected at the health facility catchment area (HFCA) level, with a negative binomial model using generalized estimating equations. pMDA was conducted in HFCAs with greater than 50 cases/1,000 people/year. Ten HFCAs with incidence rates marginally above this threshold (pMDA group) were compared to 20 HFCAs marginally below (comparison group). - Label: RESULTS NlmCategory: RESULTS content: "The pMDA HFCAs saw a 46% greater decrease in incidence at the time of intervention than the comparison areas (incidence rate ratio: 0.536 [0.337-0.852]); however, incidence increased toward the end of the season. No HFCAs saw a transmission interruption." - Label: CONCLUSION NlmCategory: CONCLUSIONS content: pMDA, implemented during one year with imperfect coverage in low transmission areas with sub-optimal vector control coverage, significantly reduced incidence. However, elimination will require additional tools. Routine data are important resources for programmatic impact evaluations and should be considered for future analyses

Pre-exposure prophylaxis with hydroxychloroquine for COVID-19 : a double-blind, placebo-controlled randomized clinical trial

Background: Pre-exposure prophylaxis (PrEP) is a promising strategy to break COVID-19 transmission. Although hydroxychloroquine was evaluated for treatment and post-exposure prophylaxis, it is not evaluated for COVID-19 PrEP yet. The aim of this study was to evaluate the efficacy and safety of PrEP with hydroxychloroquine against placebo in healthcare workers at high risk of SARS-CoV-2 infection during an epidemic period. Methods: We conducted a double-blind placebo-controlled randomized clinical trial in three hospitals in Barcelona, Spain. From 350 adult healthcare workers screened, we included 269 participants with no active or past SARS-CoV-2 infection (determined by a negative nasopharyngeal SARS-CoV-2 PCR and a negative serology against SARS-CoV-2). Participants allocated in the intervention arm (PrEP) received 400 mg of hydroxychloroquine daily for the first four consecutive days and subsequently, 400 mg weekly during the study period. Participants in the control group followed the same treatment schedule with placebo tablets. Results: 52.8% (142/269) of participants were in the hydroxychloroquine arm and 47.2% (127/269) in the placebo arm. Given the national epidemic incidence decay, only one participant in each group was diagnosed with COVID-19. The trial was stopped due to futility and our study design was deemed underpowered to evaluate any benefit regarding PrEP efficacy. Both groups showed a similar proportion of participants experiencing at least one adverse event (AE) (p=0.548). No serious AEs were reported. Almost all AEs (96.4%, 106/110) were mild. Only mild gastrointestinal symptoms were significantly higher in the hydroxychloroquine arm compared to the placebo arm (27.4% (39/142) vs 15.7% (20/127), p=0.041). Conclusions: Although the efficacy of PrEP with hydroxychloroquine for preventing COVID-19 could not be evaluated, our study showed that PrEP with hydroxychloroquine at low doses is safe. Trial registration: ClinicalTrials.govNCT04331834. Registered on April 2, 2020

Moving towards malaria elimination in southern Mozambique: Cost and cost-effectiveness of mass drug administration combined with intensified malaria control.

BACKGROUND: As new combinations of interventions aiming at interrupting malaria transmission are under evaluation, understanding the associated economic costs and benefits is critical for decision-making. This study assessed the economic cost and cost-effectiveness of the Magude project, a malaria elimination initiative implemented in a district in southern Mozambique (i.e. Magude) between August 2015-June 2018. This project piloted a combination of two mass drug administration (MDA) rounds per year for two consecutive years, annual rounds of universal indoor residual spraying (IRS) and a strengthened surveillance and response system on the back of universal long-lasting insecticide treated net (LLIN) coverage and routine case management implemented by the National Malaria Control Program (NMCP). Although local transmission was not interrupted, the project achieved large reductions in the burden of malaria in the target district. METHODS: We collected weekly economic data, estimated costs from the project implementer perspective and assessed the incremental cost-effectiveness ratio (ICER) associated with the Magude project as compared to routine malaria control activities, the counterfactual. We estimated disability-adjusted life years (DALYs) for malaria cases and deaths and assessed the variation of the ICER over time to capture the marginal costs and effectiveness associated with subsequent phases of project implementation. We used deterministic and probabilistic sensitivity analyses to account for uncertainty and built an alternative scenario by assuming the implementation of the interventions from a governmental perspective. Economic costs are provided in constant US$2015. RESULTS: After three years, the Magude project averted a total of 3,171 DALYs at an incremental cost of$2.89 million and an average yearly cost of $20.7 per targeted person. At an average cost of$19.4 per person treated per MDA round, the social mobilization and distribution of door-to-door MDA contributed to 53% of overall resources employed, with personnel and logistics being the main cost drivers. The ICER improved over time as a result of decreasing costs and improved effectiveness. The overall ICER was $987 (CI95$1,404/DALY averted, three times the gross domestic product (GDP) per capita of Mozambique, but above the threshold of interventions considered highly cost-effective (one time the GDP per capita or $468/DALY averted) and above the recently suggested thresholds based on the health opportunity cost ($537 purchasing power parity/ DALY averted). A significantly lower ICER was obtained in the implementation scenario from a governmental perspective ($441/DALY averted). CONCLUSION: Despite the initial high costs and volume of resources associated with its implementation, MDA in combination with other existing malaria control interventions, can be a cost-effective strategy to drastically reduce transmission in areas of low to moderate transmission in sub-Saharan Africa. However, further studies are needed to understand the capacity of the health system and financial affordability to scale up such strategies at regional or national level