Viral reactivations and co-infections in COVID-19 patients: a systematic review.

BACKGROUND: Viral reactivations and co-infections have been reported among COVID-19 patients. However, studies on the clinical outcomes of different viral reactivations and co-infections are currently in limit. Thus, the primary purpose of this review is to perform an overarching investigation on the cases of latent virus reactivation and co-infection in COVID-19 patients to build collective evidence contributing to improving patient health. The aim of the study was to conduct a literature review to compare the patient characteristics and outcomes of reactivations and co-infections of different viruses. METHODS: Our population of interest included confirmed COVID-19 patients who were diagnosed with a viral infection either concurrently or following their COVID-19 diagnosis. We extracted the relevant literature through a systematic search using the key terms in the online databases including the EMBASE, MEDLINE, Latin American Caribbean Health Sciences Literature (LILACS), from inception onwards up to June 2022. The authors independently extracted data from eligible studies and assessed the risk of bias using the Consensus-based Clinical Case Reporting (CARE) guidelines and the Newcastle-Ottawa Scale (NOS). Main patient characteristics, frequency of each manifestation, and diagnostic criteria used in studies were summarized in tables. RESULTS: In total, 53 articles were included in this review. We identified 40 reactivation studies, 8 coinfection studies, and 5 studies where concomitant infection in COVID-19 patients was not distinguished as either reactivation or coinfection. Data were extracted for 12 viruses including IAV, IBV, EBV, CMV, VZV, HHV-1, HHV-2, HHV-6, HHV-7, HHV-8, HBV, and Parvovirus B19. EBV, HHV-1, and CMV were most frequently observed within the reactivation cohort, whereas IAV and EBV within the coinfection cohort. In both reactivation and coinfection groups, patients reported cardiovascular disease, diabetes, and immunosuppression as comorbidities, acute kidney injury as complication, and lymphopenia and elevated D-dimer and CRP levels from blood tests. Common pharmaceutical interventions in two groups included steroids and antivirals. CONCLUSION: Overall, these findings expand our knowledge on the characteristics of COVID-19 patients with viral reactivations and co-infections. Our experience with current review indicates a need for further investigations on virus reactivation and coinfection among COVID-19 patients.

Prioritising Cochrane reviews to be updated with health equity focus.

BACKGROUND: The prioritisation of updating published systematic reviews of interventions is vital to prevent research waste and ensure relevance to stakeholders. The consideration of health equity in reviews is also important to ensure interventions will not exacerbate the existing inequities of the disadvantaged if universally implemented. This study aimed to pilot a priority setting exercise based on systematic reviews of interventions published in the Cochrane Library, to identify and prioritise reviews to be updated with a focus on health equity. METHODS: We conducted a priority setting exercise with a group of 13 international stakeholders. We identified Cochrane reviews of interventions that showed a reduction in mortality, had at least one Summary of Findings table and that focused on one of 42 conditions with a high global burden of disease from the 2019 WHO Global Burden of Disease report. This included 21 conditions used as indicators of success of the United Nations Universal Health Coverage in attaining the Sustainable Development Goals. Stakeholders prioritised reviews that were relevant to disadvantaged populations, or to characteristics of potential disadvantage within the general population. RESULTS: After searching for Cochrane reviews of interventions within 42 conditions, we identified 359 reviews that assessed mortality and included at least one Summary of Findings table. These pertained to 29 of the 42 conditions; 13 priority conditions had no reviews with the outcome mortality. Reducing the list to only reviews showing a clinically important reduction in mortality left 33 reviews. Stakeholders ranked these reviews in order of priority to be updated with a focus on health equity. CONCLUSIONS: This project developed and implemented a methodology to set priorities for updating systematic reviews spanning multiple health topics with a health equity focus. It prioritised reviews that reduce overall mortality, are relevant to disadvantaged populations, and focus on conditions with a high global burden of disease. This approach to the prioritisation of systematic reviews of interventions that reduce mortality provides a template that can be extended to reducing morbidity, and the combination of mortality and morbidity as represented in Disability-Adjusted Life Years and Quality-Adjusted Life Years.

Relevance and quality of implementation research proposals to face the challenges of public health in Latin-America and the Caribbean.

OBJECTIVES: To analyse the relevance and quality of the research proposals submitted to the 2016 call for proposals for the initiative Improving Programme Implementation through Embedded Research (iPIER-2016) to address current public health challenges in Latin America and the Caribbean. METHODS: We performed a cross-sectional study using information from 108 research proposals using quantitative and qualitative methods. We used three frameworks to analyse the relevance of the proposals: The Global Burden of Disease, the WHO Health Systems Conceptual Framework and the Sustainable Development Goals proposed in 2015 by the United Nations. We performed an index to analyse the relevance and quality of the proposals. RESULTS: Twenty seven percent of the proposals have very good relevance, one third of the proposals have quality flaws. This means their research questions are not related to implementation research or their methods are insufficient or inadequate to respond to the objective. CONCLUSIONS: The response to this call is proof of health authorities' interest in research as a tool to improve the implementation of health programs in the region. However, proposals show important variations in terms of relevance and quality among countries and training health staff in programme implementation seems a central requirement.

Evidence for Human-to-Human Transmission of Hantavirus: A Systematic Review.

BACKGROUND: Hantavirus is known to be transmitted from rodents to humans. However, some reports from Argentina and Chile have claimed that the hantavirus strain Andes virus (ANDV) can cause human-to-human transmission of the disease. The aim of this systematic review was to assess the evidence for human-to-human transmission of hantavirus. METHODS: We searched PubMed (inception to 28 February 2021), Cochrane Central, Embase, LILACS and SciELO (inception to 3 July 2020), and other sources. We included studies that assessed whether interpersonal contact with a person with laboratory-confirmed hantavirus infection led to human-to-human transmission. Two reviewers conducted screening, selection, data extraction, and risk of bias assessment. RESULTS: Twenty-two studies met the inclusion criteria. Meta-analysis was not possible due to heterogeneity. With the exception of 1 prospective cohort study of ANDV in Chile with serious risk of bias, evidence from comparative studies (strongest level of evidence available) does not support human-to-human transmission of hantavirus infection. Noncomparative studies with a critical risk of bias suggest that human-to-human transmission of ANDV may be possible. CONCLUSIONS: The balance of the evidence does not support the claim of human-to-human transmission of ANDV. Well-designed cohort and case-control studies that control for co-exposure to rodents are needed to inform public health recommendations.

Collaboration between health system decision makers and professional researchers to coproduce knowledge, a scoping review.

BACKGROUND: Recent literature uses different terms and approaches to the collaboration between researchers and health system decision-makers in the research process. In 2012, the World Health Organisation proposed to "Embed research within decision-making processes". Yet, important contributions use other terms and perspectives for the same issue. This scoping review aimed to identify these terms, approaches, their application and eventual influence on the utilization of evidence. METHODS: We searched papers published between January 2000 and February 2019 in English, Spanish, French and Portuguese in the databases of PubMed, Scielo, Google Scholar and EBSCOhost, thus accessing MedicLatina, MEDLINE Complete and eBook Collection. Our main inclusion criterion was the participation of health personnel in non-clinical research activities. We considered three domains for in depth analysis: Definition, name and description of the participation of decision makers and health staff; Forms of collaboration and actual/effective participation of health staff in research; Eventual influence on the utilization of research results. RESULTS: We identified 607 articles and selected 74 for full text analysis. Nineteen different terms are currently used in twelve countries to describe the participation of health decision-makers and staff in research activities. Most publications refer to Integrated Knowledge Translation or Embedded Research, and were published in Canada and the United Kingdom. Forty-five papers discuss the participation of health staff in research activities; 20 leading the whole process and 21 as collaborators. CONCLUSIONS: The identification of the different terms and approaches to the close collaboration of health staff and decision-makers with professional researchers is essential to promote its effective application and influence on the utilization of evidence. Yet, it is also necessary to insist in their co-participation throughout the whole investigation process as a relevant way to improve research results uptake, strengthen health systems and advance towards universal health coverage.

[Mapping of research protocols, publications, and collaborations on COVID-19 in Latin America and the CaribbeanMapeamento de protocolos de pesquisa, publicações e colaborações sobre COVID-19 na América Latina e no Caribe]. / Mapeo de protocolos de investigación, publicaciones y colaboraciones sobre la COVID-19 en América Latina y el Caribe.

Objective: To map research protocols, publications, and collaborations on coronavirus disease 2019 (COVID-19) developed in Latin America and the Caribbean (LAC). Methods: Included were research protocols registered in international platforms and research publications containing populations, data, or authors from LAC. The source of information for protocols was primarily the International Clinical Trial Registry Platform (ICTRP) of the World Health Organization; for publications, specific electronic databases and repositories pertaining to COVID-19 were used. The search for publications was conducted up to 11 November; the search for protocols, up to 30 November 2020 (both dates inclusive). Data was extracted from protocols using standardized variables from the ICTRP, and from publications following pre-established criteria. Results: Among the protocols, 63.0% were therapeutic studies, 10% focused on prevention, and 45% were collaborative; 64% of the protocols received no funding from industry; 23% of the publications were not peer-reviewed and 23% were collaborative in nature. The most frequent study designs were systematic reviews and cross-sectional studies; 47.1% of studies were conducted in health facilities and 22% in community settings; 38.0% focused on diagnosis and 27.9% on prognosis. A qualitative synthesis was performed by line of care and approach strategies. Conclusions: There was an increase in the number of collaborative research studies relative to earlier studies and in protocols not funded by industry. The proposed research agenda was covered in large part as the pandemic unfolded.

Objetivo: Mapear protocolos de pesquisa, publicações e colaborações sobre a doença causada pelo coronavírus 2019 (COVID-19, na sigla em inglês) desenvolvidos na América Latina e no Caribe (ALC). Métodos: Foram incluídos protocolos registrados em plataformas internacionais e publicações de pesquisas que consideraram população, dados e autores da ALC. A fonte de informação para os protocolos foi principalmente a Plataforma Internacional de Registros de Ensaios Clínicos (ICTRP, na sigla em inglês) da Organização Mundial da Saúde. Para as publicações, foram utilizadas bases de dados eletrônicas e repositórios específicos sobre COVID-19. As publicações foram pesquisadas até 11 de novembro, e os protocolos, até 30 de novembro de 2020 (inclusive). As informações dos protocolos foram extraídas de acordo com variáveis padronizadas da plataforma ICTRP e das publicações, segundo critérios pré-estabelecidos. Resultados: Dos protocolos, 63% eram estudos sobre terapias, 10% sobre prevenção e 45% eram colaborativos. Em relação ao financiamento, 64% dos protocolos não vieram da indústria. Em relação às publicações, 23% eram sem revisão por pares e 23% eram colaborativas. Os delineamentos mais frequentes foram revisões sistemáticas e estudos transversais; 47,1% foram realizados em serviços de saúde e 22% no âmbito comunitário; 38,0% focaram no diagnóstico e 27,9% no prognóstico. Realizou-se uma síntese qualitativa segundo a linha de cuidado e as estratégias de abordagem. Conclusões: Observou-se um aumento no número de pesquisas colaborativas (em comparação com estudos anteriores) e de protocolos não financiados pela indústria. A agenda de pesquisa proposta foi coberta, em grande parte, à medida que a pandemia progredia.

Hospital readmissions and emergency department re-presentation of COVID-19 patients: a systematic review.

Objective: To characterize the frequency, causes, and predictors of readmissions of COVID-19 patients after discharge from heath facilities or emergency departments, interventions used to reduce readmissions, and outcomes of COVID-19 patients discharged from such settings. Methods: We performed a systematic review for case series and observational studies published between January 2020 and April 2021 in PubMed, Embase, LILACS, and MedRxiv, reporting the frequency, causes, or risk factors for readmission of COVID-19 survivors/patients. We conducted a narrative synthesis and assessed the methodological quality using the JBI critical appraisal checklist. Results: We identified 44 studies including data from 10 countries. The overall 30-day median readmission rate was 7.1%. Readmissions varied with the length of follow-up, occurring <10.5%, <14.5%, <21.5%, and <30%, respectively, for 10, 30, 60, and 253 days following discharge. Among those followed up for 30 and 60 days, the median time from discharge to readmission was 3 days and 8-11 days, respectively. The significant risk factor associated with readmission was having shorter length of stay, and the important causes included respiratory or thromboembolic events and chronic illnesses. Emergency department re-presentation was >20% in four studies. Risk factors associated with mortality were male gender, advanced age, and comorbidities. Conclusions: Readmission of COVID-19 survivors is frequent, and post-discharge mortality is significant in specific populations. There is an urgent need to further examine underlying reasons for early readmission and to prevent additional readmissions and adverse outcomes in COVID-19 survivors.

Antibiotic prophylaxis for surgical procedures: a scoping review.

OBJECTIVES: To map the current evidence on surgical antibiotic prophylaxis (SAP) administration and identify knowledge gaps in the literature available in this field. METHODS: The PubMed, Cochrane Library, Epistemonikos, and Health Systems Evidence databases were searched from January 2015 to March 2020 for systematic reviews published in English, French, Portuguese, and Spanish. RESULTS: Eighty-three systematic reviews were included, the quality of the reviews was assessed using AMSTAR 2, and data were extracted for all primary outcomes. Perioperative antibiotic administration, the use of first generation cephalosporins, and surgical site infection (SSI) were the most commonly reported for timing of antibiotic administration, drug class, and primary outcome, respectively. Findings showed that, overall, SAP may reduce SSIs compared with a placebo or with no SAP. Results suggested that intraoperative SAP may lower SSI, while postoperative SAP did not show a statistically significant difference. CONCLUSIONS: Findings have confirmed the role of SAP in reducing postoperative SSI across various surgeries and do not support the use of antibiotics after surgery to prevent infections. The findings of this scoping review have enhanced the evidence base that can inform decisions regarding the development of global guidelines for the prevention of SSI. However, high-quality systematic reviews and research reflecting diverse populations and settings are needed.

[The landscape of COVID-19 clinical trials in Latin America and the Caribbean: assessment and challenges]. / El panorama de los ensayos clínicos sobre COVID-19 en América Latina y el Caribe: evaluación y desafíos.

A considerable number of clinical trials is being conducted globally in response to the COVID-19 pandemic, including in low- and middle-income countries such as those in the Latin America and Caribbean region (LAC). Yet, an abundance of studies does not necessarily shorten the path to find safe and efficacious interventions for COVID-19. We analyze the trials for COVID-19 treatment and prevention that are registered from LAC countries in the International Clinical Trials Registry Platform, and identify a trend towards small repetitive non-rigorous studies that duplicate efforts and drain limited resources without producing meaningful conclusions on the safety and efficacy of the interventions being tested. We further assess the challenges to conducting scientifically sound and socially valuable research in the LAC region in order to inform recommendations to encourage clinical trials that are most likely to produce robust evidence during the pandemic.

An overview of reviews on strategies to reduce health inequalities.

BACKGROUND: Governments are incentivized to develop and implement health action programs focused on equity to ensure progress with effective strategies or interventions. OBJECTIVE: Identify and synthesize strategies or interventions that facilitate the reduction of health inequalities. METHODS: A systematic search strategy was carried out up until August 2019 in MEDLINE (Ovid), Embase (Elsevier), Cochrane Database of Systematic Reviews, LILACS, Scopus, Scielo and Epistemonikos. In addition, a snowball strategy was used. Literature reviews (LRs) of experimental and quasi-experimental studies were included. The identified interventions and outcomes were categorized based on the recommendation by the Cochrane group in "Effective Practice and Organization of Care". The quality of the included LRs was evaluated using the AMSTAR 2 tool. RESULTS: Four thousand ninety-five articles were identified, of which 97 were included in the synthesis of evidence. Most of the studies included focused on the general population, vulnerable populations and minority populations. The subjects of general health and healthy lifestyles were the most commonly addressed. According to the classification of the type of intervention, the domain covered most was the delivery arrangements, followed by the domain of implementation strategies. The most frequent group of outcomes was the reported outcome in (clinical) patients, followed by social outcomes. CONCLUSION: The strategies that facilitate the reduction of health inequalities must be intersectoral and multidisciplinary in nature, including all sectors of the health system. It is essential to continue generating interventions focused on strengthening health systems in order to achieve adequate universal health coverage, with a process of comprehensive and quality care.

Interventions for American cutaneous and mucocutaneous leishmaniasis.

BACKGROUND: On the American continent, cutaneous and mucocutaneous leishmaniasis (CL and MCL) are diseases associated with infection by several species of Leishmania parasites. Pentavalent antimonials remain the first-choice treatment. There are alternative interventions, but reviewing their effectiveness and safety is important as availability is limited. This is an update of a Cochrane Review first published in 2009. OBJECTIVES: To assess the effects of interventions for all immuno-competent people who have American cutaneous and mucocutaneous leishmaniasis (ACML). SEARCH METHODS: We updated our database searches of the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, LILACS and CINAHL to August 2019. We searched five trials registers. SELECTION CRITERIA: Randomised controlled trials (RCTs) assessing either single or combination treatments for ACML in immuno-competent people, diagnosed by clinical presentation and Leishmania infection confirmed by smear, culture, histology, or polymerase chain reaction on a biopsy specimen. The comparators were either no treatment, placebo only, or another active compound. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our key outcomes were the percentage of participants 'cured' at least three months after the end of treatment, adverse effects, and recurrence. We used GRADE to assess evidence certainty for each outcome. MAIN RESULTS: We included 75 studies (37 were new), totalling 6533 randomised participants with ATL. The studies were mainly conducted in Central and South America at regional hospitals, local healthcare clinics, and research centres. More male participants were included (mean age: roughly 28.9 years (SD: 7.0)). The most common confirmed species were L. braziliensis, L. panamensis, and L. mexicana. The most assessed interventions and comparators were non-antimonial systemics (particularly oral miltefosine) and antimonials (particularly meglumine antimoniate (MA), which was also a common intervention), respectively. Three studies included moderate-to-severe cases of mucosal leishmaniasis but none included cases with diffuse cutaneous or disseminated CL, considered the severe cutaneous form. Lesions were mainly ulcerative and located in the extremities and limbs. The follow-up (FU) period ranged from 28 days to 7 years. All studies had high or unclear risk of bias in at least one domain (especially performance bias). None of the studies reported the degree of functional or aesthetic impairment, scarring, or quality of life. Compared to placebo, at one-year FU, intramuscular (IM) MA given for 20 days to treat L. braziliensis and L. panamensis infections in ACML may increase the likelihood of complete cure (risk ratio (RR) 4.23, 95% confidence interval (CI) 0.84 to 21.38; 2 RCTs, 157 participants; moderate-certainty evidence), but may also make little to no difference, since the 95% CI includes the possibility of both increased and reduced healing (cure rates), and IMMA probably increases severe adverse effects such as myalgias and arthralgias (RR 1.51, 95% CI 1.17 to 1.96; 1 RCT, 134 participants; moderate-certainty evidence). IMMA may make little to no difference to the recurrence risk, but the 95% CI includes the possibility of both increased and reduced risk (RR 1.79, 95% CI 0.17 to 19.26; 1 RCT, 127 participants; low-certainty evidence). Compared to placebo, at six-month FU, oral miltefosine given for 28 days to treat L. mexicana, L. panamensis and L. braziliensis infections in American cutaneous leishmaniasis (ACL) probably improves the likelihood of complete cure (RR 2.25, 95% CI 1.42 to 3.38), and probably increases nausea rates (RR 3.96, 95% CI 1.49 to 10.48) and vomiting (RR 6.92, 95% CI 2.68 to 17.86) (moderate-certainty evidence). Oral miltefosine may make little to no difference to the recurrence risk (RR 2.97, 95% CI 0.37 to 23.89; low-certainty evidence), but the 95% CI includes the possibility of both increased and reduced risk (all based on 1 RCT, 133 participants). Compared to IMMA, at 6 to 12 months FU, oral miltefosine given for 28 days to treat L. braziliensis, L. panamensis, L. guyanensis and L. amazonensis infections in ACML may make little to no difference to the likelihood of complete cure (RR 1.05, 95% CI 0.90 to 1.23; 7 RCTs, 676 participants; low-certainty evidence). Based on moderate-certainty evidence (3 RCTs, 464 participants), miltefosine probably increases nausea rates (RR 2.45, 95% CI 1.72 to 3.49) and vomiting (RR 4.76, 95% CI 1.82 to 12.46) compared to IMMA. Recurrence risk was not reported. For the rest of the key comparisons, recurrence risk was not reported, and risk of adverse events could not be estimated. Compared to IMMA, at 6 to 12 months FU, oral azithromycin given for 20 to 28 days to treat L. braziliensis infections in ACML probably reduces the likelihood of complete cure (RR 0.51, 95% CI 0.34 to 0.76; 2 RCTs, 93 participants; moderate-certainty evidence). Compared to intravenous MA (IVMA) and placebo, at 12 month FU, adding topical imiquimod to IVMA, given for 20 days to treat L. braziliensis, L. guyanensis and L. peruviana infections in ACL probably makes little to no difference to the likelihood of complete cure (RR 1.30, 95% CI 0.95 to 1.80; 1 RCT, 80 participants; moderate-certainty evidence). Compared to MA, at 6 months FU, one session of local thermotherapy to treat L. panamensis and L. braziliensis infections in ACL reduces the likelihood of complete cure (RR 0.80, 95% CI 0.68 to 0.95; 1 RCT, 292 participants; high-certainty evidence). Compared to IMMA and placebo, at 26 weeks FU, adding oral pentoxifylline to IMMA to treat CL (species not stated) probably makes little to no difference to the likelihood of complete cure (RR 0.86, 95% CI 0.63 to 1.18; 1 RCT, 70 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Evidence certainty was mostly moderate or low, due to methodological shortcomings, which precluded conclusive results. Overall, both IMMA and oral miltefosine probably result in an increase in cure rates, and nausea and vomiting are probably more common with miltefosine than with IMMA. Future trials should investigate interventions for mucosal leishmaniasis and evaluate recurrence rates of cutaneous leishmaniasis and its progression to mucosal disease.

Health system decision-makers at the helm of implementation research: development of a framework to evaluate the processes and effectiveness of embedded approaches.

BACKGROUND: Embedded approaches to implementation research (IR), whereby health system decision-makers participate actively in the research process, are gaining traction as effective approaches to optimise the delivery of health programmes and policies. However, the evidence base on the processes and effectiveness of such collaborative research remains inchoate. Standardised approaches to evaluate these initiatives are needed to identify core elements of 'embeddedness', unveil the underlying pathways of change, and assess contribution to evidence uptake in decision-making and overall outcomes of effect. The framework presented in this paper responds to this need, designed to guide the systematic evaluation of embedded IR. METHODS: This evaluation framework for embedded IR approaches is based on the experience of a joint initiative by the Pan American Health Organization/Alliance for Health Policy and Systems Research, which has supported 19 IR grants in 10 Latin American and Caribbean countries from 2014 to 2017. The conceptualisation of this framework drew on various sources of information, including empirical evidence and conceptual insights from the literature, interviews with content experts, and a prospective evaluation of the 2016 cohort that included semi-structured key informant interviews, document analysis, and a research team survey to examine key aspects of embedded research. RESULTS: We developed a widely applicable conceptual framework to guide the evaluation of embedded IR in various contexts. Focused on uncovering how this collaborative research approach influences programme improvement, it outlines expected processes and intermediate outcomes. It also highlights constructs with which to assess 'embeddedness' as well as critical contextual factors. The framework is intended to provide a structure by which to systematically examine such embedded research initiatives, proposing three key stages of evidence-informed decision-making - co-production of evidence, engagement with research, and enactment of programme changes. CONCLUSION: Rigorous evaluation of embedded IR is needed to build the evidence on its processes and effectiveness in influencing decision-making. The evaluation framework presented here addresses this gap with consideration of the complexity of such efforts. Its applicability to similar initiatives is bolstered by virtue of being founded on real-world experience; its potential to contribute to a nuanced understanding of embedded IR is significant.

[Factors and interventions that affect working conditions and environment to increase the attraction, recruitment and retention of human resources for health at the primary care level in rural, remote or underserved areas]. / Factores e intervenciones que inciden en las condiciones y medio ambiente de trabajo para incrementar la atracción, captación y retención de recursos humanos en salud en el primer nivel de atención de áreas rurales, remotas o desatendidas.

OBJECTIVE: To identify and systematize available empirical evidence on factors and interventions that affect working conditions and environment in order to increase the attraction, recruitment and retention of human resources for health at the primary care level in rural, remote or underserved areas. METHODS: Rapid review of reviews selected according to relevance, eligibility and inclusion criteria. The search was conducted on electronic and manual databases, including grey literature. AMSTAR I was used to assess the quality of systematic reviews and a thematic analysis for synthesis of the results. RESULTS: Sixteen reviews were included, one of which contained 14 reviews. Of the total, 20 reviews analyzed factors and 9 evaluated the effectiveness of interventions. The evidence on factors is abundant, but of limited quality. Individual, family and "previous exposure to a rural setting" factors were associated with higher recruitment; organizational and external context factors were important for human resource retention. Networking and professional support influenced recruitment and retention. Evidence on the effectiveness of interventions was limited, both in quantity and quality. The most frequently used intervention was incentives. CONCLUSIONS: Evidence on factors that are positively related to recruitment and retention of workers at the first level of care in rural, remote or underserved areas is sufficient and should be taken into account when designing interventions. Quality evidence on the effectiveness of interventions is scarce. More controlled studies with methodological rigor are needed, particularly in the Americas.

The landscape of COVID-19 clinical trials in Latin America and the Caribbean: assessment and challenges.

A considerable number of clinical trials is being conducted globally in response to the COVID-19 pandemic, including in low- and middle-income countries such as those in the Latin America and Caribbean region (LAC). Yet, an abundance of studies does not necessarily shorten the path to find safe and efficacious interventions for COVID-19. We analyze the trials for COVID-19 treatment and prevention that are registered from LAC countries in the International Clinical Trials Registry Platform, and identify a trend towards small repetitive non-rigorous studies that duplicate efforts and drain limited resources without producing meaningful conclusions on the safety and efficacy of the interventions being tested. We further assess the challenges to conducting scientifically sound and socially valuable research in the LAC region in order to inform recommendations to encourage clinical trials that are most likely to produce robust evidence during the pandemic.

Se está llevando a cabo un número considerable de ensayos clínicos en todo el mundo en respuesta a la pandemia de COVID-19, incluso en países de ingresos bajos y medios como los de la región de América Latina y el Caribe. Sin embargo, la abundancia de estudios no necesariamente acorta el camino para encontrar intervenciones seguras y eficaces frente a la COVID-19. Se analizaron los ensayos para el tratamiento y la prevención de la COVID-19 de los países de América Latina y el Caribe que están registrados en la Plataforma de Registros Internacionales de Ensayos Clínicos de la Organización Mundial de la Salud, y se identificó una tendencia hacia la realización de estudios pequeños, repetitivos y no rigurosos que duplican los esfuerzos y merman recursos limitados sin producir conclusiones significativas sobre la seguridad y la eficacia de las intervenciones evaluadas. Se evaluaron asimismo los desafíos que plantea la realización de investigaciones científicamente sólidas y socialmente valiosas en la región de América Latina y el Caribe a fin de brindar recomendaciones que alienten la realización de ensayos clínicos que tengan más probabilidades de producir evidencia sólida durante la pandemia.

[Skill mix of nurses and primary health care professionals: a systematic review]. / Combinação de tarefas do enfermeiro e de outros profissionais na atenção primária em saúde: uma revisão sistemática.

OBJECTIVE: To evaluate the effectiveness of the strategy of skill mix of nurses and other health care professionals in primary health care. METHODS: Systematic review of the literature aligned with the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), including observational and intervention studies. No restrictions were established for period or country of publication; studies published in Spanish, English and Portuguese were included. The search was carried out in MEDLINE, CINAHL, LILACS, EMBASE and Web of Science electronic databases. RESULTS: Eighteen studies were analyzed, including 6 from the United States; 3 from the Netherlands; 2 from the United Kingdom; 1 each from Australia, South Africa, South Korea, Scotland, Haiti and Japan; and 1 study with a prospective observational design from 8 countries. The studies reported that the skill mix among health professionals enables a better use of material resources; optimizes time spent on care; improves adhesion to treatment, quality of care and commitment and satisfaction with the work; and reduces the level of psychological distress in nursing professionals. CONCLUSIONS: The expansion of tasks of nurses and other health care professionals, and the skill mix as well as the development of interprofessional teams, are strategies that help to face a scarcity and poor distribution of human resources in urban and non-urban areas with improvement of the health care of the population and satisfaction of professionals and clients.

Chronic kidney diseases in agricultural communities: report from a workshop.

In June 2018, the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Environmental Health Sciences sponsored a workshop to identify research gaps in an increasingly common form of chronic kidney disease in agricultural communities, often termed "CKDu." The organizers invited a broad range of experts who provided diverse expertise and perspectives, many of whom had never addressed this particular epidemic. Discussion was focused around selected topics, including identifying and mitigating barriers to research in CKDu, creating a case definition, and defining common data elements. All hypotheses regarding etiology were entertained, and meeting participants discussed potential research strategies, choices in study design, and novel tools that may prove useful in this disease. Achievements of the workshop included robust cross-disciplinary discussion and preliminary planning of research goals and design. Specific challenges in implementing basic and clinical research and interventions in low- and middle-income countries were recognized. A balanced approach to leveraging local resources and capacity building without overreaching was emphasized.

Interventions for pityriasis rosea.

BACKGROUND: Pityriasis rosea is a scaly, itchy rash that mainly affects young adults and lasts for 2 to 12 weeks. The effects of many available treatments are uncertain. This is an update of a Cochrane Review first published in 2007. OBJECTIVES: To assess the effects of interventions for the management of pityriasis rosea in any individual diagnosed by a medical practitioner. SEARCH METHODS: We updated our searches of the following databases to October 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched five trials registers. We also checked the reference lists of included and excluded studies, contacted trial authors, scanned the abstracts from major dermatology conference proceedings, and searched the CAB Abstracts database. We searched PubMed for adverse effects to November 2018. SELECTION CRITERIA: Randomised controlled trials of interventions in pityriasis rosea. Treatment could be given in a single therapy or in combination. Eligible comparators were no treatment, placebo, vehicle only, another active compound, or placebo radiation treatment. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by the Cochrane. Our key outcomes were good or excellent rash improvement within two weeks, rated separately by the participant and medical practitioner; serious adverse events; resolution of itch within two weeks (participant-rated); reduction in itch score within two weeks (participant-rated); and minor participant-reported adverse events not requiring withdrawal of the treatment. MAIN RESULTS: We included 14 trials (761 participants). In general, risk of selection bias was unclear or low, but risk of performance bias and reporting bias was high for 21% of the studies. Participant age ranged from 2 to 60 years, and sex ratio was similar. Disease severity was measured by various severity indices, which the included studies did not categorise. Six studies were conducted in India, three in Iran, two in the Philippines, and one each in Pakistan, the USA, and China. The included studies were conducted in dermatology departments and a paediatric clinic. Study duration ranged from 5 to 26 months. Three studies were funded by drug manufacturers; most studies did not report their funding source. The included studies assessed macrolide antibiotics, an antiviral agent, phototherapy, steroids and antihistamine, and Chinese medicine. None of the studies measured participant-rated good or excellent rash improvement. All reported outcomes were assessed within two weeks of treatment, except for adverse effects, which were measured throughout treatment. There is probably no difference between oral clarithromycin and placebo in itch resolution (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.47 to 1.52; 1 study, 28 participants) or rash improvement (medical practitioner-rated) (RR 1.13, 95% CI 0.89 to 1.44; 1 study, 60 participants). For this comparison, there were no serious adverse events (1 study, 60 participants); minor adverse events and reduction in itch score were not measured; and all evidence was of moderate quality. When compared with placebo, erythromycin may lead to increased rash improvement (medical practitioner-rated) (RR 4.02, 95% CI 0.28 to 56.61; 2 studies, 86 participants, low-quality evidence); however, the 95% CI indicates that the result may also be compatible with a benefit of placebo, and there may be little or no difference between treatments. Itch resolution was not measured, but one study measured reduction in itch score, which is probably larger with erythromycin (MD 3.95, 95% CI 3.37 to 4.53; 34 participants, moderate-quality evidence). In the same single, small trial, none of the participants had a serious adverse event, and there was no clear difference between groups in minor adverse events, which included gastrointestinal upset (RR 2.00, CI 0.20 to 20.04; moderate-quality evidence). Two trials compared oral azithromycin to placebo or vitamins. There is probably no difference between groups in itch resolution (RR 0.83, 95% CI 0.28 to 2.48) or reduction in itch score (MD 0.04, 95% CI -0.35 to 0.43) (both outcomes based on one study; 70 participants, moderate-quality evidence). Low-quality evidence from two studies indicates there may be no difference between groups in rash improvement (medical practitioner-rated) (RR 1.02, 95% CI 0.52 to 2.00; 119 participants). In these same two studies, no serious adverse events were reported, and there was no clear difference between groups in minor adverse events, specifically mild abdominal pain (RR 5.82, 95% CI 0.72 to 47.10; moderate-quality evidence). Acyclovir was compared to placebo, vitamins, or no treatment in three trials (all moderate-quality evidence). Based on one trial (21 participants), itch resolution is probably higher with placebo than with acyclovir (RR 0.34, 95% CI 0.12 to 0.94); reduction in itch score was not measured. However, there is probably a significant difference between groups in rash improvement (medical practitioner-rated) in favour of acyclovir versus all comparators (RR 2.45, 95% CI 1.33 to 4.53; 3 studies, 141 participants). Based on the same three studies, there were no serious adverse events in either group, and there was probably no difference between groups in minor adverse events (only one participant in the placebo group experienced abdominal pain and diarrhoea). One trial compared acyclovir added to standard care (calamine lotion and oral cetirizine) versus standard care alone (24 participants). The addition of acyclovir may lead to increased itch resolution (RR 4.50, 95% CI 1.22 to 16.62) and reduction in itch score (MD 1.26, 95% CI 0.74 to 1.78) compared to standard care alone. Rash improvement (medical practitioner-rated) was not measured. The trial reported no serious adverse events in either group, and there may be no difference between groups in minor adverse events, such as headache (RR 7.00, 95% CI 0.40 to 122.44) (all results based on low-quality evidence). AUTHORS' CONCLUSIONS: When compared with placebo or no treatment, oral acyclovir probably leads to increased good or excellent, medical practitioner-rated rash improvement. However, evidence for the effect of acyclovir on itch was inconclusive. We found low- to moderate-quality evidence that erythromycin probably reduces itch more than placebo. Small study sizes, heterogeneity, and bias in blinding and selective reporting limited our conclusions. Further research is needed to investigate different dose regimens of acyclovir and the effect of antivirals on pityriasis rosea.

Embedding implementation research to enhance health policy and systems: a multi-country analysis from ten settings in Latin America and the Caribbean.

BACKGROUND: Progress towards universal health coverage requires health policies and systems that are informed by contextualised and actionable research. Many challenges impede the uptake of evidence to enhance health policy implementation and the coverage, quality, efficiency and equity of health systems. To address this need, we developed an innovative model of implementation research embedded in real-world policy and programme cycles and led directly by policy-makers and health systems decision-makers. The approach was tested in ten settings in Latin America and the Caribbean, supported under a common funding and capacity strengthening initiative. The present study aims to analyse ten embedded implementation research projects in order to identify barriers and facilitators to embedding research into policy and practice as well as to assess the programme, policy and systems improvements and the cross-cutting lessons in conducting research embedded in real-world policy and systems decision-making. METHODS: The multi-country analysis is based on the triangulation of data collected via three methods, namely (1) document review, (2) an electronic questionnaire and (3) in-depth interviews with decision-makers. Data from the document review was charted and narratively synthesised. Data from the questionnaire was used to assess three characteristics of the decision-maker's participation in embedded research, namely (1) level of engagement in different stages of research; (2) extent to which their capacities to conduct and use research were developed; and (3) the level of confidence in undertaking implementation research activities. Interview data was analysed using a thematic approach. RESULTS: The main barriers to effective delivery or scale-up of health interventions identified in the research projects were inadequate financing, fragmentation of healthcare services and information systems, limited capacity of health system stakeholders, insufficient time, cultural factors, and a lack of information. Decision-makers' experience in embedded research showed strong engagement in protocol development, moderate engagement in data collection and low engagement in data analysis. The in-depth interviews identified 17 facilitators and 8 barriers to embedding research into policy and systems. The principal facilitating factors were actionability of findings, relevance of research and engagement of decision-makers, whereas the main barriers were time and political processes. In Argentina, the research led to the development of new monitoring indicators to improve the implementation of the perinatal health policy, while in Chile, empirical findings supported the establishment of a training programme on reproductive rights, targeted to municipal health facilities. CONCLUSIONS: This multi-country analysis contributes to the evidence base for the embedded research approach to support health policy and systems decisions-making. Embedding research into policy and practice stimulates the relevance and applicability of research, while promoting decision-makers' engagement and likelihood to use research evidence in policy-making and health systems strengthening.

Risk factors for chronic kidney disease of non-traditional causes: a systematic review.

OBJECTIVES: To evaluate the potential associations between chronic kidney disease of uncertain or non-traditional etiology (CKDnT) and agrochemicals, heat stress, heavy metals, and other factors identified in the literature in any region of the world and at any time. METHODS: This was a systematic review of the most frequent exposures suspected to be possible causes of CKDnT. A search was conducted of PubMed, LILACS, World Wide Science electronic databases, among other sources. Only medium- and high-quality studies were included. The synthesis of evidence included a narrative synthesis, meta-analysis, and meta-regression. RESULTS: Four systematic reviews and 61 primary studies were included. Results of the meta-analysis suggest that exposure to agrochemicals and working in agriculture increase the risk of CKDnT, but this only reached significance for working in agriculture. When cross-sectional studies were excluded, agrochemical exposure became significant. However, there is substantial heterogeneity in the effect sizes. CONCLUSIONS: Based on the existing evidence and the precautionary principle, it is important to implement preventive measures to mitigate the damage caused by CKDnT to both agricultural workers and their communities (i.e., improvement of working conditions, cautious management of agrochemicals, etc.). More high-quality research is needed to measure impact and to build the evidence base.