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.

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.

Prevalence of asymptomatic Zika virus infection: a systematic review.

OBJECTIVE: To conduct a systematic review to estimate the prevalence of asymptomatic Zika virus infection in the general population and in specific population groups. METHODS: We searched PubMed®, Embase® and LILACS online databases from inception to 26 January 2018. We included observational epidemiological studies where laboratory testing was used to confirm positive exposure of participants to Zika virus and in which Zika virus symptom status was also recorded. We excluded studies in which having symptoms of Zika virus was a criterion for inclusion. The main outcome assessed was percentage of all Zika virus-positive participants who were asymptomatic. We used a quality-effects approach and the double arcsine transformation for the meta-analysis. FINDINGS: We assessed 753 studies for inclusion, of which 23 were included in the meta-analysis, totalling 11 305 Zika virus-positive participants. The high degree of heterogeneity in the studies (I2 = 99%) suggests that the pooled prevalence of asymptomatic Zika virus-positive participants was probably not a robust estimate. Analysis based on subgroups of the population (general population, returned travellers, blood donors, adults with Guillain-Barré syndrome, pregnant women and babies with microcephaly) was not able to explain the heterogeneity. Funnel and Doi plots showed major asymmetry, suggesting selection bias or true heterogeneity. CONCLUSION: Better-quality research is needed, using standardized methods, to determine the true prevalence of asymptomatic Zika virus and whether it varies between populations or over time.

[Establishing research priorities for chronic kidney disease of non-traditional causes in Central AmericaDeterminação de prioridades em pesquisa da doença renal crônica associada a causas não tradicionais na América Central]. / Establecimiento de prioridades de investigación en la enfermedad renal crónica de causas no tradicionales en Centroamérica.

INTRODUCTION: In 2013, the PAHO Member States recognized the epidemic of chronic kidney disease of non-traditional causes (CKDnT) as a serious public health problem. This article describes the establishment of research priorities to comprehensively address CKDnT in Central America. METHODS: Following a search of the literature for research studies carried out in Central America and prior research agendas on CKD, a virtual survey was conducted using the Delphi methodology. The respondents were identified from various sources. The first round sought to refine and add research topics and to prioritize those deemed most relevant. The second round prioritized the most relevant topics. A fuzzy-sets analysis was carried out to estimate decision thresholds and scores for each topic. RESULTS: The survey was sent to 83 Spanish-speaking and 38 English-speaking prospective respondents. The response rate was 46.2%. For the second round, the survey was sent to 56 Spanish-speaking and 16 English-speaking first-round respondents. Eighteen topics within 10 research areas were prioritized: public policies, determinants, etiology, diagnosis and treatment of CKD, primary prevention, service delivery, human resources, information systems, and funding. Research on CKDnT was found to be scarce and restricted to certain topics. CONCLUSIONS: In addition to etiological factors, great importance was assigned to aspects related to the health system response, including service delivery approaches, human resources, funding, and occupational and environmental aspects.

INTRODUÇÃO: Em 2013, os Estados Membros da OPAS reconheceram a epidemia de doença renal crônica associada a causas não tradicionais como um sério problema de saúde pública. Este artigo descreve a determinação de prioridades em pesquisa para uma abordagem ampla da doença renal crônica associada a causas não tradicionais na América Central. MÉTODOS: Foi estruturada uma pesquisa virtual com o uso da metodologia Delphi e foi feita uma busca dos estudos realizados na América Central e das agendas de pesquisa anteriores sobre doença renal crônica. Os entrevistados eram provenientes de fontes diversas. Na primeira rodada, buscou-se refinar e acrescentar tópicos de pesquisa e priorizar os mais relevantes. Na segunda rodada, foram priorizados os tópicos mais relevantes. Foi realizada uma análise com o uso de conjuntos nebulosos para estimar limiares de decisão e pontuações por tópico. RESULTADOS: A pesquisa foi enviada primeiramente a 83 indivíduos falantes da língua espanhola e 38 falantes da língua inglesa, com taxa de resposta de 46,2%. Na segunda rodada, a pesquisa foi enviada aos 56 falantes da língua espanhola e 16 falantes da língua inglesa que haviam respondido a primeira rodada da pesquisa. Foram priorizados 18 tópicos de pesquisa distribuídos em 10 áreas: políticas públicas, determinantes, etiologia, diagnóstico e tratamento da doença renal crônica, prevenção primária, prestação de serviços, recursos humanos, sistemas de informação e financiamento. Foi verificado que a pesquisa em doença renal crônica associada a causas não tradicionais é escassa e está restrita a determinados tópicos. CONCLUSÕES: Além dos fatores etiológicos, foi dada grande relevância a aspectos relacionados à resposta dos sistemas de saúde, incluindo o método de prestação de serviços, recursos humanos, financiamento e aspectos ocupacionais e ambientais.

Adherence to clinical trial registration in countries of Latin America and the Caribbean, 2015.

OBJECTIVE: To determine the prevalence of clinical trial registration in the International Clinical Trial Registry Platform (ICTRP) for studies from Latin America and the Caribbean (LAC) and to identify the key characteristics that lead to prospective and retrospective registration. METHODS: A cross-sectional study identified published, clinical trial studies through a search of PubMed, LILACS (Latin American and Caribbean Center on Health Sciences Information), and the Cochrane Central Register of Controlled Trials. Studies were included if published on 1 January - 31 December 2015, at least one author was affiliated with at least one LAC country, the clinical trial was conducted in at least one LAC site, and the full text of the article was available. A manual search of reference lists was also conducted. ICTRP registration information and key trial characteristics were compared. RESULTS: Of 1 502 CT references that met inclusion criteria, 297 were randomly-selected, 90.9% of which were published in English, 65% from Brazil, and 76.8% had a LAC author as the first author. The proportion of CT registered in the ICTRP was 59.9 %, of which 51.7% were registered prospectively. Clinicaltrials.gov was most frequently used registry (84.8%), followed by the Registro Brasileiro de Ensaios Clínicos and the Registro Público Cubano de Ensayos Clínicos. Key characteristics that favored registration were being in study phase 3 or 4 or being a multi-center study. Data was compared to a similar study from 2013 that reported a registration rate of only 19.8%. CONCLUSIONS: Registration adherence and prospective registration have increased in LAC in recent years, but the proportion of unregistered CT remains high. While there are still many challenges to overcome, the adherence strategies implemented in recent years have proven effective.

Knowledge of and attitudes toward heel prick screening for sickle cell disease in Saint Lucia.

OBJECTIVES: In the Caribbean country of Saint Lucia, umbilical-cord-blood screening for sickle cell disease (SCD) was the testing method that health care workers (HCWs) on the maternity wards of the hospitals preferred until the new heel prick (HP) testing method was introduced in the country in 2014. This SCD study sought to assess HCWs' knowledge of and attitude toward HP screening and also determine new mothers' favorability toward HP screening. METHODS: A total of 70 HCWs and 132 new mothers answered survey questionnaires in three hospitals. In addition, four focus group discussions were held, two with HCWs and two with the mothers. RESULTS: Among the HCWs interviewed, 85.7% of them had knowledge of the HP test. However, only 25.7% had attended training sessions on the procedure. Among the HCWs, 64.3% of them felt the HP test should be mandatory, 27.1% said it should not be mandatory, and 8.6% did not know if it should be mandatory. In their focus groups, the HCWs said they believed the mothers would accept the HP method. For their part, 22.0% of the mothers said they had heard about the HP test, and 63.6% reported knowing the reason why the baby would be tested. Further, 83.3% indicated that the test would be beneficial for the baby. In addition, 88.6% of the mothers said that more information on the HP test was needed. In their focus group discussions, the mothers said they were generally not concerned about the pain the heel prick method might cause the baby. CONCLUSIONS: The HCWs' knowledge of the HP screening method was high. The mothers trust HCWs, and the mothers would accept the HP procedure irrespective of their knowledge of the test and any discomfort associated with this screening method.

[Incorporating health equity into implementation research: review of conceptual modelsIncorporação da igualdade em saúde na pesquisa de implementação: revisão de modelos conceituais]. / Incorporación de equidad en salud en la investigación sobre implementación: revisión de los modelos conceptuales.

OBJECTIVE: Search for conceptual frameworks or models that incorporate aspects of health equity into implementation research and prepare a systematic synthesis of them. METHODS: A systematic search was done of MEDLINE-PubMed, Embase, and LILACS (1965-2016), and Scopus (1998-2016) databases, employing, in addition, a snowball strategy and gray literature search. Article type was assessed, along with elements that were included on implementation research, the science of implementation, and health equity. RESULTS: A total of 701 articles were found, of which 100 were included for review of relevance. Of these, 19 articles related to conceptual frameworks: 12 were general, five were on ethnic or racial disparities, and two related to child health. The most frequent categories were financing, infrastructure, advocacy, quality, internal barriers, and coverage. The least frequent were other sectors, outpatient needs, health status, and equity impact assessment. CONCLUSIONS: In order to reduce health gaps and with them health inequities, it becomes necessary to have a consolidated implementation research framework that includes aspects of health equity. This framework would facilitate improving implementation processes for interventions, services, and health programs.

OBJETIVO: Fazer uma busca e revisão sistemática dos marcos ou modelos conceituais que abrangem aspectos de igualdade em saúde em pesquisa de implementação. MÉTODOS: Busca sistemática nas bases de dados MEDLINE-PubMed, Embase e LILACS (1965­2016) e Scopus (1998­2016) com o uso de estratégia de amostragem em bola de neve e busca da literatura cinzenta. Foram avaliados o tipo de artigo e os elementos contidos sobre pesquisa de implementação (implementation research, IR), ciência de implementação e igualdade em saúde. RESULTADOS: Foram identificados 701 artigos, dos quais 100 foram incluídos na revisão. Destes, 19 artigos estavam relacionados aos marcos conceituais: 12 gerais, cinco sobre disparidades étnicas ou raciais e dois relacionados com saúde infantil. As categorias mais frequentes dos marcos conceituais foram: financiamento, infraestrutura, defesa da causa, qualidade, barreiras internas e cobertura. As menos frequentes foram: outros setores, necessidades dos pacientes ambulatoriais, estado de saúde e avaliação do impacto na equidade. CONCLUSÕES: Para reduzir as lacunas em saúde e as desigualdades em saúde, faz-se necessário dispor de um modelo consolidado de pesquisa de implementação no qual sejam incluídos os aspectos de igualdade em saúde. Este modelo contribuiria para melhorar os processos de implementação das intervenções, serviços e programas de saúde.

Embedding research to improve program implementation in Latin America and the Caribbean.

In the last 10 years, implementation research has come to play a critical role in improving the implementation of already-proven health interventions by promoting the systematic uptake of research findings and other evidence-based strategies into routine practice. The Alliance for Health Policy and Systems Research and the Pan American Health Organization implemented a program of embedded implementation research to support health programs in Latin America and the Caribbean (LAC) in 2014-2015. A total of 234 applications were received from 28 countries in the Americas. The Improving Program Implementation through Embedded Research (iPIER) scheme supported 12 implementation research projects led by health program implementers from nine LAC countries: Argentina, Bolivia, Brazil, Chile, Colombia, Mexico, Panama, Peru, and Saint Lucia. Through this experience, we learned that the "insider" perspective, which implementers bring to the research proposal, is particularly important in identifying research questions that focus on the systems failures that often manifest in barriers to implementation. This paper documents the experience of and highlights key conclusions about the conduct of embedded implementation research. The iPIER experience has shown great promise for embedded research models that place implementers at the helm of implementation research initiatives.

[Health-worker barriers to syphilis screening in pregnant women in Bolivia's Los Andes network]. / Barreras del personal de salud para el tamizaje de sífilis en mujeres embarazadas de la Red Los Andes, Bolivia.

OBJECTIVE: Identify health-worker barriers that keep pregnant women who receive prenatal care from being screened for syphilis (Los Andes Health Network, Bolivia). METHODS: Semi-structured interviews were done with 46 health care providers and 249 clinical health records of pregnant women were analyzed in eight public health facilities in the Los Andes network. RESULTS: Health-worker barriers to syphilis screening in pregnant women included lack of time by personnel to raise awareness of the benefit of syphilis screening; some mentioned that syphilis tests should only be done in facilities that attend deliveries and have a laboratory; lack of communication between clinicians and laboratory personnel; and problems with provision of supplies and reagents. The clinical record review found that only 55.4% contained syphilis laboratory results and only 37.4% of perinatal clinical histories had records of laboratory results. The interviews found that providers believe that syphilis screening is done in 100% of pregnant women receiving prenatal care. CONCLUSION: Syphilis screening is not being done according to Bolivia's strategy for the elimination of congenital syphilis, and is not done on more than half of pregnant women in prenatal care with perinatal clinical history records. This is not perceived by health professionals and can become a barrier to syphilis screening in pregnant women.

Active and latent tuberculosis in Brazilian correctional facilities: a cross-sectional study.

BACKGROUND: Tuberculosis (TB) rates among prisoners are more than 20 times that of the general population in Brazil, yet there are limited data available to facilitate the development of effective interventions in this high-transmission setting. We aimed to assess risk factors for TB infection and evaluate the yield of mass screening for active disease among inmates. METHODS: We administered a questionnaire and tuberculin skin test (TST) to a population-based sample of inmates from 12 prisons in Central-West Brazil and collected sera for HIV testing and two sputum samples for smear microscopy and culture from participants reporting a cough of any duration. Hierarchical Poisson regression models were used to evaluate factors associated with latent tuberculosis infection (LTBI). RESULTS: We recruited 3,380 inmates, of which 2,861 (84.6%) were males from 8 prisons, and 519 (15.4%) were females from 4 prisons. Among the 1,020 (30%) subjects who reported a cough, we obtained sputum from 691 (68%) and identified 31 cases of active TB for a point prevalence of 917 (95% CI, 623-1302) per 100,000 prisoners. Evaluation of the two sputum smear samples failed to identify 74% of the TB cases, and 29% of the cases reported less than 2 weeks of symptoms. Obtaining a second culture identified an additional 7 (24%) cases. The prevalences of LTBI were 22.5% and 11.7% for male and female prisoners, respectively and duration of incarceration (in years) was associated with LTBI in male and female in the multivariable model (1.04, 95% CI, 1.01-1.07 and 1.34, 95% CI, 1.06-1.70, respectively). The prevalence of LTBI is 8.6% among newly incarcerated inmates, among whom LTBI prevalence significantly increased by 5% with each year of incarceration. CONCLUSIONS: Although the overall LTBI prevalence among inmates in Central-West Brazil is low, tuberculosis incidence is high (>1,800/100,00), likely due to the high force of infection among a largely susceptible inmate population. Efforts to reduce transmission in prisons may require mass screening for active TB, utilizing sputum culture in case-detection protocols.

Laparoscopy for the management of acute lower abdominal pain in women of childbearing age.

BACKGROUND: This is an updated version of the original review, published in Issue 1, 2011, of The Cochrane Library. Acute lower abdominal pain is common, and making a diagnosis is particularly challenging in premenopausal women, as ovulation and menstruation symptoms overlap with symptoms of appendicitis, early pregnancy complications and pelvic infection. A management strategy involving early laparoscopy could potentially provide a more accurate diagnosis, earlier treatment and reduced risk of complications. OBJECTIVES: To evaluate the effectiveness and harms of laparoscopy for the management of acute lower abdominal pain in women of childbearing age. SEARCH METHODS: The Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, PsycINFO, LILACS and CINAHL were searched (October 2013). The International Clinical Trials Registry Platform (ICTRP) was also searched. No new studies were included in this updated version. SELECTION CRITERIA: Randomised controlled trials (RCTs) that included women of childbearing age who presented with acute lower abdominal pain, non-specific lower abdominal pain or suspected appendicitis were included. Trials were included if they evaluated laparoscopy with open appendicectomy, or laparoscopy with a wait and see strategy. Study selection was carried out by two review authors independently. DATA COLLECTION AND ANALYSIS: Data from studies that met the inclusion criteria were independently extracted by two review authors and the risk of bias assessed. We used standard methodological procedures as expected by The Cochrane Collaboration. A summary of findings table was prepared using GRADE criteria. MAIN RESULTS: A total of 12 studies including 1020 participants were incorporated into the review. These studies had low to moderate risk of bias, mainly because allocation concealment or methods of sequence generation were not adequately reported. In addition, it was not clear whether follow-up was similar for the treatment groups. The index test was incorporated as a reference standard in the laparoscopy group, and differential verification or partial verification bias may have occurred in most RCTs. Overall the quality of the evidence was low to moderate for most outcomes, as per the GRADE approach.Laparoscopy was compared with open appendicectomy in eight RCTs. Laparoscopy was associated with an increased rate of specific diagnoses (seven RCTs, 561 participants; odds ratio (OR) 4.10, 95% confidence interval (CI) 2.50 to 6.71; I(2) = 18%), but no evidence was found of reduced rates for any adverse events (eight RCTs, 623 participants; OR 0.46, 95% CI 0.19 to 1.10; I(2) = 0%). A meta-analysis of seven studies found a significant difference favouring the laparoscopic procedure in the rate of removal of normal appendix (seven RCTs, 475 participants; OR 0.13, 95% CI 0.07 to 0.24; I(2) = 0%).Laparoscopic diagnosis versus a 'wait and see' strategy was investigated in four RCTs. A significant difference favoured laparoscopy in terms of rate of specific diagnoses (four RCTs, 395 participants; OR 6.07, 95% CI 1.85 to 29.88; I(2) = 79%), but no evidence suggested a difference in rates of adverse events (OR 0.87, 95% CI 0.45 to 1.67; I(2) = 0%).   AUTHORS' CONCLUSIONS: We found that laparoscopy in women with acute lower abdominal pain, non-specific lower abdominal pain or suspected appendicitis led to a higher rate of specific diagnoses being made and a lower rate of removal of normal appendices compared with open appendicectomy only. Hospital stays were shorter. No evidence showed an increase in adverse events when any of these strategies were used.

Inflammatory response to bioceramic and epoxy resin-based endodontic sealers implanted in mice subcutaneous tissue: An in vivo study.

To evaluate the inflammatory tissue response to BioRoot™ RCS (BR) and AH Plus Jet (AHPJ) sealers implanted in mice subcutaneous tissue. It was hypothesized that the inflammatory tissue response to BR would be milder than to AHPJ. An in vivo study was carried out using isogenic mice. The sealers were implanted during standardized surgical procedures. The inflammatory response was evaluated by microscopic analysis and von Kossa reaction in the reactionary tissue around the specimens after 7, 21, and 63 days. For comparisons, a zinc oxide and eugenol sealer (ZOE) was used as a positive control, in addition to a negative control without a sealer (n = 10 per group/period). All statistical analyses considered a significance level of 5%. All endodontic sealers triggered an inflammatory tissue response after 7 days. BR had a higher inflammatory cell count and a thicker fibrous capsule when compared with AHPJ, but both were less inflammatory than ZOE (p < .001). After 21 days, BR continued to trigger an intense inflammatory tissue response, higher in both microscopic parameters compared to AHPJ, and a thicker fibrous capsule than ZOE (p < .001). After 63 days, the inflammatory tissue response decreased in BR, matching the fibrous capsule thickness with AHPJ and ZOE. BR promoted intense calcium precipitation in all study periods. After 63 days, AHPJ and BR sealers were more biocompatible to subcutaneous mice tissue, but AHPJ present better early inflammatory response, as well as BR showed potential bioactivity. RESEARCH HIGHLIGHTS: The inflammatory tissue response triggered by a bioceramic endodontic sealer (BR) was not milder than that triggered by an epoxy-resin based endodontic sealer (AHPJ) during the first 3 weeks, considering the microscopic analysis of the reactionary tissue.

Comparison of national health research priority-setting methods and characteristics in Latin America and the Caribbean, 2002-2012.

OBJECTIVE: To compare health research priority-setting methods and characteristics among countries in Latin America and the Caribbean during 2002 - 2012. METHODS: This was a systematic review that identified national health research policies and priority agendas through a search of ministry and government databases related to health care institutions. PubMed, LILACS, the Health Research Web, and others were searched for the period from January 2002 - February 2012. The study excluded research organized by governmental institutions and specific national strategies on particular disease areas. Priority-setting methods were compared to the "nine common themes for good practice in health research priorities." National health research priorities were compared to those of the World Health Organization's Millennium Development Goals (MDG). RESULTS: Of the 18 Latin American countries assessed, 13 had documents that established national health research priorities; plus the Caribbean Health Research Council had a research agenda for its 19 constituents. These 14 total reports varied widely in terms of objectives, content, dissemination, and implementation; most provided a list of strategic areas, suggestions, and/or sub-priorities for each country; however, few proposed specific research topics and questions. CONCLUSIONS: Future reports could be improved by including more details on the comprehensive approach employed to identify priorities, on the information gathering process, and on practices to be undertaken after priorities are set. There is a need for improving the quality of the methodologies utilized and coordinating Regional efforts as countries strive to meet the MDG.

Ultra-processed food consumption during pregnancy and newborn weight / Consumo de alimentos ultraprocessados durante a gestação e peso ao nascer do recém-nascido

Abstract Objectives: to assess the association between pregnant women's consumption of ultra-processed foods and newborn body weight. Methods: prospective study with pregnant women (n=214) selected from all Basic Health Units in the city of Pinhais, Paraná. Socioeconomic, demographic, and health data were collected. Food consumption data were assessed using a 24-hour dietary recall and tabulated with GloboDiet software. Daily relative energy intake of ultra-processed food was estimated and logistic regression analysis was utilized. The infuence of covariates on the association analysis was also explored (e.g., income and education). Results: ultra-processed foods contributed to 26.9% of pregnant women's total energy intake. About 5.7% of newborns were classifed as small-for-gestational-age and 10.7% as large-for-gestational-age. A borderline statistically signifcant association was observed between large-for-gestational-age newborn weight and maternal consumption of ultra-processed foods (OR= 1.027; p=0.048). Additionally, family income was associated with the consumption of ultra-processed foods (OR= 0.144; p=0.008). With each additional 1% consumption of ultra-processed foods, mothers' likelihood of having large-for-gestational-age babies increased by about 2.7%. Conclusions: the study reveals a trend of positive association between the weight of large-for-gestational-age newborns and the consumption of ultra-processed foods by pregnant women, but not for small-for-gestational-age children.

Resumo Objetivos: avaliar a associação entre o consumo de alimentos ultraprocessados por gestantes e o peso de recém-nascidos. Métodos: estudo prospectivo com gestantes (n=214) selecionadas em Unidades Básicas de Saúde em Pinhais, Paraná. Dados socioeconômicos, demográfcos e de saúde foram coletados. Dados de consumo alimentar foram coletados por recordatório de 24-horas físico e entrados no software GloboDiet. O consumo diário relativo de energia proveniente de alimentos ultraprocessados foi estimado e a análise de regressão logística foi utilizada, considerando covariáveis como renda familiar e escolaridade. Resultados: o consumo de alimentos ultraprocessados pelas gestantes representou 26,9% da energia total. Cerca de 5,7% de recém-nascidos foram classifcados como pequenos para idade gestacional (PIG) e 10,7% como grandes para idade gestacional (GIG). Foi observada uma associação estatisticamente signifcativa limítrofe entre o peso dos recém-nascidos GIG e o consumo materno de alimentos ultraprocessados (OR= 1,027; p=0,048). Além disso, a renda familiar esteve associada com o consumo de alimentos ultraprocessados (OR=0,144; p=0,008). A cada 1% adicional de consumo de alimentos ultraprocessados, a probabilidade de as mães terem recém-nascidos GIG aumentou cerca de 2,7%. Conclusões: o estudo revela uma tendência de associação positiva entre o peso de recém-nascidos GIG e o consumo de alimentos ultraprocessados por mulheres grávidas, mas não para crianças PIG.

Subjects' Perception in Quantifying Printed and Digital Photos of Food Portions.

Although digital photos have the potential to improve the precision of reported portions in dietary assessment, there are few studies investigating its accuracy in comparison to printed photos. The aim of this study was to evaluate the perception of adults in quantifying food portion sizes using printed and digital photos, displayed on computer-screens and tablets. In total, 1165 evaluations were performed for 60 photos of portion sizes in Brazil. Each participant (n = 58) attended two sessions in the study center, with an interval of at least one week. In each session, twelve food portions were prepared and randomly evaluated by each participant in its printed and digital forms. The mean error (difference between the estimated and true portions) was not significantly different between the printed photos (2.1 g ± 47.2) and the digital ones (-6.4 g ± 53.7). The agreement on using the printed and digital photos was 91% and 90%, respectively. Furthermore, the use of the tablet was more prone to underestimation when compared to printed and computer-screen photos (p < 0.001). Overall, participants did not present major difficulties in perceiving the portion sizes using the printed and digital photos, but the use of tablets led to less accurate results, indicating that this needs to be further evaluated.

Understanding the relation between Zika virus infection during pregnancy and adverse fetal, infant and child outcomes: a protocol for a systematic review and individual participant data meta-analysis of longitudinal studies of pregnant women and their infants and children.

INTRODUCTION: Zika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes. METHODS AND ANALYSIS: We will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty. ETHICS AND DISSEMINATION: The IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals. TRIAL REGISTRATION NUMBER: PROSPERO International prospective register of systematic reviews (CRD42017068915).

An overview of financial sources being utilized to support Zika Virus published research.

BACKGROUND: Since its initial detection in Brazil in 2015, Zika Virus (ZIKV) has spread rapidly throughout most of the Caribbean and South, Central and North America. An upsurge in congenital syndrome associated with ZIKV and Guillain-Barre Syndrome (GBS) has been associated with the increase in ZIKV. This amplification in numbers led to the need for funded research initiatives focusing on various countries globally and on specific experimental types. OBJECTIVES: To determine the financial institutions involved in the production of primary research into the ZIKV epidemic. This research also intends to draw attention to the investigative areas that are dominating, experimental types being conducted and the geographical areas that are producing the bulk of the research utilizing available funds. METHODS: A cross sectional search of published primary research was conducted using Pan American Health Organization (PAHO) Zika platform and PubMed between January 2007 and October 2016. Titles, abstract and full articles were assed and one researcher extracted data. Information was crossed checked by a second researcher to ensure accuracy. FINDINGS: 268 articles were included and investigations occurred across 48 countries with Brazil and USA dominating the research. Applied Research and Laboratory based studies were most frequently utilized. 38.1% of articles did not report financial sources. Public institutions were the major known contributors. Other financiers included private, non-profits and mixed funders exclusive of public sources. 156 individual financial bodies assisted with National Institute of Health being most frequently mentioned followed by The National Council for Scientific and Technological Development (CNPq) and the Institut Pasteur. Virus, vectors and reservoirs was most frequently used (99/268, 36.9%) followed by clinical management (70/268, 26.1%) and epidemiology (46/268, 17.2%). INTERPRETATION: The evidence suggests international efforts to fund ZIKV research and a need to foster collaborative and synchronized priority setting for resource allocation.

[Composite Index of health Inequity for a Middle Income Country]. / Indice compuesto de inequidad en salud para un país de mediano ingreso.

OBJECTIVE: To develop and validate a composite index of health inequity based on mortality by grouped causes. METHODS: An ecological study in a middle-income Latin American country, with aggregate indicators available from municipalities and departments, which were selected from health observatories, research groups and health authorities. They were divided into intolerable and "not completely avoidable" according to current scientific progress, and were added in categories: traffic accident, aggression, kidney disease, HIV infection, intestinal parasitic diseases, syphilis, fecal / oral transmission disease, tuberculosis, disease Vector-borne diseases, respiratory disease, cerebral hemorrhagic / ischemic events, maternal mortality, lower mortality 5 years, meningitis. After analysis of main components, a composite index of health inequity (IIS) is obtained for men and women. Internal consistency was evaluated using Cronbach's Alpha coefficient. Concurrent validation was done with proportion of people in Unsatisfied Basic Needs (UBN), Human Development Index (HDI), Life Expectancy at Birth (LEB), among others. RESULTS: IIS is built showing higher values for women in most municipalities and departments; And for sites with high HDI, high LEB and low UBN. Cronbach's alpha was 0.6688, IIS-men and 0.725, IIS-women. CONCLUSIONS: An IIS was obtained, is valid and reproducible. The role of big cities in inequities in health is highlighted, probably due to the effect of intolerable health.

OBJETIVO: Desarrollar y validar un índice compuesto de inequidad en salud basado en mortalidad por grupos de causas. MÉTODOS: Estudio ecológico en país de mediano ingreso latinoamericano, con indicadores agregados disponibles de municipios y departamentos, que se seleccionaron a partir de observatorios de salud, grupos de investigación y autoridades sanitarias. Se dividen en intolerables y "no completamente evitables" según el avance científico actual, y se agregan en categorías: accidente de tránsito, agresiones, enfermedad renal, infección por VIH, parasitosis intestinal, sífilis, enfermedad de transmisión fecal/oral, tuberculosis, enfermedad transmitidas por vectores, enfermedad respiratoria, eventos hemorrágicos/ isquémicos cerebrales, mortalidad materna, mortalidad menores 5 años, meningitis. Luego de análisis de componentes principales se obtiene índice compuesto multidimensional de inequidad en salud (IIS) para hombres y mujeres. Consistencia interna se evalúa mediante coeficiente Alpha de Cronbach. Se hace validación concurrente con proporción de personas en Necesidades Básicas Insatisfechas (NBI), Índice de Desarrollo Humano (IDH), Expectativa de Vida al Nacer (EVN) entre otros. RESULTADOS: Se construye IIS que muestra valores más altos para las mujeres en la mayoría de municipios y departamentos; y para lugares con IDH alto, EVN alta y NBI bajas. El alpha de Cronbach fue 0.6688, IIS-hombres y 0.725, IIS-mujeres. CONCLUSIONES: Se obtiene IIS factible, reproducible y mutidimensional. Se destaca el papel de las grandes ciudades en las inequidades en salud, probablemente por el efecto de los intolerables en salud.

Risk of bias and confounding of observational studies of Zika virus infection: A scoping review of research protocols.

INTRODUCTION: Given the severity and impact of the current Zika virus (ZIKV) outbreak in the Americas, numerous countries have rushed to develop research studies to assess ZIKV and its potential health consequences. In an effort to ensure that studies are comprehensive, both internally and externally valid, and with reliable results, the World Health Organization, the Pan American Health Organization, Institut Pasteur, the networks of Fiocruz, the Consortia for the Standardization of Influenza Seroepidemiology (CONSISE) and the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) have generated six standardized clinical and epidemiological research protocols and questionnaires to address key public health questions on ZIKV. METHODS: We conducted a systematic search of ongoing study protocols related to ZIKV research. We analyzed the content of protocols of 32 cohort studies and 13 case control studies for systematic bias that could produce erroneous results. Additionally we aimed to characterize the risks of bias and confounding in observational studies related to ZIKV and to propose ways to minimize them, including the use of six newly standardized research protocols. RESULTS: Observational studies of ZIKV face an array of challenges, including measurement of exposure and outcomes (microcephaly and Guillain-Barré Syndrome). Potential confounders need to be measured where known and controlled for in the analysis. Selection bias due to non-random selection is a significant issue, particularly in the case-control design, and losses to follow-up is equally important for the cohort design. CONCLUSION: Observational research seeking to answer key questions on the ZIKV should consider these restrictions and take precautions to minimize bias in an effort to provide reliable and valid results. Utilization of the standardized research protocols developed by the WHO, PAHO, Institut Pasteur, and CONSISE will harmonize the key methodological aspects of each study design to minimize bias at different stages of the study. Biases need to be considered by researchers implementing the standardized protocols as well as by users of observational epidemiological studies of ZIKV.