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Objectives Several studies have shown an inverse association between diabetes mellitus and prostate cancer (PCa). Some researchers suggest that this relationship is due to reduced PCa detection in diabetics due to lower prostate-specific antigen (PSA) levels compared to non-diabetics. Our objective is to analyze the impact of diabetes on PSA in asymptomatic men without known prostate pathology and without prior prostate intervention. Methods We searched Medline (via PubMed), Embase and Scopus. We included studies that reported the relationship between serum PSA levels and diabetes or diabetes treatment in asymptomatic adult men without known prostate pathology, and without prior prostate intervention. Pooled mean differences were compared between diabetics and non-diabetics. Results Of 2,392 screened abstracts, thirteen studies met the inclusion criteria and 8 (62%) reported appropriate measures that could be included in a meta-analysis. Eleven (85%) examined the influence of diabetes on PSA levels and 8 (62%) evaluated the influence of diabetes treatments on PSA levels. Overall diabetics had a significantly lower PSA level compared to non-diabetics (mean difference: −0.07 ng/mL; 95% CI −0.10, −0.04). Conclusions Diabetes and related factors (such as disease duration, severity and treatment) were significantly associated with lower PSA levels among asymptomatic men, yet differences were small and are unlikely to influence PCa detection in a screening setting.

To explore differences in the clinical management of men and women in the 5 years after detecting a solitary pulmonary nodule (SPN) by chest radiograph or CT in routine clinical practice. We followed up 545 men and 347 women with an SPN detected by chest radiograph or CT in a retrospective cohort of 25,422 individuals undergoing routine thoracic imaging in 2010–2011. We compared the frequency of each management strategy (no further test, immediate intervention or follow up) according to sex by means of chi-squared. We estimated the relative risk of women versus men of having been followed up instead of an immediate intervention using multivariate logistic regression. We compared by sex the time between detection of the nodule and lung cancer diagnosis, the time between diagnosis and death by means of Mann-Whitney U test and the cumulative effective dose of radiation in each management strategy by means of t test. Women were more likely than men to have follow-up rather than immediate intervention (aRR = 1.8, CI 1.3–2.7, p = 0.002), particularly in those who underwent CT (aRR = 4.2, CI 1.9–9.3, p

Scientific societies have provided guidelines to reduce PSA-specific harms. We studied the potential non-compliance of PSA testing with current guidelines in general practice. A cross-sectional study of a random sample of 1291 patients with a PSA test was performed between January and April 2018 in primary health care. Patients with a previous prostate cancer diagnosis or those who were being followed-up for previous high PSA values were excluded. Two independent researchers classified whether each test was potentially non-compliant with recommendations. We estimated frequencies of potentially non-compliant PSA determinations and calculated prevalence ratios (PR) to assess their relationship with possible explanatory variables. A total of 66% (95% CI: 62–69%) of PSA requests in asymptomatic patients were potentially non-compliant with the current guideline. This was associated with having a previous diagnosis of neoplasm (PR adjusted by age and life expectancy: 1.18, 95% CI: 1.02–1.37) as well as being a current consumer of tobacco, alcohol, or other drugs (PR: 0.80, 95% CI: 0.67–0.97). Real world data shows that patients are still frequently exposed to overdiagnosis risk with a PSA potentially non-compliant with recommendations. Patients diagnosed with another neoplasm or non-consumers of toxic substances were more exposed, probably due to increased contact with doctors or health-seeking behaviour.

Cysticercosis is a parasitic infection caused by the metacestode larval stage (cysticercus) of Taenia solium. In humans, cysticercosis may infect the central nervous system and cause neurocysticercosis, which is responsible for over 50,000 deaths per year worldwide and is the major cause of preventable epilepsy cases, especially in low-income countries. Cysticercosis infection is endemic in many less developed countries where poor hygiene conditions and free-range pig management favor their transmission. A cross-sectional study was conducted in 680 children from a rural primary school in Gakenke district (Northern province of Rwanda). Stool samples were collected from participants and analyzed using the Kato-Katz method (KK), formol-ether concentration (FEC), and/or copro-antigen enzyme-linked immunosorbent assay (CoAg-ELISA) to detect taeniasis. Blood samples were collected and analyzed using enzyme-linked immunoelectrotransfer blot (EITB) and antigen enzyme-linked immunosorbent assay (Ag-ELISA) to detect human cysticercosis. The overall proportion of taeniasis positivity was 0.3% (2/680), and both cases were also confirmed by CoAg-ELISA. A total of 13.3% (76/572) of the children studied were positive to cysticercosis (T. solium-specific serum antibodies detected by EITB), of whom 38.0% (27/71) had viable cysticercus (T. solium antigens by Ag-ELISA). This study provides evidence of the highest cysticercosis prevalence reported in Rwanda in children to date. Systematic investigations into porcine and human cysticercosis as well as health education and hygiene measures for T. solium control are needed in Gakenke district.

Diabetes is a major public health problem, increasingly affecting low- and middle-income countries. The project CEAD (Contextualizing Evidence for Action in Diabetes in low-resource settings) aims to evaluate the implementation of comprehensive diabetes care in two low-resource settings in Ecuador and to stimulate context-led health systems innovations to improve diabetes care and reduce inequity. The mixed-methods approach includes a 24-month retrospective study to assess the current level of implementation of comprehensive diabetes care and participants will be followed up prospectively for two years to assess changes in healthcare and clinical outcomes from the outset of the research. We will include individuals diagnosed with type-2 diabetes aged over 18 years, who are accessing diabetes care in health facilities in the study districts. Varied stakeholders (patients and family members, community members, healthcare workers and decision-makers) will interpret the underlying causes of the observed weaknesses and propose solutions to strengthen diabetes-related healthcare in focus group discussions (FG). A second set of FG will analyze perceived improvements in healthcare based on prospective cohort findings and consider the success/failure of any context-led innovations occurring throughout the research. Our study will demonstrate how evidence can be contextualized to stimulate local innovations and overcome weaknesses of diabetes-related healthcare in low resource settings.

Background Universal antiretroviral therapy (ART) for all pregnant/ breastfeeding women living with Human Immunodeficiency Virus (HIV), known as Prevention of mother-to child transmission of HIV (PMTCT) Option B+ (PMTCTB+), is being scaled up in most countries in Sub-Saharan Africa. In the transition to PMTCTB+, many countries face challenges with proper implementation of the HIV care cascade. We aimed to describe the feasibility of a PMTCTB+ approach in the public health sector in Swaziland. Methods Lifelong ART was offered to a cohort of HIV+ pregnant women aged ≥16 years at the first antenatal care (ANC1) visit in 9 public sector facilities, between 01/2013 and 06/2014. The study enrolment period was divided into 3 phases (early: 01–06/2013, mid: 07–12/2013 and late: 01–06/2014) to account for temporal trends. Kaplan-Meier estimates and Cox proportional-hazards regression models were applied for ART initiation and attrition analyses. Results Of 665 HIV+ pregnant women, 496 (74.6%) initiated ART. ART initiation increased in later study enrolment phases (mid: aHR: 1.41; later: aHR: 2.36), and decreased at CD4 ≥ 500 (aHR: 0.69). 52.9% were retained in care at 24 months. Attrition was associated with ANC1 in the third trimester (aHR: 2.37), attending a secondary care facility (aHR: 1.98) and ART initiation during later enrolment phases (mid aHR: 1.48; late aHR: 1.67). Of 373 women eligible, 67.3% received a first VL. 223/251 (88.8%) were virologically suppressed (

Summary Shortages of vaccines for epidemic diseases, such as cholera, meningitis, and yellow fever, have become common over the past decade, hampering efforts to control outbreaks through mass reactive vaccination campaigns. Additionally, various epidemiological, political, and logistical challenges, which are poorly documented in the literature, often lead to delays in reactive campaigns, ultimately reducing the effect of vaccination. In June 2015, a cholera outbreak occurred in Juba, South Sudan, and because of the global shortage of oral cholera vaccine, authorities were unable to secure sufficient doses to vaccinate the entire at-risk population—approximately 1 million people. In this Personal View, we document the first public health use of a reduced, single-dose regimen of oral cholera vaccine, and show the details of the decision-making process and timeline. We also make recommendations to help improve reactive vaccination campaigns against cholera, and discuss the importance of new and flexible context-specific dose regimens and vaccination strategies.

Introduction: Prostate-specific antigen (PSA) is the main tool for early detection, risk stratification and monitoring of prostate cancer (PCa). However, there are controversies about the use of PSA as a population screening test because of the high potential for overdiagnosis and overtreatment associated. The net benefit of screening is unclear and according to the available recommendations, it should be offered to well-informed men with an adequate health status and a life-expectancy of at least 10 years or to men at elevated risk of having PCa. In addition, the factors that influence test results are unclear, as is impact of false positive or negative results on patient health. Our objective is to assess the clinical and analytical factors associated with the presence of false positive and false negative results and the diagnostic/therapeutic process followed by these patients. Methods and analysis: A prospective observational cohort study will be carried out. We will include a cohort of patients with a positive PSA result (1.081 patients) and a sample of patients with negative results (572 patients); both will be followed for 2 years by reviewing medical records to assess the variables associated with these results, as well as characteristics of patient management after a positive PSA value. We will include those patients with a PSA determination from 2 hospitals in the Valencian Community. Patients who have been previously diagnosed with prostate cancer or who are being followed for previous high PSA values will be excluded. Discussion: The study will estimate the frequency of false positive and false negative PSA results in routine clinical practice, and allow us to quantify the potential harm caused. Study registration: Clinicaltrials.gov (https://clinicaltrials.gov/): NCT03978299, June 7, 2019.

Background Although public-private partnerships have become common in the health sector, the evidence supporting their effectiveness is limited, and when the products or services provided by the private partner are harmful to health inherent conflicts of interest may be difficult to overcome. The objective of this study is to appraise the evidence describing process or effectiveness of public-private partnerships (PPPs) that aim to promote population health, and analyse how characteristics such as independence or competing interests influence the results of their evaluation. Methods We carried out a systematic search of Medline and Web of Science to identify scientific reports evaluating the process or effectiveness of PPPs that aim to promote population health. Two reviewers applied inclusion criteria, extracted and evaluated study quality. We classified PPPs according to the health problem tackled, the independence of the evaluation, and the potential for competition between business interests of the private partner and health promotion activity undertaken. We classified the conclusions of the evaluation as positive (supportive/tentatively supportive) or negative (semi-critical/critical). Results We identified 36 studies evaluating 25 PPPs. Evaluations that were favourable to the use of PPPs in health promotion were more frequently classed as “not independent” and of poor quality. On the other hand, negative evaluations were more common when the PPP involved a private partner with a high potential for competition between the health promotion activity undertaken and their financial interests. PPPs that sought to prevent non-communicable diseases were more frequently negatively evaluated compared to PPPs tackling infectious disease or other types of health problem. Almost all of the evaluations evaluated process, with only 2 papers reporting quantitative health related outcomes. Conclusions There is still a lack of sound evidence supporting the effectiveness of public-private partnerships in health promotion, and the evidence base is skewed by non-independent evaluations. Public health actors should abstain from engaging in agreements with industries whose business interests have a high potential for competition with the health promotion activity undertaken.

ObjectivesTo determine the factors associated with lung cancer diagnosis and mortality after detecting a solitary pulmonary nodule (SPN) in routine clinical practice, in men and in women for both chest radiograph and CT.Materials and methodsA 5-year follow-up of a retrospective cohort of of 25,422 (12,594 men, 12,827 women) patients aged ≥35 years referred for chest radiograph or CT in two hospitals in Spain (2010-2011). SPN were detected in 893 (546 men, 347 women) patients. We estimated the cumulative incidence of lung cancer at 5-years, the association of patient and nodule characteristics with SPN malignancy using Poisson logistic regression, stratifying by sex and type of imaging test. We calculated lung cancer specific mortality rate by sex and SPN detection and hazard rates by cox regression.Results133 (14.9%) out of 893 patients with an SPN and 505 (2.06%) of the 24,529 patients without SPN were diagnosed with lung cancer. Median diameter of SPN in women who developed cancer was larger than in men. Men who had a chest radiograph were more likely to develop a lung cancer if the nodule was in the upper-lobes, which was not the case for women. In patients with an SPN, smoking increased the risk of lung cancer among men (chest radiograph: RR = 11.3, 95%CI 1.5-83.3; CT: RR = 7.5, 95%CI 2.2, 26.0) but smoking was not significantly associated with lung cancer diagnosis or mortality among women with an SPN. The relative risk of lung cancer diagnosis in women with SPN versus those without was much higher compared to men (13.7; 95%CI 9.2, 20.4 versus 6.2; 95%CI 4.9,7.9).ConclusionThe factors associated with SPN malignancy and 5-year lung cancer mortality were different among men and women, especially regarding smoking history and SPN characteristics, where we observed a relatively high rate of lung cancer diagnosis among female non-smokers.

To assess the risk of lung cancer and specific mortality rate in patients with and without solitary pulmonary nodules (SPN) on chest radiograph and CT. This prospective study included 16,078 patients ≥35 years old (893 of them had an SPN detected with either chest radiograph or CT) and 15,185 without SPN. Patients were followed up for 18 months or until being diagnosed with lung cancer. Risk and mortality lung cancer were calculated in both groups with Poisson regression. In patients with SPN, incidence of lung cancer was 8.3 % (95 % CI 6.0–11.2) on radiograph and 12.4 % (95 % CI 9.3–15.9) on CT. A chronic obstructive pulmonary disease in patients with radiographs (odds ratio 2.62; 95 % CI 1.03, 6.67) and smoking habit (odds ratio 20.63; 95 % CI 3.84, 110.77) in patients with CT were associated with a higher probability of lung cancer. Large nodule size and spiculated edge were associated with lung cancer on both CT and radiograph. Lung cancer-specific mortality was lower in patients with SPN than in those without SPN (1.73/1000 person-years, 95 % CI 1.08–2.88 vs. 2.15/1000 person-years, 95 % CI 1.25–3.96). The risk of lung cancer for patients with SPN is higher in clinical populations than in screening studies. Moreover, patients with SPN showed lower mortality than those without SPN. • Lung cancer risk is 8 % for SPN detected on routine radiographs. • Lung cancer risk is 12.4 % for SPN detected in routine chest CT. • Smoking, COPD, SPN diameter and edge were predictors of malignancy. • Lung cancer risk of SPN in routine practice seems higher than in screening.

Supplemental Digital Content is Available in the Text., Background: In January 2013, Swaziland launched a prevention of mother-to-child transmission of HIV (PMTCT) B+ implementation study in rural Shiselweni. We aimed to identify patient and health service determinants of combined antiretroviral therapy (ART) initiation to help guide national implementation of PMTCT B+. Methods: This prospective cohort study uses routine data from registers and patient files in the PMTCT B+ pilot zone and a neighboring health zone where PMTCT A was the standard of care. All HIV-positive women not on combined ART at the first antenatal care visit between January 28, 2013 and December 31, 2013 were included. Results: 399 women from the PMTCT B+ zone and 183 from the PMTCT A zone are included. The overall proportion of women who had not started an antiretroviral intervention before 32 weeks' gestation was lower in the PMTCT A zone (13% vs 25%, P = 0.003), yet a higher proportion women with CD4 350 (80% vs 59%, P < 0.001). Among women with CD4 350, high proportions of missing socio-demographic data made it impossible to make any firm conclusions to this respect. Conclusions: This study not only demonstrates challenges in initiating pregnant women on ART, but also identifies opportunities offered by PMTCT B+ for improving treatment initiation among women with lower CD4 counts.

Background Leprosy continues to be a public health problem in many countries. Difficulties faced by health services include late diagnosis, under-reporting of new cases, adequate monitoring of disabilities and treatment. Furthermore, systematic follow-up after completion of treatment is important, when new disabilities may occur, or existing disabilities may get worse. The objective of the present study was to determine the prevalence of leprosy-associated grade 2 disabilities (G2D) after completion of multidrug therapy (MDT) and to identify factors associated with G2D. Methods We performed a cross-sectional study of 222 leprosy cases registered in Vitória da Conquista, Bahia state, Brazil from 2001–2014. We performed a clinical examination of the study participants and collected socio-economic and clinical information by interview. We identified factors associated with grade 2 disability (G2D) using logis tic regression. Results In total, 38 (17.1%) participants were diagnosed with G2D, and 106 (47.7%) with grade 1 disabilities (G1D). The following independent factors were significantly associated with G2D: occurrence of leprosy reaction (adjusted OR = 2.5; 95%CI = 1.09–5.77), thickening and/or tenderness of one or more nerve trunks (adjusted OR = 3.0; CI = 1.13–8.01) and unemployment (adjusted OR = 7.17; CI = 2.44–21.07). Conclusions This study shows that physical disabilities remain after completion of MDT and frequently occur in an endemic area in Brazil. Finding new ways to reduce the burden of disability are urgently needed, and may include systematic follow-up of patients after treatment completion combined with evidence-based preventative measures., Author summary Leprosy is a Neglected Tropical Disease that is still common in many countries. Patients who have had leprosy often suffer long-term physical disabilities. For some patients, disabilities occur after finishing treatment or existing disabilities may get worse. We contacted 222 leprosy patients who had previously completed multidrug therapy (MDT) in a typical endemic area in Brazil and assessed leprosy-associated disabilities, and the associated clinical or sociodemographic factors. We found that 17.1% of the participants had severe (grade 2) disabilities. Disabilities were more common among patients who had had a leprosy reaction, thickening and/or tenderness of one or more nerve trunks and were unemployed. The findings are important because we show that physical disabilities occur frequently after treatment completion in this area, and that patients need long-term follow-up by the health system. Integrated measures that consider clinical and socio-economic aspects are also needed to reduce leprosy burden after completion of treatment, such as devising of public policies, implementation of clinical monitoring and the development of evidence-based guidelines for follow-up after release from MDT.

Introduction In June 2015, a cholera outbreak was declared in Juba, South Sudan. In addition to standard outbreak control measures, oral cholera vaccine (OCV) was proposed. As sufficient doses to cover the at-risk population were unavailable, a campaign using half the standard dosing regimen (one-dose) targeted high-risk neighborhoods and groups including neighbors of suspected cases. Here we report the operational details of this first public health use of a single-dose regimen of OCV and illustrate the feasibility of conducting highly targeted vaccination campaigns in an urban area. Methodology/Principal findings Neighborhoods of the city were prioritized for vaccination based on cumulative attack rates, active transmission and local knowledge of known cholera risk factors. OCV was offered to all persons older than 12 months at 20 fixed sites and to select groups, including neighbors of cholera cases after the main campaign (‘case-triggered’ interventions), through mobile teams. Vaccination coverage was estimated by multi-stage surveys using spatial sampling techniques. 162,377 individuals received a single-dose of OCV in the targeted neighborhoods. In these neighborhoods vaccine coverage was 68.8% (95% Confidence Interval (CI), 64.0–73.7) and was highest among children ages 5–14 years (90.0%, 95% CI 85.7–94.3), with adult men being less likely to be vaccinated than adult women (Relative Risk 0.81, 95% CI: 0.68–0.96). In the case-triggered interventions, each lasting 1–2 days, coverage varied (range: 30–87%) with an average of 51.0% (95% CI 41.7–60.3). Conclusions/Significance Vaccine supply constraints and the complex realities where cholera outbreaks occur may warrant the use of flexible alternative vaccination strategies, including highly-targeted vaccination campaigns and single-dose regimens. We showed that such campaigns are feasible. Additional work is needed to understand how and when to use different strategies to best protect populations against epidemic cholera., Author summary Oral cholera vaccine (OCV) is becoming part of the standard cholera-control toolkit, although experience in deploying OCV is limited. Adapting vaccination strategies to the global availability of vaccines and the local context (i.e., population movement, security constraints, etc.) is key to maximize the impact of OCV as a cholera-control tool. Here we describe the operational details of the first field use of a single-dose of OCV, which was deployed in a targeted manner, both at high-risk neighborhoods and then to neighbors of suspected cases after the main OCV campaign when sporadic cholera case reports continued. We show that it is feasible to conduct micro- and macro-targeted vaccination campaigns in urban areas like Juba with moderate to high coverage and without social unrest due to vaccinating some groups and not others. Flexible and context-adapted OCV dosing regimens and strategies should be considered in future deployments of the vaccine.

Home-based HIV counselling and testing (HBHCT) has the potential to increase HIV testing uptake in sub-Saharan Africa (SSA) but data on linkage to HIV care after HBHCT are scarce. We conducted a systematic review of linkage to care after HBHCT in SSA. Five databases were searched for studies published between 1(st) January 2000 and 19(th) August 2016 that reported on linkage to care among adults newly identified with HIV infection through HBHCT. Eligible studies were reviewed, assessed for risk of bias and findings summarised using the PRISMA guidelines. 14 studies from six countries met the eligibility criteria; 9 used specific strategies (point-of-care CD4 count testing, follow-up counselling, provision of transport funds to clinic, and counsellor facilitation of HIV clinic visit) in addition to routine referral to facilitate linkage to care. Time intervals for ascertaining linkage ranged from 1 week to 12 months post-HBHCT. Linkage ranged from 8.2% [95% confidence interval (CI), 6.8%-9.8%] to 99.1% (95% CI, 96.9%-99.9%). Linkage was generally lower ( 80%) if additional strategies were used. Only 1 study assessed linkage by means of a randomised trial. 5 studies had data on cotrimoxazole (CTX) prophylaxis and 12 on ART eligibility and initiation. CTX uptake among those eligible ranged from 0% to 100%. The proportion of persons eligible for ART ranged from 16.5% (95% CI, 12.1-21.8) to 77.8% (95% CI, 40.0-97.2). ART initiation among those eligible ranged from 14.3% (95% CI, 0.36%-57.9%) to 94.9% (95% CI, 91.3%-97.4%). Additional linkage strategies, whilst seeming to increase linkage, were not associated with higher uptake of CTX and/or ART. Most of the studies were susceptible to risk of outcome ascertainment bias. A pooled analysis was not performed because of heterogeneity across studies with regard to design, setting, and the key variable definitions. Only few studies from SSA investigated linkage to care among adults newly diagnosed with HIV through HBHCT. Linkage was often low after routine referral but higher if additional interventions were used to facilitate it. The effectiveness of linkage strategies should be confirmed through randomised controlled trials. This article is protected by copyright. All rights reserved.

The Ebola epidemic in West Africa was stopped by an enormous concerted effort of local communities and national and international organizations. It is not clear, however, how much the public health response and behavioural changes in affected communities, respectively, contributed to ending the outbreak. Here, we analyse the epidemic in Lofa County, Liberia, lasting from March to November 2014, by reporting a comprehensive time line of events and estimating the time-varying transmission intensity using a mathematical model of Ebola transmission. Model fits to the epidemic show an alternation of peaks and troughs in transmission, consistent with highly heterogeneous spread. This is combined with an overall decline in the reproduction number of Ebola transmission from early August, coinciding with an expansion of the local Ebola treatment centre. We estimate that healthcare seeking approximately doubled over the course of the outbreak, and that isolation of those seeking healthcare reduced their reproduction number by 62% (mean estimate, 95% credible interval (CI) 59–66). Both expansion of bed availability and improved healthcare seeking contributed to ending the epidemic, highlighting the importance of community engagement alongside clinical intervention. This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’.

Supplemental Digital Content is Available in the Text., Objective: To assess the programmatic quality (coverage of testing, counseling, and retesting), cost, and outcomes (viral suppression, treatment decisions) of routine viral load (VL) monitoring in Swaziland. Design: Retrospective cohort study of patients undergoing routine VL monitoring in Swaziland (October 1, 2012 to March 31, 2013). Results: Of 5563 patients eligible for routine VL testing monitoring in the period of study, an estimated 4767 patients (86%) underwent testing that year. Of 288 patients with detectable VL, 210 (73%) underwent enhanced adherence counseling and 202 (70%) had a follow-up VL within 6 months. Testing coverage was slightly lower in children, but coverage of retesting was similar between and age groups and sexes. Of those with a follow-up test, 126 (62%) showed viral suppression. The remaining 78 patients had World Health Organization–defined virologic failure; 41 (53%) were referred by the doctor for more adherence counseling, and 13 (15%) were changed to second-line therapy, equating to an estimated rate of 1.2 switches per 100 patient-years. Twenty-four patients (32%) were transferred out, lost to follow-up, or not reviewed by doctor. The “fully loaded” cost of VL monitoring was $35 per patient-year. Conclusions: Achieving good quality VL monitoring is feasible and affordable in resource-limited settings, although close supervision is needed to ensure good coverage of testing and counseling. The low rate of switch to second-line therapy in patients with World Health Organization–defined virologic failure seems to reflect clinician suspicion of ongoing adherence problems. In our study, the main impact of routine VL monitoring was reinforcing adherence rather than increasing use of second-line therapy.

Objective We aimed to evaluate the population’s awareness about the radiation exposure associated with five specific imaging tests, and their preference regarding three different formats for receiving the information before undergoing an imaging test. Methods A quantitative and qualitative evaluation through a survey and focal groups including general population from two health departments in Spain. The sampling was carried out in stages (according to health department size) and stratified by age and sex, to get a representative sample. We randomly selected the participants from these stages to be contacted by telephone by a trained nurse. Oral informed consent was obtained. Results Of 602 participants in the quantitative survey, 418 (70.3%) stated that they were aware of the risk associated with radiation. While the majority of these 418 participants knew that x-rays involve radiation (85.4%), fewer were aware that CT (42%) and mammography (38%) also involve radiation, and a substantial proportion believed, incorrectly, that MRI (38%) and ultrasound (18.4%) expose patients to radiation. The population preference was to receive the information using both oral and written formats, accompanied by a table showing the equivalence of the radiation associated with the imaging test to either a number of chest X-rays and exposure number of days of background radiation. Discussion The general population does not receive enough information regarding radiation exposure and the associated risks related to imaging tests. Initiatives should be designed to reinforce the patient’s awareness when ordering a diagnostic imaging test.

Background People who are newly diagnosed with pulmonary tuberculosis (TB) typically receive a standard first-line treatment regimen that consists of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol followed by four months of isoniazid and rifampicin. Fixed-dose combinations (FDCs) of these drugs are widely recommended. Objectives To compare the efficacy, safety, and acceptability of anti-tuberculosis regimens given as fixed-dose combinations compared to single-drug formulations for treating people with newly diagnosed pulmonary tuberculosis. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL, published in the Cochrane Library, Issue 11 2015); MEDLINE (1966 to 20 November 2015); EMBASE (1980 to 20 November 2015); LILACS (1982 to 20 November 2015); the metaRegister of Controlled Trials; and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), without language restrictions, up to 20 November 2015. Selection criteria Randomized controlled trials that compared the use of FDCs with single-drug formulations in adults (aged 15 years or more) newly diagnosed with pulmonary TB. Data collection and analysis Two review authors independently assessed studies for inclusion, and assessed the risk of bias and extracted data from the included trials. We used risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with 95% confidence intervals (CIs). We attempted to assess the effect of treatment for time-to-event measures with hazard ratios and their 95% CIs. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used the fixed-effect model when there was little heterogeneity and the random-effects model with moderate heterogeneity. We used an I² statistic value of 75% or greater to denote significant heterogeneity, in which case we did not perform a meta-analysis. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Main results We included 13 randomized controlled trials (RCTs) in the review, which enrolled 5824 participants. Trials were published between 1987 and 2015 and included participants in treatment with newly diagnosed pulmonary TB in countries with high TB prevalence. Only two trials reported the HIV status of included participants. Overall there is little or no difference detected between FDCs and single-drug formulations for most outcomes reported. We did not detect a difference in treatment failure between FDCs compared with single-drug formulations (RR 1.28, 95% CI 0.82 to 2.00; 3606 participants, seven trials, moderate quality evidence). Relapse may be more frequent in people treated with FDCs compared to single-drug formulations, although the confidence interval (CI) includes no difference (RR 1.28, 95% CI 1.00 to 1.64; 3621 participants, 10 trials, low quality evidence). We did not detect any difference in death between fixed-dose and single-drug formulation groups (RR 0.96, 95% CI 0.67 to 1.39; 4800 participants, 11 trials, moderate quality evidence). When we compared FDCs with single-drug formulations we found little or no difference for sputum smear or culture conversion at the end of treatment (RR 0.99, 95% CI 0.96 to 1.02; 2319 participants, seven trials, high quality evidence), for serious adverse events (RR 1.45, 95% CI 0.90 to 2.33; 3388 participants, six trials, moderate quality evidence), and for adverse events that led to discontinuation of therapy (RR 0.96, 95% CI 0.56 to 1.66; 5530 participants, 13 trials, low quality evidence). We conducted a sensitivity analysis excluding studies at high risk of bias and this did not alter the review findings. Authors' conclusions Fixed-dose combinations and single-drug formulations probably have similar effects for treating people with newly diagnosed pulmonary TB. PLAIN LANGUAGE SUMMARY Fixed-dose combinations for treating pulmonary tuberculosis What are fixed-dose combinations and how might they improve care of people with tuberculosis Tuberculosis (TB) is an important health problem, especially in developing countries. The treatment for pulmonary TB in new patients includes four oral medicines taken for six months, sometimes as fixed-dose combinations (FDCs) that are combined in one tablet, or taken separately as single-drug formulations. The World Health Organization recommends prescribers use fixed-dose combinations to reduce the number of tablets that people take. On the supply side, this might reduce prescribing errors and improve drug supply efficiency; on the patient's side, FDCS simplify treatment and improve adherence. We conducted a review to assess the efficacy, safety, and acceptability of FDCs compared with single-drug formulations for treating people with newly diagnosed pulmonary TB. What the research says We searched for relevant trials up to 20 November 2015, and included 13 randomized controlled trials that enrolled 5824 people. Trials were published between 1987 and 2015 and included participants in treatment with newly diagnosed pulmonary TB in countries with high TB prevalence. Only two trials reported the HIV status of included participants. There is probably little or no difference in FDCs compared to single-drug formulations for treatment failure (moderate quality evidence); relapse may be more frequent (low quality evidence); and the number of deaths were similar (moderate quality evidence). There is little or no difference in sputum smear or culture conversion (high quality evidence), and no difference was shown for serious adverse events (moderate quality evidence) or adverse events that led to discontinuation of therapy (low quality evidence). Authors' conclusions We concluded that fixed-dose combinations have similar efficacy to single-drug formulations for treating people with newly diagnosed pulmonary TB.

Summary Background Oral cholera vaccines represent a new effective tool to fight cholera and are licensed as two-dose regimens with 2–4 weeks between doses. Evidence from previous studies suggests that a single dose of oral cholera vaccine might provide substantial direct protection against cholera. During a cholera outbreak in May, 2015, in Juba, South Sudan, the Ministry of Health, Medecins Sans Frontieres, and partners engaged in the first field deployment of a single dose of oral cholera vaccine to enhance the outbreak response. We did a vaccine effectiveness study in conjunction with this large public health intervention. Methods We did a case-cohort study, combining information on the vaccination status and disease outcomes from a random cohort recruited from throughout the city of Juba with that from all the cases detected. Eligible cases were those aged 1 year or older on the first day of the vaccination campaign who sought care for diarrhoea at all three cholera treatment centres and seven rehydration posts throughout Juba. Confirmed cases were suspected cases who tested positive to PCR for Vibrio cholerae O1. We estimated the short-term protection (direct and indirect) conferred by one dose of cholera vaccine (Shanchol, Shantha Biotechnics, Hyderabad, India). Findings Between Aug 9, 2015, and Sept 29, 2015, we enrolled 87 individuals with suspected cholera, and an 898-person cohort from throughout Juba. Of the 87 individuals with suspected cholera, 34 were classified as cholera positive, 52 as cholera negative, and one had indeterminate results. Of the 858 cohort members who completed a follow-up visit, none developed clinical cholera during follow-up. The unadjusted single-dose vaccine effectiveness was 80·2% (95% CI 61·5–100·0) and after adjusting for potential confounders was 87·3% (70·2–100·0). Interpretation One dose of Shanchol was effective in preventing medically attended cholera in this study. These results support the use of a single-dose strategy in outbreaks in similar epidemiological settings. Funding Medecins Sans Frontieres.

Summary Objectives To explore clinical and socioeconomic factors related to congenital syphilis in Posadas, Argentina. Methods Data were collected from 102 mothers who had given birth to an infant with congenital syphilis at Dr. Ramon Madariaga Central Hospital (2005–2007) and 306 control mothers. Clinical and demographic information were collected from clinical records, and socioeconomic details were obtained by interview. Multivariable logistic regression was used to explore the relationships between congenital syphilis and clinical and socioeconomic factors. Results Receiving the recommended number of prenatal health checks had a clear protective effect on congenital syphilis in the univariate analysis (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.31–0.86), as did being in a stable relationship (OR 0.23, 95% CI 0.14–0.38). Furthermore, women with secondary education or above were over four-times less likely to have a child with congenital syphilis compared to women who had not completed primary school education, even after controlling for the number of prenatal health checks and other factors (adjusted OR 0.24, 95% CI 0.08–0.72). In addition, women with previous stillborn births were over three-times more likely to have a baby with congenital syphilis after controlling for education and prenatal care (adjusted OR 3.37, 95% CI 1.24–9.16). Conclusions There is a clear opportunity for reducing the burden of congenital syphilis by promoting syphilis screening and treatment in women with previous stillborn births. In addition, the potential impact of more general policies addressing social determinants of health, such as those improving education, must not be overlooked.

Eur J Clin Invest 2011; 41 (7): 793–805 Abstract Background More clinically meaningful diagnostic tests are needed in exocrine pancreatic cancer (EPC). K-ras mutations are the most frequently acquired genetic alteration in EPC. We analysed the diagnostic utility of detecting K-ras mutations through a systematic analysis of the literature. Methods We searched PubMed using suitable medical subject headings and text words. Original research articles that evaluated the diagnostic accuracy of detecting K-ras mutations for diagnosis of EPC were selected. Two investigators independently extracted data from each study regarding the methodology used, the methodological quality of the study, the diagnostic accuracy reported and the authors’ conclusions about clinical applicability of the test. Combined estimates for the sensitivity and specificity of K-ras were determined using bivariate meta-analysis; heterogeneity was explored using meta-regression. Results We assessed 34 studies from 30 published articles. The research reports were prone to numerous methodological biases and often lacked vital information for assessing external validity. The sensitivity of detecting K-ras status ranged from 0% through 100%, and the specificity from 58% through 100%. Diagnostic accuracy was highest when cytohistological samples were used: sensitivity and specificity were 76·5% (66·7–84·2) and 91·8% (87·6–94·1), respectively. Studies conducted in a clinically relevant population observed lower accuracy than case–control designs (68·4% vs. 82·7%). Conclusions Because of the numerous methodological limitations of studies, the utility of analysing K-ras mutations for the diagnosis of EPC remains unknown. Flaws in diagnostic biomarkers with well-established biological properties, as K-ras, become even more relevant when the promises of ‘personalized medicine’ are pondered.

International audience; The diagnostic utility of detecting K- mutations for the diagnosis of exocrine pancreatic cancer (EPC) has not been properly studied, and few reports have analysed a clinically relevant spectrum of patients. The objective was to evaluate the clinical validity of detecting K- mutations in the diagnosis of EPC in a large sample of clinically relevant patients. We prospectively identified 374 patients in whom one of the following diagnoses was suspected at hospital admission: EPC, chronic pancreatitis, pancreatic cysts, and cancer of the extrahepatic biliary system. Mutations in the K- oncogene were analysed by PCR and artificial RFLP in 212 patients. The sensitivity and specificity of the K- mutational status for the diagnosis of EPC were 77.7% (95% CI: 69.2-84.8) and 78.0% (68.1-86.0), respectively. The diagnostic accuracy was hardly modified by sex and age. In patients with either mutated K- or CEA > 5 ng/ml, the sensitivity and specificity were 81.0% (72.9-87.6) and 62.6% (72.9-87.6), respectively. In patients with mutated K- and CEA > 5 ng/ml the sensitivity was markedly reduced. In comparisons with a variety of non-EPC patient groups sensitivity and specificity were both always greater than 75%. In this clinically relevant sample of patients the sensitivity and specificity of K- mutations were not sufficiently high for independent diagnostic use. However, it seems premature to rule out the utility of K- analysis in conjunction with other genetic and 'omics' technologies.

Background: We evaluated whether articles on molecular diagnostic tests interpret appropriately the clinical applicability of their results.Methods: We selected original-research articles published in 2006 that addressed the diagnostic value of a molecular test. We defined overinterpretation of clinical applicability by means of prespecified rules that evaluated study design, conclusions regarding applicability, presence of statements suggesting the need for further clinical evaluation of the test, and diagnostic accuracy. Two reviewers independently evaluated the articles; consensus was reached after discussion and arbitration by a third reviewer.Results: Of 108 articles included in the study, 82 (76%) used a design that used healthy controls or alternative-diagnosis controls, only 15 (11%) addressed a clinically relevant population similar to that in which the test might be applied in practice, 104 articles (96%) made definitely favorable or promising statements regarding clinical applicability, and 61 (56%) of the articles apparently overinterpreted the clinical applicability of their findings. Articles published in journals with higher impact factors were more likely to overinterpret their results than those with lower impact factors (adjusted odds ratio, 1.71 per impact factor quartile; 95% CI, 1.09–2.69; P = 0.020). Overinterpretation was more common when authors were based in laboratories than in clinical settings (adjusted odds ratio, 18.7; 95% CI, 1.41–249; P = 0.036).Conclusions: Although expectations are high for new diagnostic tests based on molecular techniques, the majority of published research has involved preclinical phases of research. Overinterpretation of the clinical applicability of findings for new molecular diagnostic tests is common.

Objectives To adapt the Quality Assessment of Diagnostic Accuracy Assessment (QUADAS) to the particular methodological challenges posed by research on ‘-omics’-based diagnostic tests. Design and methods We generated new guidelines by appraising the suitability of each criterion from QUADAS to ‘-omics’-based diagnostic research, and by adding new items that addressed specific sources of error. In addition, we defined four phases in the evaluation of a diagnostic test. Results Twelve of the 14 criteria from QUADAS were retained in the new tool. The items relating to selection criteria and the description of the test were reformulated, and the criteria about external validation and the availability of clinical data were applied only in studies in the last research phase. Four new items were incorporated to QUADOMICS related to pre-analytical conditions and methods to avoid overfitting. Conclusions QUADOMICS is an adaptation of QUADAS to the special nature of ‘-omics’-based diagnostic research. The tool adds new items that assess quality issues specific to this research, and may enhance the application of ‘-omics’-based discoveries to clinical \and public health practice.

Objectives To evaluate the feasibility (population reached, costs) and effectiveness (positivity rates, linkage to care) of two strategies of community-based HIV testing and counselling (HTC) in rural Swaziland. Methods Strategies used were mobile HTC (MHTC) and home-based HTC (HBHTC). Information on age, sex, previous testing and HIV results was obtained from routine HTC records. A consecutive series of individuals testing HIV-positive were followed up for 6 months from the test date to assess linkage to care. Results A total of 9 060 people were tested: 2 034 through MHTC and 7 026 through HBHTC. A higher proportion of children and adolescents (

Objectives To assess the impact of initiatives aiming to increase clinician awareness of radiation exposure; to explore the challenges they face when communicating with patients; to study what they think is the most appropriate way of communicating the long-term potential risks of medical radiological exposure to patients. Design A quantitative and qualitative evaluation through a survey and focal groups. Setting San Juan Hospital and Dr Peset Hospital (Southeast Spain) and clinicians from Spanish scientific societies. Participants The surveys were answered (a) in person (216: all the radiologists (30), urologists (14) and surgeons (44) working at both participant hospitals; a sample of general practitioners from the catchment area of one hospital (45), and a consecutive sample of radiologists attending a scientific meeting (60)) or (b) electronically through Spanish scientific societies (299: radiologists (45), pneumologists (123), haematologists (75) and surgeons (40)). Clinicians were not randomly selected and thus the results are limited by the diligence of the individuals filling out the survey. Primary and secondary outcome measures Clinicians9 knowledge and practices regarding medical radiological exposure, and what they considered most appropriate for communicating information to patients. Results Nearly 80% of the clinicians surveyed had never heard of the European recommendations. Fewer than 20% of the clinicians surveyed identified correctly the radiation equivalence dose of intravenous urography or barium enema. It was reported by 31.7% that they inform patients about the long-term potential risks of ionising radiation. All participants agreed that the most appropriate way to present information is a table with a list of imaging tests and their corresponding radiation equivalence dose in terms of chest X-rays and background radiation exposure. Conclusions Medical radiological exposure is frequently underestimated and rarely explained to patients. With a clear understanding of medical radiological exposure and proper communication tools, clinicians will be able to accurately inform patients.

Diagnostic accuracy may be overestimated when using certain study designs; thus, the inclusion of studies using different designs in meta-analyses may have important effects on their results, and influence clinical decision making. The main aim of this study was to explore the influence of heterogeneity (based on the inclusion of different study designs) on diagnostic accuracy in a sample of published meta-analyses of diagnostic accuracy studies. We identified 30 systematic reviews which included 95 separate meta-analyses combining the results from a total of 976 individual studies. We classified each individual study according to the study design (case-control studies, clinically relevant patient series or other), and each meta-analysis according to the heterogeneity of the included studies. Furthermore, we registered how the methodological quality of the individual studies was assessed. Finally, for each meta-analysis, the summary measure of diagnostic accuracy was categorised as Good, Fair or Poor. We used logistic regression to assess the relationship between reporting good diagnostic accuracy and heterogeneity. Meta-analyses with heterogeneous populations were over three times more likely to report good diagnostic accuracy compared to meta-analyses that included only clinically relevant patient series (adjusted odds ratio 3.07 95% CI 1.16-8.11). The combination of studies that use different designs, within the same meta-analysis, may lead to higher estimates of diagnostic accuracy.

Objectives To assess the magnitude and pattern of socioeconomic inequality in current smoking in low and middle income countries. Methods We used data from the World Health Survey [WHS] in 48 low-income and middle-income countries to estimate the crude prevalence of current smoking according to household wealth quintile. A Poisson regression model with a robust variance was used to generate the Relative Index of Inequality [RII] according to wealth within each of the countries studied. Results In males, smoking was disproportionately prevalent in the poor in the majority of countries. In numerous countries the poorest men were over 2.5 times more likely to smoke than the richest men. Socioeconomic inequality in women was more varied showing patterns of both pro-rich and pro-poor inequality. In 20 countries pro-rich relative socioeconomic inequality was statistically significant: the poorest women had a higher prevalence of smoking compared to the richest women. Conversely, in 9 countries women in the richest population groups had a statistically significant greater risk of smoking compared to the poorest groups. Conclusion Both the pattern and magnitude of relative inequality may vary greatly between countries. Prevention measures should address the specific pattern of smoking inequality observed within a population.

Placing health in the agendas of all policy makers remains a challenge. Finding new ways to boost Health in All Policies should be a continuous process. Currently, health information initiatives gather core health statistics, indicators related to healthcare, along with individual level risk factors such as smoking or obesity. However, there is a lack of identifiable information showing the effect of non-primary health policies on population health. A research agenda is proposed, focusing on three related areas that would frame health information in such a way that the implications for decision-makers from non-health sectors are clear: (a) research in order to provide solid and quantitative evidence linking the social and environmental determinants of health with their ultimate health outcomes; (b) research that shows and quantifies the effect of policies and specific interventions on these determinants; and (c) the development of policy-linked indicators which provide a quantitative estimate of the health that would be gained (or disease burden that could be avoided) by adoption of a specific policy.

Good health governance requires appropriate health intelligence, and consequently, health information needs to be reshaped in order to foster health policy innovation. Several key aspects should pervade the new approaches to the management of health information: advocacy, monitoring broad health determinants, accountability, and transparency. Strong advocacy is needed if we wish to convince non-health sectors of the relevance of health in their policies. Successful advocacy is based on new and innovative ways of framing health information which contributes to moving health higher up the media, public, and policy agendas. The goal is to put across the effects that all societal sectors have on health and well-being. Advocacy in the terms mentioned is also required to transform public health from an underfunded pyramidal bureaucracy into a strengthened public health with higher-profile leadership. This represents a shift of approach from an individual-centred prevention linked to health services to a public health that makes healthy choices easier and is capable of promoting multifaceted policies from diverse sectors emerging through network governance.

Analyses of errors in diagnostic studies have led to improvements in the methodological quality of traditional laboratory research. However, since features of genomics and proteomics research ("-omics") differ from those of traditional research, sources of error are also likely to be distinct. We examine the main sources of error that are particularly relevant to "-omics"-based diagnostic techniques through the analysis of primary research papers which address these potential errors, their solutions, and the resulting spurious effect on diagnostic accuracy prediction. The main sources of error described in "-omics"-based research are mainly associated with chance: over-fitting and inadequate sample size; variation: preanalytical variation (specimen collection and management), analytical variation (test procedures and reproducibility) and biological variation. We conclude that "-omics"-based research is prone to several errors. We have characterized them and shown the range of available solutions. This is a key step in the application of genomic discoveries to clinical and public health practice.

Introduction The finding of a solitary pulmonary nodule (SPN) ( Methods 4681 consecutive patients ≥35 years referred for a thoracic imaging test in two hospitals in the Community of Valencia, Spain in 2010 were included. Six expert radiologists independently classified each imaging report according to the presence or absence of a SPN. Other variables, such as patient demographics diagnosis suspicion, smoking habit, the referral clinical department, type of radiological test performed, and clinical setting were ascertained from medical records. The association between SPNs and patient/clinical characteristics was assessed with unconditional logistic regression. Results SPNs were observed in 351 patients (7.5%) and their prevalence varied according to patient characteristics and the referral department, with oncology (15.4%), primary care (10.7%) and pneumology (9.8%), being the highest. After controlling for other factors, SPNs were more common in men (aOR 1.47, 95% CI 1.25 to 1.75), and in smokers (aOR 1.62, 95% CI 1.41 to 1.82). Conclusions At least one in every 13 patients undergoing a thoracic imaging test during routine clinical care will show a SPN. The follow-up of these patients is needed in order to estimate their predictive value for lung cancer, and avoid the initiation of an unnecessary cascade of clinical procedure in benign lesions.

Background: QUADOMICS is an adaptation of QUADAS (a quality assessment tool for use in systematic reviews of diagnostic accuracy studies), which takes into account the particular challenges presented by '-omics' based technologies. Our primary objective was to evaluate the applicability and consistency of QUADOMICS. Subsequently we evaluated and describe the methodological quality of a sample of recently published studies using the tool. Methodology/Principal Findings: 45'-omics'- based diagnostic studies were identified by systematic search of Pubmed using suitable MeSH terms (>Genomics>, >Sensitivity and specificity>, >Diagnosis>). Three investigators independently assessed the quality of the articles using QUADOMICS and met to compare observations and generate a consensus. Consistency and applicability was assessed by comparing each reviewer's original rating with the consensus. Methodological quality was described using the consensus rating. Agreement was above 80% for all three reviewers. Four items presented difficulties with application, mostly due to the lack of a clearly defined gold standard. Methodological quality of our sample was poor; studies met roughly half of the applied criteria (mean ± sd, 54.7±18.4°%). Few studies were carried out in a population that mirrored the clinical situation in which the test would be used in practice, (6, 13.3%);none described patient recruitment sufficiently; and less than half described clinical and physiological factors that might influence the biomarker profile (20, 44.4%). Conclusions: The QUADOMICS tool can consistently be applied to diagnostic '-omics' studies presently published in biomedical journals. A substantial proportion of reports in this research field fail to address design issues that are fundamental to make inferences relevant for patient care. © 2010 Parker et al., This work was supported by the Spanish Agency for Health Technology Assessment, Exp PI06/90311, Instituto de Salud Carlos III and CIBER en Epidemiología y Salud Pública (CIBERESP) in Spain

Objective To determine the prevalence of solitary pulmonary nodules (SPNs) in chest radiology studies and patient’s features associated with malignancy in a non-high-risk clinical population. Methods Patients ≥35 years were referred for thoracic imaging in two hospitals (2010-2011). Eight radiologists determined the presence and characteristics of SPN. Selected variables were collected from radiological register and medical records. Observer agreement in the diagnosis of SPN was assessed. Results 25,529 patients were included: 23,102 (90.5 %) underwent chest radiograph and 2,497 (9.5 %) a CT. The prevalence of SPN was 2.1 % (95 % CI 1.9 – 2.3) in radiographs and 17.0 % (95 % CI 15.5 – 18.5) in CT. In patients undergoing chest radiograph, detection of SPN with an irregular border was more frequent among smokers. In patients who had a CT, larger SPNs appeared to be associated with 60 years of age or over, diagnosis of a respiratory illness, or male gender. In addition, an irregular border was also more common among men. Conclusions The prevalence of SPNs detected by both radiograph and CT was lower than that shown in screening studies. Patient characteristics such as age, sex, respiratory disease, or smoking habit were associated with nodule characteristics that are known to be related with malignancy. Key Points • There is a lower SPN prevalence in the clinical population than in screening studies. • SPN prevalence is associated with some patient characteristics: sex, age, imaging test. • Nodule characteristics related to malignancy were associated with some patient characteristics.

In December, 2014, an outbreak of suspected meningitis was investigated in Ituri District, northeastern Democratic Republic of Congo (DRC). Ituri shares borders with Uganda and South Sudan, is well known for political instability, and houses a large displaced population with limited access to health care. Meningitis was suspected by health workers due to neck spasm, interpreted as neck stiffness. However, further investigations (see appendix for details) suggested that bacterial meningitis was not the cause of this outbreak. In the outbreak response that followed, participants provided verbal informed consent prior to interviews, lumbar puncture, and urine collection and the Government of DRC approved the outbreak investigation plan.

BackgroundGiven that most evidence-based recommendations for managing type 2 diabetes mellitus (T2DM) are generated in high-income settings, significant challenges for their implementation exist in Latin America and the Caribbean region (LAC), where the rates of T2DM and related mortality are increasing. The aim of this study is to identify the facilitators and barriers to successful management of T2DM in LAC, from the perspectives of patients, their families or caregivers, healthcare professionals, and/or other stakeholders.MethodsWe conducted a systematic review in MEDLINE, Web of Science, SciELO, and LILACS. We included studies of disease management, prevention of complications and risk factor management. We qualitatively synthesized the verbatim text referring to barriers and/or facilitators of diabetes management according to the Theoretical Domain Framework and described their relative frequencies.FindingsWe included 60 studies from 1,595 records identified. 54 studies (90%) identified factors related to the environmental context and resources, highlighting the importance of questions related to health care access or lack of resources in the health system, and the environmental context and living conditions of the patients. Issues related to "social influences" (40 studies) and "social/professional role and identity" (37 studies) were also frequently addressed, indicating the negative impact of lack of support from family and friends and clinicians' paternalistic attitude. 25 studies identified patients beliefs as important barriers, identifying issues such as a lack of patients' trust in the effectiveness of the medication and/or the doctor's advice, or preferences for alternative therapies.ConclusionsSuccessful diabetes management in LAC is highly dependent on factors that are beyond the control of the individual patients. Successful disease control will require emphasis on public policies to reinforce health care access and resources, the promotion of a patient-centred care approach, and health promoting infrastructures at environmental level.