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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 (

This study investigated the unresolved issue of antigen-dependency and antigen-specificity of autoimmune disease suppression by CD4+CD25+ T cells (T regs). Based on autoimmune ovarian disease (AOD) in day 3 thymectomized (d3tx) mice and polyclonal T regs expressing the Thy1.1 marker, we determined: (a) the location of recipient T cell suppression, (b) the distribution of AOD-suppressing T regs, and (c) the relative efficacy of male versus female T regs. Expansion of recipient CD4+ T cells, activation/memory marker expression, and IFN-γ production were inhibited persistently in the ovary-draining LNs but not elsewhere. The cellular changes were reversed upon Thy1.1+ T reg depletion, with emergence of potent pathogenic T cells and severe AOD. Similar changes were detected in the regional LNs during autoimmune dacryoadenitis and autoimmune prostatitis suppression. Although the infused Thy1.1+ T regs proliferated and were disseminated in peripheral lymphoid organs, only those retrieved from ovary-draining LNs adoptively suppressed AOD at a suboptimal cell dose. By depriving d3tx recipients of ovarian antigens, we unmasked the supremacy of ovarian antigen-exposed female over male T regs in AOD suppression. Thus, disease suppression by polyclonal T regs depends on endogenous antigen stimulation; this occurs in a location where potent antigen-specific T regs accumulate and continuously negate pathogenic T cell response.

Oral tolerance was first detailed almost 100 years ago, and since then, it has been shown repeatedly that feeding a wide variety of nonpathogenic antigens can inhibit subsequent systemic immune responses. All systemic immune responses are susceptible, but the degree and scope of the suppression depends on the nature and dose of the fed antigen. Oral tolerance has been described in most mammals, including humans, and it may be the homeostatic mechanism that prevents hypersensitivity to food antigens, as is found in celiac disease. A similar process may prevent the aberrant immune responses to commensal bacteria that occur in inflammatory bowel disease. The ability of oral tolerance to modulate experimental models of autoimmune and inflammatory disease has led to clinical trials in such diseases as rheumatoid arthritis, multiple sclerosis, and type I diabetes, with only variable success. Despite intense research, the exact mechanisms responsible for the systemic tolerance and the reasons why tolerance is the default response to many fed antigens remain controversial. Early studies suggested that CD8(+) "suppressor" T cells were important, but it is now accepted that it may involve either anergy/deletion of CD4(+) T cells, or the induction of regulatory CD4(+) T cells that produce IL-10 and/or TGFbeta. There may also be a role for CD4(+) CD25(+) T(reg), but how and when all these different mechanisms operate is still unclear. The ability of fed antigens to induce tolerance probably reflects their uptake by "quiescent" antigen-presenting cells in the intestine, with presentation to specific CD4(+) T cells in the absence of costimulation, or with the involvement of inhibitory costimulatory molecules. Dendritic cells in the Peyer's patches or mucosal lamina propria are the most likely APCs involved, but it remains to be determined exactly where these interactions occur and what the precise nature of the relevant dendritic cells is.

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.

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.

The intestinal immune system discriminates between invasive pathogens and antigens that are harmless, such as food proteins and commensal bacteria. The latter groups of antigens normally induce tolerance and a breakdown in this homeostatic process can lead to diseases such as coeliac disease or Crohn's disease. The nature ofthe intestinal immune response depends on how antigen is presented to CD4+ T cells by dendritic cells (DCs). Both oral tolerance and priming are influenced by the numbers and activation status of DCs in the gut and its draining lymphoid tissues, and our current work indicates that dietary proteins are taken up preferentially by DCs in the lamina propria of the small intestine. These then migrate to interact with antigen-specific CD4+ T cells in the mesenteric lymph node. In vivo and in vitro studies using purified lamina propria DCs suggest these may play a unique role in the regulation of intestinal immune responses. We propose that local DCs are the gatekeepers of the mucosal immune system, inducing tolerance under physiological conditions, but being sufficiently responsive to inflammatory stimuli to allow T cell priming and protective immunity when necessary. In addition, we will discuss evidence that adjuvant vectors such as ISCOMS may be effective mucosal vaccines due to an ability to activate intestinal DCs.

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.

OBJETIVO: El objetivo principal es evaluar la proporción de vías venosas periféricas canalizadas en el servicio de urgencias que no cumplen criterios de adecuación. Como objetivos secundarios se relacionan estas vías venosas periféricas no adecuadas con el motivo de consulta en el servicio y se cuantifica el coste generado de dichas vías venosas periféricas canalizadas innecesariamente. MÉTODOS: Estudio observacional transversal. Determinamos adecuación de la vía venosa periférica según unos criterios basados en el uso que se dé en el servicio de urgencias. Las variables independientes son los datos socio-demográficos que caractericen a la población, motivo de consulta, zona de exploración, turno asistido y destino del paciente. Los datos se obtienen mediante la revisión de la Historia Clínica de cada usuario a estudio. Se realiza un análisis descriptivo de la muestra y posteriormente, se hace un análisis univariante y multivariante para estudiar la relación entre las características de los pacientes y la adecuación de la vía venosa periférica. RESULTADOS PRELIMINARES: Tras la recogida de 294 (64,1%) de la muestra, un total de 143 (48,6%) fueron portadores de vía venosa periférica. 66 varones frente a 55 mujeres, con una media de edad de 57 años. Casi en su totalidad fueron valorados en los boxes. El número de altas fue 114(79,7%)y del ingreso hospitalario 24 (16,7%). Durante el turno de mañana se atendieron 77 pacientes (53,8%), en la tarde 36 (25,1%) y por la noche 30(20,9%). De los 143 pacientes recogidos hasta el momento con vía venosa periférica, 39 [27,3%, (IC95% 20,5% - 35,2%)] no cumplen criterios de adecuación. Tras el análisis no hubo asociación significativa entre las variables estudiadas. Se estima que el gasto económico con dicho porcentaje de inadecuación sería de 367,2€ por cada 1000 vías canalizadas, sólo contando coste material. CONCLUSIONES: Con los datos obtenidos podemos concluir que casi una de cada tres vías canalizadas en el servicio de urgencias es innecesaria, generando un gran coste económico y personal. Son un elevado número de vías inadecuadas que se deberían evitar.