Systematic screening of gender violence and domestic violence among HIV-positive patients: the VIHOLETA study.

We conducted a multicentre observational study in people living with HIV (PLHIV) on antiretroviral therapy in Alicante (Spain) from 2019 to 2020 aiming to analyse the prevalence of abuse and assess treatment adherence according to this variable. We used the Abuse Assessment Screen tool, the simplified medication adherence questionnaire and the medication possession ratio to assess outcomes.. Of the 161 included PLHIV, 53 (32.9%) had suffered abuse (27 emotional abuse, 6 physical abuse, 3 sexual abuse, 13 emotional and physical abuse, 4 unknown type). Seven (4.3%) had suffered abuse in the last year (5 emotional, 2 physical). Abuse had lasted a median of 48 months (interquartile range 12-81). HIV status was considered as a cause of violence by 9.4% of victims. In the multivariable analysis, only abuse was independently associated with non-adherence [adjusted odds ratio (aOR) 3.92; 95% confidence interval (CI) 1.80-8.84; p = 0.0007]. Abuse (aOR 6.14; 95% CI 1.63-27.70; p = 0.001) and previous incarceration (aOR 15.08 95% CI 2.71-104.71; p = 0.003) were associated with detectable viral load. In conclusion, the prevalence of abuse is high in PLHIV, hampering adherence and virological success. Abuse screening tools should be incorporated into routine HIV care.

Factors Associated with Acute Community-Acquired Pyelonephritis Caused by Extended-Spectrum ß-Lactamase-Producing Escherichia coli.

This study aimed to identify the factors associated with the presence of extended-spectrum ß-lactamase-(ESBL) in patients with acute community-acquired pyelonephritis (APN) caused by Escherechia coli (E. coli), with a view of optimising empirical antibiotic therapy in this context. We performed a retrospective analysis of patients with community-acquired APN and confirmed E. coli infection, collecting data related to demographic characteristics, comorbidities, and treatment. The associations of these factors with the presence of ESBL were quantified by fitting multivariate logistic models. Goodness-of-fit and predictive performance were measured using the ROC curve. We included 367 patients of which 51 presented with ESBL, of whom 90.1% had uncomplicated APN, 56.1% were women aged ≤55 years, 33.5% had at least one mild comorbidity, and 12% had recently taken antibiotics. The prevalence of ESBL-producing E. coli was 13%. In the multivariate analysis, the factors independently associated with ESBL were male sex (OR 2.296; 95% CI 1.043-5.055), smoking (OR 4.846, 95% CI 2.376-9.882), hypertension (OR 3.342, 95% CI 1.423-7.852), urinary incontinence (OR 2.291, 95% CI 0.689-7.618) and recurrent urinary tract infections (OR 4.673, 95% CI 2.271-9.614). The area under the ROC curve was 0.802 (IC 95% 0.7307-0.8736), meaning our model can correctly classify an individual with ESBL-producing E. coli infection in 80.2% of cases.

Chagas disease screening in pregnant Latin American women: Adherence to a systematic screening protocol in a non-endemic country.

BACKGROUND: Chagas disease (CD) is a chronic parasitic disease caused by Trypanosoma cruzi and is endemic to continental Latin America. In Spain, the main transmission route is congenital. We aimed to assess adherence to regional recommendations of universal screening for CD during pregnancy in Latin American women in the province of Alicante from 2014 to 2018. METHODOLOGY/PRINCIPAL FINDINGS: Retrospective quality study using two data sources: 1) delivery records of Latin American women that gave birth in the 10 public hospitals of Alicante between January 2014 and December 2018; and 2) records of Chagas serologies carried out in those centers between May 2013 and December 2018. There were 3026 deliveries in Latin American women during the study period; 1178 (38.9%) underwent CD serology. Screening adherence ranged from 17.2% to 59.3% in the different health departments and was higher in Bolivian women (48.3%). Twenty-six deliveries (2.2%) had a positive screening; CD was confirmed in 23 (2%) deliveries of 21 women. Bolivians had the highest seroprevalence (21/112; 18.7%), followed by Colombians (1/333; 0.3%) and Ecuadorians (1/348; 0.3%). Of 21 CD-positive women (19 Bolivians, 1 Colombian, 1 Ecuadorian), infection was already known in 12 (57.1%), and 9 (42.9%) had already been treated. Only 1 of the 12 untreated women (8.3%) was treated postpartum. Follow-up started in 20 of the 23 (87.0%) neonates but was completed only in 11 (47.8%); no cases of congenital transmission were detected. Among the 1848 unscreened deliveries, we estimate 43 undiagnosed cases of CD and 1 to 2 undetected cases of congenital transmission. CONCLUSIONS/SIGNIFICANCE: Adherence to recommendations of systematic screening for CD in Latin American pregnant women in Alicante can be improved. Strategies to strengthen treatment of postpartum women and monitoring of exposed newborns are needed. Currently, there may be undetected cases of congenital transmission in our province.

Enhanced Immunogenicity and Protective Efficacy of a Campylobacter jejuni Conjugate Vaccine Coadministered with Liposomes Containing Monophosphoryl Lipid A and QS-21.

Campylobacter jejuni is among the most common causes of diarrheal disease worldwide and efforts to develop protective measures against the pathogen are ongoing. One of the few defined virulence factors targeted for vaccine development is the capsule polysaccharide (CPS). We have developed a capsule conjugate vaccine against C. jejuni strain 81-176 (CPS-CRM) that is immunogenic in mice and nonhuman primates (NHPs) but only moderately immunogenic in humans when delivered alone or with aluminum hydroxide. To enhance immunogenicity, two novel liposome-based adjuvant systems, the Army Liposome Formulation (ALF), containing synthetic monophosphoryl lipid A, and ALF plus QS-21 (ALFQ), were evaluated with CPS-CRM in this study. In mice, ALF and ALFQ induced similar amounts of CPS-specific IgG that was significantly higher than levels induced by CPS-CRM alone. Qualitative differences in antibody responses were observed where CPS-CRM alone induced Th2-biased IgG1, whereas ALF and ALFQ enhanced Th1-mediated anti-CPS IgG2b and IgG2c and generated functional bactericidal antibody titers. CPS-CRM + ALFQ was superior to vaccine alone or CPS-CRM + ALF in augmenting antigen-specific Th1, Th2, and Th17 cytokine responses and a significantly higher proportion of CD4+ IFN-γ+ IL-2+ TNF-α+ and CD4+ IL-4+ IL-10+ T cells. ALFQ also significantly enhanced anti-CPS responses in NHPs when delivered with CPS-CRM compared to alum- or ALF-adjuvanted groups and showed the highest protective efficacy against diarrhea following orogastric challenge with C. jejuni This study provides evidence that the ALF adjuvants may provide enhanced immunogenicity of this and other novel C. jejuni capsule conjugate vaccines in humans.IMPORTANCECampylobacter jejuni is a leading cause of diarrheal disease worldwide, and currently no preventative interventions are available. C. jejuni is an invasive mucosal pathogen that has a variety of polysaccharide structures on its surface, including a capsule. In phase 1 studies, a C. jejuni capsule conjugate vaccine was safe but poorly immunogenic when delivered alone or with aluminum hydroxide. Here, we report enhanced immunogenicity of the conjugate vaccine delivered with liposome adjuvants containing monophosphoryl lipid A without or with QS-21, known as ALF and ALFQ, respectively, in preclinical studies. Both liposome adjuvants significantly enhanced immunity in mice and nonhuman primates and improved protective efficacy of the vaccine compared to alum in a nonhuman primate C. jejuni diarrhea model, providing promising evidence that these potent adjuvant formulations may enhance immunogenicity in upcoming human studies with this C. jejuni conjugate and other malaria and HIV vaccine platforms.

Research Recommendations for Improving Measurement of Treatment Effectiveness in Depression.

Background: Despite the steadily escalating psychological and economic burden of depression, there is a lack of evidence for the effectiveness of available interventions on functioning areas beyond symptomatology. Therefore, the main objective of this study was to give an insight into the current measurement of treatment effectiveness in depression and to provide recommendations for its improvement. Materials and Methods: The study was based on a multi-informant approach, comparing data from a systematic literature review, an expert survey with representatives from clinical practice (130), and qualitative interviews with patients (11) experiencing depression. Results: Current literature places emphasis on symptomatic outcomes and neglects other domains of functioning, whereas clinicians and depressed patients highlight the importance of both. Interpersonal relationships, recreation and daily activities, communication, social participation, work difficulties were identified as being crucial for recovery. Personal factors, neglected by the literature, such as self-efficacy were introduced by experts and patients. Furthermore, clinicians and patients identified a number of differences regarding the areas improved by psychotherapeutic or pharmacological interventions that were not addressed by the pertinent literature. Conclusion: Creation of a new cross-nationally applicable measure of psychosocial functioning, broader remission criteria, report of domain-specific information, and a personalized approach in treatment decision-making are the first crucial steps needed for the improvement of the measurement of treatment effectiveness in depression. A better measurement will facilitate the clinical decision making and answer the escalating burden of depression.

The biological response modifier AM3 attenuates the inflammatory cell response and hepatic fibrosis in rats with biliary cirrhosis.

BACKGROUND: An inflammatory immune system response ensues in the liver and in the systemic circulation in cirrhosis, where it contributes to hepatic fibrosis and peripheral vasodilation. Modulation of the inflammatory response without increasing susceptibility to infection is a therapeutic target in cirrhosis. AM3 is a low-toxicity biological response modifier with regulatory effects on innate and adaptative immunity, and the ability to normalise the production of tumour necrosis factor alpha (TNFalpha). AIMS: This was an experimental study to investigate the effects of oral AM3 on the systemic and hepatic inflammatory response, liver fibrosis and on the haemodynamic abnormalities of portal hypertension in rats with biliary cirrhosis. DESIGN: Bile-duct ligated rats received a 3-week oral course of AM3 or placebo. RESULTS: In cirrhotic rats, AM3 blunted the inflammatory switch of circulating and intrahepatic monocytes and T-cells to TNFalpha and interferon gamma (IFNgamma) production, respectively. AM3 modified the intrahepatic polarisation pattern of the regulatory cytokines, decreasing the mRNA expression of transforming growth factor beta1 (TGFbeta1), interleukin 4 (IL4), and IFNgamma, and increasing that of IL10. Total and IFNgamma-producing natural killer (NK) cells were lowered by AM3 in the peripheral blood and liver of cirrhotic rats. The immunomodulatory effects of AM3 led to reduced hepatic fibrogenesis in cirrhotic rats, as shown by decreased area of liver fibrosis, hydroxyproline content and mRNA expression of procollagen alpha1(I). Besides, AM3 lowered portal pressure and systemic hyperaemia. CONCLUSIONS: The biological response modifier AM3 reverses the concurrent inflammatory immune system activation in peripheral blood and liver of experimental established cirrhosis, which results in reductions of hepatic fibrosis, portal pressure and peripheral vasodilation.

Mesenteric Th1 polarization and monocyte TNF-alpha production: first steps to systemic inflammation in rats with cirrhosis.

A systemic inflammatory state with increased circulating tumor necrosis factor alpha (TNF-alpha) has been related to the bacterial infection susceptibility and hemodynamic derangement of patients with cirrhosis. We compared the activation status of immune cell subpopulations defined by 4-color cytometry in mesenteric and peripheral lymph nodes and blood of rats with CCl(4)-cirrhosis to define the immune response initiation site, the T-cell and monocyte contribution to pro-inflammatory cytokine production, as well as the pathogenic role of enteric bacteria in the cirrhosis immune response. Th1 cells and monocytes were expanded in the mesenteric nodes (P < .001) and blood (P < .001) of rats with cirrhosis, and activated to produce interferon gamma (P < .0001) and TNF-alpha (P < .0001), respectively. The greater numbers of recently activated CD134(+) Th cells in mesenteric nodes compared with blood, the correlation between their numbers in mesenteric nodes and blood (r = 0.66, P < .001), and the expansion of activated CD45RC(-) Th cells, which are unable to re-enter lymph nodes, in mesenteric nodes but not in blood or axillary nodes points to mesenteric nodes as the origin site of activated Th cells. Abrogation of bacterial translocation by bowel decontamination reduced the number of activated Th cells and monocytes, and normalized interferon gamma production by Th cells and TNF-alpha production by monocytes in mesenteric nodes and blood, respectively. In conclusion, in cirrhosis, enteric bacteria start off an orchestrated immune response cascade in mesenteric nodes involving Th1 polarization and monocyte activation to TNF-alpha production. Later, the recirculation of these activated effector immune cells into blood promotes systemic inflammation.

Tumour necrosis factor-alpha expression by activated monocytes and altered T-cell homeostasis in ascitic alcoholic cirrhosis: amelioration with norfloxacin.

BACKGROUND/AIMS: To investigate the distribution and activation state of circulating monocytes and T-cell subsets, their contribution to tumour necrosis factor-alpha (TNFalpha) production, and their potential relationship with bacterial products of enteric origin in alcoholic cirrhosis. METHODS: Peripheral blood monocytes and T-lymphocytes from 60 cirrhotic patients and 24 controls were characterized by four-color flow-cytometry after labelling of differentiation antigens and cytokines, before and after a 4-week course of norfloxacin or placebo. RESULTS: Monocytes from ascitic patients showed increased number, enhanced CD80 and HLA-DR surface levels, and spontaneous intracytoplasmic TNFalpha expression, when compared to non-ascitic patients and controls. Blood TNFalpha levels directly correlated with the amount of TNFalpha expressed by monocytes. In ascitic patients, there was a collapse of virgin CD4(+) and CD8(+) T-cell subsets; and, an expansion of activated CD4(+) T-cells. The above abnormalities were mainly restricted to ascitic patients with high serum levels of lypolysaccharide-binding-protein. Norfloxacin normalized the number of monocytes, reduced their activated phenotype and ability to produce TNFalpha and improved the abnormal T-cell homeostasis. CONCLUSIONS: In ascitic cirrhosis with high lipolysaccharide-binding-protein, monocytes are spontaneously activated to produce TNFalpha and are major contributors to the elevated serum TNFalpha. The T-cell compartment is profoundly depleted. Enteric bacterial products play a relevant role in these immune cellular abnormalities.

Manual de normas técnicas y procedimientos en atención primaria de salud / Manual technical standards and procedures in primary health care

Este manual tiene como fin ser una guía clara y concisa de los procedimientos técnicos esenciales, para asegurar la calidad de las actividades del equipo de salud, en la prevención y promoción de la atenciónprimaria de salud, en nuetras comunidades. Esta basado en las normas y guías de la OMS/OPS y UNICEF