Acetazolamide-induced pulmonary oedema: A disproportionality analysis from the EudraVigilance database.

To our knowledge, no prior study has analysed a possible association between acetazolamide and pulmonary oedema. The aim of this study was to use data from the EudraVigilance to detect a safety signal for acetazolamide-induced pulmonary oedema. We performed a disproportionality analysis (case-noncase method), calculating reporting odds ratios (RORs) up to 22 February 2024. Among 11 684 208 spontaneous cases of adverse reactions registered in EudraVigilance, 38 275 were pulmonary oedemas. Acetazolamide was involved in 31 cases. In more than half of those cases, the patients received a single dose of acetazolamide after undergoing cataract surgery: latency was 10-90 min. Remarkably, there were five cases of positive rechallenge and six cases resulted in death. The ROR for acetazolamide was 3.63 (95% CI 2.55-5.17). Disproportionality was also observed in VigiBase®: ROR 4.44 (95% CI 3.34-5.90). Our study confirms a signal that suggests a risk of serious pulmonary oedema associated with acetazolamide.

Analysis of heat stroke and heat exhaustion cases in EudraVigilance pharmacovigilance database.

BACKGROUND: The frequency and intensity of heat waves have increased and will keep increasing. This meteorological phenomenon, which is considered one of the most dangerous, can affect the entire population, but certain populations are at greater risk. Concretely, elderly people are more prompt to suffer from chronic diseases and therefore to be on medication that can interact with the different temperature-regulating systems of the body. So far, there are no published studies that have analyzed pharmacovigilance databases to characterize the association between specific pharmaceuticals and heat-related adverse reactions. OBJECTIVE: Therefore, in this study, we aimed to investigate the reported cases of heat exhaustion or heat stroke, associated with any drug notified to the European pharmacovigilance database (EudraVigilance). METHOD: The Basque Country Pharmacovigilance Unit selected spontaneous reports recorded in EudraVigilance from January 1, 1995, to January 10, 2022. "Heat Stroke" and "Heat Exhaustion" preferred terms were selected. Non-cases, used as controls, were all the other adverse drug reaction reports recorded in EudraVigilance for the same time period. RESULTS: In total, 469 cases were obtained. Mean age: 49.74 ± 8 years, 62.5% were male, and the majority (94.7%) were considered serious by EU criteria. Fifty-one active substances fulfilled the criteria to generate a signal of disproportionate reporting. CONCLUSIONS: The majority of implicated drugs belong to therapeutic groups that are already mentioned in different heat-illness prevention plans. But we also show that drugs aimed to treat multiple sclerosis and several cytokines were also associated with heat-related adverse effects.

Assessment of a venous thromboembolism prophylaxis shared decision-making intervention (DASH-TOP) using the decisional conflict scale: a mixed-method study.

BACKGROUND: Venous thromboembolism (VTE) in pregnancy is a major cause of maternal morbidity and death. The use of low-molecular-weight heparin (LMWH), despite being the standard of care to prevent VTE, comes with some challenges. Shared decision-making (SDM) interventions are recommended to support patients and clinicians in making preference-sensitive decisions. The quality of the SDM process has been widely assessed with the decisional conflict scale (DCS). Our aim is to report participants' perspectives of each of the components of an SDM intervention (DASH-TOP) in relation to the different subscales of the DCS. METHODS: Design: A convergent, parallel, mixed-methods design. PARTICIPANTS: The sample consisted of 22 health care professionals, students of an Applied Clinical Research in Health Sciences (ICACS) master program. INTERVENTION: We randomly divided the participants in three groups: Group 1 received one component (evidence -based information), Group 2 received two components (first component and value elicitation exercises), and Group 3 received all three components (the first two and a decision analysis recommendation) of the SDM intervention. ANALYSIS: For the quantitative strand, we used a non-parametric test to analyze the differences in the DCS subscales between the three groups. For the qualitative strand, we conducted a content analysis using the decisional conflict domains to deductively categorize the responses. RESULTS: Groups that received more intervention components experienced less conflict and better decision-making quality, although the differences between groups were not statistically significant. The decision analysis recommendation improved the efficacy with the decision-making process, however there are some challenges when implementing it in clinical practice. The uncertainty subscale showed a high decisional conflict for all three groups; contributing factors included low certainty of the evidence-based information provided and a perceived small effect of the drug to reduce the risk of a VTE event. CONCLUSIONS: The DASH-TOP intervention reduced decisional conflict in the decision -making process, with decision analysis being the most effective component to improve the quality of the decision. There is a need for more implementation research to improve the delivery of SDM interventions in the clinical encounter.

Clinical Performance of a Standardized Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Interferon-γ Release Assay for Simple Detection of T-Cell Responses After Infection or Vaccination.

BACKGROUND: We evaluated a standardized interferon-γ (IFN-γ) release assay (IGRA) for detection of T-cell immune response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or vaccination. METHODS: This prospective study included patients with coronavirus disease 2019 (COVID-19) with different severity of illness and follow-up (FU), vaccinated subjects, and healthy unvaccinated persons. SARS-CoV-2 T-cell response was measured using a specific quantitative IGRA in whole blood (Euroimmun, Germany) and TrimericS-IgG and neutralizing antibodies with validated serological platforms. Positivity of reverse transcription-polymerase chain reaction or vaccination was considered as the reference standard. RESULTS: A total of 239 individuals were included (152 convalescent, 54 vaccinated, and 33 uninfected unvaccinated). Overall sensitivity, specificity, and positive- and negative-predictive values (95% confidence interval) of the IGRA were 81.1% (74.9-86%), 90.9% (74.5-97.6%), 98.2% (94.5-99.5%), and 43.5% (31.8-55.9%), respectively. All vaccinated SARS-CoV-2-naive subjects had positive IGRA at 3 months. In convalescent subjects the magnitude of IFN-γ responses and IGRA accuracy varied according to disease severity and duration of FU, with the best performance in patients with severe COVID-19 at 3 months and the worst in those with mild disease at 12 months. The greatest contribution of IGRA to serological tests was observed in patients with mild disease and long-term FU (incremental difference, 30.4%). CONCLUSIONS: The IGRA was a reliable method of quantifying T-cell response after SARS-COV-2 infection or vaccination. In convalescent patients, the sensitivity is largely dependent on disease severity and time since primary infection. The assay is more likely to add clinical value to serology in patients with mild infections.

SARS-CoV-2-reactive antibody detection after SARS-CoV-2 vaccination in hematopoietic stem cell transplant recipients: Prospective survey from the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group.

This is a multicenter prospective observational study that included a large cohort (n = 397) of allogeneic (allo-HSCT; (n = 311) and autologous (ASCT) hematopoietic stem cell transplant (n = 86) recipients who were monitored for antibody detection within 3-6 weeks after complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination from February 1, 2021, to July 20, 2021. Most patients (n = 387, 97.4%) received mRNA-based vaccines. Most of the recipients (93%) were vaccinated more than 1 year after transplant. Detectable SARS-CoV-2-reactive antibodies were observed in 242 (78%) of allo-HSCT and in 73 (85%) of ASCT recipients. Multivariate analysis in allo-HSCT recipients identified lymphopenia < 1 × 109 /ml (odds ratio [OR] 0.33, 95% confidence interval [95% CI] 0.16-0.69, p = .003), active graft versus host disease (GvHD; OR 0.51, 95% CI 0.27-0.98, p = .04) and vaccination within the first year of transplant (OR 0.3, 95% CI 0.15-0.9, p = .04) associated with lower antibody detection whereas. In ASCT, non-Hodgkin's lymphoma (NHL; OR 0.09, 95% CI 0.02-0.44, p = .003) and active corticosteroid therapy (OR 0.2, 95% CI 0.02-0.87, p = .03) were associated with lower detection rate. We report an encouraging rate of SARS-CoV-2-reactive antibodies detection in these severe immunocompromised patients. Lymphopenia, GvHD, the timing of vaccine, and NHL and corticosteroids therapy should be considered in allo-HSCT and ASCT, respectively, to identify candidates for SARS-CoV-2 antibodies monitoring.

Pericarditis caused by Mycobacterium africanum: case report.

BACKGROUND: Mycobacterium africanum is a member of the Mycobacterium tuberculosis complex (MTBC) and is endemic in West Africa, where it causes up to half of all cases of pulmonary tuberculosis. Here, we report the first isolation of Mycobacterium africanum from the pericardial effusion culture of a patient with tuberculous pericarditis. CASE PRESENTATION: A 31-year-old man, native from Senegal, came to the emergency room with massive pericardial effusion and cardiac tamponade requiring pericardiocentesis. M. africanum subtype II was identified in the pericardial fluid. The patient completed 10 months of standard treatment, with a favorable outcome. CONCLUSIONS: We report the first case of tuberculous pericarditis caused by Mycobacterium africanum, which provide evidence that this microorganism can cause pericardial disease and must be considered in patients from endemic areas presenting with pericardial effusion.

Homeostatic alterations related to total antioxidant capacity, elemental concentrations and isotopic compositions in aqueous humor of glaucoma patients.

Glaucoma is a multifactorial eye disease, characterized by progressive optic neurodegeneration. Elevation of the intraocular pressure is the main risk factor for glaucoma and is a consequence of an imbalance in the aqueous humor hydrodynamics, the physiology of which is influenced by the homeostatic equilibrium of essential elements, oxidative stress, and antioxidants. The aim of this work was to study local alterations in glaucomatous patients from two different, but connected, points of view: (i) the total antioxidant capacity (as an indicator of oxidative damage) and (ii) the concentration of mineral elements and their isotopic composition. Such objective was pursued using aqueous humor from patients diagnosed with pseudoexfoliation glaucoma (PEXG, n = 17) and primary open-angle glaucoma (POAG, n = 5) and age-matched control subjects (n = 16). The total antioxidant capacity (TAC) was examined in both aqueous humor and 60 serum samples (n = 20 controls, n = 20 for PEXG, and n = 20 for POAG), both showing higher TAC for the glaucoma population. The concentrations of the essential mineral elements (Cu, Fe, Mg, Na, P, and Zn) and the isotopic compositions of Cu and Zn were determined in aqueous humor using single-collector and multi-collector inductively coupled plasma-mass spectrometry, respectively. Significant differences were established for Mg and P levels when comparing the results for glaucomatous patients with those for the control population (p < 0.01 and p < 0.05 for Mg and P respectively, ANOVA and Kruskal-Wallis). The Zn isotopic composition was significantly shifted from that for the control population for PEXG patients. A significant difference in the isotopic composition of Zn was also established between the PEXG and POAG glaucoma cohorts.

Women's values and preferences on low-molecular-weight heparin and pregnancy: a mixed-methods systematic review.

BACKGROUND: Venous thromboembolism (VTE) in pregnancy is an important cause of maternal morbidity and mortality. Low-molecular-weight heparin (LMWH) is the cornerstone of prophylaxis and treatment of thrombotic events during pregnancy. LMWH has fewer adverse effects than other anticoagulants, does not cross the placenta, and is safe for the fetus. However, the use of LMWH during pregnancy is sensitive to womens' underlying preferences. The objective of this review is to systematically assess women's values and preferences research evidence on this topic. METHODS: We searched four electronic databases from inception to March 2022, and included studies examining values and preferences of using LMWH among pregnant women at risk of VTE. We followed a convergent integrated mixed-methods design to compare and contrast quantitative outcomes (utility and non-utility measures) and qualitative findings. We assessed the certainty of the values and preferences evidence with the GRADE approach for quantitative findings, and with GRADE-CERqual for qualitative evidence. Results were presented in a conjoint display. RESULTS: We screened 3,393 references and identified seven eligible studies. The mixed methods analysis resulted in four themes. Datasets confirmed each other in that: 1) the majority of women consider that benefits of treatment outweigh the inconveniences of daily injections; and 2) main concerns around medication are safety and injections administration. Quantitative outcomes expanded on the qualitative findings in that: 3) participants who perceived a higher risk of VTE were more willing to take LMWH. Finally, we found a discrepancy between the datasets around: 4) the amount of information preferred to make the decision; however, qualitative data expanded to clarify that women prefer making informed decisions and receive support from their clinician in their decision-making process. CONCLUSIONS: We are moderately confident that in the context of pregnancy, using LMWH is preferred by women given its net beneficial balance. Integrating data from different sources of evidence, and representing them in a jointly manner helps to identify patient's values and preferences. Our results may inform clinical practice guidelines and support shared decision-making process in the clinical encounter for the management of VTE in the context of pregnancy.

Combination therapy of specific aeroallergens immunotherapy and omalizumab, in children with severe asthma.

BACKGROUND: In most cases, severe asthma in children has an allergic etiology, but allergen-specific immunotherapy (AIT) is contraindicated. OBJECTIVE: This study aimed at analyzing the safety and efficacy of AIT in patients with severe asthma treated with omalizumab (OM). METHODS: A descriptive real-life study was carried out by reviewing medical records. Effectiveness was measured by the degree of control (CAN questionnaire), number of hospitalizations per year, number of exacerbations per year, and maintenance treatment and lung function (FEV1). Some adverse reactions occurred (AAI-EAACI-WAO guidelines). RESULTS: The retrospective study included 29 patients up to 18 years of age with severe asthma with OM plus AIT treatment. AIT treatment was started in a cluster schedule when patients treated with OM achieved disease control. Before starting AIT, patients were treated with OM for 1 year for achieving asthmatic control. AIT to mites (51%), Alternaria (37.9%), or pollens (10.3%) was administered. After one year with OM plus AIT,statistically significant differences in CAN scores and FEV1 measures were observed (P < 0.001). No patients under treatment with OM plus AIT required hospital admission. During the clustering schedule, only 3/64 doses showed systemic adverse reactions. During the AIT maintenance treatment, 348 doses were administered, with no significant adverse reactions. CONCLUSION: In this population-based study in children with severe asthma, the combined treatment with OM plus AIT was safe and effective. This strategy allows these pediatric patients to be safely treated with AIT.

Long-term outcome of omalizumab-assisted desensitisation to cow's milk and eggs in patients refractory to conventional oral immunotherapy: real-life study.

BACKGROUND: Oral immunotherapy (OIT) is a promising approach to cow's milk and egg allergies, but reactions are frequent and some patients cannot be desensitized. OBJECTIVE: To evaluate long-term OIT outcomes with omalizumab (OMZ) in paediatric patients with severe egg and/or milk allergies. METHODS: This retrospective real-life study analysed findings in children with Immunoglobulin E-mediated allergy to cow's milk and/or hen eggs refractory to conventional OIT, who underwent OIT with OMZ in our department between 1 January 2010 and 31 December 2015. RESULTS: In all, 41 patients were included (median age: 7 years; interquartile range [IQR]: 5.5-9.5); 26/41 (63.4%) underwent OIT for milk, 8/41 (19.5%) for egg and 7/41 (17.1%) for both. The median time between initiation of OMZ and OIT was 27 weeks (IQR: 22-33). Forty (97.56%) patients reached the maintenance phase (200 mL of cow's milk and 30 mL of raw egg or 1 cooked egg) in a median time of 27 weeks (IQR: 18-37). The median total time with OMZ was 117 weeks (IQR: 88-144). During the OMZ period, 2.44% (1/41) of patients presented anaphylaxis. After discontinuation of OMZ, 29.3% (12/41) presented anaphylaxis, 50% of them had a poor adherence to daily ingestion. One patient (2.44%) was diagnosed with eosinophilic esophagitis after 2 years of discontinuation of OMZ. Currently, after a median time of 9 years (IQR: 7-10) since the initiation of OMZ, 75.6% (31/41) are desensitized (27/31 without OMZ). CONCLUSIONS: Omalizumab allows desensitisation of children with severe allergies to cow's milk and/or egg without developing severe reactions while receiving this treatment. However, discontinuation of OMZ leads to severe allergic reactions, and hence must be monitored carefully.

Performance of Saliva Specimens for the Molecular Detection of SARS-CoV-2 in the Community Setting: Does Sample Collection Method Matter?

Data on the performance of saliva specimens for diagnosing coronavirus disease 2019 (COVID-19) in ambulatory patients are scarce and inconsistent. We assessed saliva-based specimens for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcriptase PCR (RT-PCR) in the community setting and compared three different collection methods. This prospective study was conducted in three primary care centers. RT-PCR was performed on paired nasopharyngeal swabs (NPS) and saliva samples collected from outpatients with a broad clinical spectrum of illness. To assess differences in collection methods, saliva specimens were obtained in a different way in each of the participating centers: supervised collection (SVC), oropharyngeal washing (OPW), and self-collection (SC). Pairs of NPS and saliva samples from 577 patients (median age, 39 years; 44% men; 42% asymptomatic) were collected and tested, and 120 (20.8%) gave positive results. The overall agreement with NPS results and kappa coefficients (κ) for saliva samples obtained by SVC, OPW, and SC were 95% (κ = 0.85), 93.4% (κ = 0.76), and 93.3% (κ = 0.76), respectively. The sensitivities (95% confidence intervals [95% CI]) of the saliva specimens ranged from 86% (72.6% to 93.7%) for SVC to 66.7% (50.4% to 80%) for SC samples. Sensitivity was higher for samples with lower cycle threshold (CT ) values. The best RT-PCR performance was observed for SVC, with sensitivities (95% CI) of 100% (85.9% to 100%) in symptomatic individuals and 88.9% (50.7% to 99.4%) in asymptomatic individuals at CT values of ≤30. We conclude that saliva is an acceptable specimen for the detection of SARS-CoV-2 in the community setting. Specimens collected under supervision perform comparably to NPS and can effectively identify individuals at higher risk of transmission under real-life conditions.

Omalizumab outcomes for up to 6 years in pediatric patients with severe persistent allergic asthma.

BACKGROUND: Various studies have assessed omalizumab outcomes in the clinical practice setting but follow-up and/or number of patients included were limited. We aim to describe the long-term outcomes of pediatric patients with severe persistent allergic asthma receiving omalizumab in the largest real-life cohort reported to date. METHODS: ANCHORS was a multicenter, observational, retrospective cohort study conducted in 25 Pediatric Allergy and Pulmonology units in Spain. We collected data of patients < 18 years and initiating omalizumab between 2006 and 2018, from the year prior to omalizumab initiation to discontinuation or last available follow-up. The primary outcome was the evolution of the annual number of moderate-to-severe exacerbations compared with the baseline period. RESULTS: Of the 484 patients included, 101 (20.9%) reached 6 years of treatment. The mean ± standard deviation number of exacerbations decreased during the first year of treatment (7.9 ± 6.6 to 1.1 ± 2.0, P < .001) and remained likewise for up to 6 years. The other clinical parameters assessed also improved significantly during the first year and stabilized or continued to improve thereafter. The percentage of patients experiencing adverse events was consistently low, and the main reason for discontinuation was good disease evolution. CONCLUSION: In this large, long-term, observational study, moderate-to-severe exacerbations decreased significantly from the first year of treatment with omalizumab. The beneficial effect was maintained in the long term, along with a good safety profile. Our results position omalizumab as an effective long-term treatment in pediatric patients with severe persistent allergic asthma.

Characterization of severe asthma in the pediatric population.

INTRODUCTION AND OBJECTIVES: Relationship between the causal mechanisms of pediatric severe asthma and severity of symptoms would be helpful for developing personalized strategies for treatment and prevention. MATERIALS AND METHODS: For this study, 698 medical histories of asthmatics between 6 and 18 years of age were reviewed in a period of 2 years. Variables analyzed were: age, sex, ethnicity, perinatological history, allergy history, asthma predictive index (API), exposure to tobacco, heavy traffic or epithelium, lung function, age of onset of symptoms, hospitalization admissions/PICU, systemic corticosteroids, daily symptoms control, device prescribe for daily control, and adherence. RESULTS: A total of 86 children with severe asthma were included (12.3%). Mean age 13.3 +/- 1.86 years, sex ratio1:1, mean age of symptom onset 2.765 +/- 3.06 years, mean IgE 1076.18KU / L +/- 1136, mean eosinophils 604c / mcl +/- 511.9, mean of FEV1 93.15% +/- 16.3. Evidently, 70 children (81.4%) had positive API, 68 (79.1%) rhinitis, 34 (39.5%) atopic dermatitis. 73 (83.9%) sensitized to inhalants and 56 (65.1%) to dermatophagoides, 39 (45.3%) passive smokers, 19 (22.1%) exposure to heavy traffic; 55 (64%) showed symptoms with exercise, 35 (40.7%) had audible wheezing. The mean systemic corticosteroid cycles/year was 3.63 +/- 3.23, mean PICU admissions 0.36 +/- 0.83, mean hospital admissions 4.31 +/- 5.3, average emergency room visits/year 19.44 +/- 16.28. 38 (56.7%) had good adherence, 44 (51%) used an MDI device and 39 (45.3%) used dry powder. CONCLUSIONS: Children with severe asthma meet the following criteria: premature, positive API, rhinitis, atopic dermatitis, high IgE, eosinophilia, passive smokers, exposure to heavy traffic, decreased lung function, and low adherence to controller medication.

Pressure injuries during the SARS-CoV-2 pandemic: A retrospective, case-control study.

AIM OF STUDY: The main objective of this study was to ascertain whether severe alterations in hypoxemic, inflammatory, and nutritional parameters in patients diagnosed with SARS-CoV-2 infection were associated with the occurrence and severity of developed dependency-related injuries. The secondary objective was to determine whether there were prognostic factors associated with the occurrence and severity of developed dependency-related injuries during the SARS-CoV-2 pandemic. MATERIAL AND METHODS: A retrospective, single-centre, case-control study was conducted to compare SARS-CoV-2 patients who developed dependency-related injuries after the first 48 h after admission with a control group made up of SARS-CoV-2 patients without dependency-related injuries. The cases of the 1987 patients diagnosed with SARS-CoV-2 infection during the study period were reviewed. Data from 94 patients who developed dependency-related injuries and from 190 patients who did not develop them during hospital admission were analysed. RESULTS: High baseline dependency levels, prolonged hospital stays, and low oxygen saturation levels on arrival in emergency department triage were associated with the occurrence of dependency-related injuries among patients diagnosed with SARS-CoV-2 infection. CONCLUSIONS: SARS-CoV-2 infection can lead to complications such as dependency-related injuries. Although there are several non-modifiable variables associated with the occurrence of dependency-related injuries in these patients, it is essential to conduct further research and introduce consensus guidelines to reduce their incidence and prevalence.

Comprehensive primary health care and non-communicable diseases management: a case study of El Salvador.

BACKGROUND: One of today's greatest challenges in public health worldwide - and especially its key management from Primary Health Care (PHC) - is the growing burden of non-communicable diseases (NCDs). In El Salvador, since 2009 the Minister of Health (MoH) has scaled up a national public health system based on a comprehensive PHC approach. A national multi-sectorial strategic plan for a comprehensive approach to NCDs has also been developed. This analysis explores stakeholders' perceptions related to the management of NCDs in PHC and, in particular, the role of social participation. METHODS: A case-study was developed consisting of semi structured interviews and official document reviews. Semi-structured interviews were developed with chronic patients (14) and PHC professionals working in different levels within PHC (12). Purposive sampling was used to recruit participants. A non-pure, deductive approach was implemented for coding. After grouping codes into potential themes, a thematic framework was elaborated through a reflexive approach and the triangulation of the data. The research was conducted between March and August of 2018 in three different departments of El Salvador. RESULTS: The structure and the functioning of the Salvadoran PHC system and its intersectoral approach is firstly described. The interdisciplinary PHC-team brings holistic health care closer to the communities in which health promoters play a key role. The findings reflect the generally positive perception of the PHC system in terms of accessibility, quality and continuity of care by chronic patients. Community engagement and the National Health Forum are ensuring accountability through social controllership mechanisms. However, certain challenges were also noted during the interviews related to the shortage of medication and workforce; coordination between the levels of care and the importance of prevention and health promotion programmes for NCDs. CONCLUSIONS: The Salvadoran PHC and its comprehensive approach to NCDs with an emphasis on intersectoral participation has been positively perceived by the range of stakeholders interviewed. Social engagement and the NHF works as a driving force to ensure accountability as well as in the promotion of a preventive culture. The challenges identified provide keys to amplify knowledge for addressing inequalities in health by strengthening PHC and its NCDs management.

Community and health staff perceptions on non-communicable disease management in El Salvador's health system: a qualitative study.

BACKGROUND: Non-communicable Diseases (NCDs) are the leading cause of global mortality and disability with a rising burden in low- and middle-income countries. Their multifactorial aetiology, and their requirement of long-term care, implies the need for comprehensive approaches. From 2009, the Ministry of Health (MoH) in El Salvador has developed a national public health system based on comprehensive primary health care. This study aims to describe the different stakeholders' perceptions about the management of NCDs along the pathways of care in this health system. METHODS: During three fieldwork periods in 2018, three complementary qualitative data collection methods were deployed and conducted in settings with high prevalence of NCDs within El Salvador. First, illness narrative methodology was used to document the life histories of people living with a chronic disease and being treated in second and third level health facilities. Second, through social mapping, support resources that NCD patients used throughout the process of their illness within the same settings were analysed. Third, semi-structured interviews were conducted in the same locations, with both chronic patients and health personnel working at different levels of the primary health care setting. Participants were recruited through purposive and snowball sampling, and a deductive approach was implemented for coding during the analysis phase. After grouping codes into potential themes, a thematic framework was developed using a reflexive approach and following triangulation of the data. RESULTS: This innovative approach of combining three well-defined qualitative methods identified key implications for the implementation of a comprehensive approach to NCD management in resource-poor settings. The following elements are identified: 1) social risk factors and barriers to care; 2) patient pathways to NCD care; 3) available resources identified through social connections mapping; 4) trust in social connections; and 5) community health promotion and NCD prevention management. CONCLUSIONS: The Salvadoran public health system has been able to strengthen its comprehensive approach to NCDs, combining a clinical approach - including long-term follow-up - with a preventive community-based strategy. The structural collaboration between the health system and the (self-) organised community has been essential for identifying failings, discuss tensions and work out adapted solutions.

Isotopically Enriched Tracers and Inductively Coupled Plasma Mass Spectrometry Methodologies to Study Zinc Supplementation in Single-Cells of Retinal Pigment Epithelium in Vitro.

Mass spectrometry-based techniques, such as inductively coupled plasma mass spectrometry (ICPMS) and laser ablation (LA) ICPMS, combined with an isotope pattern deconvolution mathematical tool are proposed for a better understanding of supplementation studies in cultured cells. An in vitro model of human retinal pigment epithelium (HRPEsv) cells was treated with different concentrations (0-150 µm Zn, 1 mL) of enriched stable isotope tracers of Zn in the form of sulfate and/or gluconate. Supplementations with t68ZnSO4 or t70Zn-gluconate alone and in combination (1:1 molar ratio) were investigated to evaluate the exogenous contribution and distribution of Zn in the treated cells. In order to obtain not only the Zn concentration for a cell population (mineralized cells) but also single cell information about the contribution of exogenous Zn and their distribution within micrometer cells structures, LA-ICPMS was employed to directly analyze cryopreserved cells. natZn, t68Zn, and t70Zn molar fraction images obtained from cells and cell aggregates allowed confirming the uptake of exogenous Zn by HRPEsv cells, being t68Zn and t70Zn molar fractions close to 1 in the cell nuclei. Under the selected experimental conditions tested (24 h treatments), no significant differences were obtained in the Zn distribution depending on its chemical form.

Fractures Related to Tenofovir: A Case/Noncase Study in the European Pharmacovigilance Database.

BACKGROUND: There is no clear consensus on the relationship between tenofovir (TDF) and fracture risk because the studies published so far present contradictory findings. STUDY QUESTION: Our objective was to detect, from the European pharmacovigilance database (EudraVigilance), a signal of fracture risk during TDF exposure in patients infected with HIV. METHODS: Herein, we analyze all the cases of fractures suspected to be related to TDF recorded in EudraVigilance between 2001 and November 10, 2016. A case/noncase method was used to assess the association between fractures and TDF, calculating proportional reporting ratios (PRRs) and their 95% confidence intervals (CIs) as a measure of disproportionality. According to the Medical Dictionary for Regulatory Activities (MedDRA) terminology, osteoporotic fractures are included in High Level Group Term (HLGT) "Fractures" and traumatic fractures in HLGT "Bone and joint injuries," so, we selected cases included in both HLGTs. The noncases used as controls were all the remaining adverse drug reaction reports recorded in EudraVigilance during the same period. RESULTS: There were 68,113 cases of fractures in the 4,776,472 reports recorded in EudraVigilance during the study period. TDF was involved in 181 cases. The median latency period until the appearance of fracture was 995 days. TDF was present as the only suspect drug in 140 cases. The PRR of TDF and fractures was 1.11 (95% CI, 0.96-1.28). Nevertheless, disproportionality was observed for some types of fractures: osteoporotic fractures (PRR 17.24; 95% CI, 9.90-30.01), bone fissure (PRR 16.60; 95% CI, 6.11-45.10), and pathological fracture (PRR 4.40; 95% CI, 2.77-7.00). CONCLUSIONS: Our findings do not show a disproportionality for fractures in patients treated with TDF, although disproportionality was found for some types of fractures, mainly osteoporotic fractures.

Quantitative Imaging of Specific Proteins in the Human Retina by Laser Ablation ICPMS using Bioconjugated Metal Nanoclusters as Labels.

A sensitive methodology using antibody-conjugated gold nanoclusters (AuNCs) was developed for the quantitative bioimaging of specific proteins in biological tissues by laser ablation (LA) coupled to inductively coupled plasma-mass spectrometry (ICPMS). Determination of metallothioneins (MT1/2 protein isoforms) images in human retina tissue sections was carried out as a proof of concept. AuNCs used as label were conjugated to the selected antibody through carbodiimide coupling. A stoichiometry of AuNCs/available antibody of 1:1 was obtained. The high amplification provided by AuNC labels allowed for obtaining the distribution of MT1/2 in the neurosensory retina layers (5 µm thick sections) by LA-ICPMS. Elemental images of 197Au+ were quantified with gelatin matrix-matched standards and then converted to 2D quantitative images of MT1/2 concentration. For validation purposes, average concentrations of MT1/2 obtained in the human retinal layers by LA-ICPMS were successfully compared with those obtained with a commercial ELISA kit.

Novel domain architectures and functional determinants in atypical annexins revealed by phylogenomic analysis.

The fundamental cellular role and molecular interactions of annexins in vesicle trafficking and membrane remodeling remain to be further clarified in order to better understand and exploit their contributions to health and disease. We focused on distinctive features of atypical annexins from all domains of life using phylogenomic, molecular systematic and experimental approaches, to extend the current paradigm and better account for annexin diversity of structure, function and mechanistic role in membrane homeostasis. The analysis of gene duplications, organization of domain architectures and profile hidden Markov models of subfamily orthologs defined conserved structural features relevant to molecular interactions and functional divergence of seven family clades ANXA-G. Single domain annexins of bacteria, including cyanobacteria, were frequently coupled to enzymatic units conceivably related to membrane metabolism and remodeling. Multiple ANX domains (up to 20) and various distinct functional domains were observed in unique annexins. Canonical type 2 calcium binding ligands were well-preserved in roughly half of all ANX domains, but alternative structural motifs comprised of 'KGD', cysteine or tryptophan residues were prominently conserved in the same strategic interhelical loops. Selective evolutionary constraint, site-specific location and co-occurrence in all kingdoms identify alternative modes of fundamental binding interactions for annexins.