Explore the vast range of titles available.

Inflammation is a predominant aspect of neurodegenerative diseases and experimental studies performed in animal models of Parkinson’s disease (PD) suggesting that a sustained neuroinflammation exacerbates the nigrostriatal degeneration pathway. The central role of microglia in neuroinflammation has been studied as a target for potential neuroprotective drugs for PD, for example nonsteroidal anti-inflammatory drugs (NSAIDs) and matrix metalloproteinases (MMP) inhibitors that regulates microglial activation and migration. The aim of this study was to investigate the neuroprotective response of the iminosugar 1-deoxynojirimycin (1-DNJ) and compare its effect with a combined treatment with ibuprofen. MPTP-treated mice were orally dosed with ibuprofen and/or 1-DNJ 1. Open-field test was used to evaluate behavioral changes. Immunohistochemistry for dopaminergic neurons marker (TH + ) and microglia markers (Iba-1 + ; CD68 + ) were used to investigate neuronal integrity and microglial activation in the substantia nigra pars compacta (SNpc). The pro-inflammatory cytokines TNF-α and IL-6 were analysed by qPCR. Treatments with either 1-DNJ or Ibuprofen alone did not reduce the damage induced by MPTP intoxication. However, combined treatment with 1-DNJ and ibuprofen prevents loss of mesencephalic dopaminergic neurons, decreases the number of CD68 + / Iba-1 + cells, the microglia/neurons interactions, and the pro-inflammatory cytokines, and improves behavioral changes when compared with MPTP-treated animals. In conclusion, these data demonstrate that the combined treatment with a MMPs inhibitor (1-DNJ) plus an anti-inflammatory drug (ibuprofen) has neuroprotective effects open for future therapeutic interventions. Graphical Abstract MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a protoxicant that, after crossing the Blood Brain Barrier, is metabolized by astrocytic MAO-B to MPDP+, a pyridinium intermediate, which undergoes further two-electron oxidation to yield the toxic metabolite MPP+ (methyl-phenyltetrahydropyridinium) that is then selectively transported into nigral neurons via the mesencephalic dopamine transporter. In this study, we demonstrated that MPTP induced death of dopaminergic neurons, microgliosis, increase of gliapses, motor impairment and neuroinflammation in mice, which were inhibited by combined 1-deoxynojirimycin and ibuprofen treatment.

Background and ImportanceThe use of antibiotics in acute bronchial aspiration is common, although there is little evidence that it provides benefits, and it exposes patients to increased microbiological resistance and the appearance of side effects from the use of antibiotics.Aim and ObjectivesCompare mortality, change of ventilation modality, ICU admission and hospital stay of patients with aspiration who receive prophylactic antibiotic therapy, with patients who do not receive antibiotics.Material and MethodsRetrospective descriptive observational study of patients with acute bronchial aspiration (January 2022 to March/2023). Demographic and clinical data were collected from the patient‘s medical history; and medication-related information from the electronic prescription software available in the hospital.Results267 patients (50.6% women). Average 81.62 years. Services: Emergencies (75.7%), Internal (12.4%). Charlson index 6.10 (SD 2.73). Risk of bronchial aspiration in 71 patients (26.6%). 231 (86.5%) antibiotic, 36 (13.5%) without antibiotic. Amoxicillin-clavulanic acid was most commonly used (59.2%). Antibiotic treatment duration 6.64 days (SD 4.40). Seven complications secondary to antibiotics. Antibiotic indicated in 28 patients (10.5%). 30 patients (11.2%) changed ventilatory modality, 21 patients (7.9%) were admitted to the ICU. 97 patients (36.3%) died (days until death 5.75 days), of which 75 (77.1%) received antibiotics.Conclusion and RelevanceProphylactic antibiotics during acute aspiration do not reduce mortality or the need for ICU admission, but rather increase the need to change ventilation modality. The hospital stay in prophylactic antibiotic therapy is longer compared to patients who do not receive antibiotics.References and/or AcknowledgementsConflict of InterestNo conflict of interest.

Tadiri et al explore the influence of sex and gender domains on COVID-19 cases and mortality. Among the many unknowns regarding severe acute respiratory syndrome SARS-CoV-2 and COVID-19 is the way in which sex and gender affect the risk of acquiring the virus, illness presentation, disease management and outcomes. Sex, a biological attribute, and gender, a social construct, may both influence an individual's susceptibility, vulnerability and exposure to infectious disease. Immune function differs between sexes and has been shown to affect an individual's likelihood of acquiring infection upon exposure, or developing complications. Indeed, early research has shown that these sex differences in immune response may lead to worse COVID-19 outcomes for males in terms of ability to recover from severe infection. Gender, which comprises roles, norms and behaviors that may vary by sex, is associated with an individual's likelihood of exposure. Several institutions, including the Canadian Institutes of Health Research, have appealed to researchers to include sex and gender variables in data analysis, to improve the effectiveness of health interventions and promote gender and health equity goals.

Background and importanceMedication overdose headache (MOH) is a secondary headache disorder occurring on 15 or more days per month developing as a consequence of regular overdose of headache medication for more than 3 months.The prevalence of MOH is approximately 1–2% and is higher in women than in men. Many medications used to treat headaches have the potential for causing MOH. Currently, MOH secondary to triptans is increasing and leads to MOH sooner than with other medications. Anxiety and depression may be risk factors for the evolution of migraine into MOH.Aim and objectivesTo determine the prevalence of patients treated with triptans at risk of MOH (regular intake for ≥10 days/month for >3 months) and the profile in our health area; to identify and communicate to the prescribers those patients with overuse of triptans; and to inform all clinicians about MOH: aetiology, clinical features, diagnosis and treatment.Material and methodsWe analysed the dispensation records of all patients treated with triptans over 3 months (June 2019–September 2019). Data collected were sex, age, monthly intake frequency and co-medication. We alerted prescribers by email, including management and de-prescription recommendations for MOH. We posted content about MOH in our blog.ResultsThe prevalence of patients treated with triptans was 0.50%; 47 of 538 patients taking triptans (8.7%) were at risk of MOH. Their median age was 55 years and most were women (79%). Median monthly intake was 16 doses (10–48). Thirty patients (64%) had prescriptions for anxiety and/or depression and 13 patients (28%) had preventive therapy prescriptions for headache. Twenty-nine prescribers were notified by email. Dispensation record history, co-medication, MOH management guide and patient education leaflets were attached.Conclusion and relevanceMOH is a common problem in clinical practice that needs to be properly managed to increase the likelihood of successful chronic daily headache treatment. The results obtained in our population were similar to published studies, both in prevalence and in patient profile. However, the MOH rate was still lacking as it needs a clinician diagnosis. In 6 months we will collect information about the evolution of these patients, and we expect that our intervention will lead to treatment optimisation, better use of triptans and headache relief.References and/or acknowledgementsNo conflict of interest.

Background Patient attitudes about health and healthcare have emerged as important outcomes to assess in clinical studies. Gender is increasingly recognized as an intersectional social construct that may influence health. Our objective was to determine potential sex differences in self-reported overall health and access to healthcare and whether those differences are influenced by individual social factors in two relatively similar countries. Methods Two public health surveys from countries with high gender equality (measured by UN GII) and universal healthcare systems, Canada (CCHS2014, n  = 57,041) and Austria (AT-HIS2014, n  = 15,212), were analysed. Perceived health was assessed on a scale of 1 (very bad) to 4 (very good) and perceived unmet healthcare needs was reported as a dichotomous variable (yes/no). Interactions between sex and social determinants (i.e. employment, education level, immigration and marital status) on outcomes were analysed. Results Individuals in both countries reported high perceived health (Scoring > 2, 85.0% in Canada, 79.9% in Austria) and a low percentage reported unmet healthcare needs (4.6% in Canada, 10.7% in Austria). In both countries, sex and several social factors were associated with high perceived health, and a sex-by-marital status interaction was observed, with a greater negative impact of divorce for men. Female sex was positively associated with unmet care needs in both countries, and sex-by-social factors interactions were only detected in Canada. Conclusions The intersection of sex and social factors in influencing patient-relevant outcomes varies even among countries with similar healthcare and high gender equality.

Sharing health data for research purposes across international jurisdictions has been a challenge due to privacy concerns. Two privacy enhancing technologies that can enable such sharing are synthetic data generation (SDG) and federated analysis, but their relative strengths and weaknesses have not been evaluated thus far. In this study we compared SDG with federated analysis to enable such international comparative studies. The objective of the analysis was to assess country-level differences in the role of sex on cardiovascular health (CVH) using a pooled dataset of Canadian and Austrian individuals. The Canadian data was synthesized and sent to the Austrian team for analysis. The utility of the pooled (synthetic Canadian + real Austrian) dataset was evaluated by comparing the regression results from the two approaches. The privacy of the Canadian synthetic data was assessed using a membership disclosure test which showed an F1 score of 0.001, indicating low privacy risk. The outcome variable of interest was CVH, calculated through a modified CANHEART index. The main and interaction effect parameter estimates of the federated and pooled analyses were consistent and directionally the same. It took approximately one month to set up the synthetic data generation platform and generate the synthetic data, whereas it took over 1.5 years to set up the federated analysis system. Synthetic data generation can be an efficient and effective tool for enabling multi-jurisdictional studies while addressing privacy concerns.

BackgroundThe scale-up of HCV treatment for HIV/HCV coinfected individuals is occurring, the majority with a history of injecting drug use.PurposeWe assess the implications for achieving the World Health Organisation HCV incidence elimination target (80% reduction from 2015–2030) among HIV-infected (HIV+) people who inject drugs (PWID) and all PWID, using dynamic modelling.Material and methodsA joint HIV and HCV transmission model among PWID was based on published data and the HERACLES cohort (prospective cohort of HIV/HCV coinfected individuals in care from 2015–2017). The model was stratified by HIV stage, HCV stage and PWID status (young PWID (<10 years’ injecting), old PWID (>10 years’ injecting), ex PWID). We simulated: 45%/60% chronic HCV prevalence and 20%/40% HIV prevalence among PWID injecting for <10 years and >10 years, respectively, 54% chronic HCV among HIV +ever PWID (PWID +ex PWID). We assumed HCV treatment among diagnosed coinfected ever-PWID of 10.5%/year from 2004–2014, and 33%/year from 2015 (from HERACLES). We projected the impact of current treatment, and scaled-up treatment (among HIV +PWID or all PWID) from 2018 on HCV prevalence/incidence among HIV +PWID and all PWID.ResultsWe projected that 28% and 32% of HCV +PWID and HCV +ex PWID, respectively, were HIV/HCV coinfected in 2015. Current treatment rates could reduce the number of diagnosed coinfected PWID by 75% from 2015–2030. However, this would only reduce HCV incidence by a relative 25% and 16% among HIV +PWID and all PWID, respectively. If all coinfected PWID were diagnosed and treated annually from 2018, this could reduce chronic HCV prevalence by 74% among HIV+ PWID by 2030, but only halve the incidence. Greater impact could be achieved through scaling-up treatment to all PWID.ConclusionHCV elimination among HIV +PWID will not be achieved by treating coinfected PWID alone: efforts should focus on HCV diagnosis and treatment among both coinfected and monoinfected PWID. Scaling-up treatment to all PWID.References and/or acknowledgementsNo conflict of interest.

BackgroundStrategic plans have been developed to eradicate HCV worldwide.Understanding patient factors associated with being untreated for HCV would help in supporting extra efforts in those patients to achieve HCV elimination in the coming years.PurposeWe evaluated the implementation of our country’s strategy in HIV/HCV coinfected patients and barriers to lower treatment implementation in this population.Material and methodsThe HERACLES cohort is a multicentre, prospective observational cohort initiated in April 2015, which includes HIV-infected patients with active chronic HCV coinfection in follow-up at 19 centres for the care of HIV-infected patients from 1 May 2015 to 1 May 2017 (accession number: NCT02511496).The main study outcome was receipt of HCV DAAs treatment from 1 May 2015 to 1 May 2017.Variables identified as factors associated with lower treatment rate implementation were included in a logistic regression model for HCV treatment uptake.ResultsOf the 15,556 HIV patients in care, 3075 (19.7%) presented with active chronic HCV infection and constituted the study population. By the end of the follow-up, 1957 patients initiated HCV therapy (63.6%).In the multivariate analysis, an age lower than 50 years (OR (95% CI)=1,379 (1,109 to 1,713)), absence of or minimal liver fibrosis (F3: OR (95% CI)=9,866 (7,496 to 12,985); F4: OR (95% CI)=14.865 (10,786 to 12,985)), treatment-naïve patients (DAAs+Peg-IFN/RBV: OR: 95% CI=6.493: (3.081 to 10.878)), HCV genotype 3 infection (OR (95% CI)=0.689 (0.523–0.908)), people who injected drugs using opioid substitutive therapy (OST-PWIDs: OR: 95% CI=0.738: (0.588–0.927)), and recent PWIDs were identified as significant independent risk factors associated with low DAA implementation (OR: 95% CI=0.22 (0.005 to 0.092)).ConclusionIn the study period, a high number of HIV/HCV coinfected patients from our cohort received DAA therapy.We identified factors, which did not include prioritisation of DAAs uptake strategy, that limited the access to HCV therapy. The low treatment uptake in several populations seriously jeopardises the completion of the HCV elimination in the coming years.References and/or acknowledgementsNo conflict of interest.

Gender refers to the socially constructed roles, behaviours, expressions and identities of girls, women, boys, men and gender diverse people. Gender-related factors are seldom assessed as determinants of health outcomes, despite their powerful contribution. The Gender Outcomes INternational Group: to Further Well-being Development (GOING-FWD) project developed a standard five-step methodology applicable to retrospectively identify gender-related factors and assess their relationship to outcomes across selected cohorts of non-communicable chronic diseases from Austria, Canada, Spain, Sweden. Step 1 (identification of gender-related variables): Based on the gender framework of the Women Health Research Network (ie, identity, role, relations and institutionalised gender), and available literature for a certain disease, an optimal ‘wish-list’ of gender-related variables was created and discussed by experts. Step 2 (definition of outcomes): Data dictionaries were screened for clinical and patient-relevant outcomes, using the International Consortium for Health Outcome Measurement framework. Step 3 (building of feasible final list): a cross-validation between variables per database and the ‘wish-list’ was performed. Step 4 (retrospective data harmonisation): The harmonisation potential of variables was evaluated. Step 5 (definition of data structure and analysis): The following analytic strategies were identified: (1) local analysis of data not transferable followed by a meta-analysis combining study-level estimates; (2) centrally performed federated analysis of data, with the individual-level participant data remaining on local servers; (3) synthesising the data locally and performing a pooled analysis on the synthetic data and (4) central analysis of pooled transferable data. The application of the GOING-FWD multistep approach can help guide investigators to analyse gender and its impact on outcomes in previously collected data.

Sex and gender-based differences in cardiovascular health (CVH) has been explored in the context of high-income countries. However, these relationships have not been examined in low- and middle-income countries. The main aim of this study was to examine how sex and gender-related factors are associated with cardiovascular risk factors of people in South Asian countries. We conducted a retrospective analysis of the World Health Organization's \"STEPwise approach to surveillance of risk factors for non-communicable disease\" or \"STEPS\" from six South Asian countries, surveys conducted between 2014-2019. The main outcomes were CVH as measured by a composite measure of STEPS-HEART health index (smoking, physical activity, fruit and vegetable consumption, overweight/obesity, diabetes and hypertension), values ranging from 0 (worst) to 6 (best or ideal) and self-reported occurrence of cardiovascular disease (ie, heart attack and stroke). Multivariate linear and logistic regression models were performed. Multiple imputation with chained equations was performed. The final analytic sample consisted of 33 106 participants (57.5% females). The mean STEPS-HEART index score in the South Asian population was 3.43 [SD: 0.92]. Female sex (β: 0.05, 95% confidence interval (CI) = 0.01-0.08,  < 0.05) was significantly associated with better CVH compared to males. Being married (β  = -0.30, 95% CI = -0.37, -0.23 vs β  = -0.23, 95% CI = -0.29, -0.17;  < 0.001) and having a household size ≥5 (β  = -0.15, 95% CI = -0.24, -0.06 vs β  = -0.11, 95% CI = -0.16, -0.04;  < 0.01) were associated with poorer CVH, more so in males. Being married was also associated with high risk of CVD (OR  = 2.54, 95% CI = 1.68-3.86,  < 0.001 vs OR  = 1.19, 95% CI = 0.84-1.68,  = 0.31), significant in males. Among the South Asian population, being female may be advantageous in having an ideal CVH. However, gender-related factors such as marital status and large household size were associated with poorer CVH and greater risk of CVD, regardless of sex.