Introducing a core dataset for real-world data in multiple sclerosis registries and cohorts: Recommendations from a global task force.

BACKGROUND: As of September 2022, there was no globally recommended set of core data elements for use in multiple sclerosis (MS) healthcare and research. As a result, data harmonisation across observational data sources and scientific collaboration is limited. OBJECTIVES: To define and agree upon a core dataset for real-world data (RWD) in MS from observational registries and cohorts. METHODS: A three-phase process approach was conducted combining a landscaping exercise with dedicated discussions within a global multi-stakeholder task force consisting of 20 experts in the field of MS and its RWD to define the Core Dataset. RESULTS: A core dataset for MS consisting of 44 variables in eight categories was translated into a data dictionary that has been published and disseminated for emerging and existing registries and cohorts to use. Categories include variables on demographics and comorbidities (patient-specific data), disease history, disease status, relapses, magnetic resonance imaging (MRI) and treatment data (disease-specific data). CONCLUSION: The MS Data Alliance Core Dataset guides emerging registries in their dataset definitions and speeds up and supports harmonisation across registries and initiatives. The straight-forward, time-efficient process using a dedicated global multi-stakeholder task force has proven to be effective to define a concise core dataset.

Risk of cancer with immunosuppressants compared to immunomodulators in multiple sclerosis: A nested case-control study within the French nationwide claims database.

PURPOSE: The objective was to compare the risk of malignancies in real-world settings between exclusive immunosuppressant (IS) and immunomodulator (IM) use in multiple sclerosis (MS). METHODS: A nested case-control study was designed within a new-user cohort of all patients with MS who initiated a first IM or IS between 2008 and 2014, and without cancer history, using the information of the SNDS nationwide French claims database. Incident cancer cases were matched with up to six controls on year of birth, sex, initiation date, and disease risk score of cancer. A conditional logistic regression (odds ratio [95% confidence interval]) was used to compare exclusive IS versus IM use during follow-up and according to three use durations. RESULTS: From 28 720 newly treated patients with MS, 407 incident cancers were observed during the follow-up with 2324 matched controls. A significant increase in cancer risk was observed for IS compared with IM (1.36 [1.05, 1.77]), with similar increases for the first 2 years of use but not for ≥2 years (1.06 [0.65, 1.75]). Similar increase was also observed for IS with indications other than MS (1.37 [1.04, 1.81]) but not for IS indicated only in MS (1.03 [0.45, 2.34]). CONCLUSIONS: Compared with IM, a 37% increase in cancer risk was observed for IS with indications other than MS and used for a short duration (≤2 years) but not for IS indicated only in MS. The absence of risk for prolonged exposure of IS with indications other than MS is not in favor of a causal relation with these drugs.

Incidence and risk of cancer among multiple sclerosis patients: A matched population-based cohort study.

BACKGROUND AND PURPOSE: Studies have not yet found conclusive results on the risk of cancer in patients with multiple sclerosis (MS). This study aimed to compare the incidence of all cancers and of specific types of cancer between MS patients and the general population by age and by sex. METHODS: All prevalent MS patients identified between 2008 and 2014 in the nationwide French health care database (Système National des Données de Santé) and without history of malignancy were included in a cohort study and followed up until cancer occurrence, date of death, or 31 December 2015, whichever came first. MS patients were matched based on sex and year of birth to non-MS controls from the general population without cancer before index date. Incidence rate was reported per 100,000 person-years (PY), and risk of cancer was estimated by type of cancer, age, and sex using a Cox model (hazard ratio [HR] and its 95% confidence interval [CI]). RESULTS: Overall, 576 cancers per 100,000 PY were observed in MS patients versus 424 per 100,000 PY in the control population. The risk of cancer was higher among MS patients than among population controls whether considered overall (HR = 1.36, 95% CI = 1.29-1.43) or for prostate (HR = 2.08, 95% CI = 1.68-2.58), colorectal and anal (HR = 1.35, 95% CI = 1.16-1.58), trachea, bronchus, and lung (HR = 2.36, 95% CI = 1.96-2.84), and to a lesser extent, breast cancer (HR = 1.12, 95% CI = 1.03-1.23). CONCLUSIONS: MS patients were associated with increased risk of cancer compared to population controls.

Antimicrobial resistance in Neisseria gonorrhoeae isolates from foreign-born population in the European Gonococcal Antimicrobial Surveillance Programme.

OBJECTIVES: International spread has contributed substantially to the high prevalence of antimicrobial resistant (AMR) Neisseria gonorrhoeae infections worldwide. We compared the prevalence of AMR gonococcal isolates among native persons to foreign-born (reporting country different from country of birth) persons, and describe the epidemiological and clinical characteristics of foreign-born patients and their associations to AMR. METHODS: We analysed isolates and patient data reported to the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) 2010-2014 (n=9529). RESULTS: Forty-three per cent of isolates had known country of birth and 17.2% of these were from persons born abroad. Almost 50% of foreign-born were from the WHO European Region (13.1% from non-European Union [EU] and the European Economic Area [EEA] countries). Compared with isolates from natives, isolates from foreign-born had a similar level (p>0.05) of azithromycin resistance (7.5% vs 7.2%), ciprofloxacin resistance (50.0% vs 46.3%) and of decreased susceptibility to ceftriaxone (1.9% vs 2.8%); a lower rate of cefixime resistance (5.7% vs 3.6%, p=0.02), and a higher proportion of isolates producing penicillinase (8.4% vs 11.7%, p=0.02). Among isolates from persons born outside EU/EEA, the level of decreased susceptibility to ceftriaxone was higher (1.8% vs 3.5%, p=0.02), particularly in those from the WHO Eastern Mediterranean Region and non-EU/EEA WHO European countries (1.9% vs 9.6% and 8.7%, respectively, p<0.01). In multivariable analysis, foreign-born patients with AMR isolates were more likely to be from non-EU/EEA WHO European countries (adjusted OR [aOR]: 3.2, 95% CI 1.8 to 5.8), WHO Eastern Mediterranean countries (aOR: 1.8, 95% CI 1.1 to 3.3) and heterosexual males (aOR: 1.8, 95% CI 1.2 to 2.7). CONCLUSIONS: Importation of AMR strains remains an important threat in the EU/EEA. Research to improve understanding of sexual networks within foreign born and sexual tourism populations could help to inform effective tailor-made interventions. The Euro-GASP demonstrates the public health value of quality-assured surveillance of gonococcal AMR and the need for strengthened AMR surveillance, particularly in the non-EU/EEA WHO European Region.

Identifying Patients With Relapsing-Remitting Multiple Sclerosis Using Algorithms Applied to US Integrated Delivery Network Healthcare Data.

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) has a major impact on affected patients; therefore, improved understanding of RRMS is important, particularly in the context of real-world evidence. OBJECTIVES: To develop and validate algorithms for identifying patients with RRMS in both unstructured clinical notes found in electronic health records (EHRs) and structured/coded health care claims data. METHODS: US Integrated Delivery Network data (2010-2014) were queried for study inclusion criteria (possible multiple sclerosis [MS] base cohort): one or more MS diagnosis code, patients aged 18 years or older, 1 year or more baseline history, and no other demyelinating diseases. Sets of algorithms were developed to search narrative text of unstructured clinical notes (EHR clinical notes-based algorithms) and structured/coded data (claims-based algorithms) to identify adult patients with RRMS, excluding patients with evidence of progressive MS. Medical records were reviewed manually for algorithm validation. Positive predictive value was calculated for both EHR clinical notes-based and claims-based algorithms. RESULTS: From a sample of 5308 patients with possible MS, 837 patients with RRMS were identified using only the EHR clinical notes-based algorithms and 2271 patients were identified using only the claims-based algorithms; 779 patients were identified using both algorithms. The positive predictive value was 99.1% (95% confidence interval [CI], 94.2%-100%) for the EHR clinical notes-based algorithms and 94.6% (95% CI, 89.1%-97.8%) to 94.9% (95% CI, 89.8%-97.9%) for the claims-based algorithms. CONCLUSIONS: The algorithms evaluated in this study identified a real-world cohort of patients with RRMS without evidence of progressive MS that can be studied in clinical research with confidence.

Decline in reported AIDS cases in Brazil after implementation of the test and treat initiative.

BACKGROUND: To evaluate the trends in AIDS detection and the AIDS-attributed death rate in Brazil between 2007 and 2015 and to determine the population characteristics associated with AIDS detection. METHODS: Surveillance data including demographics, mode of HIV transmission, AIDS cases, and AIDS-attributed deaths were analysed. A logistic regression model was fitted to assess the trends in AIDS cases by mode of HIV transmission throughout the study period. A segmented Poisson regression model was used to assess changes in the trends of AIDS detection and mortality rates before (2007-2014) and after (2015) the introduction of the Test and Treat Initiative. RESULTS: In the segmented Poisson regression, the decline in the AIDS detection rate from 2007 to 2014 was 2.0% annually (i.e., the odds ratio (OR) for annual decline was 0.98 (95% [CI: 0.98-1.00, p-value < 0.001). The observed AIDS detection rate in 2015 was 7.7 cases per 100,000, which was 60% lower than the regression estimate of 19.8 for the hypothetical absence of the Test and Treat Initiative. The reduction in AIDS-attributed deaths from 2007 to 2014 was 8.0% annually (i.e., the OR for annual decline was 0.92 (95% [CI: 0.91-0.95, p-value < 0.001). The observed AIDS mortality rate in 2015 was 0.49 cases per 100,000, which was 73% lower than the regression estimate of 2.1 for the hypothetical absence of the Test and Treat Initiative in 2015. CONCLUSIONS: Our results reveal a fairly stable AIDS detection rate from 2007 to 2014, with a sudden significant drop in 2015. This drop may be related to the increasing trends in rapid testing, the number of new HIV diagnoses, the number of patients on antiretroviral therapy (ART), and a median CD4 count at ART enrolment. Further evaluation of the effects of the Test and Treat Initiative on AIDS diagnosis and mortality is needed and must be strengthened with additional data from subsequent years.

High risk human papillomavirus prevalence and genotype distribution among women infected with HIV in Manaus, Amazonas.

BACKGROUND: Human immunodeficiency virus (HIV)-positive women have a high prevalence of human papillomavirus (HPV), and are infected with a broader range of HPV types than HIV-negative women. We aimed to determine the prevalence of cervical cytologic abnormalities, high-risk (HR)-HPV prevalence, type distribution according to the severity of cervical lesions and CD4 cell count and identify factors associated with HR-HPV infection among women living with HIV in Manaus, Amazonas. METHODS: We enrolled 325 women living with HIV that attended an infectious diseases referral hospital. Each woman underwent a gynecological exam, cervical cytology, HR-HPV detection by Polymerase chain Reaction (PCR) using the BD Onclarity™ HPV Assay, colposcopy and biopsy, when necessary. We assessed the associations between potential risk factors and HR-HPV infection. RESULTS: Overall, 299 (92.0%) women had a PCR result. The prevalence of HR-HPV- infection was 31.1%. The most prevalent HR-HPV types were: 56/59/66 (32.2%), 35/39/68 (28.0%), 52 (21.5%), 16 (19.4%), and 45 (12.9%). Among the women with HR-HPV infection (n = 93), 43.0% had multiple infections. Women with HPV infection showed higher prevalence of cervical abnormalities than that HPV-negative (LSIL: 22.6% vs. 1.5%; HSIL: 10.8% vs. 0.0%). The prevalence of HR-HPV among women with cytological abnormalities was 87.5% for LSIL and 100.0% for HSIL. Women with CD4 < 200 cell/mm3 showed the highest HR-HPV prevalence (59.3%) although this trend was not statistically significant (p-value = 0.62). The mean CD4 cell count decreased with increasing severity of cervical lesions (p-value = 0.001). The multivariable analysis showed that increasing age was associated with a decreased risk of HR-HPV infection with an adjusted prevalence odds ratio of 0.9 (95.0% CI: 0.9-1.0, p-value: 0.03) for each additional year. The only factor statistically significant associated with HR-HPV infection was CD4 cell count. CONCLUSIONS: HR-HPV and abnormal cytology prevalence are high among women in the Amazonas. The low CD4 cell count was an important determinant of HPV infection and abnormal cytological findings. HPV quadrivalent vaccination used in Brazil might not offer protection for an important fraction of HPV-related disease burden in women living with HIV. This is partly explained by the high presence of non targeted vaccine HR-HPVs, such as the HPV genotype groups 56/59/66, 35/39/68 and individually HPV-52 and HPV-45, some of which contribute to high-grade lesion.

Pharmacological intervention in hypertension using beta-blockers: Real-world evidence for long-term effectiveness.

The study objective was to compare the long-term incidence and risk of mortality and cardiovascular outcomes in patients with hypertension initiating bisoprolol, other ß-blockers or other antihypertensive therapies. Cohort analysis using UK Clinical Practice Research Datalink (CPRD). Adult patients with first diagnosis of hypertension recorded between 2000 and 2014, with ≥365 days of registration to first event and initiating monotherapies of bisoprolol, other ß-blockers or drugs other than ß-blockers within 6 months of diagnosis were included. Incidence rates (IR) for each treatment cohort were compared using adjusted hazard ratio (HR) and 95% confidence intervals (CI) obtained from Cox regression analyses. Of 100,066 patients included, 539 were prescribed bisoprolol, 3701 other ß-blockers, and 95,826 drugs other than ß-blockers. Patients receiving bisoprolol had significantly increased survival from 2 up to <15 years (HR for <15 years 0.34; 95% CI 0.18-0.67) versus other ß-blockers, and from 5 to <15 years (HR for <15 years 0.52; 95% CI 0.27-1.00) versus drugs other than ß-blockers. Over time, the risk of arrhythmia was higher in the bisoprolol cohort versus other ß-blockers, and risks of arrhythmia and angina were higher versus drugs other than ß-blockers. No differences in the risk of embolism, stroke, and myocardial infarction (MI) were found between cohorts. Over time, mortality and cardiovascular outcome IRs decreased in each cohort. In conclusion, bisoprolol showed sustained benefit on survival, evident from 2 years after treatment initiation versus other ß-blockers, and from 5 years versus drugs other than ß-blockers, providing long-term evidence supporting the use of bisoprolol in patients with hypertension in primary care.

Drug resistance in antiretroviral-naive children newly diagnosed with HIV-1 in Manaus, Amazonas.

Objectives: To determine the prevalence of drug resistance mutations (DRM), the prevalence of drug susceptibility [transmitted drug resistance (TDR)] and the prevalence of HIV-1 variants among treatment-naive HIV-infected children in Manaus, Amazonas state, Brazil. Methods: Children born to HIV-infected mothers and diagnosed with HIV in an HIV reference service centre and with available pol sequence between 2010 and 2015 prior to antiretroviral initiation were included. TDR was identified using the Calibrated Population Resistance Tool. HIV-1 subtypes were defined by Rega and phylogenetic analyses. Results: One hundred and seventeen HIV-infected children with a median age of 3.7 years were included. Among them, 28.2% had been exposed to some form of prevention of mother-to-child transmission (PMTCT). HIV DRM were present in 21.4% of all children. Among PMTCT-exposed children, 3% had NRTI mutations, 15.2% had NNRTI mutations and 3% had PI mutations. Among PMTCT-unexposed children, 1.2% had NRTI mutations, 21.4% had non-NNRTI mutations and 1.2% had PI mutations. The most common DRM was E138A (8.5%). The prevalence of TDR was 16.2%; 21.1% among PMTCT-exposed children and 14.3% among PMTC-unexposed children. The analysis of HIV-1 subtypes revealed that 80.2% were subtype B, 6.0% were subtype C, 3.4% were subtype F1 and 10.3% were possible unique recombinant forms (BF1, 4.3%; DB, 4.3%; BC, 0.9%; KC, 0.9%). Conclusions: We report a high prevalence of DRM in this population, including in almost a quarter of children with no reported PMTCT. The high prevalence of TDR observed might compromise ART effectiveness. Results show extensive HIV-1 diversity and expansion of subtype C, which highlights the need for surveillance of HIV-1 subtypes in Amazonas state.

Transitioning from antenatal surveillance surveys to routine HIV testing: a turning point in the mother-to-child transmission prevention programme for HIV surveillance in Brazil.

BACKGROUND: In Brazil, due to the rapid increase in programmes for the prevention of mother-to-child transmission (PMTCT), routine programme data are widely available. The objective of this study was to assess the utility of programmatic data to replace HIV surveillance based on the antenatal care (ANC) surveillance survey (SS). METHODS: We analysed ANC SS data from 219 maternity service clinics. PMTCT variables were extracted from the ANC SS data collection form, which allowed us to capture and compare the ANC SS data and PMTCT HIV test results for each pregnant woman who completed the ANC SS. Both the PMTCT programme and the ANC SS tested for HIV using sequential ELISA and western blot for confirmation. We assessed the completeness (% missing) of the PMTC data included in the ANC SS. RESULTS: Of the 36,713 pregnant women who had ANC SS HIV tests performed, 30,588 also underwent PMTCT HIV testing. The HIV prevalence rate from routine PMTCT testing was 0.36%, compared to 0.38% from the ANC SS testing (relative difference -0.05%; absolute difference -0.02%). The relative difference in prevalence rates between pregnant women in northern Brazil and pregnant women central-west Brazil was -0.98 and 0.66, respectively. Of the 29,856 women who had HIV test results from both the PMTCT and ANC SS, the positive percent agreement of the PMTCT versus the surveillance test was 84.1% (95% confidence interval [CI]: 74.8-91.0), and the negative percent agreement was 99.9% (95% CI: 99.9-100.0). The PMTCT HIV testing uptake was 86.4%. The ANC SS HIV prevalence was 0.33% among PMTCT non-refusers and 0.59% among refusers, with a percent bias of -10.80% and a differential prevalence ratio of 0.56. Syphilis and HIV testing results were complete in 98% and 97.6% of PMTCT reports, respectively. The reported HIV status for the women at clinic entry was missing. CONCLUSIONS: Although there were consistent HIV prevalence estimates from the PMTCT data and the ANC SS, the overall positive percent agreement of 84.1% falls below the World Health Organization benchmark of 94.7%. Therefore, Brazil must continue to reinforce data collection practices and ensure the quality of recently introduced rapid HIV testing before replacing the PMTCT data with surveillance techniques. However, some regions with better results could be prioritized to pilot the use of PMTCT data for surveillance.

HIV and syphilis in the context of community vulnerability among indigenous people in the Brazilian Amazon.

BACKGROUND: Contextual factors shape the risk of acquiring human immunodeficiency virus (HIV) and syphilis. We estimated the prevalence of both infections among indigenous people in nine indigenous health districts of the Brazilian Amazon and examined the context of community vulnerability to acquiring these infections. METHODS: We trained 509 health care workers to screen sexually active populations in the community for syphilis and HIV using rapid testing (RT). We then assessed the prevalence of HIV and syphilis using RT. A multivariable analysis was used to identify factors associated with syphilis infection (sociodemographic, condom use, intrusion, population mobility, and violence). RESULTS: Of the 45,967 indigenous people tested, the mean age was 22.5 years (standard deviation: 9.2), and 56.5% were female. Overall, for HIV, the prevalence was 0.13% (57/43,221), and for syphilis, the prevalence was 1.82% (745/40,934). The prevalence in men, women, and pregnant women for HIV was 0.16%, 0.11%, and 0.07%, respectively, and for syphilis, it was 2.23%, 1.51%, and 1.52%, respectively. The district Vale do Javari had the highest prevalence of both infections (HIV: 3.38%, syphilis: 1.39%). This district also had the highest population mobility and intrusion and the lowest availability of prenatal services. Syphilis infection was independently associated with age (odds ratio [OR] 1.04, 95% confidence interval [CI]: 1.03-1.05), male sex (OR 1.32, 95% CI: 1.14-1.52), and mobility (moderate: OR: 7.46, 95% CI: 2.69-20.67; high: OR 7.09, 95% CI: 3.79-13.26). CONCLUSIONS: The large-scale integration of RT in remote areas increased case detection among pregnant women, especially for syphilis, in districts with higher vulnerability. Mobility is an important risk factor, especially in districts with higher vulnerability. Contextually appropriate approaches that address this factor could contribute to the long-term success of HIV and syphilis control programs.

Home-based counseling and testing for HIV and syphilis - an evaluation of acceptability and quality control, in remote Amazonas State, Brazil.

OBJECTIVE: Home-based, voluntary counselling and testing (HBCT) can help scale up early diagnosis. We aimed to evaluate the acceptance of HBCT for HIV and syphilis, estimate the prevalence among home-tested individuals and assess the performance of point-of-care testing by health staff using dried tube specimens (DTS) in a remote municipality of the Amazon region. METHODS: Community health teams conducted door-to-door outreach in the urban area of São Gabriel da Cachoeira, Amazonas. HBCT for HIV and syphilis was offered to all residents aged ≥15 years. To provide an external quality assurance (EQA) of the healthcare workers' (HCW') ability to perform testing, DTS panels of reference samples were reconstituted and tested by the workers. RESULTS: HBCT was offered to 1752 individuals and accepted by 1501 (85.6%). Those tested had a median age 32.0 years, 64.4% were women and 85.1% were indigenous; none were previously tested using a rapid test. The prevalence of HIV was 0.37% in men and 0.0% in women; the prevalence of syphilis was 1.12% in men and 2.69% in women. Eleven HCW tested 44 DTS samples for HIV and 44 for syphilis. EQA testing revealed that workers interpreted 55.8% and 90.7% of HIV and syphilis reference samples correctly. CONCLUSIONS: HBCT was acceptable and successful in reaching untested individuals. However, there were concerns with the quality of test performance, highlighting the need for continual evaluation and retraining of community HCW. As Brazil scales up HIV and syphilis testing, our findings highlight how HBCT can maximise coverage in similar remote areas and improve knowledge about prevalence of these infections.

Sexual Violence Against Men Who Have Sex with Men in Brazil: A Respondent-Driven Sampling Survey.

We estimated the prevalence of sexual violence (SV) experience among men who have sex with men (MSM) in Brazil and identified its associated risk factors. We recruited 3859 MSM through respondent driven sampling. A multivariable hierarchical analysis was performed using an ecological model. The prevalence of having ever experienced SV was 15.9 % (95 % confidence interval [CI] 14.7-17.1). SV experience was independently associated with discrimination due to sexual orientation (odds ratio [OR] 3.05; 95 % CI 2.10-4.42), prior HIV testing (OR 1.81; 95 % CI 1.25-2.63), ≤14 years at first sex (OR 1.86; 95 % CI 1.28-2.71), first sex with a man (OR 1.89; 95 % CI 1.28-2.79), presenting STI symptoms (last year) (OR 1.66; 95 % CI 1.12-2.47), and having suicidal ideas (last 6 months) (OR 2.08; 95 % CI 1.30-3.35). The high levels of SV against MSM in Brazil place them at a markedly higher risk of SV than the general population. Homophobic prejudice is the strongest determinant of SV and urgently needs to be included at the forefront of the national response to SV.

Point-of-care screening for syphilis and HIV in the borderlands: challenges in implementation in the Brazilian Amazon.

BACKGROUND: Point-of-care (POC) screening for HIV and syphilis using rapid testing was implemented in indigenous communities in the triple-border area of the Brazilian Amazon. We describe the context of the early introduction of POC screening, explore hindering and enabling factors for POC implementation, and recommend strategies for feasible, viable, and sustainable syphilis and HIV screening interventions. METHODS: This was a qualitative study based on grounded theory methodology. Data were collected using in-depth interviews, semi-structured questionnaires, and field observations and were analysed using the framework approach. Qualitative information was complemented by quantitative data for descriptive purposes. RESULTS: An overall high score for vulnerability to acquiring HIV and syphilis was observed among the indigenous communities. Health professionals reported satisfactory rapid testing acceptance, although concerns were raised about the pain of the fingerprick. Counselling-related challenges included ensuring the accuracy of translations, collaborating with translators and communicating positive test results. Over 3 months, 86.7% of the syphilis-positive individuals began treatment, and all of them notified their partners. Accessibility, measured as travel time via the local transportation network, was a barrier to health care access. A lack of gasoline for boats and other transportation was also a hindering factor at all levels of implementation. CONCLUSIONS: The recommendations address the preparation phase at the coordination level as well as at the training level. Tools such as strengths, weaknesses, opportunities, and threats (SWOT) analyses; checklists; context-adapted protocols; and fact sheets are very simple methods to facilitate implementation. The findings of this study are important because they may inform the implementation of new health technologies in low-resource national disease control programmes in remote communities.

Prevalence of visual impairment in El Salvador: inequalities in educational level and occupational status.

OBJECTIVE: To examine the prevalence of blindness, visual impairment, and related eye diseases and conditions among adults in El Salvador, and to explore socioeconomic inequalities in their prevalence by education level and occupational status, stratified by sex. METHODS: Based upon the Rapid Assessment of Avoidable Blindness (RAAB) methodology, this nationwide sample comprised 3 800 participants (3 399 examined) ≥ 50 years old from 76 randomly selected clusters of 50 persons each. The prevalence of blindness, visual impairment and related eye diseases and conditions, including uncorrected refractive error (URE), was calculated for categories of education level and occupational status. Multiple logistic regression models were fitted to calculate odds ratios (ORs) and 95% confidence intervals (CIs) and stratified by sex. RESULTS: Age-adjusted prevalence was 2.4% (95% CI: 2.2-2.6) for blindness (men: 2.8% (95% CI: 2.5-3.1); women: 2.2% (95% CI: 1.9-2.5)) and 11.8% (95% CI: 11.6-12.0) for moderate visual impairment (men: 10.8% (95% CI: 10.5-11.1); women: 12.6% (95% CI: 12.4-12.8)). The proportion of visual impairment due to cataract was 43.8% in men and 33.5% in women. Inverse gradients of socioeconomic inequalities were observed in the prevalence of visual impairment. For example, the age-adjusted OR (AOR) was 3.4 (95% CI: 2.0-6.4) for visual impairment and 4.3 (95% CI: 2.1-10.4) for related URE in illiterate women compared to those with secondary education, and 1.9 (95% CI: 1.1-3.1) in cataract in unemployed men. CONCLUSIONS: Blindness and visual impairment prevalence is high in the El Salvador adult population. The main associated conditions are cataract and URE, two treatable conditions. As socioeconomic and gender inequalities in ocular health may herald discrimination and important barriers to accessing affordable, good-quality, and timely health care services, prioritization of public eye health care and disability policies should be put in place, particularly among women, the unemployed, and uneducated people.

Drug Utilization Studies in Pregnant Women for Newly Licensed Medicinal Products: A Contribution from IMI ConcePTION.

Purpose: Studies focusing on safety outcomes typically require large populations to comprehensively characterise the patient groups exposed to the medicines under investigation. However, there is often less information for subpopulations, such as pregnant or breastfeeding women, particularly when new medicines are considered. It is important to understand what information can be obtained from drug utilization studies (DUS) involving pregnant women in the early years postmarketing to provide supportive information for safety studies. The aims of this literature review are to (1) identify and review DUS for new medicines in pregnancy and breastfeeding and (2) list and summarise key information items to be reported in a DUS for new medicines in pregnancy. Methods: To identify postmarketing DUS of new prescription medicines or enantiomers in pregnancy, a systematic literature review was undertaken in PubMed and Embase between January 2015 and June 2022. In addition, the complete database of the ENCePP EU PAS Register was systematically searched to June 2022. Results: We identified 11 published DUS on new medicines in pregnancy from the ENCePP EU PAS Register and none from other sources. No studies on breastfeeding were identified. The 11 identified publications reported the medicine's use for the first 3 to 5 years after marketing approval. No reports assessed utilization in the first 3 years of approval. It was usual to issue interim reports annually (7 studies). All studies concerned conditions managed in ambulatory care (primary care and outpatient facilities) and included some primary care prescribing. Most (n = 8) only had prescribing/dispensing data available at individual level for ambulatory care; outpatient prescribing was included in three of these studies Three studies held a limited amount of in-hospital prescribing data. A DUS can confirm at an early stage whether there are sufficient exposed pregnancies in available data sources to ensure a safety study is powered to detect a difference in the prevalence of adverse pregnancy or infant outcomes or if additional data from other databases are needed. A DUS may also help address methodological considerations such as selection of comparators. DUS can be performed embedded in a DUS in the general population, in a cohort of women of childbearing age, or in a cohort of pregnant women. Conclusion: This review summarises key aspects of a DUS for new medicines in pregnancy. DUS for new medicines in pregnancy should be planned before marketing, scheduled for the first 3 to 5 years after release, with annual interim/progress reports, and reported in peer-reviewed journals. By offering detailed information on data sources, exposure timing, prevalence and location, coprescribing, comorbidities, coexposures, and demographics, a DUS will offer a firm foundation for safety studies and will help to contextualize spontaneous reporting of serious adverse events.

Bone mass, fracture risk, and associated factors in postmenopausal women living with HIV.

OBJECTIVE: The aim of this study was to assess the prevalence of low bone mass (osteopenia/osteoporosis), the factors associated with low bone mass, and the risk of fractures in Brazilian postmenopausal women living with HIV (WLH) in the Amazon region. METHODS: This is a cohort study with a cross-sectional assessment at baseline conducted between March 2021 to August 2022 with 100 postmenopausal WLH undergoing antiretroviral therapy (ART) between 45 and 60 years of age and 100 age-matched HIV-negative women. Data on bone mineral density in the lumbar spine (LS) and femoral neck (FN) were collected using dual x-ray absorptiometry and the 10-year risk of hip and major osteoporotic fractures was assessed using the Fracture Risk Assessment tool (FRAX). RESULTS: The age of menopause onset occurred earlier in WLH ( P < 0.001). No differences in prevalence of osteoporosis and osteopenia in LS and FN were observed except for a lower T score in FN in WLH ( P = 0.039). The FRAX for major osteoporotic fracture and hip fracture were low in both groups, despite the mean of both FRAX scores was higher in WLH ( P < 0.001). Multivariate analysis showed that years since menopause onset, higher body mass index and higher FRAX major osteoporotic fracture were associated with the WLH group, while a higher frequency of physical activity was registered in the HIV-negative group. Multivariate analysis also showed that in WLH, a lower T score in FN was associated with years since menopause onset and body mass index and that the number of years since menopause onset was associated with a lower T score in the LS and a higher score in the FRAX hip fracture. CONCLUSIONS: Our findings show a high prevalence of low bone mass (osteopenia/osteoporosis) in Brazilian postmenopausal women from the Amazon region. Women living with HIV have higher FRAX scores than HIV-negative women and a lower T score in the FN.

Improving Data Collection in Pregnancy Safety Studies: Towards Standardisation of Data Elements in Pregnancy Reports from Public and Private Partners, A Contribution from the ConcePTION Project.

INTRODUCTION AND OBJECTIVE: The ConcePTION project aims to improve the way medication use during pregnancy is studied. This includes exploring the possibility of developing a distributed data processing and analysis infrastructure using a common data model that could form a foundational platform for future surveillance and research. A prerequisite would be that data from various data access providers (DAPs) can be harmonised according to an agreed set of standard rules concerning the structure and content of the data. To do so, a reference framework of core data elements (CDEs) recommended for primary data studies on drug safety during pregnancy was previously developed. The aim of this study was to assess the ability of several public and private DAPs using different primary data sources focusing on multiple sclerosis, as a pilot, to map their respective data variables and definitions with the CDE recommendations framework. METHODS: Four pregnancy registries (Gilenya, Novartis; Aubagio, Sanofi; the Organization of Teratology Information Specialists [OTIS]; Aubagio, Sanofi; the Dutch Pregnancy Drug Register, Lareb), two enhanced pharmacovigilance programmes (Gilenya PRIM, Novartis; MAPLE-MS, Merck Healthcare KGaA) and four Teratology Information Services (UK TIS, Jerusalem TIS, Zerifin TIS, Swiss TIS) participated in the study. The ConcePTION primary data source CDE includes 51 items covering administrative functions, the description of pregnancy, maternal medical history, maternal illnesses arising in pregnancy, delivery details, and pregnancy and infant outcomes. For each variable in the CDE, the DAPs identified whether their variables were: identical to the one mentioned in the CDE; derived; similar but with a divergent definition; or not available. RESULTS: The majority of the DAP data variables were either directly taken (85%, n = 305/357, range 73-94% between DAPs) or derived by combining different variables (12%, n = 42/357, range 0-24% between DAPs) to conform to the CDE variables and definitions. For very few of the DAP variables, alignment with the CDE items was not possible, either because of divergent definitions (1%, n = 3/357, range 0-2% between DAPs) or because the variables were not available (2%, n = 7/357, range 0-4% between DAPs). CONCLUSIONS: Data access providers participating in this study presented a very high proportion of variables matching the CDE items, indicating that alignment of definitions and harmonisation of data analysis by different stakeholders to accelerate and strengthen pregnancy pharmacovigilance safety data analyses could be feasible.

Sexual risk behaviours and barriers to HIV testing among clients of female sex workers in Guatemala: a qualitative study.

Few interventions have targeted clients of female sex workers in Central America, despite their potential role in HIV/STI prevention. Semi-structured interviews were conducted with 30 clients of female sex workers on attitudes towards prevention of HIV/STIs, barriers to condom use and behaviour towards HIV/STI testing and treatment in Escuintla, Guatemala. Despite high knowledge of condoms as an HIV/STI preventive measure, the decision to use them was often based on the client's social judgment of the woman's sexual conduct. Regular clients reported lower condom use. Clients' risk perception diminished with the awareness of the public HIV/STI clinic addressed to female sex workers. Most preferred private clinics to increase confidentiality and were reluctant to take the HIV test for fear of a positive result. Outreach programmes offering HIV/STI counselling and testing to clients of female sex workers could increase their test uptake and health-seeking behaviour and reduce potential transmission to the general population.

The CLARION study: first report on safety findings in patients newly initiating treatment with cladribine tablets or fingolimod for multiple sclerosis.

OBJECTIVES: As part of the CLARION study: (1) characterize the incidence of severe infections, herpes zoster, and malignancies in patients newly initiating cladribine or fingolimod for relapsing multiple sclerosis (MS); (2) estimate the incidence of severe lymphopenia among cladribine users; and (3) describe prior/subsequent disease-modifying therapy (DMT) in both cohorts. METHODS: Patients were identified from seven participating MS registries/data sources. The incidence rate (IR) of each outcome per 1000 patient-years and its 95% confidence interval (95%CI) were estimated for cohorts using Poisson regression. RESULTS: By cut-off date (01-April-2020), 742 cladribine and 867 fingolimod users were included. Mean follow-up was ∼1 year. The IR for severe infections from all contributing sources (except Denmark) was: cladribine, 7.37 (2.76,19.6); fingolimod, 6.55 (2.46,17.4). The corresponding IR for herpes zoster was 5.51 (1.78,17.1) and 3.27 (0.82,13.1), respectively, while values for opportunistic infections were 0 (0,6.76) and 1.63 (0.23,11.6), respectively. There were no events of progressive multifocal leukoencephalopathy in either cohort. The IR of severe lymphopenia was 63.9 (40.7,100.1) in 349 cladribine users from contributing sources. The IR of malignancies (cut-off date 01-April-2022) was 3.55 (1.59,7.90) for the cladribine cohort (n = 1035) and 3.55 (1.48,8.52) for the fingolimod cohort (n = 843) from three MS registries/data sources. In the combined data sources, 36.8% of cladribine and 27.4% of fingolimod users were DMT-naïve; after initiation of study treatment, 2.5% and 20.2% switched to another DMT, respectively. CONCLUSION: No new safety signal was observed in patients treated with cladribine tablets, although results are limited by a relatively short duration of follow-up.