High-Resolution Geospatial Mapping of Zero-Dose and Underimmunized Children Following Nigeria's 2021 Multiple Indicator Cluster Survey/National Immunization Coverage Survey.

BACKGROUND: "Zero-dose" children are those who are without any routine vaccination or are lacking the first dose of the diphtheria, tetanus, and pertussis-containing vaccine. Based on global estimates from the World Health Organization/United Nations Children's Fund in 2022, Nigeria has the highest number of zero-dose children, with >2.3 million unvaccinated. METHODS: We used data from the 2021 Nigeria Multiple Indicator Cluster Survey/National Immunization Coverage Survey to identify zero-dose and underimmunized children. Geospatial modeling techniques were employed to determine the prevalence of zero-dose children and predict risk areas with underimmunized children at a high resolution (1 × 1 km). RESULTS: Zero-dose and underimmunized children are more prevalent in socially deprived groups. Univariate and multivariate bayesian analyses showed positive correlations between the prevalence of zero-dose and underimmunized children and factors such as stunting, contraceptive prevalence, and literacy. The prevalence of zero-dose and underimmunized children varies significantly by region and ethnicity, with higher rates observed in the country's northern parts. Significant heterogeneity in the distribution of undervaccinated children was observed. CONCLUSIONS: Nigeria needs to enhance its immunization system and coverage. Geospatial modeling can help deliver vaccines effectively to underserved communities. By adopting this approach, countries can ensure equitable vaccine access and contribute to global vaccination objectives.

Do efficacy results obtained from randomized controlled trials translate to effectiveness data from observational studies for relapsing-remitting multiple sclerosis?

BACKGROUND: Randomized controlled trials are considered the gold standard in regulatory decision making, as observational studies are known to have important methodological limitations. However, real-world evidence may be helpful in specific situations. This review investigates how the effect estimates obtained from randomized controlled trials compare to those obtained from observational studies, using drug therapy for relapsing-remitting multiple sclerosis as an example. STUDY DESIGN AND SETTING: A systematic review of randomized controlled trials and observational studies was conducted. The primary outcome was the annualized relapse rate. Using (network) meta-analysis together with posterior predictive distributions, the drug-specific rate ratios from the network of randomized controlled trials were compared with those from the network of observational studies. RESULTS: Effect estimates from 26 observational studies showed greater magnitudes and were less precise compared to estimates obtained from 21 randomized controlled trials. Twenty of the 28 treatment comparisons between designs had similar rate ratios. Seven inconsistencies in observed rate ratios could be attributed to two specific disease-modifying therapies. CONCLUSION: In this case study, estimates from observational studies predominantly agreed with estimates from randomized controlled trials given their posterior predictive distributions. Multiple observational studies together may therefore supplement additional pivotal randomized controlled trials in relapsing-remitting multiple sclerosis, for instance facilitating the extrapolation of trial results to the broader patient population.

Comparison of antipsychotic drug use in children and adolescents in the Netherlands before and during the COVID-19 pandemic.

This study aims to describe the patterns and trends in antipsychotic prescription among Dutch youth before and during the corona virus disease 2019 (COVID-19) pandemic (between 2017 and 2022). The study specifically aims to determine whether there has been an increase or decrease in antipsychotic prescription among this population, and whether there are any differences in prescription patterns among different age and sex groups. The study utilized the IADB database, which is a pharmacy prescription database containing dispensing data from approximately 120 community pharmacies in the Netherlands, to analyze the monthly prevalence and incidence rates of antipsychotic prescription among Dutch youth before and during the pandemic. The study also examined the prescribing patterns of the five most commonly used antipsychotics and conducted an autoregressive integrated moving average (ARIMA) analysis using data prior to the pandemic, to predict the expected prevalence rate during the pandemic. The prescription rate of antipsychotics for Dutch youth was slightly affected by the pandemic, with a monthly prevalence of 4.56 [4.50-4.62] per 1000 youths before COVID-19 pandemic and 4.64 [4.59-4.69] during the pandemic. A significant increase in prevalence was observed among adolescent girls aged 13-19 years. The monthly incidence rate remained stable overall, but rose for adolescent girls aged 13-19 years. Aripiprazole, and Quetiapine had higher monthly prevalence rates during the pandemic, while Risperidone and Pipamperon had lower rates. Similarly, the monthly incidence rates of Aripiprazole and Olanzapine went up, while Risperidone went down. Furthermore, the results from the ARIMA analysis revealed that despite the pandemic, the monthly prevalence rate of antipsychotic prescription was within expectation. The findings of this study suggest that there has been a moderate increase in antipsychotic prescription among Dutch youth during the COVID-19 pandemic, particularly in adolescent females aged 13-19 years. However, the study also suggests that factors beyond the pandemic may be contributing to the rise in antipsychotic prescription in Dutch youth.

High-resolution geospatial mapping of zero-dose and under-immunized children following Nigeria's 2021 multiple indicator cluster survey/national immunization coverage survey (MICS/NICS).

BACKGROUND: The "zero-dose" children are those without any routine vaccination or lacking the first dose of the diphtheria-tetanus-pertussis-containing vaccine. As per 2022 WHO/UNICEF estimates, globally, Nigeria has the highest number of zero-dose with over 2.3 million unvaccinated. METHODS: We used data from the 2021 Nigeria Multiple Indicator Cluster Survey - National Immunisation Coverage Survey to identify zero-dose and under-immunized children. Geospatial modelling techniques were employed to determine the prevalence of zero-dose children and predict risk areas with under-immunized at a high resolution of 1x1 km. RESULTS: Both zero-dose and under-immunized children are more prevalent in socially deprived groups. Univariate and multivariate Bayesian analyses showed positive correlations between the prevalence of zero-dose and under-immunized children with factors like stunting, contraceptive prevalence, and literacy. The prevalence of zero-dose and under-immunized children varies significantly by region and ethnicity, with higher rates observed in the country's northern parts. Significant heterogeneity in the distribution of under-vaccinated children was observed. CONCLUSIONS: Nigeria needs to enhance its immunization system and coverage. Geospatial modelling can help deliver vaccines effectively to underserved communities. By adopting this approach, countries can ensure equitable vaccine access and contribute to global vaccination objectives.

Estimating disparities in breast cancer screening programs towards mortality, case fatality, and DALYs across BRICS-plus.

BACKGROUND: Numerous studies over the past four decades have revealed that breast cancer screening (BCS) significantly reduces breast cancer (BC) mortality. However, in BRICS-plus countries, the association between BCS and BC case fatality and disability are unknown. This study examines the association of different BCS approaches with age-standardized mortality, case-fatality, and disability-adjusted life years (DALYs) rates, as well as with other biological and sociodemographic risk variables, across BRICS-plus from a national and economic perspective. METHODS: In this ecological study applying mixed-effect multilevel regression models, a country-specific dataset was analyzed by combining data from the Global Burden of Disease study 2019 on female age-standardized BC mortality, incidence, and DALYs rates with information on national/regional BCS availability (against no such program or only a pilot program) and BCS type (only self-breast examination (SBE) and/or clinical breast examination (CBE) [SBE/CBE] versus SBE/CBE with mammographic screening availability [MM and/or SBE/CBE] versus SBE/CBE/mammographic with digital mammography and/or ultrasound (US) [DMM/US and/or previous tests] in BRICS-plus countries. RESULTS: Compared to self/clinical breast examinations (SBE/CBE) across BRICS-plus, more complex BCS program availability was the most significant predictor of decreased mortality [MM and/or SBE/CBE: - 2.64, p < 0.001; DMM/US and/or previous tests: - 1.40, p < 0.001]. In the BRICS-plus, CVD presence, high BMI, second-hand smoke, and active smoking all contributed to an increase in BC mortality and DALY rate. High-income and middle-income regions in BRICS-plus had significantly lower age-standardized BC mortality, case-fatality, and DALYs rates than low-income regions when nationwide BC screening programs were implemented. CONCLUSIONS: The availability of mammography (digital or traditional) and BCS is associated with breast cancer burden in BRICS-plus countries, with regional variations. In light of high-quality evidence from previous causal studies, these findings further support the preventive role of mammography screening for BCS at the national level. Intervening on BCS related risk factors may further reduce the disease burden associated with BC.

Sex disparities in treatment patterns after metformin initiation among patients with type 2 diabetes mellitus.

PURPOSE: To assess sex differences in treatment patterns after metformin initiation among type 2 diabetes mellitus (T2D) patients. METHODS: A cohort study was conducted using the Groningen Initiative to ANalyze Type 2 diabetes Treatment (GIANTT) primary care database. Patients aged ≥18 years initiating metformin were followed 2-5 years. Markov modeling was conducted to estimate treatment transition rates and calculate adjusted hazard ratios (aHR) with 95% confidence intervals (CI) comparing men with women adjusted for age, HbA1c level at initiation, and cardiovascular disease history. Kaplan-Meier analyses and Cox proportional-hazards models were used to determine the time to and likelihood of getting treatment intensification. HbA1c levels at initiation and intensification were compared using Mann-Whitney U tests. RESULTS: In total, 11 508 metformin initiators were included (50.1% women). The most common transition after initiation was a dose increase (probability women 0.52, men 0.59, no significant difference). Women were more likely than men to switch to any other non-insulin hypoglycemic agent after initiation (aHR 1.66; 95% CI 1.31-2.12), after dose increase (aHR 1.48; 95% CI 1.10-1.98) and after dose decrease (aHR 2.64; 95% CI 1.28-5.46). Time to intensification was longer, time to switching was shorter, and HbA1c levels at initiation and intensification were lower for women than men. CONCLUSIONS: Sex disparities were observed in treatment transitions after metformin initiation. Women more often switched treatment than men, which suggest that prescribers acknowledge more tolerance or other problems for metformin in women. Men intensified treatment earlier and at higher HbA1c levels, indicative of a higher need for treatment intensification.

Chronic Use of Hydrochlorothiazide and Risk of Skin Cancer in Caucasian Adults: A PharmLines Initiative Inception Cohort Study.

Photosensitizing properties of hydrochlorothiazide may increase skin cancer risk. To date, study findings on the association between hydrochlorothiazide use and skin cancer risk are inconsistent, notably regarding confounding and dose-response. The aim of this study was to investigate the association between hydrochlorothiazide use and incidence of skin cancer in a cohort of unselected Caucasian adults, taking dosing into account. As part of the PharmLines Initiative, which links data from the Lifelines Cohort Study and prescription database IADB.nl, patients aged ≥ 40 years were included from Lifelines, a prospective population-based cohort study in the north of the Netherlands. Skin cancer incidence was compared between subjects starting hydrochlorothiazide treatment (n = 608), subjects starting treatment with other antihypertensives (n = 508), and non-antihypertensive long-term medication users (n = 1,710). Cox regression analyses were performed to obtain hazard ratios, adjusted for potential confounders. The risk of any skin cancer, keratinocyte carcinoma, basal cell carcinoma and squamous cell carcinoma was not significantly increased in general hydrochlorothiazide users. A clear association was observed between high cumulative hydrochlorothiazide use (≥ 5,000 defined daily dose; ≥ 125,000 mg) and the risk of any skin cancer (adjusted hazard ratio 5.32, 95% confidence interval (95% CI) 2.40-11.81), keratinocyte carcinoma (adjusted hazard ratio 7.31, 95% CI 3.12-17.13), basal cell carcinoma (adjusted hazard ratio 7.72, 95% CI 3.11-19.16) and squamous cell carcinoma (adjusted hazard ratio 19.63, 95% CI 3.12-123.56). These findings should lead to awareness with high use of hydrochlorothiazide in Caucasian adults.

Exposure to psychotropic drugs before and during pregnancy: what has changed over the last two decades?

Trends in prescribing psychotropic drugs before and during pregnancy may have changed over the years, but actual information is lacking. We therefore compared and assessed the exposure and acceptance rates of classes of antipsychotic (+ lithium), anxiolytic, sedative/hypnotic, antidepressant, and psychostimulant before and during pregnancy in the past two decades. All singleton pregnancies with ≥1 prescription of psychotropic drug from six months before pregnancy until child's birthdate were identified in the pregnancy subset of the IADB.nl prescription database. The prescription patterns of psychotropics were distinguished as continuation rate (CR), initiation rate (IR), discontinuation rate (DR), total exposure rate (TER), and acceptance rate. Singleton pregnancies exposed to psychotropic drugs before and during pregnancy increased from 118.4 to 136.5 (per 1000 singleton pregnancies) between decades. Changing trends were observed in decade 2, including a high increase in the TER of antipsychotic class (3.3 to 6.8) and antidepressant class (23.0 to 40.6). A marked increase for individual drugs was seen for sertraline (TER: 0.6 to 6.6 and PAT: 35.3% to 82.5%), citalopram (TER: 2.3 to 10.0 and PAT: 51.1% to 74.6%), and quetiapine (TER: 0.4 to 3.1 and PAT: 57.1% to 66.0%). Although the total exposure rates of five classes of psychotropics in singleton pregnancies increased in decade 2, only antidepressant class had a higher acceptance rate during pregnancy. Certain SSRI antidepressants and atypical antipsychotics were more frequently prescribed in decade 2 than in decade 1, reflecting that treatment options were preferred for safer treatment choices.

Switching pattern and dose adjustment of antidepressants before and during pregnancy.

The purpose of the study is to examine the switching pattern and dose adjustment of antidepressants (ADs) prescribed to women from six months before to six months during pregnancy in the Netherlands. The recorded dispenses or refills were collected from the University of Groningen IADB.nl pregnancy subset for all singleton pregnancies in which the mother received ≥ 1 prescription of an AD dispensed before pregnancy and was present in the database at least six months after conception. The rates of continuation, discontinuation, and switching between 2001 and 2020 were assessed for the ADs studied. The mean number of Defined Daily Doses (DDDs) of the most frequently continued ADs used was calculated both before and during pregnancy, and a paired t-test was used to test for significant changes. The continuation rates for AD users, especially for SSRI and SNRI continued users, increased over time from 27% and 19% (2001-2005) to 65% and 65% (2016-2020). The switching rate between ADs remained consistently low from the start of the study (2001-2005) at 2.0% to the end of the study (2016-2020) at 2.3%. Most women who switched between antidepressants during pregnancy received a different SSRI monotherapy (85%), followed by an SNRI (6%), a TCA (4%), and an "other AD" (4%). In most cases observed, the dose adjustment for the mean DDDs during pregnancy compared to the mean DDDs before pregnancy only changed little (less than 10%). Continued use of SSRIs among singleton pregnancies doubled over the study period. The low rate of AD switching and little changes in the DDD adjustment for most AD continuers indicate that pregnant women prefer to continue their prepregnancy medication rather than switch it. Most observed findings cohere with the Dutch national guidelines for antidepressant use during pregnancy.

Attitudes towards deprescribing and patient-related factors associated with willingness to stop medication among older patients with type 2 diabetes (T2D) in Indonesia: a cross-sectional survey study.

BACKGROUND: Deprescribing of preventive medication is recommended in older patients with polypharmacy, including people with type 2 diabetes (T2D). It seems that many patients in low-middle-income countries are not willing to have their medicines deprescribed. This study aims to assess attitudes of Indonesian patients with T2D towards deprescribing in general and regarding specific cardiometabolic medicines, and factors influencing their willingness to stop medicines. METHODS: Primary care patients with T2D of ≥60 years in Indonesia completed the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire. Attitudes in general and for cardiometabolic medicines were reported descriptively. Proportions of patients willing to stop one or more medicines when recommended by different healthcare professionals were compared with Chi-square test. Multiple regression analysis was used to analyse the influence between patient-related factors and the willingness to stop medicines. RESULTS: The survey was completed by 196 participants (median age 69 years, 73% female). The percentages willing to stop medicines were 69, 67, and 41%, when the general practitioner (GP), the specialist, or the pharmacist initiates the process (p-value < 0.001). Higher perceived burden of medicines (p-value = 0.03) and less concerns about stopping (p-value < 0.001) were associated with a higher willingness to stop medicines if proposed by the GP. Patients using multiple glucose-regulating medicines were less willing to stop (p-value = 0.02). Using complementary or alternative medicines was not associated with the willingness to stop. If proposed by their pharmacist, patients without substantial education were more willing to stop than educated patients. CONCLUSIONS: Only two-thirds of older people with T2D in Indonesia were willing to stop one or more of their medicines if the GP or specialist recommended this, and even less when the pharmacist proposed this. Attention should be given to concerns about stopping specific medicines, especially among patients using multiple glucose-lowering medicines, who may be more eligible but were less willing to accept deprescribing.