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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 × 1â 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.
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Cobertura Vacinal , Humanos , Nigéria/epidemiologia , Lactente , Cobertura Vacinal/estatística & dados numéricos , Feminino , Masculino , Pré-Escolar , Teorema de Bayes , Programas de Imunização , Vacinação/estatística & dados numéricos , Prevalência , Criança , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagemRESUMO
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.
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Esclerose Múltipla Recidivante-Remitente , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Estudos Observacionais como Assunto/métodos , Resultado do Tratamento , Projetos de PesquisaRESUMO
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.
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Antipsicóticos , COVID-19 , Humanos , Adolescente , Antipsicóticos/uso terapêutico , Países Baixos/epidemiologia , COVID-19/epidemiologia , Feminino , Masculino , Criança , Adulto Jovem , Prescrições de Medicamentos/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Prevalência , SARS-CoV-2RESUMO
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.
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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.
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Neoplasias da Mama , Detecção Precoce de Câncer , Feminino , Humanos , Neoplasias da Mama/diagnóstico por imagem , Anos de Vida Ajustados por Deficiência , Mamografia , Efeitos Psicossociais da DoençaRESUMO
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.
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Diabetes Mellitus Tipo 2 , Metformina , Humanos , Feminino , Masculino , Adolescente , Adulto , Metformina/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Estudos de Coortes , Hemoglobinas Glicadas , Estudos Retrospectivos , Quimioterapia Combinada , Hipoglicemiantes/uso terapêuticoRESUMO
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.
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Carcinoma Basocelular , Carcinoma de Células Escamosas , Neoplasias Cutâneas , Humanos , Adulto , Hidroclorotiazida/efeitos adversos , Estudos de Coortes , Estudos Prospectivos , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/tratamento farmacológico , Carcinoma Basocelular/induzido quimicamente , Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/tratamento farmacológico , Carcinoma de Células Escamosas/epidemiologia , Fatores de RiscoRESUMO
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.
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Ansiolíticos , Antipsicóticos , Gravidez , Criança , Feminino , Humanos , Antipsicóticos/uso terapêutico , Psicotrópicos/uso terapêutico , Antidepressivos/uso terapêutico , Ansiolíticos/uso terapêutico , Prescrições de MedicamentosRESUMO
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.
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Inibidores da Recaptação de Serotonina e Norepinefrina , Feminino , Humanos , Gravidez , Antidepressivos/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina , Países BaixosRESUMO
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.
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Doenças Cardiovasculares , Desprescrições , Diabetes Mellitus Tipo 2 , Clínicos Gerais , Humanos , Feminino , Idoso , Masculino , Estudos Transversais , Indonésia/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Inquéritos e Questionários , PolimedicaçãoRESUMO
INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic accelerated the provision of telepharmacy services. However, little is known about the knowledge, perception, and willingness of pharmacy students as future key players in telepharmacy adoption to provide such a service, particularly in a setting without well-established telepharmacy services before the COVID-19 pandemic. OBJECTIVE: With this survey we aimed to assess the level of knowledge, perception, and willingness to provide telepharmacy services and to identify associated factors among pharmacy students in Indonesia. METHODS: We applied a multicenter cross-sectional study design with convenience sampling technique among pharmacy students in three public universities in Bandung City, Surabaya City, and Special Region of Yogyakarta, Indonesia. The knowledge, perception, and willingness to provide telepharmacy services were assessed using an online questionnaire. Ordinal regression analysis was performed to determine factors associated with a high knowledge level, whereas binary logistic regression analyses were performed to determine factors associated with a positive perception of telepharmacy services. Odds ratios (ORs) with 95% confidence intervals (CIs) were reported. RESULTS: Among 313 respondents, 83.4% were female, and the mean age was 20 years. Although only 13.2% showed a high knowledge level, 66.5% showed a positive perception of telepharmacy services and 97.4% were willing to provide telepharmacy services in the future. An increase in age (OR 1.33; 95% CI 1.14-1.54) and being advance in smartphone usage (OR 5.21; 95% CI 2.03-13.42) are associated with an increased likelihood of having a high knowledge level about telepharmacy services. Male students had a lower likelihood of having a positive perception of telepharmacy services than females (OR 0.46; 95% CI 0.24-0.85). CONCLUSION: Despite limited knowledge of telepharmacy, the majority of pharmacy students reported a positive perception and willingness to provide telepharmacy services in their future careers. Therefore, telepharmacy practice models must be included as a subject course in the curriculum, better preparing future pharmacists to perform their roles effectively. Furthermore, student-specific factors such as age and expertise in smartphone usage that associated with knowledge and gender that associated with perception should be considered to facilitate telepharmacy adoption in Indonesia.
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COVID-19 , Estudantes de Farmácia , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Estudos Transversais , Indonésia , Pandemias , COVID-19/epidemiologia , PercepçãoRESUMO
PURPOSE: Varenicline is an effective treatment for smoking cessation. While clinical trials did not confirm a causal role, case reports suggested a possible link of varenicline with neuropsychiatric adverse drug events (NPAEs). This study aims to investigate the risk of NPAEs associated with varenicline initiation among the general population in a real-world setting. METHODS: We conducted a sequence symmetry analysis (SSA) based on the University of Groningen IADB.nl prescription database. We selected incident users of both varenicline and marker drugs for NPAEs, including depression, anxiety and sleep disorder within different time-intervals. Adjusted sequence ratios (aSR) were calculated for each time-interval. RESULTS: Within 365-days' time-interval 1066 patients were incident users of both varenicline and NPAE marker drugs. In total, 505 patients were prescribed varenicline before NPAE marker drugs and 561 vice versa (crude sequence ratio [cSR] 0.90, 95% CI: 0.80-1.02). After adjustments for trends in prescriptions, overall a null association was found (aSR 1.00, 95% CI: 0.89-1.13). Regarding specific NPAEs, no increased risks were found for depression nor anxiety within any time-interval. A small transient increased risk was found for sleep disorders, particularly in earlier time-intervals 3 and 6 months (aSRs 1.52, 95% CI: 1.10-2.11 and 1.45, 95% CI: 1.15-1.83, respectively). Subgroup and sensitivity analyses showed similar findings. CONCLUSIONS: Varenicline initiation was unlikely to be associated with an increased risk of taking anti-depressants nor anti-anxiety drugs. Yet a small, but statistically significant, transient association with drugs for sleep disorders was noticed, possibly associated with withdrawal symptoms caused by smoking cessation.
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Abandono do Hábito de Fumar , Benzazepinas , Bupropiona , Humanos , Quinoxalinas/efeitos adversos , Vareniclina/efeitos adversosRESUMO
BACKGROUND: Although antibiotic treatment is recommended for acute exacerbations of chronic obstructive pulmonary disease (AECOPD), its value in real-world settings is still controversial. OBJECTIVES: This study aimed to evaluate the short- and long-term effects of antibiotic treatment on AECOPD outpatients. METHODS: A cohort study was conducted under the PharmLines Initiative. We included participants with a first recorded diagnosis of COPD who received systemic glucocorticoid treatment for an AECOPD episode. The exposed and reference groups were defined based on any antibiotic prescription during the AECOPD treatment. The short-term outcome was AECOPD treatment failure within 14-30 days after the index date. The long-term outcome was time to the next exacerbation. Adjustment for confounding was made using propensity scores. RESULTS: Of the 1,105 AECOPD patients, antibiotics were prescribed to 518 patients (46.9%) while 587 patients (53.1%) received no antibiotics. The overall antibiotic use was associated with a relative risk reduction of AECOPD treatment failure by 37% compared with the reference group (adjusted odds ratio [aOR] 0.63 [95% CI: 0.40-0.99]). Protective effects were similar for doxycycline, macrolides, and co-amoxiclav, although only the effect of doxycycline was statistically significant (aOR 0.53 [95% CI: 0.28-0.99]). No protective effect was seen for amoxicillin (aOR 1.49 [95% CI: 0.78-2.84]). The risk of and time to the next exacerbation was similar for both groups. CONCLUSION: Overall, antibiotic treatment, notably with doxycycline, supplementing systemic glucocorticoids reduces short-term AECOPD treatment failure in real-world outpatient settings. No long-term beneficial effects of antibiotic treatment on AECOPD were found for the prevention of subsequent exacerbations.
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Doxiciclina , Doença Pulmonar Obstrutiva Crônica , Antibacterianos/uso terapêutico , Estudos de Coortes , Progressão da Doença , Doxiciclina/uso terapêutico , Humanos , Pacientes AmbulatoriaisRESUMO
BACKGROUND: Nonadherence to medication in tuberculosis (TB) hampers optimal treatment outcomes. Digital health technology (DHT) seems to be a promising approach to managing problems of nonadherence to medication and improving treatment outcomes. OBJECTIVE: This paper systematically reviews the effect of DHT in improving medication adherence and treatment outcomes in patients with TB. METHODS: A literature search in PubMed and Cochrane databases was conducted. Randomized controlled trials (RCTs) that analyzed the effect of DHT interventions on medication adherence outcomes (treatment completion, treatment adherence, missed doses, and noncompleted rate) and treatment outcomes (cure rate and smear conversion) were included. Adult patients with either active or latent TB infection were included. The Jadad score was used for evaluating the study quality. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline was followed to report study findings. RESULTS: In all, 16 RCTs were selected from 552 studies found, and 6 types of DHT interventions for TB were identified: 3 RCTs examined video directly observed therapy (VDOT), 1 examined video-observed therapy (VOT), 1 examined an ingestible sensor, 1 examined phone call reminders, 2 examined medication monitor boxes, and 8 examined SMS text message reminders. The outcomes used were treatment adherence, including treatment completion, treatment adherence, missed dose, and noncompleted rate, as well as clinical outcomes, including cure rate and smear conversion. In treatment completion, 4 RCTs (VDOT, VOT, ingestible sensor, SMS reminder) found significant effects, with odds ratios and relative risks (RRs) ranging from 1.10 to 7.69. Treatment adherence was increased in 1 study by SMS reminders (RR 1.05; 95% CI 1.04-1.06), and missed dose was reduced in 1 study by a medication monitor box (mean ratio 0.58; 95% CI 0.42-0.79). In contrast, 3 RCTs of VDOT and 3 RCTs of SMS reminders did not find significant effects for treatment completion. Moreover, no improvement was found in treatment adherence in 1 RCT of VDOT, missed dose in 1 RCT of SMS reminder, and noncompleted rate in 1 RCT of a monitor box, and 2 RCTs of SMS reminders. For clinical outcomes such as cure rate, 2 RCTs reported that phone calls (RR 1.30; 95% CI 1.07-1.59) and SMS reminders (OR 2.47; 95% CI 1.13-5.43) significantly affected cure rates. However, 3 RCTs found that SMS reminders did not have a significant impact on cure rate or smear conversion. CONCLUSIONS: It was found that DHT interventions can be a promising approach. However, the interventions exhibited variable effects regarding effect direction and the extent of improving TB medication adherence and clinical outcomes. Developing DHT interventions with personalized feedback is required to have a consistent and beneficial effect on medication adherence and outcomes among patients with TB.
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Telefone Celular , Envio de Mensagens de Texto , Tuberculose , Adulto , Tecnologia Biomédica , Humanos , Adesão à Medicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistemas de Alerta , Resultado do TratamentoRESUMO
BACKGROUND: While Alzheimer disease (AD) and vascular dementia (VaD) may be accelerated by hypercholesterolemia, the mechanisms underlying this association are unclear. We tested whether dysregulation of cholesterol catabolism, through its conversion to primary bile acids (BAs), was associated with dementia pathogenesis. METHODS AND FINDINGS: We used a 3-step study design to examine the role of the primary BAs, cholic acid (CA), and chenodeoxycholic acid (CDCA) as well as their principal biosynthetic precursor, 7α-hydroxycholesterol (7α-OHC), in dementia. In Step 1, we tested whether serum markers of cholesterol catabolism were associated with brain amyloid accumulation, white matter lesions (WMLs), and brain atrophy. In Step 2, we tested whether exposure to bile acid sequestrants (BAS) was associated with risk of dementia. In Step 3, we examined plausible mechanisms underlying these findings by testing whether brain levels of primary BAs and gene expression of their principal receptors are altered in AD. Step 1: We assayed serum concentrations CA, CDCA, and 7α-OHC and used linear regression and mixed effects models to test their associations with brain amyloid accumulation (N = 141), WMLs, and brain atrophy (N = 134) in the Baltimore Longitudinal Study of Aging (BLSA). The BLSA is an ongoing, community-based cohort study that began in 1958. Participants in the BLSA neuroimaging sample were approximately 46% male with a mean age of 76 years; longitudinal analyses included an average of 2.5 follow-up magnetic resonance imaging (MRI) visits. We used the Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 1,666) to validate longitudinal neuroimaging results in BLSA. ADNI is an ongoing, community-based cohort study that began in 2003. Participants were approximately 55% male with a mean age of 74 years; longitudinal analyses included an average of 5.2 follow-up MRI visits. Lower serum concentrations of 7α-OHC, CA, and CDCA were associated with higher brain amyloid deposition (p = 0.041), faster WML accumulation (p = 0.050), and faster brain atrophy mainly (false discovery rate [FDR] p = <0.001-0.013) in males in BLSA. In ADNI, we found a modest sex-specific effect indicating that lower serum concentrations of CA and CDCA were associated with faster brain atrophy (FDR p = 0.049) in males.Step 2: In the Clinical Practice Research Datalink (CPRD) dataset, covering >4 million registrants from general practice clinics in the United Kingdom, we tested whether patients using BAS (BAS users; 3,208 with ≥2 prescriptions), which reduce circulating BAs and increase cholesterol catabolism, had altered dementia risk compared to those on non-statin lipid-modifying therapies (LMT users; 23,483 with ≥2 prescriptions). Patients in the study (BAS/LMT) were approximately 34%/38% male and with a mean age of 65/68 years; follow-up time was 4.7/5.7 years. We found that BAS use was not significantly associated with risk of all-cause dementia (hazard ratio (HR) = 1.03, 95% confidence interval (CI) = 0.72-1.46, p = 0.88) or its subtypes. We found a significant difference between the risk of VaD in males compared to females (p = 0.040) and a significant dose-response relationship between BAS use and risk of VaD (p-trend = 0.045) in males.Step 3: We assayed brain tissue concentrations of CA and CDCA comparing AD and control (CON) samples in the BLSA autopsy cohort (N = 29). Participants in the BLSA autopsy cohort (AD/CON) were approximately 50%/77% male with a mean age of 87/82 years. We analyzed single-cell RNA sequencing (scRNA-Seq) data to compare brain BA receptor gene expression between AD and CON samples from the Religious Orders Study and Memory and Aging Project (ROSMAP) cohort (N = 46). ROSMAP is an ongoing, community-based cohort study that began in 1994. Participants (AD/CON) were approximately 56%/36% male with a mean age of 85/85 years. In BLSA, we found that CA and CDCA were detectable in postmortem brain tissue samples and were marginally higher in AD samples compared to CON. In ROSMAP, we found sex-specific differences in altered neuronal gene expression of BA receptors in AD. Study limitations include the small sample sizes in the BLSA cohort and likely inaccuracies in the clinical diagnosis of dementia subtypes in primary care settings. CONCLUSIONS: We combined targeted metabolomics in serum and amyloid positron emission tomography (PET) and MRI of the brain with pharmacoepidemiologic analysis to implicate dysregulation of cholesterol catabolism in dementia pathogenesis. We observed that lower serum BA concentration mainly in males is associated with neuroimaging markers of dementia, and pharmacological lowering of BA levels may be associated with higher risk of VaD in males. We hypothesize that dysregulation of BA signaling pathways in the brain may represent a plausible biologic mechanism underlying these results. Together, our observations suggest a novel mechanism relating abnormalities in cholesterol catabolism to risk of dementia.
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Ácidos e Sais Biliares/metabolismo , Demência/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Ácidos e Sais Biliares/biossíntese , Demência/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Incidência , Masculino , Metabolômica , Pessoa de Meia-Idade , Farmacoepidemiologia , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Circulating desphospho-uncarboxylated matrix γ-carboxyglutamate (Gla) protein (dp-ucMGP), a marker of vitamin K status, is associated with renal function and may serve as a potentially modifiable risk factor for incident chronic kidney disease (CKD). We aimed to assess the association between circulating dp-ucMGP and incident CKD. METHODS: We included 3969 participants with a mean age of 52.3 ± 11.6 years, of whom 48.0% were male, enrolled in the general population-based Prevention of REnal and Vascular ENd-stage Disease study. Study outcomes were incident CKD, defined as either development of an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 or microalbuminuria. Associations of dp-ucMGP with these outcomes were quantified using Cox proportional hazards models and were adjusted for potential confounders. RESULTS: Median plasma dp-ucMGP was 363 [interquartile range (IQR) 219-532] pmol/L and mean serum creatinine- and serum cystatin C-based eGFR (eGFRSCr-SCys) was 95.4 ± 21.8 mL/min/1.73 m2. During 7.1 years of follow-up, 205 (5.4%) participants developed incident CKD and 303 (8.4%) developed microalbuminuria. For every doubling of plasma dp-ucMGP, hazard ratios for the development of incident CKD and microalbuminuria were 1.85 [95% confidence interval (CI) 1.59-2.16; P < 0.001] and 1.19 (95% CI 1.07-1.32; P = 0.001), respectively. These associations lost significance after adjustment for baseline eGFRSCr-SCys [0.99 (95% CI 0.88-1.12; P = 0.86)] and baseline age [1.03 (95% CI 0.94-1.14; P = 0.50)], respectively. CONCLUSIONS: The associations of plasma dp-ucMGP with incident CKD and microalbuminuria were driven by the respective baseline effects of renal function and age.
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Insuficiência Renal Crônica , Vitamina K , Adulto , Biomarcadores , Proteínas de Ligação ao Cálcio , Estudos de Coortes , Proteínas da Matriz Extracelular/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologiaRESUMO
AIM: To assess the effects of a targeted and tailored pharmacist-led intervention among patients with type 2 diabetes (T2DM) who are nonadherent to antihypertensive drugs. METHODS: A cluster-randomised controlled trial was conducted in 10 community health centres (CHCs) in Indonesia among T2DM patients aged ≥18 years who reported nonadherence to antihypertensive drugs according to the Medication Adherence Report Scale (MARS-5). Patients in CHCs randomised to the intervention group received a tailored intervention based on their adherence barriers (eg, forgetfulness, lack of knowledge, lack of motivation and/or other drug-related problems) using a simple question-based flowchart at baseline and 1-month follow-up. Patients in control CHCs received usual care. Primary outcome was the between-group difference in change in MARS-5 score from baseline to 3-month follow-up. Secondary outcomes included changes in patients' blood pressure and their medication beliefs. Differences in difference in primary and secondary outcomes between groups were assessed using general linear models. RESULTS: In total, 201 patients were screened for eligibility, 113 met the inclusion criteria and participated, and 89 (79%) patients had complete follow-up. Forgetfulness (42%) and lack of knowledge (18%) were the most common adherence barriers identified at baseline. The intervention improved medication adherence by 4.62 points on the MARS-5 scale (95% CI 0.93 to 8.34, P value = 0.008). There were no significant changes in blood pressure levels and beliefs about antihypertensive drugs. CONCLUSION: A tailored low-cost pharmacist-led intervention aimed at nonadherent T2DM patients resulted in an improvement in medication adherence to antihypertensive drugs. There were no significant changes in secondary outcomes.
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Anti-Hipertensivos , Diabetes Mellitus Tipo 2 , Adolescente , Adulto , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Indonésia/epidemiologia , Adesão à Medicação , FarmacêuticosRESUMO
AIMS: Polypharmacy is common in people with diabetes and is associated with the use of potentially inappropriate medication (PIM). This study aimed to assess trends in the prevalence of polypharmacy and PIM in older and middle-aged people with diabetes. METHODS: A repeated cross-sectional study using the University Groningen IADB.nl prescription database was conducted. All people aged 45 years and over who were treated for diabetes registered in the period 2012-2016 were included. Polypharmacy was assessed for three age groups. PIMs were assessed using Beers criteria for people ≥65 years old, and PRescribing Optimally in Middle-aged People's Treatments (PROMPT) criteria for 45-64 years old. Chi-square tests and regression analysis were applied. RESULTS: The prevalence of polypharmacy increased significantly in all age groups in the study period. In 2016, the prevalence of polypharmacy was 36.9% in patients aged 45-54 years, 50.3% in those aged 55-64 years, and 66.2% in those aged ≥65 years. The prevalence of older people with at least one PIM decreased by 3.1%, while in the middle-aged group this prevalence increased by 0.9% from 2012 to 2016. The most common PIMs in both age groups were the use of long-term high-dose proton pump inhibitors, benzodiazepines and strong opioids without laxatives. Of those, only benzodiazepines showed a decreasing trend. CONCLUSIONS: Polypharmacy increased in older and middle-aged people with diabetes. While the prevalence of PIM decreased over time in older age, this trend was not observed in middle-aged people with diabetes. Efforts are needed to decrease the use of PIMs in populations already burdened with many drugs, notably at middle age.
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Diabetes Mellitus , Lista de Medicamentos Potencialmente Inapropriados , Idoso , Estudos Transversais , Humanos , Prescrição Inadequada , Pessoa de Meia-Idade , Polimedicação , PrevalênciaRESUMO
BACKGROUND: Previously treated tuberculosis (TB) patients are a widely reported risk factor for multidrug-resistant tuberculosis. Identifying patients' problems during treatment is necessary to control TB, especially in a high-burden setting. We therefore explored barriers to successful TB treatment from the patients' perspective, aiming to identify potential patient-centred care strategies to improve TB treatment outcome in Indonesia. METHODS: A qualitative study was conducted in a province of Indonesia with high TB prevalence. Participants from various backgrounds (i.e., TB patients, physicians, nurses, pharmacists, TB activist, TB programmers at the district and primary care levels) were subject to in-depth interviews and focus group discussions (FGDs). All interviews and FGDs were transcribed verbatim from audio and visual recordings and the respective transcriptions were used for data analysis. Barriers were constructed by interpreting the codes' pattern and co-occurrence. The information's trustworthiness and credibility were established using information saturation, participant validation and triangulation approaches. Data were inductively analysed using the Atlas.ti 8.4 software and reported following the COREQ 32-items. RESULTS: We interviewed 63 of the 66 pre-defined participants and identified 15 barriers. The barriers were classified into three themes, i.e., socio-demography and economy; knowledge and perception and TB treatment. Since the barriers can be interrelated, we determined five main barriers across all barrier themes, i.e., lack of TB knowledge, stigmatisation, long distance to the health facility, adverse drug reaction and loss of household income. CONCLUSION: The main treatment barriers can be considered to strengthen patient-centred care for TB patients in Indonesia. A multi-component approach including TB patients, healthcare providers, broad community and policy makers is required to improve TB treatment success.
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Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose , Grupos Focais , Pessoal de Saúde , Humanos , Pesquisa Qualitativa , Tuberculose/tratamento farmacológicoRESUMO
BACKGROUND: From January to May 2019, large measles outbreaks affected Nigeria. Borno state was the most affected, recording 15,237 suspected cases with the state capital of Maiduguri having 1125 cases investigated and line-listed by March 2019. In Borno state, 22 of the 27 Local Government Areas (LGAs or Districts), including 37 internally displaced persons (IDPs) camps were affected. In response to the situation, an outbreak response immunization (ORI) campaign was conducted in the 13 most affected LGAs. In addition to conventional vaccination teams, special teams were deployed in security compromised areas, areas with migrants, and for nomadic and IDPs. Here we describe the outbreak and the ORI campaign. We also assess the measles-containing vaccine (MCV) coverage and vaccine effectiveness (VE) in order to quantify the population-level impact. METHODS: We reviewed the ORI activities, and conducted an analysis of the surveillance and the outbreak investigation reports. We assessed VE of MCV by applying the screening-method. Sensitivity analyses were also conducted to assess the effect of final classification of cases on the VE of MCV. The MCV coverage was assessed by a post-campaign coverage survey after completion of the ORI through a quantitative survey in the 12 LGAs that were accessible. RESULTS: Of the total 15,237 reported measles cases, 2002 cases were line-listed and investigated, and 737 were confirmed for measles by week 9 of 2019. Of the investigated cases 67.3% (n = 1348) were between 9 and 59 months of age. Among the 737 confirmed cases, only 9% (n = 64) stated being vaccinated with at least 1 dose of MCV. The overall VE for MCV was 98.4% (95%CI: 97.8-98.8). No significant differences were observed in the VE estimates of lab-confirmed and epi-linked cases when compared to the original estimates. The aggregated weighted vaccination coverage was 85.7% (95% CI: 79.6-90.1). CONCLUSION: The experience in Borno demonstrates that adequate VE can be obtained in conflict-affected areas. In complex emergencies affected by measles outbreaks, health authorities may consider integration with other health strategies and the engagement of security personnel as part of the ORI activities.