Impact of the COVID-19 pandemic on antidepressant consumption in the Central region of Portugal: interrupted time series.

PURPOSE: To evaluate the impact of the pandemic on the consumption of antidepressive agents in Central Portugal. METHODS: To estimate the causal effect of the pandemic an interrupted time series analysis was conducted. Data of antidepressant drugs monthly dispensed in community pharmacies between Jan-2010 and Dec-2021 were provided by the regional Health Administration. Anti-Parkinson dopaminergic agents and statins, theoretically not influenced by COVID-19 pandemics, were used as comparator series. The number of packages was converted into defined daily doses and presented as defined daily doses/1000 inhabitants/day. A Bayesian structural time-series model with CausalImpact on R/RStudio was used to predict the counterfactual. Analyses with different geographical granularity (9 sub-regions and 78 municipalities) were performed. RESULTS: When compared to counterfactual, regional consumption non-significantly increased after the pandemic declaration, with a relative effect of + 1.30% [95%CI -1.6%:4.2%]. When increasing the granularity, differences appeared between sub-region with significant increases in Baixo Mondego + 6.5% [1.4%:11.0%], Guarda + 4.4% [1.1%:7.7%] or Cova da Beira + 4.1% [0.17%:8.3%], but non-significant variation in the remaining 6 sub-regions. Differences are more obvious at municipality level, ranging from increases of + 37.00% [32.00%:42.00%] to decreases of -11.00% [-17.00%:-4.20%]. Relative impact positively correlated with percentage of elderly in the municipality (r = 0.301; p = 0.007), and negatively with population density (r=-0.243; p = 0.032). No other predicting variables were found. CONCLUSION: Antidepressant consumption suffered very slight variations at regional level after the COVID-19 pandemic declaration. Analysis with higher granularity allowed identifying municipalities with higher impact (increase or decrease). The absence of clear association patterns suggests other causal hypotheses of the differences.

Impact of COVID-19 on tuberculosis notifications.

The COVID-19 pandemic has significantly impacted the control of diseases by overwhelming healthcare systems, and tuberculosis (TB) notifications may have been affected. This study aimed to analyze the impact of COVID-19 on TB notifications in the Sao Paulo State. This is a retrospective study examining TB notifications extracted from the TBweb database (Jan 2015 to Dec 2022). We conducted an interrupted time series (ITS) analysis of TB notifications using the declaration of the COVID-19 pandemic as the interrupting event (Bayesian causal impact analysis). A total of 177,103 notifications of TB incident cases were analyzed, revealing a significant decrease in 2020 (13%) and in 2021 (9%), which lost significance in 2022. However, changes were not associated with population density or the area of the regions. Future analyses of the effects of TB underdiagnosis might help describe the impact of underreporting on future TB incidence and mortality.

Influence of automated indexing in Medical Subject Headings (MeSH) selection for pharmacy practice journals.

BACKGROUND: The Medical Subject Headings (MeSH) thesaurus is the controlled vocabulary used to index articles in MEDLINE. MeSH were mainly manually selected until June 2022 when an automated algorithm, the Medical Text Indexer (MTI) automated was fully implemented. A selection of automated indexed articles is then reviewed (curated) by human indexers to ensure the quality of the process. OBJECTIVE: To describe the association of MEDLINE indexing methods (i.e., manual, automated, and automated + curated) on the MeSH assignment in pharmacy practice journals compared with medical journals. METHODS: Original research articles published between 2016 and 2023 in two groups of journals (i.e., the Big-five general medicine and three pharmacy practice journals) were selected from PubMed using journal-specific search strategies. Metadata of the articles, including MeSH terms and indexing method, was extracted. A list of pharmacy-specific MeSH terms had been compiled from previously published studies, and their presence in pharmacy practice journal records was investigated. Using bivariate and multivariate analyses, as well as effect size measures, the number of MeSH per article was compared between journal groups, geographic origin of the journal, and indexing method. RESULTS: A total of 8479 original research articles was retrieved: 6254 from the medical journals and 2225 from pharmacy practice journals. The number of articles indexed by the various methods was disproportionate; 77.8 % of medical and 50.5 % of pharmacy manually indexed. Among those indexed using the automated system, 51.1 % medical and 10.9 % pharmacy practice articles were then curated to ensure the indexing quality. Number of MeSH per article varied among the three indexing methods for medical and pharmacy journals, with 15.5 vs. 13.0 in manually indexed, 9.4 vs. 7.4 in automated indexed, and 12.1 vs. 7.8 in automated and then curated, respectively. Multivariate analysis showed significant effect of indexing method and journal group in the number of MeSH attributed, but not the geographical origin of the journal. CONCLUSIONS: Articles indexed using automated MTI have less MeSH than manually indexed articles. Articles published in pharmacy practice journals were indexed with fewer number of MeSH compared with general medical journal articles regardless of the indexing method used.

Clinical pharmacy key performance indicators for hospital inpatient setting: a systematic review.

BACKGROUND: Key performance indicators (KPIs) are quantifiable measures used to monitor the quality of health services. Implementation guidelines for clinical pharmacy services (CPS) do not specify KPIs. AIM: To assess the quality of the studies that have developed KPIs for CPS in inpatient hospital settings. METHOD: A systematic review was conducted by searching in Web of Science, Scopus, and PubMed, supplemented with citation analyses and grey literature searches, to retrieve studies addressing the development of KPIs in CPS for hospital inpatients. Exclusions comprised drug- or disease-specific studies and those not written in English, French, Portuguese, or Spanish. The Appraisal of Indicators through Research and Evaluation (AIRE) instrument assessed methodological quality. Domain scores and an overall score were calculated using an equal-weight principle. KPIs were classified into structure, process, and outcome categories. The protocol is available at https://doi.org/10.17605/OSF.IO/KS2G3 . RESULTS: We included thirteen studies that collectively developed 225 KPIs. Merely five studies scored over 50% on the AIRE instrument, with domains #3 (scientific evidence) and #4 (formulation and usage) displaying low scores. Among the KPIs, 8.4% were classified as structure, 85.8% as process, and 5.8% as outcome indicators. The overall methodological quality did not exhibit a clear association with a major focus on outcomes. None of the studies provided benchmarking reference values. CONCLUSION: The KPIs formulated for evaluating CPS in hospital settings primarily comprised process measures, predominantly suggested by pharmacists, with inadequate evidence support, lacked piloting or validation, and consequently, were devoid of benchmarking reference values.

Data quality review of the Brazilian nosocomial infections surveillance system.

BACKGROUND: Surveillance of healthcare-associated infections (HAIs) is an essential component of hospital infection prevention and control systems. We aimed to assess the quality of the data compiled by the Brazilian HAI Surveillance System from pediatric (PICUs) and neonatal intensive care units (NICUs), between 2012 and 2021. METHODS: Data Quality Review, including adherence, completeness, internal consistency, consistency over time, and consistency of population trend, were computed at both national and state levels based on quality metrics from World Health Organization Toolkit. Incidence rates (or incidence density) of ventilator-associated pneumonia (VAP) and central line-associated bloodstream infection (CLABSI) were obtained from the Brazilian National Nosocomial Infections Surveillance (NNIS) system. Data on sepsis-related mortality, spanning the period from 2012 to 2021, were extracted from the Brazilian National Health Service database (DATASUS). Additionally, correlations between sepsis-related mortality and incidence rates of VAP or CLABSI were calculated. RESULTS: Throughout the majority of the study period, adherence to VAP reporting remained below 75%, exhibiting a positive trend post-2016. Widespread outliers, as well as inconsistencies over time and in population trends, were evident across all 27 states. Only four states maintained consistent adherence levels above 75% for more than 8 years regarding HAI incidence rates. Notably, CLABSI in NICUs boasted the highest reporting adherence among all HAIs, with 148 periods out of 270 (54.8%) exhibiting reporting adherence surpassing 75%. Three states achieved commendable metrics for CLABSI in PICUs, while five states demonstrated favorable results for CLABSI in NICUs. CONCLUSIONS: While adherence to HAI report is improving among Brazilian states, an important room for improvement in the Brazilian NNIS exists. Additional efforts should be made by the Brazilian government to improve the reliability of HAI data, which could serve as valuable guidance for hospital infection prevention and control policies.

Impact of harm minimization interventions on reducing blood-borne infection transmission and some injecting behaviors among people who inject drugs: an overview and evidence gap mapping.

BACKGROUND: This study aimed to synthetize the evidence on the effectiveness of harm minimization interventions on reducing blood-borne infection transmission and injecting behaviors among people who inject drugs (PWID) through a comprehensive overview of systematic reviews and evidence gap mapping. METHODS: A systematic review was conducted with searches in PubMed and Scopus to identify systematic reviews assessing the impact of interventions aimed at reducing the harms associated with injectable drug use. The overall characteristics of the studies were extracted and their methodological quality was assessed using AMSTAR-2. An evidence gap map was constructed, highlighting the most frequently reported outcomes by intervention (CRD42023387713). RESULTS: Thirty-three systematic reviews were included. Of these, 14 (42.2%) assessed the impact of needle/syringe exchange programs (NSEP) and 11 (33.3%) examined opioid agonist therapy (OAT). These interventions are likely to be associated with reductions of HIV/HCV incidence (10-40% risk reduction for NSEP; 50-60% for OAT) and sharing injecting paraphernalia (50% for NSEP, 25-85% for OAT), particularly when combined (moderate evidence). Behavioral/educational interventions were assessed in 12 reviews (36.4%) with most authors in favor/partially in favor of the use of these approaches (moderate evidence). Take-home naloxone programs and supervised-injection facilities were each assessed in two studies (6.1%), which reported inconclusive results (limited/inconsistent evidence). Most authors reported high levels of heterogeneity and risk of bias. Other interventions and outcomes were inadequately reported. Most systematic reviews presented low or critically low quality. CONCLUSION: The evidence is sufficient to support the effectiveness of OAT, NSEP and their combination in reducing blood-borne infection transmission and certain injecting behaviors among PWID. However, evidence of other harm minimizations interventions in different settings and for some outcomes remain insufficient.

Effects of inpatient creatinine testing frequency on acute kidney injury identification and staging: a historical cohort study.

BACKGROUND: Acute kidney injury (AKI) is a multifactorial condition often induced by drugs commonly used in hospitals. Identifying and staging AKI necessitates frequent monitoring of renal function. AIM: To assess the impact of real-world hospital practices regarding serum creatinine (SCr) testing on the identification and staging of AKI, and its implications for adjusting drug doses. METHOD: A historical cohort study utilizing hospital records from all adult patients admitted between 01/06/2018 and 31/12/2020 was conducted. Patients with no SCr assessment during their stay or those with an SCr at admission ≥ 2 mg/dL were excluded. AKI was determined using two criteria, namely AKIN and KDIGO, considering the time intervals between two SCr tests as outlined in the criteria. Additionally, patients with SCr increases exceeding AKI limits, regardless the time interval, were also identified. The estimated glomerular filtration rate (eGFR) and kinetic eGFR (KeGFR) were calculated. RESULTS: During the study period, 17,269 hospitalizations and 62,255 SCr tests were recorded. Among the 17,032 hospitalizations with a length of stay > 48 h, 46.8% experienced periods with no SCr tests performed for more than 48 h. Any stage of AKI was identified in 7.0% of patients and in 9.1% using AKI and KDIGO criteria, respectively. Ignoring time limits in both criteria revealed potential AKI in 1942 patients (11.2%), indicating a potential underdiagnosis of AKI by 37.5% or 19.1%, depending on the criteria used. A total of 76 drugs requiring dose adjustment in patients with eGFR ≤ 50 ml/min were prescribed in 78.5% admissions. These drugs were prescribed in 87.9% of patients potentially underdiagnosed with AKIN and in 88.9% with KDIGO. CONCLUSION: There is a need for changes in the established hospital procedures to ensure more frequent testing of SCr levels. Implementing an advanced scope of practice for clinical pharmacists could support these changes.

Mapping the concept of health care integration: A lexicographic analysis of scientific literature.

BACKGROUND: Systems fragmentation is a major challenge for an efficient organization, integration being a potential solution also proposed in health care field, including pharmacy as a player. However, the use of different terms and definitions in the literature hinders the comparison of different integration initiatives. OBJECTIVE: To identify and map the terms used in scientific literature regarding integration in health care and to characterize each emerging topic. METHODS: A lexicographic analysis of the integration of healthcare systems literature indexed in PubMed was conducted. Ten different systematic searches, four using only Medical Subject Headings (MeSH) and six using text words, were conducted in March 2023. Journal scattering was analyzed following Bradford's distribution using the Leimkuhler model. An overall text corpus was created with titles and abstracts of all the records retrieved. The corpus was lemmatized, and the most used bigrams were tokenized as single strings. To perform a topic modeling, the lemmatized corpus text was analyzed using IRaMuTeQ, producing descending hierarchic classification and a correspondence analysis. The 50 words with higher chi-square statistics in each class were considered as representative of the class. RESULTS: A total of 42,479 articles published from 1943 to 2023 in 4469 different journals were retrieved. The MeSH "Delivery of Health Care, Integrated", created in the 1996 MeSH update, was the most productive retrieving 33.7 % of the total articles but also retrieving 22.6 % of articles not retrieved in any other search. The text word "Integration" appeared in 15,357 (36.2 %) records. The lexicographic analysis resulted in 7 classes, named as: Evidence and implementation, Quantitative research, Professional education, Qualitative research, Governance and leadership, Clinical research, and Financial resources. Association between the classes and the searches or the text-words used ranged from moderate to weak demonstrating the lack of a standard pattern of use of terms in literature regarding healthcare integration. CONCLUSIONS: The term "integration" and the MeSH "Delivery of Health Care, Integrated" are the most used to represent the concept of integration in healthcare and should be the preferred terms in the literature.

[Variability in Drug Procurement within Group 1B of the Pharmaceutical Specialized Scheme in Brazil]. / Variabilidade de preços de aquisição de medicamentos do grupo 1B do Componente Especializado da Assistência Farmacêutica.

In the Brazilian Health System (SUS), drugs covered by the Specialized Pharmaceutical Scheme (CEAF) receive federal funding and can be procured either centrally (Group 1A) or by individual states (Federal Units - UF) (Group 1B). Unlike other countries where national procurement prices are negotiated centrally by the government, public procurement in Brazil follows a public auction procedure, potentially resulting in varying purchase prices. To facilitate price comparisons, it is a legal requirement to register public acquisitions in the Health Prices Registry (BPS). This study aimed to assess the variability in the procurement prices for Group 1B drugs across the 27 Brazilian states during 2021. Data on the acquisitions of Group 1B drugs by the 27 Health Secretariats were obtained from the BPS. Drugs with no reported reimbursement prices as of December 2021 were excluded from the analysis. The total reimbursement amount for each state was sourced from the SUS Ambulatory Information System. The findings revealed significant variability in drug procurement prices both across and within states. The study underscored a potential disparity in CEAF access, favoring wealthier states (those with larger populations and higher economic status) by securing lower drug prices.

No Sistema Único de Saúde os medicamentos do grupo 1 do Componente Especializado da Assistência Farmacêutica (CEAF) são financiados pela União e adquiridos de forma centralizada (grupo 1A) ou por cada Unidade Federativa (UF) (grupo 1B). Diferentemente de outros países onde se negocia um preço fixo a ser praticado no sistema público, no Brasil as aquisições são realizadas por licitação, o que pode levar a diferentes preços. Para permitir a comparação de preços, foi pactuada a obrigatoriedade de registro das aquisições públicas no Banco de Preços em Saúde (BPS). O estudo teve como objetivo analisar a variabilidade dos preços de medicamentos do grupo 1B adquiridos pelas UF do Brasil em 2021. Foram obtidas as aquisições de medicamentos do grupo 1B realizadas pelas Secretarias de Estado das 27 UF por consulta ao BPS excluindo-se os medicamentos sem preço de ressarcimento estabelecido em dezembro/2021. Foi obtido do Sistema de Informações Ambulatoriais o ressarcimento para cada UF. Verificou-se grande variabilidade dos preços de aquisição para cada medicamento entre as UF e dentro da mesma UF. O estudo demonstrou potencial iniquidade de acesso ao CEAF, privilegiando com menores preços UF mais favorecidas (maior população e riqueza).

Impact of COVID-19 on tuberculosis notifications

ABSTRACT The COVID-19 pandemic has significantly impacted the control of diseases by overwhelming healthcare systems, and tuberculosis (TB) notifications may have been affected. This study aimed to analyze the impact of COVID-19 on TB notifications in the Sao Paulo State. This is a retrospective study examining TB notifications extracted from the TBweb database (Jan 2015 to Dec 2022). We conducted an interrupted time series (ITS) analysis of TB notifications using the declaration of the COVID-19 pandemic as the interrupting event (Bayesian causal impact analysis). A total of 177,103 notifications of TB incident cases were analyzed, revealing a significant decrease in 2020 (13%) and in 2021 (9%), which lost significance in 2022. However, changes were not associated with population density or the area of the regions. Future analyses of the effects of TB underdiagnosis might help describe the impact of underreporting on future TB incidence and mortality.

Discrepancies among equations to estimate the glomerular filtration rate for drug dosing decision making in aged patients: a cross sectional study.

BACKGROUND: Patients often require adjustments to drug doses due to impaired renal function. Glomerular filtration rate (GFR) estimation using various equations can result in discrepancies, potentially leading to different dose adjustment recommendations. AIM: To determine the clinical significance of discrepancies observed between different equations used to estimate GFR for drug dose adjustments in a real-world group of patients over 65 years in primary care. METHOD: The Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Berlin Initiative Study 1 equations were applied to estimate GFR in a group of patients over 65 years old attending a primary care center. Results were compared using Bland-Altman plots, and limits of agreement (LoA) and overall bias were calculated. Regression analyses were conducted to identify the null difference GFR and the slope of differences for each pairwise comparison. RESULTS: A total of 1886 patients were analyzed. Differences between patient-adjusted and body surface area (BSA)-normalized versions of the equations were not clinically relevant for dose adjustments, with LoAs below 20 mL/min. However, discrepancies among the original versions of several equations presented LoAs over 30 mL/min. Greater differences were found between CG and MDRD or CKD-EPI equations. CONCLUSION: Clinically relevant differences in GFR estimation were observed among different equations, potentially impacting drug dose adjustments. However, discrepancies were not considered significant when comparing patient-adjusted and BSA-normalized versions of the equations, particularly for patients with BSA close to the average.

Variabilidade de preços de aquisição de medicamentos do grupo 1B do Componente Especializado da Assistência Farmacêutica / Variability in Drug Procurement within Group 1B of the Pharmaceutical Specialized Scheme in Brazil

Resumo No Sistema Único de Saúde os medicamentos do grupo 1 do Componente Especializado da Assistência Farmacêutica (CEAF) são financiados pela União e adquiridos de forma centralizada (grupo 1A) ou por cada Unidade Federativa (UF) (grupo 1B). Diferentemente de outros países onde se negocia um preço fixo a ser praticado no sistema público, no Brasil as aquisições são realizadas por licitação, o que pode levar a diferentes preços. Para permitir a comparação de preços, foi pactuada a obrigatoriedade de registro das aquisições públicas no Banco de Preços em Saúde (BPS). O estudo teve como objetivo analisar a variabilidade dos preços de medicamentos do grupo 1B adquiridos pelas UF do Brasil em 2021. Foram obtidas as aquisições de medicamentos do grupo 1B realizadas pelas Secretarias de Estado das 27 UF por consulta ao BPS excluindo-se os medicamentos sem preço de ressarcimento estabelecido em dezembro/2021. Foi obtido do Sistema de Informações Ambulatoriais o ressarcimento para cada UF. Verificou-se grande variabilidade dos preços de aquisição para cada medicamento entre as UF e dentro da mesma UF. O estudo demonstrou potencial iniquidade de acesso ao CEAF, privilegiando com menores preços UF mais favorecidas (maior população e riqueza).

Abstract In the Brazilian Health System (SUS), drugs covered by the Specialized Pharmaceutical Scheme (CEAF) receive federal funding and can be procured either centrally (Group 1A) or by individual states (Federal Units - UF) (Group 1B). Unlike other countries where national procurement prices are negotiated centrally by the government, public procurement in Brazil follows a public auction procedure, potentially resulting in varying purchase prices. To facilitate price comparisons, it is a legal requirement to register public acquisitions in the Health Prices Registry (BPS). This study aimed to assess the variability in the procurement prices for Group 1B drugs across the 27 Brazilian states during 2021. Data on the acquisitions of Group 1B drugs by the 27 Health Secretariats were obtained from the BPS. Drugs with no reported reimbursement prices as of December 2021 were excluded from the analysis. The total reimbursement amount for each state was sourced from the SUS Ambulatory Information System. The findings revealed significant variability in drug procurement prices both across and within states. The study underscored a potential disparity in CEAF access, favoring wealthier states (those with larger populations and higher economic status) by securing lower drug prices.

Empirical antimicrobial therapy based on active surveillance cultures in ICU patients

Objetivo: Avaliar o valor preditivo da colonização prévia por Acinetobacter baumannii (CRAB) e Pseudomonas aeruginosa (CRPA) resistente a carbapenêmicos estabelecida em culturas de vigilância para infecção subsequente por esses patógenos em pacientes internados em UTI. Métodos: Foi realizado um estudo de coorte com pacientes internados na unidade de terapia intensiva por pelo menos 48 h. Foram medidos os valores preditivos negativos e positivos, sensibilidade e especificidade das culturas de vigilância em CRAB e CRPA. Resultados: Foram incluídos 693 pacientes infectados. Pacientes previamente colonizados por CRAB e CRPA tiveram maior probabilidade de serem infectados por esses patógenos: OR ajustado: 10,34 (6,58 - 16,45; p < 0,001) e 2,30 (3,88 - 10,26; p < 0,001), respectivamente. Encontramos altos valores preditivos negativos de culturas de vigilância para CRAB (87,18%) e CRPA (88,30%) e alta especificidade 91,96% e 90,13%, respectivamente. Conclusões: Pacientes não colonizados por CRAB e CRPA mostraram-se menos propensos à infecção por esses patógenos. Esses achados podem contribuir para a escolha da terapia antimicrobiana empírica e desencorajar a prescrição de antibióticos contra esses patógenos em pacientes sem colonização prévia.

Objective: To assess the predictive value of prior carbapenem-resistant Acinetobacter baumannii (CRAB) and Pseudomonas aeruginosa (CRPA) colonization established in surveillance cultures for subsequent infection by these pathogens in ICU patients. Methods: A cohort study was performed with patients admitted to the intensive care unit for at least 48 h. Negative and positive predictive values, sensitivity, and specificity of surveillance cultures in CRAB and CRPA were measured. Results: 693 infected patients were included. Patients previously colonized by CRAB and CRPA were more likely to be infected by these pathogens: adjusted OR: 10.34 (6.58 - 16.45; p < 0.001) and 2.30 (3.88 - 10.26; p < 0.001), respectively. We found high negative predictive values of surveillance cultures for CRAB (87.18%) and CRPA (88.30%) and high specificity 91.96% and 90.13%, respectively. Conclusions: Patients not colonized by CRAB and CRPA were less prone to infection by these pathogens. These findings may contribute to the choice of empirical antimicrobial therapy and discourage the prescription of antibiotics against these pathogens in patients without previous colonization.

Heterogeneity in protocols and outcomes to study the effect of renin-angiotensin system blockers in inflammatory bowel disease: A systematic review.

BACKGROUND: The renin-angiotensin system (RAS) has been associated with inflammatory bowel disease (IBD), supporting translational relevance of RAS blockers. Comparability of study design/outcomes is fundamental for data analysis/discussion. OBJECTIVES: We aimed at evaluating the heterogeneity among protocols and outcomes to study the effect of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in IBD. METHODS: This study was performed and reported in accordance with the Cochrane recommendations and PRISMA (PROSPERO-CRD42022323853). Systematic searches were performed in PubMed, Scopus and Web of Science. Studies that met the inclusion criteria were selected. Quality assessment of the studies was done with the SYRCLES's risk of bias tools for animal studies. RESULTS: Thirty-five pre-clinical studies and six clinical studies were included. Chemical induction of colitis was the most used model, but variable doses of the induction agent were reported. All studies reported at least a disease activity index, a macroscopic score, or a histologic assessment, but these scores were methodologically heterogeneous and reported for different characteristics. Great heterogeneity was also found in drug interventions. Inflammatory markers assessed as outcomes were different across studies. CONCLUSION: Lack of standardization of protocols and outcomes among studies threatens the evidence on how RAS blockers influence IBD outcomes.

Development and validation of a Medication Adherence Universal Questionnaire: the MAUQ.

BACKGROUND: Different questionnaires assess self-reported medication adherence and others quantify aspects of patients attitudes towards medication, but not together in a single instrument. Gathering these two aspects in a single instrument could reduce patients survey burden. AIM: The aim of this study was to develop the Medication Adherence Universal Questionnaire (MAUQ) using the Maastricht Utrecht Adherence in Hypertension short version (MUAH-16) factorial structure as the hypothesized model. METHOD: A multistep process started with the modification of the MUAH-16 to obtain the MAUQ. Patients using at least one antihypertensive medicine were recruited. The two questionnaires, the MUAH-16 and MAUQ, were applied. A confirmatory factor analysis (CFA) was performed using the initial MUAH-16 s-order 4-factor model. An additional bifactor model with four uncorrelated factors and an overall score was tested. The comparative fit index (CFI), root mean square error of approximation (RMSEA) with confidence intervals (CIs), and standardized root mean squared residual (SRMR) were used to assess both models. RESULTS: A sample of 300 hypertensive patients completed the instruments. The CFA with the second-order 4-factor solution resulted in similar results for the MUAH-16 and MAUQ: CFIs of 0.934 and 0.930, RMSEAs of 0.043 [CI 0.030-0.056] and 0.045 [CI 0.031-0.057] and SRMRs of 0.060 and 0.061, respectively. The CFA with the bifactor model showed slightly better results for both the MUAH-16 and MAUQ: CFIs of 0.974 and 0.976, RMSEAs of 0.030 [CI 0.005-0.046] and 0.028 [CI 0.001-0.044], and SRMRs of 0.043 and 0.044, respectively. CONCLUSION: CFA demonstrated that the MAUQ presented a better fit to both models than the MUAH-16, obtaining a robust universal free instrument to assess medicine-taking behaviour and four medicine beliefs components.

Chemical Constituents, Anticancer and Anti-Proliferative Potential of Limonium Species: A Systematic Review.

Limonium species represent a source of bioactive compounds that have been widely used in folk medicine. This study aimed to synthesize the anticancer and anti-proliferative potential of Limonium species through a systematic review. Searches were performed in the electronic databases PubMed/MEDLINE, Scopus, and Scielo and via a manual search. In vivo or in vitro studies that evaluated the anticancer or anti-proliferative effect of at least one Limonium species were included. In total, 942 studies were identified, with 33 articles read in full and 17 studies included for qualitative synthesis. Of these, 14 (82.35%) refer to in vitro assays, one (5.88%) was in vivo, and two (11.76%) were designed as in vitro and in vivo assays. Different extracts and isolated compounds from Limonium species were evaluated through cytotoxic analysis against various cancer cells lines (especially hepatocellular carcinoma-HepG2; n = 7, 41.18%). Limonium tetragonum was the most evaluated species. The possible cellular mechanism involved in the anticancer activity of some Limonium species included the inhibition of enzymatic activities and expression of matrix metalloproteinases (MMPs), which suggested anti-metastatic effects, anti-melanogenic activity, cell proliferation inhibition pathways, and antioxidant and immunomodulatory effects. The results reinforce the potential of Limonium species as a source for the discovery and development of new potential cytotoxic and anticancer agents. However, further studies and improvements in experimental designs are needed to better demonstrate the mechanism of action of all of these compounds.