Étude de la validité de mesures de l'observance du traitement médicamenteux antidiabétique

La mesure de l’observance du traitement demeure un défi dans certains contextes compte tenu des limites des différentes méthodes de mesure. La validité des mesures de l’observance calculée à partir des données de pharmacie et des mesures auto-rapportées de l’observance du traitement antidiabétique n’a pas été étudiée de façon exhaustive. La recherche avait pour objectifs d’évaluer la validité 1) de mesures de l’observance des polythérapies antidiabétiques tirées des données de pharmacie et 2) de mesures auto-rapportées de l’observance du traitement. Une cohorte de nouveaux utilisateurs d’au moins deux antidiabétiques oraux a été construite à partir des données de la Régie de l’assurance maladie du Québec (RAMQ).Quatre mesures de l’observance des polythérapies ont été calculées: la proportion de jours couverts (PJC) par au moins une classe de médicaments, la PJC moyenne des différentes classes, la PJC par toutes les classes et le taux de possession quotidienne de polypharmacie (DPPR). Les hospitalisations toute cause et les hospitalisations liées au diabète ont été utilisées comme critères de validation. Pour le deuxième objectif, quatre mesures auto-rapportées de l’observance du traitement ont été complétées par un échantillon de patients diabétiques de type 2 de la province de Québec, à travers une enquête web. Il s’agit d’une mesure à quatre items (SR-4), de la version française modifiée de la MMAS-8, de la proportion de pilules non prises et d’une mesure à un item (SR-1). Le taux d’hémoglobine glyquée (HbA1c) mesuré entre 3 et 6mois après l’enquête web a été utilisé comme critère de validation. Des analyses de courbes ROC ont été conduites pour évaluer la validité des mesures de l’observance des polythérapies. Le seuil optimal de l’observance pour identifier les individus observants de leur traitement a été déterminé en utilisant la méthode de la «distance minimale». Des analyses de courbes ROC, des analyses de régression linéaire et des analyses factorielles (MMAS-8 uniquement) ont été conduites pour l’évaluation de la validité des mesures auto-rapportées. Enfin, la cohérence interne de la MMAS-8 a été évaluée par le calcul de l’alpha de Cronbach. Pour les mesures de l’observance des polythérapies, les aires sous la courbe ROC (AUCs)pour, respectivement, la PJC par au moins une classe, la PJC moyenne, la PJC par toutes les classes et le DPPR étaient de 0,54 (IC 95%: 0,52-0;56), 0,51 (0,49-0,53), 0,50 (0,48-0,52) et 0,51 (0,49-0,53) avec l’hospitalisation toute cause comme critère et 0,55 (0,53-0,57), 0,53 (0,51-0,55), 0,51 (0,49-0,53) et 0,53 (0,51-0,55) avec l’hospitalisation liée au diabète comme critère. Le seuil optimal pour classer les individus comme observants du traitement était de 95,7 % selon les deux critères de validation Les AUCs pour les mesures auto-rapportées, faibles et non-statistiquement significatives, étaient de 0,51 (0,4-0,59), 0,52 (0,43-0,60), 0,53 (0,45-0,60) et 0,52 (0,44-0,59),respectivement pour la SR-4, la MMAS-8, la proportion de pilules non prises et la SR-1.Selon les résultats de la régression linéaire dans l’échantillon total, aucune des mesures n’était associée de façon statistiquement significative à l’HbA1c, mais l’association entre laSR-4 et l’HbA1c était proche de la significativité statistique (coefficient de régression de -0,25, valeur-p de 0,07). Dans le sous-échantillon des participants ayant un HbA1c ≥ 7 %, laSR-4, la MMAS-8 et la SR-1 étaient associées de façon statistiquement significative àl’HbA1c. L’analyse factorielle de la MMAS-8 a montré qu’elle est constituée de deux sous échelles. Une sous-échelle évaluant la non-observance intentionnelle et une sous-échelle évaluant la non-observance non-intentionnelle. La cohérence interne de la MMAS-8 était faible puisque l’alpha de Cronbach de 0,60 était inférieur à la valeur seuil suggérée (0,70)pour juger de la bonne cohérence interne des mesures. En conclusion, les résultats suggèrent que la PJC par au moins une classe de médicaments est la méthode la plus valide pour le calcul de l’observance des polythérapies antidiabétiques à partir des données de pharmacie. Les résultats suggèrent également qu’un niveau minimum de 95 % de PJC devrait être considéré pour classer les individus comme observant de leur traitement. Pour la mesure auto-rapportée de l’observance du traitement, les résultats soutiennent la validité prédictive de la SR-4, la SR-1 et la MMAS-8. Enfin, si on utilise la MMAS-8 pour évaluer l’observance du traitement antidiabétique, on devrait distinguer les scores de chaque sous-échelle pour permettre une intervention adaptée en cas de non-observance.Measurement of adherence remains a challenge in some contexts because the different measurement methods have limitations. The validity of pharmacy-based measures of adherence and self-reported measures of adherence to antidiabetes drug treatment has not been comprehensively studied. The research objectives were thus to assess the validity of 1) four measures of pharmacybased adherence to oral antidiabetes multi-drug treatment and 2) four self-reported measures of adherence. We built a cohort of new users of at least two oral antidiabetes drugs using the Quebec health insurance Board (RAMQ) medico-administrative data. Four pharmacy-based adherence measures were calculated from these data: the proportion of days covered (PDC) by at least one class of drugs, the mean PDC, the PDC by all classes of drugs and the daily polypharmacy possession rate (DPPR). All-cause hospitalization and diabetes-related hospitalization were used as validation criteria. For the second objective, four self-reported measures of adherence were completed during a web survey by a sample of individuals with type 2 diabetes of the Canadian province of Quebec: a 4-item scale (SR-4), a French version of the 8-item Morisky medication adherence scale (MMAS-8), the self-reported proportion of pills missed and a single-item scale (SR-1). Measures of HbA1c taken between 3 and 6 months after the web survey were used as the validation criterion. To assess the validity of the pharmacy-based adherence measures, we conducted ROC curve analyses. In addition, the optimal threshold of adherence to classify individuals as adherent to their treatment was assessed using the method of the "minimum distance". ROC curve analyses, linear regression analyses and factor analyses (MMAS-8 only) were performed to assess the validity of the self-reported measures. Finally, we assessed the internal consistency of the MMAS-8 by calculating Cronbach's alpha. For pharmacy-based adherence to oral antidiabetes multi-drug treatment, the areas under the ROC curves (AUCs), for respectively, the PDC by at least one class of drugs, the mean vi PDC, the PDC by all classes of drugs and the DPPR were 0.54 (95% CI: 0.52-0.56), 0.51 (0.49-0.53), 0.50 (0.48-0.52) and 0.51 (0.49-0.53) with all-cause hospitalization as criterion, and 0.55 (0.53-0.57), 0.53 (0.51-0.55), 0.51 (0.49-0.53) and 0.53 (0.51-0.55) with diabetes-related hospitalization as criterion. The optimal threshold to classify individuals as adherent to their treatment was 95.7% according to the two validation criteria. AUCs for the self-reported measures (low and non-statistically significant) were 0.51 (0.43- 0.59), 0.52 (0.43-0.60), 0.53 (0.45-0.60) and 0.52 (0.44-0.59), for the SR-4, the MMAS-8, the proportion of pills missed and the SR-1, respectively. According to the results of the linear regression analyses in the total sample, all the measures were non-significantly associated with HbA1c, but the association between the SR-4 and HbA1c was close to statistical significance (regression coefficient of -0.25, p-value of 0.07). In the subsample of participants with HbA1c ≥ 7%, the SR-4, the MMAS-8 and the SR-1 were significantly associated with HbA1c. Factor analyses of the MMAS-8 showed that it is made of two subscales: a subscale assessing intentional non-adherence and a subscale assessing nonintentional non-adherence. The internal consistency of the MMAS-8 was low since the Cronbach's alpha of 0.60 was below the suggested threshold value of 0.70. In conclusion, the results suggest that the PDC by at least one class of drugs is the most valid method for calculating pharmacy-based adherence to oral antidiabetes multi-drug treatment. The results also suggest that a minimum level of 95% of PDC should be considered for classifying individuals as adherent to their treatment. For the self-reported measures of adherence, the results support the predictive validity of the SR-1, the SR-4 and the MMAS-8 with a slight superiority of the SR-4. Finally, if the MMAS-8 is used to assess adherence to antidiabetes drug treatment, results suggest that the score of each subscale should be used separately to identify the type of non-adherence in order to provide appropriate intervention to the patient

Polypharmacy definitions for multimorbid older adults need stronger foundations to guide research, clinical practice and public health.

There are numerous definitions of polypharmacy to describe the use of many medications among older adults, but there is a need to clarify if they are purposive and meaningful. By means of a systematic review, we identified definitions of polypharmacy used in multimorbid older adults (≥65 years). We evaluated if the definitions align among the domains of research, clinical practice, and public health and appraised whether concepts of polypharmacy are based on strong foundations. More than 46 definitions of polypharmacy were retrieved from 348 publications (research: n = 243; clinical practice: n = 88; public health: n = 17). Several thresholds based on the number of medications were mentioned. The majority of the publications (n = 202, 58%) used a minimal threshold of five medications. Heterogeneous qualitative definitions were identified, mostly stating that polypharmacy is “more drugs than needed”. There was no significant divergence between domains as to the type of definitions used, although qualitative definitions were more common in clinical practice. Nearly half (n = 156, 47%) of the publications provided no justification for the polypharmacy definition used. The wide variety of definitions for polypharmacy precludes comparisons, appropriate identification and management of polypharmacy in multimorbid older adults. Standardized definitions would allow more coherent judgments regarding the individual and collective stakes of polypharmacy

Revisiting the internal consistency and factorial validity of the 8-item Morisky Medication Adherence Scale

Objective: To assess the internal consistency and factorial validity of the adapted French 8-item Morisky Medication Adherence Scale in assessing adherence to noninsulin antidiabetic drug treatment.Study Design and Setting: In a cross-sectional web survey of individuals with type 2 diabetes of the Canadian province of Quebec, self-reported adherence to the antidiabetes drug treatment was measured using the Morisky Medication Adherence Scale-8. We assessed the internal consistency of the Morisky Medication Adherence Scale-8 with Cronbach’s alpha, and factorial validity was assessed by identifying the underlying factors using exploratory factor analyses.Results: A total of 901 individuals completed the survey. Cronbach’s alpha was 0.60. Two factors were identified. One factor comprised five items: stopping medication when diabetes is under control, stopping when feeling worse, feeling hassled about sticking to the prescription, reasons other than forgetting and a cross-loading item (i.e. taking drugs the day before). The second factor comprised three other items that were all related to forgetfulness in addition to the cross-loading item.Conclusion: Cronbach’s alpha of the adapted French Morisky Medication Adherence Scale-8 was below the acceptable value of 0.70. This observed low internal consistency of the scale is probably related to the causal nature of the items of the scale but not necessarily a lack of reliability. The results suggest that the adapted French Morisky Medication Adherence Scale-8 is a two-factor scale assessing intentional (first factor) and unintentional (second factor) non-adherence to the noninsulin antidiabetes drug treatment. The scale could be used to separately identify these outcomes using scores obtained on each of the sub-scale

Polypharmacy Definitions for Multimorbid Older Adults Need Stronger Foundations to Guide Research, Clinical Practice and Public Health

There are numerous definitions of polypharmacy to describe the use of many medications among older adults, but there is a need to clarify if they are purposive and meaningful. By means of a systematic review, we identified definitions of polypharmacy used in multimorbid older adults (≥65 years). We evaluated if the definitions align among the domains of research, clinical practice, and public health and appraised whether concepts of polypharmacy are based on strong foundations. More than 46 definitions of polypharmacy were retrieved from 348 publications (research: n = 243; clinical practice: n = 88; public health: n = 17). Several thresholds based on the number of medications were mentioned. The majority of the publications (n = 202, 58%) used a minimal threshold of five medications. Heterogeneous qualitative definitions were identified, mostly stating that polypharmacy is "more drugs than needed". There was no significant divergence between domains as to the type of definitions used, although qualitative definitions were more common in clinical practice. Nearly half (n = 156, 47%) of the publications provided no justification for the polypharmacy definition used. The wide variety of definitions for polypharmacy precludes comparisons, appropriate identification and management of polypharmacy in multimorbid older adults. Standardized definitions would allow more coherent judgments regarding the individual and collective stakes of polypharmacy

Genomic Epidemiology of SARS-CoV-2 in Western Burkina Faso, West Africa.

BACKGROUND: After its initial detection in Wuhan, China, in December 2019, SARS-CoV-2 has spread rapidly, causing successive epidemic waves worldwide. This study aims to provide a genomic epidemiology of SARS-CoV-2 in Burkina Faso. METHODS: Three hundred and seventy-seven SARS-CoV-2 genomes obtained from PCR-positive nasopharyngeal samples (PCR cycle threshold score < 35) collected between 5 May 2020, and 31 January 2022 were analyzed. Genomic sequences were assigned to phylogenetic clades using NextClade and to Pango lineages using pangolin. Phylogenetic and phylogeographic analyses were performed to determine the geographical sources and time of virus introduction in Burkina Faso. RESULTS: The analyzed SARS-CoV-2 genomes can be assigned to 10 phylogenetic clades and 27 Pango lineages already described worldwide. Our analyses revealed the important role of cross-border human mobility in the successive SARS-CoV-2 introductions in Burkina Faso from neighboring countries. CONCLUSIONS: This study provides additional insights into the genomic epidemiology of SARS-CoV-2 in West Africa. It highlights the importance of land travel in the spread of the virus and the need to rapidly implement preventive policies. Regional cross-border collaborations and the adherence of the general population to government policies are key to prevent new epidemic waves

Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso

The emergence of HIV-1 drug resistance (HIVDR) is a public health problem that affects women and children. Local data of HIVDR is critical to improving their care and treatment. So, we investigated HIVDR in mothers and infants receiving antiretroviral therapy (ART) at Saint Camille Hospital of Ouagadougou, Burkina Faso. This study included 50 mothers and 50 infants on ART. CD4 and HIV-1 viral load were determined using FACSCount and Abbott m2000rt respectively. HIVDR was determined in patients with virologic failure using ViroSeq HIV-1 Genotyping System kit on the 3130 Genetic Analyzer. The median age was 37.28 years in mothers and 1.58 year in infants. Sequencing of samples showed subtypes CRF02_AG (55.56%), CRF06_cpx (33.33%) and G (11.11%). M184V was the most frequent and was associated with highlevel resistance to 3TC, FTC, and ABC. Other mutations such as T215F/Y, D67N/E, K70R, and K219Q were associated with intermediate resistance to TDF, AZT, and 3TC. No mutation to LPV/r was detected among mothers and infants. The findings of HIVDR in some mothers and infants suggested the change of treatment for these persons

INSIGHTS INTO THE INTERPLAY BETWEEN KIR GENE FREQUENCIES AND CHRONIC HBV INFECTION IN BURKINA FASO

Background/Objective: The receptors of natural killer cells "Killer Cell Immunoglobulin-Like Receptor" (KIR) regulate the activity of Natural killer cells in the innate response against viral infections. To date there is no accurate method to identify high risk groups for cirrhosis and HCC in Sub-Saharan Africa. Therefore, this investigation was undertaken to assess the association between KIR genes frequencies and chronic infection HBV infection in Burkina Faso’s population. Methods: Chronic HBV carriers and healthy patients were selected for this study. The viral load for HBV were performed to confirm the serological status for HBV of the studied cohort. In addition, SSP-PCR was used to characterize the frequencies of KIR genes. Results: The study suggested that inhibitory genes KIR2DL2, KIR2DL3 and activator gene KIR2DS2 (p˂0.001 for all and OR = 2.82; 2.48 and 3.84 respectively) might be associated with chronic stages of HBV infection.  While inhibitory genes KIR3DL1 (p = 0.0018 OR = 0.49), KIR3DL2 (p = 0.005 OR = 0.40), the activator gene KIR2DS1 (p = 0.014 OR = 0.47) and the pseudo gene KIR2DP1 (p = 0.011 OR = 0.49) could be associated with immunity against HBV infection. Patients who carried the KIR3DL2 gene had a high HBV viral load compared to the rest of the study population. Conclusion: Our data showed an evidence of correlation between the propensity of developing chronic HBV infection and certain KIR gene frequencies and that KIR3DL1, KIR3DL2, KIR2DS1 and KIR2DP1 might confer a protective status against chronic HBV infection in Burkina Faso’s patients

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Utilisation des bases de données médico-administratives du Québec pour des études en santé mentale : opportunités, défis méthodologiques et limites – cas de la dépression chez les personnes diabétiques

L’utilisation des bases de données médico-administratives pour les études sur des questions de santé mentale est très fréquente compte tenu du grand nombre de personnes représentées dans ces bases de données et aussi du fait qu’elles portent sur plusieurs années. Plusieurs défis, liés par exemple à l’identification des personnes ayant une maladie d’intérêt ou exposées à un facteur de risque, sont à surmonter à travers des études de validation pour garantir une utilisation optimale de ces ressources. Par ailleurs, des limites (absence de certaines informations pertinentes) et la couverture d’une seule partie de la population par le régime public d’assurance médicaments du Québec sont à considérer dans l’interprétation et la généralisation des résultats des recherches à partir de ces bases de données.Dans cet article, nous avons réalisé un survol de l’utilisation des bases de données médico-administratives pour des études épidémiologiques, en utilisant comme exemple le cas spécifique de la dépression. Nous avons en particulier utilisé ces bases de données pour déterminer l’incidence de la dépression parmi les personnes diabétiques du Québec. Cela a nécessité l’utilisation d’un algorithme préalablement validé (dans une autre province) que nous avons modifié pour définir et identifier les cas de dépression dans les bases de données de la Régie de l’assurance maladie du Québec (RAMQ). Nous avons observé une incidence de dépression de 9,47/1000 personnes-années sur un suivi de 8 ans. Enfin, nous avons évalué l’impact de la dépression sur l’adhésion et la persistance aux traitements antidiabétiques ainsi que les facteurs qui affectent l’utilisation des médicaments par ces patients. Nos résultats suggèrent que la dépression a un impact négatif sur l’utilisation des médicaments antidiabétiques et permettent d’identifier des pistes de solution.The use of medico-administrative databases for studies on mental health issues is very common because of the large number of people in these databases and the possibility to carry out long-term studies. Several challenges, such as identifying people with a disease of interest or being exposed to a risk factor, have to be overcome through validation studies to ensure an optimal use of these resources. Moreover, limits (lack of certain relevant information) and the coverage of about 40% of Quebec’s population by the public drug plan are to be considered in the interpretation and generalization of research results based on these data sources.In the specific case of depression, we used these databases to determine the incidence of depression among diabetic individuals in Quebec. This required the use of a previously validated algorithm (validated in another province) that we modified to define and identify the cases of depression in the RAMQ databases. We observed an incidence of depression of 9.47 persons years over a follow-up of 8 years. Finally, we assessed the impact of depression on adherence and persistence with antidiabetic drugs as well as the factors that affect patients’ use of these drugs. Our results suggest that depression has a negative impact on the use of antidiabetic drugs and allow the identification of possible solutions

Optimal threshold of adherence to lipid lowering drugs in predicting acute coronary syndrome, stroke, or mortality: A cohort study.

OBJECTIVE:Thresholds defining medication adherence are rarely evidence-based. A threshold of 0.8 is typically presumed to achieve improved outcomes. We aimed to assess the optimal threshold of adherence to lipid-lowering drugs (LLD) in predicting cardiovascular-related (CV) outcomes in patients with hypertension. DESIGN:Cohort study of new users of LLDs. SETTING:Comprehensive healthcare administrative databases of the province of Alberta (Canada) from 2008 to 2016. PARTICIPANTS:Patients with hypertension, who were new users of LLDs. Patients who had the outcomes prior to the initiation of LLD were excluded. MAIN OUTCOMES MEASURES:Hospitalization for acute coronary syndrome (ACS)/stroke, CV-related mortality and all-cause mortality. STATISTICAL ANALYSIS:Adherence to LLDs was assessed as the proportion of days covered (PDC) by any LLD, from drug initiation to censoring, outcome, or study end. Three methods were used to assess the threshold: Contal and O'Quigley method, minimum distance method, and Youden's J index. Cox regressions were used to assess the risk associated with each method-specific threshold and Akaike information criteria were used to retain the optimal threshold after adjustment. RESULTS:52229 patients were included; 4.0% were hospitalized for ACS/stroke, 3.4% died, and 1.3% died from CV-related cause. In predicting ACS/stroke, CV-related and all-cause mortality, the optimal adherence threshold was 0.52 (range: 0.51-0.54), 0.79 (0.45-0.87), and 0.84 (0.79-0.89), respectively. These results were consistent among patients aged ≥ 65 years (n = 19804). However, the results varied among those aged < 65 years, where the incidence rates of outcomes were low. CONCLUSION:In new-users of LLDs with hypertension, approximately 50% days covered by LLDs may be enough to prevent long-term occurrence of ACS, or stroke. However, a threshold near 0.80 may be needed to prevent or reduce the risk of all-cause or CV-related mortality