Psychosocial predictors of non-adherence to chronic medication: systematic review of longitudinal studies

Hanneke E Zwikker,1 Bart J van den Bemt,1,2 Johanna E Vriezekolk,1 Cornelia H van den Ende,1 Sandra van Dulmen3–51Departments of Rheumatology and Pharmacy, 2Department of Pharmacy, Radboud University Medical Centre, 3Department of Primary and Community Care, Radboud University Medical Centre, Nijmegen, 4Netherlands Institute for Health Services Research, the Netherlands; 5Department of Health Science, Buskerud University College, Drammen, NorwayObjectives: Several cross-sectional studies suggest that psychosocial factors are associated with non-adherence to chronic preventive maintenance medication (CPMM); however, results from longitudinal associations have not yet been systematically summarized. Therefore, the objective of this study was to systematically synthesize evidence of longitudinal associations between psychosocial predictors and CPMM non-adherence.Materials and methods: PUBMED, EMBASE, CINAHL, and PsychINFO databases were searched for studies meeting our inclusion criteria. The reference lists and the ISI Web of Knowledge of the included studies were checked. Studies were included if they had an English abstract, involved adult populations using CPMM living in Western countries, and if they investigated associations between psychosocial predictors and medication non-adherence using longitudinal designs. Data were extracted according to a literature-based extraction form. Study quality was independently judged by two researchers using a framework comprising six bias domains. Studies were considered to be of high quality if ≥four domains were free of bias. Psychosocial predictors for non-adherence were categorized into five pre-defined categories: beliefs/cognitions; coping styles; social influences and social support; personality traits; and psychosocial well-being. A qualitative best evidence synthesis was performed to synthesize evidence of longitudinal associations between psychosocial predictors and CPMM non-adherence.Results: Of 4,732 initially-identified studies, 30 (low-quality) studies were included in the systematic review. The qualitative best evidence synthesis demonstrated limited evidence for absence of a longitudinal association between CPMM non-adherence and the psychosocial categories. The strength of evidence for the review's findings is limited by the low quality of included studies.Conclusion: The results do not provide psychosocial targets for the development of new interventions in clinical practice. This review clearly demonstrates the need for high-quality, longitudinal research to identify psychosocial predictors of medication non-adherence.Keywords: medication adherence, psychosocial factors, systematic review, longitudinal studies, somatic and chronic disease

Psychological and somatic predictors of perceived and measured ocular dryness of patients with primary Sjogren's syndrome

Objective. To test if age, disease activity, pain, fatigue, and depression are associated with subjective and objective ocular dryness of patients with primary Sjogren's syndrome (pSS). Methods. Sixty female patients with pSS and 60 age matched healthy controls filled out visual analog scale (VAS) scores of ocular dryness and pain, and questionnaires regarding fatigue (Multidimensional Fatigue Inventory) and depression (Zung). Lacrimal tear production was measured by Schirmer I test. As surrogate indicators of disease activity the erythrocyte sedimentation rate, hemoglobin concentration, and total serum immunoglobulin G were determined. Results. Perceived ocular sicca symptoms were not related to Schirmer I test scores. The rate of tear production was related to age (r = -0.47, p <0.001), disease activity (r = -0.27, p <0.05), and pain (r = 0.42, p <0.001). Age and pain together explained 42% of the variance of the Schirmer I test results. Conclusion. Not unexpectedly, age and disease activity were associated with ocular dryness, but contrary to expectation, pain was associated with more instead of less tear production. We did not find evidence that pain, fatigue, or depression are associated with reduced tear production or perceived ocular dryness

Comparing methotrexate monotherapy with methotrexate plus leflunomide combination therapy in psoriatic arthritis (COMPLETE-PsA): a double-blind, placebo-controlled, randomised, trial

Background Conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) are the preferred first-line treatment in patients with psoriatic arthritis, although there is a paucity of evidence for the efficacy of conventional synthetic DMARDs and especially their combination. We aimed to investigate whether a combination of methotrexate plus leflunomide is superior to methotrexate monotherapy at improving disease activity in patients with psoriatic arthritis. Methods This single centre, investigator-initiated, double-blind, randomised, placebo-controlled trial was conducted at Sint Maartenskliniek in the Netherlands (locations included Boxmeer, Geldrop, Woerden, and Nijmegen). Patients aged 16 years or older with a clinical diagnosis of psoriatic arthritis and active disease (defined as two or more swollen joints; dactylitis counting as one swollen joint) were included. Patients were randomly allocated (1:1) and stratified by high disease activity (psoriatic arthritis disease activity score [PASDAS] ≥5·4) to either methotrexate plus leflunomide (combination therapy) or methotrexate plus placebo (monotherapy), using computer-generated stratified variable block randomisation. In both groups, patients received oral methotrexate 15 mg per week for the first 4 weeks and 25 mg per week thereafter combined with two leflunomide 10 mg tablets once per day or two placebo tablets. During the study period, the patients, nurses, researchers, and treating physicians were all masked to treatment allocation. The primary outcome was the difference in mean PASDAS at week 16, adjusted for baseline PASDAS, between the combination and monotherapy groups, assessed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register (NL7404) on Dec 3, 2018. Findings Between Feb 19, 2019, and March 11, 2021, 82 patients were screened for eligibility. Four patients were ineligible and 78 were enrolled and randomly assigned to either methotrexate plus leflunomide (n=39) or methotrexate plus placebo (n=39). 50 (64%) of 78 patients were male, 28 (36%) were female, and the median age of patients was 55·0 years (IQR 42·0–64·0). Methotrexate plus leflunomide combination therapy was superior to methotrexate monotherapy at week 16 (PASDAS 3·1 [SD 1·4] vs 3·7 [SD 1·3]; treatment difference –0·6, 90% CI –1·0 to –0·1; p=0·025). There were no study deaths. The most frequently occurring adverse events were nausea or vomiting (17 [44%] of 39 patients in the methotrexate plus leflunomide group vs 11 [28%] of 39 in the methotrexate plus placebo group), tiredness (9 [23%] vs 13 [33%]) and elevated alanine aminotransferase (12 [31%] vs 7 [18%]. Generally, the incidence of mostly mild adverse events was higher in the methotrexate plus leflunomide group than in the methotrexate plus placebo group. Interpretation Methotrexate plus leflunomide combination therapy results in greater improvement in disease activity according to PASDAS in patients with psoriatic arthritis. However, methotrexate plus leflunomide combination therapy is less well tolerated than methotrexate monotherapy. Funding Regional Junior Researcher Grant from the Sint Maartenskliniek

Impact of Dry Eye Syndrome on Vision-Related Quality of Life in a Non-Clinic-Based General Population

<p>Abstract</p> <p>Background</p> <p>Dry eye syndrome (DES) is a common ocular disorder occurring in general population. The purpose of this study is to evaluate the impact of DES on vision-related quality of life (QoL) in a non-clinic-based general population.</p> <p>Methods</p> <p>This population-based cross-sectional study enrolled subjects older than 40 years, who took part in an epidemiological study on dry eye in Sanle Community, Shanghai. Apart from the collection of sociodemographics, dry eye symptoms, and other clinical data, a Chinese version of the 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) was administered to all subjects. Comparisons of the NEI VFQ-25 subscale item scores and composite score were made among subgroups divided according to the presence of dry eye symptoms or signs. Multivariate regression analysis was performed to investigate the relationship between the clinical variables and the VFQ-25 composite score.</p> <p>Results</p> <p>A total of 229 participants were enrolled in the study, with an average age of (60.7 ±10.1) years old. Majority of these participants were female (59.8 %, 137/229). The total DES symptom scores (TDSS) in subjects either with definite DES or only with dry eye symptoms were significantly higher (F = 60.331, P < 0.001). The values of tear break-up time (TBUT) and Schirmer test were significantly lower in participants with DES and those with dry eye signs only (F = 55.158 and 40.778, P < 0.001). The composite score of the NEI VFQ-25 was significantly lower in subjects with DES (F = 4.901, P = 0.003). Moreover, the subscale scores of ocular pain and mental health were significantly lower in those with either DES or dry eye symptoms only (F = 10.962 and 7.362 respectively, both P < 0.001). The multiple regression analysis showed that the TDSS had a significant negative correlation with the VFQ-25 composite score as well as with the subscale score for ocular pain and mental health, even after the adjustment of all other factors (all P < 0.01).</p> <p>Conclusions</p> <p>The symptoms of dry eye are associated with an adverse impact on vision-related QoL in non-clinic-based general population, which is mainly represented as more ocular pain and discomfort, and impaired mental health as well. Apart from clinical examination, it is also important to refer to subjective symptoms and QoL scores when assessing the severity of DES.</p