Meta-analysis of factors associated with antidiabetic drug prescribing for type 2 diabetes mellitus.

BACKGROUND: There is a lack of consensus on prescribing alternatives to initial metformin therapy and intensification therapy for type 2 diabetes mellitus (T2DM) management. This review aimed to identify/quantify factors associated with prescribing of specific antidiabetic drug classes for T2DM. METHODS: Five databases (Medline/PubMed, Embase, Scopus, Web of Science) were searched using the synonyms of each concept (patients with T2DM, antidiabetic drugs and factors influencing prescribing) in both free text and Medical Subject Heading (MeSH) forms. Quantitative observational studies evaluating factors associated with antidiabetic prescribing of metformin, sulfonylurea, thiazolidinedione, Dipeptidyl-peptidase 4 inhibitors (DPP4-I), sodium glucose transporter 2 inhibitors (SGLT2-I), Glucagon-Like peptide receptor agonist (GLP1-RA) and insulin in outpatient settings and published from January 2009 to January 2021 were included. Quality assessment was performed using a Newcastle-Ottawa scale. The validation was done for 20% of identified studies. The pooled estimate was measured using a three-level random-effect meta-analysis model based on odds ratio [95% confidence interval]. Age, sex, body mass index (BMI), glycaemic control (HbA1c) and kidney-related problems were quantified. RESULTS: Of 2331 identified studies, 40 met the selection criteria. Of which, 36 and 31 studies included sex and age, respectively, while 20 studies examined baseline BMI, HbA1c and kidney-related problems. The majority of studies (77.5%, 31/40) were rated as good and despite that the overall heterogeneity for each studied factor was more than 75%, it is mostly related to within-study variance. Older age was significantly associated with higher sulfonylurea prescription (1.51 [1.29-1.76]), yet lower prescribing of metformin (0.70 [0.60-0.82]), SGLT2-I (0.57 [0.42-0.79]) and GLP1-RA (0.52 [0.40-0.69]); while higher baseline BMI showed opposite significant results (sulfonylurea: 0.76 [0.62-0.93], metformin: 1.22 [1.08-1.37], SGLT2-I: 1.88 [1.33-2.68], and GLP1-RA: 2.35 [1.54-3.59]). Both higher baseline HbA1c and having kidney-related problems were significantly associated with lower metformin prescription (0.74 [0.57-0.97], 0.39 [0.25-0.61]), but more insulin prescriptions (2.41 [1.87-3.10], 1.52 [1.10-2.10]). Also, DPP4-I prescriptions were higher for patients with kidney-related problems (1.37 [1.06-1.79]) yet lower among patients with higher HbA1c (0.82 [0.68-0.99]). Sex was significantly associated with GLP1-RA and thiazolidinedione prescribing (F:M; 1.38 [1.19-1.60] and 0.91 [0.84-0.98]). CONCLUSION: Several factors were identified as potential determinants of antidiabetic drug prescribing. The magnitude and significance of each factor differed by antidiabetic class. Patient's age and baseline BMI had the most significant association with the choice of four out of the seven studied antidiabetic drugs followed by the baseline HbA1c and kidney-related problems which had an impact on three studied antidiabetic drugs, whereas sex had the least impact on prescribing decision as it was associated with GLP1-RA and thiazolidinedione only.

Using the theoretical domains framework to explore behavioural determinants for medication taking in patients following percutaneous coronary intervention.

OBJECTIVES: To investigate relationships between factors influencing medication taking and behavioural determinants in patients who have undergone percutaneous coronary intervention (PCI). METHODS: A cross-sectional survey using a postal questionnaire distributed to PCI patients. The questionnaire was iteratively developed by the research team with reference to the theoretical domains framework (TDF) of behavioural determinants, reviewed for face and content validity and piloted. Data were analysed using descriptive and principal component analysis (PCA). Inferential analysis explored relationships between PCA component scores and factors influencing medicating taking behaviour. KEY FINDINGS: Adjusted response rate was 62.4% (325/521). PCA gave three components: (C1) Self-perceptions of knowledge and abilities in relation to medication taking; (C2) Aspects relating to activities and support in medication taking; (C3) Emotional aspects in taking medication. Generally, respondents held very positive views. Statistically significant relationships between all three components and self-reported chest pain/discomfort indicated patients with ongoing chest pain/discomfort post-PCI are more likely to have behavioural determinants and beliefs which make medication taking challenging. Respondents who were on 10 or more medications had lower levels of agreement with the C2 and C3 statements indicating challenges associated with their activities/support and anxieties in medication taking. CONCLUSIONS: PCI patients show links between TDF behavioural determinants and factors influencing medication taking for those reporting chest pain or polypharmacy. Further research needs to explore the effective design and implementation of behavioural change interventions to reduce the challenge of medication taking.

A cross-sectional survey of the access of older people in the Scottish Highlands to general medical practices, community pharmacies and prescription medicines.

BACKGROUND: Access to medicines and healthcare is more problematic in remote and rural areas. OBJECTIVES: To quantify issues of access to general practitioners (GPs), community pharmacies and prescribed medicines in older people resident in the Scottish Highlands. METHODS: Anonymized questionnaires were mailed to a random sample of 2000 older people (≥60 years) resident in the Scottish Highlands. Questionnaire items were: access and convenience to GP and pharmacy services (10 items); prescribed medicines (13 items); attitudinal statements based on the Theoretical Domains Framework (12 items); quality of life (SF8, 8 items); and demographics (12 items). Results were analysed using descriptive, inferential and spatial statistics, and principal component analysis (PCA) of attitudinal items. RESULTS: With a response rate of 54.2%, the majority reported convenient access to GPs (89.1%) and community pharmacies (84.3%). Older age respondents (p < 0.0001) were more likely to state that their access to GP services was not convenient and those in rural areas to community pharmacies (p < 0.01). For access to prescribed medicines, those in poorer health (p < 0.001) and taking five or more regular prescribed medicines (p = 0.002) were more likely to state access not convenient. PCA identified three components of beliefs of capabilities, emotions and memory. Those with poorer health had more negative scores for all (p < 0.001). Those reporting issues of access to prescribed medicines had more negative scores for beliefs of capabilities (p < 0.001) while those of older age, living alone, and taking five or more regular prescribed medicines (all p < 0.001) had more negative scores for emotions. CONCLUSION: While the majority of respondents have convenient access to their GP practice, pharmacy and prescribed medicines, there is a need for further review of the pharmaceutical care of those of older age with poorer health, living alone in the more remote and rural areas and taking five or more prescribed medicines.

Nicorandil, Gastrointestinal Adverse Drug Reactions and Ulcerations: A Systematic Review.

INTRODUCTION: Nicorandil is a popular anti-anginal drug in Europe and Japan. Apart from some common adverse drug reactions (ADR), its safety is satisfactory. Several reports have suggested a link between nicorandil, gastrointestinal (GI) ulceration and fistulas. The review aims to critically appraise, synthesize and present the available evidence of all known GI ADR per anatomical location. METHODS: The study complied with the PRISMA statement. Literature and pharmacovigilance databases were used to provide rate and/or calculate parameters (median age, median dose, history of symptoms, length of therapy and healing time after withdrawal of the drug). Differences in distribution of quantitative variables were analyzed via Mann-Whitney test. Correlation between quantitative variables was assessed with a Spearman's correlation coefficient. A p value <0.05 was significant. RESULTS: Oral ulcerations occur in 0.2% of the subjects, anal ulcerations are present between 0.07% and 0.37% of patients. Oral and distal GI involvements are the most common ADR (28-29% and 27-31% of all GI ADR, respectively). The hepatobiliary system, the pancreas and salivary glands are not affected by nicorandil exposure. The time to develop oral ulcerations is 74 weeks among people on <30 mg/day compared to only 7.5 weeks in individuals on higher regimens (p = 0.47). There is a significant correlation between dose and ulcer healing time (Spearman's 0.525, p < 0.001). CONCLUSIONS: Ulcerative disease is a very commonly reported GI ADR. A delayed ulcerative tendency supports the hypothesis of an ulcerogenic metabolite. Nicorandil seems to act as a cause of the ulcerations, but appears to also work in synergy with other promoting factors. Whether the action of the metabolites relies on a specific mechanism or a simple chemical ulceration is still to be established.

Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits.

N-acetyl-l-cysteine (NAC) has long been used therapeutically for the treatment of acetaminophen (paracetamol) overdose, acting as a precursor for the substrate (l-cysteine) in synthesis of hepatic glutathione (GSH) depleted through drug conjugation. Other therapeutic uses of NAC have also emerged, including the alleviation of clinical symptoms of cystic fibrosis through cysteine-mediated disruption of disulfide cross-bridges in the glycoprotein matrix in mucus. More recently, however, a wide range of clinical studies have reported on the use of NAC as an antioxidant, most notably in the protection against contrast-induced nephropathy and thrombosis. The results from these studies are conflicting and a consensus is yet to be reached regarding the merits or otherwise of NAC in the antioxidant setting. This review seeks to re-evaluate the mechanism of action of NAC as a precursor for GSH synthesis in the context of its activity as an "antioxidant". Results from recent studies are examined to establish whether the pre-requisites for effective NAC-induced antioxidant activity (i.e. GSH depletion and the presence of functional metabolic pathways for conversion of NAC to GSH) have received adequate consideration in the interpretation of the data. A key conclusion is a reinforcement of the concept that NAC should not be considered to be a powerful antioxidant in its own right: its strength is the targeted replenishment of GSH in deficient cells and it is likely to be ineffective in cells replete in GSH.

Evidence-based case report: multiple thrombotic episodes associated with lenalidomide and dexamethasone therapy for multiple myeloma.

Lenalidomide in combination with dexamethasone is a treatment for patients with relapsed or refractory myeloma. Although this combination demonstrates a high level of efficacy, it further exacerbates the hypercoaguable state that exists within myeloma. Thromboprophylactic regimen require careful selection and if warfarin is chosen, assiduous monitoring is required to ensure it will be clinically effective. We report the case of one patient who experienced multiple thrombotic events despite anticoagulant or antiplatelet thromboprophylaxis and review the contributing factors.