Compliance with Prescription Guidelines for Glucose-Lowering Therapies According to Renal Function: Real-Life Study in Inpatients of Internal Medicine, Endocrinology and Cardiology Units

Background and objectives: Renal failure is a contraindication for some glucose-lowering drugs and requires dosage adjustment for others, particularly biguanides, sulfonylureas, and inhibitors of dipeptidyl peptidase 4. In this study, we assessed adherence to prescription recommendations for glucose-lowering drugs according to renal function in hospitalized diabetic subjects. Materials and Methods: This prospective cohort study was carried out over a 2-year period in a university hospital. Glomerular filtration rate (GFR) was determined by averaging all measurements performed during hospitalization. Glucose-lowering drug dosages were analyzed according to the recommendations of the relevant medical societies. Results: In total, 2071 diabetic patients (53% hospitalized in cardiology units) were examined. GFR was <30 mL/min/1.73 m2 in 13.4% of these patients, 30–44 in 15.1%, 45–60 in 18.3%, and >60 in 53.3%. Inappropriate oral glucose-lowering treatments were administered to 273 (13.2%) patients, including 53 (2.6%) with a contraindication. In cardiology units, 53.1% and 14.3% of patients had GFRs of <60 and <30 mL/min/1.73 m2, respectively, and 179 (15.4%) patients had a contraindication or were prescribed an excessive dose of glucose-lowering drugs. Conclusions: We showed that the burden of inappropriate prescriptions is high in diabetic patients. Given the high number of patients receiving these medications, particularly in cardiology units, a search for potential adverse effects related to these drugs should be performed.

The role of bempedoic acid in the management of dyslipidaemia

Bempedoic acid is a new oral lipid-lowering therapy which has been licenced for use in the United Kingdom. It can be used alone, with a statin, or with other lipid-lowering therapies where the target level for low density lipoprotein has not been achieved with these therapies alone. Bempedoic acid with ezetimibe can be prescribed for people who are unable to tolerate statins. This combination has received NICE approval following a technology appraisal. This paper discusses the place for of bempedoic acid as a lipid lowering drug and consider the mode of action, licensed indications, adverse drug reactions and the NICE technology appraisal recommendations.

Monitoring Utilization Trends of Glucose-Lowering Drugs for Type 2 Diabetes in Older Adults by Frailty Status

Using Medicare fee-for-service data from 2013-17, we identified a cohort of patients with type 2 diabetes (T2D) who initiated a glucose-lowering drug (mean [SD] age, 74.8 (6.9) years). Amongst frail patients (CFI≥0.20), metformin use remained stable from 29.1% to 29.4%, whereas sulfonylureas (25.8% to 22.1%) and insulin (21.2% to 19.0%) use declined. Amongst non-frail patients (CFI &lt;0.20), metformin (35.3% to 33.1%) and sulfonylurea (26.2% to 22.2%) use decreased whereas insulin (11.7% to 10.6%) use remained stable. DPP-4i and glitazones use remained stable whereas the use of newer agents such as SGLT-2i and GLP-1 RA increased steadily over the study period in both frail and non-frail patients, though their use remains low ( &lt;8%). In conclusion, sulfonylureas and insulin accounted for about one-third of initiated glucose-lowering medications and were more frequently used by frail patients, though their use declined steadily over time with the availability of newer agents.

Fatality in a body packer: the first reported case in Saudi Arabia

Background Body packers use different methods and materials to pack drugs inside their bodies. These could be simple or sophisticated to ensure a successful transfer or concealment of the drug with minimal risk to the packer. Different drugs were reported with cocaine and heroin being the most common. The packer presents to health facilities whenever they develop complications like drug leakage or intestinal obstruction, or they can be detected after a fatal event as an incidental finding in autopsy. Case presentation A body packer who was in detention suffered pain and died shortly after that. The autopsy not only revealed severe coronary atherosclerosis but also unveiled 10 rubber packages filled with methamphetamine and cannabis, and one package was found ruptured in the mouth. Toxicological analysis showed a blood level of methamphetamine 3.66 mg/L which was considered a cause of death. While methamphetamine was reported in cases of body packers, cannabis is rarely concealed by body packers for several reasons including its cost compared to the risk of packing. Conclusions This is the first reported case of fatality in body packers in Saudi Arabia and Arab countries. This should put into consideration the need for screening suspicious cases who are involved or suspected to be involved with drugs. Effective screening in specific facilities is needed to reduce fatalities and at the same time lowering drug smuggling.

Comparative Analysis of Three Pairs of Surrogate Redox Partners for in Vitro Activity Reconstitution of Class I Cytochrome P450 Enzymes

Cytochrome P450 enzymes (P450s) are highly attractive biocatalysts due to their versatile catalytic activities. A vast majority of P450s require redox partner (RP) proteins to sequentially transfer two electrons for O2 activation and substrate oxidation. However, little information is available on cognate RPs for P450s, which greatly limits P450 function exploration and practical application. Thus, the stategy of building various hybrid P450 catalytic systems with surrogate RPs has often adopted to engineer P450 biocatalysts for different purposes. In this study, we comprehensively compare three pairs of frequently-used surrogate redox partners SelFdx1499/SelFdR0978, Adx/AdR and Pdx/PdR and in terms of their electron transfer properties. The three selected bacterial Class I P450s to accept electrons from RPs include PikC, P450sca-2 and CYP-sb21, which are responsible for production of macrolide antibiotics, the cholesterol-lowering drug pravastatin, and a hair-growth-stimulating agent. Both experimental studies and structural analysis show that SelFdx1499/SelFdR0978 is the most promising RP compared to Adx/AdR and Pdx/PdR. The results provide insights into the domination for P450-redox partner interactions in modulating the catalytic activity of P450s. This study not only produces a more active biocatalyst but also suggests a general chose for a universal reductase which would facilitate engineering of P450 catalyst.

The role of different lipid measures for incident hypertension during more than 12 years follow-up: Tehran Lipid and Glucose Study

To examine the associations of different lipid measures and related indices with incident hypertension during a median follow-up of 12.89 years. Fasting levels of total cholesterol (TC), triglycerides (TG), high and low density lipoprotein cholesterol (HDL-C and LDL-C, respectively), and related indices (TC/HDL-C and TG/HDL-C) were determined in 7335 Iranian adults (men=3270) free of hypertension, aged 39.0 [standard deviation (SD):13.2] years. Multivariate Cox proportional hazard regression was applied and lipid parameters were considered either as categorical or continuous variables. During follow-up, 2413 (men=11260) participants experienced hypertension. Using the first quartile as reference, significant trends were found between quartiles of TG, HDL-C, TC/HDL-C, and TG/HDL-C in multivariate models; moreover considering these measures as continuous variables, a 1 SD increase in each of these parameters was significantly associated with risk of incident hypertension; the corresponding hazard ratios and confidence intervals were 1.06(1.02-1.10), 0.94(0.89-0.98), 1.04(1.01-1.09), and 1.04(1.01-1.07), respectively. The association between lipid measures and incident hypertension did not change after excluding lipid lowering drug users and those with type 2 diabetes mellitus and were independent of the baseline categories of blood pressure (P for interaction > 0.08). To take into account the nutrition data, a re-analysis on a subgroup (n=1705), showed that a 1-SD increase in TG and TG/HDL-C were associated with incident hypertension, after adjusting for dietary cofounders [1.15(1.08–1.24) and 1.03(1.01–1.04), respectively]. These findings indicate that TG, TG/HDL-C, and TC/HDL-C were independently associated with higher risk while HDL-C was associated with lower risk of incident hypertension.

Efficacy of Probucol on cognitive function in Alzheimers disease: Study protocol for a double-blind, placebo-controlled, randomised phase II trial (PIA Study)

Preclinical, clinical and epidemiological studies support the hypothesis that aberrant systemic metabolism of amyloid-beta (Aβ) in the peripheral circulation is causally related to the development of Alzheimers disease (AD). Specifically, recent studies suggest that increased plasma concentrations of lipoprotein-Aβ compromises the brain microvasculature, resulting in extravasation and retention of the lipoprotein-Aβ moiety. The latter results in an inflammatory response and neurodegeneration ensues. Probucol, a historic cholesterol-lowering drug, has been shown in murine models to suppress lipoprotein-Aβ secretion, concomitant with maintaining blood-brain-barrier function and suppressing neurovascular inflammation. Probucol has also been shown to protect cognitive function in dietary-induced amyloidogenic mice. This protocol details the Probucol in Alzheimers Study (PIA-study), a double-blind, randomised, placebo-controlled drug intervention trial investigating if Probucol attenuates cognitive decline in patients with mild-to-moderate AD. Objectives: The primary objective of the 104-week study is to assess whether Probucol supports cognitive function and delays brain atrophy in AD patients. A secondary objective is to determine whether Probucol treatment will reduce cerebral amyloid burden.

Use of electronic patient data overview with alerts in primary care increases prescribing of lipid-lowering medications in patients with type 2 diabetes

Aims/hypothesis We aimed to assess whether general practices (GPs) using an electronic disease management program (DMP) with population overviews, including alerts when patients failed to receive guideline-recommended prescription medications, increased prescriptions of lipid-lowering drugs for patients with type 2 diabetes with no history of lipid-lowering treatment. Methods This observational study included 165 GPs that reached a high level of use of the DMP in 2012 and a control group of 135 GPs who reached a high level of use in 2013 and, hence, who were less exposed to the DMP throughout 2012. A binary measure for having been prescribed and filled lipid-lowering drugs at any time within a 12-month exposure period was derived for all patients with type 2 diabetes who did not receive a prescription for lipid-lowering drugs in the baseline year prior to the study period (i.e. 2011). Results were derived using ORs from multivariate logistic regression analyses. Subgroup stratification based on age, sex, diabetes duration, deprivation status and Charlson Comorbidity Index (CCI) score was conducted and assessed. Placebo tests were carried out to assess bias from selection to treatment. Results Patients who did not receive a prescription of lipid-lowering drugs in the year prior to being listed with GPs that used the DMP had statistically significant greater odds of receiving a prescription of lipid-lowering medications when compared with individuals who attended control GPs (OR 1.23 [95% CI 1.09, 1.38]). When the analysis period was shifted back by 2 years, no significant differences in lipid-lowering drug prescription between the two groups were found to occur, which indicates that these results were not driven by selection bias. Subgroup analyses showed that the increase in lipid-lowering drug prescriptions was primarily driven by changes among male participants (OR 1.32 [95% CI 1.12, 1.54]), patients aged 60–70 years (OR 1.40 [95% CI 1.13, 1.74]), patients with a diabetes duration of ≤5 years (OR 1.33 [95% CI 1.13, 1.56]), non-deprived patients (OR 1.25 [95% CI 1.08, 1.45]) and patients without comorbidities (CCI score = 0; OR 1.27 [95% CI 1.11, 1.45]). Conclusions/interpretation Access to population overviews using a DMP with alerts of clinical performance measures with regard to adhering to guideline-recommended prescription of medications can increase GP prescriptions of lipid-lowering drugs. Graphical abstract

Erosive cheilitis as an early manifestation in DRESS syndrome

Drug reaction with eosinophilia and systemic symptoms (DRESS) is part of Severe cutaneous adverse reactions. Allopurinol, an uric acid-lowering drug, had been incriminated in several cases of Allopurinol-induced Dress syndrome.Through this paper, we present a case of Allopurinol-induced DRESS syndrome with initial oral mucosal involvement.