Impact of modified-release opioid use on clinical outcomes following total hip and knee arthroplasty: a propensity score-matched cohort study

Modified-release opioids are often prescribed for the management of moderate to severe acute pain following total hip and knee arthroplasty, despite recommendations against their use due to increasing concerns regarding harm. The primary objective of this multicentre study was to examine the impact of modified-release opioid use on the incidence of opioid-related adverse events compared with immediate-release opioid use, among adult inpatients following total hip or knee arthroplasty. Data for total hip and knee arthroplasty inpatients receiving an opioid analgesic for postoperative analgesia during hospitalisation were collected from electronic medical records of three tertiary metropolitan hospitals in Australia. The primary outcome was the incidence of opioid-related adverse events during hospital admission. Patients who received modified with or without immediate-release opioids were matched to those receiving immediate-release opioids only (1:1) using nearest neighbour propensity score matching with patient and clinical characteristics as covariates. This included total opioid dose received. In the matched cohorts, patients given modified-release opioids (n = 347) experienced a higher incidence of opioid-related adverse events overall, compared with those given immediate-release opioids only (20.5%, 71/347 vs. 12.7%, 44/347; difference in proportions 7.8% [95%CI 2.3–13.3%]). Modified-release opioid use was associated with an increased risk of harm when used for acute pain during hospitalisation after total hip or knee arthroplasty.     

Genome-Wide Meta-Analysis Identifies Three Novel Susceptibility Loci and Reveals Ethnic Heterogeneity of Genetic Susceptibility for IgA Nephropathy

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Feasibility and validity of ecological momentary assessment in adolescents with high-functioning autism and Asperger's disorder

Ecological Momentary Assessment (EMA) may increase accuracy of data compared with retrospective questionnaires by assessing behaviours as they occur, hence decreasing recall biases and increasing ecological validity. This study examined the feasibility and concurrent validity of an EMA tool for adolescents with High-Functioning Autism Spectrum Disorders (HFASD). Thirty-one adolescents with HFASD completed a mobile phone EMA application that assessed stressors and coping for two weeks. Parents and adolescents also completed retrospective measures of the adolescent's coping/stressors. Moderate compliance with the EMA tool was achieved and some concurrent validity was established with the retrospective measure of coping. Concordance was found between the types of stressors reported by parents and adolescents but not the quantity. The results suggest adolescents with HFASD are capable of reporting on their stressors and coping via EMA. EMA has the potential to be a valuable research tool in this population.     

Pharmacokinetics and pharmacodynamics of 3,3′-diindolylmethane (DIM) in regulating gene expression of phase II drug metabolizing enzymes

3,3′-Diindolylmethane (DIM) has been investigated as a potential anti-cancer chemopreventive agent in many preclinical and clinical studies. In this study, we sought to characterize the pharmacokinetics of DIM and to build a pharmacokinetic (PK) and pharmacodynamic (PD) model of the DIM-induced gene expression of phase II drug metabolizing enzymes (DME), which potentially links DIM’s molecular effects to its in vivo chemopreventive efficacy. DIM (10 mg/kg) was administered intravenously (i.v.) to male Sprague–Dawley rats and blood samples were collected at selected time points for 48 h. The plasma concentration of DIM was determined using a validated HPLC method. The mRNA expression of NQO1, GSTP1 and UGT1A1 in blood lymphocytes was measured using quantitative PCR. An indirect response model was employed to relate the concentration of DIM to the expression of the genes NQO1, GSTP1 and UGT1A1, which were chosen as PD markers for DIM. After i.v. administration, the plasma concentration of DIM declined quickly, and the expression of target genes increased significantly, peaking at 1–2 h and then returning to basal levels after 24 h. The parameters in the PK–PD model were estimated. The PK–PD model aptly described the time delay and magnitude of gene expression induced by DIM. Our results indicate that DIM is effective at inducing various phase II DME, which are capable of detoxify carcinogens. This PK–PD modeling approach provides a framework for evaluating the acute effects of DIM or other similar drugs in clinical trials.     

Potentially inappropriate prescribing in a falls clinic using the STOPP and START criteria

International Journal of Clinical Pharmacy - Background Potentially inappropriate prescribing is increasingly common in older patients with falls. However, published indicators to assess...     

Higher Dietary Energy Density is Associated with Stunting but not Overweight and Obesity in a Sample of Urban Malaysian Children

Although diets with high energy density are associated with increased risk of overweight and obesity, it is not known whether such diets are associated with undernutrition. This study assessed the relationship between dietary energy density (ED) and nutritional status of 745 urban 1- to 10-year-old children. Dietary intakes were obtained using food recall and record for two days. Dietary energy density was based on food and caloric beverages. Higher dietary ED was associated with lower intakes of carbohydrate, sugar, vitamins C and D, and calcium but higher fat, fiber, iron, and folate intakes. While intakes of fruits and milk/dairy products decreased, meat, fish, and legume intakes increased with higher dietary ED. Stunting, but not other growth problems, was associated with higher dietary ED. Future studies should confirm the cause-and-effect relationship between higher dietary ED and stunting.     

Hot-melt extrusion microencapsulation of quercetin for taste-masking

Besides its poor dissolution rate, the bitterness of quercetin also poses a challenge for further development. Using carnauba wax, shellac or zein as the shell-forming excipient, this work aimed to microencapsulate quercetin by hot-melt extrusion for taste-masking. In comparison with non-encapsulated quercetin, the microencapsulated powders exhibited significantly reduced dissolution in the simulated salivary pH 6.8 medium indicative of their potentially good taste-masking efficiency in the order of zein?>?carnauba wax?>?shellac. In vitro bitterness analysis by electronic tongue confirmed the good taste-masking efficiency of the microencapsulated powders. In vitro digestion results showed that carnauba wax and shellac-microencapsulated powders presented comparable dissolution rate with the pure quercetin in pH 1.0 (gastric) and 6.8 (intestine) medium; while zein-microencapsulated powders exhibited a remarkably slower dissolution rate. Crystallinity of quercetin was slightly reduced after microencapsulation while its chemical structure remained unchanged. Hot-melt extrusion microencapsulation could thus be an attractive technique to produce taste-masked bioactive powders.     

Cutting Edge Issues in Autoimmune Gastritis

Autoimmune gastritis is the outcome of a pathological CD4 T cell-mediated autoimmune response directed against the gastric H/K-ATPase. Silent initially, the gastric lesion becomes manifest in humans by the development of megaloblastic pernicious anemia arising from vitamin B12 deficiency. Cutting edge issues in this disease relate to its epidemiology, immunogenetics, a role for Helicobacter pylori as an infective trigger through molecular mimicry, its immunopathogenesis, associated organ-specific autoimmune diseases, laboratory diagnosis, and approaches to curative therapy.     

Improved quantification of amyloid burden and associated biomarker cut-off points: results from the first amyloid Singaporean cohort with overlapping cerebrovascular disease

European Journal of Nuclear Medicine and Molecular Imaging - The analysis of the [11C]PiB-PET amyloid images of a unique Asian cohort of 186 participants featuring overlapping vascular diseases...     

Evolving Pattern of Laparoscopic Gastric Band Access Port Complications

Laparoscopic gastric banding (LGB) is the commonest bariatric procedure in Australia. The commonest complication of LGB is access port or tubing (AP/T) problems, requiring revisional surgery. The aim of this study was to document the evolving pattern of AP/T complications. All patients whose LGB procedure (Allergan(TM) Bands) and AP/T revision (Allergan(TM) port revision sets) were performed by one surgeon (1999 to 2008) were included, giving 167 AP/T revisions in 124 patients out of a total 1,928 LGB patients. All patient follow-up details were prospectively recorded and retrospectively analysed. Incidence of LGB AP/T problems was 8.7%. Mean time to first AP/T revision was 2 years. Over the last 4 years of the series, the number of LGB insertions was constant, but the number of AP/T revisions progressively increased. Twenty-seven percent of AP/T revision patients required two or more AP/T revisions. Sixty-two percent of the AP/T complications were leaks. Half the AP complications were flipping of the AP. There was no correlation of AP/T problems with any changes to port design to date. Infection rate for LGB insertion was 0.67%. The incidence of LGB AP/T complications progressively increases with duration after LGB insertion. Occurrence of one AP/T problem appears to select a subgroup more likely to experience further AP/T problems. To date, revisions of port design do not appear to have solved AP/T problems. Recent introduction of a significantly redesigned port may reduce AP/T failures.