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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Cytokine networks in destructive periodontal disease

BACKGROUND Cytokines are important regulatory proteins, produced by activated cells, which act by binding high affinity cell surface receptors. They are involved in almost all aspects of cell biology and form interacting networks, with cascades of sequential cell activation. They often show overlapping activities ( redundancy ) or the same cytokine may have a variety of different effects (pleiotropy). In excess, certain cytokines are damaging and proinflammatory. Tumour necrosis factor a (TNFα) and interleukin-I (IL-I) are markedly proinflammatory, inducing bone resorption, collagenase and prostaglandin E₂ production.
OBJECTIVE: This paper focuses on the role of TNFa and IL-l in the cytokine networks of destructive chronic per-iodontitis; specifically their regulation by T cell cytokines, receptor antagonists and inhibitory soluble forms of the IL-l and TNF receptors.
CONCLUSION: A hypothesis is proposed that destructive periodontal disease may be due to disregulation of these inhibitors, rather than an overproduction of IL-l and TNFα per se.     

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.     

Commentary on “A novel treatment strategy for newly diagnosed high-grade T1 bladder cancer: Gemcitabine and cisplatin adjuvant chemotherapy—A single-institution experience.”

Background

Management of high-grade T1 (formerly T1G3) bladder cancer continues to be controversial. Should patients with T1G3 bladder cancer have an immediate radical cystectomy or should they receive intravesical bacillus Calmette-Guérin preserving bladder? Gemcitabine and cisplatin (GC) adjuvant chemotherapy may help to strike a balance between intravesical and early cystectomy. For purposes of this study, we continue to refer high-grade T1 lesion as “T1G3.”

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.     

针刺抽吸法诱导建立椎间盘退行性变的动物模型

目的:用针刺抽吸法建立椎间盘退行性变动物模型,分析其可行性和优点。方法:实验于2006-10/2007-03在苏州大学附属第一医院骨科实验室完成。新西兰大白兔18只,用持针器夹持21G皮肤穿刺针从椎间隙正前方刺入L3～4、L4～5、L5～6椎间盘的纤维环,深度控制在5mm,拔出针芯,抽吸出部分髓核组织。术前及术后4,8,12周分别对造模后椎间盘及对照椎间盘(L2～3)行免疫组织化学及组织学观察。结果:新西兰大白兔18只均进入结果分析。①组织学观察:苏木精-伊红染色可见对照组髓核组织中有着大量髓核细胞,造模组第4周髓核细胞数量不断减少,第12周时髓核中主要为纤维软骨组织,伴有极少量髓核细胞。Ⅱ型胶原免疫组织化学检测可见:对照组髓核组织间质呈强阳性染色,而各模型组呈弱阳性染色。随着造模时间的延长,染色逐渐减弱,说明髓核组织中Ⅱ型胶原的含量逐渐减少。②髓核细胞凋亡率:对照组、实验组4,8,12周的髓核细胞凋亡率为(3±1)%,(17±4)%,(36±2)%,(23±5)%,差异有显著性意义(F=113.86,P=0.0001<0.01)。结论:纤维环穿刺吸出部分髓核的方法在不破坏自身免疫屏障的前提下可诱导兔椎间盘的缓慢退行性变,为干细胞、髓核细胞、基因治疗等提供有效的动物模型。