Effectiveness of diclofenac versus paracetamol in knee osteoarthritis: a randomised controlled trial in primary care

Background

The effectiveness of diclofenac versus paracetamol in primary care patients with pain caused by knee osteoarthritis is unclear.

Aim

To assess the effectiveness of diclofenac compared with paracetamol over a period of 2, 4, and 12 weeks in patients with knee osteoarthritis.

Design and setting

Randomised controlled trial in general practice.

Method

There were 104 patients included in the study, they were aged ≥45 years consulting their GP with knee pain caused by knee osteoarthritis. Patients were randomly allocated to diclofenac (n = 52) or paracetamol (n = 52) for at least 2 weeks. Primary outcomes were daily knee pain severity, and knee pain and function measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS).

Results

Over a period of 2- and 4-weeks follow-up, no significant difference in daily knee pain was found between the patient groups: estimated differences of 0.5 (95% CI = −0.2 to 1.3) and −0.2 (95% CI = −1.0 to 0.7), respectively. Over the 12-weeks follow-up, no significant differences were found between both groups for KOOS pain: estimated difference of −2.8 (95% CI = −10.7 to 5.1) and KOOS function of −2.7 (−10.6 to 5.0).

Conclusion

Over a period of 2- and 4-weeks follow-up no significant difference in daily measured knee pain severity was found between primary care patients with knee osteoarthritis taking paracetamol or diclofenac. Also, over a period of 12-weeks follow-up no significant differences were found regarding KOOS pain and KOOS function between both groups. Patients more frequently reported minor adverse events after taking diclofenac (64%) than paracetamol (46%).     

Efficacy of Heat Treatment of Factor VIII Concentrate

Two batches of heat-treated factor VIII concentrate were found to contain anti-HIV-positive plasma donations. The batches were dry-heat-treated at 68 degrees C for 2 and 24 h, respectively. No HIV seroconversions occurred in 13 susceptible haemophiliacs receiving a total of 540 bottles of these factor VIII preparations.     

Age-dependent neurological phenotypes in a mouse model of PRRT2-related diseases

Paroxysmal kinesigenic dyskinesia is an episodic movement disorder caused by dominant mutations in the proline-rich transmembrane protein PRRT2, with onset in childhood and typically with improvement or resolution by middle age. Mutations in the same gene may also cause benign infantile seizures, which begin in the first year of life and typically remit by the age of 2 years. Many details of PRRT2 function at the synapse, and the effects of mutations on neuronal excitability in the pathophysiology of epilepsy and dyskinesia, have emerged through the work of several groups over the last decade. However, the age dependence of the phenotypes has not been explored in detail in transgenic models. Here, we report our findings in heterozygous and homozygous Prrt2 knockout mice that recapitulate the age dependence of dyskinesia seen in the human disease. We show that Prrt2 deletion reduces the levels of synaptic proteins in a dose-dependent manner that is most pronounced at postnatal day 5 (P5), attenuates at P60, and disappears by P180. In a test for foot slippage while crossing a balance beam, transient loss of coordination was most pronounced at P60 and less prominent at age extremes. Slower traverse time was noted in homozygous knockout mice only, consistent with the ataxia seen in rare individuals with biallelic loss of function mutations in Prrt2. We thus identify three age-dependent phenotypic windows in the mouse model, which recapitulate the pattern seen in humans with PRRT2-related diseases.

     

Cytotoxic T lymphocyte precursor (CTL-p) frequency analysis in unrelated donor bone marrow transplantation: two case studies

HLA 'matched' unrelated donor bone marrow transplantation (BMT) is associated with an increased incidence and severity of acute graft-versus-host disease (GVHD) in comparison with HLA-identical sibling transplants. Using a limiting dilution analysis system for quantitating frequencies of alloreactive cytotoxic T lymphocyte precursors (CTL-p), we previously demonstrated a correlation between CTL-p frequency and HLA disparity between responder and stimulator, and between CTL-p frequency and the incidence of acute GVHD following HLA A, B, DR matched unrelated donor BMT. In this study we assayed CTL-p frequencies in two HLA 'matched' unrelated donor/patient pairs, with single HLA antigenic mismatches detected by allogenotyping or isoelectric focusing but not by HLA serology, and demonstrated that the CTL-ps were specifically directed at the mismatched antigen. Both class I and class II antigens were detected. These data, and our previous work, suggest that high CTL-p frequencies in HLA 'matched' unrelated pairs are indicative of HLA antigenic variants undetected by serology but recognized by molecular typing, and that these are responsible for the value of the assay in predicting acute GVHD after BMT. We propose that this assay system be used in aiding final donor selection before unrelated or mismatched related donor BMT.     

Inter- and Intra-Subject Variability of Neuromagnetic Resting State Networks

Functional connectivity studies conducted at the group level using magnetoencephalography (MEG) suggest that resting state networks (RSNs) emerge from the large-scale envelope correlation structure within spontaneous oscillatory brain activity. However, little is known about the consistency of MEG RSNs at the individual level. This paper investigates the inter- and intra-subject variability of three MEG RSNs (sensorimotor, auditory and visual) using seed-based source space envelope correlation analysis applied to 5 min of resting state MEG data acquired from a 306-channel whole-scalp neuromagnetometer (Elekta Oy, Helsinki, Finland) and source projected with minimum norm estimation. The main finding is that these three MEG RSNs exhibit substantial variability at the single-subject level across and within individuals, which depends on the RSN type, but can be reduced after averaging over subjects or sessions. Over- and under-estimations of true RSNs variability are respectively obtained using template seeds, which are potentially mislocated due to inter-subject variations, and a seed optimization method minimizing variability. In particular, bounds on the minimal number of subjects or sessions required to obtain highly consistent between- or within-subject averages of MEG RSNs are derived. Furthermore, MEG RSN topography positively correlates with their mean connectivity at the inter-subject level. These results indicate that MEG RSNs associated with primary cortices can be robustly extracted from seed-based envelope correlation and adequate averaging. MEG thus appears to be a valid technique to compare RSNs across subjects or conditions, at least when using the current methods.     

釉基质蛋白对人牙髓细胞成牙本质分化的影响

目的 探讨釉基质蛋白对人牙髓细胞(human dental pulp cells,HDPC)成牙本质分化的影响,为牙本质的组织工程学研究提供有效的生物活性物质.方法 将HDPC接种于6孔板(2×105个/孔)后分为5组,分别加入含1、10、100 mg/L釉基质蛋白(enamel matrix proteins,EMP)(分别为EMP 1、10、100 mg/L组)、10-8 mol/L地塞米松及100 mg/L抗坏血酸(dexamethasone and ascorbic acid,Dex-AA组)、单纯基础培养液(对照组).于培养1、5、10 d分别用碱性磷酸酶(alkaline phosphatase,ALP)试剂盒检测ALP活性,实时荧光定量反转录聚合酶链反应技术检测成牙本质相关基因牙本质基质蛋白1(dentine matrix protein-1,DMP-1)及牙本质涎磷蛋白(dentine sialophosphoprotein,DSPP)的表达,应用2-△△CT方法得出具体数值并进行单因素方差分析与Post Hoe 检验,用茜素红染色检测并定量分析矿化情况.结果 各组ALP水平呈时间依赖性上调,培养1d后各组ALP活性与对照组相比差异均无统计学意义;5 d后EMP 10、100 mg/L组及Dex-AA组ALP活性显著增高,分别达到7.573±0.267、6.119±0.502、5.846±0.096,与对照组相比差异均有统计学意义(P＜0.05);10 d后10 mg/L EMP组及Dex-AA组ALP活性增高更显著,分别达21.035±0.149、13.223±0.797,与对照组(5.825±0.404)相比差异均有统计学意义(P＜0.01).培养1d后各组DMP-1及DSPP mRNA水平均较对照组显著升高,差异均有统计学意义(P＜0.01);培养10 d后10 mg/L EMP组DMP-1和DSPP表达水平均显著增高,分别达到14.791±0.164、12.238±0.421.培养10 d后各组均有矿化,10 mg/L EMP组钙离子浓度[(191.8±2.0) μmol/L]显著高于对照组[(81.1±8.1)μmol/L],差异有统计学意义(P＜0.01).结论 适当浓度的EMP对HDPC的成牙本质分化有一定的促进作用.