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%).     

Effectiveness of Conservative,Surgical, and Postsurgical Interventions for Trigger Finger,Dupuytren Disease,and De Quervain Disease: A Systematic Review

Objectives

To provide an evidence-based overview of the effectiveness of conservative and (post)surgical interventions for trigger finger, Dupuytren disease, and De Quervain disease.

Educating and Training a Workforce for Nutrition in a Post-2015 World

Nearly all countries in the world today are burdened with malnutrition, manifesting as undernutrition, micronutrient deficiencies, and/or overweight and obesity. Despite some progress, efforts to alleviate malnutrition are hampered by a shortage in number, skills, and geographic coverage, of a workforce for nutrition. Here, we report the findings of the Castel Gandolfo workshop, a convening of experts from diverse fields in March 2014 to consider how to develop the capacity of a global cadre of nutrition professionals for the post-2015 development era. Workshop participants identified several requirements for developing a workforce for nutrition, including an ability to work as part of a multisectoral team; communication, advocacy, and leadership skills to engage decision makers; and a set of technical skills to address future challenges for nutrition. Other opportunities were highlighted that could immediately contribute to capacity development, including the creation of a consortium to link global North and South universities, online training modules for middle managers, and practical, hands-on experiences for frontline nutrition workers. Institutional and organizational support is needed to enable workshop recommendations on education and training to be effectively implemented and sustained. The findings from the Castel Gandolfo workshop can contribute to the delivery of successful nutrition-relevant actions in the face of mounting external pressures and informing and attaining the forthcoming Sustainable Development Goals.     

Blood coagulation factors as inflammatory mediators

After the first observations about blood coagulation by Hippocrates, it took until the early 1900s before the classic theory of blood coagulation was presented. As more and more other coagulation factors were discovered, the four-factor coagulation scheme became more complex, but better understood, leading to the current coagulation cascade. As during the last decade it turned out that coagulation factors might do more than just promoting (or inhibiting) blood coagulation, new scientific avenues were pursued focusing on coagulation-independent properties of individual coagulation factors. This led to the current understanding that coagulation factors, like tissue factor (TF), FVII, FX, and thrombin, are important players in inflammation, vascular development, angiogenesis, and tumorigenesis. However, the molecular mechanism by which coagulation factors exert their pleiotropic effects in pathophysiology remains one of the major challenges in the field. This overview presents current insight in how the main coagulation factors might induce inflammation.     

Self-rated health among older adults: a cross-national comparison

Self-rated health (SRH) may have different implications in various social and cultural settings. However, few studies are available concerning SRH among older persons across countries. The aim of this study was to analyse whether there are cross-national differences in the association between status characteristics, several diseases common among older persons, activities of daily living (ADL), and SRH. The study base was the Comparison of Longitudinal European Studies on Aging (CLESA), which includes data from six population-based studies on aging conducted in Finland, Israel, Italy, The Netherlands, Spain and Sweden. The study population comprised 5,629 persons, with participants from all countries except Italy. Logistic regression analyses were used to assess the relationship between status characteristics, health conditions, ADL and SRH. To examine whether the association among status characteristics, health conditions, ADL and outcome differed across the CLESA countries, interaction terms defined as variable*country were considered separately for each variable. Regression analyses revealed that sex, education, lifetime occupation, heart disease and respiratory disease were differently distributed across countries. Among homogeneous factors, marital status (OR=1.21), hypertension (OR=1.41), stroke (OR=1.67), diabetes (OR=2.15), cancer (OR=1.47), musculoskeletal diseases (OR=2.44), and ADL (OR=2.72) turned out to be significantly associated with fair or poor SRH. The results indicate that there are differences in self-ratings of health across countries. These differences cannot be explained entirely by status characteristics, self-reported diseases or functional ability. However, an important finding was that in all countries most of the indicators of medical and functional health were homogeneously associated with SRH.     

Human adult bone marrow mesenchymal stem cells repair experimental conduction block in rat cardiomyocyte cultures.

OBJECTIVES: We evaluated whether human adult bone marrow-derived mesenchymal stem cells (hMSCs) could repair an experimentally induced conduction block in cardiomyocyte cultures. BACKGROUND: Autologous stem cell therapy is a novel treatment option for patients with heart disease. However, detailed electrophysiological characterization of hMSCs is still lacking. METHODS: Neonatal rat cardiomyocytes were seeded on multi-electrode arrays. After 48 h, abrasion of a 200- to 450-microm-wide channel caused conduction block. Next, we applied adult hMSCs (hMSC group, n = 8), human skeletal myoblasts (myoblast group, n = 7), rat cardiac fibroblasts (fibroblast group, n = 7), or no cells (control group, n = 7) in a channel-crossing pattern. Cross-channel electrical conduction was analyzed after 24 and 48 h. Intracellular action potentials of hMSCs and cardiomyocytes were recorded. Immunostaining for connexins and intercellular dye transfer (calcein) assessed the presence of functional gap junctions. RESULTS: After creation of conduction block, two asynchronously beating fields of cardiomyocytes were present. Application of hMSCs restored synchronization between the two fields in five of eight cultures after 24 h. Conduction velocity across hMSCs (0.9 +/- 0.4 cm/s) was approximately 11-fold slower than across cardiomyocytes (10.4 +/- 5.8 cm/s). No resynchronization occurred in the myoblast, fibroblast, or control group. Intracellular action potential recordings indicated that conduction across the channel presumably occurred by electrotonic impulse propagation. Connexin-43 was present along regions of hMSC-to-cardiomyocyte contact, but not along regions of cardiomyocyte-to-myoblast or cardiomyocyte-to-fibroblast contact. Calcein transfer from cardiomyocytes to hMSCs was observed within 24 h after co-culture initiation. CONCLUSIONS: Human mesenchymal stem cells are able to repair conduction block in cardiomyocyte cultures, probably through connexin-mediated coupling.     

Monitoring Therapy with Vitamin K Antagonists in Patients with Lupus Anticoagulant: Effect on Different Tests for INR Determination

Background: Lupus anticoagulant (antiphospholipid antibodies) is associated with venous and arterial thrombosis in patients with and without autoimmune disorders. Vitamin K antagonists are the treatment of choice in patients with thrombosis, of which the dose is titrated by INR monitoring. Several recent reports suggest that the presence of the lupus anticoagulant disturbs the INR test and may lead to unreliable results with a large variation in INR values, dependent on the reagents used.Methods: We studied 11 lupus anticoagulant positive patients and 11 lupus anticoagulant negative patients, all using vitamin K antagonists. The INR value was determined using seven different tests and the variation in INR values was compared between the two groups. The amidolytic Factor X levels were used as an phospholipid independent measure for intensity of warfarin therapy. Factor VII and X activity were measured to assess the stability of warfarin therapy.Results: The variation of the results with different INR tests within one patient was minimal and comparable in the two groups for INR's in the therapeutic range. The coefficient of variation for the cases and control group was 10.43 and 9.35, respectively. Variation in both groups increased at supratherapeutic levels of anticoagulation and when the anticoagulation was unstable (measured with Factor X/Factor VII ratio). The relationship between INR values and Factor X analysis revealed no influence of the lupus anticoagulant.Conclusions: In this study, lupus anticoagulant antibodies do not disturb INR laboratory tests. Differences in INR measurements are seen in patients with a high intensity of anticoagulation and in patients who either just started or in whom no stable anticoagulation has been achieved.Abbreviated Abstract. This study investigates the influence of lupus anticoagulant on INR determination tests in patients treated with warfarin. Eleven cases and eleven lupus anticoagulant negative control patients, also on warfarin therapy, were included. Seven INR results per patient were obtained using different laboratory tests. A factor X assay was performed to obtain an independent measure for the intensity of warfarin therapy.The variation of INR results between the cases and controls revealed no difference in these groups. In addition, the relationship between INR values and Factor X analysis indicated no influence of the lupus anticoagulant. What was observed was an increased difference in INR values in patients with a high intensity of anticoagulation and in patients who either just started or in whom no stable anticoagulation has been achieved     

Prothrombin 20210A mutation: a mild risk factor for venous thromboembolism but not for arterial thrombotic disease and pregnancy-related complications in a family study

BACKGROUND: The prothrombin 20210A mutation has been associated with an increased risk of venous thromboembolism (VTE). Its relationship with arterial disease and pregnancy-related complications is, however, still uncertain. The aim of this study was to estimate the incidences of first venous and arterial thrombotic events and pregnancy-related complications in relatives of patients with the mutation. METHODS: After clinical classification, the presence of the mutation was determined in first-degree relatives of consecutive patients with the mutation and a history of VTE or premature atherosclerosis. Relatives with and without the mutation were compared. RESULTS: Of all relatives, 204 (50%) were heterozygous, 5 were homozygous, and 198 had a normal genotype. The annual incidence of a first episode of VTE was 0.35% and 0.18% in carriers and noncarriers, respectively (odds ratio [OR], 1.9; 95% confidence interval [CI], 0.9-4.1); the annual incidence of a first arterial thrombosis was 0.22% and 0.15% in carriers and noncarriers, respectively (OR, 2.3; 95% CI, 0.8-6.3). The annual incidence of a first myocardial infarction was 0.14% (95% CI, 0.05%-0.23%) and 0.05% (0.01%-0.14%) in carriers and noncarriers, respectively (OR, 4.7; 95% CI, 1.0-22.5; P =.06). In particular, homozygous carriers were at increased risk of VTE (OR, 6.0; 95% CI, 1.3-27.2), whereas a history of VTE in the proband influenced the risk of VTE in the relatives. Women with the mutation did not experience significantly more pregnancy-related complications than their relatives with a normal genotype. CONCLUSIONS: The prothrombin mutation is a mild risk factor for VTE within families of carriers but does not seem to play an important role in arterial thrombotic disease, with the exception of myocardial infarction, or in pregnancy-related complications.     

Task-related motivation and academic achievement in children and adolescents with ADHD

European Child & Adolescent Psychiatry - Academic impairment in individuals with attention-deficit/hyperactivity disorder (ADHD) is in part due to reduced motivation for academic tasks, which...     

Assessing the predictive ability of the Suicide Crisis Inventory for near‐term suicidal behavior using machine learning approaches

ObjectiveThis study explores the prediction of near‐term suicidal behavior using machine learning (ML) analyses of the Suicide Crisis Inventory (SCI), which measures the Suicide Crisis Syndrome, a presuicidal mental state.MethodsSCI data were collected from high‐risk psychiatric inpatients (N = 591) grouped based on their short‐term suicidal behavior, that is, those who attempted suicide between intake and 1‐month follow‐up dates (N = 20) and those who did not (N = 571). Data were analyzed using three predictive algorithms (logistic regression, random forest, and gradient boosting) and three sampling approaches (split sample, Synthetic minority oversampling technique, and enhanced bootstrap).ResultsThe enhanced bootstrap approach considerably outperformed the other sampling approaches, with random forest (98.0% precision; 33.9% recall; 71.0% Area under the precision‐recall curve [AUPRC]; and 87.8% Area under the receiver operating characteristic [AUROC]) and gradient boosting (94.0% precision; 48.9% recall; 70.5% AUPRC; and 89.4% AUROC) algorithms performing best in predicting positive cases of near‐term suicidal behavior using this dataset.ConclusionsML can be useful in analyzing data from psychometric scales, such as the SCI, and for predicting near‐term suicidal behavior. However, in cases such as the current analysis where the data are highly imbalanced, the optimal method of measuring performance must be carefully considered and selected.