Improving osteoarthritis management in primary healthcare: results from a quasi-experimental study

BACKGROUND: To improve quality of care for patients with hip and knee osteoarthritis (OA), general practitioners (GPs) and physiotherapists (PTs) in a Norwegian municipality initiated an intervention. The intervention aimed to increase provision of core OA treatment (information, exercise, and weight control) prior to referral for surgery, rational use of imaging for assessing OA and improve communication between healthcare professionals. This study assessed the effectiveness of this intervention. METHODS: Forty-eight PTs and one hundred one GPs were invited to the intervention that included two interactive workshops outlining best practice and an accompanying template for PT discharge reports. Using interrupted time series research design, the study period was divided into three: pre-implementation, transition (implementation) and post-implementation. Comparing the change between pre- and post-implementation, the primary outcome was patient-reported quality of OA care measured with the OsteoArthritis Quality Indicator questionnaire. Secondary outcomes were number of PT discharge reports, information included in GP referral letters to orthopaedic surgeon, the proportion of GP referral letters indicating use of core treatment, and the use of imaging within OA assessment. Analyses involved linear mixed and logistic regression models. RESULTS: The PT workshop had 30 attendees, and 31 PTs and 33 GPs attended the multidisciplinary workshop. Two hundred eight and one hundred twenty-five patients completed the questionnaire during pre- and post-implementation, respectively. The adjusted model showed a small, statistically non-significant, increase in mean total score for quality of OA care (mean change = 4.96, 95% CI -0.18, 10.12, p:0.057), which was mainly related to items on OA core treatment. Patients had higher odds of reporting receipt of information on treatment alternatives (odds ratio (OR) 1.9, 95% CI 1.08, 3.24) and on self-management (OR 2.4, 95% CI 1.33, 4.32) in the post-implementation phase. There was a small, statistically non-significant, increase in the proportion of GP referral letters indicating prior use of core treatment modalities. There were negligible changes in the number of PT discharge reports, in the information included in the GP referral letters, and in the use of imaging for OA assessment. CONCLUSION: This study suggests that a primary care intervention including two inter-active workshops can shift the quality of care towards best practice recommendations. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02876120

Development of a Sensitive Microplate Assay for Characterizing RNA Methyltransferase Activity: Implications for Epitranscriptomics and Drug Development

RNA methylation is a ubiquitous post-transcriptional modification found in diverse RNA classes and is a critical regulator of gene expression. In this study, we used Zika virus RNA methyltransferase (MTase) to develop a highly sensitive microplate assay that uses a biotinylated RNA substrate and radiolabeled AdoMet coenzyme. The assay is fast, highly reproducible, exhibits linear progress-curve kinetics under multiple turnover conditions, has high sensitivity in competitive inhibition assays, and significantly lower background levels compared with the currently used method. Using our newly developed microplate assay, we observed no significant difference in the catalytic constants of the full-length nonstructural protein 5 enzyme and the truncated MTase domain. These data suggest that, unlike the Zika virus RNA-dependent RNA polymerase activity, the MTase activity is unaffected by RNA-dependent RNA polymerase-MTase interdomain interaction. Given its quantitative nature and accuracy, this method can be used to characterize various RNA MTases, and, therefore, significantly contribute to the field of epitranscriptomics and drug development against infectious diseases

Pulse pressure and age at menopause

BACKGROUND: The objective of this study was to study the association of early age at menopause with pulse pressure (PP), a marker of arterial stiffness, and PP change. METHODS: The effect of natural menopause was studied in 2484 women from the Atherosclerosis Risk in Communities (ARIC) Study who had not used hormone replacement therapy and who had not had a hysterectomy. The cross-sectional association of age with PP was evaluated in the entire cohort. The cross-sectional association of recalled age at menopause was evaluated in the 1688 women who were postmenopausal at baseline. PP change over 6 years was assessed in relation to menopausal age separately in women who were postmenopausal at baseline and in those whose menopause occurred during the 6-year interval. RESULTS: Chronological age was strongly and positively associated with PP in cross-sectional analyses, but not independently associated with PP change. While menopausal age was not associated cross-sectionally with PP, early age at menopause (age<45) was significantly and independently associated with a slightly larger increase in PP (8.4, 95% CI 7.0–9.8) than later menopause (6.5, 95% CI 5.8;7.2). However, among normotensive women the difference was not statistically significant (p = 0.07, 6.1 vs 4.7). CONCLUSIONS: Early age at menopause may be related to a greater increase in arterial stiffness, but the effect appears to be small and further evidence is needed

The structure of logical consequence : proof-theoretic conceptions

The model-theoretic analysis of the concept of logical consequence has come under heavy criticism in the last couple of decades. The present work looks at an alternative approach to logical consequence where the notion of inference takes center stage. Formally, the model-theoretic framework is exchanged for a proof-theoretic framework. It is argued that contrary to the traditional view, proof-theoretic semantics is not revisionary, and should rather be seen as a formal semantics that can supplement model-theory. Specifically, there are formal resources to provide a proof-theoretic semantics for both intuitionistic and classical logic. We develop a new perspective on proof-theoretic harmony for logical constants which incorporates elements from the substructural era of proof-theory. We show that there is a semantic lacuna in the traditional accounts of harmony. A new theory of how inference rules determine the semantic content of logical constants is developed. The theory weds proof-theoretic and model-theoretic semantics by showing how proof-theoretic rules can induce truth-conditional clauses in Boolean and many-valued settings. It is argued that such a new approach to how rules determine meaning will ultimately assist our understanding of the apriori nature of logic

Anti-exceptionalism about logic as tradition rejection

While anti-exceptionalism about logic (AEL) is now a popular topic within the philosophy of logic, there’s still a lack of clarity over what the proposal amounts to. currently, it is most common to conceive of AEL as the proposal that logic is continuous with the sciences. Yet, as we show here, this conception of AEL is unhelpful due to both its lack of precision, and its distortion of the current debates. Rather, AEL is better understood as the rejection of certain traditional properties of logic. The picture that results is not of one singular position, but rather a cluster of often connected positions with distinct motivations, understood in terms of their rejection of clusters of the various traditional properties. In order to show the fruitfulness of this new conception of AEL, we distinguish between two prominent versions of the position, metaphysical and epistemological AEL, and show how the two positions need not stand or fall together