Systematic review and meta-analysis of clinical effectiveness of self-management interventions in Parkinson’s disease

BACKGROUND: Parkinson's disease is a complex neurodegenerative condition with significant impact on quality of life (QoL), wellbeing and function. The objective of this review is to evaluate the clinical effectiveness of self-management interventions for people with Parkinson's disease, taking a broad view of self-management and considering effects on QoL, wellbeing and function. METHODS: Systematic searches of four databases (MEDLINE, Embase, PsycINFO, Web of Science) were conducted for studies evaluating self-management interventions for people with Parkinson's disease published up to 16th November 2020. Original quantitative studies of adults with idiopathic Parkinson's disease were included, whilst studies of atypical Parkinsonism were excluded. Full-text articles were independently assessed by two reviewers, with data extracted by one reviewer and reliability checked by a second reviewer, then synthesised through a narrative approach and, for sufficiently similar studies, a meta-analysis of effect size was conducted (using a random-effects meta-analysis with restricted maximum likelihood method pooled estimate). Interventions were subdivided into self-management components according to PRISMS Taxonomy. Risk of bias was examined with the Cochrane Risk of Bias 2 (RoB2) tool or ROBIN-I tool as appropriate. RESULTS: Thirty-six studies were included, evaluating a diverse array of interventions and encompassing a range of study designs (RCT n = 19; non-randomised CT n = five; within subject pre- and post-intervention comparisons n = 12). A total of 2884 participants were assessed in studies across ten countries, with greatest output from North America (14 studies) and UK (six studies). Risk of bias was moderate to high for the majority of studies, mostly due to lack of participant blinding, which is not often practical for interventions of this nature. Only four studies reported statistically significant improvements in QoL, wellbeing or functional outcomes for the intervention compared to controls. These interventions were group-based self-management education and training programmes, either alone, combined with multi-disciplinary rehabilitation, or combined with Cognitive Behaviour Therapy; and a self-guided community-based exercise programme. Four of the RCTs evaluated sufficiently similar interventions and outcomes for meta-analysis: these were studies of self-management education and training programmes evaluating QoL (n = 478). Meta-analysis demonstrated no significant difference between the self-management and the control groups with a standardised mean difference (Hedges g) of - 0.17 (- 0.56, 0.21) p = 0.38. By the GRADE approach, the quality of this evidence was deemed "very low" and the effect of the intervention is therefore uncertain. Components more frequently observed in effective interventions, as per PRISMS taxonomy analysis, were: information about resources; training or rehearsing psychological strategies; social support; and lifestyle advice and support. The applicability of these findings is weakened by the ambiguous and at times overlapping nature of self-management components. CONCLUSION: Approaches and outcomes to self-management interventions in Parkinson's disease are heterogenous. There are insufficient high quality RCTs in this field to show effectiveness of self-management interventions in Parkinson's disease. Whilst it is not possible to draw conclusions on specific intervention components that convey effectiveness, there are promising findings from some studies, which could be targeted in future evaluations

Risk of gastrointestinal bleeding with direct oral anticoagulants: a systematic review and network meta-analysis

Background: Direct oral anticoagulants are increasingly used for a wide range of indications. However, data are conflicting about the risk of major gastrointestinal bleeding with these drugs. We compared the risk of gastrointestinal bleeding with direct oral anticoagulants, warfarin, and low-molecular-weight heparin. Methods: For this systematic review and meta-analysis, we searched MEDLINE and Embase from database inception to April 1, 2016, for prospective and retrospective studies that reported the risk of gastrointestinal bleeding with use of a direct oral anticoagulant compared with warfarin or low-molecular-weight heparin for all indications. We also searched the Cochrane Library for systematic reviews and assessment evaluations, the National Health Service (UK) Economic Evaluation Database, and ISI Web of Science for conference abstracts and proceedings (up to April 1, 2016). The primary outcome was the incidence of major gastrointestinal bleeding, with all gastrointestinal bleeding as a secondary outcome. We did a Bayesian network meta-analysis to produce incidence rate ratios (IRRs) with 95% credible intervals (CrIs). Findings: We identified 38 eligible articles, of which 31 were included in the primary analysis, including 287 692 patients exposed to 230 090 years of anticoagulant drugs. The risk of major gastrointestinal bleeding with direct oral anticoagulants did not differ from that with warfarin or low-molecular-weight heparin (factor Xa vs warfarin IRR 0·78 [95% CrI 0·47−1·08]; warfarin vs dabigatran 0·88 [0·59−1·36]; factor Xa vs low-molecular-weight heparin 1·02 [0·42−2·70]; and low-molecular-weight heparin vs dabigatran 0·67 [0·20−1·82]). In the secondary analysis, factor Xa inhibitors were associated with a reduced risk of all severities of gastrointestinal bleeding compared with warfarin (0·25 [0.07–0.76]) or dabigatran (0.24 [0.07–0.77]). Interpretation: Our findings show no increase in risk of major gastrointestinal bleeding with direct oral anticoagulants compared with warfarin or low-molecular-weight heparin. These findings support the continued use of direct oral anticoagulants. Funding: Leeds Teaching Hospitals Charitable Foundation

After the great inventions: technological change in UK cotton spinning, 1780–1835

This article analyses the improvement of cotton-spinning technologies in the years after the great inventions of Hargreaves, Arkwright, and Crompton. While these ‘macro-inventions’ have attracted considerable historical attention, our understanding of the major changes in types and sizes of spinning machines used in the UK between the 1780s and the onset of state-collected factory statistics in the 1830s is still largely based on the experience of high-profile firms or specific technologies and regions. A new dataset of 1,465 machinery advertisements published in newspapers in England, Scotland, and Ireland between 1780 and 1835 allows us to examine the temporal and spatial dimensions of the market for cotton-spinning machinery, the timings of transitions between different spinning machines, and increases in machine size. The article demonstrates the importance of post-invention technical improvements in the cotton industry, showing that the productivity increases associated with the initial transition from hand to machine spinning have been overstated and that larger gains were made in the ‘micro-invention’ phase, when spinning machines became larger and faster, and required fewer workers to operate them

High prevalence of irritable bowel syndrome-type symptoms in microscopic colitis: implications for treatment.

Patients with microscopic colitis (MC) often present with abdominal pain and diarrhoea, and previous data suggest that there may be overlap between MC and irritable bowel syndrome (IBS). We evaluated the prevalence of IBS-type symptoms in patients with MC, and assess the impact of these symptoms on psychological health and quality of life.We conducted a cross-sectional survey of individuals with a histological diagnosis of MC, collecting demographic data, Rome III IBS-type symptoms, and mood, somatization, and quality of life data.In total, 151 (31.6%) of 478 individuals with a new diagnosis of MC completed questionnaires, 52 (34.4%) of whom reported IBS-type symptoms. The commonest histological subtype was collagenous colitis (51.7%, n = 78), followed by lymphocytic colitis (39.1%, n = 59). Individuals with IBS-type symptoms had significantly higher levels of anxiety [Hospital Anxiety and Depression Scale (HADS) anxiety score 8.6 versus 5.1, p < 0.001], depression (HADS depression score 6.2 versus 3.6, p = 0.001), and somatoform-type behaviour (Patient Health Questionnaire 15 score 12.7 versus 8.0, p < 0.001) compared with individuals who did not. Those with IBS-type symptoms scored significantly worse across all domains of the 36-item Short Form questionnaire, except for physical functioning.More than one third of individuals with MC reported IBS-type symptoms, although whether this is due to ongoing inflammation is unclear. These individuals had higher levels of anxiety, depression, and somatization, and impaired quality of life. Identifying concomitant IBS in individuals with MC may have important implications for management decisions

Sex differences in mathematics and reading achievement are inversely related: within- and across-nation assessment of 10 years of PISA data

We analyzed one decade of data collected by the Programme for International Student Assessment (PISA), including the mathematics and reading performance of nearly 1.5 million 15 year olds in 75 countries. Across nations, boys scored higher than girls in mathematics, but lower than girls in reading. The sex difference in reading was three times as large as in mathematics. There was considerable variation in the extent of the sex differences between nations. There are countries without a sex difference in mathematics performance, and in some countries girls scored higher than boys. Boys scored lower in reading in all nations in all four PISA assessments (2000, 2003, 2006, 2009). Contrary to several previous studies, we found no evidence that the sex differences were related to nations’ gender equality indicators. Further, paradoxically, sex differences in mathematics were consistently and strongly inversely correlated with sex differences in reading: Countries with a smaller sex difference in mathematics had a larger sex difference in reading and vice versa. We demonstrate that this was not merely a between-nation, but also a within-nation effect. This effect is related to relative changes in these sex differences across the performance continuum: We did not find a sex difference in mathematics among the lowest performing students, but this is where the sex difference in reading was largest. In contrast, the sex difference in mathematics was largest among the higher performing students, and this is where the sex difference in reading was smallest. The implication is that if policy makers decide that changes in these sex differences are desired, different approaches will be needed to achieve this for reading and mathematics. Interventions that focus on high-achieving girls in mathematics and on low achieving boys in reading are likely to yield the strongest educational benefits

Free Will in a Quantum World?

In this paper, I argue that Conway and Kochen’s Free Will Theorem (1,2) to the conclusion that quantum mechanics and relativity entail freedom for the particles, does not change the situation in favor of a libertarian position as they would like. In fact, the theorem more or less implicitly assumes that people are free, and thus it begs the question. Moreover, it does not prove neither that if people are free, so are particles, nor that the property people possess when they are said to be free is the same as the one particles possess when they are claimed to be free. I then analyze the Free State Theorem (2), which generalizes the Free Will Theorem without the assumption that people are free, and I show that it does not prove anything about free will, since the notion of freedom for particles is either inconsistent, or it does not concern our common understanding of freedom. In both cases, the Free Will Theorem and the Free State Theorem do not provide any enlightenment on the constraints physics can pose on free will

Higgs production in CP-violating supersymmetric cascade decays: probing the `open hole' at the Large Hadron Collider

A benchmark CP-violating supersymmetric scenario (known as 'CPX-scenario' in the literature) is studied in the context of the Large Hadron Collider (LHC). It is shown that the LHC, with low to moderate accumulated luminosity, will be able to probe the existing `hole' in the $m_{h_1}$-$\tan\beta$ plane, which cannot be ruled out by the LEP data. We explore the parameter space with cascade decay of third generation squarks and gluino with CP-violating decay branching fractions. We propose a multi-channel analysis to probe this parameter space some of which are background free at an integrated luminosity of 5-10 fb$^{-1}$. Specially, multi-lepton final states (3\l,\, 4\l and like sign di-lepton) are almost background free and have $5\sigma$ reach for the corresponding signals with very early data of LHC for both 14 TeV and 7 TeV center of mass energy.Comment: 24 pages, 9 figures, references added as in the journal versio

An alternative approach to measuring treatment persistence with antipsychotic agents among patients with schizophrenia in the Veterans Health Administration

Prior studies have demonstrated the importance of treatment persistence with anti-psychotic agents in sustaining control of schizophrenic symptoms. However, the conventional approach in measuring treatment persistence tended to use only the first prescription episode even though some patients received multiple prescriptions (or multiple treatment episodes) of the same medication within one year following the initiation of the index drug. In this study, we used data from the Veterans Health Administration in the United States to assess the extent to which patients received multiple prescriptions. The study found that about a quarter of the patients had two or more treatment episodes and that levels of treatment persistence tended to vary across treatment episodes. Based on these results, we offered an alternative approach in which we calculated treatment persistence with typical and atypical antipsychotic agents separately for patients with one, two, or three treatment episodes. Considering that patients with different number of treatment episodes might differ in disease profiles, this treatment episode-specific approach offered a fair comparison of the levels of treatment persistence across patients with different number of treatment episodes. Future research needs to extend the analyses beyond two antipsychotic classes to individual antipsychotic agents. A more comprehensive assessment using appropriate analytic methods should help physicians make prescription choices that will ultimately improve the care of patients with schizophrenia

Structure formation in active networks

Structure formation and constant reorganization of the actin cytoskeleton are key requirements for the function of living cells. Here we show that a minimal reconstituted system consisting of actin filaments, crosslinking molecules and molecular-motor filaments exhibits a generic mechanism of structure formation, characterized by a broad distribution of cluster sizes. We demonstrate that the growth of the structures depends on the intricate balance between crosslinker-induced stabilization and simultaneous destabilization by molecular motors, a mechanism analogous to nucleation and growth in passive systems. We also show that the intricate interplay between force generation, coarsening and connectivity is responsible for the highly dynamic process of structure formation in this heterogeneous active gel, and that these competing mechanisms result in anomalous transport, reminiscent of intracellular dynamics

Higgs boson enhancement effects on squark-pair production at the LHC

We study the Higgs boson effects on third-generation squark-pair production in proton-proton collision at the CERN Large Hadron Collider (LHC), including \Stop \Stop^*, \Stop\Sbot^*, and \Sbot \Sbot^*. We found that substantial enhancement can be obtained through s-channel exchanges of Higgs bosons at large $\tan\beta$, at which the enhancement mainly comes from $b\bar b$, $b\bar c$, and $c\bar b$ initial states. We compute the complete set of electroweak (EW) contributions to all production channels. This completes previous computations in the literature. We found that the EW contributions can be significant and can reach up to 25% in more general scenarios and at the resonance of the heavy Higgs boson. The size of Higgs enhancement is comparable or even higher than the PDF uncertainties and so must be included in any reliable analysis. A full analytical computation of all the EW contributions is presented.Comment: 23 pages, 7 figures, 1 tabl