Biomechanical factors associated with the development of tibiofemoral knee osteoarthritis: protocol for a systematic review and meta-analysis

INTRODUCTION: Altered biomechanics, increased joint loading and tissue damage, might be related in a vicious cycle within the development of knee osteoarthritis (KOA). We have defined biomechanical factors as joint-related factors that interact with the forces, moments and kinematics in and around a synovial joint. Although a number of studies and systematic reviews have been performed to assess the association of various factors with the development of KOA, a comprehensive overview focusing on biomechanical factors that are associated with the development of KOA is not available. The aim of this review is (1) to identify biomechanical factors that are associated with (the development of) KOA and (2) to identify the impact of other relevant risk factors on this association. METHODS AND ANALYSIS: Cohort, cross-sectional and case–control studies investigating the association of a biomechanical factor with (the development of) KOA will be included. MEDLINE, EMBASE, CINAHL and SPORTDiscus will be searched from their inception until August 2015. 2 reviewers will independently screen articles obtained by the search for eligibility, extract data and score risk of bias. Quality of evidence will be evaluated. Meta-analysis using random effects model will be applied in each of the biomechanical factors, if possible. ETHICS AND DISSEMINATION: This systematic review and meta-analysis does not require ethical approval. The results of this systematic review and meta-analysis will be disseminated through publications in peer-reviewed journals and presentations at (inter)national conferences. TRIAL REGISTRATION NUMBER: CRD42015025092

Association of malalignment, muscular dysfunction, proprioception, laxity and abnormal joint loading with tibiofemoral knee osteoarthritis - a systematic review and meta-analysis

Background: To investigate (1) the association of specific biomechanical factors with knee osteoarthritis and knee osteoarthritis development, and (2) the impact of other relevant risk factors on this association.Methods: MEDLINE, EMBASE, CINAHL and SPORTDiscus were searched up until April 2017. Studies were included if they fulfilled the following criteria: the study 1) assessed the association of a biomechanical factor with knee osteoarthritis, or knee osteoarthritis development; 2) reported on skeletal malalignment, muscular dysfunction, impaired proprioception, laxity and abnormal loading during gait; 3) was a cohort study with participants developing knee osteoarthritis and participants not developing knee osteoarthritis, or a case-control or cross-sectional study with participants with knee osteoarthritis and without knee osteoarthritis. Risk of bias was assessed with the QUIPS tool and meta-analyses were performed using random effects models.Results: Of 6413 unique studies identified, 59 cross-sectional studies were eligible for meta-analyses (9825 participants, 5328 with knee osteoarthritis). No cohort studies fulfilled the inclusion criteria. Compared with healthy controls, patients with knee osteoarthritis have higher odds of having lower muscle strength, proprioception deficits, more medial varus-valgus laxity and less lateral varus-valgus laxity. Patients with medial knee osteoarthritis have higher odds of having a higher knee adduction moment than healthy controls. Level of evidence was graded as 'very low' to 'moderate' quality. Due to large between study differences moderation of other risk factors on biomechanical risk factors could not be evaluated.Conclusions: Patients with knee osteoarthritis are more likely to display a number of biomechanical characteristics. The causal relationship between specific biomechanical factors and the development of knee osteoarthritis could not be determined as no longitudinal studies were included. There is an urgent need for high quality, longitudinal studies to evaluate the impact of specific biomechanical factors on the development of knee osteoarthritis.Trial Registration: (PROSPERO ID: CRD42015025092)

Trends in the use of disease-modifying therapies among reproductive-aged women with multiple sclerosis in the United States from 2010 to 2019

Purpose: Multiple sclerosis (MS) is a chronic disease of the central nervous system that disproportionately affects women, with typical onset during reproductive age. Several disease-modifying therapies (DMTs) are FDA-approved to slow disease progression, but are not indicated for use during pregnancy. Our objective was to describe trends over time (2010–2019) in monthly point prevalence of DMT use among reproductive-age women, overall and by generic name. Methods: This study used administrative claims data from the US during 2009–2019 to identify women age 15–44 with MS and continuous insurance coverage for ≥12 months. DMTs were identified using prescription fills and procedural claims for alemtuzumab, daclizumab, dimethyl fumarate, fingolimod, glatiramer acetate, interferon beta, mitoxantrone, natalizumab, ocrelizumab, and teriflunomide. Monthly prevalent use was defined as ≥1 days' supply of a DMT in the month. Age- and region-standardized monthly prevalence was estimated nonparametrically. Results: Among 42 281 reproductive-aged women over 818 179 person-months, DMT use increased from a minimum monthly prevalence of 49.3% (February, 2011) to a maximum of 58.7% (April, 2019). In 2010, prevalence of injectable DMTs was 43.1% compared to 2.5% for oral DMTs; by 2014, however, oral DMTs (26.5%) surpassed injectable DMTs (23.7%) as the most common route of administration. In the most recent data available (December, 2019), the most common DMTs were dimethyl fumarate, glatiramer acetate, and fingolimod. Conclusions: DMT use among reproductive-aged women has rapidly evolved during the past decade. Collaborative treatment decision making between women with MS and clinicians may help optimize MS care and improve DMT uptake during reproductive years

Health Care Utilization and Comorbidity History of North Carolina Medicaid Beneficiaries in a Controlled Substance "Lock-in" Program

BACKGROUND Medicaid "lock-in" programs (MLIPs) are a widely used strategy for addressing potential misuse of prescription drugs among beneficiary populations. However, little is known about the health care needs and attributes of beneficiaries selected into these programs. Our goal was to understand the characteristics of those eligible, enrolled, and retained in a state MLIP. METHODS Demographics, comorbidities, and health care utilization were extracted from Medicaid claims from June 2009 through June 2013. Beneficiaries enrolled in North Carolina's MLIP were compared to those who were MLIP-eligible, but not enrolled. Among enrolled beneficiaries, those completing the 12-month MLIP were compared to those who exited prior to 12 months. RESULTS Compared to beneficiaries who were eligible for, but not enrolled in the MLIP (N = 11,983), enrolled beneficiaries (N = 5,424) were more likely to have: 1) substance use (23% versus 14%) and mental health disorders, 2) obtained controlled substances from multiple pharmacies, and 3) visited more emergency departments (mean: 8.3 versus 4.2 in the year prior to enrollment). One-third (N = 1,776) of those enrolled in the MLIP exited the program prior to completion. LIMITATIONS Accurate information on unique prescribers visited by beneficiaries was unavailable. Time enrolled in Medicaid differed for beneficiaries, which may have led to underestimation of covariate prevalence. CONCLUSIONS North Carolina's MLIP appears to be successful in identifying subpopulations that may benefit from provision and coordination of services, such as substance abuse and mental health services. However, there are challenges in retaining this population for the entire MLIP duration

A 'civilized' drink and a 'civilizing' industry: wine growing and cultural imagining in colonial New South Wales

My starting point for this thesis was the absence of a foundation history of Australian wine growing conducted by an historian rather than researchers in other disciplines or the media. I have used existing work on wine history in New South Wales from 1788 to 1901 alongside a significant body of new research to create an historical argument suitable for incorporation into more broadly-themed narratives of Australian history and to inform studies of wine growing in other academic fields. My main argument is that although wine growing proved of little economic value in colonial primary production compared with nation-building commodities - such as pastoralism, wheat growing and gold - advocates of the cultivation of wine grapes believed wine growing embodied beneficial, even transformative, cultural value so they persisted in attempting to create a ‘civilizing’ industry producing a ‘civilized’ drink despite lacklustre consumption of their product and very modest profits. Several times, from 1788 to 1901, these advocates spoke out or wrote about wine and wine growing as capable of creating order in a wild or ‘savage’ landscape and within a settler society shaped culturally by shifting adaptations to both imported and ‘native’ influences in agriculture as well as alcohol production, consumption and distribution. While the methodological framework employed here falls mainly within cultural and economic history, sociological theories have contributed to findings on causation. The result is a comprehensive narrative of colonial wine growing in New South Wales enriched by links to key developments in Australian colonial history and with reference to wine growing in other British colonies or former territories

Missing data approaches in longitudinal studies of aging: A case example using the National Health and Aging Trends Study

Purpose Missing data is a key methodological consideration in longitudinal studies of aging. We described missing data challenges and potential methodological solutions using a case example describing five-year frailty state transitions in a cohort of older adults. Methods We used longitudinal data from the National Health and Aging Trends Study, a nationally-representative cohort of Medicare beneficiaries. We assessed the five components of the Fried frailty phenotype and classified frailty based on their number of components (robust: 0, prefrail: 1–2, frail: 3–5). One-, two-, and five-year frailty state transitions were defined as movements between frailty states or death. Missing frailty components were imputed using hot deck imputation. Inverse probability weights were used to account for potentially informative loss-to-follow-up. We conducted scenario analyses to test a range of assumptions related to missing data. Results Missing data were common for frailty components measured using physical assessments (walking speed, grip strength). At five years, 36% of individuals were lost-to-follow-up, differentially with respect to baseline frailty status. Assumptions for missing data mechanisms impacted inference regarding individuals improving or worsening in frailty. Conclusions Missing data and loss-to-follow-up are common in longitudinal studies of aging. Robust epidemiologic methods can improve the rigor and interpretability of aging-related research

Comparative effectiveness and harms of antibiotics for outpatient diverticulitis two nationwide cohort studies

Background: Outpatient diverticulitis is commonly treated with either a combination of metronidazole and a fluoroquinolone (metronidazole-with-fluoroquinolone) or amoxicillin-clavulanate alone. The U.S. Food and Drug Administration advised that fluoroquinolones be reserved for conditions with no alternative treatment options. The comparative effectiveness of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for diverticulitis is uncertain. Objective: To determine the effectiveness and harms of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for outpatient diverticulitis. Design: Active-comparator, new-user, retrospective cohort studies. Setting: Nationwide population-based claims data on U.S. residents aged 18 to 64 years with private employer-sponsored insurance (2000 to 2018) or those aged 65 years or older with Medicare (2006 to 2015). Participants: Immunocompetent adults with diverticulitis in the outpatient setting. Intervention: Metronidazole-with-fluoroquinolone or amoxicillin-clavulanate. Measurements: 1-year risks for inpatient admission, urgent surgery, and Clostridioides difficile infection (CDI) and 3-year risk for elective surgery. Results: In MarketScan (IBM Watson Health), new users of metronidazole-with-fluoroquinolone (n = 106 361) and amoxicillin-clavulanate (n = 13 160) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [95% CI, -0.3 to 0.6]), 1-year urgent surgery risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]), 3-year elective surgery risk (risk difference, 0.2 percentage points [CI, -0.3 to 0.7]), or 1-year CDI risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]) between groups. In Medicare, new users of metronidazole-with-fluoroquinolone (n = 17 639) and amoxicillin-clavulanate (n = 2709) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [CI, -0.7 to 0.9]), 1-year urgent surgery risk (risk difference, -0.2 percentage points [CI, -0.6 to 0.1]), or 3-year elective surgery risk (risk difference, -0.3 percentage points [CI, -1.1 to 0.4]) between groups. The 1-year CDI risk was higher for metronidazole-with-fluoroquinolone than for amoxicillin-clavulanate (risk difference, 0.6 percentage points [CI, 0.2 to 1.0]). Limitation: Residual confounding is possible, and not all harms associated with these antibiotics, most notably drug-induced liver injury, could be assessed. Conclusion: Treating diverticulitis in the outpatient setting with amoxicillin-clavulanate may reduce the risk for fluoroquinolone-related harms without adversely affecting diverticulitis-specific outcomes

A method of strategic evaluation of energy performance of Building Integrated Photovoltaic in the urban context

This paper presents an integrated bottom-up approach aimed at helping those dealing with strategical analysis of installation of Building Integrated Photo Voltaic (BIPV) to estimate the electricity production potential along with the energy needs of urban buildings at the district scale. On the demand side, hourly energy profiles are generated using dynamic building simulation taking into account actual urban morphologies. On the supply side, electricity generated from the system is predicted considering both the direct and indirect components of solar radiation as well as local climate variables. Python-based Algorithm editor Grasshopper is used to interlink four types of modelling and simulation tools as 1) generation of 3-D model, 2) solar radiation analysis, 3) formatting weather files (TMY data set) and 4) dynamic energy demand. The method has been demonstrated for a cluster of 20 buildings located in the Yasar University in Izmir (Turkey), for which it is found the BIPV system could achieve an annual renewable share of 23%, in line with the Renewable Energy Directive target of 20%. Quantitatively-compared demand and supply information at hourly time step shows that only some energy needs can be met by BIPV, so there is a need for an appropriate matching strategy to better exploit the renewable energy potential

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results