Challenging reductionism in analyses of EU-Russia energy relations

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A more representative chamber: representation and the House of Lords

Since 1997 there has been substantive reform of the House of Lords in an effort to make the chamber ‘more democratic and more representative’. Whilst the Labour government failed to press ahead with any of the proposed plans for further reform following the removal of the bulk of the hereditary peers in 1999, it remained committed to the notion that such reform must make the second chamber ‘more representative’. The coalition government's programme advocates a long-term aspiration for a House wholly or mainly elected on the basis of proportional representation, and a short-term approach based on additional appointments to ensure a balance of the parties. What is clear in all of these proposals for reform is a desire for the House of Lords to become more representative than it is at present. However, what is less clear is what is meant by ‘representative’ – who the House of Lords is supposed to represent, and what form representation will take. Moreover, in proposing to make the chamber more representative, either through appointment or election, little attention has been paid to how the current House of Lords provides representation. This article examines these questions in the context of Pitkin's classic conceptions of representation and peers' attitudes towards their own representative rol

Risk factors for dislocation after primary total hip replacement:a systematic review and meta-analysis of 125 studies involving approximately five million hip replacements

Background:&nbsp;Dislocation following total hip replacement is associated with repeated admissions to hospital and substantial costs to the health system. Factors influencing dislocation following primary total hip replacement are not well understood. We aimed to assess the association of various factors with dislocation risk following primary total hip replacement. Methods:&nbsp;We did a systematic review and meta-analysis of longitudinal studies reporting associations of patient-related, surgery-related, implant-related, and hospital-related factors with dislocation risk after primary total hip replacement. We searched MEDLINE, Embase, Web of Science, and the Cochrane Library for all relevant articles published up to March 8, 2019. Summary measures of association were calculated with relative risks (RRs) and 95% CIs. This study is registered on PROSPERO, number CRD42019121378. Findings:&nbsp;We identified 149 articles based on 125 unique studies with data on 4 633 935 primary total hip replacements and 35 264 dislocations. The incidence of dislocation ranged from 0&middot;12% to 16&middot;13%, with an overall pooled incidence of 2&middot;10% (95% CI 1&middot;83&ndash;2&middot;38) over a weighted mean follow-up duration of 6 years. Based on the median year of data collection, a significant decline in dislocation rates was observed from 1971 to 2015. The risk of dislocation did not differ significantly between male versus female patients (RR 0&middot;97; 95% CI 0&middot;88&ndash;1&middot;08), was higher in those aged 70 years and older than in those younger than 70 years (1&middot;27; 1&middot;02&ndash;1&middot;57), and was lower in those from high versus low income groups (0&middot;79; 0&middot;74&ndash;0&middot;85). White ethnicity (only when compared with Asian ethnicity), drug use disorder, and social deprivation were significantly associated with increased dislocation risk. The risk of dislocation was higher in patients with body-mass index (BMI) of 30 kg/m2&nbsp;or higher than in those with BMI lower than 30 kg/m2&nbsp;(RR 1&middot;38; 95% CI 1&middot;03&ndash;1&middot;85). Medical factors and those related to surgical history that were significantly associated with increased dislocation risk included neurological disorder, psychiatric disease, comorbidity indices, previous surgery including spinal fusion, and surgical indications including avascular necrosis, rheumatoid arthritis, inflammatory arthritis, and osteonecrosis. Surgical factors such as the anterolateral, direct anterior, or lateral approach, and posterior approach with short external rotator and capsule repair were significantly associated with reduced dislocation risk. At the implant level, larger femoral head diameters, elevated acetabular liners, dual mobility cups, cemented fixations, and standard femoral neck lengths significantly reduced the risk of dislocation. Hospital-related factors such as experienced surgeons and high surgeon procedure volume significantly reduced the risk of dislocation. Interpretation:&nbsp;Dislocation following primary total hip replacement has declined over time. Surgical approaches that reduce dislocation risk can be used by clinicians during primary total hip replacement, and alternative bearings such as dual mobility can be used in individuals at high risk of dislocation. Modifiable risk factors such as high BMI and comorbidities might also be amenable to optimisation before surgery. </div

Secondary prevention of fractures after hip fracture:a qualitative study of effective service delivery

There is variation in how services to prevent secondary fractures after hip fracture are delivered and no consensus on best models of care. This study identifies healthcare professionals' views on effective care for the prevention of these fractures. It is hoped this will provide information on how to develop services.Hip fracture patients are at high risk of subsequent osteoporotic fractures. Whilst fracture prevention services are recommended, there is variation in delivery and no consensus on best models of care. This study aims to identify healthcare professionals' views on effective care for prevention of secondary fracture after hip fracture.Forty-three semi-structured interviews were undertaken with healthcare professionals involved in delivering fracture prevention across 11 hospitals in one English region. Interviews explored views on four components of care: (1) case finding, (2) osteoporosis assessment, (3) treatment initiation, and (4) monitoring and coordination. Interviews were audio-recorded, transcribed, anonymised and coded using NVivo software.Case finding: a number of approaches were discussed. Multiple methods ensured there was a 'backstop' if patients were overlooked. Osteoporosis assessment: there was no consensus on who should conduct this. The location of the dual energy X-ray absorptiometry (DXA) scanner influenced the likelihood of patients receiving a scan. Treatment initiation: it was felt this was best done in inpatients rather request initiation in the post-discharge/outpatients period. Monitoring (adherence): adherence was a major concern, and participants felt more monitoring could be conducted by secondary care. Coordination of care: participants advocated using dedicated coordinators and formal and informal methods of communication. A gap between primary and secondary care was identified and strategies suggested for addressing this.A number of ways of organising effective fracture prevention services after hip fracture were identified. It is hoped that this will help professionals identify gaps in care and provide information on how to develop services

Predicting incident radiographic knee osteoarthritis in middle-aged women within 4 years:the importance of knee-level prognostic factors.

ObjectiveDevelop and internally validate risk models and a clinical risk score tool to predict incident radiographic knee osteoarthritis (RKOA) in middle‐aged women.MethodsWe analysed 649 women in the Chingford 1000 Women study. The outcome was incident RKOA, defined as Kellgren/Lawrence grade 0‐1 at baseline and ≥2 at year 5. We estimated predictors' effects on the outcome using logistic regression models. Two models were generated. The clinical model considered patient characteristics, medication, biomarkers, and knee symptoms. The radiographic model considered the same factors, plus radiographic factors (e.g., angle between the acetabular roof and ilium's vertical cortex (hip α‐angle)). The models were internally validated. Model performance was assessed using calibration and discrimination (area under the receiver characteristic curve, AUC).ResultsThe clinical model contained age, quadriceps circumference, and a cartilage degradation marker (CTX‐II) as predictors (AUC = 0.692). The radiographic model contained older age, greater quadriceps circumference, knee pain, knee baseline Kellgren/Lawrence grade 1 (versus 0), greater hip α‐angle, greater spinal bone mineral density, and contralateral RKOA at baseline as predictors (AUC = 0.797). Calibration tests showed good agreement between the observed and predicted incident RKOA. A clinical risk score tool was developed from the clinical model.ConclusionTwo models predicting incident RKOA within 4 years were developed; including radiographic variables improved model performance. First‐time predictor hip α‐angle and contralateral RKOA suggest osteoarthritis origins beyond the knee. The clinical tool has the potential to help physicians identify patients at risk of RKOA in routine practice, but should be externally validated

Progression of chronic pain and associated health-related quality of life and healthcare resource use over 5 years after total knee replacement: evidence from a cohort study

Objective As part of the STAR Programme, a comprehensive study exploring long-term pain after surgery, we investigated how pain and function, health-related quality of life (HRQL), and healthcare resource use evolved over 5 years after total knee replacement (TKR) for those with and without chronic pain 1 year after their primary surgery. Methods We used data from the Clinical Outcomes in Arthroplasty Study prospective cohort study, which followed patients undergoing TKR from two English hospitals for 5 years. Chronic pain was defined using the Oxford Knee Score Pain Subscale (OKS-PS) where participants reporting a score of 14 or lower were classified as having chronic pain 1-year postsurgery. Pain and function were measured with the OKS, HRQL using the EuroQoL-5 Dimension, resource use from yearly questionnaires, and costs estimated from a healthcare system perspective. We analysed the changes in OKS-PS, HRQL and resource use over a 5-year follow-up period. Multiple imputation accounted for missing data. Results Chronic pain was reported in 70/552 operated knees (12.7%) 1 year after surgery. The chronic pain group had worse pain, function and HRQL presurgery and postsurgery than the non-chronic pain group. Those without chronic pain markedly improved right after surgery, then plateaued. Those with chronic pain improved slowly but steadily. Participants with chronic pain reported greater healthcare resource use and costs than those without, especially 1 year after surgery, and mostly from hospital readmissions. 64.7% of those in chronic pain recovered during the following 4 years, while 30.9% fluctuated in and out of chronic pain. Conclusion Although TKR is often highly beneficial, some patients experienced chronic pain postsurgery. Although many fluctuated in their pain levels and most recovered over time, identifying people most likely to have chronic pain and supporting their recovery would benefit patients and healthcare systems

Diaphragm Abnormalities in Patients with End-Stage Heart Failure: NADPH Oxidase Upregulation and Protein Oxidation

Patients with heart failure (HF) have diaphragm abnormalities that contribute to disease morbidity and mortality. Studies in animals suggest that reactive oxygen species (ROS) cause diaphragm abnormalities in HF. However, the effects of HF on ROS sources, antioxidant enzymes, and protein oxidation in the diaphragm of humans is unknown. NAD(P)H oxidase, especially the Nox2 isoform, is an important source of ROS in the diaphragm. Our main hypothesis was that diaphragm from patients with HF have heightened Nox2 expression and p47phox phosphorylation (marker of enzyme activation) that is associated with elevated protein oxidation. We collected diaphragm biopsies from patients with HF and brain-dead organ donors (controls). Diaphragm mRNA levels of Nox2 subunits were increased 2.5–4.6-fold over controls (p \u3c 0.05). Patients also had increased protein levels of Nox2 subunits (p47phox, p22phox, and p67phox) and total p47phox phosphorylation, while phospho-to-total p47phox levels were unchanged. The antioxidant enzyme catalase was increased in patients, whereas glutathione peroxidase and superoxide dismutases were unchanged. Among markers of protein oxidation, carbonyls were increased by ~40% (p \u3c 0.05) and 4-hydroxynonenal and 3-nitrotyrosines were unchanged in patients with HF. Overall, our findings suggest that Nox2 is an important source of ROS in the diaphragm of patients with HF and increases in levels of antioxidant enzymes are not sufficient to maintain normal redox homeostasis. The net outcome is elevated diaphragm protein oxidation that has been shown to cause weakness in animals

Models of care for the delivery of secondary fracture prevention after hip fracture:a health service cost, clinical outcomes and cost-effectiveness study within a region of England.

Background Professional bodies have produced comprehensive guidance about the management of hip fracture. They recommend orthogeriatric services focusing on achieving optimal recovery, and fracture liaison services (FLSs) focusing on secondary fracture prevention. Despite such guidelines being in place, there is significant variation in how services are structured and organised between hospitals. Objectives To establish the clinical effectiveness and cost-effectiveness of changes to the delivery of secondary fracture prevention services, and to identify barriers and facilitators to changes. Design A service evaluation to identify each hospital’s current models of care and changes in service delivery. A qualitative study to identify barriers and facilitators to change. Health economics analysis to establish NHS costs and cost-effectiveness. A natural experimental study to determine clinical effectiveness of changes to a hospital’s model of care. Setting Eleven acute hospitals in a region of England. Participants Qualitative study – 43 health professionals working in fracture prevention services in secondary care. Interventions Changes made to secondary fracture prevention services at each hospital between 2003 and 2012. Main outcome measures The primary outcome is secondary hip fracture. Secondary outcomes include mortality, non-hip fragility fracture and the overall rate of hip fracture. Data sources Clinical effectiveness/cost-effectiveness analyses – primary hip fracture patients identified from (1) Hospital Episode Statistics (2003–13, n = 33,152); and (2) Clinical Practice Research Datalink (1999–2013, n = 11,243). Results Service evaluation – there was significant variation in the organisation of secondary fracture prevention services, including staffing levels, type of service model (consultant vs. nurse led) and underlying processes. Qualitative – fracture prevention co-ordinators gave multidisciplinary health professionals capacity to work together, but communication with general practitioners was challenging. The intervention was easily integrated into practice but some participants felt that implementation was undermined by under-resourced services. Making business cases for a service was particularly challenging. Natural experiment – the impact of introducing an orthogeriatrician on 30-day and 1-year mortality was hazard ratio (HR) 0.73 [95% confidence interval (CI) 0.65 to 0.82] and HR 0.81 (95% CI 0.75 to 0.87), respectively. Thirty-day and 1-year mortality were likewise reduced following the introduction or expansion of a FLS: HR 0.80 (95% CI 0.71 to 0.91) and HR 0.84 (95% CI 0.77 to 0.93), respectively. There was no significant impact on time to secondary hip fracture. Health economics – the annual cost in the year of hip fracture was estimated at £10,964 (95% CI £10,767 to £11,161) higher than the previous year. The annual cost associated with all incident hip fractures in the UK among those aged ≥ 50 years (n = 79,243) was estimated at £1215M. At a £30,000 per quality-adjusted life-year threshold, the most cost-effective model was introducing an orthogeriatrician. Conclusion In hip fracture patients, orthogeriatrician and nurse-led FLS models are associated with reductions in mortality rates and are cost-effective, the orthogeriatrician model being the most cost-effective. There was no evidence for a reduction in second hip fracture. Qualitative data suggest that weaknesses lie in treatment adherence/monitoring, a possible reason for the lack of effectiveness on second hip fracture outcome. The effectiveness on non-hip fracture outcomes remains unanswered. Future work Reliable estimates of health state utility values for patients with hip and non-hip fractures are required to reduce uncertainty in health economic models. A clinical trial is needed to assess the clinical effectiveness and cost-effectiveness of a FLS for non-hip fracture patients. Funding The National Institute for Health Research (NIHR) Health Services and Delivery Research programme and the NIHR Musculoskeletal Biomedical Research Unit, University of Oxford

Nocardia kroppenstedtii sp. nov., a novel actinomycete isolated from a lung transplant patient with a pulmonary infection

An actinomycete, strain N1286T, isolated from a lung transplant patient with a pulmonary infection, was provisionally assigned to the genus Nocardia. The strain had chemotaxonomic and morphological properties typical of members of the genus Nocardia and formed a distinct phyletic line in the Nocardia 16S rRNA gene tree. It was most closely related to Nocardia farcinica DSM 43665T (99.8% gene similarity) but was distinguished from the latter by a low level of DNA:DNA relatedness. These strains were also distinguished by a broad range of phenotypic properties. On the basis of these data, it is proposed that isolate N1286T (=DSM 45810T = NCTC 13617T) should be classified as the type strain of a new Nocardia species for which the name Nocardia kroppenstedtii is proposed

Better post-operative prediction and management of chronic pain in adults after total knee replacement:the multidisciplinary STAR research programme including RCT

Background: The treatment of osteoarthritis with knee replacement aims to reduce pain and disability. However, some people experience chronic pain. Objectives: To improve outcomes for people with chronic pain after knee replacement by identifying post-surgical predictors and effective interventions, characterising patient pathways and resource use, developing and evaluating a new care pathway, and exploring non-use of services. Design: The programme comprised systematic reviews, national database analyses, a cohort study, intervention development, a randomised controlled trial, health economic analyses, qualitative studies and stakeholder engagement. Extensive and meaningful patient and public involvement underpinned all studies. Setting: NHS, secondary care, primary care. Participants: People with, or at risk of, chronic pain after knee replacement and health-care professionals involved in the care of people with pain. Interventions: A care pathway for the management of people with pain at 3 months after knee replacement. Main outcome measures: Patient-reported outcomes and cost-effectiveness over 12 months. Data sources: Literature databases, the National Joint Registry, Hospital Episode Statistics, patient- reported outcomes, the Clinical Practice Research Datalink, the Clinical Outcomes in Arthroplasty Study, the Support and Treatment After joint Replacement randomised trial, interviews with 90 patients and 14 health-care professionals, and stakeholder events. Review methods: Systematic reviews of cohort studies or randomised trials, using meta-analysis or narrative synthesis. Results: In the Clinical Outcomes in Arthroplasty Study cohort, 14% of people experienced chronic pain 1 year after knee replacement. By 5 years, 65% reported no pain, 31% fluctuated and 4% remained in chronic pain. People with chronic pain had a worse quality of life, higher primary care costs, and more frequent analgesia prescriptions, particularly for opioids, than those not in chronic pain. People with chronic pain after knee replacement who made little or no use of services often felt nothing more could be done, or that further treatments may have no benefit or cause harm. People described a feeling of disconnection from their replaced knee. Analysis of UK databases identified risk factors for chronic pain after knee replacement. Pre- operative predictors were mild knee pain, smoking, deprivation, body mass index between 35 and 40 kg/m2 and knee arthroscopy. Peri- and post-operative predictors were mechanical complications, infection, readmission, revision, extended hospital stay, manipulation under anaesthetic and use of opioids or antidepressants. In systematic reviews, pre-operative exercise and education showed no benefit in relation to chronic pain. Peri-operative interventions that merit further research were identified. Common peri- operative treatments were not associated with chronic pain. There was no strong evidence favouring specific post-operative physiotherapy content. We evaluated the Support and Treatment After joint Replacement care pathway in a multicentre randomised controlled trial. We randomised 363 people with pain at 3 months after knee replacement from eight NHS Trusts in England and Wales. At 12 months’ follow-up, the intervention group had lower mean pain severity (adjusted difference –0.65, 95% confidence interval –1.17 to -0.13; p = 0.014) and pain interference (adjusted difference –0.68, 95% confidence interval –1.29 to -0.08; p = 0.026), as measured on the Brief Pain Inventory subscales (scale 0–10). People receiving the Support and Treatment After joint Replacement pathway had lower NHS and Personal Social Services costs (–£724, 95% confidence interval –£150 to £51) and higher quality-adjusted life-years (0.03, 95% confidence interval –0.008 to 0.06) than those with usual care. The Support and Treatment After joint Replacement pathway was cost-effective with an incremental net monetary benefit at the £20,000 per quality-adjusted life-year threshold of £1256 (95% confidence interval £164 to £2348), indicating a 98.79% probability that the intervention is the cost-effective option. Participants found the Support and Treatment After joint Replacement pathway acceptable, with opportunities to receive information and discuss concerns while ensuring further treatment and support. In systematic reviews considering treatments for chronic pain after surgery we identified some unifactorial interventions that merit further research after knee replacement. Health-care professionals delivering and implementing the Support and Treatment After joint Replacement pathway valued its focus on neuropathic pain and psychosocial issues, enhanced patient care, formalised referrals, and improved pain management. Stakeholders supported pathway implementation. Limitations: Database analyses were limited to factors recorded in data sets. Pain was only measured 6 months after surgery. However, analyses including large numbers of centres and patients should be generalisable across the NHS. In many studies found in systematic reviews, long-term pain was not a key outcome. Conclusions: The Support and Treatment After joint Replacement pathway is a clinically effective and cost-effective, acceptable intervention for the management of chronic pain after knee replacement. Unifactorial interventions merit further study before inclusion in patient care. People with pain should be empowered to seek health care, with the support of health-care professionals. Future work: Future work should include research relating to the implementation of the Support and Treatment After joint Replacement pathway into the NHS, an assessment of its long-term clinical effectiveness and cost-effectiveness and wider application, and an evaluation of new interventions for incorporation in the pathway. It will also be important to design and conduct research to improve communication between patients and health-care professionals before surgery; explore whether or not education and support can enable earlier recognition of chronic pain; consider research that may identify how to support people’s feelings of disconnectedness from their new knee; and design and evaluate a pre-surgical intervention based on risk factors. Study registration: All systematic reviews were registered on PROSPERO (CRD42015015957, CRD42016041374 and CRD42017041382). The Support and Treatment After joint Replacement randomised trial was registered as ISRCTN92545361. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 11, No. 3. See the NIHR Journals Library website for further project information