Search

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.

Background: Apolipoprotein B (apoB) is emerging as the crucial lipoprotein trait for the role of lipoprotein lipids in the aetiology of coronary heart disease. In this study, we evaluated the effects of genetically predicted apoB on outcomes in first-degree relatives. Methods: Data on lipoprotein lipids and disease outcomes in first-degree relatives were obtained from the UK Biobank study. We did a univariable mendelian randomisation analysis using a weighted genetic instrument for apoB. For outcomes with which apoB was associated at a false discovery rate (FDR) of less than 5%, multivariable mendelian randomisation analyses were done, including genetic instruments for LDL cholesterol and triglycerides. Associations between apoB and self-reported outcomes in first-degree relatives were characterised for 12 diseases (including heart disease, stroke, and hypertension) and parental vital status together with age at death. Estimates were inferred causal effects per 1 SD elevated lipoprotein trait (for apoB, 1 SD=0·24 g/L). Replication of estimates for lifespan and type 2 diabetes was done using conventional two-sample mendelian randomisation with summary estimates from genome-wide association study consortia. Findings: In univariable mendelian randomisation, genetically elevated apoB in participants was identified to lead to a shorter lifespan in parents (fathers: 0·89 years of life lost per 1 SD higher apoB in offspring, 95% CI 0·63–1·16, FDR-adjusted p=4·0 × 10⁻¹⁰; mothers: 0·48 years of life lost per 1 SD higher apoB in offspring, 0·25–0·71, FDR-adjusted p=1·7 × 10⁻⁴). The effects were strengthened to around 2 years of life lost in multivariable mendelian randomisation and were replicated in conventional two-sample mendelian randomisation (odds ratio [OR] of surviving to the 90th centile of lifespan: 0·38 per 1 SD higher apoB in offspring, 95% CI 0·22–0·65). Genetically elevated apoB caused higher risks of heart disease in all first-degree relatives and a higher risk of stroke in mothers. Findings in first-degree relatives were replicated in two-sample multivariable mendelian randomisation, which identified apoB to increase (OR 2·32 per 1 SD higher apoB, 95% CI 1·49–3·61) and LDL cholesterol to decrease (0·34 per 1 SD higher LDL cholesterol, 0·21–0·54) the risk of type 2 diabetes. Interpretation: Higher apoB shortens lifespan, increases risks of heart disease and stroke, and in multivariable analyses that account for LDL cholesterol, increases risk of diabetes. Funding: British Heart Foundation, UK Medical Research Council, and UK Research and Innovation.

Background: Circulating lipoprotein lipids cause coronary heart disease (CHD). However, the precise way in which one or more lipoprotein lipid-related entities account for this relationship remains unclear. Using genetic instruments for lipoprotein lipid traits implemented through multivariable Mendelian randomisation (MR), we sought to compare their causal roles in the aetiology of CHD. Methods and findings: We conducted a genome-wide association study (GWAS) of circulating non-fasted lipoprotein lipid traits in the UK Biobank (UKBB) for low-density lipoprotein (LDL) cholesterol, triglycerides, and apolipoprotein B to identify lipid-associated single nucleotide polymorphisms (SNPs). Using data from CARDIoGRAMplusC4D for CHD (consisting of 60,801 cases and 123,504 controls), we performed univariable and multivariable MR analyses. Similar GWAS and MR analyses were conducted for high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I. The GWAS of lipids and apolipoproteins in the UKBB included between 393,193 and 441,016 individuals in whom the mean age was 56.9 y (range 39–73 y) and of whom 54.2% were women. The mean (standard deviation) lipid concentrations were LDL cholesterol 3.57 (0.87) mmol/L and HDL cholesterol 1.45 (0.38) mmol/L, and the median triglycerides was 1.50 (IQR = 1.11) mmol/L. The mean (standard deviation) values for apolipoproteins B and A-I were 1.03 (0.24) g/L and 1.54 (0.27) g/L, respectively. The GWAS identified multiple independent SNPs associated at P < 5 × 10−8 for LDL cholesterol (220), apolipoprotein B (n = 255), triglycerides (440), HDL cholesterol (534), and apolipoprotein A-I (440). Between 56%–93% of SNPs identified for each lipid trait had not been previously reported in large-scale GWASs. Almost half (46%) of these SNPs were associated at P < 5 × 10−8 with more than one lipid-related trait. Assessed individually using MR, LDL cholesterol (odds ratio [OR] 1.66 per 1-standard-deviation–higher trait; 95% CI: 1.49–1.86; P < 0.001), triglycerides (OR 1.34; 95% CI: 1.25–1.44; P < 0.001) and apolipoprotein B (OR 1.73; 95% CI: 1.56–1.91; P < 0.001) had effect estimates consistent with a higher risk of CHD. In multivariable MR, only apolipoprotein B (OR 1.92; 95% CI: 1.31–2.81; P < 0.001) retained a robust effect, with the estimate for LDL cholesterol (OR 0.85; 95% CI: 0.57–1.27; P = 0.44) reversing and that of triglycerides (OR 1.12; 95% CI: 1.02–1.23; P = 0.01) becoming weaker. Individual MR analyses showed a 1-standard-deviation–higher HDL cholesterol (OR 0.80; 95% CI: 0.75–0.86; P < 0.001) and apolipoprotein A-I (OR 0.83; 95% CI: 0.77–0.89; P < 0.001) to lower the risk of CHD, but these effect estimates attenuated substantially to the null on accounting for apolipoprotein B. A limitation is that, owing to the nature of lipoprotein metabolism, measures related to the composition of lipoprotein particles are highly correlated, creating a challenge in making exclusive interpretations on causation of individual components. Conclusions: These findings suggest that apolipoprotein B is the predominant trait that accounts for the aetiological relationship of lipoprotein lipids with risk of CHD.

Ecologically intact ecosystems are becoming increasingly limited on the planet, making their identification and conservation an important priority. Intact forest landscapes (IFLs) are defined as forests that are mainly free of significant anthropogenic degradation and at least 500 km2 in size. Here we define a new metric, the Last of the Wild in each Ecoregion (LWE), as a preliminary scoping of the most intact parts of each ecoregion. IFL and LWE are approaches among a broad family of techniques to mapping ecological integrity at the global scale. Although both implicitly include species integrity as a dimension of intactness, this is inferred rather than directly measured. We assessed whether LWE areas or IFL were better at capturing species where they are most abundant using species distribution data for a set of forest species for which range-wide data were available and human activity limits the range. We found that IFL and LWE methods identified areas where species we assessed are either absent or at too low an abundance to be ecologically functional. As such many IFL/LWE polygons did not have intact fauna. We also show that 54.7% of the terrestrial realm (excluding Antarctica) has at least one species recorded as extinct and that two thirds of IFL/LWE areas overlap with areas where species have gone extinct in the past 500 years. The results show that neither IFL or LWE identifies areas of ecologically intact fauna adequately, underscoring a strong need to obtain additional site-level survey data to confirm faunal intactness.

© 2017 The Healthcare Infection Society Background Umbilical venous catheters (UVCs) or peripherally inserted central catheters (PICCs), widely used in high-risk neonates, may have a threshold dwell time for subsequent increased risk of central-line-associated bloodstream infection (CLABSI). Aim To evaluate the CLABSI risks in neonates having either UVC, PICC, or those having both sequentially. Methods The study included 3985 infants who had UVC or PICC inserted between 2007 and 2009 cared for in 10 regional neonatal intensive care units: 1392 having UVC only (group 1), 1317 PICC only (group 2), and 1276 both UVC and PICC (group 3). Findings There were 403 CLABSIs among 6000 venous catheters inserted, totalling 43,302 catheter-days. CLABSI rates were higher in group 3 infants who were of lowest gestation (16.9 per 1000 UVC-days and 12.5 per 1000 PICC-days; median: 28 weeks) when compared with group 1 (3.3 per 1000 UVC-days; 37 weeks) and group 2 (4.8 per 1000 PICC-days; 30 weeks). Life table and Kaplan–Meier hazard analysis showed that UVC CLABSI rate increased stepwise to 42 per 1000 UVC-days by day 10, with the highest rate in group 3 (85 per 1000 UVC-days). PICC CLABSI rates remained relatively stable at 12–20 per 1000 PICC-days. Compared to PICC, UVC had a higher adjusted CLABSI risk controlled for dwell time. Among group 3, replacing UVC electively before day 4 may have a trend of lower CLABSI risk than late replacement. Conclusion There was no cut-off duration beyond which PICC should be removed electively. Early UVC removal and replacement by PICC before day 4 might be considered.

Acoustic emission monitoring is often used in the diagnosis of electrical and mechanical incipient faults in high-voltage apparatus. Partial discharges are a source of failure in power transformers, and the differentiation from other sources of acoustic emissions is of the utmost importance. This paper reports the development of a new sensor concept-mandrel-based fiber-optic sensor-for the detection of incipient faults in oil-filled power transformers, taking direct measurements inside a transformer. These sensors can be placed in the inner surface of the transformer tank wall, not affecting the insulation integrity of the structure, and improving fault detection and location. The applicability of these acoustic sensors in air, water, and oil is investigated and the paper presents the promising results obtained, which will enable the industrial development of practical solutions.

This article reports the development of two sensing head configurations based on extrinsic and intrinsic fiber Fabry-Perot interferometers for the detection of incipient faults in oil-filled power transformers. The performances of the sensing heads are characterized and compared with the situations where it operates in air, water, and oil and promising results are obtained, which will allow the industrial development of practical solutions. © 2010 Wiley Periodicals, Inc. Microwave Opt Technol Lett 52: 1129–1134, 2010; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.25139

Acoustic emission monitoring is often used in the diagnosis of electrical and mechanical incipient faults in the high voltage apparatus. Partial discharges are a major source of insulation failure in electric power transformers, and the differentiation from other sources of acoustic emission is of the utmost importance. This paper reports the development of a new sensor concept — a fiber laser sensor based on a phase-shifted chirped fiber grating — for the acoustic emission detection of incipient faults in oil-filled power transformers. These sensors can be placed in the inner surface of the transformer tank wall, not affecting the insulation integrity of the structure and improving fault detection and location. The performance of the sensing head is characterized and compared for different surrounding media: air, water, and oil. The results obtained indicate the feasibility of this sensing approach for the industrial development of practical solutions.

Acoustic emission monitoring is often used in the diagnosis of electrical and mechanical incipient faults in high voltage apparatus. Partial discharges are a major source of insulation failure in power transformers and the differentiation from other sources of acoustic emissions is of the utmost importance. Also, it is important to give an indication of the PD source location in order to obtain a useful diagnosis. This paper reports the developments in partial discharges source location through the associated acoustic emissions using three different algorithms.

Partial discharges are a major source of insulation failure in electric power transformers. Their detection can be achieved through the associated acoustic emissions, and this work reports on the investigation of a fibre laser sensor based on a phase-shifted chirped fibre grating for acoustic emission detection in the power transformer environment. The performance of the sensing head is characterized and compared for different surrounding media: air, water and oil.

Acoustic emission monitoring is often used in the diagnosis of electrical and mechanical incipient faults in high voltage apparatus. A great number of methods are available for condition monitoring and diagnosis of power transformer insulation, but only a few can take direct measurements inside a transformer. Partial discharges are a major source of insulation failure in power transformers and their detection can be achieved through the associated acoustic emissions. This paper reports the development of two sensing head configurations based on extrinsic and intrinsic fiber Fabry-Perot interferometers for the detection of incipient faults in oil-filled power transformers. These sensors can be placed inside the transformer tank without affecting the insulation integrity, improving fault detection and location. The performances of the sensing heads are characterized and compared with the situations where it operates in air, water and oil and promising results are obtained, which will allow the industrial development of practical solutions.

World Renewable Energy Congress VII, Cologne, Germany, June 29-July 05, 2002