Low iodine diet advice and differentiated thyroid cancer treatment: A historic exploration in three UK centres.

BACKGROUND AND AIMS: Patients with differentiated thyroid cancer are often advised to follow a low iodine diet (LID) one to two weeks before radioiodine remnant ablation (RRA). We describe treatment practices and ablation success rates in centres (C1, C2, C3) in the UK with different approaches to LID advice. METHODS: Historic cohort of patients with differentiated thyroid cancer treated with RRA in 2015/16 in C1 (n = 50, 1-week LID), C2 (n = 59, 2-week LID) and C3 (n = 108, no LID advice). Response to RRA was stratified as excellent, indeterminate, or incomplete by the adapted American Thyroid Association Dynamic Risk Stratification Score. RESULTS: There was little difference in age, sex and staging between centres, but the percentage receiving 1.1 GBq vs higher administered activities differed (C1:22%, C2:44%, C3:15%, p < 0.001). Excellent response was recorded for: C1:48%, C2:36%, C3:49% (p = 0.61). Differences in RRA preparation and outcome assessment at C3 precluded comparison across all centres. Adjusted odds ratio for excellent response at C2 vs C1 was 0.57 (95%CI: 0.25,1.32), p = 0.19. CONCLUSIONS: There was no evidence that advising a LID for 2-weeks before RRA improves outcomes compared to 1-week. For definitive recommendations on LIDs prior to RRA, a prospective multi-centre study with a more homogenous approach to patient management or, randomised controlled trial, is needed.

The effect of surgical approach in total knee replacement on outcomes. An analysis of 875,166 elective operations from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man.

BACKGROUND: Total knee replacement (TKR) is clinically and cost-effective. The surgical approach employed influences the outcome, however there is little generalisable and robust evidence to guide practice. We compared outcomes between the common primary TKR surgical approaches. METHODS: 875,166 primary TKRs captured in the National Joint Registry, linked to hospital inpatient, mortality and patient reported outcome measures (PROMs) data, with up to 15.75 years follow-up were analysed. There were 10 surgical approach groups: medial parapatellar, midvastus, subvastus, lateral parapatellar, 'other' and their minimally invasive versions. Survival methods were used to compare revision rates and 45-day mortality. Groups were compared using Cox proportional hazards regression and Flexible Parametric Survival Modelling (FPM). Confounders included age at surgery, sex, risk group (indications additional to osteoarthritis), American Society of Anesthesiologists grade, TKR fixation, year of primary, body mass index, and for mortality, deprivation and Charlson comorbidity subgroups. PROMs were analysed with regression modelling or non-parametric methods. RESULTS: The conventional midvastus approach was associated with lower revision rates (Hazard Rate Ratio (HRR) 0.80 (95% CI 0.71-0.91) P = 0.001) and the lateral parapatellar with higher revision rates (HRR 1.35 (95% CI 1.12-1.63) P = 0.002) compared to the conventional medial parapatellar approach. Mortality rates were similar between approaches. PROMs showed statistically significant, but not clinically important, differences. CONCLUSIONS: There is little difference in PROMs between the various surgical approaches in TKR with all resulting in good outcomes. However, the conventional midvastus approach (used in 3% of cases) was associated with a 20% reduced risk of revision surgery compared to the most commonly used knee approach (the conventional medial parapatellar: used in 91.9% of cases). This data supports the use of the midvastus approach and thus surgeons should consider utilising this approach more frequently. Minimally invasive approaches did not appear to convey any clinical advantage in this study over conventional approaches for primary TKR.

Patellar resurfacing during primary total knee replacement is associated with a lower risk of revision surgery.

AIMS: Debate remains whether the patella should be resurfaced during total knee replacement (TKR). For non-resurfaced TKRs, we estimated what the revision rate would have been if the patella had been resurfaced, and examined the risk of re-revision following secondary patellar resurfacing. METHODS: A retrospective observational study of the National Joint Registry (NJR) was performed. All primary TKRs for osteoarthritis alone performed between 1 April 2003 and 31 December 2016 were eligible (n = 842,072). Patellar resurfacing during TKR was performed in 36% (n = 305,844). The primary outcome was all-cause revision surgery. Secondary outcomes were the number of excess all-cause revisions associated with using TKRs without (versus with) patellar resurfacing, and the risk of re-revision after secondary patellar resurfacing. RESULTS: The cumulative risk of all-cause revision at ten years was higher (p < 0.001) in primary TKRs without patellar resurfacing (3.54% (95% confidence interval (CI) 3.47 to 3.62)) compared to those with resurfacing (3.00% (95% CI 2.91 to 3.11)). Using flexible parametric survival modelling, we estimated one 'excess' revision per 189 cases performed where the patella was not resurfaced by ten years (equivalent to 2,842 excess revisions in our cohort). The risk of all-cause re-revision following secondary patellar resurfacing was 4.6 times higher than the risk of revision after primary TKR with patellar resurfacing (at five years from secondary patellar resurfacing, 8.8% vs 1.9%). CONCLUSION: Performing TKR without patellar resurfacing was associated with an increased risk of revision. Secondary patellar resurfacing led to a high risk of re-revision. This represents a potential substantial healthcare burden that should be considered when forming treatment guidelines and commissioning services. Cite this article: Bone Joint J 2021;103-B(5):864-871.

Choice between implants in knee replacement: protocol for a Bayesian network meta-analysis, analysis of joint registries and economic decision model to determine the effectiveness and cost-effectiveness of knee implants for NHS patients-The KNee Implant Prostheses Study (KNIPS).

INTRODUCTION: Knee replacements are highly successful for many people, but if a knee replacement fails, revision surgery is generally required. Surgeons and patients may choose from a range of implant components and combinations that make up knee replacement constructs, all with potential implications for how long a knee replacement will last. To inform surgeon and patient decisions, a comprehensive synthesis of data from randomised controlled trials is needed to evaluate the effects of different knee replacement implants on overall construct survival. Due to limited follow-up in trials, joint registry analyses are also needed to assess the long-term survival of constructs. Finally, economic modelling can identify cost-effective knee replacement constructs for different patient groups. METHODS AND ANALYSIS: In this protocol, we describe systematic reviews and network meta-analyses to synthesise evidence on the effectiveness of knee replacement constructs used in total and unicompartmental knee replacement and analyses of two national joint registries to assess long-term outcomes. Knee replacement constructs are defined by bearing materials and mobility, constraint, fixation and patella resurfacing. For men and women in different age groups, we will compare the lifetime cost-effectiveness of knee replacement constructs. ETHICS AND DISSEMINATION: Systematic reviews are secondary analyses of published data with no ethical approval required. We will design a common joint registry analysis plan and provide registry representatives with information for submission to research or ethics committees. The project has been assessed by the National Health Service (NHS) REC committee and does not require ethical review.Study findings will be disseminated to clinicians, researchers and administrators through open access articles, presentations and websites. Specific UK-based groups will be informed of results including National Institute for Health Research and National Institute for Health and Care Excellence, as well as international orthopaedic associations and charities. Effective dissemination to patients will be guided by our patient-public involvement group and include written lay summaries and infographics. PROSPERO REGISTRATION NUMBER: CRD42019134059 and CRD42019138015.

A Comparison of the Surgical Practice of Potential Revision Outlier Joint Replacement Surgeons With Non-outliers: A Case Control Study From the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man.

BACKGROUND: The National Joint Registry for England, Wales, Northern Ireland and the Isle of Man (NJR) has monitored the performance of consultant surgeons performing primary total hip (THR) or knee replacements (KR) since 2007. The aims of this study were: 1) To describe the surgical practice of consultant hip and knee replacement surgeons in the National Joint Registry for England and Wales (NJR), stratified by potential outlier status for revisions. 2) To compare the practice of revision outlier and non-outlier surgeons. METHODS: We combined NJR primary THR and KR data from 2008-2017 separately with relevant anonymised NJR outlier notification records. We described the surgical practice of outliers and non-outliers by surgical workload, implant choice, and patients' clinical and demographic characteristics. We explored associations between surgeon-level factors and outlier status with conditional logistic regression models. RESULTS: We included 764,888 primary THRs by 3213 surgeons and 889,954 primary KRs by 3084 surgeons performed between 2008-2017. One hundred and eleven (3.5%) THR and 114 (3.7%) KR consultant surgeons were potential revision outliers. Surgeons who used more types of implant had increased odds of being an outlier (KR: OR/additional implant = 1.35, 95%CI 1.17-1.55; THR: OR = 1.12, 95%CI 1.06-1.18). CONCLUSIONS: The use of more types of implant is associated with increased risk of being a potential revision outlier. Further research is required to understand why surgeons use many different implants and to what extent this is responsible for the effects observed here.

Patients Receiving a Primary Unicompartmental Knee Replacement Have a Higher Risk of Revision but a Lower Risk of Mortality Than Predicted Had They Received a Total Knee Replacement: Data From the National Joint Registry for England, Wales, Northern Ireland, and the Isle of Man.

BACKGROUND: To determine unicompartmental (UKR) and total knee replacement (TKR) revision rates, compare UKR revision rates with what they would have been had they received TKR instead, and assess subsequent re-revision and 90-day mortality rates. METHODS: Using National Joint Registry data, we estimated UKR and TKR revision and mortality rates. Flexible parametric survival modeling (FPM) was used to model failure in TKR and make estimates for UKR. Kaplan-Meier estimates were used to compare cumulative re-revision for revised UKRs and TKRs. RESULTS: Ten-year UKR revision rates were 2.5 times higher than expected from TKR, equivalent to 70 excess revisions/1000 cases within 10 years (5861 excess revisions in this cohort). Revision rates were 2.5 times higher for the highest quartile volume UKR surgeons compared to the same quartile for TKR and 3.9 times higher for the lowest quartiles respectively. Re-revision rates of revised TKRs (10 years = 17.5%, 95% confidence interval [CI] 16.4-18.7) were similar to revised UKRs (15.2%, 95% CI 13.4-17.1) and higher than revision rates following primary TKR (3.3%, 95% CI 3.1-3.5). Ninety-day mortality rates were lower after UKR compared with TKR (0.08% vs 0.33%) and lower than predicted had UKR patients received a TKR (0.18%), equivalent to 1 fewer death per 1000 cases. CONCLUSION: UKR revision rates were substantially higher than TKR even when demographics and caseload differences were accounted for; however, fewer deaths occur after UKR. This should be considered when forming treatment guidelines and commissioning services. Re-revision rates were similar between revised UKRs and TKRs, but considerably higher than for primary TKR, therefore UKR cannot be considered an intermediate procedure.

Reducing cardiovascular disease risk among families with familial hypercholesterolaemia by improving diet and physical activity: a randomised controlled feasibility trial.

OBJECTIVE: Familial hypercholesterolaemia (FH) elevates low-density lipoprotein cholesterol (LDL-C) and increases cardiovascular disease (CVD) risk. This study aimed to provide evidence for the feasibility of conducting a randomised controlled trial to evaluate the efficacy of an intervention designed to improve diet and physical activity in families with FH. DESIGN: A parallel, randomised, waitlist-controlled, feasibility pilot trial. SETTING: Three outpatient lipid clinics in the UK. PARTICIPANTS: Families that comprised children (aged 10-18 years) and their parent with genetically diagnosed FH. INTERVENTION: Families were randomised to either 12-week usual care or intervention. The behavioural change intervention aimed to improve dietary, physical activity and sedentary behaviours. It was delivered to families by dietitians initially via a single face-to-face session and then by four telephone or email follow-up sessions. OUTCOME MEASURES: Feasibility was assessed via measures related to recruitment, retention and intervention fidelity. Postintervention qualitative interviews were conducted to explore intervention acceptability. Behavioural (dietary intake, physical activity and sedentary time) and clinical (blood pressure, body composition and blood lipids) outcomes were collected at baseline and endpoint assessments to evaluate the intervention's potential benefit. RESULTS: Twenty-one families (38% of those approached) were recruited which comprised 22 children and 17 adults with FH, and 97% of families completed the study. The intervention was implemented with high fidelity and the qualitative data revealed it was well accepted. Between-group differences at the endpoint assessment were indicative of the intervention's potential for improving diet in children and adults. Evidence for potential benefits on physical activity and sedentary behaviours was less apparent. However, the intervention was associated with improvements in several CVD risk factors including LDL-C, with a within-group mean decrease of 8% (children) and 10% (adults). CONCLUSIONS: The study's recruitment, retention, acceptability and potential efficacy support the development of a definitive trial, subject to identified refinements. TRIAL REGISTRATION NUMBER: ISRCTN24880714.

The effect of surgical approach in total hip replacement on outcomes: an analysis of 723,904 elective operations from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man.

BACKGROUND: Total hip replacement (THR) is clinically and cost-effective. The surgical approach employed influences the outcome; however, there is little generalisable and robust evidence to guide practice. METHODS: A total of 723,904 primary THRs captured in the National Joint Registry, linked to hospital inpatient, mortality and patient-reported outcome measures (PROMs) data with up to 13.75 years follow-up, were analysed. There were seven surgical approach groups: conventional posterior, lateral, anterior and trans-trochanteric groups and minimally invasive posterior, lateral and anterior. Survival methods were used to compare revision rates and 90-day mortality. Groups were compared using Cox proportional hazards and Flexible Parametric Survival Modelling (FPM). Confounders included age at surgery, sex, risk group (indications additional to osteoarthritis), American Society of Anesthesiologists grade, THR fixation, thromboprophylaxis, anaesthetic, body mass index (BMI) and deprivation. PROMs were analysed with regression modelling or non-parametric methods. RESULTS: Unadjusted analysis showed a higher revision risk than the referent conventional posterior for the conventional lateral, minimally invasive lateral, minimally invasive anterior and trans-trochanteric groups. This persisted with all adjusted FPM and adjusted Cox models, except in the Cox model including BMI where the higher revision rate only persisted for the conventional lateral approach (hazard rate ratio (HRR) 1.12 [95% CI 1.06,1.17] P < 0·001) and trans-trochanteric approaches (HRR 1.48 [95% CI 1.14,1.91] P = 0.003). PROMs demonstrated statistically, but not clinically, significant differences. Self-reported complications were more frequent with the conventional lateral approach, and the risk of 90-day mortality was higher (HRR 1.15 [95%CI 1.01-1.30] P = 0.029). CONCLUSIONS: Lateral approaches for THR are associated with worse outcomes, including more deaths and revisions, than the posterior approach. We recommend the posterior approach should be considered the current standard approach for THR. Large well-designed studies are needed to assess any potential benefits from using minimally invasive posterior approaches and the conventional anterior approach.

What change in body mass index is associated with improvement in percentage body fat in childhood obesity? A meta-regression.

OBJECTIVE: Using meta-regression this paper sets out the minimum change in body mass index-SD score (BMI-SDS) required to improve adiposity as percentage body fat for children and adolescents with obesity. DESIGN: Meta-regression. SETTING: Studies were identified as part of a large-scale systematic review of the following electronic databases: AMED, Embase, MEDLINE via OVID, Web of Science and CENTRAL via Cochrane library. PARTICIPANTS: Individuals aged 4-19 years with a diagnosis of obesity according to defined BMI thresholds. INTERVENTIONS: Studies of lifestyle treatment interventions that included dietary, physical activity and/or behavioural components with the objective of reducing obesity were included. Interventions of <2 weeks duration and those that involved surgical and/or pharmacological components (eg, bariatric surgery, drug therapy) were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: To be included in the review, studies had to report baseline and post-intervention BMI-SDS or change measurements (primary outcome measures) plus one or more of the following markers of metabolic health (secondary outcome measures): adiposity measures other than BMI; blood pressure; glucose; inflammation; insulin sensitivity/resistance; lipid profile; liver function. This paper focuses on adiposity measures only. Further papers in this series will report on other outcome measures. RESULTS: This paper explores the potential impact of BMI-SDS reduction in terms of change in percentage body fat. Thirty-nine studies reporting change in mean percentage body fat were analysed. Meta-regression demonstrated that reduction of at least 0.6 in mean BMI-SDS ensured a mean reduction of percentage body fat mass, in the sense that the associated 95% prediction interval for change in mean percentage body fat was wholly negative. CONCLUSIONS: Interventions demonstrating reductions of 0.6 BMI-SDS might be termed successful in reducing adiposity, a key purpose of weight management interventions. TRIAL REGISTRATION NUMBER: CRD42016025317.

The Association of Body Mass Index with Risk of Long-Term Revision and 90-Day Mortality Following Primary Total Hip Replacement: Findings from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man.

BACKGROUND: The influence of obesity on outcomes following total hip replacement is unclear. Restriction of total hip replacement on the basis of body mass index (BMI) has been suggested. The purpose of this study was to assess the influence of BMI on the risk of revision and 90-day mortality. METHODS: This was a population-based, longitudinal cohort study of the National Joint Registry (NJR) for England, Wales, Northern Ireland and the Isle of Man. Using data recorded from April 2003 to December 2015, linked to Office for National Statistics data, we ascertained revision and 90-day mortality rates following primary total hip replacement by BMI category. The probability of revision was estimated using Kaplan-Meier methods. Associations of BMI with revision and mortality were explored using adjusted Cox proportional hazards regression models. RESULTS: We investigated revision and 90-day mortality among 415,598 and 413,741 primary total hip replacements, respectively. Each data set accounts for approximately 52% of the total number of recorded operations in the NJR. Thirty-eight percent of the patients were classified as obese. At 10 years, class-III obese patients had the highest cumulative probability of revision (6.7% [95% confidence interval (CI), 5.5% to 8.2%]), twice that of the underweight group (3.3% [95% CI, 2.2% to 4.9%]). When the analysis was adjusted for age, sex, American Society of Anesthesiologists [ASA] grade, year of operation, indication, and fixation type, compared with patients with normal BMI, significantly elevated hazard ratios (HRs) for revision were observed for patients in the BMI categories of class-I obese (≥30 to <35 kg/m) (HR, 1.14 [95% CI, 1.07 to 1.22]), class-II obese (≥35 to <40 kg/m) (HR, 1.30 [95% CI, 1.19 to 1.40]), and class-III obese (≥40 to ≤60 kg/m) (HR, 1.43 [95% CI, 1.27 to 1.61]) (p < 0.0005 for all). Underweight patients had a substantially higher cumulative probability of 90-day mortality (1.17%; 95% CI, 0.86% to 1.58%) compared with patients with normal BMI (0.43%; 95% CI, 0.39% to 0.48%). The risk of 90-day mortality was significantly higher for the underweight group (HR, 2.09 [95% CI, 1.51 to 2.89]; p < 0.0005) and significantly lower for patients who were categorized as overweight (HR, 0.70; 95% CI, 0.61 to 0.81; p < 0.0005), class-I obese (HR, 0.69 [95% CI, 0.59 to 0.81]; p < 0.0005), and class-II obese (HR, 0.79 [95% CI, 0.63 to 0.98]; p = 0.049) compared with patients with normal BMI. CONCLUSIONS: Although long-term revision rates following total hip replacement were higher among obese patients, we believe that the rates remained acceptable by contemporary standards and were balanced by a lower risk of 90-day mortality. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Using long term mortality to determine which perioperative risk factors of mortality following hip and knee replacement may be causal.

Observational studies have identified surgical factors that are associated with a reduced risk of mortality after joint replacement. It is not clear whether these are causal or reflect patient selection. Data on the first primary hip (n = 424,156) and knee replacements (n = 469,989) performed for osteoarthritis in the National Joint Registry were analysed. Flexible parametric survival modelling was used to determine if risk factors for mortality in the perioperative period persisted. To explore selection bias, standardised mortality ratios were calculated for all-cause, respiratory and smoking related cancer mortality using population rates. Selection was apparent for hip resurfacing, combined spinal and general anaesthetic and unicondylar knee implants; reduced mortality was observed for many years for both all and other causes of mortality with a waning effect. Mechanical thromboprophylaxis was also suggestive of selection although patients receiving aspirin had sustained reduced mortality, possibly due to to a cardioprotective effect. Posterior approach for hips was ambiguous with a possible causal component. Spinal anaesthesia was suggestive of a causal effect. We are reliant on observational data when it is not feasible to undertake randomised trials. Our approach of looking at long term mortality risks for perioperative interventions provides further insights to differentiate causal interventions from selection. We recommend the use of aspirin chemothromboprophylaxis, the posterior approach and spinal anaesthetic in total hip replacement due to the apparent causal effect on reduced mortality.

The risk of developing cancer following metal-on-metal hip replacement compared with non metal-on-metal hip bearings: Findings from a prospective national registry "The National Joint Registry of England, Wales, Northern Ireland and the Isle of Man".

BACKGROUND AND PURPOSE: Over 1 million metal-on-metal hip replacements were implanted. Even well-functioning implants produce wear debris that can cause tissue damage, disseminate and cause DNA damage. We aimed to establish if there was an association between metal-on-metal hip replacement and the risk of subsequently developing cancer compared with alternative hip replacements. METHODS: We performed a population based prospective longitudinal cohort study using data from the National Joint Registry linked to Hospital Episode Statistics (n = 403,881 patients). We examined the incidence of a new diagnosis of cancer in patients who received a metal-on-metal bearing in comparison with those who received a non metal-on-metal bearing. Kaplan-Meier estimates of time to first cancer diagnosis were used with Cox proportional hazards regression models to assess the effect on the time to cancer diagnosis for all cancer types, haematological, malignant melanoma, urinary tract cancers or prostate cancer in men. RESULTS: The maximum follow up available was 11.8 years with 25% of patients followed up for more than 6.8 years (mean follow up 4.6 years; median 4.3; IQR 2.1-6.8; range 0.01-11.8). Analyses by gender that adjusted for age at primary and presence or absence of linked Welsh (PEDW) records showed no increase in the risk of developing cancer according to the bearing surface implanted for all cancers, haematological cancers, malignant melanoma, urinary tract cancers or prostate cancer in men. For patients receiving a second hip replacement, there was also no difference. CONCLUSION: We have demonstrated that there is currently no evidence of an increase in the risk of cancer following primary hip replacement according to the type of bearing material used. Although the risk of revision in metal-on-metal bearing hip replacements is higher, it is reassuring that the risk of a new diagnosis of cancer is not currently increased. Despite the long term follow up available in this study, the latency period for some cancers is very long and therefore continued monitoring is required to ensure no new patterns emerge that may indicate need for universal screening.

Implications of Introducing New Technology: Comparative Survivorship Modeling of Metal-on-Metal Hip Replacements and Contemporary Alternatives in the National Joint Registry.

BACKGROUND: New medical technologies are often used widely without adequate supporting data, a practice that can lead to widespread catastrophic failure such as occurred with metal-on-metal (MoM) hip replacements. We determined both how revision rates would have differed if, instead of receiving MoM hip replacements, patients had received existing alternatives and the subsequent cumulative re-revision rates of the patients who did receive MoM hip replacements compared with alternatives. METHODS: This study is a population-based longitudinal cohort study of patient data recorded in the National Joint Registry (NJR) for England, Wales and Northern Ireland between April 2003 and December 2014. We ascertained implant failure rates separately among stemmed MoM total hip replacement (THR) and hip-resurfacing procedures and, using flexible parametric survival modeling, compared them with the failure rates that would have been expected had existing alternatives been used. We used Kaplan-Meier survivorship analysis to compare cumulative re-revision of patients who received stemmed MoM primary replacements that failed and of those who underwent hip resurfacing that failed with those whose non-MoM THRs had failed. RESULTS: In all, 37,555 patients underwent MoM hip resurfacing, with a 10-year revision rate of 12.6% (95% confidence interval [CI]: 12.2% to 13.1%) compared with a predicted revision rate of 4.8% if alternative implants had been used. The 32,024 stemmed MoM THRs had a 19.8% (95% CI: 18.9% to 20.8%) 10-year failure rate compared with an expected rate of 3.9% if alternatives had been used. For every 100 MoM hip-resurfacing procedures, there were 7.8 excess revisions by 10 years, and for every 100 stemmed MoM THR procedures, there were 15.9, which equates to 8,021 excess first revisions. Seven-year re-revision rates were 14.9% (95% CI: 13.8% to 16.2%) for stemmed non-MoM THRs, 18.0% (95% CI: 15.7% to 20.7%) for MoM hip resurfacing, and 19.8% (95% CI: 17.0% to 23.0%) for stemmed MoM THRs. CONCLUSIONS: This study highlights the consequences of widespread and poorly monitored adoption of a medical technology. Over 1 million MoM hip prostheses were implanted worldwide. The excess failure on a global scale will be enormous. This practice of adopting new technologies without adequate supporting data must not be repeated. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Infrared Radiation in the Thermosphere Near the End of Solar Cycle 24.

Observations of thermospheric infrared radiative cooling by carbon dioxide (CO2) and nitric oxide (NO) from 2002 to 2018 are presented. The time span covers more than 6,000 days including most of solar cycle (SC) 23 and the entirety of SC 24 to date. Maxima of infrared cooling rate profiles (nW/m3) are smaller during SC 24 than SC 23, indicating a cooler thermosphere. Rates of global infrared power (W) from CO2 are now at levels observed during the deep solar minimum of 2009. Rates of NO power are still larger than those observed during 2009 and are being maintained at an elevated level by geomagnetic activity. During SC 24 to date, the thermosphere has radiated 70% of the energy of the mean of the past five cycles and would require an additional 1,690 days at current infrared radiation rates to reach that amount.

Choice of implant combinations in total hip replacement: systematic review and network meta-analysis.

Objective To compare the survival of different implant combinations for primary total hip replacement (THR). Design Systematic review and network meta-analysis. Data sources Medline, Embase, The Cochrane Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and the EU Clinical Trials Register.Review methods Published randomised controlled trials comparing different implant combinations. Implant combinations were defined by bearing surface materials (metal-on-polyethylene, ceramic-on-polyethylene, ceramic-on-ceramic, or metal-on-metal), head size (large ≥36 mm or small <36 mm), and fixation technique (cemented, uncemented, hybrid, or reverse hybrid). Our reference implant combination was metal-on-polyethylene (not highly cross linked), small head, and cemented. The primary outcome was revision surgery at 0-2 years and 2-10 years after primary THR. The secondary outcome was the Harris hip score reported by clinicians.Results 77 studies were included in the systematic review, and 15 studies (3177 hips) in the network meta-analysis for revision. There was no evidence that the risk of revision surgery was reduced by other implant combinations compared with the reference implant combination. Although estimates are imprecise, metal-on-metal, small head, cemented implants (hazard ratio 4.4, 95% credible interval 1.6 to 16.6) and resurfacing (12.1, 2.1 to 120.3) increase the risk of revision at 0-2 years after primary THR compared with the reference implant combination. Similar results were observed for the 2-10 years period. 31 studies (2888 patients) were included in the analysis of Harris hip score. No implant combination had a better score than the reference implant combination.Conclusions Newer implant combinations were not found to be better than the reference implant combination (metal-on-polyethylene (not highly cross linked), small head, cemented) in terms of risk of revision surgery or Harris hip score. Metal-on-metal, small head, cemented implants and resurfacing increased the risk of revision surgery compared with the reference implant combination. The results were consistent with observational evidence and were replicated in sensitivity analysis but were limited by poor reporting across studies.Systematic review registration PROSPERO CRD42015019435.

The Main Cause of Death Following Primary Total Hip and Knee Replacement for Osteoarthritis: A Cohort Study of 26,766 Deaths Following 332,734 Hip Replacements and 29,802 Deaths Following 384,291 Knee Replacements.

BACKGROUND: Patients undergoing primary total joint replacement are selected for surgery and thus (other than having a transiently increased mortality rate postoperatively) have a lower mortality rate than age and sex-matched individuals do. Understanding the causes of death following joint replacement would allow targeted strategies to reduce the risk of death and optimize outcome. We aimed to determine the rates and causes of mortality for patients undergoing primary total hip or knee replacement compared with individuals in the general population who were matched for age and sex. METHODS: We compared causes and rates of mortality between age and sex-matched individuals in the general population (National Joint Registry for England, Wales and Northern Ireland; Hospital Episode Statistics; and Office for National Statistics) and a linked cohort of 332,734 patients managed with total hip replacement (26,766 of whom died before the censoring date) and 384,291 patients managed with primary total knee replacement (29,802 of whom died before the censoring date) from 2003 through 2012. RESULTS: The main causes of death were malignant neoplasms (33.8% [9,037] of 26,766 deaths in patients with total hip replacement and 33.3% [9,917] of 29,802 deaths in patients with total knee replacement), circulatory system disorders (32.8% [8,784] of the deaths in patients with total hip replacement and 33.3% [9,932] of the deaths in patients with total knee replacement), respiratory system disorders (10.9% [2,928] of the deaths in patients with total hip replacement and 9.8% [2,932] of the deaths in patients with total knee replacement), and digestive system diseases (5.5% [1,465] of the deaths in patients with total hip replacement and 5.3% [1,572] of the deaths in patients with total knee replacement). There was a relative reduction in mortality (39%) compared with the individuals in the general population that equalized to the rate in the general population by 7 years for hips (overall standardized mortality ratio [SMR], 0.61; 95% confidence interval [CI], 0.60 to 0.62); for knees, the relative reduction (43%) partially attenuated by 7 years but still had not equalized to the rate in the general population (overall SMR, 0.57; 95% CI, 0.56 to 0.57). Ischemic heart disease was the most common cause of death within 90 days (29% [431] of the deaths in patients with primary hip replacement and 31% [436] of the deaths in patients with primary knee replacement). There was an elevated risk of death from circulatory, respiratory, and (most markedly) digestive system-related causes within 90 days postoperatively compared with 91 days to 1 year postoperatively. CONCLUSIONS: Ischemic heart disease is the leading cause of death in the 90 days following total joint replacement, and there is an increase in postoperative deaths associated with digestive system-related disease following joint replacement. Interventions targeted at reducing these diseases may have the largest effect on mortality in total joint replacement patients. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Identifying Cardiovascular Risk in Survivors of Childhood Leukaemia Treated with Haematopoietic Stem Cell Transplantation and Total Body Irradiation
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BACKGROUND: Survivors of childhood with haematopoietic stem cell transplantation and total body irradiation (HSCT/TBI) have an increased cardiometabolic risk without overt obesity. AIM: To describe cardiometabolic risk in HSCT/TBI survivors and identify anthropometric measurements of adiposity representative of cardiometabolic risks in HSCT/TBI survivors. METHOD: Childhood leukaemia survivors treated with HSCT/TBI (n = 21, 11 males) were compared with chemotherapy-only (n = 31) and obese non-leukaemic controls (n = 30). All subjects (16-26 years) had blood pressure and auxological measurements (body mass index, waist and hip circumferences) and blood tests (triglycerides, high-density lipoprotein [HDL], and oral glucose tolerance tests). Central adiposity was defined as either increased waist circumference (WC), waist-to-height ratio (WHtR) (>0.5), or waist-to-hip ratio (WHR) (males >0.9, females >0.85). RESULTS: HSCT/TBI survivors showed higher prevalence of hypertriglyceridaemia than both comparison groups and higher prevalence of reduced HDL compared to the chemotherapy-only group. The WHR reported a higher prevalence of increased adiposity in HSCT/TBI survivors compared with WC and WHtR, but such differences were not observed in the other groups. In the HSCT survivors, WHR had the highest number of significant associations with metabolic risk factors, and metabolic risks worsen with time elapsed since primary treatment. CONCLUSIONS: HSCT/TBI survivors have high cardiometabolic risk that is not sufficiently reflected by WC alone. WHR is a useful surrogate marker for increased cardiometabolic risk in HSCT/TBI survivors.
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The choice between hip prosthetic bearing surfaces in total hip replacement: a protocol for a systematic review and network meta-analysis.

BACKGROUND: Prosthetic hip implants have many combinations of bearing surface materials, sizes, and fixation techniques, which can determine the quality of life of patients after primary total hip replacement (THR) and the likelihood of needing revision surgery. When an implant fails, patients require revision THR, which is distressing to the patient and expensive for the health care payer. Primary THR is one of the most common elective procedures performed worldwide, with over 300,000 performed annually in the USA and over 80,000 in England and Wales. It is important to review all available randomised controlled trial (RCT) evidence to determine which implant bearing surface materials, size, and fixation technique are most effective for patients. METHODS/DESIGN: This is a protocol for a systematic review and meta-analysis of RCTs comparing outcomes of hip implant bearing surfaces, size, and fixation techniques used in THR. Implant combinations compared in the literature include four bearing surface combinations (metal-on-polyethylene, metal-on-metal, ceramic-on-polyethylene, and ceramic-on-ceramic); two femoral head sizes (large vs small heads); and four fixation techniques (uncemented, cemented, hybrid, and reverse hybrids). The primary outcome will be revision surgery. We will also collect data on patient characteristics, mortality, quality of life, and other outcomes. In network meta-analysis, we will estimate the relative effectiveness of every implant bearing surface, head size (large vs small), and fixation permutation, using evidence where implants have been compared directly in an RCT and indirectly through common comparators in different RCTs. DISCUSSION: There has been much debate about materials used for prosthetic implants in THR. Different combinations of prosthetic materials, sizes, and fixation, can vary widely in cost and fail at different rates for different patient groups. Given the number of THRs performed yearly, and the increasing use of expensive implants, it is important to review evidence to inform surgeons, patients, and health care providers of optimal implant bearing combinations for given patient characteristics. This review will inform a cost-effectiveness model that will include evidence from other sources, to determine the most effective and cost-effective implant bearing combination for patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015019435.

Good outcome of total hip replacement in patients with cerebral palsy: A comparison of 389 patients and 425,813 controls from the National Joint Registry for England and Wales.

BACKGROUND AND PURPOSE: People with cerebral palsy (CP) often have painful deformed hips, but they are seldom treated with hip replacement as the surgery is considered to be high risk. However, few data are available on the outcome of hip replacement in these patients. PATIENTS AND METHODS: We linked Hospital Episode Statistics (HES) records to the National Joint Registry for England and Wales to identify 389 patients with CP who had undergone hip replacement. Their treatment and outcomes were compared with those of 425,813 patients who did not have CP. Kaplan-Meier estimates were calculated to describe implant survivorship and the curves were compared using log-rank tests, with further stratification for age and implant type. Reasons for revision were quantified as patient-time incidence rates (PTIRs). Nationally collected patient-reported outcomes (PROMS) before and 6 months after operation were compared if available. Cumulative mortality (Kaplan-Meier) was estimated at 90 days and at 1, 3, and 5 years. RESULTS: The cumulative probability of revision at 5 years post-surgery was 6.4% (95% CI: 3.8-11) in the CP cohort as opposed to 2.9% (CI 2.9-3%) in the non-CP cohort (p < 0.001). Patient-reported outcomes showed that CP patients had worse pain and function preoperatively, but had equivalent postoperative improvement. The median improvement in Oxford hip score at 6 months was 23 (IQR: 14-28) in CP and it was 21 (14-28) in non-CP patients. 91% of CP patients reported good or excellent satisfaction with their outcome. The cumulative probability of mortality for CP up to 7 years was similar to that in the controls after stratification for age and sex. INTERPRETATION: Hip replacement for cerebral palsy appears to be safe and effective, although implant revision rates are higher than those in patients without cerebral palsy.

Reduced insulin sensitivity in childhood survivors of haematopoietic stem cell transplantation is associated with lipodystropic and sarcopenic phenotypes.

BACKGROUND: Survivors of childhood acute lymphoblastic leukaemia (ALL) treated with haematopoietic stem cell transplantation and total body irradiation (HSCT/TBI) have a high cardiometabolic risk despite lacking overt clinical obesity. This study characterised body composition using different methodologies and explored associations with reduced insulin sensitivities in a group of ALL survivors treated with/without HSCT/TBI. PROCEDURE: Survivors of childhood ALL treated with HSCT/TBI (n = 20,10 M) were compared with Chemotherapy-only (n = 31), and an obese non-leukaemic controls (n = 30). All subjects (aged 16-26 years) were investigated with: auxology (BMI, waist and hip circumferences), DEXA (total and regional fat, fat-free mass), abdominal MRI (subcutaneous, visceral, intramuscular fat), oral glucose tolerance tests (impaired glucose tolerance or diabetes, insulin sensitivity) and serum adiponectin. RESULTS: HSCT/TBI Group displayed a higher prevalence of abnormal glucose tolerance (45%); lower insulin sensitivity; lower lean mass with higher prevalence of reduced fat-free mass index (from DEXA); higher visceral and intramuscular, and lower subcutaneous fat on MRI, compared with the Chemotherapy-only and Obese controls. BMI was lowest in HSCT/TBI Group. Waist-to-hip and android-to-gynoid ratios were similar between HSCT/TBI and Obese Groups. Insulin sensitivity adjusted for visceral fat mass was lower in the HSCT/TBI than the Chemotherapy-only and Obese groups. Adiponectin in the HSCT/TBI Group was lower than the Chemotherapy-only group, and correlated negatively with time post HSCT/TBI. CONCLUSIONS: HSCT/TBI survivors have an increased risk of abnormal glucose tolerance and reduced insulin sensitivity with reduced subcutaneous and increased visceral fat distribution, increased total fat mass and reduced lean mass.