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  • Temporal trends and patterns in heart failure incidence: a population-based study of 4 million individuals.

    25 December 2017

    BACKGROUND: Large-scale and contemporary population-based studies of heart failure incidence are needed to inform resource planning and research prioritisation but current evidence is scarce. We aimed to assess temporal trends in incidence and prevalence of heart failure in a large general population cohort from the UK, between 2002 and 2014. METHODS: For this population-based study, we used linked primary and secondary electronic health records of 4 million individuals from the Clinical Practice Research Datalink (CPRD), a cohort that is representative of the UK population in terms of age and sex. Eligible patients were aged 16 years and older, had contributed data between Jan 1, 2002, and Dec 31, 2014, had an acceptable record according to CPRD quality control, were approved for CPRD and Hospital Episodes Statistics linkage, and were registered with their general practice for at least 12 months. For patients with incident heart failure, we extracted the most recent measurement of baseline characteristics (within 2 years of diagnosis) from electronic health records, as well as information about comorbidities, socioeconomic status, ethnicity, and region. We calculated standardised rates by applying direct age and sex standardisation to the 2013 European Standard Population, and we inferred crude rates by applying year-specific, age-specific, and sex-specific incidence to UK census mid-year population estimates. We assumed no heart failure for patients aged 15 years or younger and report total incidence and prevalence for all ages (>0 years). FINDINGS: From 2002 to 2014, heart failure incidence (standardised by age and sex) decreased, similarly for men and women, by 7% (from 358 to 332 per 100 000 person-years; adjusted incidence ratio 0·93, 95% CI 0·91-0·94). However, the estimated absolute number of individuals with newly diagnosed heart failure in the UK increased by 12% (from 170 727 in 2002 to 190 798 in 2014), largely due to an increase in population size and age. The estimated absolute number of prevalent heart failure cases in the UK increased even more, by 23% (from 750 127 to 920 616). Over the study period, patient age and multi-morbidity at first presentation of heart failure increased (mean age 76·5 years [SD 12·0] to 77·0 years [12·9], adjusted difference 0·79 years, 95% CI 0·37-1·20; mean number of comorbidities 3·4 [SD 1·9] vs 5·4 [2·5]; adjusted difference 2·0, 95% CI 1·9-2·1). Socioeconomically deprived individuals were more likely to develop heart failure than were affluent individuals (incidence rate ratio 1·61, 95% CI 1·58-1·64), and did so earlier in life than those from the most affluent group (adjusted difference -3·51 years, 95% CI -3·77 to -3·25). From 2002 to 2014, the socioeconomic gradient in age at first presentation with heart failure widened. Socioeconomically deprived individuals also had more comorbidities, despite their younger age. INTERPRETATION: Despite a moderate decline in standardised incidence of heart failure, the burden of heart failure in the UK is increasing, and is now similar to the four most common causes of cancer combined. The observed socioeconomic disparities in disease incidence and age at onset within the same nation point to a potentially preventable nature of heart failure that still needs to be tackled. FUNDING: British Heart Foundation and National Institute for Health Research.

  • Trabecular Metal Acetabular Components Reduce the Risk of Revision Following Primary Total Hip Arthroplasty: A Propensity Score Matched Study From the National Joint Registry for England and Wales.

    12 December 2017

    BACKGROUND: Trabecular metal (TM)-coated acetabular components are increasingly used in both primary and revision total hip arthroplasty (THA). However, previous studies assessing TM acetabular components have been small single-center cohorts with most lacking a control group. We compared revision rates following primary THA between TM and non-TM-coated acetabular components. METHODS: A retrospective observational study was performed using National Joint Registry data, which included primary THAs with the same cementless acetabular component (either TM or non-TM coated). TM and non-TM implants were matched for multiple potential confounding factors using propensity scores. Outcomes following primary THA (revision for all-cause acetabular indications, aseptic acetabular loosening, and infection) were compared between matched groups using competing risk regression analysis. RESULTS: In 18,200 primary THAs (9100 TM and 9100 non-TM), the overall prevalence of acetabular revision, revision for aseptic acetabular loosening, and septic revision was 1.2%, 0.13%, and 0.59% respectively. Five-year revision rates for all-causes (1.0% vs 1.8%, sub-hazard ratio [SHR] 0.57, 95% confidence interval [CI] 0.43-0.76, P < .001), aseptic acetabular loosening (0.1% vs 0.2%, SHR 0.35, 95% CI 0.14-0.90, P = .029), and infection (0.5% vs 0.9%, SHR 0.51, 95% CI 0.34-0.76, P = .001) were all lower in TM compared with non-TM implants. CONCLUSION: Following primary THA, TM-coated acetabular implants had a reduced risk of both aseptic and septic revision compared with non-TM implants. Although absolute differences in revision risk were small, they may be clinically significant if TM designs were implanted in more complex cases.

  • Development of a Prediction Model for Stress Fracture During an Intensive Physical Training Program: The Royal Marines Commandos.

    15 January 2018

    BACKGROUND: Stress fractures (SFs) are one of the more severe overuse injuries in military training, and therefore, knowledge of potential risk factors is needed to assist in developing mitigating strategies. PURPOSE: To develop a prediction model for risk of SF in Royal Marines (RM) recruits during an arduous military training program. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: RM recruits (N = 1082; age range, 16-33 years) who enrolled between September 2009 and July 2010 were prospectively followed through the 32-week RM training program. SF diagnosis was confirmed from a positive radiograph or magnetic resonance imaging scan. Potential risk factors assessed at week 1 included recruit characteristics, anthropometric assessment, dietary supplement use, lifestyle habits, fitness assessment, blood samples, 25(OH)D, bone strength as measured by heel broadband ultrasound attention, history of physical activity, and previous and current food intake. A logistic least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation was used to select potential predictors among 47 candidate variables. Model performance was assessed using measures of discrimination (c-index) and calibration. Bootstrapping was used for internal validation of the developed model and to quantify optimism. RESULTS: A total of 86 (8%) volunteer recruits presented at least 1 SF during training. Twelve variables were identified as the most important risk factors of SF. Variables strongly associated with SF were age, body weight, pretraining weightbearing exercise, pretraining cycling, and childhood intake of milk and milk products. The c-index for the prediction model, which represents the model performance in future volunteers, was 0.73 (optimism-corrected c-index, 0.68). Although 25(OH)D and VO2max had only a borderline statistically significant association with SF, the inclusion of these factors improved the performance of the model. CONCLUSION: These findings will assist in identifying recruits at greater risk of SF during training and will support interventions to mitigate this injury risk. However, external validation of the model is still required.

  • Corrigendum

    8 January 2018

  • Systematic review of the clinical effectiveness and cost-effectiveness of 64-slice or higher computed tomography angiography as an alternative to invasive coronary angiography in the investigation of coronary artery disease.

    8 January 2018

    OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness, in different patient groups, of the use of 64-slice or higher computed tomography (CT) angiography, instead of invasive coronary angiography (CA), for diagnosing people with suspected coronary artery disease (CAD) and assessing people with known CAD. DATA SOURCES: Electronic databases were searched from 2002 to December 2006. REVIEW METHODS: Included studies were tabulated and sensitivity, specificity, positive and negative predictive values calculated. Meta-analysis models were fitted using hierarchical summary receiver operating characteristic curves. Summary sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratios for each model were reported as a median and 95% credible interval (CrI). Searches were also carried out for studies on the cost-effectiveness of 64-slice CT in the assessment of CAD. RESULTS: The diagnostic accuracy and prognostic studies enrolled over 2500 and 1700 people, respectively. The overall quality of the studies was reasonably good. In the pooled estimates, 64-slice CT angiography was highly sensitive (99%, 95% CrI 97 to 99%) for patient-based detection of significant CAD (defined as 50% or more stenosis), while across studies the negative predictive value (NPV) was very high (median 100%, range 86 to 100%). In segment-level analysis compared with patient-based detection, sensitivity was lower (90%, 95% CrI 85 to 94%, versus 99%, 95% CrI 97 to 99%) and specificity higher (97%, 95% CrI 95 to 98%, versus 89%, 95% CrI 83 to 94%), while across studies the median NPV was similar (99%, range 95 to 100%, versus 100%, range 86 to 100%). At individual coronary artery level the pooled estimates for sensitivity ranged from 85% for the left circumflex (LCX) artery to 95% for the left main artery, specificity ranged from 96% for both the left anterior descending (LAD) artery and LCX to 100% for the left main artery, while across studies the positive predictive value (PPV) ranged from 81% for the LCX to 100% for the left main artery and NPV was very high, ranging from 98% for the LAD (range 95 to 100%), LCX (range 93 to 100%) and right coronary artery (RCA) (range 94 to 100%) to 100% for the left main artery. The pooled estimates for bypass graft analysis were 99% (95% CrI 95 to 100%) sensitivity, 96% (95% CrI 86 to 99%) specificity, with median PPV and NPV values across studies of 93% (range 90 to 95%) and 99% (range 98 to 100%), respectively. This compares with, for stent analysis, a pooled sensitivity of 89% (95% CrI 68 to 97%), specificity 94% (95% CrI 83 to 98%), and median PPV and NPV values across studies of 77% (range 33 to 100%) and 96% (range 71 to 100%), respectively. Sixty-four-slice CT is almost as good as invasive CA in terms of detecting true positives. However, it is somewhat poorer in its rate of false positives. It seems likely that diagnostic strategies involving 64-slice CT will still require invasive CA for CT test positives, partly to identify CT false positives, but also because CA provides other information that CT currently does not, notably details of insertion site and distal run-off for possible coronary artery bypass graft (CABG). The high sensitivity of 64-slice CT avoids the costs of unnecessary CA in those referred for investigation but who do not have CAD. Given the possible, although small, associated death rate, avoiding these unnecessary CAs through the use of 64-slice CT may also confer a small immediate survival advantage. This in itself may be sufficient to outweigh the very marginally inferior rates of detection of true positives by strategies involving 64-slice CT. The avoidance of unnecessary CA through the use of 64-slice CT also appears likely to result in overall cost savings in the diagnostic pathway. Only if both the cost of CA is relatively low and the prevalence of CAD in the presenting population is relatively high (so that most patients will go on to CA) will the use of 64-slice CT be likely to result in a higher overall diagnostic cost per patient. CONCLUSIONS: The main value of 64-slice CT may at present be to rule out significant CAD. It is unlikely to replace CA in assessment for revascularisation of patients, particularly as angiography and angioplasty are often done on the same occasion. Further research is needed into the marginal advantages and costs of 256-slice machines compared with 64-slice CT, the usefulness of 64-slice CT in people with suspected acute coronary syndrome, the potential of multislice computed tomography to examine plaque morphology, the role of CT in identifying patients suitable for CABG, and the concerns raised about repetitive use, or use of 64-slice or higher CT angiography in younger individuals or women of childbearing age.

  • Association between NICE guidance on biologic therapies with rates of hip and knee replacement among rheumatoid arthritis patients in England and Wales: An interrupted time-series analysis.

    9 January 2018

    OBJECTIVE: To estimate the impact of NICE approval of tumor necrosis factor inhibitor (TNFi) therapies on the incidence of total hip replacement (THR) and total knee replacement (TKR) among rheumatoid arthritis (RA) patients in England and Wales. METHODS: Primary care data [Clinical Practice Research Datalink (CPRD)] for the study period (1995-2014) were used to identify incident adult RA patients. The age and sex-standardised 5-year incidence of THR and TKR was calculated separately for RA patients diagnosed in each six-months between 1995-2009. We took a natural experimental approach, using segmented linear regression to estimate changes in level and trend following the publication of NICE TA 36 in March 2002, incorporating a 1-year lag. Regression coefficients were used to calculate average change in rates, adjusted for prior level and trend. RESULTS: We identified 17,505 incident RA patients of whom 465 and 650 underwent THR and TKR surgery, respectively. The modeled average incidence of THR and TKR over the biologic-era was 6.57/1000 person years (PYs) and 8.51/1000 PYs, respectively, with projected (had pre-NICE TA 36 level and trend continued uninterrupted) figures of 5.63/1000 PYs and 12.92 PYs, respectively. NICE guidance was associated with a significant average decrease in TKR incidence of -4.41/1000 PYs (95% C.I. -6.88 to -1.94), equating to a relative 34% reduction. Overall, no effect was seen on THR rates. CONCLUSIONS: Among incident RA patients in England and Wales, NICE guidance on TNFi therapies for RA management was temporally associated with reduced rates of TKR but not THR.

  • Bone density, microarchitecture, and material strength in chronic kidney disease patients at the time of kidney transplantation.

    19 January 2018

    Bone health is assessed by bone mineral density (BMD). Other techniques such as trabecular bone score and microindentation could improve the risk of fracture's estimation. Our chronic kidney disease (CKD) patients presented worse bone health (density, microarchitecture, mechanical properties) than controls. More than BMD should be done to evaluate patients at risk of fracture. INTRODUCTION: BMD measured by dual-energy X-ray absorptiometry (DXA) is used to assess bone health in end-stage renal disease (ESRD) patients. Recently, trabecular bone score (TBS) and microindentation that can measure microarchitectural and mechanical properties of bone have demonstrated better correlation with fractures than DXA in different populations. We aimed to characterize bone health (BMD, TBS, and strength) and calcium/phosphate metabolism in a cohort of 53 ESRD patients undergoing kidney transplantation (KT) and 94 controls with normal renal function. METHODS: Laboratory workout, lumbar spine/hip BMD measurements (using DXA), lumbar spine TBS, and bone strength were carried out. The latter was assessed with an impact microindentation device, standardized as percentage of a reference value, and expressed as bone material strength index (BMSi) units. Multivariable linear regression was used to study differences between cases and controls adjusted by age, gender, and body mass index. RESULTS: Among cases, serum calcium was 9.6 ± 0.7 mg/dl, phosphorus 4.4 ± 1.2 mg/dl, and intact parathyroid hormone 214 pg/ml [102-390]. Fourteen patients (26.4%) had prevalent asymptomatic fractures in spinal X-ray. BMD was significantly lower among ESRD patients compared to controls: lumbar 0.966 ± 0.15 vs 0.982 ± 0.15 (adjusted p = 0.037), total hip 0.852 ± 0.15 vs 0.902 ± 0.13 (adjusted p < 0.001), and femoral neck 0.733 ± 0.15 vs 0.775 ± 0.12 (adjusted p < 0.001), as were TBS (1.20 [1.11-1.30] vs 1.31 [1.19-1.43] (adjusted p < 0.001)) and BMSi (79 [71.8-84.2] vs 82. [77.5-88.9] (adjusted p = 0.005)). CONCLUSIONS: ESRD patients undergoing transplant surgery have damaged bone health parameters (density, microarchitecture, and mechanical properties) despite acceptably controlled hyperparathyroidism. Detecting these abnormalities may assist in identifying patients at high risk of post-transplantation fractures.