Background There is limited evidence about the impact of specific patterns of multi-morbidity on health-related quality of life (HRQoL) from large samples of adult subjects. Methods We used data from the English General Practice Patient Survey 2011-2012. We defined multi-morbidity as the presence of two or more of 12 self-reported conditions or another (unspecified) long-term health problem. We investigated differences in HRQoL (EQ-5D scores) associated with combinations of these conditions after adjusting for age, gender, ethnicity, socio-economic deprivation and the presence of a recent illness or injury. Analyses were based on 831,537 responses from patients aged 18 years or older in 8,254 primary care practices in England.Results Of respondents, 23 % reported two or more chronic conditions (ranging from 7 % of those under 45 years of age to 51 % of those 65 years or older). Multimorbidity was more common among women, White individuals and respondents from socio-economically deprived areas. Neurological problems, mental health problems, arthritis and long-term back problem were associated with the greatest HRQoL deficits. The presence of three or more conditions was commonly associated with greater reduction in quality of life than that implied by the sum of the differences associated with the individual conditions. The decline in quality of life associated with an additional condition in people with two and three physical conditions was less for older people than for younger people. Multimorbidity was associated with a substantially worse HRQoL in diabetes than in other long-term conditions. With the exception of neurological conditions, the presence of a comorbid mental health problem had a more adverse effect on HRQoL than any single comorbid physical condition. Conclusion Patients with multi-morbid diabetes, arthritis, neurological, or long-term mental health problems have significantly lower quality of life than other people. People with long-term health conditions require integrated mental and physical healthcare services.

Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are recognised and proven interventions for patients with advanced arthritis. Studies to date have demonstrated a steady increase in the requirement for primary and revision procedures. Projected estimates made for the United States show that by 2030 the demand for primary TKA will grow by 673% and for revision TKA by 601% from the level in 2005. For THA the projected estimates are 174% and 137% for primary and revision surgery, respectively. The purpose of this study was to see if those predictions were similar for England and Wales using data from the National Joint Registry and the Office of National Statistics. Analysis of data for England and Wales suggest that by 2030, the volume of primary and revision TKAs will have increased by 117% and 332%, respectively between 2012 and 2030. The data for the United States translates to a 306% cumulative rate of increase between 2012 and 2030 for revision surgery, which is similar to our predictions for England and Wales. The predictions from the United States for primary TKA were similar to our upper limit projections. For THA, we predicted an increase of 134% and 31% for primary and revision hip surgery, respectively. Our model has limitations, however, it highlights the economic burden of arthroplasty in the future in England and Wales as a real and unaddressed problem. This will have significant implications for the provision of health care and the management of orthopaedic services in the future.

BackgroundEnd-stage renal disease is a long-term irreversible decline in kidney function requiring renal replacement therapy: kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation, followed by immunosuppressive therapy (induction and maintenance therapy) to reduce the risk of kidney rejection and prolong graft survival.ObjectivesTo review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect®, Novartis Pharmaceuticals UK Ltd) and rabbit anti-human thymocyte immunoglobulin (rATG) (Thymoglobulin®, Sanofi) as induction therapy, and immediate-release tacrolimus (TAC) (Adoport®, Sandoz; Capexion®, Mylan; Modigraf®, Astellas Pharma; Perixis®, Accord Healthcare; Prograf®, Astellas Pharma; Tacni®, Teva; Vivadex®, Dexcel Pharma), prolonged-release tacrolimus (Advagraf®Astellas Pharma), belatacept (BEL) (Nulojix®, Bristol-Myers Squibb), mycophenolate mofetil (MMF) (Arzip®, Zentiva; CellCept®, Roche Products; Myfenax®, Teva), mycophenolate sodium (MPS) (Myfortic®, Novartis Pharmaceuticals UK Ltd), sirolimus (SRL) (Rapamune®, Pfizer) and everolimus (EVL) (Certican®, Novartis) as maintenance therapy in adult renal transplantation.MethodsClinical effectiveness searches were conducted until 18 November 2014 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science (via ISI), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted until 18 November 2014 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Database (via Wiley Online Library), Web of Science (via ISI), Health Economic Evaluations Database (via Wiley Online Library) and the American Economic Association’s electronic bibliography (via EconLit, EBSCOhost). Included studies were selected according to predefined methods and criteria. A random-effects model was used to analyse clinical effectiveness data (odds ratios for binary data and mean differences for continuous data). Network meta-analyses were undertaken within a Bayesian framework. A new discrete time–state transition economic model (semi-Markov) was developed, with acute rejection, graft function (GRF) and new-onset diabetes mellitus used to extrapolate graft survival. Recipients were assumed to be in one of three health states: functioning graft, graft loss or death.ResultsEighty-nine randomised controlled trials (RCTs), of variable quality, were included. For induction therapy, no treatment appeared more effective than another in reducing graft loss or mortality. Compared with placebo/no induction, rATG and BAS appeared more effective in reducing biopsy-proven acute rejection (BPAR) and BAS appeared more effective at improving GRF. For maintenance therapy, no treatment was better for all outcomes and no treatment appeared most effective at reducing graft loss. BEL + MMF appeared more effective than TAC + MMF and SRL + MMF at reducing mortality. MMF + CSA (ciclosporin), TAC + MMF, SRL + TAC, TAC + AZA (azathioprine) and EVL + CSA appeared more effective than CSA + AZA and EVL + MPS at reducing BPAR. SRL + AZA, TAC + AZA, TAC + MMF and BEL + MMF appeared to improve GRF compared with CSA + AZA and MMF + CSA. In the base-case deterministic and probabilistic analyses, BAS, MMF and TAC were predicted to be cost-effective at £20,000 and £30,000 per quality-adjusted life-year (QALY). When comparing all regimens, only BAS + TAC + MMF was cost-effective at £20,000 and £30,000 per QALY.LimitationsFor included trials, there was substantial methodological heterogeneity, few trials reported follow-up beyond 1 year, and there were insufficient data to perform subgroup analysis. Treatment discontinuation and switching were not modelled.Future workHigh-quality, better-reported, longer-term RCTs are needed. Ideally, these would be sufficiently powered for subgroup analysis and include health-related quality of life as an outcome.ConclusionOnly a regimen of BAS induction followed by maintenance with TAC and MMF is likely to be cost-effective at £20,000–30,000 per QALY.Study registrationThis study is registered as PROSPERO CRD42014013189.FundingThe National Institute for Health Research Health Technology Assessment programme.

Highlights Revised UK suspected-cancer guidance liberalised investigation of patients. Diagnostic interval was longer for patients with newly introduced referral criteria. Scope remains to reduce diagnostic interval further.

The National Institute for Health Research Health Technology Assessment programme.

Without clinical guideline on the optimal timing for primary total hip replacement (THR), patients often receive the operation with delay. Delaying THR may negatively affect long-term health-related quality of life, but its economic effects are unclear. We evaluated the costs and health benefits of timely primary THR for functionally independent adult patients with end-stage osteoarthritis (OA) compared to non-surgical therapy followed by THR after progression to functional dependence (delayed THR), and non-surgical therapy alone (Medical Therapy), from a German Social Health Insurance (SHI) perspective. Data from hip arthroplasty registers and a systematic review of the published literature were used to populate a tunnel-state modified Markov lifetime model of OA treatment in Germany. A 5% annual discount rate was applied to costs (2013 prices) and health outcomes (Quality Adjusted Life Years, QALY). The expected future average cost of timely THR, delayed THR and medical therapy in women at age 55 were €27,474, €27,083 and €28,263, and QALYs were 20.7, 16.7, and 10.3, respectively. QALY differences were entirely due to health-related quality of life differences. The discounted cost per QALY gained by timely over delayed (median delay of 11 years) THR was €1270 and €1338 in women treated at age 55 and age 65, respectively, and slightly higher than this for men. Timely THR is cost-effective, generating large quality of life benefits for patients at low additional cost to the SHI. With declining healthcare budgets, research is needed to identify the characteristics of those able to benefit the most from timely THR.

BackgroundIn breast cancer patients, sentinel lymph node biopsy is carried out at the same time as the removal of the primary tumour to postoperatively test with histopathology for regional metastases in the sentinel lymph node. Those patients with positive test results are then operated on 2–4 weeks after primary surgery to remove the lymph nodes from the axilla (axillary lymph node dissection, ALND). New molecular tests RD-100i [one-step nucleic acid amplification (OSNA); based on messenger RNA amplification to identify the cytokeratin-19 (CK19) gene marker] (Sysmex, Norderstedt, Germany) and Metasin (using theCK19and mammaglobin gene markers) (Cellular Pathology, Princess Alexandra Hospital NHS Trust, Harlow, UK) are intended to provide an intraoperative diagnosis, thereby avoiding the need for postoperative histopathology and, in positive cases, a second operation for ALND.ObjectiveTo evaluate the clinical effectiveness and cost-effectiveness of using OSNA and Metasin in the NHS in England for the intraoperative diagnosis of sentinel lymph nodes metastases, compared with postoperative histopathology, the current standard.Data sourcesElectronic databases including MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library and the Health Economic Evaluations Database as well as clinical trial registries, grey literature and conference proceedings were searched up to July 2012.Review methodsA systematic review of the evidence was carried out using standard methods. Single-gate studies were used to estimate the accuracy of OSNA with histopathology as the reference standard. The cost-effectiveness analysis adapted an existing simulation model of the long-term costs and health implications of early breast cancer diagnostic outcomes. The model accounted for the costs of an extended first operation with intraoperative testing, the loss of health-related quality of life (disutility) from waiting for postoperative test results, disutility and costs of a second operation, and long-term costs and disutility from lymphoedema related to ALND, adjuvant therapy, locoregional recurrence and metastatic recurrence.ResultsA total of 724 references were identified in the searches, of which 17 studies assessing test accuracy were included in the review, 15 on OSNA and two on Metasin. Both Metasin studies were unpublished. OSNA sensitivity of 84.5% [95% confidence interval (CI) 74.7% to 91.0%] and specificity of 91.8% (95% CI 87.8% to 94.6%) for patient nodal status were estimated in a meta-analysis of five studies [unadjusted for tissue allocation bias (TAB)]. At these values and a 20% node-positive rate, OSNA resulted in lifetime discounted cost-savings of £498 and a quality-adjusted life-year (QALY) loss of 0.048 relative to histopathology, that is, £4324 saved per QALY lost. The most favourable plausible scenario for OSNA in terms of the node-positive rate (range 10–40%), diagnostic accuracy values (91.3% sensitivity and 94.2% specificity, from three reports that adjusted for TAB), the costs of histopathology, OSNA and second surgery, and long-term costs and utilities resulted in a maximum saving per QALY lost of £10,500; OSNA sensitivity and specificity would need to be ≥ 95% for this figure to be ≥ £20,000.LimitationsThere is limited evidence on the diagnostic test accuracy of intraoperative tests. The quality of information on costs of resource utilisation during the diagnostic pathway is low and no evidence exists on the disutility of waiting for a second surgery. No comparative studies exist that report clinical outcomes of intraoperative diagnostic tests. These knowledge gaps have more influence on the decision than current uncertainty in the performance of postoperative histopathology in standard practice.ConclusionsOne-step nucleic acid amplification is not cost-effective for the intraoperative diagnosis of sentinel lymph node metastases. OSNA is less accurate than histopathology and the consequent loss of health benefits in this patient group is not compensated for by health gains elsewhere in the health system that may be obtained with the cost-savings made. The evidence on Metasin is insufficient to evaluate its cost-effectiveness.Study registrationThis study is registered as PROSPERO CRD42012002889.FundingThe National Institute for Health Research Health Technology Assessment programme.

Importance risk factors for delirium in hospital inpatients are well established, but less is known about whether delirium occurring in the community or during an emergency admission to hospital care might be predicted from routine primary-care records. Objectives identify risk factors in primary-care electronic health records (PC-EHR) predictive of delirium occurring in the community or recorded in the initial episode in emergency hospitalisation. Test predictive performance against the cumulative frailty index. Design Stage 1: case-control; Stages 2 and 3: retrospective cohort. Setting clinical practice research datalink: PC-EHR linked to hospital discharge data from England. Subjects Stage 1: 17,286 patients with delirium aged ≥60 years plus 85,607 controls. Stages 2 and 3: patients ≥ 60 years (n = 429,548 in 2015), split into calibration and validation groups. Methods Stage 1: logistic regression to identify associations of 110 candidate risk measures with delirium. Stage 2: calibrating risk factor weights. Stage 3: validation in independent sample using area under the curve (AUC) receiver operating characteristic. Results fifty-five risk factors were predictive, in domains including: cognitive impairment or mental illness, psychoactive drugs, frailty, infection, hyponatraemia and anticholinergic drugs. The derived model predicted 1-year incident delirium (AUC = 0.867, 0.852:0.881) and mortality (AUC = 0.846, 0.842:0.853), outperforming the frailty index (AUC = 0.761, 0.740:0.782). Individuals with the highest 10% of predicted delirium risk accounted for 55% of incident delirium over 1 year. Conclusions a risk factor model for delirium using data in PC-EHR performed well, identifying individuals at risk of new onsets of delirium. This model has potential for supporting preventive interventions.