Associations with baseline visual acuity in 12,414 eyes starting treatment for neovascular AMD.

AIMS: To determine baseline visual acuity before the start of treatment for neovascular age-related macular degeneration (AMD), compare median and visual acuity states between treatment sites and investigate the association of socio-demographic and clinical characteristics with baseline acuity. METHODS: Anonymised demographic and clinical data, collected as part of routine clinical care, were extracted from electronic medical records at treating National Health Service (NHS) Trusts. Analyses were restricted to eyes with baseline visual acuity recorded at treatment initiation. Associations with baseline acuity were investigated using multivariate linear regression. RESULTS: Analysis included 12,414 eyes of 9116 patients at 13 NHS Trusts. Median baseline acuity was LogMAR 0.46 (interquartile range = 0.26-0.80) and 34.5% of eyes had good acuity, defined as LogMAR ≤0.3. Baseline acuity was positively associated with second-treated eye status, younger age, lower socio-economic deprivation, independent living, and female sex. There was little evidence of association between baseline acuity and distance to the nearest treatment centre, systemic or ocular co-morbidity. Despite case-mix adjustments, there was evidence of significant variation of baseline visual acuity between sites. CONCLUSIONS: Despite access to publicly funded treatment within the NHS, variation in visual acuity at the start of neovascular AMD treatment persists. Identifying the characteristics associated with poor baseline acuity, targeted health awareness campaigns, professional education, and pathway re-design may help to improve baseline acuity, the first eye gap, and visual acuity outcomes.

Associations with visual acuity outcomes after 12 months of treatment in 9401 eyes with neovascular AMD.

OBJECTIVE: To record visual acuity outcomes after 12 months of treatment for neovascular age-related macular degeneration (NvAMD), investigate variation between sites and explore associations with baseline characteristics and care processes. METHODS AND ANALYSIS: Anonymised demographic and clinical data were extracted from electronic medical records at treating National Health Service (NHS) Trusts. Associations with acuity outcomes were investigated using multivariate linear and logistic regression. RESULTS: Analysis included 9401 eyes (7686 patients) treated at 13 NHS Trusts. From baseline to month 12, median acuity improved from LogMAR 0.50 (IQR 0.30-0.80) to 0.40 (0.22-0.74) and the proportion of eyes with LogMAR ≥0.3 increased from 34.5% to 39.8%. Baseline visual acuity was the strongest predictor of visual acuity outcomes. For each LogMAR 0.1 worsening of baseline acuity, the acuity at 12 months was improved by LogMAR 0.074 (95% CI 0.073 to 0.074) and the odds of a 'poor' acuity outcome was multiplied by 1.66 (95% CI 1.61 to 1.70). Younger age, independent living status, lower socioeconomic deprivation, timely loading phase completion and higher number of injections were associated with better acuity outcomes. Despite case-mix adjustments, there was evidence of significant variation in acuity outcomes between sites. CONCLUSIONS: Even after adjustment for other variables, variation in acuity outcomes after NvAMD treatment within the NHS remains. Meaningful comparison of outcomes between different providers requires adjustment for a range of baseline characteristics, not visual acuity alone. Identifying best practice at sites with better outcomes and adapting local care processes are required to tackle this health inequality.

Complications and mortality associated with olecranon fractures in the elderly: a retrospective cohort comparison from a large level one trauma centre.

Background: Olecranon fractures in the elderly have an increasing incidence. This retrospective study aims to identify the complications and survivorship of these patients. Methods: All patients >70 years old treated for an olecranon fracture at our institution were identified between 2007 and 2019. Loss of reduction and/or metalwork loosening was recorded. Also noted were wound healing problems, deep/superficial infections, and any subsequent treatment including return to surgery and/or removal of metalwork. Results: From a total of 177 cases, 28 presented with concomitant fractures (16%), half of which were hip fractures. The largest treatment group underwent tension band wiring (n = 82, 46%, mean age 80.8 yrs). Twenty-one of these suffered failure of fixation (26%), all requiring return to surgery. The second largest treatment group underwent plating (n = 50 28%, mean age 80.1 yrs). Four of these suffered failure of fixation (8%), all requiring return to surgery. Forty-four patients were treated non-operatively (25%, mean age 83.8 yrs). Two patients suffered other complications (4.5%). Overall 1 year survivorship was 0.82. Discussion: Olecranon fractures in the elderly have higher than expected 1 year mortality rates. Operative management results in high complication rates, often requiring return to surgery for metalwork problems. Significant consideration of treatment options is required in this cohort.

Association of multimorbidity and changes in health-related quality of life following myocardial infarction: a UK multicentre longitudinal patient-reported outcomes study.

BACKGROUND: Multimorbidity is prevalent for people with myocardial infarction (MI), yet previous studies investigated single-health conditions in isolation. We identified patterns of multimorbidity in MI survivors and their associations with changes in HRQoL. METHODS: In this national longitudinal cohort study, we analysed data from 9566 admissions with MI from 77 National Health Service hospitals in England between 2011 and 2015. HRQoL was measured using EuroQol 5 dimension (EQ5D) instrument and visual analogue scale (EQVAS) at hospitalisation, 6, and 12 months following MI. Latent class analysis (LCA) of pre-existing long-term health conditions at baseline was used to identify clusters of multimorbidity and associations with changes in HRQoL quantified using mixed effects regression analysis. RESULTS: Of 9566 admissions with MI (mean age of 64.1 years [SD 11.9], 7154 [75%] men), over half (5119 [53.5%] had multimorbidities. LCA identified 3 multimorbidity clusters which were severe multimorbidity (591; 6.5%) with low HRQoL at baseline (EQVAS 59.39 and EQ5D 0.62) which did not improve significantly at 6 months (EQVAS 59.92, EQ5D 0.60); moderate multimorbidity (4301; 47.6%) with medium HRQoL at baseline (EQVAS 63.08, EQ5D 0.71) and who improved at 6 months (EQVAS 71.38, EQ5D 0.76); and mild multimorbidity (4147, 45.9%) at baseline (EQVAS 64.57, EQ5D 0.75) and improved at 6 months (EQVAS 76.39, EQ5D 0.82). Patients in the severe and moderate groups were more likely to be older, women, and presented with NSTEMI. Compared with the mild group, increased multimorbidity was associated with lower EQ-VAS scores (adjusted coefficient: -5.12 [95% CI -7.04 to -3.19] and -0.98 [-1.93 to -0.04] for severe and moderate multimorbidity, respectively. The severe class was more likely than the mild class to report problems in mobility, OR 9.62 (95% confidence interval: 6.44 to 14.36), self-care 7.87 (4.78 to 12.97), activities 2.41 (1.79 to 3.26), pain 2.04 (1.50 to 2.77), and anxiety/depression 1.97 (1.42 to 2.74). CONCLUSIONS: Among MI survivors, multimorbidity clustered into three distinct patterns and was inversely associated with HRQoL. The identified multimorbidity patterns and HRQoL domains that are mostly affected may help to identify patients at risk of poor HRQoL for which clinical interventions could be beneficial to improve the HRQoL of MI survivors. TRIAL REGISTRATION: ClinicalTrials.gov NCT01808027 and NCT01819103.

Survivorship of fixed vs mobile bearing unicompartmental knee replacement: A systematic review and meta-analysis of sixty-four studies and National Joint Registries.

BACKGROUND: Unicompartmental knee replacement (UKR) prostheses can use fixed (FB) or mobile bearing (MB) constructs. We compared survivorship and failure modes of both designs. METHODS: The inclusion criteria were studies published between 2005 and 2020 with minimum average follow-up of five years reporting the survival and/or number of revisions of specific designs in medial and lateral UKRs. Pooled rate of revision per 100 patient years (PTIR) was estimated using a random effects model. RESULTS: Seventy cohorts of 17,405 UKRs with weighted mean follow-up of 7.3 years (0.1-29.4 years) were included. A total of 170,923 UKRs were identified in registry reports at a weighted mean implant survival time of 15.4 years. PTIR in MB UKR versus FB UKR was similar [1.45 vs 1.40, (p = 0.8)]. In cohort studies, the overall PTIR for MB was also similar to FB [1.03 vs 0.78, (p = 0.1)]. For medial UKR, the PTIR for MB was marginally greater but not significantly different to FB [0.96 vs 0.81, (p = 0.3)], whilst for lateral UKR, the PTIR for MB was significantly worse than for FB [2.20 vs 0.72, (p < 0.01)]. Polyethylene wear is more common in FB implants, whilst MB implants are revised more often for bearing dislocation. CONCLUSIONS: Overall implant survival in mid- to long-term studies is similar for MB versus FB medial UKRs. MB have a four-fold higher risk of revision in comparison to FB when used for lateral UKR.

Risk Factors for Revision of Polished Taper-Slip Cemented Stems for Periprosthetic Femoral Fracture After Primary Total Hip Replacement: A Registry-Based Cohort Study from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man.

BACKGROUND: Total hip replacement (THR) with a cemented polished taper-slip (PTS) femoral stem has excellent long-term results but is associated with a higher postoperative periprosthetic femoral fracture (PFF) risk compared with composite beam stems. This study aimed to identify risk factors associated with PFF revision following THR with PTS stems. METHODS: In a retrospective cohort study, 299,019 primary THRs using PTS stems from the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man (NJR) were included, with a median follow-up of 5.2 years (interquartile range [IQR], 3.1 to 8.2 years). The adjusted hazard ratio (HR) of PFF revision was estimated for each variable using multivariable Cox survival regression analysis. RESULTS: Of 299,019 THR cases, 1,055 underwent revision for PFF at a median time of 3.1 years (IQR, 1.0 to 6.1 years). The mean age (and standard deviation) was 72 ± 9.7 years, 64.3% (192,365 patients) were female, and 82.6% (247,126 patients) had an American Society of Anesthesiologists (ASA) class of 1 or 2. Variables associated with increased PFF were increasing age (HR, 1.02 per year), intraoperative fracture (HR, 2.57 [95% confidence interval (CI), 1.42 to 4.66]), ovaloid (HR, 1.96 [95% CI, 1.22 to 3.16]) and round cross-sectional shapes (HR, 9.58 [95% CI, 2.29 to 40.12]), increasing stem offset (HR, 1.07 per millimeter), increasing head size (HR, 1.04 per millimeter), THR performed from 2012 to 2016 (HR, 1.45 [95% CI, 1.18 to 1.78]), cobalt-chromium stem material (HR, 6.7 [95% CI, 3.0 to 15.4]), and cobalt-chromium stems with low-viscosity cement (HR, 22.88 [95% CI, 9.90 to 52.85]). Variables associated with a decreased risk of PFF revision were female sex (HR, 0.52 [95% CI, 0.45 to 0.59]), increasing stem length (HR, 0.97 per millimeter), and a ceramic-on-polyethylene bearing (HR, 0.55 [95% CI, 0.36 to 0.85]). CONCLUSIONS: Increased risk of PFF revision was associated with PTS stems that are short, have high offset, are used with large femoral heads, are made of cobalt-chromium, or have ovaloid or round cross-sectional shapes. Large increases in PFF risk were associated with cobalt-chromium stems used with low-viscosity cement. Further study is required to confirm causation. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

A calcar collar is protective against early periprosthetic femoral fracture around cementless femoral components in primary total hip arthroplasty: a registry study with biomechanical validation.

AIMS: The aim of this study was to estimate the 90-day risk of revision for periprosthetic femoral fracture associated with design features of cementless femoral stems, and to investigate the effect of a collar on this risk using a biomechanical in vitro model. MATERIALS AND METHODS: A total of 337 647 primary total hip arthroplasties (THAs) from the United Kingdom National Joint Registry (NJR) were included in a multivariable survival and regression analysis to identify the adjusted hazard of revision for periprosthetic fracture following primary THA using a cementless stem. The effect of a collar in cementless THA on this risk was evaluated in an in vitro model using paired fresh frozen cadaveric femora. RESULTS: The prevalence of early revision for periprosthetic fracture was 0.34% (1180/337 647) and 44.0% (520/1180) occurred within 90 days of surgery. Implant risk factors included: collarless stem, non-grit-blasted finish, and triple-tapered design. In the in vitro model, a medial calcar collar consistently improved the stability and resistance to fracture. CONCLUSION: Analysis of features of stem design in registry data is a useful method of identifying implant characteristics that affect the risk of early periprosthetic fracture around a cementless femoral stem. A collar on the calcar reduced the risk of an early periprosthetic fracture and this was confirmed by biomechanical testing. This approach may be useful in the analysis of other uncommon modes of failure after THA. Cite this article: Bone Joint J 2019;101-B:779-786.

'Warning: allergic to penicillin': association between penicillin allergy status in 2.3 million NHS general practice electronic health records, antibiotic prescribing and health outcomes.

BACKGROUND: The prevalence of reported penicillin allergy (PenA) and the impact these records have on health outcomes in the UK general population are unknown. Without such data, justifying and planning enhanced allergy services is challenging. OBJECTIVES: To determine: (i) prevalence of PenA records; (ii) patient characteristics associated with PenA records; and (iii) impact of PenA records on antibiotic prescribing/health outcomes in primary care. METHODS: We carried out cross-sectional/retrospective cohort studies using patient-level data from electronic health records. Cohort study: exact matching across confounders identified as affecting PenA records. Setting: English NHS general practices between 1 April 2013 and 31 March 2014. Participants: 2.3 million adult patients. Outcome measures: prevalence of PenA, antibiotic prescribing, mortality, MRSA infection/colonization and Clostridioides difficile infection. RESULTS: PenA prevalence was 5.9% (IQR = 3.8%-8.2%). PenA records were more common in older people, females and those with a comorbidity, and were affected by GP practice. Antibiotic prescribing varied significantly: penicillins were prescribed less frequently in those with a PenA record [relative risk (RR)  = 0.15], and macrolides (RR = 4.03), tetracyclines (RR = 1.91) nitrofurantoin (RR = 1.09), trimethoprim (RR = 1.04), cephalosporins (RR = 2.05), quinolones (RR = 2.10), clindamycin (RR = 5.47) and total number of prescriptions were increased in patients with a PenA record. Risk of re-prescription of a new antibiotic class within 28 days (RR = 1.32), MRSA infection/colonization (RR = 1.90) and death during the year subsequent to 1 April 2013 (RR = 1.08) increased in those with PenA records. CONCLUSIONS: PenA records are common in the general population and associated with increased/altered antibiotic prescribing and worse health outcomes. We estimate that incorrect PenA records affect 2.7 million people in England. Establishing true PenA status (e.g. oral challenge testing) would allow more people to be prescribed first-line antibiotics, potentially improving health outcomes.

Prospective observational cohort study of the association between antiplatelet therapy, bleeding and thrombosis in patients with coronary stents undergoing noncardiac surgery.

BACKGROUND: The perioperative management of antiplatelet therapy in noncardiac surgery patients who have undergone previous percutaneous coronary intervention (PCI) remains a dilemma. Continuing dual antiplatelet therapy (DAPT) may carry a risk of bleeding, while stopping antiplatelet therapy may increase the risk of perioperative major adverse cardiovascular events (MACE). METHODS: Occurrence of Bleeding and Thrombosis during Antiplatelet Therapy In Non-Cardiac Surgery (OBTAIN) was an international prospective multicentre cohort study of perioperative antiplatelet treatment, MACE, and serious bleeding in noncardiac surgery. The incidences of MACE and bleeding were compared in patients receiving DAPT, monotherapy, and no antiplatelet therapy before surgery. Unadjusted risk ratios were calculated taking monotherapy as the baseline. The adjusted risks of bleeding and MACE were compared in patients receiving monotherapy and DAPT using propensity score matching. RESULTS: A total of 917 patients were recruited and 847 were eligible for inclusion. Ninety-six patients received no antiplatelet therapy, 526 received monotherapy with aspirin, and 225 received DAPT. Thirty-two patients suffered MACE and 22 had bleeding. The unadjusted risk ratio for MACE in patients receiving DAPT compared with monotherapy was 1.9 (0.93-3.88), P=0.08. There was no difference in MACE between no antiplatelet treatment and monotherapy 1.03 (0.31-3.46), P=0.96. Bleeding was more frequent with DAPT 6.55 (2.3-17.96) P=0.0002. In a propensity matched analysis of 177 patients who received DAPT and 177 monotherapy patients, the risk ratio for MACE with DAPT was 1.83 (0.69-4.85), P=0.32. The risk of bleeding was significantly greater in the DAPT group 4.00 (1.15-13.93), P=0.031. CONCLUSIONS: OBTAIN showed an increased risk of bleeding with DAPT and found no evidence for protective effects of DAPT from perioperative MACE in patients who have undergone previous PCI.

Evaluation of the Methods and Management of Acute Coronary Events (EMMACE)-3: protocol for a longitudinal study.

INTRODUCTION: Patients with cardiovascular disease are living longer and are more frequently accessing healthcare resources. The Evaluation of the Methods and Management of Acute Coronary Events (EMMACE)-3 national study is designed to improve understanding of the effect of quality of care on health-related outcomes for patients hospitalised with acute coronary syndrome (ACS). METHODS AND ANALYSIS: EMMACE-3 is a longitudinal study of 5556 patients hospitalised with an ACS in England. The study collects repeated measures of health-related quality of life, information about medications and patient adherence profiles, a survey of hospital facilities, and morbidity and mortality data from linkages to multiple electronic health records. Together with EMMACE-3X and EMMACE-4, EMMACE-3 will assimilate detailed information for about 13 000 patients across more than 60 hospitals in England. ETHICS AND DISSEMINATION: EMMACE-3 was given a favourable ethical opinion by Leeds (West) Research Ethics committee (REC reference: 10/H131374). On successful application, study data will be shared with academic collaborators. The findings from EMMACE-3 will be disseminated through peer-reviewed publications, at scientific conferences, the media, and through patient and public involvement. STUDY REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01808027. Information about the study is also available at EMMACE.org.

Mortality and missed opportunities along the pathway of care for ST-elevation myocardial infarction: a national cohort study.

AIMS: To examine the association between cumulative missed opportunities for care (CMOC) and mortality in patients with ST-elevation myocardial infarction (STEMI). METHODS: A cohort study of 112,286 STEMI patients discharged from hospital alive between January 2007 and December 2010, using data from the Myocardial Ischaemia National Audit Project (MINAP). A CMOC score was calculated for each patient and included: pre-hospital ECG, acute use of aspirin, timely reperfusion, prescription at hospital discharge of aspirin, thienopyridine inhibitor, ACE-inhibitor (or equivalent), HMG-CoA reductase inhibitor and ß-blocker, and referral for cardiac rehabilitation. Mixed-effects logistic regression models evaluated the effect of CMOC on risk-adjusted 30-day and 1-year mortality (RAMR). RESULTS: 44.5% of patients were ineligible for ≥1 care component. Of patients eligible for all nine components, 50.6% missed ≥1 opportunity. Pre-hospital ECG and timely reperfusion were most frequently missed, predicting further missed care at discharge (pre-hospital ECG incident rate ratio [95% CI]: 1.64 [1.58-1.70]; timely reperfusion 9.94 [9.51-10.40]). Patients ineligible for care had higher RAMR than those eligible for care (30-days: 1.7% vs. 1.1%; 1-year: 8.6% vs. 5.2%), whilst those with no missed care had lower mortality than patients with ≥4 CMOC (30-days: 0.5% vs. 5.4%, adjusted OR (aOR) per CMOC group 1.22, 95% CI: 1.05-1.42; 1-year: 3.2% vs. 22.8%, aOR 1.23, 1.13-1.34). CONCLUSIONS: Opportunities for care in STEMI are commonly missed and significantly associated with early and later mortality. Thus, outcomes after STEMI may be improved by greater attention to missed opportunities to eligible care.

An international cross-sectional survey of antimicrobial stewardship programmes in hospitals.

OBJECTIVES: To report the extent and components of global efforts in antimicrobial stewardship (AMS) in hospitals. METHODS: An Internet-based survey comprising 43 questions was disseminated worldwide in 2012. RESULTS: Responses were received from 660 hospitals in 67 countries: Africa, 44; Asia, 50; Europe, 361; North America, 72; Oceania, 30; and South and Central America, 103. National AMS standards existed in 52% of countries, 4% were planning them and 58% had an AMS programme. The main barriers to implementing AMS programmes were perceived to be a lack of funding or personnel, a lack of information technology and prescriber opposition. In hospitals with an existing AMS programme, AMS rounds existed in 64%; 81% restricted antimicrobials (carbapenems, 74.3%; quinolones, 64%; and cephalosporins, 58%); and 85% reported antimicrobial usage, with 55% linking data to resistance rates and 49% linking data to infection rates. Only 20% had electronic prescribing for all patients. A total of 89% of programmes educated their medical, nursing and pharmacy staff on AMS. Of the hospitals, 38% had formally reviewed their AMS programme: reductions were reported by 96% of hospitals for inappropriate prescribing, 86% for broad-spectrum antibiotic use, 80% for expenditure, 71% for healthcare-acquired infections, 65% for length of stay or mortality and 58% for bacterial resistance. CONCLUSIONS: The worldwide development and implementation of AMS programmes varies considerably. Our results should inform and encourage the further evaluation of this with a view to promoting a worldwide stewardship framework. The prospective measurement of well-defined outcomes of the impact of these programmes remains a significant challenge.

Trends in hospital treatments, including revascularisation, following acute myocardial infarction, 2003-2010: a multilevel and relative survival analysis for the National Institute for Cardiovascular Outcomes Research (NICOR).

OBJECTIVE: To investigate temporal changes in survival after acute myocardial infarction (AMI) by early invasive strategy. METHODS: Accelerated failure time and 6-month relative survival analyses stratified by thrombolysis or primary percutaneous coronary intervention (PPCI) for ST elevation myocardial infarction (STEMI) and coronary angiography for non-STEMI (NSTEMI) encompassing 583 466 patients across 247 hospitals in England and Wales over hospital admission periods 2003-2004, 2005-2006, 2007-2008 and 2009-2010. RESULTS: Survival improved significantly for STEMI patients who received reperfusion therapy (time ratio (TR) 1.47, 95% CI 1.22 to 2.78) and was stable for those who did not (TR 1.02, 95% CI 0.85 to 1.22). While there were significant improvements in survival for NSTEMI patients who underwent coronary angiography (TR 1.39, 95% CI 1.18 to 1.62), there was a significant decline for those who did not (TR 0.70, 95% CI 0.65 to 0.75). Patients without reperfusion therapy or coronary angiography had a greater number of comorbidities, but the use of secondary prevention medications was comparable with patients who received reperfusion therapy or coronary angiography. There was a significant hospital-level survival effect, with higher crude 6-month mortality in hospitals in the lowest coronary angiography and PPCI quartiles (angiography Q1: 16.4% vs Q4: 12.8%; PPCI Q1: 15.8% vs Q4: 12.4%). CONCLUSIONS: Survival rates after AMI have improved. Whereas survival estimates for STEMI patients who did not receive reperfusion therapy were stable, they worsened for NSTEMI patients not receiving coronary angiography.

Age-dependent inequalities in improvements in mortality occur early after acute myocardial infarction in 478,242 patients in the Myocardial Ischaemia National Audit Project (MINAP) registry.

BACKGROUND: Mortality rates after acute myocardial infarction (AMI) have declined, but there is uncertainty regarding the extent of improvements in early mortality in the elderly. METHODS: Mixed-effects regression analysis of 30-day mortality using data from 478,242 patients with AMI at 215 hospitals in England and Wales stratified by STEMI/NSTEMI, sex, and age group. A hospital opportunity-based composite score (OBCS) for aspirin, ACE-inhibitor, statin, ß blocker, and referral for cardiac rehabilitation was used as measure of quality of hospital care. RESULTS: 30-day mortality rates (95% CI) fell from 10.7% (10.6 to 10.9%) in 2004/5 to 8.4% (8.3 to 8.6%) in 2008/9. The median (IQR) hospital OBCSs increased over time, 2004/5: 87.3 (7.2), 2006/7: 88.9 (6.3), 2008/9: 90.3 (6.1), P<0.001, and were similar between age groups (18 to <65 years, 65 to 79 years, and ≥ 80 years) for STEMI: 89.4 (6.5) vs. 89.4 (6.6), vs. 89.2 (6.5) and NSTEMI: 88.6 (7.3) vs. 88.8 (7.0) vs. 88.9 (7.0), respectively For males, all age groups except patients <65 years demonstrated a significant decrease in adjusted mortality. For females, only patients ≥ 80 years demonstrated a significant reduction in adjusted mortality. A 1% increase in hospital OBCS was associated with a 1% decrease in 30-day mortality (95% CI: 0.99 to 0.99, P<0.001). CONCLUSION: In England and Wales, for patients with AMI there are age and sex-dependent differences in improvements in 30-day mortality. Whereas young males with AMI have reached an acceptable performance plateau, all other groups are either improving or, more importantly, are yet to demonstrate this.

Mixed-effects Gaussian process functional regression models with application to dose-response curve prediction.

We propose a new semiparametric model for functional regression analysis, combining a parametric mixed-effects model with a nonparametric Gaussian process regression model, namely a mixed-effects Gaussian process functional regression model. The parametric component can provide explanatory information between the response and the covariates, whereas the nonparametric component can add nonlinearity. We can model the mean and covariance structures simultaneously, combining the information borrowed from other subjects with the information collected from each individual subject. We apply the model to dose-response curves that describe changes in the responses of subjects for differing levels of the dose of a drug or agent and have a wide application in many areas. We illustrate the method for the management of renal anaemia. An individual dose-response curve is improved when more information is included by this mechanism from the subject/patient over time, enabling a patient-specific treatment regime.

Resolving inequalities in care? Reduced mortality in the elderly after acute coronary syndromes. The Myocardial Ischaemia National Audit Project 2003-2010.

AIMS: To examine age-dependent in-hospital mortality for hospitalization with acute coronary syndromes (ACS) in England and Wales. METHODS AND RESULTS: Mixed-effects regression analysis using data from 616 011 ACS events at 255 hospitals as recorded in the Myocardial Ischemia National Audit Project (MINAP) 2003-2010; 102 415 (16.7%) patients were aged <55 years and 72 721 (11.9%) ≥85 years. Patients ≥85 years with ST-elevation myocardial infarction (STEMI) were less likely to receive emergency reperfusion therapy than those <55 years (RR = 0.27, 95% CI: 0.25-0.28). Older patients had greater lengths of stay (P< 0.001) and higher in-hospital mortality (P< 0.001). For STEMI and non-ST-elevation myocardial infarction (NSTEMI), there were reductions in in-hospital mortality from 2003 to 2010 across all age groups including the very elderly. For STEMI ≥ 85 years, in-hospital mortality reduced from 30.1% in 2003 to 19.4% in 2010 (RR = 0.54, 95% CI: 0.38-0.75, P< 0.001), and for NSTEMI ≥ 85 years, from 31.5% in 2003 to 20.4% in 2010 (RR = 0.56, 95% CI: 0.42-0.73, P< 0.001). Findings were upheld after multi-level adjustment (base = 2003): male STEMI 2010 OR = 0.60, 95% CI: 0.48-0.75; female STEMI 2010 OR = 0.55, 95% CI: 0.42-0.71; male NSTEMI OR = 0.50, 95% CI: 0.42-0.60; female NSTEMI OR = 0.49, 95% CI: 0.40-0.59. CONCLUSION: For patients hospitalized with ACS in England and Wales, there have been substantial reductions in in-hospital mortality rates from 2003 to 2010 across all age groups. The temporal improvements in mortality were similar for sex and type of acute myocardial infarction. Age-dependent inequalities in the management of ACS were apparent.

Agreement between computed tomography and ultrasound on abdominal aortic aneurysms and implications on clinical decisions.

OBJECTIVES: The United Kingdom abdominal aortic aneurysm (AAA) screening programme refers aneurysms with ultrasound (US) diameters of ≥5.5 cm to vascular services for consideration of computed tomography (CT) and intervention. We investigated the discrepancy between US and CT, implications on clinical decisions and question at which stage CT be used. DESIGN/METHODS: AAA USs over 5 years were retrospectively analysed. Patients included had aneurysms measuring ≥5 cm on US with subsequent CT within 2 months (n = 123). Based on maximum US diameters, 44 patients had aneurysms between 5 and 5.4 cm (group I) and 79 patients ≥5.5 cm (group II). Results were cross-referenced. Correlation and limits of agreement were calculated. Two radiologists re-measured 44 pairs of CT/US scans and the inter-observer bias in determining discrepancies between imaging modalities calculated. RESULTS: Mean difference between imaging modalities was 0.21 cm (±0.39 cm, p < 0.001). Limits of agreement were -0.55 to 0.96 cm, exceeding clinical acceptability. Mean difference was higher and significant in group I (0.39 cm, p < 0.001) compared to group II (0.10 cm, p > 0.05). Seventy-percent of group I patients had CT scans revealing diameters of ≥5.5 cm. Inter-observer bias was not significant. CONCLUSION: Significant differences between imaging modalities, more in US diameters of below 5.5 cm, exist. We recommend AAAs measuring ≥5 cm on US should undergo earlier referral to a vascular service and CT.

Impact of missing data on standardised mortality ratios for acute myocardial infarction: evidence from the Myocardial Ischaemia National Audit Project (MINAP) 2004-7.

BACKGROUND: Standardised mortality ratios (SMR) are often used to depict cardiovascular care. Data missingness, data quality, temporal variation and case-mix can, however, complicate the assessment of clinical performance. OBJECTIVES: To study Primary Care Trust (PCT) 30-day SMRs for STEMI and NSTEMI whilst considering the impact of missing data for age, sex and IMD score. DESIGN: Observational study using data from the Myocardial Ischaemia National Audit Project (MINAP) database to generate PCT SMR maps and funnel plots for England, 2004-2007. PATIENTS: 217,157 PATIENTS: 40.4% STEMI and 59.6% NSTEMI. RESULTS: 95% CI 30-day unadjusted mortality: STEMI 5.8% to 6.2%; NSTEMI 6.6% to 6.9%; relative risk, 95% CI 1.14, 1.10 to 1.19. Median (IQR) data missingess by PCT for composite of age, sex and IMD score was 1.4% (0.7% to 2.2%). For STEMI and NSTEMI statistically significant predictors of mortality were mean age (STEMI: P<0.001; NSTEMI: P<0.001), proportion of females (STEMI: P<0.001; NSTEMI: P<0.001) and proportion of missing ages (STEMI: P=0.02; NSTEMI: P<0.001). Proportion of missing sex also predicted 30-day mortality for NSTEMI (P=0.01). Maps of SMRs demonstrated substantial mortality variation, but no evidence of North / South divide. There were significant correlations between STEMI and NSTEMI observed (R² 0.72) and standardised mortality (R² 0.49) rates. PCT data aggregation gave an acceptable model fit in terms of deviance explained. For STEMI there were 33 (21.7%) regions below the 99.8% lower limit of the associated performance funnel plot, and 28 (18.4%) for NSTEMI; the inclusion of missing data did not affect the distribution of SMRs. CONCLUSIONS: The proportion of missing data was associated with 30-day mortality for STEMI and NSTEMI, however it did not influence the distribution of PCTs within the funnel plots. There was considerable variation in mortality not attributable to key patient-specific factors, supporting the notion of regional-dependent variation in STEMI and NSTEMI care.

The response to sertraline in men with chronic pelvic pain syndrome.

OBJECTIVES: Male chronic pelvic pain syndrome (CPPS) is difficult to manage. Although antidepressants are frequently used in clinical practice, to date no interventional study has been published. We investigated men with CPPS to assess their response to the serotonin specific reuptake inhibitor (SSRI) antidepressant, sertraline. METHODS: Men with CPPS underwent a four glass test to exclude an infective cause for their symptoms. They were randomised to sertraline or matched placebo for 13 weeks after which they were unblinded. They were then allowed to either continue sertraline or cross over to active treatment for a further 13 weeks. Prostatic symptom severity (PSS) and frequency (PSF) scores, the Hospital Anxiety and Depression (HAD) scale and a psychosexual (PSex) questionnaire were completed at 0, 6, 13, and 26 weeks. Statistical analysis was by the Mann-Whitney U and Wilcoxon signed rank tests. RESULTS: 14 men enrolled. At week 13 there was a mean reduction in PSS scores of 6.1 in the active and 2.0 in placebo group, and in PSF scores of 3.6 and 1.0, respectively. There was no statistically significant difference in the PSS and PSF scores between the active versus placebo group because of the small subject numbers. If analysed as a case series, there was a significant reduction in PSS (11.7; p = 0.01) and PSF (5.9; p = 0.03) from baseline following 13 weeks of sertraline. There was also a decrease in mean HAD depression score from 4.6 at baseline to 2.4. CONCLUSION: Sertraline led to a significant improvement in prostatic symptom severity and frequency from baseline following 13 weeks of treatment. Although this analysis does not exclude a placebo effect, the randomised placebo controlled findings show a trend to improvement with sertraline when compared to placebo.