Spinal Mobilization and Manipulation in Horses.

There is a growing body of evidence to support the use of spinal mobilization and manipulation techniques in equine practice. Outcome parameters reported across studies include measures of joint motion, nociception, muscle tone, and performance. Spinal examination procedures include static and dynamic assessments of the quantity and the quality of both active and passive movements. Tiered treatment approaches are recommended to stage the application of various therapies based on ease, cost, and efficacy.

Correction to: The comorbidity burden of type 2 diabetes mellitus: patterns, clusters and predictions from a large English primary care cohort.

The original article [1] contains an omitted grant acknowledgement and affiliation as relates to the contribution of co-author, Rafael Perera-Salazar. As such, the following two amendments should apply to the original article.

The comorbidity burden of type 2 diabetes mellitus: patterns, clusters and predictions from a large English primary care cohort.

BACKGROUND: The presence of additional chronic conditions has a significant impact on the treatment and management of type 2 diabetes (T2DM). Little is known about the patterns of comorbidities in this population. The aims of this study are to quantify comorbidity patterns in people with T2DM, to estimate the prevalence of six chronic conditions in 2027 and to identify clusters of similar conditions. METHODS: We used the Clinical Practice Research Datalink (CPRD) linked with the Index of Multiple Deprivation (IMD) data to identify patients diagnosed with T2DM between 2007 and 2017. 102,394 people met the study inclusion criteria. We calculated the crude and age-standardised prevalence of 18 chronic conditions present at and after the T2DM diagnosis. We analysed longitudinally the 6 most common conditions and forecasted their prevalence in 2027 using linear regression. We used agglomerative hierarchical clustering to identify comorbidity clusters. These analyses were repeated on subgroups stratified by gender and deprivation. RESULTS: More people living in the most deprived areas had ≥ 1 comorbidities present at the time of diagnosis (72% of females; 64% of males) compared to the most affluent areas (67% of females; 59% of males). Depression prevalence increased in all strata and was more common in the most deprived areas. Depression was predicted to affect 33% of females and 15% of males diagnosed with T2DM in 2027. Moderate clustering tendencies were observed, with concordant conditions grouped together and some variations between groups of different demographics. CONCLUSIONS: Comorbidities are common in this population, and high between-patient variability in comorbidity patterns emphasises the need for patient-centred healthcare. Mental health is a growing concern, and there is a need for interventions that target both physical and mental health in this population.

Patient consultation rate and clinical and NHS outcomes: a cross-sectional analysis of English primary care data from 2.7 million patients in 238 practices.

BACKGROUND: Primary care workload is high and increasing in the United Kingdom. We sought to examine the association between rates of primary care consultation and outcomes in England. METHODS: Cross sectional observational study of routine electronic health care records in 283 practices from the Clinical Practice Research Datalink from April 2013 to March 2014. Outcomes included mortality rate, hospital admission rate, Quality and Outcomes Framework (QOF) performance and patient satisfaction. Relationships between consultation rates (with a general practitioner (GP) or nurse) and outcomes were investigated using negative binomial and ordinal logistic regression models. RESULTS: Rates of GP and nurse consultation (per patient person-year) were not associated with mortality or hospital admission rates: mortality incidence rate ratio (IRR) per unit change in GP/ nurse consultation rate = 1.01, 95% CI [0.98 to 1.04]/ 0.97, 95% CI [0.93 to 1.02]; hospital admission IRR per unit change in GP/ nurse consultation rate = 1.02, 95% CI [0.99 to 1.04]/ 0.98, 95% CI [0.94 to 1.032]. Higher rates of nurse but not GP consultation were associated with higher QOF achievement: OR = 1.91, 95% CI [1.39 to 2.62] per unit change in nurse consultation rate vs. OR = 1.04, 95% CI [0.87 to 1.24] per unit change in GP consultation rate. The association between the rates of GP/ nurse consultations and patient satisfaction was mixed. CONCLUSION: There are few associations between primary care consultation rates and outcomes. Previously identified demographic and staffing factors, rather than practice workload, appear to have the strongest relationships with mortality, admissions, performance and satisfaction. Studies with more detailed patient-level data would be required to explore these findings further.

Automated Software System to Promote Anticoagulation and Reduce Stroke Risk: Cluster-Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Oral anticoagulants (OAC) substantially reduce risk of stroke in atrial fibrillation, but uptake is suboptimal. Electronic health records enable automated identification of people at risk but not receiving treatment. We investigated the effectiveness of a software tool (AURAS-AF [Automated Risk Assessment for Stroke in Atrial Fibrillation]) designed to identify such individuals during routine care through a cluster-randomized trial. METHODS: Screen reminders appeared each time the electronic health records of an eligible patient was accessed until a decision had been taken over OAC treatment. Where OAC was not started, clinicians were prompted to indicate a reason. Control practices continued usual care. The primary outcome was the proportion of eligible individuals receiving OAC at 6 months. Secondary outcomes included rates of cardiovascular events and reports of adverse effects of the software on clinical decision-making. RESULTS: Forty-seven practices were randomized. The mean proportion-prescribed OAC at 6 months was 66.3% (SD=9.3) in the intervention arm and 63.9% (9.5) in the control arm (adjusted difference 1.21% [95% confidence interval -0.72 to 3.13]). Incidence of recorded transient ischemic attack was higher in the intervention practices (median 10.0 versus 2.3 per 1000 patients with atrial fibrillation; P=0.027), but at 12 months, we found a lower incidence of both all cause stroke (P=0.06) and hemorrhage (P=0.054). No adverse effects of the software were reported. CONCLUSIONS: No significant change in OAC prescribing occurred. A greater rate of diagnosis of transient ischemic attack (possibly because of improved detection or overdiagnosis) was associated with a reduction (of borderline significance) in stroke and hemorrhage over 12 months. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com. Unique Identifier: ISRCTN55722437.

Clinical workload in UK primary care: a retrospective analysis of 100 million consultations in England, 2007-14.

BACKGROUND: Primary care is the main source of health care in many health systems, including the UK National Health Service (NHS), but few objective data exist for the volume and nature of primary care activity. With rising concerns that NHS primary care workload has increased substantially, we aimed to assess the direct clinical workload of general practitioners (GPs) and practice nurses in primary care in the UK. METHODS: We did a retrospective analysis of GP and nurse consultations of non-temporary patients registered at 398 English general practices between April, 2007, and March, 2014. We used data from electronic health records routinely entered in the Clinical Practice Research Datalink, and linked CPRD data to national datasets. Trends in age-standardised and sex-standardised consultation rates were modelled with joinpoint regression analysis. FINDINGS: The dataset comprised 101,818,352 consultations and 20,626,297 person-years of observation. The crude annual consultation rate per person increased by 10·51%, from 4·67 in 2007-08, to 5·16 in 2013-14. Consultation rates were highest in infants (age 0-4 years) and elderly people (≥85 years), and were higher for female patients than for male patients of all ages. The greatest increases in age-standardised and sex-standardised rates were in GPs, with a rise of 12·36% per 10,000 person-years, compared with 0·9% for practice nurses. GP telephone consultation rates doubled, compared with a 5·20% rise in surgery consultations, which accounted for 90% of all consultations. The mean duration of GP surgery consultations increased by 6·7%, from 8·65 min (95% CI 8·64-8·65) to 9·22 min (9·22-9·23), and overall workload increased by 16%. INTERPRETATION: Our findings show a substantial increase in practice consultation rates, average consultation duration, and total patient-facing clinical workload in English general practice. These results suggest that English primary care as currently delivered could be reaching saturation point. Notably, our data only explore direct clinical workload and not indirect activities and professional duties, which have probably also increased. This and additional research questions, including the outcomes of workload changes on other sectors of health care, need urgent answers for primary care provision internationally. FUNDING: Department of Health Policy Research Programme.

Telephone triage for management of same-day consultation requests in general practice (the ESTEEM trial): a cluster-randomised controlled trial and cost-consequence analysis.

BACKGROUND: Telephone triage is increasingly used to manage workload in primary care; however, supporting evidence for this approach is scarce. We aimed to assess the effectiveness and cost consequences of general practitioner-(GP)-led and nurse-led telephone triage compared with usual care for patients seeking same-day consultations in primary care. METHODS: We did a pragmatic, cluster-randomised controlled trial and economic evaluation between March 1, 2011, and March 31, 2013, at 42 practices in four centres in the UK. Practices were randomly assigned (1:1:1), via a computer-generated randomisation sequence minimised for geographical location, practice deprivation, and practice list size, to either GP-led triage, nurse-led computer-supported triage, or usual care. We included patients who telephoned the practice seeking a same-day face-to-face consultation with a GP. Allocations were concealed from practices until after they had agreed to participate and a stochastic element was included within the minimisation algorithm to maintain concealment. Patients, clinicians, and researchers were not masked to allocation, but practice assignment was concealed from the trial statistician. The primary outcome was primary care workload (patient contacts, including those attending accident and emergency departments) in the 28 days after the first same-day request. Analyses were by intention to treat and per protocol. This trial was registered with the ISRCTN register, number ISRCTN20687662. FINDINGS: We randomly assigned 42 practices to GP triage (n=13), nurse triage (n=15), or usual care (n=14), and 20,990 patients (n=6695 vs 7012 vs 7283) were randomly assigned, of whom 16,211 (77%) patients provided primary outcome data (n=5171 vs 5468 vs 5572). GP triage was associated with a 33% increase in the mean number of contacts per person over 28 days compared with usual care (2·65 [SD 1·74] vs 1·91 [1·43]; rate ratio [RR] 1·33, 95% CI 1·30-1·36), and nurse triage with a 48% increase (2·81 [SD 1·68]; RR 1·48, 95% CI 1·44-1·52). Eight patients died within 7 days of the index request: five in the GP-triage group, two in the nurse-triage group, and one in the usual-care group; however, these deaths were not associated with the trial group or procedures. Although triage interventions were associated with increased contacts, estimated costs over 28 days were similar between all three groups (roughly £75 per patient). INTERPRETATION: Introduction of telephone triage delivered by a GP or nurse was associated with an increase in the number of primary care contacts in the 28 days after a patient's request for a same-day GP consultation, with similar costs to those of usual care. Telephone triage might be useful in aiding the delivery of primary care. The whole-system implications should be assessed when introduction of such a system is considered. FUNDING: Health Technology Assessment Programme UK National Institute for Health Research.

Estimating the diagnostic accuracy of rheumatoid factor in UK primary care: a study using the Clinical Practice Research Datalink.

OBJECTIVE: To investigate the diagnostic accuracy of RF as a test for RA in primary care and its impact on referral times using the Clinical Practice Research Datalink. METHODS: We identified all patients with a first RF test recorded in the Clinical Practice Research Datalink between 1 January 2000 and 31 December 2008 and those diagnosed with RA within 2 years of testing. We calculated likelihood ratios (LRs), sensitivity, specificity and predictive values of RF for a diagnosis of RA. We compared time to hospital referral in those testing positive and negative using Kaplan-Meier failure curves and log-rank tests. RESULTS: Of 62 436 first RF tests, 4679 (7.5%) were positive. There were 1753 incident cases of RA, of which 57.8% were seropositive. The positive LR for RF was 9.5 (95% CI 9.0, 10.0) and the negative LR was 0.5 (95% CI 0.4, 0.5). Sensitivity and specificity were 57.8% (95% CI 55.4%, 60.1%) and 93.9% (95% CI 93.7%, 94.1%) and the positive predictive value and negative predictive value were 21.4% (95% CI 20.3%, 22.6%) and 98.7% (95% CI 98.6%, 98.8%), respectively. Median time to first hospital contact after the first RF test in those with seropositive vs seronegative results was 54 days (95% CI 49, 58) vs 150 (95% CI 147, 152). CONCLUSION: Only 2.8% of patients undergoing RF testing were diagnosed with RA, suggesting that RF is used to screen patients with musculoskeletal symptoms rather than those with more specific features of RA. A positive RF test may be helpful in diagnosing RA in primary care but performs badly in excluding RA and may delay referral.

Missing laboratory test data in electronic general practice records: analysis of rheumatoid factor recording in the clinical practice research datalink.

PURPOSE: To investigate whether information from the literature could be used to identify periods of practice data in an electronic healthcare database during which rheumatoid factor (RF) test results are likely to be missing-not-at-random (MNAR). METHODS: RF tests recorded in the Clinical Practice Research Datalink (CPRD) were identified and defined as having a positive, negative or missing result. The proportion of positive test results was then calculated based on (i) complete-case analysis (ii) after restriction to tests from practice years with no missing test results and (iii) following multiple imputation of missing test results. The same three analyses were then carried out after excluding practice years with a proportion of positive tests incompatible with the missing completely at random (MCAR) assumption. RESULTS: We identified 127,969 RF test records, 30.4% of which did not have an associated test result. Among tests with results available, 19% were positive. Both multiple imputation of the 38,867 missing test results and restriction of the study population to the 491 practice years with complete data had little impact on the percentage of positive tests. Following exclusion of the 544 practice years in which data were likely to be MNAR the percentage of positive tests in all analyses decreased to ~7%. CONCLUSIONS: Recording of RF tests and RF test results in the CPRD is incomplete, with data likely to be MNAR in many practices. Exclusion of practice years with a high proportion of positive tests brought the distribution of positive tests in the study in line with the literature.

BLOod Test Trend for cancEr Detection (BLOTTED): protocol for an observational and prediction model development study using English primary care electronic health record data.

BACKGROUND: Simple blood tests can play an important role in identifying patients for cancer investigation. The current evidence base is limited almost entirely to tests used in isolation. However, recent evidence suggests combining multiple types of blood tests and investigating trends in blood test results over time could be more useful to select patients for further cancer investigation. Such trends could increase cancer yield and reduce unnecessary referrals. We aim to explore whether trends in blood test results are more useful than symptoms or single blood test results in selecting primary care patients for cancer investigation. We aim to develop clinical prediction models that incorporate trends in blood tests to identify the risk of cancer. METHODS: Primary care electronic health record data from the English Clinical Practice Research Datalink Aurum primary care database will be accessed and linked to cancer registrations and secondary care datasets. Using a cohort study design, we will describe patterns in blood testing (aim 1) and explore associations between covariates and trends in blood tests with cancer using mixed-effects, Cox, and dynamic models (aim 2). To build the predictive models for the risk of cancer, we will use dynamic risk modelling (such as multivariate joint modelling) and machine learning, incorporating simultaneous trends in multiple blood tests, together with other covariates (aim 3). Model performance will be assessed using various performance measures, including c-statistic and calibration plots. DISCUSSION: These models will form decision rules to help general practitioners find patients who need a referral for further investigation of cancer. This could increase cancer yield, reduce unnecessary referrals, and give more patients the opportunity for treatment and improved outcomes.

Changing clinical practice through patient specific reminders available at the time of the clinical encounter: systematic review and meta-analysis.

OBJECTIVE: To synthesise current evidence for the influence on clinical behaviour of patient-specific electronically generated reminders available at the time of the clinical encounter. DATA SOURCES: PubMed, Cochrane library of systematic reviews; Science Citation Index Expanded; Social Sciences Citation Index; ASSIA; EMBASE; CINAHL; DARE; HMIC were searched for relevant articles. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: We included controlled trials of reminder interventions if the intervention was: directed at clinician behaviour; available during the clinical encounter; computer generated (including computer generated paper-based reminders); and generated by patient-specific (rather than condition specific or drug specific) data. STUDY APPRAISAL AND SYNTHESIS METHODS: Systematic review and meta-analysis of controlled trials published since 1970. A random effects model was used to derive a pooled odds ratio for adherence to recommended care or achievement of target outcome. Subgroups were examined based on area of care and study design. Odds ratios were derived for each sub-group. We examined the designs, settings and other features of reminders looking for factors associated with a consistent effect. RESULTS: Altogether, 42 papers met the inclusion criteria. The studies were of variable quality and some were affected by unit of analysis errors due to a failure to account for clustering. An overall odds ratio of 1.79 [95% confidence interval 1.56, 2.05] in favour of reminders was derived. Heterogeneity was high and factors predicting effect size were difficult to identify. LIMITATIONS: Methodological diversity added to statistical heterogeneity as an obstacle to meta-analysis. The quality of included studies was variable and in some reports procedural details were lacking. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: The analysis suggests a moderate effect of electronically generated, individually tailored reminders on clinician behaviour during the clinical encounter. Future research should concentrate on identifying the features of reminder interventions most likely to result in the target behaviour.

Use and risk of side effects of antiresorptive medication in people with intellectual disabilities.

Background: Recent studies show that adults with intellectual disabilities (ID) have high incidence of major osteoporotic fracture, especially hip fracture. In those ≥ 50 years, women and men with ID have an approximately two and four times higher rate of hip fracture than women and men without ID. Increased awareness of osteoporotic fracture risk in ID may lead to wider use of antiresorptive drugs (bisphosphonates and denosumab) in this population. We aimed to compare, between people with and without ID, the incidence of 1) major side effects, namely medication related osteoporosis of the jaw (ONJ) and oesophagitis; 2) oral pathology, which can be a risk factor for ONJ. Methods: Exploratory study investigating safety of first line osteoporosis medication within the population of a previous study comparing fracture incidence in people with and without ID in the GOLD database of the Clinical Practice Research Datalink 1998-2017. Results: The percentage of people on antiresorptive drugs was identical in the ID and non ID group (1.4%). The number of individuals who developed ONJ and oesophagitis during the study was too low to allow an accurate estimate of incidence of the events and a comparison between the two groups. The incidence of any oral pathology was 119.31 vs 64.68/10000 person year in the ID vs non ID group. Conclusions: Medication related ONJ and oesophagitis are rare in people with and without ID. There is no reason based on our findings to use antiresorptives differently in people with ID as in the rest of the population. However, the potential for side effects of antiresorptives will inherently increase with wider use of these drugs. Given the higher incidence of oral pathology in people with ID, which could put them at higher risk of ONJ, precautions should be taken to prevent this complication by attention to oral health.

Fracture rates have recently been shown to be substantially higher in people with intellectual disabilities (ID). This finding is likely to lead to the wider use of bone strengthening (antiresorptive) agents in this group, namely bisphosphonates and denosumab. These drugs are effective at reducing the risk of fractures, but carry potential adverse effects. One of these is the rare but serious condition osteonecrosis of the jaw (ONJ). We studied general practice records to investigate whether the incidence of this problem is higher in people with ID taking these drugs. We also looked at the incidence of oral conditions that may put an individual at higher risk of it, including periodontitis, dental abscess, and tooth extractions. The recording of ONJ in people with ID was extremely low, no different from the general population in our study, although we were using general practice rather than dental records. However, dental problems that might predispose to it were recorded nearly twice as frequently in the group with ID. The other side effect we looked at was oesophagitis, which was not found to be more common in people with ID taking bisphosphonates. This study highlights the need to provide good oral hygiene, dental care and surveillance in people with ID receiving antiresorptive drug therapy.

Full Blood Count Trends for Colorectal Cancer Detection in Primary Care: Development and Validation of a Dynamic Prediction Model.

Colorectal cancer has low survival rates when late-stage, so earlier detection is important. The full blood count (FBC) is a common blood test performed in primary care. Relevant trends in repeated FBCs are related to colorectal cancer presence. We developed and internally validated dynamic prediction models utilising trends for early detection. We performed a cohort study. Sex-stratified multivariate joint models included age at baseline (most recent FBC) and simultaneous trends over historical haemoglobin, mean corpuscular volume (MCV), and platelet measurements up to baseline FBC for two-year risk of diagnosis. Performance measures included the c-statistic and calibration slope. We analysed 250,716 males and 246,695 females in the development cohort and 312,444 males and 462,900 females in the validation cohort, with 0.4% of males and 0.3% of females diagnosed two years after baseline FBC. Compared to average population trends, patient-level declines in haemoglobin and MCV and rise in platelets up to baseline FBC increased risk of diagnosis in two years. C-statistic: 0.751 (males) and 0.763 (females). Calibration slope: 1.06 (males) and 1.05 (females). Our models perform well, with low miscalibration. Utilising trends could bring forward diagnoses to earlier stages and improve survival rates. External validation is now required.

Trends in the full blood count blood test and colorectal cancer detection: a longitudinal, case-control study of UK primary care patient data.

Background: The full blood count (FBC) is a common blood test performed in general practice. It consists of many individual parameters that may change over time due to colorectal cancer. Such changes are likely missed in practice. We identified trends in these FBC parameters to facilitate early detection of colorectal cancer. Methods: We performed a retrospective, case-control, longitudinal analysis of UK primary care patient data. LOWESS smoothing and mixed effects models were derived to compare trends in each FBC parameter between patients diagnosed and not diagnosed over a prior 10-year period. Results: There were 399,405 males (2.3%, n = 9,255 diagnosed) and 540,544 females (1.5%, n = 8,153 diagnosed) in the study. There was no difference between cases and controls in FBC trends between 10 and four years before diagnosis. Within four years of diagnosis, trends in many FBC levels statistically significantly differed between cases and controls, including red blood cell count, haemoglobin, white blood cell count, and platelets (interaction between time and colorectal cancer presence: p <0.05). FBC trends were similar between Duke's Stage A and D colorectal tumours, but started around one year earlier in Stage D diagnoses. Conclusions: Trends in FBC parameters are different between patients with and without colorectal cancer for up to four years prior to diagnosis. Such trends could help earlier identification.

Colorectal cancer is a common type of cancer in the UK. It is the second most common cause of cancer-related death in the UK. Chances of surviving depend heavily on the tumour stage at diagnosis, which represents how much the tumour has developed. If diagnosed and treated at the earliest stage, where the tumour is confined to the colon, nine in 10 patients are expected to be alive five years later. If diagnosed at the latest stage, when the cancer has spread outside the colon, this drops to one in 10 surviving. The majority of UK patients with colorectal cancer are diagnosed with late-stage tumours, so are likely to die. Detecting and treating the cancer earlier can save lives. There is a blood test called the Full Blood Count, which is commonly ordered by doctors for many reasons. This test includes many blood levels, such as haemoglobin, which carries oxygen around the body. Growing tumours cause subtle changes in the blood levels over time, but it is unclear what these changes are and if they could help find cancer in the early stages. In our study, we looked at blood tests from almost one million patients in the UK, including around 17,000 with colorectal cancer. We checked how blood levels change over 10 years before diagnosis. We found that in the few years before patients are diagnosed, patients usually had blood levels that rapidly started increasing or declining (depending on the blood level) and this was often not seen in patients without colorectal cancer. Our study highlights that using trends over time in blood test results may be useful to identify colorectal cancer. Such trends could facilitate earlier detection because they were present for years before diagnosis. That would improve the chances of successful treatment and chances of survival.

Incidence of fractures in people with intellectual disabilities over the life course: a retrospective matched cohort study.

Background: Current osteoporosis guidelines do not identify individuals with intellectual disabilities (ID) as at risk of fracture, potentially missing opportunities for prevention. We aimed to assess the incidence of fractures in people with ID over the life course. Methods: Descriptive analysis of open cohort study using anonymised electronic health records from the UK Clinical Practice Research Datalink, linked to the Hospital Episode Statistics database (Jan 1, 1998-Dec 31, 2017). All individuals with ID were matched on age and sex to five individuals without ID.  We calculated the incidence rate (95% CI) per 10000 person-years (py) and incidence rate ratio (IRR, 95% CI) to compare fractures between individuals with and without ID (age 1-17 and ≥18 years) for any fracture, and in those aged 18-49 and ≥ 50 years for major osteoporotic fracture (vertebra, shoulder, wrist, hip), and for hip fracture. Findings: 43176 individuals with ID (15470 children aged 1-17 years; 27706 adults aged ≥ 18 years) were identified and included (40.4% females) along with 215733 matched control individuals.  The median age at study entry was 24 (10th-90th centiles 3-54) years. Over a median (10th-90th centile) follow-up of 7.1 (0.9-17.6) and 6.5 (0.8-17.6) years, there were 5941 and 24363 incident fractures in the ID and non ID groups respectively. Incidence of any fracture was 143.5 (131.8-156.3) vs 120.7 (115.4-126.4)/10000 py (children), 174.2 (166.4-182.4)/10000 py vs 118.2 (115.3-121.2)/10000 py (adults) in females. In males it was 192.5 (182.4-203.2) vs 228.5 (223.0-234.1)/10000 py (children), 155.6 (149.3-162.1)/10000 py vs 128.4 (125.9-131.0)/10000 py (adults). IRR for major osteoporotic fracture was 1.81 (1.50-2.18) age 18-49 years, 1.69 (1.53-1.87) age ≥ 50 years in women. In men it was 1.56 (1.36-1.79) age 18-49 years, 2.45 (2.13-2.81) age ≥ 50 years. IRR for hip fracture was 7.79 (4.14-14.65) age 18-49 years, 2.28 (1.91-2.71) age ≥ 50 years in women. In men it was 6.04 (4.18-8.73) age 18-49 years, 3.91 (3.17-4.82) age ≥ 50 years. Comparable rates of major osteoporotic fracture and of hip fracture occurred approximately 15 and 20 years earlier respectively in women and 20 and 30 years earlier respectively in men with ID than without ID. Fracture distribution differed profoundly, hip fracture 9.9% vs 5.0% of any fracture in adults with ID vs without ID. Interpretation: The incidence, type, and distribution of fractures in people with intellectual disabilities suggest early onset osteoporosis. Prevention and management strategies are urgently required, particularly to reduce the incidence of hip fracture. Funding: National Institute for Health and Care Research.

Pulmonary arterial pressure in fattened Angus steers at moderate altitude influences early postmortem mitochondria functionality and meat color during retail display.

Pulmonary hypertension is a noninfectious disease of cattle at altitudes > 1524 m (5,000 ft). Mean pulmonary arterial pressures (PAP) are used as an indicator for pulmonary hypertension in cattle. High PAP cattle (≥50 mmHg) entering the feedlot at moderate elevations have lower feed efficiency as compared to low PAP cattle (< 50 mmHg). The impact of pulmonary arterial pressure on mitochondrial function, oxidative phosphorylation (OXPHOS) protein abundance, and meat color was examined using longissimus lumborum (LL) from high (98 ± 13 mmHg; n = 5) and low (41 ± 3 mmHg; n = 6) PAP fattened Angus steers (live weight of 588 ± 38 kg) during early postmortem period (2 and 48 h) and retail display (days 1 to 9), respectively. High PAP muscle had greater (P = 0.013) OXPHOS-linked respiration and proton leak-associated respiration than low PAP muscles at 2 h postmortem but rapidly declined to be similar (P = 0.145) to low PAP muscle by 48 h postmortem. OXPHOS protein expression was higher (P = 0.045) in low PAP than high PAP muscle. During retail display, redness, chroma, hue, ratio of reflectance at 630 and 580 nm, and metmyoglobin reducing activity decreased faster (P < 0.05) in high PAP steaks than low PAP. Lipid oxidation significantly increased (P < 0.05) in high PAP steaks but not (P > 0.05) in low PAP. The results indicated that high PAP caused a lower OXPHOS efficiency and greater fuel oxidation rates under conditions of low ATP demand in premortem beef LL muscle; this could explain the lower feed efficiency in high PAP feedlot cattle compared to low PAP counterparts. Mitochondrial integral function (membrane integrity or/and protein function) declined faster in high PAP than low PAP muscle at early postmortem. LL steaks from high PAP animals had lower color stability than those from the low PAP animals during simulated retail display, which could be partially attributed to the loss of muscle mitochondrial function at early postmortem by ROS damage in high PAP muscle.

The impact of pulmonary arterial pressure (PAP) on mitochondrial function, oxidative phosphorylation protein abundance, and meat color was examined using longissimus lumborum (LL) from high (98 ± 13 mmHg) and low (41 ± 3 mmHg) PAP fattened Angus steers (live weight of 588 ± 38 kg) during early postmortem period (2 and 48 h) and retail display (days 1 to 9), respectively. The results indicated that high PAP caused a lower oxidative phosphorylation efficiency and greater fuel oxidation rates under conditions of positive energy balance in beef LL muscle. This could explain the lower feed efficiency in high PAP feedlot cattle compared to low PAP counterparts. Mitochondrial integral function declined faster in high PAP than low PAP muscle at early postmortem. LL steaks from high PAP animals had lower color stability than those from the low PAP animals during simulated retail display, which could be partially attributed to the loss of muscle mitochondrial function at early postmortem in high PAP muscle.

Non-invasive and minimally invasive glucose monitoring devices: a systematic review and meta-analysis on diagnostic accuracy of hypoglycaemia detection.

BACKGROUND: The use of minimally and non-invasive monitoring systems (including continuous glucose monitoring) has increased rapidly over recent years. Up to now, it remains unclear how accurate devices can detect hypoglycaemic episodes. In this systematic review and meta-analysis, we assessed the diagnostic accuracy of minimally and non-invasive hypoglycaemia detection in comparison to capillary or venous blood glucose in patients with type 1 or type 2 diabetes. METHODS: Clinical Trials.gov, Cochrane Library, Embase, PubMed, ProQuest, Scopus and Web of Science were systematically searched. Two authors independently screened the articles, extracted data using a standardised extraction form and assessed methodological quality using a review-tailored quality assessment tool for diagnostic accuracy studies (QUADAS-2). The diagnostic accuracy of hypoglycaemia detection was analysed via meta-analysis using a bivariate random effects model and meta-regression with regard to pre-specified covariates. RESULTS: We identified 3416 nonduplicate articles. Finally, 15 studies with a total of 733 patients were included. Different thresholds for hypoglycaemia detection ranging from 40 to 100 mg/dl were used. Pooled analysis revealed a mean sensitivity of 69.3% [95% CI: 56.8 to 79.4] and a mean specificity of 93.3% [95% CI: 88.2 to 96.3]. Meta-regression analyses showed a better hypoglycaemia detection in studies indicating a higher overall accuracy, whereas year of publication did not significantly influence diagnostic accuracy. An additional analysis shows the absence of evidence for a better performance of the most recent generation of devices. CONCLUSION: Overall, the present data suggest that minimally and non-invasive monitoring systems are not sufficiently accurate for detecting hypoglycaemia in routine use. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2018 CRD42018104812.

Measuring the complexity of general practice consultations: a Delphi and cross-sectional study in English primary care.

BACKGROUND: The complexity of general practice consultations may be increasing and varies in different settings. A measure of complexity is required to test these hypotheses. AIM: To develop a valid measure of general practice consultation complexity applicable to routine medical records. DESIGN AND SETTING: Delphi study to select potential indicators of complexity followed by a cross-sectional study in English general practices to develop and validate a complexity measure. METHOD: The online Delphi study over two rounds identified potential indicators of consultation complexity. The cross-sectional study used an age-sex stratified random sample of patients and general practice face-to-face consultations from 2013/2014 in the Clinical Practice Research Datalink. The authors explored independent relationships between each indicator and consultation duration using mixed-effects regression models, and revalidated findings using data from 2017/2018. The proportion of complex consultations in different age-sex groups was assessed. RESULTS: A total of 32 GPs participated in the Delphi study. The Delphi panel endorsed 34 of 45 possible complexity indicators after two rounds. After excluding factors because of low prevalence or confounding, 17 indicators were retained in the cross-sectional study. The study used data from 173 130 patients and 725 616 face-to-face GP consultations. On defining complexity as the presence of any of these 17 factors, 308 370 consultations (42.5%) were found to be complex. Mean duration of complex consultations was 10.49 minutes, compared to 9.64 minutes for non-complex consultations. The proportion of complex consultations was similar in males and females but increased with age. CONCLUSION: The present consultation complexity measure has face and construct validity. It may be useful for research, management and policy, and for informing decisions about the range of resources needed in different practices.

Assessing the severity of cardiovascular disease in 213 088 patients with coronary heart disease: a retrospective cohort study.

OBJECTIVE: Most current cardiovascular disease (CVD) risk stratification tools are for people without CVD, but very few are for prevalent CVD. In this study, we developed and validated a CVD severity score in people with coronary heart disease (CHD) and evaluated the association between severity and adverse outcomes. METHODS: Primary and secondary care data for 213 088 people with CHD in 398 practices in England between 2007 and 2017 were used. The cohort was randomly divided into training and validation datasets (80%/20%) for the severity model. Using 20 clinical severity indicators (each assigned a weight=1), baseline and longitudinal CVD severity scores were calculated as the sum of indicators. Adjusted Cox and competing-risk regression models were used to estimate risks for all-cause and cause-specific hospitalisation and mortality. RESULTS: Mean age was 64.5±12.7 years, 46% women, 16% from deprived areas, baseline severity score 1.5±1.2, with higher scores indicating a higher burden of disease. In the training dataset, 138 510 (81%) patients were hospitalised at least once, and 39 944 (23%) patients died. Each 1-unit increase in baseline severity was associated with 41% (95% CI 37% to 45%, area under the receiver operating characteristics (AUROC) curve=0.79) risk for 1 year for all-cause mortality; 59% (95% CI 52% to 67%, AUROC=0.80) for cardiovascular (CV)/diabetes mortality; 27% (95% CI 26% to 28%) for any-cause hospitalisation and 37% (95% CI 36% to 38%) for CV/diabetes hospitalisation. Findings were consistent in the validation dataset. CONCLUSIONS: Higher CVD severity score is associated with higher risks for any-cause and cause-specific hospital admissions and mortality in people with CHD. Our reproducible score based on routinely collected data can help practitioners better prioritise management of people with CHD in primary care.

The Full Blood Count Blood Test for Colorectal Cancer Detection: A Systematic Review, Meta-Analysis, and Critical Appraisal.

INTRODUCTION: A full blood count (FBC) blood test includes 20 components. We systematically reviewed studies that assessed the association of the FBC and diagnosis of colorectal cancer to identify components as risk factors. We reviewed FBC-based prediction models for colorectal cancer risk. METHODS: MEDLINE, EMBASE, CINAHL, and Web of Science were searched until 3 September 2019. We meta-analysed the mean difference in FBC components between those with and without a diagnosis and critically appraised the development and validation of FBC-based prediction models. RESULTS: We included 53 eligible articles. Three of four meta-analysed components showed an association with diagnosis. In the remaining 16 with insufficient data for meta-analysis, three were associated with colorectal cancer. Thirteen FBC-based models were developed. Model performance was commonly assessed using the c-statistic (range 0.72-0.91) and calibration plots. Some models appeared to work well for early detection but good performance may be driven by early events. CONCLUSION: Red blood cells, haemoglobin, mean corpuscular volume, red blood cell distribution width, white blood cell count, and platelets are associated with diagnosis and could be used for referral. Existing FBC-based prediction models might not perform as well as expected and need further critical testing.