Real-world reproducibility study characterizing patients newly diagnosed with multiple myeloma using Clinical Practice Research Datalink, a UK-based electronic health records database.

PURPOSE: We evaluated the reproducibility of a study characterizing newly-diagnosed multiple myeloma (MM) patients within an electronic health records (EHR) database using different analytic tools. METHODS: We reproduced the findings of a descriptive cohort study using an iterative two-phase approach. In Phase I, a common protocol and statistical analysis plan (SAP) were implemented by independent investigators using the Aetion Evidence Platform® (AEP), a rapid-cycle analytics tool, and SAS statistical software as a gold standard for statistical analyses. Using the UK Clinical Practice Research Datalink (CPRD) dataset, the study included patients newly diagnosed with MM within primary care setting and assessed baseline demographics, conditions, drug exposure, and laboratory procedures. Phase II incorporated analysis revisions based on our initial comparison of the Phase I findings. Reproducibility of findings was evaluate by calculating the match rate and absolute difference in prevalence between the SAS and AEP study results. RESULTS: Phase I yielded slightly discrepant results, prompting amendments to SAP to add more clarity to operational decisions. After detailed specification of data and operational choices, exact concordance was achieved for the number of eligible patients (N = 2646), demographics, comorbidities (i.e., osteopenia, osteoporosis, cardiovascular disease [CVD], and hypertension), bone pain, skeletal-related events, drug exposure, and laboratory investigations in the Phase II analyses. CONCLUSIONS: In this reproducibility study, a rapid-cycle analytics tool and traditional statistical software achieved near-exact findings after detailed specification of data and operational choices. Transparency and communication of the study design, operational and analytical choices between independent investigators were critical to achieve this reproducibility.

Epidemiology of hyperhidrosis in 2 population-based health care databases.

BACKGROUND: Population-based and clinical case reports of hyperhidrosis (HH) provide prevalence estimates that vary widely across reported studies because of differences in case ascertainment. OBJECTIVE: In this study, we specify diagnostic, symptom, and prescription codes for HH to estimate incidence and prevalence for the United Kingdom and the United States. METHODS: Data from UK and US health care databases were analyzed to ascertain HH cases and estimate incidence and prevalence from health care records during calendar years 2011 through 2013. RESULTS: On the basis of 2013 data for the United States and United Kingdom, between 1.0% and 1.6% of these populations have health care records indicating diagnosis or treatment of HH. Women accounted for approximately 60% of incident and prevalent cases in both databases. LIMITATIONS: Because the case ascertainment methods rely on available data for those seeking health care, we may have underestimated the number of HH cases in both countries. CONCLUSIONS: The findings represent a plausible estimate for incidence and prevalence of HH among persons seeking medical care for excessive sweating. Improved practices for identifying HH in clinical settings may increase the sensitivity and specificity of future studies and improve characterization and quantification of the population burden of this significant disease.

Demographic and Clinical Characteristics of COPD Patients at Different Blood Eosinophil Levels in the UK Clinical Practice Research Datalink.

Blood eosinophil count may be a useful biomarker for predicting response to inhaled corticosteroids and exacerbation risk in chronic obstructive pulmonary disease (COPD) patients. The optimal cut point for categorizing blood eosinophil counts in these contexts remains unclear. We aimed to determine the distribution of blood eosinophil count in COPD patients and matched non-COPD controls, and to describe demographic and clinical characteristics at different cut points. We identified COPD patients within the UK Clinical Practice Research Database aged ≥40 years with a FEV1/FVC <0.7, and ≥1 blood eosinophil count recorded during stable disease between January 1, 2010 and December 31, 2012. COPD patients were matched on age, sex, and smoking status to non-COPD controls. Using all blood eosinophil counts recorded during a 12-month period, COPD patients were categorized as "always above," "fluctuating above and below," and "never above" cut points of 100, 150, and 300 cells/µL. The geometric mean blood eosinophil count was statistically significantly higher in COPD patients versus matched controls (196.6 cells/µL vs. 182.1 cells/µL; mean difference 8%, 95% CI: 6.8, 9.2), and in COPD patients with versus without a history of asthma (205.0 cells/µL vs. 192.2 cells/µL; mean difference 6.7%, 95%, CI: 4.9, 8.5). About half of COPD patients had all blood eosinophil counts above 150 cells/µL; this persistent higher eosinophil phenotype was associated with being male, higher body mass index, and history of asthma. In conclusion, COPD patients demonstrated higher blood eosinophil count than non-COPD controls, although there was substantial overlap in the distributions. COPD patients with a history of asthma had significantly higher blood eosinophil count versus those without.

Prevalence of metabolic syndrome and its components among men with and without clinical benign prostatic hyperplasia: a large, cross-sectional, UK epidemiological study.

OBJECTIVES: To compare the prevalence of metabolic syndrome and the components of metabolic syndrome in men aged ≥50 years with and without clinical benign prostatic hyperplasia (BPH). SUBJECTS AND METHODS: This was a cross-sectional study using the UK Clinical Practice Research Datalink (CPRD). Men were selected from the CPRD who were aged ≥50 years and still registered as of 31 December 2011. Cohort 1 included men with clinical BPH, and cohort 2 men without clinical BPH who were matched 1:1 to those in cohort 1 by general practice, year of birth and previous years of available history (1-<2, 2-<3, 3-<4, ≥4 years of available history). The prevalence of metabolic syndrome and its components (for men alive and still registered in the CRPD as of 31 December 2011) was calculated using all available history (lifetime prevalence) and medical history from 2010 and 2011 (current prevalence). Crude odds ratios and 95% confidence intervals for the occurrence of metabolic syndrome and the occurrence of the components of metabolic syndrome were calculated by comparing men with and without BPH. RESULTS: A total of 26.5% of men with clinical BPH had metabolic syndrome compared with 20.9% of matched controls without clinical BPH (absolute difference 5.6%; P < 0.001); men with clinical BPH were therefore significantly more likely to have metabolic syndrome than matched controls without clinical BPH. Significantly greater proportions of men with clinical BPH also had each component of metabolic syndrome compared with matched controls without clinical BPH. The presence of clinical BPH was associated with a 37% increased odds of having metabolic syndrome (for both lifetime prevalence and current prevalence) compared with matched controls without clinical BPH. CONCLUSIONS: There is a significant cross-sectional association between clinical BPH and metabolic syndrome in the UK primary care population.

The relative risk of aortic aneurysm in patients with giant cell arteritis compared with the general population of the UK.

OBJECTIVES: To evaluate the risk of aortic aneurysm in patients with giant cell arteritis (GCA) compared with age-, gender- and location-matched controls. METHODS: A UK General Practice Research Database (GPRD) parallel cohort study of 6999 patients with GCA and 41 994 controls, matched on location, age and gender, was carried out. A competing risk model using aortic aneurysm as the primary outcome and non-aortic-aneurysm-related death as the competing risk was used to determine the relative risk (subhazard ratio) between non-GCA and GCA subjects, after adjustment for cardiovascular risk factors. RESULTS: Comparing the GCA cohort with the non-GCA cohort, the adjusted subhazard ratio (95% CI) for aortic aneurysm was 1.92 (1.52 to 2.41). Significant predictors of aortic aneurysm were being an ex-smoker (2.64 (2.03 to 3.43)) or a current smoker (3.37 (2.61 to 4.37)), previously taking antihypertensive drugs (1.57 (1.23 to 2.01)) and a history of diabetes (0.32 (0.19 to 0.56)) or cardiovascular disease (1.98 (1.50 to 2.63)). In a multivariate model of the GCA cohort, male gender (2.10 (1.38 to 3.19)), ex-smoker (2.20 (1.22 to 3.98)), current smoker (3.79 (2.20 to 6.53)), previous antihypertensive drugs (1.62 (1.00 to 2.61)) and diabetes (0.19 (0.05 to 0.77)) were significant predictors of aortic aneurysm. CONCLUSIONS: Patients with GCA have a twofold increased risk of aortic aneurysm, and this should be considered within the range of other risk factors including male gender, age and smoking. A separate screening programme is not indicated. The protective effect of diabetes in the development of aortic aneurysms in patients with GCA is also demonstrated.

Diet and food allergy development during infancy: birth cohort study findings using prospective food diary data.

BACKGROUND: After an era of only considering the allergenic properties of the infant diet and allergy outcomes, emerging data suggest that the overall composition of the infant diet might be a more important factor in the development of allergic disease. OBJECTIVE: We sought to assess the relationship between infant dietary patterns in the first year of life and development of food allergy by age 2 years. METHODS: We performed a nested, case-control, within-cohort study. Mothers kept prospective food diaries for the first year of life, with resultant diet data coded in a unique manner to produce new variables, which were then analyzed by using principal component analysis to identify infant feeding patterns within the study subjects. RESULTS: Principal component analysis of diet diary data from 41 infants given a diagnosis of food allergy based on results of double-blind, placebo-controlled food challenges in the first 2 years of life and their 82 age-matched control subjects provided an early infant diet pattern and an ongoing diet pattern. There was no difference between the study groups for the early infant diet pattern, but for the ongoing diet pattern, there was a significant difference between the groups (P = .001). This ongoing dietary pattern was characterized by higher intake of fruits, vegetables, and home-prepared foods, with control infants having a significantly higher healthy infant diet dietary pattern score than children who had a food allergy. CONCLUSIONS: An infant diet consisting of high levels of fruits, vegetables, and home-prepared foods is associated with less food allergy by the age of 2 years.

Prospective food diaries demonstrate breastfeeding characteristics in a UK birth cohort.

Breastfeeding duration and exclusive breastfeeding rates are universally below those recommended by World Health Organization. Due to limitations and challenges associated with researching breastfeeding characteristics, the times when exclusivity is likely to be lost and when women are most likely to discontinue breastfeeding have not yet been identified. Prospective food diaries allow reliable description of the dynamics of breastfeeding to be made to help identify these key time periods. Food diaries detailing intake from birth until the cessation of breastfeeding were analysed for 718 infants recruited into a national arm of an international multicentre birth cohort study (EuroPrevall). Analyses included linear regression analysis and Kaplan-Meier time course analysis. Breastfeeding and exclusive breastfeeding cessation rates for younger mothers (<25 years) are high in the first few weeks after delivery but slow markedly in the period 10-12 weeks after delivery. Cessation rates are consistent from 0 to 26 weeks in older mothers. This difference in feeding patterns led to significant differences between the two different age groups at 26 weeks for breastfeeding (P = 0.006) and exclusive breastfeeding at 8 weeks (P = 0.009). Forty-nine per cent of younger mothers (<25 years) stopped breastfeeding before their infant was 3 weeks old. To increase breastfeeding duration, further work is required to investigate the attitudes and perceptions associated with such high breastfeeding cessation rates in younger mothers during these very early post-natal weeks.

Comparison of Rheumatoid Arthritis Information Recorded in UK CPRD Aurum and CPRD GOLD Databases (Companion Paper 3).

Purpose: To report distribution of codes associated with a rheumatoid arthritis (RA) diagnosis recorded in Clinical Practice Research Datalink (CPRD) Aurum compared to the previously validated CPRD GOLD database as a critical step toward making decisions about CPRD Aurum's suitability for medical research. Patients and Methods: We analyzed the distribution of codes for RA diagnoses, labs, and treatments in the new CPRD Aurum database, compared to the CPRD GOLD database by selecting relevant indicators of RA diagnosis, treatment, and clinical care. We included all patients in England in CPRD Aurum and CPRD GOLD with an incident diagnosis code for RA on or after 1 January 2005 and at least two years recorded data before first RA diagnosis. Results: We found 53,083 and 18,167 patients with a new diagnosis code for RA in CPRD Aurum and CPRD GOLD, respectively. In both databases approximately 67% were female with similar mean ages at first diagnosis. There were few differences in RA-related recording patterns between the two data sources. Before first RA diagnosis, CPRD Aurum patients had more RA-specific labs and other supporting clinical codes. After diagnosis, CPRD Aurum patients had more RA diagnoses coded and more often had 10+ general RA labs than patients in CPRD GOLD. More CPRD GOLD patients had 10+ prescriptions for conventional disease-modifying antirheumatic drugs (cDMARD) compared to CPRD Aurum. Otherwise, the distribution of drugs used to treat RA was similar between databases. The standardized incidence of RA was similar between databases. Conclusion: Overall, among patients with a diagnosis code for RA, recording of diagnoses, prescription drugs, and labs were similar between CPRD Aurum and CPRD GOLD. Slight differences were found for a few variables, but overall, we found consistency between the databases. In addition, standardized incidence of RA was similar between databases.

Global Epidemiology of Hip Fractures: Secular Trends in Incidence Rate, Post-Fracture Treatment, and All-Cause Mortality.

In this international study, we examined the incidence of hip fractures, postfracture treatment, and all-cause mortality following hip fractures, based on demographics, geography, and calendar year. We used patient-level healthcare data from 19 countries and regions to identify patients aged 50 years and older hospitalized with a hip fracture from 2005 to 2018. The age- and sex-standardized incidence rates of hip fractures, post-hip fracture treatment (defined as the proportion of patients receiving anti-osteoporosis medication with various mechanisms of action [bisphosphonates, denosumab, raloxifene, strontium ranelate, or teriparatide] following a hip fracture), and the all-cause mortality rates after hip fractures were estimated using a standardized protocol and common data model. The number of hip fractures in 2050 was projected based on trends in the incidence and estimated future population demographics. In total, 4,115,046 hip fractures were identified from 20 databases. The reported age- and sex-standardized incidence rates of hip fractures ranged from 95.1 (95% confidence interval [CI] 94.8-95.4) in Brazil to 315.9 (95% CI 314.0-317.7) in Denmark per 100,000 population. Incidence rates decreased over the study period in most countries; however, the estimated total annual number of hip fractures nearly doubled from 2018 to 2050. Within 1 year following a hip fracture, post-hip fracture treatment ranged from 11.5% (95% CI 11.1% to 11.9%) in Germany to 50.3% (95% CI 50.0% to 50.7%) in the United Kingdom, and all-cause mortality rates ranged from 14.4% (95% CI 14.0% to 14.8%) in Singapore to 28.3% (95% CI 28.0% to 28.6%) in the United Kingdom. Males had lower use of anti-osteoporosis medication than females, higher rates of all-cause mortality, and a larger increase in the projected number of hip fractures by 2050. Substantial variations exist in the global epidemiology of hip fractures and postfracture outcomes. Our findings inform possible actions to reduce the projected public health burden of osteoporotic fractures among the aging population. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Fracture risk before and after total hip replacement in patients with osteoarthritis: potential benefits of bisphosphonate use.

OBJECTIVE: The association between osteoarthritis (OA) and fractures remains unclear. OA patients have increased bone mass, but no corresponding decrease in fracture rate. This study was undertaken to determine the fracture rates in patients with hip OA undergoing a total hip replacement (THR), as compared with disease-free controls, and to assess the association between bisphosphonate use and postsurgery fracture risk. METHODS: We conducted a population-based parallel-cohorts study. All patients in the UK General Practice Research Database undergoing a THR for hip OA between 1986 and 2006 constituted the exposed cohort (n = 14,133). Five disease-free controls were matched with each patient by age, sex, and practice site. Subjects were followed up for 5 years before and after surgery. Fracture rates and rate ratios (RRs) were estimated using Poisson regression. In addition, bisphosphonate use was identified among patients undergoing THR, and the data, stratified by the presence or absence of a previous fracture and by treatment propensity score, were assessed using fitted Cox models to study the effect of bisphosphonate use on the risk of fracture postsurgery. RESULTS: Patients undergoing a THR had a similar fracture risk as that in controls in the 5 years before THR, but had higher rates postsurgery, which peaked at years 2.5-5 (adjusted RR 1.24, 95% confidence interval [95% CI] 1.02-1.52). Use of bisphosphonates lowered the fracture risk among THR patients who received bisphosphonates as primary prevention (hazard ratio [HR] 0.56, 95% CI 0.38-0.82) and also among THR patients who had experienced a previous osteoporotic fracture (HR 0.48, 95% CI 0.23-0.99). CONCLUSION: This study identified a 25% increase in fracture risk at 2.5-5 years postsurgery among patients undergoing a THR. Bisphosphonate use reduced the post-THR risk of fracture when administered both as primary prevention and as secondary prevention, by 44% and 52%, respectively. This must be further confirmed in randomized controlled trials.

Changes in hip fracture rate before and after total knee replacement due to osteoarthritis: a population-based cohort study.

OBJECTIVES: Patients with knee osteoarthritis have an increase in bone mass but no corresponding decrease in risk of fracture. This study describes the rates of hip fracture in subjects with knee osteoarthritis before and after having a total knee replacement (TKR), compared with matched controls. METHODS: A population-based prospective cohort study was conducted. The study population included, from the General Practice Research Database (UK), patients 40 years and older, undergoing TKR between 1986 and end-2006 for knee osteoarthritis as 'cases' (n=20,033). Five disease-free controls (n=100,165) were randomly selected, and matched for age, gender and practice. Hip fractures were ascertained using READ codes, and yearly rates of hip fracture and rate differences were calculated for the 5 years before and after surgery, using Poisson regression. Stratified analyses were performed by age and history of fracture. RESULTS: Hip fracture rates were non-significantly reduced compared with controls before the operation. In the year after TKR, risk increased significantly (RR 1.58; 95% CI 1.14 to 2.19). Rates then declined to equal those of controls by 3 years, and continued decreasing until the end of follow-up; corresponding RR were not significant. The increased risk is greatest in younger ages and in those without previous fracture. CONCLUSIONS: The association between knee osteoarthritis and fractures is time-dependent, which may explain the current controversy in the literature. The association is also modified by TKR: subjects have a higher rate of hip fracture than matched controls after TKR, although the rates may eventually decrease.

Mortality in Wegener's granulomatosis: a bimodal pattern.

OBJECTIVE: To characterize the long-term mortality in patients with WG compared with matched population-based controls. METHODS: We used data from the General Practice Research Database, which contains the computerized records of 6.25 million patients and is representative of the population of the UK. We identified all subjects with a new diagnosis of WG in the period 1989-2004, and for each case, compared mortality with 10 controls matched for age, gender and practice. RESULTS: We identified 255 patients with a new diagnosis of WG (mean age 58.1 years, range 9-90 years, 47% females) and 2546 controls (mean age 58.1 years, range 9-89 years, 47% females). Mean follow-up was 6.4 years. The mortality for patients with WG was significantly increased during the first year after diagnosis [HR 9.0 (95% CI 5.8, 13.9)], especially for those ≤ 65 years of age [HR 19.9 (95% CI 8.8, 44.9)]. The excess mortality was less marked after the first year: 1-5 years [HR 1.68 (95% CI 1.08, 2.60)], 5-10 years [HR 2.41 (95% CI 1.43, 4.07)], but started to increase by 10-15 years [HR 4.4 (95% CI 2.0, 9.8)]. The Kaplan-Meier survival curve showed an increase in mortality after 8 years. CONCLUSIONS: Despite current therapy, patients with WG have a 9-fold increased risk of death in the first year of disease, attributed to infection, active vasculitis and renal failure. Between 1 and 8 years the risk is at its lowest, although higher than the control population. There is an increased mortality from 8 years onwards that remains unexplained.

Which Patients with Giant Cell Arteritis Will Develop Cardiovascular or Cerebrovascular Disease? A Clinical Practice Research Datalink Study.

OBJECTIVE: To evaluate the risk of cerebrovascular disease and cardiovascular disease (CVD) in patients with giant cell arteritis (GCA), and to identify predictors. METHODS: The UK Clinical Practice Research Datalink 1991-2010 was used for a parallel cohort study of 5827 patients with GCA and 37,090 age-, sex-, and location-matched controls. A multivariable competing risk model (non-cerebrovascular/CV-related death as the competing risk) determined the relative risk [subhazard ratio (SHR)] between patients with GCA compared with background controls for cerebrovascular disease, CVD, or either. Each cohort (GCA and controls) was then analyzed individually using the same multivariable model, with age and sex now present, to identify predictors of CVD or cerebrovascular disease. RESULTS: Patients with GCA, compared with controls, had an increased risk SHR (95% CI) of cerebrovascular disease (1.45, 1.31-1.60), CVD (1.49, 1.37-1.62), or either (1.47, 1.37-1.57). In the GCA cohort, predictors of "cerebrovascular disease or CVD" included increasing age, > 80 years versus < 65 years (1.98, 1.62-2.42), male sex (1.20, 1.05-1.38), and socioeconomic status, most deprived quintile versus least deprived (1.34, 1.01-1.78). These predictors were also present within the non-GCA cohort. CONCLUSION: Patients with GCA are more likely to develop cerebrovascular disease or CVD than age-, sex-, and location-matched controls. In common with the non-GCA cohort, patients who are older, male, and from the most deprived compared with least deprived areas have a higher risk of cerebrovascular disease or CVD. Further work is needed to understand how this risk may be mediated by specific behavioral, social, and economic factors.

Continuing to Confront COPD International Patient Survey: Economic Impact of COPD in 12 Countries.

BACKGROUND: The Continuing to Confront COPD International Patient Survey estimated the prevalence and burden of COPD across 12 countries. Using data from this survey we evaluated the economic impact of COPD. METHODS: This cross-sectional, population-based survey questioned 4,343 subjects aged 40 years and older, fulfilling a case definition of COPD based on self-reported physician diagnosis or symptomatology. Direct cost measures were based on exacerbations of COPD (treated and those requiring emergency department visits and/or hospitalisation), contacts with healthcare professionals, and COPD medications. Indirect costs were calculated from work loss values using the Work Productivity and Activity Impairment scale. Combined direct and indirect costs estimated the total societal costs per patient. RESULTS: The annual direct costs of COPD ranged from $504 (South Korea) to $9,981 (USA), with inpatient hospitalisations (5 countries) and home oxygen therapy (3 countries) being the key drivers of direct costs. The proportion of patients completely prevented from working due to their COPD ranged from 6% (Italy) to 52% (USA and UK) with 8 countries reporting this to be ≥20%. Total societal costs per patient varied widely from $1,721 (Russia) to $30,826 (USA) but a consistent pattern across countries showed greater costs among those with increased burden of COPD (symptoms, health status and more severe disease) and a greater number of comorbidities. CONCLUSIONS: The economic burden of COPD is considerable across countries, and requires targeted resources to optimise COPD management encompassing the control of symptoms, prevention of exacerbations and effective treatment of comorbidities. Strategies to allow COPD patients to remain in work are important for addressing the substantial wider societal costs.

Health behaviors and their correlates among participants in the Continuing to Confront COPD International Patient Survey.

BACKGROUND AND AIMS: We used data from the Continuing to Confront COPD International Patient Survey to test the hypothesis that patients with COPD who report less engagement with their disease management are also more likely to report greater impact of the disease. METHODS: This was a population-based, cross-sectional survey of 4,343 subjects aged ≥40 years from 12 countries, fulfilling a case definition of COPD based on self-reported physician diagnosis or symptomatology. The impact of COPD was measured with COPD Assessment Test, modified Medical Research Council Dyspnea Scale, and hospital admissions and emergency department visits for COPD in the prior year. The 13-item Patient Activation Measure (PAM-13) instrument and the 8-item Morisky Medication Adherence Scale (MMAS-8) were used to measure patient disease engagement and medication adherence, respectively. RESULTS: Twenty-eight percent of subjects reported being either disengaged or struggling with their disease (low engagement: PAM-13 levels 1 and 2), and 35% reported poor adherence (MMAS-8 <6). In univariate analyses, lower PAM-13 and MMAS-8 scores were significantly associated with poorer COPD-specific health status, greater breathlessness and lower BMI (PAM-13 only), less satisfaction with their doctor's management of COPD, and more emergency department visits. In multivariate regression models, poor satisfaction with their doctor's management of COPD was significantly associated with both low PAM-13 and MMAS-8 scores; low PAM-13 scores were additionally independently associated with higher COPD Assessment Test and modified Medical Research Council scores and low BMI (underweight). CONCLUSION: Poor patient engagement and medication adherence are frequent and associated with worse COPD-specific health status, higher health care utilization, and lower satisfaction with health care providers. More research will be needed to better understand what factors can be modified to improve medication adherence and patient engagement.

Incidence and risk factors for food hypersensitivity in UK infants: results from a birth cohort study.

BACKGROUND: The prevalence of food hypersensitivity in the UK is still largely open to debate. Additionally its pathogenesis is also unclear although it is known that there are differing phenotypes. Determining its prevalence, along with identifying those factors associated with its development will help to assess its clinical importance within the national setting and also add to the debate on appropriate prevention strategies. METHODS: A population based birth cohort study conducted in Hampshire, UK as part of the EuroPrevall birth cohort study. 1140 infants were recruited with 823 being followed up until 2 years of age. Infants with suspected food reactions were assessed including specific IgE measurement and skin prick testing. Diagnosis of food hypersensitivity was by positive double-blind, placebo-controlled food challenge (DBPCFC) where symptoms up to 48 h after the end of the food challenge were considered indicative of a food hypersensitivity. Factors associated with food hypersensitivity and its two phenotypes of IgE-mediated and non-IgE-mediated disease were modelled in a multivariable logistic regression analysis. RESULTS: Cumulative incidence of food hypersensitivity by 2 years of age was 5.0 %. The cumulative incidence for individual food allergens were hens' egg 2.7 % (1.6-3.8); cows' milk 2.4 % (1.4-3.5); peanut 0.7 % (0.1-1.3); soy 0.4 % (0.0-0.8); wheat 0.2 % (0.0-0.5) and 0.1 % (0.0-0.32) for fish. The cumulative incidence of IgE-mediated food allergy was 2.6 % with 2.1 % reacting to hens' egg. For non-IgE-mediated food allergy the cumulative incidence was 2.4 % (cows' milk 1.7 %). Predictors for any food hypersensitivity were wheeze, maternal atopy, increasing gestational age, age at first solid food introduction and mean healthy dietary pattern score. Predictors for IgE mediated allergy were eczema, rhinitis and healthy dietary pattern score whereas for non-IgE-mediated food allergy the predictors were dog in the home, healthy dietary pattern score, maternal consumption of probiotics during breastfeeding and age at first solid food introduction. CONCLUSIONS: Just under half the infants with confirmed food hypersensitivity had no demonstrable IgE. In an exploratory analysis, risk factors for this phenotype of food hypersensitivity differed from those for IgE-mediated food allergy except for a healthy infant diet which was associated with less risk for both phenotypes.

A population-based survival analysis describing the association of body mass index on time to revision for total hip and knee replacements: results from the UK general practice research database.

OBJECTIVES: Against a backdrop of rising levels of obesity, we describe and estimate associations of body mass index (BMI), age and gender with time to revision for participants undergoing primary total hip (THR) or knee (TKR) replacement in the UK. DESIGN: Population-based cohort study. SETTING: Routinely collected primary care data from a representative sample of general practices, including linked data on all secondary care events. PARTICIPANTS: Population-based cohort study of 63 162 patients with THR and 54 276 with TKR in the UK General Practice Research Database between 1988 and 2011. PRIMARY AND SECONDARY OUTCOMES: Risk of THR and TKR revision associated with BMI, age and gender, after adjusting for the competing risk of death. RESULTS: The 5-year cumulative incidence rate for THR was 2.2% for men and 1.8% for women (TKR 2.3% for men, 1.6% for women). The adjusted overall subhazard ratio (SHR) for patients with THR undergoing subsequent hip revision surgery, with a competing risk of death, were estimated at 1.020 (95% CI 1.009 to 1.032) per additional unit (kg/m(2)) of BMI, 1.23 (95% CI 1.10 to 1.38) for men compared with women and 0.970 (95% CI 0.967 to 0.973) per additional year of age. For patients with TKR, the equivalent estimates were 1.015 (95% CI 1.002 to 1.028) for BMI; 1.51 (95% CI 1.32 to 1.73) for gender and 0.957 (95% CI 0.951 to 0.962) for age. Morbidly obese patients with THR had a 65.5% increase (95% CI 15.4% to 137.3%, p=0.006) in the subhazard of revision versus the normal BMI group (18.5-25). The effect for TKR was smaller (a 43.9% increase) and weaker (95% CI 2.6% to 103.9%, p=0.040). CONCLUSIONS: BMI is estimated to have a small but statistically significant association with the risk of hip and knee revision, but absolute numbers are small. Further studies are needed in order to distinguish between effects for specific revision surgery indications.

Introduction of complementary foods and the relationship to food allergy.

OBJECTIVES: To address questions regarding breastfeeding, complementary feeding, allergy development, and current infant-feeding recommendations. METHODS: This was a nested, case-control within a cohort study in which mothers of 41 infants diagnosed with food allergy by the age of 2 years (according to double-blind, placebo-controlled food challenge) and their 82 age-matched controls kept prospective food diaries of how their infants were fed in the first year of life. RESULTS: Infants who were diagnosed with food allergy by the time they were 2 years of age were introduced to solids earlier (≤16 weeks of age) and were less likely to be receiving breast milk when cow's milk protein was first introduced into their diet. CONCLUSIONS: This study supports the current American Academy of Pediatrics' allergy prevention recommendations and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition recommendations on complementary feeding to not introduce solids before 4 to 6 months of age. It also supports the American Academy of Pediatrics' breastfeeding recommendations that breastfeeding should continue while solids are introduced into the diet and that breastfeeding should continue for 1 year, or longer, as mutually desired by mother and infant.

Explaining the rise in antidepressant prescribing: a descriptive study using the general practice research database.

OBJECTIVE: To explore the reasons behind the recent increase in antidepressant prescribing in the United Kingdom. Design Detailed retrospective analysis of data on general practitioner consultations and antidepressant prescribing. Data source Data were obtained from the general practice research database, which contains linked anonymised records of over 3 million patients registered in the UK. Data were extracted for all new incident cases of depression between 1993 and 2005. Review methods Detailed analysis of general practitioner consultations and antidepressant prescribing was restricted to 170 practices that were contributing data for the full duration of the study. RESULTS: In total, 189 851 people within the general practice research database experienced their first episode of depression between 1993 and 2005, of whom 150,825 (79.4%) received a prescription for antidepressants in the first year of diagnosis. This proportion remained stable across all the years examined. The incidence of new cases of depression rose in young women but fell slightly in other groups such that overall incidence increased then declined slightly (men: 7.83 cases per 1000 patient years in 1993 to 5.97 in 2005, women: 15.83 cases per 1000 patient years in 1993 to 10.06 in 2005). Antidepressant prescribing nearly doubled during the study period-the average number of prescriptions issued per patient increased from 2.8 in 1993 to 5.6 in 2004. The majority of antidepressant prescriptions were given as long term treatment or as intermittent treatment to patients with multiple episodes of depression. CONCLUSIONS: The rise in antidepressant prescribing is mainly explained by small changes in the proportion of patients receiving long term treatment. Previous clinical guidelines have focused on antidepressant initiation and appropriate targeting of antidepressants. To address the costly rise in antidepressant prescribing, future research and guidance needs to concentrate on appropriate long term prescribing for depression and regular review of medication.