Treatments for Chronic Kidney Disease: A Systematic Literature Review of Randomized Controlled Trials.

Delaying disease progression and reducing the risk of mortality are key goals in the treatment of chronic kidney disease (CKD). New drug classes to augment renin-angiotensin-aldosterone system (RAAS) inhibitors as the standard of care have scarcely met their primary endpoints until recently. This systematic literature review explored treatments evaluated in patients with CKD since 1990 to understand what contemporary data add to the treatment landscape. Eighty-nine clinical trials were identified that had enrolled patients with estimated glomerular filtration rate 13.9-102.8 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) 29.9-2911.0 mg/g, with (75.5%) and without (20.6%) type 2 diabetes (T2D). Clinically objective outcomes of kidney failure and all-cause mortality (ACM) were reported in 32 and 64 trials, respectively. Significant reductions (P < 0.05) in the risk of kidney failure were observed in seven trials: five small trials published before 2008 had evaluated the RAAS inhibitors losartan, benazepril, or ramipril in patients with (n = 751) or without (n = 84-436) T2D; two larger trials (n = 2152-2202) published onwards of 2019 had evaluated the sodium-glucose co-transporter 2 (SGLT2) inhibitors canagliflozin (in patients with T2D and UACR > 300-5000 mg/g) and dapagliflozin (in patients with or without T2D and UACR 200-5000 mg/g) added to a background of RAAS inhibition. Significant reductions in ACM were observed with dapagliflozin in the DAPA-CKD trial. Contemporary data therefore suggest that augmenting RAAS inhibitors with new drug classes has the potential to improve clinical outcomes in a broad range of patients with CKD.

Vertebral fracture as a risk factor for self-harm: a retrospective cohort study.

BACKGROUND: The prevention of self-harm is an international public health priority. It is vital to identify at-risk populations, particularly as self-harm is a risk factor for suicide. This study aims to examine the risk of self-harm in people with vertebral fractures. METHODS: Retrospective cohort study. Patients with vertebral fracture were identified within the Clinical Practice Research Datalink and matched to patients without fracture by sex and age. Incident self-harm was defined by primary care record codes following vertebral fracture. Overall incidence rates (per 10,000 person-years (PY)) were reported. Cox regression analysis determined risk (hazard ratios (HR), 95 % confidence interval (CI)) of self-harm compared to the matched unexposed cohort. Initial crude analysis was subsequently adjusted and stratified by median age and sex. RESULTS: The number of cases of vertebral fracture was 16,293, with a matched unexposed cohort of the same size. Patients were predominantly female (70.1 %), median age was 76.3 years. Overall incidence of self-harm in the cohort with vertebral fracture was 12.2 (10.1, 14.8) /10,000 PY. There was an initial crude association between vertebral fracture and self-harm, which remained after adjustment (HR 2.4 (95 %CI 1.5, 3.6). Greatest risk of self-harm was found in those with vertebral fractures who were aged below 76.3 years (3.2(1.8, 5.7)) and male (3.9(1.8, 8.5)). CONCLUSIONS: Primary care patients with vertebral fracture are at increased risk of self-harm compared to people without these fractures. Male patients aged below 76 years of age appear to be at greatest risk of self-harm. Clinicians need to be aware of the potential for self-harm in this patient group.

External validation of a model to predict women most at risk of postpartum venous thromboembolism: Maternity clot risk.

INTRODUCTION: Venous thromboembolism (VTE) is the leading cause of direct maternal mortality in high-income countries. We previously developed a risk prediction score for postpartum venous thromboembolism (VTE) in women without a previous VTE. In this paper, we provide further external validation and assess its performance across various groups of postpartum women from England. MATERIALS AND METHODS: Cohort study using primary and secondary care data covering England. We used data from QResearch comprising women with pregnancies ending in live birth or stillbirth recoded in Hospital Episodes Statistics between 2004 and 2015. Outcome was VTE in the 6 weeks postpartum. Our predictor variables included sociodemographic and lifestyle characteristics, pre-existing comorbidities, and pregnancy and delivery characteristics. RESULTS: Among 535,583 women with 700,185 deliveries, 549 VTE events were recorded (absolute risk of 7.8 VTE events per 10,000 deliveries). When we compared predicted probabilities of VTE for each woman from the original model with actual VTE events, we obtained a C-statistic of 0.67 (95% CI 0.65 to 0.70). However, our model slightly over-predicted VTE risk for the higher risk women (calibration slope = 0.84; 95% CI 0.74 to 0.94). Performance was similar across groups defined by calendar time, socioeconomic status, age group and geographical area. The score performed comparably with the existing algorithm used by the UK Royal College of Obstetrician and Gynaecologists. CONCLUSIONS: Our model enables flexibility in setting new treatment thresholds. Adopting it in clinical practice may help optimise use of low-molecular-weight heparin postpartum to maximise health gain by better targeting of high-risk groups.

Rheumatic Conditions as Risk Factors for Self-Harm: A Retrospective Cohort Study.

OBJECTIVE: To examine the risk of self-harm in rheumatic conditions. METHODS: We conducted a retrospective cohort study using data from the Clinical Practice Research Datalink. Patients with ankylosing spondylitis, fibromyalgia, osteoarthritis, or rheumatoid arthritis were identified from 1990 to 2016 and matched to patients without these conditions. Incident self-harm was defined by medical record codes following a rheumatic diagnosis. Incidence rates (per 10,000 person-years) were reported for each condition, both overall and year-on-year (2000-2016). Cox regression analysis determined risk (hazard ratio [HR] and 95% confidence interval [95% CI]) of self-harm for each rheumatic cohort compared to the matched unexposed cohort. Initial crude analysis was subsequently adjusted and stratified by age and sex. Due to nonproportionality over time, osteoarthritis was also stratified by disease duration (<1 year, ≥1 to <5 years, ≥5 to <10 years, and ≥10 years). RESULTS: The incidence of self-harm was highest in patients with fibromyalgia (HR 25.12 [95% CI 22.45-28.11] per 10,000 person-years) and lowest for osteoarthritis (HR 6.48 [95% CI 6.20-6.76]). There was a crude association with each rheumatic condition and self-harm, except for ankylosing spondylitis. Although attenuated, these associations remained after adjustment for fibromyalgia (HR 2.06 [95% CI 1.60-2.65]), rheumatoid arthritis (HR 1.59 [95% CI 1.20-2.11]), and osteoarthritis (1 to <5 years HR 1.12 [95% CI 1.01-1.24]; ≥5 to <10 years HR 1.35 [95% CI 1.18-1.54]). Age and sex were weak effect modifiers for these associations. CONCLUSION: Primary care patients with fibromyalgia, osteoarthritis, or rheumatoid arthritis (but not ankylosing spondylitis) are at increased risk of self-harm compared to people without these rheumatic conditions. Clinicians need to be aware of the potential for self-harm in patients with rheumatic conditions (particularly fibromyalgia), explore mood and risk with them, and offer appropriate support and management.

Mortality Among Patients With Polymyalgia Rheumatica: A Retrospective Cohort Study.

OBJECTIVE: To determine whether a diagnosis of polymyalgia rheumatica (PMR) is associated with premature mortality. METHODS: We extracted anonymized electronic medical records of patients ages >40 years who were eligible for linkage with the Office for National Statistics Death Registration data set, from the Clinical Practice Research Datalink from 1990 to 2016. Patients with PMR were individually matched, by age, sex, and registered general practice, with up to 5 controls without PMR. The total number and proportion of deaths and mortality rates were calculated. The mortality rate ratio (MRR) with 95% confidence interval (95% CI), adjusted for age, sex, region, smoking status, body mass index, and alcohol consumption, was calculated using Poisson regression. The 20 most common causes of death were tabulated. RESULTS: A total of 18,943 patients with PMR were matched to 87,801 controls. The mean ± SD follow-up after date of diagnosis was 8.0 ± 4.4 years in patients with PMR and 7.9 ± 4.6 years in controls. PMR was not associated with an increase in the risk of death (adjusted MRR 1.00 [95% CI 0.97-1.03]) compared to matched controls. Causes of death were broadly similar between patients with PMR and controls, although patients with PMR were slightly more likely to have a vascular cause of death recorded (24% versus 23%). CONCLUSION: A diagnosis of PMR does not appear to increase the risk of premature death. Minor variations in causes of death were observed, but overall this study is reassuring for patients with PMR and for clinicians.

Comorbidities in patients with polymyalgia rheumatica prior to and following diagnosis: A case control and cohort study.

OBJECTIVES: To determine the burden of comorbidities, including glucocorticoid (GC) related adverse effects, in patients with polymyalgia rheumatica (PMR) before and after diagnosis. METHODS: We extracted anonymised electronic medical records of patients over the age of 40 years from the Clinical Practice Research Datalink from 1990-2016. Patients with PMR were individually matched on age, sex and registered General Practice to between three and five controls. The prevalence, cumulative probability and likelihood of a range of comorbidities was estimated. Odds ratios (ORs) and hazard ratios (HRs) were calculated using conditional logistic regression and Cox proportional hazards regression respectively, adjusted for a wide range of covariates. RESULTS: 31,984 patients with PMR were matched to 149,436 controls. PMR was prospectively associated with vascular disease (adjusted HR 1.23 [95% confidence interval (CI) 1.19, 1.28]), as well as respiratory (HR 1.25 [1.18, 1.32]), renal (HR 1.34 [1.30, 1.39]), and autoimmune diseases (HR 4.68 [4.35, 5.03]). Conversely, before PMR diagnosis, the risk of cancer (adjusted OR [OR] 0.89 [0.86, 0.93]) and neurological disease (OR 0.36 [0.33, 0.40]) was significantly lower. Patients with PMR had an increased risk of comorbidities associated with glucocorticoid (GC) use. CONCLUSIONS: Patients with PMR have a high comorbidity burden, both before and after diagnosis. Whilst further work is needed to more fully understand these associations, clinicians should be aware of the high prevalence of comorbid conditions in this group and the impact that treatment with glucocorticoids may have on comorbidity.

Interstitial lung disease is a risk factor for ischaemic heart disease and myocardial infarction.

OBJECTIVES: Despite many shared risk factors and pathophysiological pathways, the risk of ischaemic heart disease (IHD) and myocardial infarction (MI) in interstitial lung disease (ILD) remains poorly understood. This lack of data could be preventing patients who may benefit from screening for these cardiovascular diseases from receiving it. METHODS: A population-based cohort study used electronic patient records from the Clinical Practice Research Datalink and linked Hospital Episode Statistics to identify 68 572 patients (11 688 ILD exposed (mean follow-up: 3.8 years); 56 884 unexposed controls (mean follow-up: 4.0 years), with 349 067 person-years of follow-up. ILD-exposed patients (pulmonary sarcoidosis (PS) or idiopathic pulmonary fibrosis (PF)) were matched (by age, sex, registered general practice and available follow-up time) to patients without ILD or IHD/MI. Rates of incident MI and IHD were estimated. HRs were modelled using multivariable Cox proportional hazards regression accounting for potential confounders. RESULTS: ILD was independently associated with IHD (HR 1.85, 95% CI 1.56 to 2.18) and MI (HR 1.74, 95% CI 1.44 to 2.11). In all disease categories, risk of both IHD and MI peaked between ages 60 and 69 years, except for the risk of MI in PS which was greatest <50 years. Men with PF were at greatest risk of IHD, while women with PF were at greatest risk of MI. CONCLUSIONS: ILD, particularly PF, is independently associated with MI and IHD after adjustment for established cardiovascular risk factors. Our results suggest clinicians should prioritise targeted assessment of cardiovascular risk in patients with ILD, particularly those aged 60-69 years. Further research is needed to understand the impact of such an approach to risk management.

Duration and Magnitude of Postoperative Risk of Venous Thromboembolism after Cholecystectomy: A Population-Based Cohort Study.

BACKGROUND: This study aimed to identify the burden and risk of venous thromboembolism (VTE) associated with cholecystectomy in England. METHODS: An historical cohort study of cholecystectomy patients from 2001 to 2011 was undertaken using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data. Crude rates and adjusted hazard ratios (HRs) were calculated for risk of VTE following cholecystectomy using Cox regression. RESULTS: 24,677 patients were identified with a rate of VTE in the first year following cholecystectomy of 2.80 per 1,000 person years (95% CI 2.18-3.59). Patients aged ≥70 vs. aged < 50 had 8.3-fold increase in risk of VTE (HR 8.27, 95% CI 3.72-18.35); patients with body mass index (BMI) > 30 vs. BMI < 30 had 2.4-fold increase in risk (HR 2.42, 95% CI 1.40-4.18); open vs. laparoscopic operation had 3-fold increase in risk (HR 2.94, 95% CI 1.55-5.55). Compared to general population, VTE risk was the highest in the first 30 days post-operatively with 9.9-fold risk following emergency cholecystectomy and 4.5-fold risk after inpatient cholecystectomy (HR 9.90, 95% CI 4.42-22.21; HR 4.54, 95% CI 2.85-7.21). CONCLUSIONS: Cholecystectomy is associated with a low absolute risk of VTE and we have identified high risk groups including the elderly, obese and those having open surgery.

Comorbidities in polymyalgia rheumatica: a systematic review.

BACKGROUND AND AIM: Comorbidities are known to exist in many rheumatological conditions. Polymyalgia rheumatica (PMR) is a common inflammatory rheumatological condition affecting older people which, prior to effective treatment, causes severe disability. Our understanding of associated comorbidities in PMR is based only on case reports or series and small cohort studies. The objective of this study is to review systematically the existing literature on the comorbidities associated with PMR. METHODS: MEDLINE, EMBASE, PsycINFO and CINAHL databases were searched for original observational research from inception to November 2016. Papers containing the words 'Polymyalgia Rheumatica' OR 'Giant Cell Arteritis' OR the terms 'PMR' OR 'GCA' were included. Article titles were reviewed based on pre-defined criteria by two reviewers. Following selection for inclusion, studies were quality assessed using the Newcastle-Ottawa tool and data were extracted. RESULTS: A total of 17,329 papers were reviewed and 41 were incorporated in this review, including three published after the search took place. Wide variations were found in study design, comorbidities reported and populations studied. Positive associations were found between PMR diagnosis and stroke, cardiovascular disease, peripheral arterial disease, diverticular disease and hypothyroidism. Two studies reported a positive association between PMR and overall malignancy rate. Seven studies reported an association between PMR and specific types of cancer, such as leukaemia, lymphoma, myeloproliferative disease and specified solid tumours, although nine studies found either no or negative association between cancer and PMR. CONCLUSION: Quantification of the prevalence of comorbidities in PMR is important to accurately plan service provision and enable identification of cases of PMR which may be more difficult to treat. This review highlights that research into comorbidities in PMR is, overall, methodologically inadequate and does not comprehensively cover all comorbidities. Future studies should consider a range of comorbidities in patients with a validated diagnosis of PMR in representative populations.

Incidence, prevalence and treatment burden of polymyalgia rheumatica in the UK over two decades: a population-based study.

OBJECTIVE: Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease in older people. Contemporary estimates of the incidence and prevalence are lacking, and no previous study has assessed treatment patterns at a population level. This study aims to address this. METHODS: We extracted anonymised electronic medical records of patients over the age of 40 years from the Clinical Practice Research Datalink in the period 1990-2016. The absolute rate of PMR per 100 000 person-years was calculated and stratified by age, gender and calendar year. Incidence rate ratios were calculated using a Poisson regression model. Among persons with PMR, continuous and total duration of treatment with glucocorticoids (GC) were assessed. RESULTS: 5 364 005 patients were included who contributed 44 million person-years of follow-up. 42 125 people had an incident diagnosis of PMR during the period. The overall incidence rate of PMR was 95.9 per 100 000 (95% CI 94.9 to 96.8). The incidence of PMR was highest in women, older age groups and those living in the South of England. Incidence appears stable over time. The prevalence of PMR in 2015 was 0.85 %. The median (IQR) continuous GC treatment duration was 15.8 (7.9-31.2) months. However, around 25% of patients received more than 4 years in total of GC therapy. CONCLUSIONS: The incidence rates of PMR have stabilised. This is the first population-based study to confirm that a significant number of patients with PMR receive prolonged treatment with GC, which can carry significant risks. The early identification of these patients should be a priority in future research.

Gout and subsequent erectile dysfunction: a population-based cohort study from England.

BACKGROUND: An association has been suggested between gout and erectile dysfunction (ED), however studies quantifying the risk of ED amongst gout patients are lacking. We aimed to precisely determine the population-level absolute and relative rate of ED reporting among men with gout over a decade in England. METHODS: We utilised the UK-based Clinical Practice Research Datalink to identify 9653 men with incident gout age- and practice-matched to 38,218 controls. Absolute and relative rates of incident ED were calculated using Cox regression models. Absolute rates within specific time periods before and after gout diagnosis were compared to control using a Poisson regression model. RESULTS: Overall, the absolute rate of ED post-gout diagnosis was 193 (95% confidence interval (CI): 184-202) per 10,000 person-years. This corresponded to a 31% (hazard ratio (HR): 1.31 95%CI: 1.24-1.40) increased relative risk and 0.6% excess absolute risk compared to those without gout. We did not observe statistically significant differences in the risk of ED among those prescribed ULT within 1 and 3 years after gout diagnosis. Compared to those unexposed, the risk of ED was also high in the year before gout diagnosis (relative rate = 1.63 95%CI 1.27-2.08). Similar findings were also observed for severe ED warranting pharmacological intervention. CONCLUSIONS: We have shown a statistically significant increased risk of ED among men with gout. Our findings will have important implications in planning a multidisciplinary approach to managing patients with gout.

Incidence of First Stroke in Pregnant and Nonpregnant Women of Childbearing Age: A Population-Based Cohort Study From England.

BACKGROUND: Pregnant women may have an increased risk of stroke compared with nonpregnant women of similar age, but the magnitude and the timing of such risk are unclear. We examined the risk of a first stroke event in women of childbearing age and compared the risk during pregnancy and in the early postpartum period with the background risk outside these periods. METHODS AND RESULTS: We conducted an open cohort study of 2 046 048 women aged 15 to 49 years between April 1, 1997, and March 31, 2014, using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care records in England. Risk of first stroke was assessed by calculating the incidence rate of stroke in antepartum, peripartum (2 days before until 1 day after delivery), and early (first 6 weeks) and late (second 6 weeks) postpartum periods compared with nonpregnant time using a Poisson regression model with adjustment for maternal age, socioeconomic group, and calendar time. A total of 2511 women had a first stroke. The incidence rate of stroke was 25.0 per 100 000 person-years (95% CI 24.0-26.0) in nonpregnant time. The rate was lower antepartum (10.7 per 100 000 person-years, 95% CI 7.6-15.1) but 9-fold higher peripartum (161.1 per 100 000 person-years, 95% CI 80.6-322.1) and 3-fold higher early postpartum (47.1 per 100 000 person-years, 95% CI 31.3-70.9). Rates of ischemic and hemorrhagic stroke both increased peripartum and early postpartum. CONCLUSIONS: Although the absolute risk of first stroke is low in women of childbearing age, healthcare professionals should be aware of a considerable increase in relative risk during the peripartum and early postpartum periods.

Recurrence risk of venous thromboembolism and hormone use in women from England: a cohort study using clinical practice research datalink.

It is vital to identify people with low recurrence risk of venous thromboembolism (VTE) so as to protect them from dangers of prolonged anticoagulation therapy. Among women who develop VTE following hormone use, the evidence as to whether their risk of recurrence is low if they cease this therapy is conflicting. We investigated whether women whose initial VTE event was hormone-related have a lower risk of VTE recurrence than women whose initial event had no obvious cause (unprovoked). A cohort study utilising the Clinical Practice Research Datalink linked to Hospital Episode Statistics data from England was conducted. We selected 4170 women aged between 15 and 64 years who were diagnosed with a first VTE event between 1997 and 2011. Cox regression models were used to obtain hazard ratios (HR). Hormone users had 29% lower recurrence risk than non-users (adjusted HR = 0·71; 95% confidence interval 0·58-0·88), a relationship which existed both in women aged 15-44 years (predominantly oral contraceptive users) and those aged 45-64 years (predominantly hormone replacement therapy users). In conclusion, having a hormone-associated VTE is associated with a lower recurrence risk than one that is unprovoked after discontinuation of the hormone-containing preparation. Prolonged anticoagulation may therefore be unjustified in such women.

The incidence of first stroke in and around pregnancy: A population-based cohort study from Sweden.

INTRODUCTION: Research has suggested that delivery is associated with an increased risk of stroke in women; however, there is a lack of contemporary estimates on the incidence of stroke in and after pregnancy compared with the baseline risk in women of childbearing age in Sweden. PATIENTS AND METHODS: All women aged 15-49 years with live births/stillbirths in 1992-2011 were identified from the Swedish Medical Birth Registry linked with the National Patient Registry. First stroke during the study period was identified. Incidence rates per 100,000 person-years and adjusted incidence rate ratios (IRRs) were calculated for antepartum, peripartum and early and late postpartum periods, compared with all other available follow-up time (time before pregnancy and after postpartum) using Poisson regression adjusted for maternal age, education attainment and calendar time. RESULTS: Of 1,124,541 women, 3094 had a first incident stroke (331 occurred during pregnancy or first 12 weeks postpartum), about half having ischaemic stroke. The incidence was 15.0 per 100,000 person-years (95% confidence interval 14.5-15.6) in non-pregnant time. The incidence was lower antepartum (7.3/100,000 person-years, 6.0-8.9; adjusted IRR = 0.7, 0.5-0.8) but higher peripartum (314.4/100,000 person-years, 247.5-399.5; adjusted IRR = 27.3, 21.4-34.9) and early postpartum (64.0/100,000 person-years, 54.1-75.7; adjusted IRR = 5.5, 4.6-6.6). The increased risk in peripartum was more evident for intracerebral haemorrhage than other types of stroke. CONCLUSION: Overall risk of stroke was low in women of childbearing age, but stroke risk peaks in the peripartum and early postpartum periods. Future work should address factors that contribute to this increased risk in order to develop approaches to attenuate risk.

Adverse Pregnancy Outcomes Among Women with Inflammatory Bowel Disease: A Population-Based Study from England.

BACKGROUND: There is limited contemporary population-based evidence on adverse birth outcomes and pregnancy-related complications for women with inflammatory bowel disease (IBD). This study provides such estimates of these risks and assesses variation by IBD type and surgical interventions. METHODS: We calculated the proportion of pregnancies in women with and without IBD between 1997 and 2012 throughout England using linked primary (Clinical Practice Research Datalink) and secondary care (Hospital Episode Statistics) data. Risk of pregnancy-related complications and adverse birth outcomes in women with Crohn's disease and ulcerative colitis were compared with risks in women without IBD using odds ratios (ORs). RESULTS: Of 364,363 singleton pregnancies resulting in live or stillbirths, 1969 (0.5%) were in women with IBD. Women with Crohn's disease were more likely to have preterm births (OR = 1.42; 95% confidence interval, 1.12-1.79), babies with low birth weights (OR = 1.39; 95% confidence interval, 1.05-1.83), and postpartum hemorrhage (OR = 1.27; 95% confidence interval, 1.04-1.55), whereas women with ulcerative colitis were only at increased risk of preterm births with an absolute risk difference of <2.7%. These risks remained independent of caesarean section. Prior surgery for IBD did not increase the risk of adverse birth outcomes or pregnancy-related complications compared with cases without surgery, however, women with IBD were more likely to have an elective caesarean section. CONCLUSIONS: Women with Crohn's disease have increased risks of some specific pregnancy-related complications and adverse birth outcomes which are independent of caesarean section, however, the absolute risk differences are small, indicating that most women with IBD will have an uncomplicated pregnancy.

No increased mortality in 109,000 first-degree relatives of celiac individuals.

BACKGROUND: Several studies have shown an excess mortality in individuals with celiac disease (CD). However, it is unknown if also first-degree relatives (FDRs) to celiac patients are at increased risk of death. AIM: We aimed to assess mortality in FDRs to celiac patients. METHODS: Individuals with CD were identified through biopsy reports (equal to Marsh grade III). Each celiac individual was matched on sex, age, county and calendar year with up to five control individuals. Through Swedish healthcare registries we identified all FDRs (father, mother, sibling, offspring) of CD individuals and controls. Through Cox regression we calculated hazard ratios (HRs) for mortality (all-cause death, circulatory, cancer and other). RESULTS: We identified 109,309 FDRs of celiac individuals and 549,098 FDRs of controls. Overall mortality was increased in FDRs to celiac individuals (HR=1.02, 95%CI=1.00-1.04, p=0.03). This corresponded to an excess risk of 5.9 deaths per 100,000 person-years of follow-up. When limiting follow-up to time since celiac diagnosis in the index individual, we found no increased risk of death (HR=1.01; 95%CI=0.98-1.03). CONCLUSION: FDRs to individuals with CD are at increased risk of death. This excess risk is however minimal and unlikely to be of any clinical importance to the individual.

Defining venous thromboembolism and measuring its incidence using Swedish health registries: a nationwide pregnancy cohort study.

OBJECTIVE: To accurately define venous thromboembolism (VTE) in the routinely collected Swedish health registers and quantify its incidence in and around pregnancy. STUDY DESIGN: Cohort study using data from the Swedish Medical Birth Registry (MBR) linked to the National Patient Registry (NPR) and the Swedish Prescribed Drug Register (PDR). SETTING: Secondary care centres, Sweden. PARTICIPANT: 509,198 women aged 15-44 years who had one or more pregnancies resulting in a live birth or stillbirth between 2005 and 2011. MAIN OUTCOME MEASURE: To estimate the incidence rate (IR) of VTE in and around pregnancy using various VTE definitions allowing direct comparison with other countries. RESULTS: The rate of VTE varied based on the VTE definition. We found that 43% of cases first recorded as outpatient were not accompanied by anticoagulant prescriptions, whereas this proportion was much lower than those cases first recorded in the inpatient register (9%). Using our most inclusive VTE definition, we observed higher rates of VTE compared with previously published data using similar methodology. These reduced by 31% (IR=142/100,000 person-years; 95% CI 132 to 153) and 22% (IR=331/100,000 person-years; 95% CI 304 to 361) during the antepartum and postpartum periods, respectively, using a restrictive VTE definition that required anticoagulant prescriptions associated with diagnosis, which were more in line with the existing literature. CONCLUSIONS: We found that including VTE codes without treatment confirmation risks the inclusion of false-positive cases. When defining VTE using the NPR, anticoagulant prescription information should therefore be considered particularly for cases recorded in an outpatient setting.

Causes of death in people with coeliac disease in England compared with the general population: a competing risk analysis.

INTRODUCTION: Quantifying excess cause-specific mortality among people with coeliac disease (CD) compared with the general population accounting for competing risks will allow accurate information to be given on risk of death from specific causes. METHOD: We identified from the Clinical Practice Research Datalink all patients with CD linked to Office for National Statistics between 1998 and 2012. We selected controls by frequency matching from the registered general practice population within 10-year age bands. We calculated the adjusted cumulative incidence (including adjustment for competing risks) and excess cumulative incidence for different causes of death up to 10 years from diagnosis. RESULTS: Of the 10 825 patients with CD, 773 died within the study period. The overall mortality rate among patients with CD was 128/10 000 person years compared with 153/10 000 in controls (HR=0.94 95% CI 0.84 to 1.01). We found no overall difference in the cumulative incidence of respiratory disease, digestive disease or cancer related death among cases and controls. The adjusted cumulative incidence of death from cardiovascular deaths was slightly lower compared with those without CD diagnosis (CD 0.32% vs controls 0.41%) with a corresponding excess cumulative incidence of -0.08% (95% CI -0.13 to -0.04). However, patients with CD had 0.15% excess risk (95% CI 0.03 to 0.27) of deaths from non-Hodgkin's lymphoma from the general population baseline risk. CONCLUSIONS: Overall, people with CD have no major excess risk of cancer, digestive disease or respiratory disease related or cardiovascular mortality compared with the general population. These findings should be reassuring to patients with CD and clinicians managing their care.

Pregnancy complications and adverse birth outcomes among women with celiac disease: a population-based study from England.

OBJECTIVES: Evidence-based information about adverse birth outcomes and pregnancy complications is crucial when counseling women with celiac disease (CD); however, limited population-based data on such risks exist. We estimated these for pregnant women with CD diagnosed before and after delivery. METHODS: We included all singleton pregnancies between 1997 and 2012 using linked primary care data from the Clinical Practice Research Datalink and secondary care Hospital Episode Statistics data. Risks of pregnancy complications (antepartum and postpartum hemorrhage, pre-eclampsia, and mode of delivery) and adverse birth outcomes (preterm birth, stillbirth, and low birth weight) were compared between pregnancies of women with and without CD using logistic/multinomial regression. Risks were stratified on the basis of whether women were diagnosed or yet undiagnosed before delivery. RESULTS: Of 363,930 pregnancies resulting in a live birth or stillbirth, 892 (0.25%) were among women with CD. Diagnosed CD was not associated with an increased risk of pregnancy complications or adverse birth outcomes compared with women without CD. However, the risk of postpartum hemorrhage and assisted delivery was slightly higher among pregnant women with diagnosed CD (adjusted odds ratio (aOR)=1.34). We found no increased risk of any pregnancy complication among those with undiagnosed CD. We only observed a 1% absolute excess risk of preterm birth and low birth weight among undiagnosed CD mothers corresponding to aOR=1.24 (95% confidence interval (CI)=0.82-1.87) and aOR=1.36 (95% CI=0.83-2.24), respectively. CONCLUSIONS: Whether diagnosed or undiagnosed during pregnancy, CD is not associated with a major increased risk of pregnancy complications and adverse birth outcomes. These findings are reassuring to both women and clinicians.