Key Points• Antepartum, we found that established risk factors only had a modest effect on rates of VTE.• Postpartum, we found that among other factors, women with stillbirth or preterm birth had high rates of VTE.Knowledge of the absolute risk (AR) for venous thromboembolism (VTE) in women around pregnancy and how potential risk factors modify this risk is crucial in identifying women who would benefit most from thromboprophylaxis. We examined a large primary care database containing 376 154 pregnancies ending in live birth or stillbirth from women aged 15 to 44 years between 1995 and 2009 and assessed the effect of risk factors on the incidence of antepartum and postpartum VTE in terms of ARs and incidence rate ratios (IRR), using Poisson regression. During antepartum, varicose veins, inflammatory bowel disease (IBD), urinary tract infection, and preexisting diabetes were associated with an increased risk for VTE (ARs, ‡139/100 000 person-years; IRRs, ‡1.8/100 000 personyears). Postpartum, the strongest risk factor was stillbirth (AR, 2444/100 000 personyears; IRR, 6.2/100 000 person-years), followed by medical comorbidities (including varicose veins, IBD, or cardiac disease), a body mass index (BMI) of 30 kg/m 2 or higher, obstetric hemorrhage, preterm delivery, and caesarean section (ARs, ‡637/100 000 person-years; IRRs, ‡1.9/100 000 person-years). Our findings suggest that VTE risk varies modestly by recognized factors during antepartum; however, women with stillbirths, preterm births, obstetric hemorrhage, caesarean section delivery, medical comorbidities, or a BMI of 30 kg/m 2 or higher are at much higher risk for VTE after delivery. These risk factors should receive careful consideration when assessing the potential need for thromboprophylaxis during the postpartum period. (Blood. 2013;121(19):3953-3961)

Summary Knowledge of the absolute and relative risk of venous thromboembolism (VTE) in and around pregnancy would be crucial in identifying when to commence and cease thromboprophylaxis in women who would benefit from such intervention. We addressed this hypothesis using a large prospective primary care database from the United Kingdom, containing details on 972 683 women aged 15–44 years between 1987 and 2004. Risks of a first VTE during antepartum, postpartum and outside of pregnancy were compared using Poisson regression. The rate of VTE during the third trimester antepartum was six times higher than time outside pregnancy [Incidence Rate Ratio (IRR) = 6·1; 95% confidence interval, 4·7–7·9]. In contrast, both the first (IRR = 1·6) and second (IRR = 2·1) trimesters conferred little increase in risk. The first 6 weeks postpartum was associated with a 22‐fold increase in risk, with the peak occurring in the first 3 weeks. Increased age was found to be associated with VTE during postpartum and outside of pregnancy, but not during antepartum. Our findings of a notably raised risk of VTE persisting for 3 weeks postpartum and of a raised antepartum risk constrained to the third trimester have implications for modifying the current recommendations for VTE prophylaxis in pregnancy and the puerperium.

Objective To develop and validate a risk prediction model for venous thromboembolism in the first six weeks after delivery (early postpartum).Design Cohort study.Setting Records from England based Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES) and data from Sweden based registry.Participants All pregnant women registered with CPRD-HES linked data between 1997 and 2014 and Swedish medical birth registry between 2005 and 2011 with postpartum follow-up.Main outcome measure Multivariable logistic regression analysis was used to develop a risk prediction model for postpartum venous thromboembolism based on the English data, which was externally validated in the Swedish data.Results 433 353 deliveries were identified in the English cohort and 662 387 in the Swedish cohort. The absolute rate of venous thromboembolism was 7.2 per 10 000 deliveries in the English cohort and 7.9 per 10 000 in the Swedish cohort. Emergency caesarean delivery, stillbirth, varicose veins, pre-eclampsia/eclampsia, postpartum infection, and comorbidities were the strongest predictors of venous thromboembolism in the final multivariable model. Discrimination of the model was similar in both cohorts, with a C statistic above 0.70, with excellent calibration of observed and predicted risks. The model identified more venous thromboembolism events than the existing national English (sensitivity 68% v 63%) and Swedish guidelines (30% v 21%) at similar thresholds.Conclusion A new prediction model that quantifies absolute risk of postpartum venous thromboembolism has been developed and externally validated. It is based on clinical variables that are available in many developed countries at the point of delivery and could serve as the basis for real time decisions on obstetric thromboprophylaxis.

BackgroundPregnant 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 ResultsWe 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.ConclusionsAlthough 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.

ObjectivePolymyalgia 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.MethodsWe 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.Results5 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.ConclusionsThe 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.

BackgroundGlucocorticoids are associated with increased fracture risk and are the mainstay of treatment in polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). However, fracture risk in these conditions has not been previously quantified. The aim of this study was to quantify the risk of fracture among patients with PMR and GCA.MethodsA retrospective cohort study was conducted using primary care records from the UK-based Clinical Practice Research Datalink. Individuals aged 40 years and over, with incident diagnoses of PMR or GCA were separately identified from 1990–2004 and followed up until 2015. For each exposed individual, four age-, sex- and practice-matched controls were randomly selected. Incidence rates of fracture per 10,000 person-years were calculated for each disease group and hazard rates were compared to the unexposed using Cox regression models.ResultsOverall, 12,136 and 2673 cases of PMR and GCA, respectively, were identified. The incidence rate of fracture was 148.05 (95% CI 141.16–155.28) in PMR and 147.15 (132.91–162.91) in GCA per 10,000 person-years. Risk of fracture was increased by 63% in PMR (adjusted hazard ratio 1.63, 95% CI 1.54–1.73) and 67% in GCA (1.67, 1.49–1.88) compared to the control populations. Fewer than 13% of glucocorticoid-treated cases were prescribed bisphosphonates.ConclusionsThis study reports, for the first time, a similar increase in fracture risk for patients with PMR and GCA. More needs to be done to improve adherence to guidelines to co-prescribe bisphosphonates. Further research needs to identify whether lower glucocorticoid starting doses and/or aggressive dose reduction reduces fracture risk.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-017-0987-1) contains supplementary material, which is available to authorized users.

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BackgroundAn association between gout and renal disease is well-recognised but few studies have examined whether gout is a risk factor for subsequent chronic kidney disease (CKD). Additionally, the impact of urate-lowering therapy (ULT) on development of CKD in gout is unclear. The objective of this study was to quantify the risk of CKD stage ≥ 3 in people with gout and the impact of ULT.MethodsThis was a retrospective cohort study using data from the Clinical Practice Research Datalink (CPRD). Patients with incident gout were identified from general practice medical records between 1998 and 2016 and randomly matched 1:1 to patients without a diagnosis of gout based on age, gender, available follow-up time and practice. Primary outcome was development of CKD stage ≥ 3 based on estimated glomerular filtration rate (eGFR) or recorded diagnosis. Absolute rates (ARs) and adjusted hazard ratios (HRs) were calculated using Cox regression models. Risk of developing CKD was assessed among those prescribed ULT within 1 and 3 years of gout diagnosis.ResultsPatients with incident gout (n = 41,446) were matched to patients without gout. Development of CKD stage ≥ 3 was greater in the exposed group than in the unexposed group (AR 28.6 versus 15.8 per 10,000 person-years). Gout was associated with an increased risk of incident CKD (adjusted HR 1.78 95% CI 1.70 to 1.85). Those exposed to ULT had a greater risk of incident CKD, but following adjustment this was attenuated to non-significance in all analyses (except on 3-year analysis of women (adjusted HR 1.31 95% CI 1.09 to 1.59)).ConclusionsThis study has demonstrated gout to be a risk factor for incident CKD stage ≥ 3. Further research examining the mechanisms by which gout may increase risk of CKD and whether optimal use of ULT can reduce the risk or progression of CKD in gout is suggested.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1746-1) contains supplementary material, which is available to authorized users.