Publications
scientifiques

IMPORTANCE: Antibiotics disrupt human microbiota and have been associated with several pediatric autoimmune diseases. Psoriasis activity has been linked to group A streptococcal and viral infections. OBJECTIVE: To determine whether antibiotic exposure and infections are independently associated with incident psoriasis in children. DESIGN, SETTING, AND PARTICIPANTS: This nested case-control study used data from the Health Improvement Network database, a population-representative electronic health records database from the United Kingdom, from June 27, 1994, through January 15, 2013. Data were analyzed from September 17, 2014, through August 12, 2015. Children aged 1 to 15 years with newly diagnosed psoriasis (n = 845) were compared with age- and sex-matched controls (n = 8450) randomly chosen at the time of psoriasis diagnosis from general practices with at least one case, excluding children with immunodeficiency, inflammatory bowel disease, and juvenile arthritis. EXPOSURES: Systemic antibacterial prescriptions and infections of the skin and other sites within 2 years before psoriasis diagnosis. MAIN OUTCOMES AND MEASURES: Incident psoriasis as determined by validated diagnostic codes. The association of antibiotic exposure and infections with incident psoriasis was determined by conditional logistic regression, adjusting for confounders. RESULTS: After adjusting for matching, country, socioeconomic deprivation, outpatient visits, and infections within the past 2 years, antibiotic exposure in the last 2 years was weakly associated with incident psoriasis (adjusted odds ratio [aOR], 1.2; 95% CI, 1.0-1.5). The associations for infections of skin (aOR, 1.5; 95% CI, 1.2-1.7) and other sites (aOR, 1.3; 95% CI, 1.1-1.6) were similar. Untreated nonskin infections (aOR, 1.5; 95% CI, 1.3-1.8) but not antibiotic-treated nonskin infections (aOR, 1.1; 95% CI, 0.9-1.4) were associated with psoriasis. Results were similar when using a lifetime exposure window. Different classes of antibiotics and age of first antibiotic exposure were also not associated with psoriasis. The findings did not substantively change when excluding periods of varying length before diagnosis. CONCLUSIONS AND RELEVANCE: Infections are associated with the development of pediatric psoriasis, but antibiotics do not appear to contribute substantially to that risk.

BACKGROUND: Large databases and population registers are increasingly used to examine adverse birth outcomes, congenital heart anomalies, in particular, following antidepressant exposures in pregnancy. Yet many studies have failed to account for other characteristics of the women who were prescribed antidepressants. OBJECTIVE: To examine the characteristics of women who are prescribed selective serotonin reuptake inhibitors (SSRIs) in pregnancy and women who are not, associations between SSRIs prescribed in pregnancy and congenital heart anomalies, and the association between social and lifestyle characteristics of pregnant women and congenital heart anomalies. METHOD: Using data from The Health Improvement Network primary care database in the United Kingdom between January 1, 1990, and January 31, 2011, we set up a comparative study including 4 cohorts of children of women with and without different antidepressant exposures before and during pregnancy. 5,154 women were receiving SSRIs before pregnancy, 2,776 were receiving SSRIs during pregnancy, 992 were receiving other antidepressants during pregnancy, and 200,213 were receiving no antidepressants before or during pregnancy. Our primary outcome was congenital heart anomalies. RESULTS: Less than 1% of children had a record of congenital heart anomalies within 5 years of birth, and there were no significant differences related to antidepressant exposure in pregnancy (women not prescribed antidepressants versus women prescribed SSRIs in first trimester: odds ratio [OR] = 1.00; 95% CI, 0.65-1.52); however, independent of antidepressant prescribing, diabetes (OR = 2.23; 95% CI, 1.79-2.77), increasing age (OR = 1.01; 95% CI, 1.00-1.02), alcohol problem (OR = 2.58; 95% CI, 1.55-4.29, illicit drug problems (OR = 1.89; 95% CI, 1.09-3.25), and obesity (OR = 1.38; 95% CI, 1.13-1.69) were associated with an increased risk of having a child with congenital heart anomalies. CONCLUSIONS: There was no difference in congenital heart anomalies in children born to women with different antidepressant prescribing exposure status. However, we confirmed an increased risk of congenital heart anomalies in children of older women and in children of women with diabetes, a body mass index above 30 kg/m(2), and a history of alcohol and illicit drug problems independent of the prescription of antidepressants. Future research in this field must account for these characteristics. On the basis of existing evidence, advising women to stop antidepressant treatment in pregnancy may be counterproductive.

OBJECTIVE: To investigate trends in incident and prevalent diagnoses of type 2 diabetes mellitus (T2DM) and its pharmacological treatment between 2000 and 2013. DESIGN: Analysis of longitudinal electronic health records in The Health Improvement Network (THIN) primary care database. SETTING: UK primary care. PARTICIPANTS: In total, we examined 8,838,031 individuals aged 0-99 years. OUTCOME MEASURES: The incidence and prevalence of T2DM between 2000 and 2013, and the effect of age, sex and social deprivation on these measures were examined. Changes in prescribing patterns of antidiabetic therapy between 2000 and 2013 were also investigated. RESULTS: Overall, 406,344 individuals had a diagnosis of T2DM, of which 203,639 were newly diagnosed between 2000 and 2013. The incidence of T2DM rose from 3.69 per 1000 person-years at risk (PYAR) (95% CI 3.58 to 3.81) in 2000 to 3.99 per 1000 PYAR (95% CI 3.90 to 4.08) in 2013 among men; and from 3.06 per 1000 PYAR (95% CI 2.95 to 3.17) to 3.73 per 1000 PYAR (95% CI 3.65 to 3.82) among women. Prevalence of T2DM more than doubled from 2.39% (95% CI 2.37 to 2.41) in 2000 to 5.32% (95% CI 5.30 to 5.34) in 2013. Being male, older, and from a more socially deprived area was strongly associated with having T2DM, (p<0.001). Prescribing changes over time reflected emerging clinical guidance and novel treatments. In 2013, metformin prescribing peaked at 83.6% (95% CI 83.4% to 83.8%), while sulfonylureas prescribing reached a low of 41.4% (95% CI 41.1% to 41.7%). Both remained, however, the most commonly used pharmacological treatments as first-line agents and add-on therapy. Thiazolidinediones and incretin based therapies (gliptins and GLP-1 analogues) were also prescribed as alternate add-on therapy options, however were rarely used for first-line treatment in T2DM. CONCLUSIONS: Prevalent cases of T2DM more than doubled between 2000 and 2013, while the number of incident cases increased more steadily. Changes in prescribing patterns observed may reflect the impact of national policies and prescribing guidelines on UK primary care.

Genital warts, 90% of which are caused by human papillomavirus types 6 and 11, are a significant problem in the UK. The cost of managing genital warts was previously estimated at £52.4 million for 2010. The objective of this study was to estimate the cost of genital warts management up to 2012 in the UK and by jurisdiction. Population statistics and the number of reported genital warts cases in genito-urinary medicine clinics were obtained and extrapolated to 2012. Cases of genital warts treated in primary care were estimated from The Health Improvement Network database. The number of visits and therapy required were estimated by genito-urinary medicine experts. Costs were obtained from the appropriate national tariffs. The model estimated there were 220,875 genital warts cases in the UK in 2012, costing £58.44 million (£265/patient). It estimated 157,793 cases in England costing £41.74 million; 7468 cases in Scotland costing £1.90 million; 7095 cases in Wales costing £1.87 million; and 3621 cases in Northern Ireland costing £948,000. The full National Health Service costs for the management of genital warts have never previously been estimated separately for each jurisdiction. Findings reveal a significant economic burden, which is important to quantify when understanding the value of quadrivalent human papilloma virus vaccination.

After developing a prognostic model, it is essential to evaluate the performance of the model in samples independent from those used to develop the model, which is often referred to as external validation. However, despite its importance, very little is known about the sample size requirements for conducting an external validation. Using a large real data set and resampling methods, we investigate the impact of sample size on the performance of six published prognostic models. Focussing on unbiased and precise estimation of performance measures (e.g. the c-index, D statistic and calibration), we provide guidance on sample size for investigators designing an external validation study. Our study suggests that externally validating a prognostic model requires a minimum of 100 events and ideally 200 (or more) events.

BACKGROUND: Before 2012, UK GPs were paid only to offer cessation advice to smokers and only to those with smoking-related disease, a minority of all smokers. From 2012, GPs are now paid to offer all smokers referral for behavioural support and medication to assist cessation at least once every 2 years. AIM: To quantify the impact of this new recommendation and payment on indicators of smoking cessation activity. DESIGN AND SETTING: Interrupted time series analysis of data from general practices in England contributing data to The Health Improvement Network (THIN). METHOD: Data were extracted on monthly rates of recorded delivery of smoking cessation advice, referral to NHS Stop Smoking Services, and prescription of smoking cessation medications, among an average of 3.3 million patients aged >16 years registered each month in THIN. ARIMA models were used to quantify changes in rates of cessation activity after the 2012 Quality and Outcomes Framework (QOF) revision compared with beforehand. RESULTS: The proportion of patients each month with a record of advice to quit smoking increased by 19.6% (95% CI = 7.9 to 31.4) in the year after the introduction of payments compared with the 8 years beforehand; the recording of referral to Stop Smoking Services increased by 38.8% (95% CI = 15.2 to 62.4). There was no significant change in prescription of smoking cessation medication, -7.7% (95% CI = -21.6 to 6.2). CONCLUSION: Paying GPs to intervene with all smokers and offer support rather than just advice to quit is associated with an increase in recording of advice and referring patients for behavioural support to stop smoking, but no change in prescribing pharmacotherapy for cessation.

BACKGROUND: Existing dementia risk scores require collection of additional data from patients, limiting their use in practice. Routinely collected healthcare data have the potential to assess dementia risk without the need to collect further information. Our objective was to develop and validate a 5-year dementia risk score derived from primary healthcare data. METHODS: We used data from general practices in The Health Improvement Network (THIN) database from across the UK, randomly selecting 377 practices for a development cohort and identifying 930,395 patients aged 60-95 years without a recording of dementia, cognitive impairment or memory symptoms at baseline. We developed risk algorithm models for two age groups (60-79 and 80-95 years). An external validation was conducted by validating the model on a separate cohort of 264,224 patients from 95 randomly chosen THIN practices that did not contribute to the development cohort. Our main outcome was 5-year risk of first recorded dementia diagnosis. Potential predictors included sociodemographic, cardiovascular, lifestyle and mental health variables. RESULTS: Dementia incidence was 1.88 (95% CI, 1.83-1.93) and 16.53 (95% CI, 16.15-16.92) per 1000 PYAR for those aged 60-79 (n = 6017) and 80-95 years (n = 7104), respectively. Predictors for those aged 60-79 included age, sex, social deprivation, smoking, BMI, heavy alcohol use, anti-hypertensive drugs, diabetes, stroke/TIA, atrial fibrillation, aspirin, depression. The discrimination and calibration of the risk algorithm were good for the 60-79 years model; D statistic 2.03 (95% CI, 1.95-2.11), C index 0.84 (95% CI, 0.81-0.87), and calibration slope 0.98 (95% CI, 0.93-1.02). The algorithm had a high negative predictive value, but lower positive predictive value at most risk thresholds. Discrimination and calibration were poor for the 80-95 years model. CONCLUSIONS: Routinely collected data predicts 5-year risk of recorded diagnosis of dementia for those aged 60-79, but not those aged 80+. This algorithm can identify higher risk populations for dementia in primary care. The risk score has a high negative predictive value and may be most helpful in 'ruling out' those at very low risk from further testing or intensive preventative activities.

BACKGROUND: UK National Dementia Strategies prioritise fair access to dementia treatments for the whole population. We investigated for the first time inequalities in NHS national dementia prescribing and how they have varied between UK countries and over time. METHOD: we investigated the association between Townsend deprivation score and anti-dementia drug prescribing in 77,045 dementia patients from UK primary care records from 2002 to 2013. RESULTS: we included 77,045 patients with recorded dementia diagnosis or anti-dementia drug prescription. Least deprived patients were 25% more likely to be initiated on anti-dementia drugs than the most deprived (adjusted incidence rate ratio 1.25, 95% confidence interval 1.19-1.31). This was driven by data from English practices where prescribing rates were consistently lower in more deprived patients compared with Scotland, Northern Ireland and Wales, where prescribing was not related to deprivation quintile. Compared with English practices, anti-dementia medication was prescribed more often in Northern Irish (1.81, 1.41-2.34) and less in Welsh practices (0.68, 0.55-0.82), with a trend towards more prescribing in Scottish practices (1.14, 0.98-1.32). Drug initiation rates were also higher in younger people and men. CONCLUSION: four years after the English National Dementia Strategy, there is no evidence that the Strategy's key objective of reducing treatment inequalities is being achieved. Higher overall anti-dementia drug prescribing in Scottish and Northern Irish practices, and differing clinical guidelines in Scotland from other UK countries might explain greater equality in prescribing in these countries. Strategies to offer treatment to more deprived people with dementia in England are needed.

OBJECTIVE: Evidence on the potential independent impact of gout on the risk of diabetes is limited to a single study of men with a high cardiovascular risk profile. Our objective was to examine this relation in the general population, particularly among women. METHODS: We conducted a sex-stratified matched cohort study using data from The Health Improvement Network (THIN), an electronic medical records database representative of the UK general population. Up to five non-gout individuals were matched to each case of incident gout by year of birth, year of enrolment and body mass index (BMI). Multivariate HRs for incident diabetes were calculated after additionally adjusting for smoking, alcohol consumption, physician visits, comorbidities and medication use. RESULTS: Among 35 339 gout patients (72.4% men, mean age of 62.7 years), the incidence rates of diabetes in women and men were 10.1 and 9.5 cases per 1000 person-years, respectively, whereas the corresponding rates were 5.6 and 7.2 cases per 1000 person-years among 137 056 non-gout subjects. The BMI-matched univariate and multivariate HRs of diabetes were higher among women compared with those among men (1.71; 95% CI 1.51 to 1.93 vs 1.22; 95% CI 1.13 to 1.31) and (1.48; 95% CI 1.29 to 1.68 vs 1.15; 95% CI 1.06 to 1.24), respectively (p values for interaction <0.001). This sex difference persisted across age-specific subgroups. CONCLUSIONS: This general population-based study suggests that gout may be independently associated with an increased risk of diabetes and that the magnitude of association is significantly larger in women than in men.

BACKGROUND: Bisphosphonates are widely used to prevent osteoporotic fractures. Some severe musculoskeletal reactions have been described with this medication; among them, some cases of carpal tunnel syndrome. Thus, the aim of this study was to explore whether bisphosphonates may be associated with this syndrome. METHODS: A cohort study was conducted to compare exposed to unexposed women; the exposed group was that composed of women having received at least one prescription of an oral bisphosphonate. For the purpose, we used information from The Health Improvement Network (THIN) database. The outcome of interest was defined as those women diagnosed with carpal tunnel syndrome. A survival analysis was performed; the Cox proportional hazard model was used to calculate hazard ratios and 95% confidence intervals, and to adjust for identified confounding variables. RESULTS: Out of a sample of 59,475 women older than 51 years, 19,825 were treated with bisphosphonates during the period studied. No differences in age distribution or mean follow-up time were observed between the two groups in comparison. Overall, there were 572 women diagnosed with carpal tunnel syndrome, 242 (1.2%) in the group exposed to bisphosphonates, and 330 (0.8%) in the unexposed. An adjusted hazard ratio of developing carpal tunnel syndrome of 1.38 (95%CI, 1.15-1.64) was found for women exposed to bisphosphonates; no significant changes in the hazard ratios were found when considering different levels of bisphosphonate exposure. CONCLUSIONS: An increased risk of carpal tunnel syndrome is associated with the use of bisphosphonates in postmenopausal women.

In this study we sought to determine if among individuals with urolithiasis, extracorporeal shock wave lithotripsy (SWL) and ureteroscopy are associated with a higher risk of incident arterial hypertension (HTN) and/or chronic kidney disease (CKD). This was measured in a population-based retrospective study of 11,570 participants with incident urolithiasis and 127,464 without urolithiasis in The Health Improvement Network. Patients with pre-existing HTN and CKD were excluded. The study included 1319 and 919 urolithiasis patients with at least one SWL or URS procedure, respectively. Multivariable Cox regression was used to estimate the hazard ratio for incident CKD stage 3-5 and HTN in separate analyses. Over a median of 3.7 and 4.1 years, 1423 and 595 of urolithiasis participants developed HTN and CKD, respectively. Urolithiasis was associated with a significant hazard ratio each for HTN of 1.42 (95% CI: 1.35, 1.51) and for CKD of 1.82 (1.67, 1.98). SWL was associated with a significant increased risk of HTN 1.34 (1.15, 1.57), while ureteroscopy was not. When further stratified as SWL to the kidney or ureter, only SWL to the kidney was significantly and independently associated with HTN 1.40 (1.19, 1.66). Neither SWL nor ureteroscopy was associated with incident CKD. Since urolithiasis itself was associated with a hazard ratio of 1.42 for HTN, an individual who undergoes SWL to the kidney can be expected to have a significantly increased hazard ratio for HTN of 1.96 (1.67, 2.29) compared with an individual without urolithiasis.

OBJECTIVE: To describe the characteristics of pregnant women with and without pregestational diabetes and to estimate the prevalence of pregestational diabetes in pregnant women recorded in a UK primary care database. METHODS: The data source for this study is The Health Improvement Network (THIN) primary care database. Pregnant women with and without diabetes aged 16 years and over were identified using diagnostic Read codes and prescriptions for antidiabetics from medical records. Data were examined on: age, body mass index (BMI), social deprivation, smoking, ethnicity and glycaemic control. The prevalence of pregestational diabetes was calculated by diabetes type and calendar year between 1995 and 2012. RESULTS: Data from 400,434 pregnancies suggests that women with pregestational diabetes were: older (median 29, 32 vs 29 years for type 1, type 2 and without diabetes, respectively), had higher BMI (median 25.0, 30.4 vs 23.9 k/m(2) for type 1, type 2 and without diabetes, respectively) and were registered with a general practice for longer than pregnant women without diabetes. The prevalence of type 1 diabetes in pregnancy increased from 1.56 to 4.09 per 1000 pregnancies between 1995 and 2015. For type 2 diabetes the increase was from 2.34 to 5.09 per 1000 pregnancies between 1995 and 2008 followed by a more rapid increase to 10.62 per 1000 pregnancies by 2012. CONCLUSIONS: Pregnant women with pregestational diabetes were older, had higher BMI and were registered for longer than women without diabetes. The prevalence of type 1 and type 2 diabetes increased in pregnancy. The prevalence of type 2 diabetes rose more rapidly with a marked increase after 2008.

OBJECTIVE: Sleep apnea is associated with hyperuricemia owing to hypoxia-induced nucleotide turnover. We undertook this study to assess the relationship between incident sleep apnea and the risk of incident gout. METHODS: Using data from The Health Improvement Network in the UK, we identified individuals with a first-ever physician diagnosis of sleep apnea. For each patient with sleep apnea, up to 5 individuals without sleep apnea were matched by sex, age, birth year, and body mass index (within ±0.5 kg/m(2) ). We estimated the incidence rates of gout and examined the relationship between sleep apnea and the risk of incident gout using a Cox proportional hazards model, adjusting for potential confounders. In addition, we assessed the rate difference in gout due to sleep apnea using an additive hazard model. RESULTS: Among 9,865 patients with newly diagnosed sleep apnea and 43,598 matched individuals without sleep apnea, we identified 270 incident cases of gout over 1 year of followup, resulting in incidence rates of 8.4 per 1,000 person-years and 4.8 per 1,000 person-years, respectively. The crude and multivariable rate ratios of incident gout in patients with sleep apnea were 1.7 (95% confidence interval [95% CI] 1.3, 2.2) and 1.5 (95% CI 1.1, 2.1), respectively. The corresponding rate differences between patients with sleep apnea and the comparison cohort were 3.6 (95% CI 1.6, 5.6) and 2.8 (95% CI 0.7, 4.9) per 1,000 person-years. The effect of sleep apnea persisted across subgroups. CONCLUSION: This general population-based study indicates that sleep apnea is independently associated with an increased risk of incident gout. Future research should examine the potential benefits of correcting sleep apnea-induced hypoxia on the risk of hyperuricemia and gout flares.

BACKGROUND: Associations between type 2 diabetes, anti-diabetic medications and pancreatic cancer are controversial. This study aims to clarify such associations with new-onset type 2 diabetes and repeated measurements of glycated haemoglobin (HbA1c) levels. METHODS: A nested case-control study was initiated from the Health Improvement Network (THIN) in UK from 1996 to 2010. Information of pancreatic cancer cases was retrieved electronically from the medical records and manually validated. Control subjects were randomly selected and frequency-matched to the cases on sex, age, and calendar years. Multivariable unconditional logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI), and adjusted for potential confounders. RESULTS: Among 1,574,768 person-years of follow-up, 529 pancreatic cancer cases and 5000 controls were identified. Type 2 diabetes, or changed HbA1c levels (rather than HbA1c levels at diabetes diagnosis) in diabetes patients (⩾4 mmol mol(-1) compared with <0 mmol mol(-1)) were followed by an increased OR of pancreatic cancer (OR, 2.16, 95% CI 1.72-2.72 and OR, 5.06, 95% CI 1.52-16.87, respectively). Among the anti-diabetic medications in diabetes patients, the OR for insulin users was 25.57 (95% CI 11.55-56.60), sulphonylureas 2.22 (95% CI 1.13, 4.40), and metformin users 1.46 (95% CI 0.85-2.52), compared with no use of any anti-diabetic medications. CONCLUSIONS: New-onset type 2 diabetes and, particularly, diabetes with rising HbA1c seem to be independent risk factors for pancreatic cancer. The relation between different anti-diabetic medications and pancreatic cancer seems to vary in strength, with the highest risk among users of insulin.

OBJECTIVE: To examine major congenital anomaly (CA) risks in children of mothers with coeliac disease (CD) compared with mothers without CD. DESIGN: Population-based cohort study. SETTING: Linked maternal-child medical records from a large primary care database from the UK. POPULATION: A total of 562,332 live singletons of mothers with and without CD in 1990-2013. METHODS: We calculated the absolute major CA risks in children whose mothers had CD, and whether this was diagnosed or undiagnosed before childbirth. Logistic regression with a generalised estimating equation was used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (95% CIs) for CAs associated with CD. MAIN OUTCOME MEASURES: Fourteen system-specific major CA groups classified according to the European Surveillance of Congenital Anomalies and neural tube defects (NTDs). RESULTS: Major CA risk in 1880 children of mothers with CD was 293 per 10,000 liveborn singletons, similar to the risk in those without CD (282; aOR 0.98, 95% CI 0.74-1.30). The risk was slightly higher in 971 children, whose mothers were undiagnosed (350; aOR 1.14, 95% CI 0.79-1.64), than in 909 children whose mothers were diagnosed (231; aOR 0.80, 95% CI 0.52-1.24). There was a three-fold increase in nervous system anomalies in the children of mothers with undiagnosed CD (aOR 2.98, 95% CI 1.06-8.33, based on five exposed cases and one had an NTD), and these women were all diagnosed with CD at least 4 years after their children were born. CONCLUSIONS: There was no statistically significant increase in risk of major CAs in children of mothers with coeliac disease overall, compared with the general population.

OBJECTIVE: To estimate the prevalence of wounds managed by the UK's National Health Service (NHS) in 2012/2013 and the annual levels of healthcare resource use attributable to their management and corresponding costs. METHODS: This was a retrospective cohort analysis of the records of patients in The Health Improvement Network (THIN) Database. Records of 1000 adult patients who had a wound in 2012/2013 (cases) were randomly selected and matched with 1000 patients with no history of a wound (controls). Patients' characteristics, wound-related health outcomes and all healthcare resource use were quantified and the total NHS cost of patient management was estimated at 2013/2014 prices. RESULTS: Patients' mean age was 69.0 years and 45% were male. 76% of patients presented with a new wound in the study year and 61% of wounds healed during the study year. Nutritional deficiency (OR 0.53; p<0.001) and diabetes (OR 0.65; p<0.001) were independent risk factors for non-healing. There were an estimated 2.2 million wounds managed by the NHS in 2012/2013. Annual levels of resource use attributable to managing these wounds and associated comorbidities included 18.6 million practice nurse visits, 10.9 million community nurse visits, 7.7 million GP visits and 3.4 million hospital outpatient visits. The annual NHS cost of managing these wounds and associated comorbidities was £5.3 billion. This was reduced to between £5.1 and £4.5 billion after adjusting for comorbidities. CONCLUSIONS: Real world evidence highlights wound management is predominantly a nurse-led discipline. Approximately 30% of wounds lacked a differential diagnosis, indicative of practical difficulties experienced by non-specialist clinicians. Wounds impose a substantial health economic burden on the UK's NHS, comparable to that of managing obesity (£5.0 billion). Clinical and economic benefits could accrue from improved systems of care and an increased awareness of the impact that wounds impose on patients and the NHS.

BACKGROUND: Little is known about the effects of human fetal exposure when a new drug is authorized unless it was specifically developed for use in pregnancy. Since many factors may contribute to adverse fetal effects, having comprehensive information about in utero exposures will enhance our ability to make correct determinations about causality. OBJECTIVE: The objective of the study was to assess the extent to which women, recruited without the intervention of health care professionals (HCPs), will provide information, suitable for research purposes, via the Internet or by phone on some potential risk factors in pregnancy. METHODS: To pilot direct-to-patient research for pharmacovigilance, we conducted a prospective, noninterventional study of medication use and lifestyle factors as part of the Pharmacoepidemiological Research on Outcomes of Therapeutics by a European ConsorTium (PROTECT) Consortium. Consenting women who self-identified as pregnant and residing in the United Kingdom (UK), Denmark (DK), The Netherlands, or Poland were recruited and could then choose to provide data every 2 or 4 weeks via the Internet or a telephonic interactive voice response system (IVRS). Self-reported drug use was compared with pharmacy register data in DK and with electronic health records in the UK. RESULTS: Recruited women were on average older and more highly educated than the general population. Most respondents chose a frequency of every 4 weeks (56.99%, 1177/2065). Only 29.83% (464/1555) of women with due dates occurring during the study provided information on pregnancy outcome. For those responding by Internet, over 90.00% (1915/2065) reported using >1 pregnancy-related medication, 83.34% (1721/2065) reported using >1 other medicine, and 23.53% (486/2065) reported only over-the-counter medications, not counting herbals and dietary supplements. Some respondents (7.16%, 148/2065) reported that they chose not to take a prescribed medication (mostly medicines for pain or inflammation, and for depression) and 1.30% (27/2065) reported using medicines that had been prescribed to a friend or family member (oxycodone, paracetamol, and medications for acid-related problems). Relatively few respondents reported using fish oil (4.60%, 95/2065), other dietary supplements (1.88%, 39/2065), herbal products (7.07%, 146/2065), or homeopathic products (1.16%, 24/2065). Most medications for chronic conditions that were listed in the Danish prescription registry were also self-reported (83.3%, 145/174 agreement), with larger discrepancies for medications indicated for short-term use (54.0%, 153/283 agreement) and pregnancy-related medications (66.1%, 78/118). CONCLUSIONS: Self-reported information on medication use as well as other potential teratogenic factors can be collected via the Internet, although recruitment costs are not insubstantial and maintaining follow-up is challenging. Direct data collection from consumers adds detail, but clinical input may be needed to fully understand patients' medical histories and capture birth outcomes.