Inflammatory skin diseases and the risk of chronic kidney disease: population-based case-control and cohort analyses.

BACKGROUND: Emerging evidence suggests an association between common inflammatory skin diseases and chronic kidney disease (CKD). OBJECTIVES: To explore the association between CKD stages 3-5 (CKD3-5) and atopic eczema, psoriasis, rosacea and hidradenitis suppurativa. METHODS: We undertook two complementary analyses; a prevalent case-control study and a cohort study using routinely collected primary care data [UK Clinical Practice Research Datalink (CPRD)]. We matched individuals with CKD3-5 in CPRD in March 2018 with up to five individuals without CKD for general practitioner practice, age and sex. We compared the prevalence of CKD3-5 among individuals with and without each inflammatory skin disease. We included individuals in CPRD with diabetes mellitus (2004-2018) in a cohort analysis to compare the incidence of CKD3-5 among people with and without atopic eczema and psoriasis. RESULTS: Our study included 56 602 cases with CKD3-5 and 268 305 controls. Cases were more likely than controls to have a history of atopic eczema [odds ratio (OR) 1·14, 99% confidence interval (CI) 1·11-1·17], psoriasis (OR 1·13, 99% CI 1·08-1·19) or hidradenitis suppurativa (OR 1·49, 99% CI 1·19-1·85), but were slightly less likely to have been diagnosed with rosacea (OR 0·92, 99% CI 0·87-0·97), after adjusting for age, sex, practice (matching factors), index of multiple deprivation, diabetes, smoking, harmful alcohol use and obesity. Results remained similar after adjusting for hypertension and cardiovascular disease. In the cohort with diabetes (N = 335 827), there was no evidence that CKD3-5 incidence was associated with atopic eczema or psoriasis. CONCLUSIONS: Atopic eczema, psoriasis and hidradenitis suppurativa are weakly associated with CKD3-5. Future research is needed to elucidate potential mechanisms and the clinical significance of our findings.

Atopic eczema and obesity: a population-based study.

BACKGROUND: Atopic eczema is a common chronic inflammatory skin disease. Research suggests an association between atopic eczema and obesity, with inconsistent evidence from European populations. OBJECTIVES: To explore the association between diagnosed atopic eczema and being overweight or obese, and whether increased atopic eczema severity was associated with higher body mass index. METHODS: We undertook a cross-sectional analysis within a cohort of adults (matched by age, sex and general practice) with and without a diagnosis of atopic eczema. We used primary care (Clinical Practice Research Datalink Gold) and linked hospital admissions data (1998-2016). We used conditional logistic regression to compare the odds of being overweight or obese (adjusting for confounders and potential mediators) in those with atopic eczema (mild, moderate and severe, and all eczema) vs. those without. RESULTS: We identified 441 746 people with atopic eczema, matched to 1 849 722 without. People with atopic eczema had slightly higher odds of being overweight or obese vs. those without [odds ratio (OR) 1·08, 95% confidence interval (CI) 1·07-1·09] after adjusting for age, asthma and socioeconomic deprivation. Adjusting for potential mediators (high-dose glucocorticoids, harmful alcohol use, anxiety, depression, smoking) had a minimal impact on effect estimates (OR 1·07, 95% CI 1·06-1·08). We saw no evidence that odds of being overweight or obese increased with increasing atopic eczema severity, and there was no association in people with severe eczema. CONCLUSIONS: We found evidence of a small overall association between atopic eczema and being overweight or obese. However, there was no association with obesity among those with the most severe eczema. Our findings are largely reassuring for this prevalent patient group who may already have an increased risk of cardiovascular disease.

Four childhood atopic dermatitis subtypes identified from trajectory and severity of disease and internally validated in a large UK birth cohort.

BACKGROUND: Atopic dermatitis (AD) disease activity and severity is highly variable during childhood. Early attempts to identify subtypes based on disease trajectory have assessed AD presence over time without incorporating severity. OBJECTIVES: To identify childhood AD subtypes from symptom severity and trajectories, and determine associations with genetic risk factors, comorbidities and demographic and environmental variables. METHODS: We split data from children in the Avon Longitudinal Study of Parents and Children birth cohort into development and validation sets. To identify subtypes, we ran latent class analyses in the development set on AD symptom reports up to age 14 years. We regressed identified subtypes on nongenetic variables in mutually adjusted, multiply imputed (genetic: unadjusted, complete case) multinomial regression analyses. We repeated analyses in the validation set and report confirmed results. RESULTS: There were 11 866 children who contributed to analyses. We identified one Unaffected/Rare class (66% of children) and four AD subtypes: Severe-Frequent (4%), Moderate-Frequent (7%), Moderate-Declining (11%) and Mild-Intermittent (12%). Symptom patterns within the first two subtypes appeared more homogeneous than the last two. Filaggrin (FLG) null mutations, an AD polygenic risk score (PRS), being female, parental AD and comorbid asthma were associated with higher risk for some or all subtypes; FLG, AD-PRS and asthma associations were stronger along a subtype gradient arranged by increasing severity and frequency; FLG and AD-PRS further differentiated some phenotypes from each other. CONCLUSIONS: Considering severity and AD trajectories leads to four well-defined and recognizable subtypes. The differential associations of risk factors among and between subtypes is novel and requires further research.

Incidence of acute complications of herpes zoster among immunocompetent adults in England: a matched cohort study using routine health data.

BACKGROUND: Herpes zoster can cause rare but serious complications; the frequency of these complications has not been well described. OBJECTIVES: To quantify the risks of acute non-postherpetic neuralgia (PHN) zoster complications, to inform vaccination policy. METHODS: We conducted a cohort study among unvaccinated immunocompetent adults with incident zoster, and age-, sex- and practice-matched control adults without zoster, using routinely collected health data from the UK Clinical Practice Research Datalink (years 2001 to 2018). Crude attributable risks of complications were estimated as the difference between Kaplan-Meier-estimated 3-month cumulative incidences in patients with zoster vs. controls. We used Cox models to obtain hazard ratios for our primary outcomes in patients with and without zoster. Primary outcomes were ocular, neurological, cutaneous, visceral and zoster-specific complications. We also assessed whether antivirals during acute zoster protected against the complications. RESULTS: In total 178 964 incident cases of zoster and 1 799 380 controls were included. The absolute risks of zoster-specific complications within 3 months of zoster diagnosis were 0·37% [95% confidence interval (CI) 0·34-0·39] for Ramsay Hunt syndrome, 0·01% (95% CI 0·0-0·01) for disseminated zoster, 0·04% (95% CI 0·03-0·05) for zoster death and 0·97% (95% CI 0·92-1·00) for zoster hospitalization. For other complications, attributable risks were 0·48% (95% CI 0·44-0·51) for neurological complications, 1·33% (95% CI 1·28-1·39) for ocular complications, 0·29% (95% CI 0·26-0·32) for cutaneous complications and 0·78% (95% CI 0·73-0·84) for visceral complications. Attributable risks were higher among patients > 50 years old. Patients with zoster had raised risks of all primary outcomes relative to controls. Antiviral prescription was associated with reduced risk of neurological complications (hazard ratio 0·61, 95% CI 0·53-0·70). CONCLUSIONS: Non-PHN complications of zoster were relatively common, which may affect cost-effectiveness calculations for zoster vaccination. Clinicians should be aware that zoster can lead to various complications, besides PHN.

Rural and urban migration to Europe in relation to cardiovascular disease risk: does it matter where you migrate from?

OBJECTIVES: To assess whether the environmental context (i.e. rural vs urban) in which individuals in low- and middle-income countries have resided most of their lives is associated with estimated cardiovascular disease (CVD) risk after migration to a high-income country. STUDY DESIGN: Data from the Research on Obesity and Diabetes among African Migrants (RODAM) study were used including 1699 Ghanaian participants aged 40-79 years who had migrated to Europe from Ghana (1549 of urban origin, 150 of rural origin). METHODS: Ten-year CVD risk was estimated using the Pooled Cohort Equation, with estimates ≥7.5% defining elevated CVD risk. Comparisons between urban and rural origin migrant groups were made using proportions and adjusted odds ratios (ORs). RESULTS: The proportion of migrants with an elevated CVD-risk score was substantially higher among rural migrants than among urban migrants (45% vs. 37%, OR = 1.44, 95% confidence interval [CI]:1.03-2.02), which persisted after adjustment for education level, site of residence in Europe (London, Amsterdam or Berlin), length of stay in Europe, physical activity, energy intake and alcohol consumption (OR = 1.67, 95% CI: 1.05-2.67). CONCLUSION: Our findings indicate that migrants who spent most of their lives in a rural setting before migration to Europe may have a higher CVD risk than those of urban origins. Further work is needed to confirm these findings in other migrant populations and to unravel the mechanisms driving the differential CVD risk between urban and rural migrants.

Intermediate hyperglycaemia and 10-year mortality in resource-constrained settings: the PERU MIGRANT Study.

AIM: To determine whether intermediate hyperglycaemia, defined by fasting plasma glucose and HbA1c criteria, is associated with mortality in a 10-year cohort of people in a Latin American country. METHODS: Analysis of the PERU MIGRANT Study was conducted in three different population groups (rural, rural-to-urban migrant, and urban). The baseline assessment was conducted in 2007/2008, with follow-up assessment in 2018. The outcome was all-cause mortality, and the exposure was intermediate hyperglycaemia, using three definitions: (1) impaired fasting glucose, defined according to American Diabetes Association criteria [fasting plasma glucose 5.6-6.9 mmol/l (100-125 mg/dl)]; (2) intermediate hyperglycaemia defined according to American Diabetes Association criteria [HbA1c levels 39-46 mmol/mol (5.7-6.4%)]; and (3) intermediate hyperglycaemia defined according to the International Expert Committee criteria [HbA1c levels 42-46 mmol/mol (6.0-6.4%)]. Crude and adjusted hazard ratios and 95% CIs were estimated using Cox proportional hazard models. RESULTS: At baseline, the mean (sd) age of the study population was 47.8 (11.9) years and 52.5% of the cohort were women. The study cohort was divided into population groups as follows: 207 people (20.0%) in the rural population group, 583 (59.7%) in the rural-to-urban migrant group and 198 (20.3%) in the urban population group. The prevalence of intermediate hyperglycaemia was: 6%, 12.9% and 38.5% according to the American Diabetes Association impaired fasting glucose definition, the International Expert Committee HbA1c -based definition and the American Diabetes Association HbA1c -based definition, respectively, and the mortality rate after 10 years was 63/976 (7%). Intermediate hyperglycaemia was associated with all-cause mortality using the HbA1c -based definitions in the crude models [hazard ratios 2.82 (95% CI 1.59-4.99) according to the American Diabetes Association and 2.92 (95% CI 1.62-5.28) according to the International Expert Committee], whereas American Diabetes Association-defined impaired fasting glucose was not [hazard ratio 0.84 (95% CI 0.26-2.68)]. In the adjusted model, however, only the American Diabetes Association HbA1c -based definition was associated with all-cause mortality [hazard ratio 1.91 (95% CI 1.03-3.53)], whereas the International Expert Committee HbA1c -based and American Diabetes Association impaired fasting glucose-based definitions were not [hazard ratios 1.42 (95% CI 0.75-2.68) and 1.09 (95% CI 0.33-3.63), respectively]. CONCLUSIONS: Intermediate hyperglycaemia defined using the American Diabetes Association HbA1c criteria was associated with an elevated mortality rate after 10 years in a cohort from Peru. HbA1c appears to be a factor associated with mortality in this Peruvian population.

Partner bereavement and risk of psoriasis and atopic eczema: cohort studies in the U.K. and Denmark.

BACKGROUND: Stress is commonly cited as a risk factor for psoriasis and atopic eczema, but such evidence is limited. OBJECTIVES: To investigate the association between partner bereavement (an extreme life stressor) and psoriasis or atopic eczema. METHODS: We conducted cohort studies using data from the U.K. Clinical Practice Research Datalink (1997-2017) and Danish nationwide registries (1997-2016). The exposed cohort was partners who experienced partner bereavement. The comparison cohort was up to 10 nonbereaved partners, matched to each bereaved partner by age, sex, county of residence (Denmark) and general practice (U.K.). Outcomes were the first recorded diagnosis of psoriasis or atopic eczema. We estimated hazard ratios (HRs) and confidence intervals (CIs) using a stratified Cox proportional hazards model in both settings, which were then pooled in a meta-analysis. RESULTS: The pooled adjusted HR for the association between bereavement and psoriasis was 1·01 (95% CI 0·98-1·04) across the entire follow-up. Similar results were found in other shorter follow-up periods. Pooled adjusted HRs for the association between bereavement and atopic eczema were 0·97 (95% CI 0·84-1·12) across the entire follow-up, 1·09 (95% CI 0·86-1·38) within 0-30 days, 1·18 (95% CI 1·04-1·35) within 0-90 days, 1·14 (95% CI 1·06-1·22) within 0-365 days and 1·07 (95% CI 1·02-1·12) within 0-1095 days. CONCLUSIONS: We found a modest increase in the risk of atopic eczema within 3 years following bereavement, which peaked in the first 3 months. Acute stress may play a role in triggering onset of new atopic eczema or relapse of atopic eczema previously in remission. We observed no evidence for increased long-term risk of psoriasis and atopic eczema following bereavement.

The association between partner bereavement and melanoma: cohort studies in the U.K. and Denmark.

BACKGROUND: Psychological stress is commonly cited as a risk factor for melanoma, but clinical evidence is limited. OBJECTIVES: This study aimed to evaluate the association between partner bereavement and (i) first-time melanoma diagnosis and (ii) mortality in patients with melanoma. METHODS: We conducted two cohort studies using data from the U.K. Clinical Practice Research Datalink (1997-2017) and Danish nationwide registries (1997-2016). In study 1, we compared the risk of first melanoma diagnosis in bereaved vs. matched nonbereaved people using stratified Cox regression. In study 2 we estimated hazard ratios (HRs) for death from melanoma in bereaved compared with nonbereaved individuals with melanoma using Cox regression. We estimated HRs separately for the U.K. and for Denmark, and then pooled the data to perform a random-effects meta-analysis. RESULTS: In study 1, the pooled adjusted HR for the association between partner bereavement and melanoma diagnosis was 0·88 [95% confidence interval (CI) 0·84-0·92] across the entire follow-up period. In study 2, we observed increased melanoma-specific mortality in people experiencing partner bereavement across the entire follow-up period (HR 1·17, 95% CI 1·06-1·30), with the peak occurring during the first year of follow-up (HR 1·31, 95% CI 1·07-1·60). CONCLUSIONS: We found decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. These findings may be partly explained by delayed detection resulting from the loss of a partner who could notice skin changes. Stress may play a role in melanoma progression. Our findings indicate the need for a low threshold for skin examination in individuals whose partners have died. What is already known about this topic? Psychological stress has been proposed as a risk factor for the development and progression of cancer, including melanoma, but evidence is conflicting. Clinical evidence is limited by small sample sizes, potential recall bias associated with self-report, and heterogeneous stress definitions. What does this study add? We found a decreased risk of melanoma diagnosis, but increased mortality associated with partner bereavement. While stress might play a role in the progression of melanoma, an alternative explanation is that bereaved people no longer have a close person to help notice skin changes, leading to delayed melanoma detection. Linked Comment: Talaganis et al. Br J Dermatol 2020; 183:607-608.

Predicting COPD 1-year mortality using prognostic predictors routinely measured in primary care.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of mortality. Patients with advanced disease often have a poor quality of life, such that guidelines recommend providing palliative care in their last year of life. Uptake and use of palliative care in advanced COPD is low; difficulty in predicting 1-year mortality is thought to be a major contributing factor. METHODS: We identified two primary care COPD cohorts using UK electronic healthcare records (Clinical Practice Research Datalink). The first cohort was randomised equally into training and test sets. An external dataset was drawn from a second cohort. A risk model to predict mortality within 12 months was derived from the training set using backwards elimination Cox regression. The model was given the acronym BARC based on putative prognostic factors including body mass index and blood results (B), age (A), respiratory variables (airflow obstruction, exacerbations, smoking) (R) and comorbidities (C). The BARC index predictive performance was validated in the test set and external dataset by assessing calibration and discrimination. The observed and expected probabilities of death were assessed for increasing quartiles of mortality risk (very low risk, low risk, moderate risk, high risk). The BARC index was compared to the established index scores body mass index, obstructive, dyspnoea and exacerbations (BODEx), dyspnoea, obstruction, smoking and exacerbations (DOSE) and age, dyspnoea and obstruction (ADO). RESULTS: Fifty-four thousand nine hundred ninety patients were eligible from the first cohort and 4931 from the second cohort. Eighteen variables were included in the BARC, including age, airflow obstruction, body mass index, smoking, exacerbations and comorbidities. The risk model had acceptable predictive performance (test set: C-index = 0.79, 95% CI 0.78-0.81, D-statistic = 1.87, 95% CI 1.77-1.96, calibration slope = 0.95, 95% CI 0.9-0.99; external dataset: C-index = 0.67, 95% CI 0.65-0.7, D-statistic = 0.98, 95% CI 0.8-1.2, calibration slope = 0.54, 95% CI 0.45-0.64) and acceptable accuracy predicting the probability of death (probability of death in 1 year, n high-risk group, test set: expected = 0.31, observed = 0.30; external dataset: expected = 0.22, observed = 0.27). The BARC compared favourably to existing index scores that can also be applied without specialist respiratory variables (area under the curve: BARC = 0.78, 95% CI 0.76-0.79; BODEx = 0.48, 95% CI 0.45-0.51; DOSE = 0.60, 95% CI 0.57-0.61; ADO = 0.68, 95% CI 0.66-0.69, external dataset: BARC = 0.70, 95% CI 0.67-0.72; BODEx = 0.41, 95% CI 0.38-0.45; DOSE = 0.52, 95% CI 0.49-0.55; ADO = 0.57, 95% CI 0.54-0.60). CONCLUSION: The BARC index performed better than existing tools in predicting 1-year mortality. Critically, the risk score only requires routinely collected non-specialist information which, therefore, could help identify patients seen in primary care that may benefit from palliative care.

Inequalities in zoster disease burden: a population-based cohort study to identify social determinants using linked data from the U.K. Clinical Practice Research Datalink.

BACKGROUND: Zoster vaccination was introduced in England in 2013, where tackling health inequalities is a statutory requirement. However, specific population groups with higher zoster burden remain largely unidentified. OBJECTIVES: To evaluate health inequalities in zoster disease burden prior to zoster vaccine introduction in England. METHODS: This population-based cohort study used anonymized U.K. primary care data linked to hospitalization and deprivation data. Individuals aged ≥ 65 years without prior zoster history (N = 862 470) were followed from 1 September 2003 to 31 August 2013. Poisson regression was used to obtain adjusted rate ratios (ARRs) for the association of sociodemographic factors (ethnicity, immigration status, individuals' area-level deprivation, care home residence, living arrangements) with first zoster episode. Possible mediation by comorbidities and immunosuppressive medications was also assessed. RESULTS: There were 37 014 first zoster episodes, with an incidence of 8·79 [95% confidence interval (CI) 8·70-8·88] per 1000 person-years at risk. In multivariable analyses, factors associated with higher zoster rates included care home residence (10% higher vs. those not in care homes), being a woman (16% higher vs. men), nonimmigrants (~30% higher than immigrants) and white ethnicity (for example, twice the rate compared with those of black ethnicity). Zoster incidence decreased slightly with increasing deprivation (ARR most vs. least deprived 0·96 (95% CI 0·92-0·99) and among those living alone (ARR 0·96, 95% CI 0·94-0·98). Mediating variables made little difference to the ARR of social factors but were themselves associated with increased zoster burden (ARR varied from 1·11 to 3·84). CONCLUSIONS: The burden of zoster was higher in specific sociodemographic groups. Further study is needed to ascertain whether these individuals are attending for zoster vaccination.

Glycated haemoglobin (HbA1c ) and fasting plasma glucose relationships in sea-level and high-altitude settings.

AIM: Higher haemoglobin levels and differences in glucose metabolism have been reported among high-altitude residents, which may influence the diagnostic performance of HbA1c . This study explores the relationship between HbA1c and fasting plasma glucose (FPG) in populations living at sea level and at an altitude of > 3000 m. METHODS: Data from 3613 Peruvian adults without a known diagnosis of diabetes from sea-level and high-altitude settings were evaluated. Linear, quadratic and cubic regression models were performed adjusting for potential confounders. Receiver operating characteristic (ROC) curves were constructed and concordance between HbA1c and FPG was assessed using a Kappa index. RESULTS: At sea level and high altitude, means were 13.5 and 16.7 g/dl (P > 0.05) for haemoglobin level; 41 and 40 mmol/mol (5.9% and 5.8%; P < 0.01) for HbA1c ; and 5.8 and 5.1 mmol/l (105 and 91.3 mg/dl; P < 0.001) for FPG, respectively. The adjusted relationship between HbA1c and FPG was quadratic at sea level and linear at high altitude. Adjusted models showed that, to predict an HbA1c value of 48 mmol/mol (6.5%), the corresponding mean FPG values at sea level and high altitude were 6.6 and 14.8 mmol/l (120 and 266 mg/dl), respectively. An HbA1c cut-off of 48 mmol/mol (6.5%) had a sensitivity for high FPG of 87.3% (95% confidence interval (95% CI) 76.5 to 94.4) at sea level and 40.9% (95% CI 20.7 to 63.6) at high altitude. CONCLUSION: The relationship between HbA1c and FPG is less clear at high altitude than at sea level. Caution is warranted when using HbA1c to diagnose diabetes mellitus in this setting.

Trends in the burden of varicella in UK general practice.

Childhood varicella vaccination has not yet been introduced in the UK. To inform decision-making about future vaccine programmes, data on the burden of varicella in general practice over a 10-year period (01/01/2005-31/12/2014) was calculated by age and ethnicity, using anonymised data from >8 million individuals in the Clinical Practice Research Datalink. Varicella consultations peaked at 20 603 in 2007, then decreased annually in all age groups to 11 243 in 2014. Each year, consultation rates were common among infants, were highest among 1-3 year olds (61·2 consultations/1000 person-years in 2007, 39·7/1000 person-years in 2014) and then fell with increasing age to <1·0/1000 person-years at ages ⩾20 years. Varicella acquisition appeared to be delayed in some ethnic groups, with lower consultation rates for children aged <3 years but increased rates for older children and adults aged ⩽40 years among those of black African, Afro-Caribbean, South Asian or other Asian ethnicity. Decreasing general practice consultation rates over time could reflect changes in healthcare utilisation, with patients seeking care in alternative settings such as Accident and Emergency Departments, although current data prevent full assessment of this. Availability of data on varicella diagnoses across all health settings would enable estimation of the total healthcare burden due to varicella and the cost-effectiveness of introducing varicella vaccination.

Obesity risk in rural, urban and rural-to-urban migrants: prospective results of the PERU MIGRANT study.

BACKGROUND: Although migration and urbanization have been linked with higher obesity rates, especially in low-resource settings, prospective information about the magnitude of these effects is lacking. We estimated the risk of obesity and central obesity among rural subjects, rural-to-urban migrants and urban subjects. METHODS: Prospective data from the PERU MIGRANT Study were analyzed. Baseline data were collected in 2007-2008 and participants re-contacted in 2012-2013. At follow-up, outcomes were obesity and central obesity measured by body mass index and waist circumference. At baseline, the primary exposure was demographic group: rural, rural-to-urban migrant and urban. Other exposures included an assets index and educational attainment. Cumulative incidence, incidence ratio (IR) and 95% confidence intervals (95% CI) for obesity and central obesity were estimated with Poisson regression models. RESULTS: At baseline, mean age (±s.d.) was 47.9 (±12.0) years, and 53.0% were females. Rural subjects comprised 20.2% of the total sample, whereas 59.7% were rural-to-urban migrants and 20.1% were urban dwellers. A total of 3598 and 2174 person-years were analyzed for obesity and central obesity outcomes, respectively. At baseline, the prevalence of obesity and central obesity was 20.0 and 52.5%. In multivariable models, migrant and urban groups had an 8- to 9.5-fold higher IR of obesity compared with the rural group (IR migrants=8.19, 95% CI=2.72-24.67; IR urban=9.51, 95% CI=2.74-33.01). For central obesity, there was a higher IR only among the migrant group (IR=1.95; 95% CI=1.22-3.13). Assets index was associated with a higher IR of central obesity (IR top versus bottom tertile 1.45, 95% CI=1.03-2.06). CONCLUSIONS: Peruvian urban individuals and rural-to-urban migrants show a higher incidence of obesity compared with their rural counterparts. Given the ongoing urbanization occurring in middle-income countries, the rapid development of increased obesity risk by rural-to-urban migrants suggests that measures to reduce obesity should be a priority for this group.

Statin use and the risk of herpes zoster: a nested case-control study using primary care data from the U.K. Clinical Research Practice Datalink.

BACKGROUND: Statins are commonly prescribed worldwide and recent evidence suggests that they may increase the risk of herpes zoster (HZ). OBJECTIVES: To quantify the effect of statin exposure on the risk of HZ in the U.K. METHODS: A matched case-control study was conducted using data from U.K. primary care and hospital records. Patients > 18 years with an incident diagnosis of HZ were matched to up to four controls for age, sex and general practice. Patients were included in the statin exposure group if they had ever used a statin, and the daily dosage of the most recent statin prescription and the time since the most recent statin prescription were also recorded. The primary outcome was an incident diagnosis of HZ. Odds ratios (ORs) were estimated from conditional logistic regression and adjusted for potential confounders. RESULTS: A total of 144 959 incident cases of HZ were matched to 549 336 controls. Adjusted analysis suggested strong evidence for an increase in the risk of HZ related to statin exposure (OR 1·13, 95% confidence interval 1·11-1·15). There was also an increased risk when dosages were increased for patients who were currently or had recently been receiving statin treatment (Ptrend < 0·001), and we found an attenuation of the increased risk of HZ in previous statin users as the time since last statin exposure increased (Ptrend < 0·001). CONCLUSIONS: These findings are consistent with the hypothesis that statin therapy leads to an increase in the risk of HZ.

The effect of sibutramine prescribing in routine clinical practice on cardiovascular outcomes: a cohort study in the United Kingdom.

BACKGROUND/OBJECTIVES: The marketing authorization for the weight loss drug sibutramine was suspended in 2010 following a major trial that showed increased rates of non-fatal myocardial infarction and cerebrovascular events in patients with pre-existing cardiovascular disease. In routine clinical practice, sibutramine was already contraindicated in patients with cardiovascular disease and so the relevance of these influential clinical trial findings to the 'real World' population of patients receiving or eligible for the drug is questionable. We assessed rates of myocardial infarction and cerebrovascular events in a cohort of patients prescribed sibutramine or orlistat in the United Kingdom. SUBJECTS/METHODS: A cohort of patients prescribed weight loss medication was identified within the Clinical Practice Research Datalink. Rates of myocardial infarction or cerebrovascular event, and all-cause mortality were compared between patients prescribed sibutramine and similar patients prescribed orlistat, using both a multivariable Cox proportional hazard model, and propensity score-adjusted model. Possible effect modification by pre-existing cardiovascular disease and cardiovascular risk factors was assessed. RESULTS: Patients prescribed sibutramine (N=23,927) appeared to have an elevated rate of myocardial infarction or cerebrovascular events compared with those taking orlistat (N=77,047; hazard ratio 1.69, 95% confidence interval 1.12-2.56). However, subgroup analysis showed the elevated rate was larger in those with pre-existing cardiovascular disease (hazard ratio 4.37, 95% confidence interval 2.21-8.64), compared with those with no cardiovascular disease (hazard ratio 1.52, 95% confidence interval 0.92-2.48, P-interaction=0.0076). All-cause mortality was not increased in those prescribed sibutramine (hazard ratio 0.67, 95% confidence interval 0.34-1.32). CONCLUSIONS: Sibutramine was associated with increased rates of acute cardiovascular events in people with pre-existing cardiovascular disease, but there was a low absolute risk in those without. Sibutramine's marketing authorization may have, therefore, been inappropriately withdrawn for people without cardiovascular disease.

Use of electronic healthcare records in large-scale simple randomized trials at the point of care for the documentation of value-based medicine.

A solid foundation of evidence of the effects of an intervention is a prerequisite of evidence-based medicine. The best source of such evidence is considered to be randomized trials, which are able to avoid confounding. However, they may not always estimate effectiveness in clinical practice. Databases that collate anonymized electronic health records (EHRs) from different clinical centres have been widely used for many years in observational studies. Randomized point-of-care trials have been initiated recently to recruit and follow patients using the data from EHR databases. In this review, we describe how EHR databases can be used for conducting large-scale simple trials and discuss the advantages and disadvantages of their use.

Maternal depression, antidepressant prescriptions, and congenital anomaly risk in offspring: a population-based cohort study.

OBJECTIVE: To estimate risks of major congenital anomaly (MCA) among children of mothers prescribed antidepressants during early pregnancy or diagnosed with depression but without antidepressant prescriptions. DESIGN: Population-based cohort study. SETTING: Linked UK maternal-child primary care records. POPULATION: A total of 349,127 singletons liveborn between 1990 and 2009. METHODS: Odds ratios adjusted for maternal sociodemographics and comorbidities (aORs) were calculated for MCAs, comparing women with first-trimester selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs) and women with diagnosed but unmedicated depression, or women without diagnosed depression. MAIN OUTCOME MEASURES: Fourteen system-specific MCA groups classified according to the European Surveillance of Congenital Anomalies and five specific heart anomaly groups. RESULTS: Absolute risks of MCA were 2.7% (95% confidence interval, 95% CI, 2.6-2.8%) in children of mothers without diagnosed depression, 2.8% (95% CI 2.5-3.2%) in children of mothers with unmedicated depression, and 2.7% (95% CI 2.2-3.2%) and 3.1% (95% CI 2.2-4.1%) in children of mothers with SSRIs or TCAs, respectively. Compared with women without depression, MCA overall was not associated with unmedicated depression (aOR 1.07, 95% CI 0.96-1.18), SSRIs (aOR 1.01, 95% CI 0.88-1.17), or TCAs (aOR 1.09, 95% CI 0.87-1.38). Paroxetine was associated with increased heart anomalies (absolute risk 1.4% in the exposed group compared with 0.8% in women without depression; aOR 1.78, 95% CI 1.09-2.88), which decreased marginally when compared with women with diagnosed but unmedicated depression (aOR 1.67, 95% CI 1.00-2.80). CONCLUSIONS: Overall MCA risk did not increase with maternal depression or with antidepressant prescriptions. Paroxetine was associated with increases of heart anomalies, although this could represent a chance finding from a large number of comparisons undertaken.

Acute infections and venous thromboembolism.

BACKGROUND: Data on the association between acute infections and venous thromboembolism (VTE) are sparse. We examined whether various hospital-diagnosed infections or infections treated in the community increase the risk of VTE. METHODS: We conducted this population-based case-control study in Northern Denmark (population 1.8 million) using medical databases. We identified all patients with a first hospital-diagnosed VTE during the period 1999-2009 (n = 15 009). For each case, we selected 10 controls from the general population matched for age, gender and county of residence (n = 150 074). We identified all hospital-diagnosed infections and community prescriptions for antibiotics 1 year predating VTE. We used odds ratios from a conditional logistic regression model to estimate incidence rate ratios (IRRs) of VTE within different time intervals of the first year after infection, controlling for confounding. RESULTS: Respiratory tract, urinary tract, skin, intra-abdominal and bacteraemic infections diagnosed in hospital or treated in the community were associated with a greater than equal to twofold increased VTE risk. The association was strongest within the first 2 weeks after infection onset, gradually declining thereafter. Compared with individuals without infection during the year before VTE, the IRR for VTE within the first 3 months after infection was 12.5 (95% confidence interval (CI): 11.3-13.9) for patients with hospital-diagnosed infection and 4.0 (95% CI: 3.8-4.1) for patients treated with antibiotics in the community. Adjustment for VTE risk factors reduced these IRRs to 3.3 (95% CI: 2.9-3.8) and 2.6 (95% CI: 2.5-2.8), respectively. Similar associations were found for unprovoked VTE and for deep venous thrombosis and pulmonary embolism individually. CONCLUSIONS: Infections are a risk factor for VTE.