Don't blame it on the sunshine, don't blame it on the moonlight, don't blame it on good times, blame it on the sociocultural factors

In this issue of Hepatology, Ventura‐Cots and colleagues present their study arguing that colder weather and fewer sunlight hours increase alcohol consumption and thus cause alcoholic cirrhosis (1). “Causality” is a key concept for this study. A recent review on the topic highlighted two nicely articulated definitions provided by Lilienfeld (‘a factor may be defined as a cause of a disease, if the incidence of the disease is diminished when exposure to this factor is likewise diminished’) and Pearl (‘X is a cause of Y if Y listens to X and decides its value in response to what it hears

Risk of venous thromboembolism in hospitalised cancer patients in England—a cohort study

Background Venous thromboembolism (VTE) is a well-recognised and life-threatening complication in patients with cancer. However, the precise risk of VTE in hospitalised cancer patients in England has not been previously reported. Methods We conducted a cohort study using linked Hospital Episodes Statistics and Office for National Statistics mortality data. We determined the risk of VTE separately for 24 cancer sites following first hospitalisation for cancer (index date) and how this varied by age, proximity from hospital admission, administration of chemotherapy and calendar time. Results Between 1998 and 2012, 3,558,660 patients were hospitalised for cancer. The cancer sites with the highest risk of VTE during initial hospitalisation for cancer were pancreatic (4.9 %), ovarian (4 %) and liver (3.8 %). The three cancer sites with the highest risk of first VTE event within 6 months from discharge were pancreatic (3.7 %), oesophagus (3 %) and stomach (2.8 %). For most cancers, the risk of VTE within 6 months from discharge was higher amongst patients who underwent chemotherapy compared to those who did not. The impact of age on risk of VTE varied considerably between cancer sites. Conclusions The risk of VTE amongst patients hospitalised for cancer varies greatly by cancer site, age, proximity from hospital admission, and chemotherapy administration.</p

Drugs for discoid lupus erythematosus

BACKGROUND: Discoid lupus erythematosus (DLE) is a chronic form of cutaneous lupus, which can cause scarring. Many drugs have been used to treat this disease and some (such as thalidomide, cyclophosphamide and azathioprine) are potentially toxic. This is an update of a Cochrane Review first published in 2000, and previously updated in 2009. We wanted to update the review to assess whether any new information was available to treat DLE, as we were still unsure of the effectiveness of available drugs and how to select the most appropriate treatment for an individual with DLE. OBJECTIVES: To assess the effects of drugs for discoid lupus erythematosus. SEARCH METHODS: We updated our searches of the following databases to 22 September 2016: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We also searched five trials databases, and checked the reference lists of included studies for further references to relevant trials. Index Medicus (1956 to 1966) was handsearched and we approached authors for information about unpublished trials. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) of drugs to treat people with DLE in any population group and of either gender. Comparisons included any drug used for DLE against either another drug or against placebo cream. We excluded laser treatment, surgery, phototherapy, other forms of physical therapy, and photoprotection as we did not consider them drug treatments. DATA COLLECTION AND ANALYSIS: At least two reviewers independently extracted data onto a data extraction sheet, resolving disagreements by discussion. We used standard methods to assess risk of bias, as expected by Cochrane. MAIN RESULTS: Five trials involving 197 participants were included. Three new trials were included in this update. None of the five trials were of high quality.'Risk of bias' assessments identified potential sources of bias in each study. One study used an inappropriate randomisation method, and incomplete outcome data were a concern in another as 15 people did not complete the trial. We found most of the trials to be at low risk in terms of blinding, but three of the five did not describe allocation concealment.The included trials inadequately addressed the primary outcome measures of this review (percentage with complete resolution of skin lesions, percentage with clearing of erythema in at least 50% of lesions, and improvement in patient satisfaction/quality of life measures).One study of fluocinonide cream 0.05% (potent steroid) compared with hydrocortisone cream 1% (low-potency steroid) in 78 people reported complete resolution of skin lesions in 27% (10/37) of participants in the fluocinonide cream group and in 10% (4/41) in the hydrocortisone group, giving a 17% absolute benefit in favour of fluocinonide (risk ratio (RR) 2.77, 95% CI 0.95 to 8.08, 1 study, n = 78, low-quality evidence). The other primary outcome measures were not reported. Adverse events did not require discontinuation of the drug. Skin irritation occurred in three people using hydrocortisone, and one person developed acne. Burning occurred in two people using fluocinonide (moderate-quality evidence).A comparative trial of two oral agents, acitretin (50 mg daily) and hydroxychloroquine (400 mg daily), reported two of the outcomes of interest: complete resolution was seen in 13 of 28 participants (46%) on acitretin and 15 of 30 participants (50%) on hydoxychloroquine (RR 0.93, 95% CI 0.54 to 1.59, 1 study, n = 58, low-quality evidence). Clearing of erythema in at least 50% of lesions was reported in 10 of 24 participants (42%) on acitretin and 17 of 25 (68%) on hydroxychloroquine (RR 0.61, 95% CI 0.36 to 1.06, 1 study, n = 49, low-quality evidence). This comparison did not assess improvement in patient satisfaction/quality of life measures. Participants taking acitretin showed a small increase in serum triglyceride, not sufficient to require withdrawal of the drug. The main adverse effects were dry lips (93% of the acitretin group and 20% of the hydroxychloroquine group) and gastrointestinal disturbance (11% of the acitretin group and 17% of the hydroxychloroquine group). Four participants on acitretin withdrew due to gastrointestinal events or dry lips (moderate-quality evidence).One trial randomised 10 people with DLE to apply a calcineurin inhibitor, pimecrolimus 1% cream, or a potent steroid, betamethasone 17-valerate 0.1% cream, for eight weeks. The study reported none of the primary outcome measures, nor did it present data on adverse events.A trial of calcineurin inhibitors compared tacrolimus cream 0.1% with placebo (vehicle) over 12 weeks in 14 people, but reported none of our primary outcome measures. In the tacrolimus group, five participants complained of slight burning and itching, and for one participant, a herpes simplex infection was reactivated (moderate-quality evidence).Topical R-salbutamol 0.5% cream was compared with placebo (vehicle) over eight weeks in one trial of 37 people with DLE. There was a significant improvement in pain and itch in the salbutamol group at two, four, six, and eight weeks compared to placebo, but the trial did not record a formal measure of quality of life. None of the primary outcome measures were reported. Changes in erythema did not show benefit of salbutamol over placebo, but we could not obtain from the trial report the number of participants with clearing of erythema in at least 50% of lesions. There were 15 events in the placebo group (experienced by 12 participants) and 24 in the salbutamol group (experienced by nine participants). None of the adverse events were considered serious (moderate-quality evidence). AUTHORS' CONCLUSIONS: Fluocinonide cream may be more effective than hydrocortisone in clearing DLE skin lesions. Hydroxychloroquine and acitretin appear to be of equal efficacy in terms of complete resolution, although adverse effects might be more frequent with acitretin, and clearing of erythema in at least 50% of lesions occurred less often in participants applying acitretin. Moderate-quality evidence found adverse events were minor on the whole. There is not enough reliable evidence about other drugs used to treat DLE. Overall, the quality of the trials and levels of uncertainty were such that there is a need for further trials of sufficient duration comparing, in particular, topical steroids with other agents

Alcohol consumption and risk of common cancers: evidence from a cohort of adults from the United Kingdom

Background: Recent guidelines from the United Kingdom recommend that men and women should drink no more than 14 units of alcohol per week. This recommendation takes into account the link between alcohol and several cancers; however, there is a dearth of high quality evidence from the UK to support this. Methods: Alcohol consumption using a detailed diary was obtained from 8,670 adults representative of the UK population in 1984/5, with follow-up data from cancer registries until 2009. Hazard ratios (HR) adjusted for several variables including cigarette smoking were calculated for cancers of the breast, lung, colorectum and prostate separately using Cox regression. Results: Units per week on a typical basis, fitted as a linear term, was associated with breast cancer in women (HR=1.27 per 10 units/week; 95% CI 1.03-1.58) and lung cancer in men (HR=1.16; 1.06-1.27). Increased risks of lung (HR=2.23; 1.18-4.24) and colorectal (HR = 2.28; 1.13-4.57) cancer were seen in men at 15-28 units/week along with higher levels of consumption. Some findings differed by alcohol type. Conclusions: Overall, alcohol consumption of 15-28 units/week may be harmful in men with respect to common cancers. A linear association between alcohol consumption and risk of breast cancer was observed in women

Effect of allopurinol on all-cause mortality in adults with incident gout: propensity score–matched landmark analysis

Objective: To examine the association between allopurinol use and all-cause mortality for patients with incident gout. Methods: We compared all-cause mortality in incident gout patients who received allopurinol for at least 6 months within the exposure window (1 year or 3 years) with those who did not, using the UK Clinical Practice Research Data-link. Landmark analysis was used to account for immortal time bias and propensity score matching was used to control for potential effects of known confounders. Results: Of 23 332 incident gout patients identified, the propensity score–matched cohorts contained 1016 patients exposed to allopurinol on the date 1 year from diagnosis (landmark date) and 1016 allopurinol non-users. Over a median follow-up period of 10 years after the landmark date, there were 437 allopurinol users and 443 allopurinol non-users who died during follow-up. Allopurinol users and non-users had similar risk for all-cause mortality (hazard ratio 0.99; 95% CI 0.87, 1.12). In the 3-year landmark analysis, 3519 allopurinol users (1280 died) were compared with 3519 non-users (1265 died). The hazard ratio for all-cause mortality was 1.01 (95% CI 0.92, 1.09). Conclusion: This propensity score–matched landmark analysis in a population of incident gout patients in the UK primary care setting found a neutral effect on the risk of all-cause mortality. Our study provides reassurance about the prescription of allopurinol for gout patients early in their disease course to prevent untoward consequences of chronic uncontrolled hyperuricaemia. However, whether higher than the commonly used dose of allopurinol could influence mortality remains to be determined

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

Rheumatoid arthritis and excess mortality: down but not out: a primary care cohort study using data from Clinical Practice Research Datalink

Objectives: To examine temporal trends in all-cause and cause-specific mortality in RA. Methods: Data from the Clinical Practice Research Datalink (CPRD) were used. Incident RA cases and four age, sex and general practice matched controls were identified from at-risk cohorts for each calendar year and followed-up for up to five years. Mortality rates and 95% confidence intervals (95% CIs) were computed. Cox-proportional hazard ratios (HRs) were calculated to estimate associations and adjusted for covariates. Temporal trend in mortality was examined using the Joinpoints Regression Program. Data management and analysis were performed using Stata v.14. Results: 21,622 cases with incident RA and 86,488 controls were included. The mortality rate (95%CI) of RA cases and controls was 26.90 (25.87-27.97) and 18.92 (18.48-19.36)/1000 person-years respectively. The mortality rate in RA cases did not change significantly between 1990 and 2004, but reduced by 7.7%/year between 2005 and 2009. However, the mortality rate in controls improved steadily by 2.2%/year between 1990 and 2009. RA associated with 32% excess risk of mortality in the entire cohort (aHR (95%CI) 1.32(1.26-1.38), but this was only 15% in cases incident after 2006 (aHR (95%CI) 1.15(1.03-1.29)). Similarly, the HR of death due to cardiovascular diseases reduced in cases incident in recent years. Conclusion: The mortality rate in RA cases incident after the year 2006 has declined significantly, with a trend towards decline in death from cardiovascular diseases. This could be due to improved management of RA. However, even in cohorts from recent years, RA still associates with higher mortality rates

Impact of gout on the risk of atrial fibrillation

OBJECTIVES: To examine the risk of atrial fibrillation (AF) at the time of first diagnosis of gout compared with matched controls and to follow incident gout patients and their matched controls after diagnosis to compare their subsequent risk of AF. METHODS: From the UK Clinical Practice Research Data-link, 45 378 incident gout patients and 45 378 age-, sex-, practice-, registration year- and index year-matched controls were identified. Index dates were initial diagnosis date for gout patients and their matched controls. The risk of AF at diagnosis [odds ratios (ORs), using conditional logistic regression] and after the diagnosis of gout [hazard ratios (HRs), using Cox proportional models] were estimated, adjusted for BMI, smoking, alcohol consumption, ischaemic heart disease, heart failure, heart valve disease, hyperthyroidism and other comorbidities and medications. RESULTS: The prevalence of AF at index date in gout patients (male, 72.3%; mean age, 62.4 +/- 15.1 years) was 7.42% (95% CI 7.18, 7.66%) and in matched controls 2.83% (95% CI 2.67, 2.98%). The adjusted OR (95% CI) was 1.45 (1.29, 1.62). The cumulative probability of AF at 1, 2, 5 and 10 years after index date was 1.08, 2.03, 4.77 and 9.68% in gout patients and 0.43, 1.08, 2.95 and 6.33% in controls, respectively (log-rank test, P < 0.001). The adjusted HR (95% CIs) was 1.09 (1.03, 1.16). CONCLUSION: This population-based study indicates that gout is independently associated with a higher risk of AF at diagnosis and the risk is also higher after the diagnosis

Epidemiology and management of gout in Taiwan: a nationwide population study

INTRODUCTION: Gout is the most common inflammatory arthritis worldwide and is the only type of chronic arthritis that potentially can be ‘cured’. However, data on gout incidence, prevalence and management, assessed at multiple time points in the same population, are sparse, particularly in Asian populations. The aim of this study was to describe trends in the epidemiology of gout in the general population of Taiwan. METHODS: The National Health Insurance Research Database was used to identify patients with gout and to estimate the prevalence and incidence of gout for each calendar year from 2005 to 2010. The pattern of gout management was also examined. RESULTS: Of 23,371,362 beneficiaries in 2010, there were 1,458,569 prevalent and 56,595 incident cases of gout, giving a prevalence of 6.24% (95% confidence interval (CI), 6.23% to 6.25%) and an incidence of 2.74 (95% CI, 2.72 to 2.76) per 1,000 person-years. The annual percentage change (APC) of the standardised prevalence was −0.7% (95% CI, −1.7% to 0.3%; P = 0.14), suggesting that the prevalence of gout was essentially the same throughout the study period. However, The APC of incidence was −13.4 (95% CI, −16.1 to −10.6) between 2005 and 2007 and −2.1 (95% CI, −10.4 to 7.1) between 2007 and 2010. Regions with the highest prevalence and incidence were eastern coastal counties and offshore islets, where indigenous people are clustered. Among prevalent gout cases in 2010, only 22.93% (95% CI, 22.87% to 23.00%) were prescribed urate-lowering treatment (ULT), which remained unchanged between 2005 and 2010 at an APC of 0.0 (95% CI, −3.8 to 4.0). Uricosuric agents were more commonly prescribed than xanthine oxidase inhibitors in Taiwan. CONCLUSIONS: In Taiwan, 1 in 16 people have gout. Whereas the incidence has decreased recently, the prevalence remains unchanged. Management of gout in Taiwan is poor, with only one in five affected people being treated with ULT

Disease activity in inflammatory bowel disease is associated with arterial vascular disease

Background and Aims: There is evidence that several inflammatory diseases are associated with increased cardiovascular risk. Whether this is true for inflammatory bowel diseases remains controversial. We aimed to assess this risk corrected for the effects of conventional vascular risk factors, and IBD disease activity.Methods: We conducted a cohort study in British general practice and hospital records from the Clinical Practice Research Datalink. We extracted the records of subjects with IBD and matched controls from 1997 to 2017. We conducted Cox proportional hazards and self-controlled case series analyses to examine the associations of IBD, disease activity and hospitalisation with the risk of myocardial infarction, stroke and cardiovascular death in a manner attempting to remove the effect of likely confounders.Results: We identified 31,175 IBD patients (16,779 UC, 10,721 Crohn’s disease and 3,675 unclassifiable cases) and 154,412 matched controls. 532 myocardial infarctions, 555 strokes and 469 cardiovascular deaths were observed in IBD cases. Our Cox regression models adjusted for potential confounders, showed no significant excess of vascular events for IBD patients overall. There was however an increased hazard of MI in ambulatory patients for acute disease (Hazard Ration 1.83 (1.28-2.62)) and chronic activity (Hazard Ratio 1.69 (1.24-2.30)). This effect of disease activity was confirmed in our case series analysis.Conclusions:Though we have found no evidence of an overall excess of vascular events in IBD patients, our findings of increased risk with more active disease suggest the potential for anti-inflammatory therapies to reduce cardiovascular risk in this patient group