Cohort profile: the National Congenital Anomaly Registration Dataset in England.

PURPOSE: The National Congenital Anomaly and Rare Disease Registration Service (NCARDRS), part of National Disease Registration Service in National Health Service England, quality assures, curates and analyses individual data on the pregnancies, fetuses, babies, children and adults with congenital anomalies and rare diseases across England. The congenital anomaly (CA) register provides a resource for patients and their families, clinicians, researchers and public health professionals in furthering the understanding of CAs. PARTICIPANTS: NCARDRS registers CAs occurring in babies born alive and stillborn, fetal losses and terminations in England. NCARDRS collects data from secondary and tertiary healthcare providers, private providers and laboratories covering fetal medicine, maternity or paediatric services. Data describe the pregnancy, mother, baby and anomaly. Established in 2015, NCARDRS expanded CA registration coverage from 22% of total births in England in 2015 to national coverage, which was achieved in 2018. Prior to 2015, data collection was performed independently by regional registers in England; these data are also held by NCARDRS. FINDINGS TO DATE: NCARDRS registers approximately 21 000 babies with CAs per year with surveillance covering around 600 000 total births, the largest birth coverage for a CA register globally. Data on prevalence, risk factors and survival for children with CAs are available. Data have been used in several peer-reviewed publications. Birth prevalence statistics, including public health indicators such as the association with maternal age, infant and perinatal mortality, are published annually. NCARDRS supports clinical audit for screening programmes and service evaluation. FUTURE PLANS: NCARDRS provides a valuable resource for the understanding of the epidemiology, surveillance, prevention and treatment of CAs. Currently, approximately 21 000 new registrations of babies or fetuses with suspected or confirmed CAs are added each year. Identifiers are collected, enabling linkage to routinely collected healthcare and population statistics, further enhancing the value of the data.

Impact of Parental Mental Health and Poverty on the Health of the Next Generation: A Multi-Trajectory Analysis Using the UK Millennium Cohort Study.

PURPOSE: Exposure to parental mental ill-health and poverty in childhood impact health across the lifecourse. Both maternal and paternal mental health may be important influences, but few studies have unpicked the complex interrelationships between these exposures and family poverty for later health. METHODS: We used longitudinal data on 10,500 children from the nationally representative UK millennium cohort study. Trajectories of poverty, maternal mental health, and secondary caregiver mental health were constructed from child age of 9 months through to 14 years. We assessed the associations of these trajectories with mental health outcomes at the age of 17 years. Population-attributable fractions were calculated to quantify the contribution of caregivers' mental health problems and poverty to adverse outcomes at the country level. RESULTS: We identified five distinct trajectories. Compared with children with low poverty and good parental mental health, those who experienced poverty and poor primary or secondary caregiver mental health (53%) had worse outcomes. Children exposed to both persistent poverty and poor caregiver mental health were at markedly increased risk of socioemotional behavioural problems (aOR 4.2; 95% CI 2.7-6.7), mental health problems (aOR 2.5; CI 1.6-3.9), and cognitive disability (aOR 1.7; CI 1.1-2.5). We estimate that 40% of socioemotional behavioural problems at the age of 17 were attributable to persistent parental caregivers' mental health problems and poverty. DISCUSSION: More than half of children growing up in the UK are persistently exposed to either one or both of poor caregiver mental health and family poverty. The combination of these exposures is strongly associated with adverse health outcomes in the next generation.

Outcomes of first emergency admissions for alcohol-related liver disease in England over a 10-year period: retrospective observational cohort study using linked electronic databases.

OBJECTIVES: To examine time trends in patient characteristics, care processes and case fatality of first emergency admission for alcohol-related liver disease (ARLD) in England. DESIGN: National population-based, retrospective observational cohort study. SETTING: Clinical Practice Research Datalink population of England, 2008/2009 to 2017/2018. First emergency admissions were identified using the Liverpool ARLD algorithm. We applied survival analyses and binary logistic regression to study prognostic trends. OUTCOME MEASURES: Patient characteristics; 'recent' General Practitioner (GP) consultations and hospital admissions (preceding year); higher level care; deaths in-hospital (including certified cause) and within 365 days. Covariates were age, sex, deprivation status, coding pattern, ARLD stage, non-liver comorbidity, coding for ascites and varices. RESULTS: 17 575 first admissions (mean age: 53 years; 33% women; 32% from most deprived quintile). Almost half had codes suggesting advanced liver disease. In year before admission, only 47% of GP consulters had alcohol-related problems recorded; alcohol-specific diagnostic codes were absent in 24% of recent admission records. Overall, case fatality rate was 15% in-hospital and 34% at 1 year. Case-mix-adjusted odds of in-hospital death reduced by 6% per year (adjusted OR (aOR): 0.94; 95% CI: 0.93 to 0.96) and 4% per year at 365 days (aOR: 0.96; 95% CI: 0.95 to 0.97). Exploratory analyses suggested the possibility of regional inequalities in outcome. CONCLUSIONS: Despite improving prognosis of first admissions, we found missed opportunities for earlier recognition and intervention in primary and secondary care. In 2017/2018, one in seven were still dying during index admission, rising to one-third within a year. Nationwide efforts are needed to promote earlier detection and intervention, and to minimise avoidable mortality after first emergency presentation. Regional variation requires further investigation.

Investigating association between inflammatory bowel disease and rotavirus vaccination in a paediatric cohort in the UK.

In the UK, the incidence and prevalence of inflammatory bowel disease (IBD) is increasing in paediatric populations. Environmental factors including acute gastroenteritis episodes (AGE) may impact IBD development. Infant rotavirus vaccination has been shown to significantly reduce AGE. This study aims to explore the association between vaccination with live oral rotavirus vaccines and IBD development. A population-based cohort study was used, analysing primary care data from the Clinical Practice Research Datalink Aurum. Participants included children born in the UK from 2010 to 2015, followed from a minimum of 6 months old to a maximum of 7 years old. The primary outcome was IBD, and the primary exposure was rotavirus vaccination. Cox regression analysis with random intercepts for general practices was undertaken, with adjustment for potential confounding factors. In a cohort of 907,477 children, IBD was recorded for 96 participants with an incidence rate of 2.1 per 100,000 person-years at risk. The univariable analysis hazard ratio (HR) for rotavirus vaccination was 1.45 (95% confidence interval (CI) 0.93-2.28). Adjustment in the multivariable model attenuated the HR to 1.19 (95% CI 0.53-2.69). This study shows no statistically significant association between rotavirus vaccination and development of IBD. However, it provides further evidence for the safety of live rotavirus vaccination.

Audit of animal-related injuries at UK veterinary schools between 2009 and 2018.

BACKGROUND: Animal-related injuries pose a significant risk to the veterinary profession. This study aimed to describe the incidence, demographics, context and consequences of animal-related injuries at UK veterinary schools. METHODS: A multicentre audit of accident records (2009-2018) across five UK veterinary schools was performed. Injury rates were stratified by school, demographics and species. The context and cause of the injury were described. Multivariable logistic models explored factors associated with medical treatment, hospital visits and time off work. RESULTS: An annual rate of 2.60 (95% confidence interval 2.48-2.72) injuries per 100 graduating students was calculated, varying between veterinary schools. Injuries were more frequently recorded in staff than students, and there were significant differences between staff and students in the activities performed preceding injury. Cats and dogs were associated with the highest number of reported injuries. However, injuries associated with cattle and horses were the most severe, with significantly higher hospital attendances and more time off work taken. LIMITATIONS: Data were based on reported injuries and likely underestimate the true injury rate. The population at risk was hard to quantify as population size and exposure were variable. CONCLUSION: Further research is recommended to explore the clinical and workplace management, including recording culture, of animal-related injuries among veterinary professionals.

Impact of poverty and family adversity on adolescent health: a multi-trajectory analysis using the UK Millennium Cohort Study.

BACKGROUND: Children exposed to poverty and family adversities including domestic violence, parental mental ill health and parental alcohol misuse may experience poor outcomes across the life course. However, the complex interrelationships between these exposures in childhood are unclear. We therefore assessed the clustering of trajectories of household poverty and family adversities and their impacts on adolescent health outcomes. METHODS: We used longitudinal data from the UK Millennium Cohort study on 11564 children followed to age 14 years. Family adversities included parent reported domestic violence and abuse, poor mental health and frequent alcohol use. We used a group-based multi-trajectory cluster model to identify trajectories of poverty and family adversity for children. We assessed associations of these trajectories with child physical, mental and behavioural outcomes at age 14 years using multivariable logistic regression, adjusting for confounders. FINDINGS: Six trajectories were identified: low poverty and family adversity (43·2%), persistent parental alcohol use (7·7%), persistent domestic violence and abuse (3·4%), persistent poor parental mental health (11·9%), persistent poverty (22·6%) and persistent poverty and poor parental mental health (11·1%). Compared with children exposed to low poverty and adversity, children in the persistent adversity trajectory groups experienced worse outcomes; those exposed to persistent poor parental mental health and poverty were particularly at increased risk of socioemotional behavioural problems (adjusted odds ratio 6·4; 95% CI 5·0 - 8·3), cognitive disability (aOR 2·1; CI 1·5 - 2·8), drug experimentation (aOR 2·8; CI 1·8 - 4·2) and obesity (aOR 1·8; CI 1·3 - 2·5). INTERPRETATION: In a contemporary UK cohort, persistent poverty and/or persistent poor parental mental health affects over four in ten children. The combination of both affects one in ten children and is strongly associated with adverse child outcomes, particularly poor child mental health. FUNDING: The National Institute for Health Research (NIHR) Policy Research Programme, NIHR Applied Research Collaboration South London (ARC South London) at King's College Hospital NHS Foundation Trust and the Medical Research Council (MRC).

"If You Don't Drink at University, You're Going to Struggle to Make Friends" Prospective Students' Perceptions around Alcohol Use at Universities in the United Kingdom.

BACKGROUND: New students arrive at university with pre-determined perceptions around how alcohol can be used as a tool to overcome anxieties and secure new friendships, which in turn influences students' drinking behaviors. From a health promotion perspective, the transition to university may present a unique yet understudied opportunity to challenge and reframe situated drinking norms. This paper explores prospective university students' perceptions of the role that alcohol plays at university and the influence that these perceptions have on behavior. METHOD: Focus groups with 46 prospective university students (aged 16-20 years) recruited from colleges and sixth forms in the North West of England. RESULTS: Through various sources of information, new students arrive at university with pre-conceived perceptions of a heavy student drinking culture and knowledge around how alcohol can be used to aid successful integration with new peers. Alcohol was viewed by new students as a social lubricant which is key to accruing social capital. Cultural presentations of the student drinker identity led prospective students to formulate negative connotations of those students who transgress from the norms of drinking. CONCLUSIONS: The findings provide new insights into how young people conceptualize alcohol at university and the impact that these perceptions have on shaping ideology and influencing drinking behavior. Breaking down these norms presents real challenges for those trying to address excessive drinking in universities, therefore, early intervention which challenges, re-frames and modifies perceptions before students arrive on campus may help to reduce the pressure and expectations to drink in social situations.

Prevalence of fetal alcohol spectrum disorder in Greater Manchester, UK: An active case ascertainment study.

BACKGROUND: Despite high levels of prenatal alcohol exposure in the UK, evidence on the prevalence of fetal alcohol spectrum disorders (FASD) is lacking. This paper reports on FASD prevalence in a small sample of children in primary school. METHODS: A 2-phase active case ascertainment study was conducted in 3 mainstream primary schools in Greater Manchester, UK. Schools were located in areas that ranged from relatively deprived to relatively affluent. Initial screening of children aged 8-9 years used prespecified criteria for elevated FASD risk (small for age; special educational needs; currently/previously in care; significant social/emotional/mental health symptoms). Screen-positive children were invited for detailed ascertainment of FASD using gold standard measures that included medical history, facial dysmorphology, neurological impairment, executive function, and behavioral difficulties. RESULTS: Of 220 eligible children, 50 (23%) screened positive and 12% (26/220) proceeded to Phase 2 assessment. Twenty had a developmental disorder, of whom 4 had FASD and 4 were assessed as possible FASD. The crude prevalence rate of FASD in these schools was 1.8% (95% CI: 1.0%, 3.4%) and when including possible cases was 3.6% (2.1%, 6.3%). None of these children had previously been identified with a developmental diagnosis. CONCLUSIONS: FASD was found to be common in these schools and most of these children's needs had not previously been identified. A larger, more definitive study that uses a random sampling technique stratified by deprivation level to select schools is needed to make inferences regarding the population prevalence of FASD.

Socioeconomic inequalities in the incidence of alcohol-related liver disease: A nationwide Danish study.

BACKGROUND: There is socio-economic inequality in total alcohol-related harm, but knowledge of inequality in the incidence of specific alcohol-related diseases would be beneficial for prevention. Registry-based studies with nationwide coverage may reveal the full burden of socioeconomic inequality compared to what can be captured in questionnaire-based studies. We examined the incidence of alcohol-related liver disease (ALD) according to socioeconomic status and age. METHODS: We used national registries to identify patients with an incident diagnosis of ALD and their socioeconomic status in 2009-2018 in Denmark. We computed ALD incidence rates by socioeconomic status (education and employment status) and age-group (30-39, 40-49, 50-59, 60-69 years) and quantified the inequalities as the absolute and relative difference in incidence rates between low and high socioeconomic status. FINDINGS: Of 17,473 patients with newly diagnosed ALD, 78% of whom had cirrhosis, 86% had a low or medium-low educational level and only 20% were employed. ALD patients were less likely to be employed in the 10 years prior to diagnosis than controls. The incidence rate of ALD correlated inversely with educational level, from 181 (95% CI, 167-197) to 910 (95% CI, 764-1086) per million person-years from the highest to the lowest educational level. By employment status, the incidence rate per million person-years was 211 (95% CI, 189-236) for employed and 3449 (95% CI, 2785-4271) for unemployed. Incidence rates increased gradually with age leading to larger inequalities in absolute numbers for older age-groups. Although ALD was rare in the younger age-groups, the relative differences in incidence rates between high and low socioeconomic status were large for these ages. The pattern of socioeconomic inequality in ALD incidence was similar for men and women. INTERPRETATION: This study showed substantial socioeconomic inequalities in ALD incidence for people aged 30-69 years. FUNDING: The study was supported by grants from the Novo Nordisk Foundation (NNF18OC0054612) and the Research Fund of Bispebjerg Hospital.

Paediatric rotavirus vaccination, coeliac disease and type 1 diabetes in children: a population-based cohort study.

BACKGROUND: Rotavirus infection has been proposed as a risk factor for coeliac disease (CD) and type 1 diabetes (T1D). The UK introduced infant rotavirus vaccination in 2013. We have previously shown that rotavirus vaccination can have beneficial off-target effects on syndromes, such as hospitalised seizures. We therefore investigated whether rotavirus vaccination prevents CD and T1D in the UK. METHODS: A cohort study of children born between 2010 and 2015 was conducted using primary care records from the Clinical Practice Research Datalink. Children were followed up from 6 months to 7 years old, with censoring for outcome, death or leaving the practice. CD was defined as diagnosis of CD or the prescription of gluten-free goods. T1D was defined as a T1D diagnosis. The exposure was rotavirus vaccination, defined as one or more doses. Mixed-effects Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CIs). Models were adjusted for potential confounders and included random intercepts for general practices. RESULTS: There were 880,629 children in the cohort (48.8% female). A total of 343,113 (39.0%) participants received rotavirus vaccine; among those born after the introduction of rotavirus vaccination, 93.4% were vaccinated. Study participants contributed 4,388,355 person-years, with median follow-up 5.66 person-years. There were 1657 CD cases, an incidence of 38.0 cases per 100,000 person-years. Compared with unvaccinated children, the adjusted HR for a CD was 1.05 (95% CI 0.86-1.28) for vaccinated children. Females had a 40% higher hazard than males. T1D was recorded for 733 participants, an incidence of 17.1 cases per 100,000 person-years. In adjusted analysis, rotavirus vaccination was not associated with risk of T1D (HR = 0.89, 95% CI 0.68-1.19). CONCLUSIONS: Rotavirus vaccination has reduced diarrhoeal disease morbidity and mortality substantial since licencing in 2006. Our finding from this large cohort study did not provide evidence that rotavirus vaccination prevents CD or T1D, nor is it associated with increased risk, delivering further evidence of rotavirus vaccine safety.

English hospital episode data analysis (1998-2018) reveal that the rise in dog bite hospital admissions is driven by adult cases.

Dog bites are a global health issue that can lead to severe health outcomes. This study aims to describe the incidence and sociodemographics of patients admitted to English National Health Service (NHS) hospitals for dog bites (1998-2018), and to estimate their annual direct health care costs. An analysis of patient level data utilising hospital episode statistics for NHS England, including: temporal trends in annual incidence of admission, Poisson models of the sociodemographic characteristics of admitted patients, and direct health care cost estimates. The incidence of dog bite admissions rose from 6.34 (95%CI 6.12-6.56) in 1998 to 14.99 (95%CI 14.67-15.31) admissions per 100,000 population in 2018, with large geographic variation. The increase was driven by a tripling of incidence in adults. Males had the highest rates of admission in childhood. Females had two peaks in admission, childhood and 35-64 years old. Two percent (2.05%, 95%CI 0.93-3.17) of emergency department attendances resulted in admission. Direct health care costs increased and peaked in the financial year 2017/2018 (admission costs: £25.1 million, emergency attendance costs: £45.7million). Dog bite related hospital admissions have increased solely in adults. Further work exploring human-dog interactions, stratified by demographic factors, is urgently needed to enable the development of appropriate risk reduction intervention strategies.

Decreasing Incidence of Alcohol-Related Liver Disease in Denmark: A 25-Year Nationwide Study.

PURPOSE: Alcohol consumption has decreased in Denmark in recent years. We aimed to illustrate and investigate the developments in the incidence, hospital care, and mortality of alcohol-related liver disease (ALD) in Denmark during the last 25 years. PATIENTS AND METHODS: Through nationwide healthcare registries, we identified all Danish patients with incident ALD in 1994-2018. We computed standardized incidence rates by sex, age, and geography, age-specific incidence rates by birth cohort, and standardized prevalence. We enumerated inpatient admissions, days of admission, outpatient visits, and emergency room visits. Lastly, we estimated relative risks of mortality, standardized mortality rates, and the proportion of deaths caused by ALD. RESULTS: The standardized incidence rate decreased from its peak at 357 per 1,000,000 in 2009 to 240 per 1,000,000 in 2018, and the decrease was evident for both sexes and all age groups below 70 years. The standardized prevalence was stable around 0.22% from 2011 onwards. There was an almost fivefold geographic variation in standardized incidence by municipalities, and age-specific incidence rates decreased sequentially with each 5-year birth cohort after 1960. The number of inpatient admissions, days of admission, and emergency room visits decreased during the study period, while the number of outpatient visits was stable. For patients diagnosed in 2014-2018 compared to 1994-1998, the relative risk of 1-year mortality was 0.83 (95% confidence interval: 0.78-0.87), and the standardized mortality along with the proportion of deaths caused by ALD decreased during the study period. CONCLUSION: The incidence of ALD decreased from 357 to 240 per 1,000,000 over the last 10 years in Denmark. During the same period, the prevalence remained stable around 0.22% and mortality decreased. Additionally, the burden of ALD on hospital care decreased significantly between 1994 and 2018. We anticipate a further decrease in the incidence of ALD in the future.

UK mothers' experiences of bottle refusal by their breastfed baby.

Little is known about bottle refusal by breastfed babies; however, an informal review of global online forums and social media suggested large numbers of mothers experiencing the scenario. This study aimed to explore UK mothers' experiences of bottle refusal by their breastfed baby in order to provide understanding of the scenario and enhance support for mothers experiencing it. A 22-point online questionnaire was developed and completed by 841 UK mothers. Findings suggest that mothers introduced a bottle to their breastfed baby due to physical, psychological and socio-cultural factors. Advice and support for mothers experiencing bottle refusal was not always helpful, and 27% of mothers reported bottle refusal as having a negative impact on their breastfeeding experience. When compared with eventual bottle acceptance, bottle refusal was significantly associated with previous experience of bottle refusal (p < .001), how frequently mothers intended to feed their baby by bottle and babies being younger at the first attempt to introduce a bottle (p < .001). This study provides a unique insight into the complexities of bottle refusal by breastfed babies and the impact it can have upon mothers' breastfeeding experiences. It generates knowledge and understanding that can help to inform practice and policies. In addition, a 'normalising' of the scenario could enable mothers, and those supporting them, to view and manage it more positively.

All-cause and cause-specific mortality rates of patients treated for alcohol use disorders: A meta-analysis.

BACKGROUND: Although alcohol use disorders (AUDs) are known to increase the relative risk of all-cause and some cause-specific mortality, the absolute mortality rates of the AUD population are unknown. Such knowledge would benefit planners of the provision of services for this population, including in prioritizing the identification and/or treatment of diseases likely to cause their death. METHODS: We conducted a systematic review of studies in English, reporting the cause-specific mortality rates among people treated for AUDs. Number of deaths by cause and total person-years of follow-up were extracted. All-cause and cause-specific mortality rates per 1000 person-years were meta-analyzed assuming random effects. RESULTS: Thirty-one studies were included. Participants were mainly middle-aged males. The quality of studies was generally good. A total of 6768 all-cause deaths in 276,990.7 person-years of follow-up (36,375 patients) were recorded, and the pooled all-cause mortality rate was 27.67/1000 person-years (py) (95% confidence interval [CI]: 23.9, 32.04). The most common cause of death in the AUD population was cardiovascular disease (CVD) (6.9/1000 py; 95% CI: 5.61, 8.49), followed by gastrointestinal deaths (5.63/1000 py; 95% CI: 4.1, 7.74), unnatural deaths (4.95/1000 py; 95% CI: 4.01, 6.09)), neoplasms, respiratory diseases, and substance use disorders. CONCLUSIONS: Patients with AUDs have increased rates of all-cause and cause-specific mortality compared with the general population. Like the general population, they are most likely to die of CVD. In contrast to the general population, gastrointestinal and unnatural deaths are the next most common causes of death. We believe these facts should be considered when planning health care services for patients with AUDs.

Hip fracture risk in patients with alcoholic cirrhosis: A population-based study using English and Danish data.

BACKGROUND & AIMS: Cirrhosis, the prevalence of which is increasing, is a risk factor for osteoporosis and fractures. However, little is known of the actual risk of hip fractures in patients with alcoholic cirrhosis. Using linked primary and secondary care data from the English and Danish nationwide registries, we quantified the hip fracture risk in two national cohorts of patients with alcoholic cirrhosis. METHODS: We followed 3,706 English and 17,779 Danish patients with a diagnosis of alcoholic cirrhosis, and we identified matched controls from the general populations. We estimated hazard ratios (HR) of hip fracture for patients vs. controls, adjusted for age, sex and comorbidity. RESULTS: The five-year hip fracture risk was raised both in England (2.9% vs. 0.8% for controls) and Denmark (4.6% vs. 0.9% for controls). With confounder adjustment, patients with cirrhosis had fivefold (adjusted HR 5.5; 95% CI 4.3-6.9), and 8.5-fold (adjusted HR 8.5; 95% CI 7.8-9.3) increased rates of hip fracture, in England and Denmark, respectively. This association between alcoholic cirrhosis and risk of hip fracture showed significant interaction with age (p <0.001), being stronger in younger age groups (under 45 years, HR 17.9 and 16.6 for English and Danish patients, respectively) than in patients over 75 years (HR 2.1 and 2.9, respectively). In patients with alcoholic cirrhosis, 30-day mortality following a hip fracture was 11.1% in England and 10.0% in Denmark, giving age-adjusted post-fracture mortality rate ratios of 2.8(95% CI 1.9-3.9) and 2.0(95% CI 1.5-2.7), respectively. CONCLUSIONS: Patients with alcoholic cirrhosis have a markedly increased risk of hip fracture and post-hip fracture mortality compared with the general population. These findings support the need for more effort towards fracture prevention in this population, to benefit individuals and reduce the societal burden. LAY SUMMARY: Alcoholic cirrhosis creates a large public health burden and is a risk factor for bone fractures. Based on data from England and Denmark, we found that hip fractures occur more than five times more frequently in people with alcoholic cirrhosis than in people without the disease. Additionally, the aftermath of the hip fracture is severe, such that up to 11% of patients with alcoholic cirrhosis die within 30 days after their hip fracture. These results suggest that efforts directed towards fracture prevention in people with alcoholic cirrhosis could be beneficial.

Liver cirrhosis in England-an observational study: are we measuring its burden occurrence correctly?

OBJECTIVES: Mortality due to liver disease (of which cirrhosis is the end stage) is increasing more than any other chronic condition in the UK. This study aims to demonstrate that (1) exclusive reliance on mortality rates may not reveal the true burden of liver cirrhosis, and (2) diverse use of diagnostic coding may produce misleading estimates. DESIGN: Observational study. SETTING: The Office for National Statistics death registry was interrogated to investigate liver cirrhosis mortality trends in England and Wales from 1968 to 2011. MAIN OUTCOME: Standardised mortality trends according to three different definitions of liver cirrhosis based on the specificity of diagnostic codes were calculated: 1 (chronic liver diseases), 2 (alcoholic and unspecified cirrhosis only) and 3 (cirrhosis as end-stage liver disease). The mortality trends were compared with incidence rates established in a previous population-based study (based on definition 3), from 1998 to 2009, to investigate discrepancies between these two measures. RESULTS: Over the study period, the overall standardised liver cirrhosis mortality rates were 8.8, 5,1 and 5.4 per 100 000 person-years for definitions 1, 2 and 3, respectively. The mortality rates for definition 3 in 1998 and 2009 were 6.2 and 5.9 per 100 000 person-years, respectively; while the equivalent incidence rates were at least threefold and sixfold higher: 23.4 and 35.9 per 100 000 person-years, respectively. This discrepancy between incidence and mortality rates was also at least threefold in men and women separately and across age groups. CONCLUSION: Mortality rates underestimated the incidence of liver cirrhosis by at least threefold between 1998 and 2009 and varied with differing definitions of disease. Mortality data should not be used exclusively as an indicator for the occurrence of liver cirrhosis in the population. Routinely collected healthcare data are available to measure occurrence of this disease. Careful consideration should be taken when selecting diagnostic codes for cirrhosis.

Adrenergic blockers and the risk for common solid cancers: a case-control study.

Laboratory studies have suggested that adrenergic blockers may inhibit the proliferation and migration of cancer cells, but epidemiological evidence of their effect on cancer incidence has proven inconsistent. We therefore conducted a case-control study using the Clinical Practice Research Datalink to assess the effect of adrenergic blockers on the incidence of prostate, lung, bowel and breast cancers. From among patients aged 18 years or older who contributed at least 2 years of prospectively gathered data between 1 January 1987 and 31 December 2012, we selected incident cases of relevant cancers and controls, frequency matched 10 : 1 by age. Logistic regression was used to adjust effect estimates for age, sex, smoking, alcohol use, and a number of potentially confounding comorbidities and coprescriptions. A total of 18 968 colorectal, 19 082 lung, 21 608 prostate and 29 109 breast cancers were identified. We found no evidence of a protective effect of adrenergic blockade in lung and prostate cancers and found a slightly increased risk for colorectal and breast cancers in users. This was largely explained by the effects of confounding in multivariate analyses, with final odds ratio estimates for lung, colorectal, breast and prostate cancers of 0.99 [95% confidence interval (0.96-1.04)], 1.14 (1.09-1.18), 1.10 (1.06-1.14), and 1.01 (0.98-1.05), respectively, for ß-blocker exposure, and final odds ratio estimates for lung, colorectal and breast cancer of 1.03 (0.97-1.09), 1.13 (1.07-1.20), and 1.08 (1.00-1.17), respectively, for α-blocker exposure. We found no evidence to suggest that adrenergic blocker use prevents common cancers. Indeed, we found a slightly increased risk for colorectal and breast cancers, which may reflect residual confounding.

What can be done to lessen morbidity associated with fetal alcohol spectrum disorders?

Fetal alcohol syndrome and its wider spectrum of presentation fetal alcohol spectrum disorders represent a range of disorders that are sometimes difficult to recognise as they may present in a way that overlaps with other conditions. This makes identification and recognition challenging, which increases the burden associated with the disorder. When considering the reduction in morbidity, both prevention of exposure to alcohol by the fetus and early identification of cases are required. This selective review seeks to highlight some of the complexities involved as well as highlighting the challenges. By considering populations particularly at risk to exploring the reality of alcohol risk it will seek to offer some solutions to begin the process of change.

Development and validation of risk prediction model for venous thromboembolism in postpartum women: multinational cohort study.

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.