Distributional inference

The making of statistical inferences in distributional form is conceptionally complicated because the epistemic 'probabilities' assigned are mixtures of fact and fiction. In this respect they are essentially different from 'physical' or 'frequency-theoretic' probabilities. The distributional form is so attractive and useful, however, that it should be pursued. Our approach is In line with Walds theory of statistical decision functions and with Lehmann's books about hypothesis testing and point estimation: loss functions are defined, risk functions are studied, unbiasedness and equivariance restrictions are made, etc. A central theme is that the loss function should be 'proper'. This fundamental concept has been explored by meteorologists, psychometrists, Bayesian statisticians, and others. The paper should be regarded as an attempt to reconcile various schools of statisticians. By accepting what we regard 88 good and useful in the various approaches we are trying to develop a nondogmatic approach

In vitro comparison of antiviral drugs against feline herpesvirus 1

BACKGROUND: Feline herpesvirus 1 (FHV-1) is a common cause of respiratory and ocular disease in cats. Especially in young kittens that have not yet reached the age of vaccination, but already lost maternal immunity, severe disease may occur. Therefore, there is a need for an effective antiviral treatment. In the present study, the efficacy of six antiviral drugs, i.e. acyclovir, ganciclovir, cidofovir, foscarnet, adefovir and 9-(2-phosphonylmethoxyethyl)-2, 6-diaminopurine (PMEDAP), against FHV-1 was compared in Crandell-Rees feline kidney (CRFK) cells using reduction in plaque number and plaque size as parameters. RESULTS: The capacity to reduce the number of plaques was most pronounced for ganciclovir, PMEDAP and cidofovir. IC(50 (NUMBER) )values were 3.2 μg/ml (12.5 μM), 4.8 μg/ml (14.3 μM) and 6 μg/ml (21.5 μM), respectively. Adefovir and foscarnet were intermediately efficient with an IC(50 (NUMBER) )of 20 μg/ml (73.2 μM) and 27 μg/ml (140.6 μM), respectively. Acyclovir was least efficient (IC(50 (NUMBER) )of 56 μg/ml or 248.7 μM). All antiviral drugs were able to significantly reduce plaque size when compared with the untreated control. As observed for the reduction in plaque number, ganciclovir, PMEDAP and cidofovir were most potent in reducing plaque size. IC(50 (SIZE) )values were 0.4 μg/ml (1.7 μM), 0.9 μg/ml (2.7 μM) and 0.2 μg/ml (0.7 μM), respectively. Adefovir and foscarnet were intermediately potent, with an IC(50 (SIZE) )of 4 μg/ml (14.6 μM) and 7 μg/ml (36.4 μM), respectively. Acyclovir was least potent (IC(50 (SIZE) )of 15 μg/ml or 66.6 μM). The results demonstrate that the IC(50 (SIZE) )values were notably lower than the IC(50 (NUMBER) )values. The most remarkable effect was observed for cidofovir and ganciclovir. None of the products were toxic for CRFK cells at antiviral concentrations. CONCLUSION: In conclusion, measuring reduction in plaque number and plaque size are two valuable and complementary means of assessing the efficacy of an antiviral drug. By using these parameters for six selected antiviral drugs, we found that ganciclovir, PMEDAP, and cidofovir are the most potent inhibitors of FHV-1 replication in CRFK cells. Therefore, they may be valuable candidates for the treatment of FHV-1 infection in cats

In vitro susceptibility of six isolates of equine herpesvirus 1 to acyclovir, ganciclovir, cidofovir, adefovir, PMEDAP and foscarnet

International audienc

Probabilistic linkage without personal information successfully linked national clinical datasets: Linkage of national clinical datasets without patient identifiers using probabilistic methods.

BACKGROUND: Probabilistic linkage can link patients from different clinical databases without the need for personal information. If accurate linkage can be achieved, it would accelerate the use of linked datasets to address important clinical and public health questions. OBJECTIVE: We developed a step-by-step process for probabilistic linkage of national clinical and administrative datasets without personal information, and validated it against deterministic linkage using patient identifiers. STUDY DESIGN AND SETTING: We used electronic health records from the National Bowel Cancer Audit (NBOCA) and Hospital Episode Statistics (HES) databases for 10,566 bowel cancer patients undergoing emergency surgery in the English National Health Service. RESULTS: Probabilistic linkage linked 81.4% of NBOCA records to HES, versus 82.8% using deterministic linkage. No systematic differences were seen between patients that were and were not linked, and regression models for mortality and length of hospital stay according to patient and tumour characteristics were not sensitive to the linkage approach. CONCLUSION: Probabilistic linkage was successful in linking national clinical and administrative datasets for patients undergoing a major surgical procedure. It allows analysts outside highly secure data environments to undertake linkage while minimising costs and delays, protecting data security, and maintaining linkage quality

Associations between pre-pregnancy psychosocial risk factors and infant outcomes: a population-based cohort study in England

BACKGROUND: Existing studies evaluating the association between maternal risk factors and specific infant outcomes such as birthweight, injury admissions, and mortality have mostly focused on single risk factors. We aimed to identify routinely recorded psychosocial characteristics of pregnant women most at risk of adverse infant outcomes to inform targeting of early intervention. METHODS: We created a cohort using administrative hospital data (Hospital Episode Statistics) for all births to mothers aged 15-44 years in England, UK, who gave birth on or after April 1, 2010, and who were discharged before or on March 31, 2015. We used generalised linear models to evaluate associations between psychosocial risk factors recorded in hospital records in the 2 years before the 20th week of pregnancy (ie, teenage motherhood, deprivation, pre-pregnancy hospital admissions for mental health or behavioural conditions, and pre-pregnancy hospital admissions for adversity, including drug or alcohol abuse, violence, and self-harm) and infant outcomes (ie, birthweight, unplanned admission for injury, or death from any cause, within 12 months from postnatal discharge). FINDINGS: Of 2 520 501 births initially assessed, 2 137 103 were eligible and were included in the birth outcome analysis. Among the eligible births, 93 279 (4·4%) were births to teenage mothers (age <20 years), 168 186 (7·9%) were births to previous teenage mothers, 51 312 (2·4%) were births to mothers who had a history of hospital admissions for mental health or behavioural conditions, 58 107 (2·7%) were births to mothers who had a history of hospital admissions for adversity, and 580 631 (27·2%) were births to mothers living in areas of high deprivation. 1 377 706 (64·5%) of births were to mothers with none of the above risk factors. Infants born to mothers with any of these risk factors had poorer outcomes than those born to mothers without these risk factors. Those born to mothers with a history of mental health or behavioural conditions were 124 g lighter (95% CI 114-134 g) than those born to mothers without these conditions. For teenage mothers compared with older mothers, 3·6% (95% CI 3·3-3·9%) more infants had an unplanned admission for injury, and there were 10·2 (95% CI 7·5-12·9) more deaths per 10 000 infants. INTERPRETATION: Health-care services should respond proactively to pre-pregnancy psychosocial risk factors. Our study demonstrates a need for effective interventions before, during, and after pregnancy to reduce the downstream burden on health services and prevent long-term adverse effects for children. FUNDING: Wellcome Trust

Identifying patients at risk of emergency admission for colorectal cancer.

BACKGROUND: Patients whose colorectal cancer is treated after an emergency admission tend to have late-stage cancer and a poor prognosis. We identified risk factors for an emergency admission by linking data from the National Bowel Cancer Audit (NBCA) and the English Hospital Episode Statistics (HES), an administrative database of all admissions to English National Health Service hospitals, which includes data on mode of admission. METHODS: We identified all adults included in the NBCA with a primary diagnosis of bowel cancer, excluding cancer of the appendix, between August 2007 and July 2011 whose record could be linked to HES. Multivariable logistic regression was used to estimate adjusted odds ratios (OR) for an emergency admission for colorectal cancer. All risk factors were adjusted for cancer site and calendar year. RESULTS: 97,909 adults were identified with a primary diagnosis of bowel cancer and 82,777 patients could be linked to HES. Patients who were older, female, of a non-white ethnic background, and more socioeconomically deprived, and those with dementia or cardiac, neurologic and liver disease had an increased risk of presenting as an emergency admission. The strongest risk factors were age (90 compared with 70 years: OR 2.99, 95% CI 2.84 to 3.15), dementia (OR 2.46, 2.18 to 2.79), and liver disease (OR 1.87, 1.69 to 2.08). CONCLUSIONS: Our study identifies risk factors that may impair health-seeking behaviour and access to healthcare. An earlier recognition of symptoms in patients with these risk factors may contribute to better outcomes

Model for risk adjustment of postoperative mortality in patients with colorectal cancer.

BACKGROUND: A model was developed for risk adjustment of postoperative mortality in patients with colorectal cancer in order to make fair comparisons between healthcare providers. Previous models were derived in relatively small studies with the use of suboptimal modelling techniques. METHODS: Data from adults included in a national study of major surgery for colorectal cancer were used to develop and validate a logistic regression model for 90-day mortality. The main risk factors were identified from a review of the literature. The association with age was modelled as a curved continuous relationship. Bootstrap resampling was used to select interactions between risk factors. RESULTS: A model based on data from 62 314 adults was developed that was well calibrated (absolute differences between observed and predicted mortality always smaller than 0·75 per cent in deciles of predicted risk). It discriminated well between low- and high-risk patients (C-index 0·800, 95 per cent c.i. 0·793 to 0·807). An interaction between age and metastatic disease was included as metastatic disease was found to increase postoperative risk in young patients aged 50 years (odds ratio 3·53, 95 per cent c.i. 2·66 to 4·67) far more than in elderly patients aged 80 years (odds ratio 1·48, 1·32 to 1·66). CONCLUSION: Use of this model, estimated in the largest number of patients with colorectal cancer to date, is recommended when comparing postoperative mortality of major colorectal cancer surgery between hospitals, clinical teams or individual surgeons