The ESCAPS study: a feasibility randomized controlled trial of early electrical stimulation to the wrist extensors and flexors to prevent post-stroke complications of pain and contractures in the paretic arm.

OBJECTIVE: To establish feasibility of initiating electrical stimulation treatment of wrist extensors and flexors in patients early after stroke to prevent muscle contractures and pain. DESIGN: Feasibility randomized controlled trial with economic evaluation. SETTING: A specialist stroke unit in Nottinghamshire. SUBJECTS: A total of 40 patients recruited within 72 hours post-stroke with arm hemiparesis. INTERVENTIONS: Participants were randomized to receive usual care or usual care and electrical stimulation to wrist flexors and extensors for 30 minutes, twice a day, five days a week for three months. Initial treatment was delivered by an occupational therapist or physiotherapist who trained participants to self-manage subsequent treatments. MEASURES: Measures of feasibility included recruitment and attrition rates, completion of treatment, and successful data collection. Outcome data on wrist range of motion, pain, arm function, independence, quality of life, and resource use were measured at 3-, 6-, and 12-months post-randomization. RESULTS: A total of 40 participants (of 215 potentially eligible) were recruited in 15 months (20 men; mean age: 72 (SD: 13.0)). Half the participants lacked mental capacity and were recruited by consultee consent. Attrition at three-month follow-up was 12.5% (death (n = 2), end-of-life care (n = 2), and unable to contact (n = 1)). Compliance varied (mean: 65 (SD: 53)) and ranged from 10 to 166 treatments per patient (target dosage was 120). Data for a valid economic analysis can be adequately collected. CONCLUSION: Early initiation of electrical stimulation was acceptable and feasible. Data collection methods used were feasible and acceptable to participants. A large definitive study is needed to determine if electrical stimulation is efficacious and cost effective.

Long-term topical corticosteroid use and risk of skin cancer: a systematic review.

OBJECTIVE: The objective of this systematic review was to synthesize available research evidence to determine the risk of skin cancer in patients with long-term use of topical corticosteroids (TCS). INTRODUCTION: Topical corticosteroids are one of the most commonly prescribed medicines in dermatology and the mainstay of the treatment of atopic dermatitis and other skin conditions such as psoriasis. They are often required for months or years to control the disease and ultimately restore patients' quality of life. In some patients, TCS may have a local immunosuppressive effect and theoretically increase the risk of skin cancer, whilst on the other hand TCS may decrease the risk of skin cancer in patients where TCS are used to treat inflammatory skin disease. To date, no systematic review has been performed to collate evidence on the effect of long-term TCS use on the risk of skin cancer. INCLUSION CRITERIA: This review considered studies that included people of all ages, genders and ethnicities, including HIV and transplant participants or participants with genetic diseases (for example, Gorlin-Goltz syndrome) This review considered studies that evaluated long-term use of topical corticosteroids. "Long-term" was defined as using TCS more than once a week for a month or longer. The review included cohort, cross-sectional and case-control observational studies exploring the association between the stated intervention and outcomes. The primary outcome measures of interest were: non-melanoma skin cancer (keratinocyte carcinoma), cutaneous squamous cell carcinoma (cSSC), basal cell carcinoma (BCC) or melanoma skin cancer. Genital and oral skin cancers are considered to be slightly different so we did not include them in this review. METHODS: We performed a comprehensive search of MEDLINE, Embase and LILACS on November 9, 2017 to identify observational epidemiological studies assessing the association between long-term TCS use and skin cancer. We also searched EThOS at the British Library and three drug safety databases to identify unpublished work. The titles, abstracts and full text identified from the search were assessed independently by two authors against pre-specified inclusion/exclusion criteria. Methodological quality was not assessed as no articles were found which met the inclusion criteria. Data extraction was not possible as no articles were found which met the inclusion criteria. It was not possible to complete data synthesis as no articles were found which met the inclusion criteria. RESULTS: A total of 1703 potentially relevant studies were identified following a comprehensive electronic search. After abstract and title screening, 51 full texts were assessed for eligibility criteria. Of these, no study met the inclusion criteria. No additional records were identified from searching unpublished literature. CONCLUSIONS: We did not find any studies that could help us establish if long-term TCS use is associated with skin cancer. Future research using primary care databases might give a better understanding regarding long-term use of TCS and skin cancer.

'When it goes back to my normal I suppose': a qualitative study using online focus groups to explore perceptions of 'control' among people with eczema and parents of children with eczema in the UK.

OBJECTIVE: To inform the development of a core outcome set for eczema by engaging with people with eczema and parents of children with eczema to understand their experiences and understanding of the concept 'eczema control'. DESIGN: 37 participants took part in a total of six semi-structured online focus groups held in a typed chatroom with 5-7 participants per group. Three groups involved adults with eczema and three groups involved parents of children with eczema. Framework analysis was used for data analysis. SETTING: A community-based sample was recruited from across the UK via social media and email. PARTICIPANTS: 19 adults aged 17-61 years (15/19 female, 16/19 white) and 18 parents of children with eczema aged 9 months-17 years (9/18 female, 18/19 white). RESULTS: Four main themes were identified:(1) 'Commonalities and differences in the experiences of control': a reduction in symptoms such as itch and sleep loss characterised eczema control, but what level was acceptable differed across participants;(2) 'Eczema control goes beyond the skin': psychological factors, social factors, the constant scratching and the impact on everyday activities are a variety of ways an individual can be impacted;(3) 'Stepping up and down of treatment': participants' stepped-up treatment in response to loss of control, but several factors complicated this behaviour. Control needed to be maintained after stepped-up treatment ended to be acceptable; and (4) 'How to measure control': self-report was generally preferred to allow frequent measurements and to capture unobservable features. Although most thought their eczema needed to be measured frequently, many also felt that this was not always realistic or desirable. CONCLUSIONS: 'Eczema control' is a complex experience for people with eczema and parents of children with the condition. These experiences could have important implications on how long-term control should be measured in eczema clinical trials and clinical practice.

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.

Long-term topical corticosteroid use and risk of skin cancer: a systematic review protocol.

REVIEW QUESTION/OBJECTIVE: The objective of this systematic review is to synthesize the best available research evidence to determine the risk of skin cancer in patients on long-term use of topical corticosteroids. Specifically the review question is: In people using long-term (regular use over one month) topical corticosteroids, what is the risk of developing skin cancer (clinically or histologically confirmed basal cell carcinoma, squamous cell carcinoma or melanoma)?

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.

How Often Do Comparative Randomised Controlled Trials in the Field of Eczema Fail to Directly Compare the Treatments Being Tested?

The objective of the study was to identify all parallel design randomised controlled trials (RCTs) comparing treatments for eczema in recent dermatology literature that have failed to report a between-group analysis. The GREAT database (www.greatdatabase.org.uk) was searched to identify parallel group RCTs comparing two or more interventions published in the English language in the last decade, 2004 to 2013. The primary outcome was the number of studies that had not reported a between-group analysis for any of the outcomes. Where possible we re-analysed the data to determine whether a between-group analysis would have given a different conclusion to that reported. Out of a total of 304 RCTs in the study period, 173 (56.9%) met the inclusion criteria. Of the 173 eligible studies, 12 (6.9%) had not conducted a between-group analysis for any of the reported outcomes. There was no clear improvement over time. Five of the eight studies that were re-analysed yielded non-significant between-group differences yet reported significant within-group comparisons. All but one of the 12 studies implied that the experimental intervention was successful despite not undertaking any between-group comparisons. Although the proportion of all RCTs that fail to report an appropriate between-group analysis is small, the fact that any scientist who purports to compare one treatment against another then chooses to omit the key comparison statistic is worrying.

Causes of death in people with liver cirrhosis in England compared with the general population: a population-based cohort study.

OBJECTIVES: There is a need for unbiased estimates of cause-specific mortality by etiology in patients with liver cirrhosis. The aim of this study is to use nationwide linked electronic routine healthcare data from primary and secondary care alongside the national death registry data to report such estimates. METHODS: We identified from the linked Clinical Practice Research Datalink (CPRD) and English Hospital Episode Statistics adults with an incident diagnosis of liver cirrhosis linked to the Office for National Statistics between 1998 and 2009. Age-matched controls from the CPRD general population were selected. We calculated the cumulative incidence (adjusting for competing risks) and excess risk of death by 5 years from diagnosis for different causes of death, stratified by etiology and stage of disease. RESULTS: Five thousand one hundred and eighteen patients with cirrhosis were matched to 152,903 controls. Among compensated patients, the 5-year excess risk of liver-related death was higher than that of any other cause of death for all patients, except those of unspecified etiology. For example, those of alcohol etiology had 30.8% excess risk of liver-related death (95% confidence interval (CI): 27.9%, 33.1%) compared with 9.9% excess risk of non-liver-related death. However, patients of unspecified etiology had a higher excess risk of non-liver-related compared with liver-related death (10.7% vs. 6.7%). This was due to a high excess risk of non-liver neoplasm death (7.7%, 95% CI: 5.9%, 9.5%). All decompensated patients had a higher excess of liver-related mortality than any other cause. CONCLUSIONS: In order to reduce associated mortality among people with liver cirrhosis, patients' care pathways need to be tailored depending on the etiology and stage of the disease.

Diagnosis of liver cirrhosis in England, a cohort study, 1998-2009: a comparison with cancer.

OBJECTIVES: There is no routine registration of the occurrence of newly diagnosed cases of cirrhosis in the United Kingdom. This study seeks to determine precise estimates and trends of the incidence of cirrhosis in England, and directly compare these figures with those for the 20 most commonly diagnosed cancers in the United Kingdom. METHODS: We used the Clinical Practice Research Datalink and linked English Hospital Episode Statistics to perform a population-based cohort study. Adult incident cases with a diagnosis of cirrhosis between January 1998 and December 2009 were identified. We described trends in incidence by sex and etiology. We performed a direct standardization to estimate the number of people being newly diagnosed with cirrhosis in 2009, and calculated the change in incidence between 1998 and 2009. RESULTS: A total of 5,118 incident cases of cirrhosis were identified, 57.9% were male. Over the 12-year period, crude incidence increased by 50.6%. Incidence increased for both men and women and all etiology types. We estimated approximately 17,000 people were newly diagnosed with cirrhosis in 2009 in the United Kingdom, greater than that of the fifth most common cancer non-Hodgkin's lymphoma. The percentage change in incidence of cirrhosis between 1998 and 2009 for both men (52.4%) and women (38.3%) was greater than that seen for the top four most commonly diagnosed cancers in the United Kingdom (breast, lung, bowel, and prostate). CONCLUSIONS: The occurrence of cirrhosis increased more than that of the top four cancers during 1998 to 2009 in England. Strategies to monitor and reduce the incidence of this disease are urgently needed.

1 and 5 year survival estimates for people with cirrhosis of the liver in England, 1998-2009: a large population study.

BACKGROUND & AIMS: Large, population-based studies that have included the full spectrum of cirrhosis estimating survival, taking into account time-at-risk are lacking. We aimed to report 1- and 5-year average survival rates for people with cirrhosis to be used in a clinical and healthcare policy setting. METHODS: We used the Clinical Practice Research Datalink and linked English Hospital Episode Statistics to identify adult cases of cirrhosis from January 1998 to December 2009. We estimated 1- and 5-year survival according to whether time-at-risk was ambulatory or followed an emergency hospital admission related to liver disease, stratified by age, sex, and aetiology to be used in a clinical setting. We used a multivariate Cox-proportional hazards model with a time-varying variable, adjusted for Baveno IV stage of cirrhosis at diagnosis, age, aetiology, and sex. RESULTS: We identified 5118 incident cases. Average survival probabilities at 1- and 5-years were 0.84 (95% CI 0.83-0.86) and 0.66 (95% CI 0.63-0.68) for the ambulatory group and 0.55 (95% CI 0.53-0.57) and 0.31 (95% CI 0.29-0.33) following hospitalisation, respectively. A hospital admission at diagnosis or subsequently for liver disease substantially impaired prognosis independent of stage of cirrhosis (HR=2.78, 95% CI 2.53, 3.06). CONCLUSIONS: Emergency hospitalisation for liver disease heralds a downturn in a patient's outlook independent of their stage of cirrhosis. Our results provide population-based clinically translatable estimates of prognosis for the purposes of healthcare delivery and planning and communication to patients.

Nature of auditory processing disorder in children.

OBJECTIVE: We tested the specific hypothesis that the presentation of auditory processing disorder (APD) is related to a sensory processing deficit. METHODS: Randomly chosen, 6- to 11-year-old children with normal hearing (N = 1469) were tested in schools in 4 regional centers across the United Kingdom. Caregivers completed questionnaires regarding their participating children's listening and communication skills. Children completed a battery of audiometric, auditory processing (AP), speech-in-noise, cognitive (IQ, memory, language, and literacy), and attention (auditory and visual) tests. AP measures separated the sensory and nonsensory contributions to spectral and temporal perception. RESULTS: AP improved with age. Poor-for-age AP was significantly related to poor cognitive, communication, and speech-in-noise performance (P < .001). However, sensory elements of perception were only weakly related to those performance measures (r < 0.1), and correlations between auditory perception and cognitive scores were generally low (r = 0.1-0.3). Multivariate regression analysis showed that response variability in the AP tests, reflecting attention, and cognitive scores were the best predictors of listening, communication, and speech-in-noise skills. CONCLUSIONS: Presenting symptoms of APD were largely unrelated to auditory sensory processing. Response variability and cognitive performance were the best predictors of poor communication and listening. We suggest that APD is primarily an attention problem and that clinical diagnosis and management, as well as further research, should be based on that premise.

The natural history of hepatitis C with severe hepatic fibrosis.

BACKGROUND/AIMS: To examine the morbidity and mortality of patients with severe fibrosis secondary to HCV infection, within a population unbiased by tertiary referral. METHODS: One hundred and fifty HCV infected patients were identified from the Trent HCV study with a liver biopsy taken before 2002 demonstrating severe fibrosis (Ishak stage > or =4). Follow-up data were extracted from the database and hospital records. RESULTS: Median follow-up was 51 months. Of the 131 patients with no prior history of decompensation, 33 (25%) died (n=25) or were transplanted (n=8), after a median interval of 42 months. The probability of survival without liver transplantation was 97%, 88%, and 78% at 1, 3, and 5 years, respectively. Hepatocellular carcinoma and/or decompensation was diagnosed in 33 (25%), after a median interval of 41 months. In multivariate analysis, combination antiviral therapy was associated with improved survival. Prognosis was not affected by the Ishak stage at index biopsy. There was a worse prognosis for the 19 patients with previous decompensation; 17 (89%) having either died (n=15) or been transplanted (n=2). CONCLUSIONS: This study demonstrates that severe liver fibrosis (Ishak stage > or = 4) secondary to hepatitis C is associated with a poor prognosis, that may be improved following combination antiviral treatment.

Children born weighing less than 1701 g: visual and cognitive outcomes at 11-14 years.

BACKGROUND AND OBJECTIVE: Few studies of low birthweight children have explored the relationship between later visual morbidity and neuropsychological function. This study evaluated these outcomes using a geographically defined cohort. METHODS: Prospective study of retinopathy of prematurity (ROP) in infants born weighing <1701 g, undertaken in 1985-7. 254 of the survivors consented to ophthalmic examination at 10-13 years. Four children were severely disabled and could not complete the tests. 198 of the remaining agreed to neuropsychological assessment at 11-14 years (British Ability Scales II (BAS), Movement Assessment Battery (ABC), Neale Analysis of Reading Ability). RESULTS: At 10-13 years, 99/198 children had an adverse ophthalmic outcome (AOO) (reduced acuity n=48, myopia n=40, strabismus n=36, colour defect n=2, field defect n=1). There were no significant differences between children with AOO and those with a normal ophthalmic outcome with regard to sex, gestation, birth weight, neonatal cranial scan appearances and social class. 106/198 had ROP; 98 had mild ROP with no increased risk of AOO in later childhood. All eight children with severe ROP had an AOO in later childhood. Children with an AOO performed worse on the BAS, ABC and reading ability tests. CONCLUSIONS: At age 10-13, 50% of children born <1701 g have an AOO. These children are not simply those with earlier gestations, lower birth weight or ROP. Children with AOO have a worse neuropsychological outcome. The next step is to determine whether there are visual interventions which can improve ophthalmic outcome and whether a better neuropsychological outcome follows.

The reliability of balance, mobility and self-care measures in a population of adults with a learning disability known to a physiotherapy service.

OBJECTIVE: To estimate the reliability of three measures of balance, mobility and activity for use in clinical and research physiotherapy, with adults with a learning disability. DESIGN: Prospective study to investigate test-retest and inter-rater reliability. SETTING: Participants' homes and day centres. MEASURES: The Berg Balance Scale (BBS), the Rivermead Mobility Index (RMI) and the Barthel Activities of Daily Living Index (BI). PARTICIPANTS: Of the 181 adults known to the Nottingham Community Physiotherapy Service for Adults with Learning Disabilities, 64 with a known Rivermead Mobility score of less than three were excluded. Of 117 randomized, a further 21 were found to fail this criteria, 27 had acute medical, social or behavioural problems, 22 were unable to participate or refused: therefore 47 entered the study. METHODS: Participants were visited in their own homes by two researchers on two occasions, one week apart and rated independently by each rater. Agreement was assessed with the kappa statistic (kappa) and percentage agreement for each item in each scale, and described using standard classification. Intraclass correlation coefficients for inter-rater and test-retest total scores and average differences of total scores, their standard deviations and limits of agreement, were calculated. RESULTS: For inter-rater observations, the Barthel Index and the Rivermead Mobility Index had almost perfect agreement (kappa = 0.86-1.00 and 0.89-1.00 respectively), with the Berg Balance Scale having substantial to almost perfect agreement (kappa = 0.74-1.00). For test-retest comparisons, both the Barthel Index and the Rivermead Mobility Index demonstrated moderate to almost perfect agreement (kappa = 0.57-1.00 and 0.45-1.00 respectively). Kappa scores for the Berg Balance Scale varied from low to almost perfect agreement (kappa = 0.37-1.00). CONCLUSIONS: The Berg Balance Scale, Rivermead Mobility Index and Barthel Activities of Daily Living Index are all reliable clinical and research tools for physiotherapists working with adults with learning disabilities.

Strabismus in children of birth weight less than 1701 g.

OBJECTIVE: To prospectively study infants of birth weight less than 1701 g in the East Midlands of England in the mid 1980s at 10 to 12 years of age to determine the incidence and risk factors for strabismus in children born preterm. METHODS: Low-birth-weight children (n = 572) who had been examined during the neonatal period were invited for a follow-up visit at age 10 to 12 years; 169 eleven-year-old schoolchildren born at full term were also recruited (the school cohort). RESULTS: Of the original 572 children, 293 consented to further examination. There was no significant difference between children who were examined and those who were not in terms of birth weight, gestational age, retinopathy of prematurity, and cranial ultrasound abnormalities. Compared with the school cohort (n = 5 [3.0%]; 95% confidence interval, 1.0%-9.1%), the low-birth-weight cohort had a significant increase in the prevalence of strabismus (n = 59 [20.1%]; 95% confidence interval, 15.9%-25.0%; P<.001). Compared with published data, there was a relative increase in the occurrence of exotropia in the low-birth-weight study cohort. Multivariate analysis, by backward logistic regression, indicated that retinopathy of prematurity, birth weight, cerebral palsy, anisometropia, and refractive error were all independently associated with strabismus (P<.05). CONCLUSIONS: The results of this study confirm the increased prevalence of strabismus in a low-birth-weight population. This study also provides more detailed information on risk factors and strabismus types.

Long-term ophthalmic outcome of low birth weight children with and without retinopathy of prematurity.

OBJECTIVE: A prospective study of retinopathy of prematurity (ROP) of 505 infants who weighed <1701 g at birth was undertaken in the mid-1980s. This cohort was traced at 10 to 12 years of age to determine how low birth weight alone and ROP might influence their ophthalmic outcome. METHODS: Outcome measures were 1) visual functions (visual acuity, contrast sensitivity, stereoacuity, perimetry, and color vision), 2) presence of strabismus, and 3), measurements of eye size and the dimensions of its components including refractive state. A total of 169 11-year-olds who were born at term were recruited as control subjects and examined under the same conditions. RESULTS: A total of 448 of the original cohort were traced, and 254 consented to a further examination. Compared with the control group, the follow-up cohort differed significantly with reduced visual functions and increased incidence of both myopia and strabismus. Compared with published data, eye size was smaller in the low birth weight cohort. To summarize the ophthalmic data, we defined ophthalmic morbidity as visual acuity below 0.0 log units or the presence of strabismus, myopia, color vision defect, or visual field defect. The rate of ophthalmic morbidity was 50.8% (n = 129/254) in the study cohort compared with 19.5% (n = 33/169) in the control group. The highest rate of ophthalmic morbidity was associated with severe ROP (stages 3/4), although those with no ROP had a less favorable outcome than the control group. CONCLUSION: This study shows that low birth weight children are at increased risk of visual impairments compared with children who are born at full term. Visual impairments are associated with low birth weight per se and severe ROP. Regressed mild ROP is only a risk factor for strabismus. The functional significance of these deficits is largely unknown.