Trends in reported sun bed use, sunburn, and sun care knowledge and attitudes in a U.K. region: results of a survey of the Northern Ireland population.

BACKGROUND: Sunburn and sun bed use increase risk of malignant melanoma, the incidence of which continues to rise. OBJECTIVES: To document trends in reported sun bed use, sunburn, and sun care knowledge and attitudes in a U.K. region where there have been 20 years of sun-related health promotion campaigns. METHODS: In 2000, 2004 and 2008, a 'care in the sun' module was included in the Northern Ireland (NI) Omnibus survey. Each year 2200 subjects aged 16 years and over were randomly selected and invited to complete a sun-related questionnaire. Proportions of respondents were analysed by demographic and socioeconomic factors, with differences tested using z-tests and the χ(2) -squared test. RESULTS: In total, 3623 persons responded (response rate 50-59%). Skin cancer knowledge in 2008 was high at 97%. Skin type reporting was inaccurate and since 2000 has become weighted towards the darker Fitzpatrick skin types IV and V (χ(2) = 21·5, P = 0·006). Reported sunburn rose over the 8-year period to 60% in 2008, with 39% of those aged 16-24 years reporting sunburn at least once in the previous year. Twenty per cent reported sun bed use in 2008, a fall from 28% in 2004 (P = 0·01), with greater reported use among those aged 16-24 years (24%) and among women (31% vs. 9% men, P < 0·001). Tanning was reported to make respondents feel healthier (42%) and more attractive (47%), with these attitudes more likely among young women. CONCLUSIONS: Skin cancer and sun care knowledge is good among the NI population but reported behaviours of sun bed use and sunburn pose risks for further rises in skin cancer. Barriers for future sun care campaigns to address include poorer sun care knowledge among men, poor skin type awareness, and women's attitudes regarding the health and attractiveness of tanning. Sun bed use, although high, has fallen, possibly in response to recent campaigns.

Public at risk: a survey of sunbed parlour operating practices in Northern Ireland.

BACKGROUND: The International Agency for Research on Cancer has identified artificial ultraviolet (UV) radiation as a class 1 carcinogen. The contribution of sunbeds to malignant melanoma has been estimated at 100 deaths per year in the U.K. The sunbed industry is growing and claims self-regulation. OBJECTIVES: To explore the standards of operation and client protection for sunbed users. METHODS: An observational study of tanning parlour practices was conducted by Environmental Health Practitioners who made unannounced visits to the majority of known commercial tanning parlours in Northern Ireland (population 1.77 million) during July/August 2007. Descriptive statistics were produced and comparisons between groups were made using chi(2) analysis. RESULTS: All 332 premises visited cooperated with the survey. The UV type in machines was unknown in 71.2% of premises while 15.6% reported using type 4, high-dose UV devices; 36.2% of premises did not regularly service sunbeds or were unsure. Unsupervised use of sunbeds was reported in 8.6% of parlours and 3.4% provided a home sunbed service. Eye protection was available in 97.6% of premises but 34.6% charged for the service and only 79.6% sanitized these between use. Of the responders 15.9% were members of the Sunbed Association. These were more likely to have maintenance records and operating manuals but were also more likely to provide a home sunbed service. CONCLUSIONS: This study highlights the need for improved standards of regulation of the sunbed industry to protect clients from excessive and dangerous levels of UV radiation in a population where the numbers of melanomas continue to rise.

The clinical effectiveness and cost-effectiveness of enzyme replacement therapy for Gaucher's disease: a systematic review.

OBJECTIVES: The aim of this review is to determine the clinical effectiveness and cost-effectiveness of enzyme replacement therapy (ERT) in the treatment of symptomatic Gaucher's disease. DATA SOURCES: Major electronic databases were searched from their inception to August 2003; and updated from January 2003 to July/August 2004. REVIEW METHODS: Databases were searched for studies that met the criteria and selected data were extracted and evaluated. Studies were assessed for their relevance to the UK context and the review objective. The bibliographic databases were also searched to identify existing cost studies, economic evaluations and models. A Markov decision model was constructed based on patients moving between states defined by the modified Severity Score Index (SSI). Most of the parameters were derived from the published literature. ERT was assumed to restore patients to full health in the base case. RESULTS: Sixty-three studies were included, all suggestive of benefit with ERT. However, the way in which the effects translate into patient well-being and survival or the need for services and resources has not been reliably estimated. Quality of life improvements with ERT have been reported. Nonetheless, studies based on the Short Form 36 (SF-36) indicate that patients treated with ERT continue to have reduced health-related quality of life (HRQoL) compared with the general population. No study attached utility values to quality of life measures for ERT-treated patients. Thirty-one studies relevant to the natural history of the disease were found. Sixteen looked at multiple clinical characteristics of a cohort of patients with type I Gaucher's disease. There was considerable within-study and between-study heterogeneity, but all showed that Gaucher's disease was a progressive condition. Some suggested that the disease may become more indolent in adulthood; however, studies were discrepant on this point. Most disease is diagnosed in adulthood, although about one-quarter presented in childhood, these patients having the most severe symptoms and greatest rate of progression. Modelling of natural history was undertaken using the five papers that reported the SSI for each patient, along with patient-level data on age, age at diagnosis, splenectomy status and genotype, to address the question of whether disease stabilises in adulthood and the degree of correlation between phenotype and genotype. Analysis of the available data suggested that disease progression is likely to slow markedly in adulthood and that genotype is a useful predictor of clinical expression of the disease. Five studies looked at quality of life. Data on this topic were also obtained from the registries. The evidence suggests that the vast majority of the clinical characteristics of type I Gaucher's disease have little impact on subjective HRQoL and that therefore for the majority of people with type I Gaucher's disease this may not be a severe condition. Bone and skeletal symptoms contribute most to the morbidity of the disease and can lead to severe pain and immobility. The mean cost per patient treated was approximately pounds sterling 86,000 per annum in England and Wales. The cost per patient varied considerably by dose. Four existing economic evaluations were found, all of which calculated a very high cost per quality-adjusted life-year (QALY). Using the Markov decision model, ERT was assumed to restore patients to full health in the base case. The estimated incremental cost per QALY [incremental cost-effectiveness ratio (ICER)] in the base case ranged from pounds sterling 380,000 to pounds sterling 476,000 per QALY, depending on genotype. Univariate sensitivity analyses examined ERT not restoring full health, more severe disease progression in the untreated cohort, and only treating the most severely affected patients. These produced ICERs of approximately pounds sterling 1.4 million, pounds sterling 296,000 and pounds sterling 275,000 per QALY, respectively. The base-case unit cost of the drug is pounds sterling 2.975. The unit cost would have had to be reduced ten-fold, to pounds sterling 0.30, to obtain an ICER of pounds sterling 30,000 per QALY. At a unit cost of pounds sterling 1 the ICER would be pounds sterling 120,000 per QALY. CONCLUSIONS: Although ERT for treating the 'average' Gaucher's disease patient exceeds the normal upper threshold for cost-effectiveness seen in NHS policy decisions by over ten-fold, some argue that since orphan drug legislation encouraged the manufacture of Cerezyme, and Gaucher's disease can be defined as an orphan disease, the NHS has little option but to provide it, despite its great expense. More information is required before the generalisability of the findings can be determined. Although data from the UK have been used wherever possible, these were very thin indeed. Nonetheless, even large errors in estimates of the distribution of genotype, genotype--phenotype associations, effectiveness and numbers of patients will not reduce the ICER to anywhere near the upper level of treatments usually considered cost-effective. Further research could help to clarify the many uncertainties that exist. However, although doing so will be of clinical interest, it is questionable whether, within the current pricing environment, such research would have any substantive impact on policy decisions. It is highly improbable that, whatever the findings of such research, the ICER could be brought down by the orders of magnitude required to make ERT an efficient use of health service resources. (The possible exception to this would be investigating the most efficient alternative treatment strategies for using ERT in a paediatric population only.) Moreover, if under equity considerations for orphan diseases the NHS feels it is important to provide this drug, regardless of its cost-effectiveness, then refining the precision of the ICER estimate also becomes superfluous.

Mutation analysis in Irish families with glomuvenous malformations.

BACKGROUND: Glomuvenous malformations (GVMs) are rare bluish lesions that can affect the skin and mucosal surfaces. They represent defects in vasculogenesis. Lesions can occur sporadically or in an autosomal dominant mode of inheritance. Recent studies have shown that mutations in the glomulin gene (GLMN) on chromosome 1p21-22 are responsible for familial GVMs. OBJECTIVES: To search for mutations in GLMN in Irish families with GVMs. METHODS: We identified four Irish families with GVMs and confirmed linkage to chromosome 1p21-22 in these cases. We sequenced the glomulin gene in all affected and unaffected members of the families. Results Linkage analysis showed that affected individuals from the families shared a common haplotype. Mutation analysis revealed a delAAGAA mutation in exon 3 of the glomulin gene in all four families with GVMs. CONCLUSIONS: We confirm that mutations in the glomulin gene are responsible for GVMs and suggest a founder Irish mutation in the glomulin gene in four Irish families.

Miliary neonatal hemangiomatosis with fulminant heart failure and cardiac septal hypertrophy in two infants.

Miliary neonatal hemangiomatosis is a rare, life-threatening condition associated with cutaneous and multiorgan involvement. We report two infants with this condition who had fulminant cardiac failure and cardiac septal hypertrophy. The first was a 5-day-old boy who presented with increasing numbers of cutaneous hemangiomata associated with worsening cardiac failure. Magnetic resonance imaging (MRI) showed extensive hepatic hemangioma. Despite treatment with systemic corticosteroids and subcutaneous interferon alfa-2b his disease progressed. Hepatic artery embolization was unsuccessful. The infant died of congestive cardiac failure at 6 weeks of age. Postmortem examination showed a massively enlarged cardiac interventricular septum and biventricular hypertrophy. The second patient was a 1-week-old girl who also had cutaneous hemangioma and cardiac decompensation. MRI showed extensive intrahepatic involvement. She was treated early with corticosteroids and interferon alpha, which resulted in involution of the cutaneous and hepatic lesions. Cardiac septal hypertrophy did not persist at late follow-up, and the association of miliary neonatal hemangiomatosis and cardiac septal hypertrophy has not yet been established.

Bayesian methods for design and analysis of cost-effectiveness trials in the evaluation of health care technologies.

We review the development of Bayesian statistical methods for the design and analysis of randomized controlled trials in the assessment of the cost-effectiveness of health care technologies. We place particular emphasis on the benefits of the Bayesian approach; the implications of skew cost data; the need to model the data appropriately to generate efficient and robust inferences instead of relying on distribution-free methods; the importance of making full use of quantitative and structural prior information to produce realistic inferences; and issues in the determination of sample size. Several new examples are presented to illustrate the methods. We conclude with a discussion of the key areas for future research.

Bayesian assessment of sample size for clinical trials of cost-effectiveness.

The authors present an analysis of the choice of sample sizes for demonstrating cost-effectiveness of a new treatment or procedure, when data on both cost and efficacy will be collected in a clinical trial. The Bayesian approach to statistics is employed, as well as a novel Bayesian criterion that provides insight into the sample size problem and offers a very flexible formulation.

A framework for cost-effectiveness analysis from clinical trial data.

We present a general Bayesian framework for cost-effectiveness analysis (CEA) from clinical trial data. This framework allows for very flexible modelling of both cost and efficacy related trial data. A common CEA technique is established for this wide class of models through linking mean efficacy and mean cost to the parameters of any given model. Examples are given in which efficacy may be measured as a continuous, binary, ordinal or time-to-event outcome, and in which costs are modelled as distributed normally, log-normally, as a mixture or non-parametrically. A case study is presented, illustrating the methodology and illuminating the role of prior information.

Bayesian cost-effectiveness analysis from clinical trial data.

A key tool for assessing the relative cost-effectiveness of two treatments in health economics is the incremental C/E acceptability curve. We present Bayesian computations for this curve in the case where data on both costs and efficacy are available from a clinical trial. Analysis is given under various formulations of prior information. A case study is analysed in which reasonable prior information is shown to strengthen substantially the posterior inference, leading to a more conclusive assessment of cost-effectiveness. Calculations can be performed using readily available Bayesian software.

Inference for the cost-effectiveness acceptability curve and cost-effectiveness ratio.

The aim of this article is to consider Bayesian and frequentist inference methods for measures of incremental cost effectiveness in data obtained via a clinical trial. The most useful measure is the cost-effectiveness (C/E) acceptability curve. Recent publications on Bayesian estimation have assumed a normal posterior distribution, which ignores uncertainty in estimated variances, and suggest unnecessarily complicated methods of computation. We present a simple Bayesian computation for the C/E acceptability curve and a simple frequentist analogue. Our approach takes account of errors in estimated variances, resulting in calculations that are based on distributions rather than normal distributions. If inference is required about the C/E ratio, we argue that the standard frequentist procedures give unreliable or misleading inferences, and present instead a Bayesian interval.

Intestinal obstruction after lung transplantation in children with cystic fibrosis.

BACKGROUND/PURPOSE: Distal intestinal obstruction syndrome (DIOS) occurs in 15% of patients with cystic fibrosis (CF). The authors reviewed their experience to determine the incidence, risk factors, and natural history of adhesive intestinal obstruction and DIOS after lung transplantation. METHODS: Eighty-three bilateral transplants were performed in 70 CF patients between January 1990 and September 1998. All were on pancreatic enzymes preoperatively, and none had preoperative bowel preparation. Fifty-six patients (80%) had prior gastrostomy (n = 54) or jejunostomy (n = 2). Eighteen patients (25.7%) had a previous laparotomy for meconium ileus (n = 8), fundoplication (n = 4), liver transplant (n = 1), jejunal atresia (n = 1), Janeway gastrostomy takedown (n = 1), pyloromyotomy (n = 1), free air (n = 1), or appendectomy (n = 1). RESULTS: After lung transplantation, 7 patients (10%) required laparotomy for bowel obstruction (6 during the same hospitalization, and 1 during a subsequent hospitalization). The causes of obstruction were adhesions only (n = 1), DIOS only (n = 2), and a combination of DIOS and adhesions (n = 4). Adhesiolysis was performed in the 5 patients with adhesions, and a small bowel resection was also performed in 1 patient. DIOS was treated by milking secretions distally without an enterotomy (n = 3) with an enterotomy and primary closure (n = 1) or with an end ileostomy and mucus fistula (n = 2). Five had recurrent DIOS early postoperatively. One resolved with intestinal lavage, 2 were treated successfully with hypaque disimpaction, and 2 underwent reoperation; 1 required an ileostomy. The most important risk factor for posttransplant obstruction was a previous major abdominal operation. Obstruction occurred in 7 of 18 (39%) who had undergone a prior laparotomy versus 0 of 52 who had not (P < .001, chi2). CONCLUSIONS: (1) The incidence of intestinal obstruction is high after lung transplantation in children with CF. (2) Previous laparotomy is a significant risk factor. (3) Recurrent obstruction after surgery for this condition is common. (4) Preventive measures such as pretransplant bowel preparation and early postoperative bowel lavage may be beneficial in these patients.

Photopheresis in the treatment of refractory bronchiolitis obliterans complicating lung transplantation.

Photopheresis has been successfully used to treat heart allograft rejection and has had some initial success in the treatment of bronchiolitis obliterans (BO) following lung transplantation. This report describes five patients treated with photopheresis after the failure of augmented immunosuppression for BO. Four patients had a temporary stabilization of their airflow obstruction, and minimal side effects of the procedure were noted, although there were consequences from additional augmented immunosuppression (principally sepsis). Photopheresis may provide a safe modality for the treatment of BO that is unresponsive to standard and augmented immunosuppression.

Airway responsiveness to inhaled albuterol in patients with pulmonary hypertension.

We studied patients with pulmonary hypertension who had evidence of bronchial responsiveness to inhaled albuterol. The records of all patients evaluated for lung transplantation were reviewed: the charts of patients with pulmonary hypertension, either primary (PPH, n = 46) or Eisenmenger's syndrome (n = 12), were abstracted. Measurements of lung function revealed equal numbers of patients with normal, restrictive, obstructive, and mixed abnormalities. None were more than moderate. Airway responsiveness was defined as an increase of forced expiratory volume in 1 second (FEV1) > 15% or forced expiratory flow between 25% and 75% of the vital capacity (FEF25-75) > 25%. Of the 24 PPH and nine Eisenmenger's patients, 14 and four, respectively, had reversible airflow obstruction. These patients were more likely to have a history of atopic disease and to have responded to calcium channels blockers during hemodynamic monitoring. They did not have more severe pulmonary hypertension, as measured by hemodynamic monitoring. Four patients had a history of asthma, which required hospitalization in three. Reversible airflow obstruction occurred in half of the patients with pulmonary hypertension and was clinically important in at least three.

Renal manifestations of tuberous sclerosis complex.

Patients with tuberous sclerosis complex (TSC) are at increased risk of renal disease, predominantly angiomyolipomas and renal cysts. We retrospectively reviewed clinical data of 71 patients diagnosed with TSC. Progression of renal lesions was noted. TSC patients with renal lesions were compared with TSC patients without renal disease. Fifteen of 38 patients had renal abnormalities by imaging at presentation. Six of 9 with initially normal kidneys subsequently developed new lesions. Although not of statistical significance, there was a trend toward increased retinal hamartomas, cardiac rhabdomyomas, and skin lesions in those patients who also had renal abnormalities. Renal disease should be considered and sought in all patients with TSC, both at initial presentation and subsequently, since renal disease is a very significant cause of morbidity and mortality.