Impact of specialist ataxia centres on health service resource utilisation and costs across Europe: cross-sectional survey.

BACKGROUND: Little is known about the costs of treating ataxia and whether treatment at a specialist ataxia centre affects the cost of care. The aim of this study was to investigate whether patients who attended specialist ataxia centres in three European countries reported differences in their health care use and costs compared with patients who did not attend a specialist ataxia centre. We compared mean resource use and health service costs per patient affected by ataxia in the United Kingdom, Italy and Germany over a 12-month period. Data were obtained from a survey distributed to people with ataxia in the three countries. We compared mean resource use for each contact type and costs, stratifying patients by whether they were currently attending a specialist ataxia centre or had never attended one. RESULTS: Responses were received from 181 patients from the United Kingdom, 96 from Italy and 43 from Germany. Differences in the numbers of contacts for most types of health service use between the specialist ataxia centre and non-specialist ataxia centre groups were non-significant. In the United Kingdom the mean total cost per patient was €2209 for non-specialist ataxia centre patients and €1813 for specialist ataxia centre patients (P = 0.59). In Italy these figures were €2126 and €1971, respectively (P = 0.84). In Germany they were €2431 and €4087, respectively (P = 0.19). Inpatient stays made the largest contribution to total costs. CONCLUSIONS: Within each country, resource use and costs were broadly similar for specialist ataxia centre and non-specialist ataxia centre groups. There were differences between countries in terms of health care contacts and costs.

Patient pathways for rare diseases in Europe: ataxia as an example.

BACKGROUND: Progressive ataxias are rare and complex neurological disorders that represent a challenge for the clinicians to diagnose and manage them. This study explored the patient pathways of individuals attending specialist ataxia centres (SAC) compared with non-specialist settings. We investigated specifically how diagnosis was reached, the access to healthcare services, treatments, and care satisfaction. The focus of this study was on early intervention, coordination of treatment to understand the care provision in different countries. METHODS: A patient survey was done in the UK, Germany and Italy to gather information about diagnosis and management of the ataxias in specialist (SAC) and non-specialist settings, utilisation of other primary and secondary health care services, and patients' satisfaction of received treatment. RESULTS: Patients gave positive feedback about the role of SAC in understanding their condition, ways to manage their ataxia (p < 0.001; UK) and delivering care adapted to their needs (p < 0.001; UK), in coordinating referrals to other healthcare specialists, and in offering opportunities to take part in research studies. Similar barriers for patients were identified in accessing the SACs among the selected countries, UK, Germany, and Italy. CONCLUSIONS: This study provides crucial information about the ataxia patients care pathways in three European countries. Overall, the results showed a trend in patients' satisfaction being better in SAC compared to non-SAC. The outcomes can be used now for policy recommendations on how to improve treatment and care for people with these very rare and complex neurological diseases across Europe.

The attitude of patients with progressive ataxias towards clinical trials.

BACKGROUND: The development of new therapies may rely on the conduct of human experimentation as well as later clinical trials of therapeutic interventions. Ethical considerations seek to protect the patient from risk but few have sought to ascertain the attitude to such risk of patients with progressive debilitating or terminal conditions, for which no mitigating or curative therapies exist. Such understanding is also important if recruitment is to be maximized. We therefore sought to define the motivations for and barriers to trial participation amongst patients with progressive ataxias, as well as their condition-specific trial preferences. METHODS: We conducted an online survey consisting of 29 questions covering four key domains (demographics, personal motivation, drug therapy and study design) relating to the design of clinical trials. Two major ataxia charities, Ataxia UK and the Friedreich's Ataxia Research Alliance (FARA) sent the survey to their members. Responses were analysed by disease and by ambulatory status. RESULTS: Of 342 respondents, 204 reported a diagnosis of Friedreich's ataxia (FRDA), 55 inherited cerebellar ataxia (CA) and 70 idiopathic CA. The most important symptoms to be addressed by a trial were considered to be balance problems and ambulation, although these were superseded by speech problems in wheelchair users. Common motivations for participation were potential benefits to self and others. Reasons for non-participation included concerns about side effects, and the burden and cost of travel. Financial reimbursement for expenses was reported to be likely to increase trial engagement, Phase two trials were the most popular to participate in, and the use of a placebo arm was seen as a disincentive. Across all disease subgroups, drug repurposing trials proved popular and just under 70% of participants would be prepared to undergo intrathecal drug administration. CONCLUSIONS: Knowledge of motivations for and barriers to trial participation as well as the acceptability of investigations, time commitments and routes of drug administration should inform better, more patient focused trial design. This in turn may improve recruitment and retention of participants to future trials.

Diagnosis and management of progressive ataxia in adults.

Progressive ataxia in adults can be difficult to diagnose, owing to its heterogeneity and the rarity of individual causes. Many patients remain undiagnosed ('idiopathic' ataxia). This paper provides suggested diagnostic pathways for the general neurologist, based on Ataxia UK's guidelines for professionals. MR brain scanning can provide diagnostic clues, as well as identify 'structural' causes such as tumours and multiple sclerosis. Advances in molecular genetics, including the wider and cheaper availability of 'next-generation sequencing', have enabled clinicians to identify many more cases with a genetic cause. Finally, autoimmunity is probably an under-recognised cause of progressive ataxia: as well as patients with antigliadin antibodies there are smaller numbers with various antibodies, including some associated with cancer. There are a few treatable ataxias, but also symptomatic treatments to help people with the spectrum of complications that might accompany progressive ataxias. Multidisciplinary team involvement and allied health professionals' input are critical to excellent patient care, including in the palliative phase. We can no longer justify a nihilistic approach to the management of ataxia.

Guidelines on the diagnosis and management of the progressive ataxias.

The progressive ataxias are a group of rare and complicated neurological disorders, knowledge of which is often poor among healthcare professionals (HCPs). The patient support group Ataxia UK, recognising the lack of awareness of this group of conditions, has developed medical guidelines for the diagnosis and management of ataxia. Although ataxia can be a symptom of many common conditions, the focus here is on the progressive ataxias, and include hereditary ataxia (e.g. spinocerebellar ataxia (SCA), Friedreich's ataxia (FRDA)), idiopathic sporadic cerebellar ataxia, and specific neurodegenerative disorders in which ataxia is the dominant symptom (e.g. cerebellar variant of multiple systems atrophy (MSA-C)). Over 100 different disorders can lead to ataxia, so diagnosis can be challenging. Although there are no disease-modifying treatments for most of these entities, many aspects of the conditions are treatable, and their identification by HCPs is vital. The early diagnosis and management of the (currently) few reversible causes are also of paramount importance. More than 30 UK health professionals with experience in the field contributed to the guidelines, their input reflecting their respective clinical expertise in various aspects of ataxia diagnosis and management. They reviewed the published literature in their fields, and provided summaries on "best" practice, including the grading of evidence available for interventions, using the Guideline International Network (GIN) criteria, in the relevant sections.A Guideline Development Group, consisting of ataxia specialist neurologists and representatives of Ataxia UK (including patients and carers), reviewed all sections, produced recommendations with levels of evidence, and discussed modifications (where necessary) with contributors until consensus was reached. Where no specific published data existed, recommendations were based on data related to similar conditions (e.g. multiple sclerosis) and/or expert opinion. The guidelines aim to assist HCPs when caring for patients with progressive ataxia, indicate evidence-based (where it exists) and best practice, and act overall as a useful resource for clinicians involved in managing ataxic patients. They do, however, also highlight the urgent need to develop effective disease-modifying treatments, and, given the large number of recommendations based on "good practice points", emphasise the need for further research to provide evidence for effective symptomatic therapies.These guidelines are aimed predominantly at HCPs in secondary care (such as general neurologists, clinical geneticists, physiotherapists, speech and language therapists, occupational therapists, etc.) who provide care for individuals with progressive ataxia and their families, and not ataxia specialists. It is a useful, practical tool to forward to HCPs at the time referrals are made for on-going care, for example in the community.

Factors associated with discrimination among minority college students.

OBJECTIVES: To assess minority college undergraduate and graduate students' self-reported stress, ethnic identity, and skin complexion as predictors of perceptions of racial discrimination. METHODS: The participants (N = 172) were college-aged minority students. A hierarchical multiple regression analysis was conducted to examine the predictive relationship of the study variables on perceived racial discrimination. RESULTS: Skin complexion (ß = .34, p < .05) and ethnic identity (ß = .25, p < .05) had a positive (increased frequency) relationship with racial discrimination. When separated by sex, stress was a statistically significant predictor ß = .24, p < .05) of racial discrimination for males only. CONCLUSIONS: Understanding the predictors of perceived racial discrimination may allow for the development of interventions that alleviate the stress associated with discrimination.

A meta-analysis of school-based obesity prevention programs demonstrates limited efficacy of decreasing childhood obesity.

Childhood obesity is a global concern. The objectives of this meta-analytical study were to evaluate the effectiveness of school-based childhood obesity prevention programs, and to examine program components (moderators). The methods included searching databases (PubMed, Google Scholar, and the university's EBSCOhost Web service) as well as handsearching reference lists of articles published in English. Selection criteria for studies to be included in the meta-analysis were limited to studies that reported body mass index (BMI) or skinfold thickness as outcome measures and were school-based obesity prevention interventions; cross-sectional design studies were excluded. We hypothesized the meta-analysis would yield a summary effect size of magnitude which would indicate that school-based interventions have been effective in improving children's BMI or skinfold thickness values. A total of 26 114 children from 27 school-based childhood obesity prevention programs provided 54 effect sizes. A random-effects model calculated a small summary effect size of 0.039 (95% confidence interval -0.013 to 0.092). Heterogeneity among studies was observed which disappeared after pooling studies that used a randomized controlled trial design with one program moderator (physical activity or nutrition). We failed to accept our hypothesis and concluded that overall, school-based interventions have not been effective for improving body mass index or skinfold thickness to curb childhood obesity; however, randomized controlled trials that focused on physical activity or nutrition appeared to produce promising results.

The rheological properties of pharmaceutical foam: implications for use.

We have evaluated various aerosol foam types having different compositions and related physico-chemical properties. The foams assessed were hydroethanolic, emulsion, and aqueous based. Composition, appearance, loss on drying, and rheological properties were analysed to characterise the macrostructure of the different aerosol foams. To confirm the validity of the vane rheological technique used, and facilitate intuitive understanding of the data, similar data were collected for a commercial shaving foam. Of the physico-chemical parameters that were evaluated, rheological properties were distinct among hydroethanolic, emulsion, and aqueous aerosol foam types. The results indicate that beyond composition differences, physico-chemical differences do exist between these aerosol foam types. The viscoelastic flow properties provided an insight of the macrostructure of materials that have been foamed.

Functional graft poly(N-isopropyl acrylamide)s using reversible addition-fragmentation chain transfer (RAFT) polymerisation.

A series of NIPAM/4-vinyl benzyl chloride copolymers were substituted with 4(5)-imidazole dithioic acid or N-pyrrole dithioic acid to form multi-functional linear dithioate-functional polymers, which can be used as macromolecular transfer agents in a controlled radical polymerisation (RAFT) process. The presence of imidazole dithioate or N-pyrrole dithioate units along the NIPAM copolymer was determined by (1)H NMR, which showed broad CH-imidazole or CH-N-pyrrole resonances. Subsequent reaction of these multi-branch point polymers to produce graft polymers was achieved by reaction with NIPAM in the presence of AIBN. The graft polymers are produced as mixtures containing the desired product and linear polymer. The linear polymer is produced following transfer to the pendant dithioate group. Some of the branched polymers formed from the imidazole dithioate polymers were insoluble in water whilst others were found to be water soluble only in the presence of copper(II) ions. The use of N-pyrrole dithioate groups was found to substantially increase the solubility of the branched polymers in conventional solvents.

Effectiveness of intermediate-fidelity simulation training technology in undergraduate nursing education.

AIM: The aim of this paper is to present the results of a study designed to determine the effect of scenario-based simulation training on nursing students' clinical skills and competence. BACKGROUND: Using full-scale, realistic, medical simulation for training healthcare professionals is becoming more and more common. Access to this technology is easier than ever before with the opening of several simulation centres throughout the world and the availability on the market of more sophisticated and affordable patient simulators. However, there is little scientific evidence proving that such technology is better than more traditional techniques in the education of, for example, undergraduate nursing students. METHODS: A pretest/post-test design was employed with volunteer undergraduate students (n = 99) from second year Diploma of Higher Education in Nursing programme in United Kingdom using a 15-station Objective Structured Clinical Examination. Students were randomly allocated to either a control or an experimental group. The experimental group, as well as following their normal curriculum, were exposed to simulation training. Subsequently, all students were re-tested and completed a questionnaire. The data were collected between 2001 and 2003. RESULTS: The control and experimental groups improved their performance on the second Objective Structured Clinical Examination. Mean test scores, respectively, increased by 7.18 and 14.18 percentage points. The difference between the means was statistically significant (P < 0.001). However, students' perceptions of stress and confidence, measured on a 5-point Likert scale, was very similar between groups at 2.9 (1, not stressful; 5, very stressful) and 3.5 (1, very confident; 5, not confident) for the control group, and 3.0 and 3.4 for the experimental group. CONCLUSIONS: Intermediate-fidelity simulation is a useful training technique. It enables small groups of students to practise in a safe and controlled environment how to react adequately in a critical patient care situation. This type of training is very valuable to equip students with a minimum of technical and non-technical skills before they use them in practice settings.

Simultaneous determination of tretinoin and clindamycin phosphate and their degradation products in topical formulations by reverse phase HPLC.

A new HPLC method based on reverse phase separation and photodiode-array detection has been developed for the simultaneous determination of tretinoin and clindamycin phosphate, and their degradation products in topical formulations. The method has been shown to be stability indicating, accurate, and precise for two different formulation vehicles. Separation was achieved on a reverse phase C18 column (Lichrospher, RP18, 5 microm, 25 cm x 4.6 mm ID, Phenomenex, USA) using a simple gradient with aqueous-acetonitrile and aqueous-methanol mobile phases. The method recovery averaged 100.3% for tretinoin and 99.6% for clindamycin phosphate at a concentration range between 80% and 120% of the label claim. The method can be applied to assess the stability of tretinoin and clindamycin phosphate in pharmaceutical formulations containing tretinoin and clindamycin phosphate individually or in combination as active drugs.

Retention and distribution of two 99mTc-DTPA labelled vaginal dosage forms.

UNLABELLED: To objectively evaluate the performance of new vaginal dosage forms, it is important to determine their time of residence and their distribution. This paper describes the in vivo characteristics of a reference and test product in this situation. METHOD: A randomised cross-over study was performed in the same phase of the menstrual cycle in eight pre-menopausal women. The retention and distribution of a commercially available vaginal clotrimazole cream and a test gel product, each "labelled" with 99mTc-DTPA was assessed by gamma scintigraphy for 24 h after administration of the products. Mass balance analysis was attempted by collecting and counting sanitary napkins worn for the study time. RESULTS: Within individuals there was little variation in the clearance of the formulations, but wide variation between individuals with a range between 81 and 1% of the administered doses retained by 24 h. The losses appeared to occur mainly at times of urination with 12 +/- 8% (cream) and 20 +/- 23% (gel) collected on the sanitary napkins, but 46 +/- 34% (cream) and 38 +/- 22% gel activity not accounted for by 24 h. The intravaginal distribution of activity was similar for each product. CONCLUSIONS: Radioactive tracer methods are useful in assessing and comparing vaginal dosage forms.