A multicentre, randomised controlled trial to compare the clinical and cost-effectiveness of Lee Silverman Voice Treatment versus standard NHS Speech and Language Therapy versus control in Parkinson's disease: a study protocol for a randomised controlled trial.

BACKGROUND: Parkinson's disease (PD) affects approximately 145,519 people in the UK. Speech impairments are common with a reported prevalence of 68%, which increase physical and mental demands during conversation, reliance on family and/or carers, and the likelihood of social withdrawal reducing quality of life. In the UK, two approaches to Speech and Language Therapy (SLT) intervention are commonly available: National Health Service (NHS) SLT or Lee Silverman Voice Treatment (LSVT LOUD®). NHS SLT is tailored to the individuals' needs per local practice typically consisting of six to eight weekly sessions; LSVT LOUD® comprises 16 sessions of individual treatment with home-based practice over 4 weeks. The evidence-base for their effectiveness is inconclusive. METHODS/DESIGN: PD COMM is a phase III, multicentre, three-arm, unblinded, randomised controlled trial. Five hundred and forty-six people with idiopathic PD, reporting speech or voice problems will be enrolled. We will exclude those with a diagnosis of dementia, laryngeal pathology or those who have received SLT for speech problems in the previous 2 years. Following informed consent and completion of baseline assessments, participants will be randomised in a 1:1:1 ratio to no-intervention control, NHS SLT or LSVT LOUD® via a central computer-generated programme, using a minimisation procedure with a random element, to ensure allocation concealment. Participants randomised to the intervention groups will start treatment within 4 (NHS SLT) or 7 (LSVT LOUD®) weeks of randomisation. PRIMARY OUTCOME: Voice Handicap Index (VHI) total score at 3 months. Secondary outcomes include: VHI subscales, Parkinson's Disease Questionnaire-39; Questionnaire on Acquired Speech Disorders; EuroQol-5D-5 L; ICECAP-O; resource utilisation; adverse events and carer quality of life. Mixed-methods process and health economic evaluations will take place alongside the trial. Assessments will be completed before randomisation and at 3, 6 and 12 months after randomisation. The trial started in December 2015 and will run for 77 months. Recruitment will take place in approximately 42 sites around the UK. DISCUSSION: The trial will test the hypothesis that SLT is effective for the treatment of speech or voice problems in people with PD compared to no SLT. It will further test whether NHS SLT or LSVT LOUD® provide greater benefit and determine the cost-effectiveness of both interventions. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number (ISRCTN) Registry, ID: 12421382. Registered on 18 April 2016.

The treatment of stable paediatric forearm fractures using a cast that may be removed at home: comparison with traditional management in a randomised controlled trial.

We investigated whether, in the management of stable paediatric fractures of the forearm, flexible casts that can be removed at home are as clinically effective, cost-effective and acceptable to both patient and parent as management using a cast conventionally removed in hospital. A single-centre randomised controlled trial was performed on 317 children with a mean age of 9.3 years (2 to 16). No significant differences were seen in the change in Childhood Health Assessment Questionnaire index score (p = 0.10) or EuroQol 5-Dimensions domain scores between the two groups one week after removal of the cast or the absolute scores at six months. There was a significantly lower overall median treatment cost in the group whose casts were removed at home (£150.88 (sem 1.90) vs £251.62 (sem 2.68); p < 0.001). No difference was seen in satisfaction between the two groups (p = 0.48).

Topical therapies for the treatment of localized plaque psoriasis in primary care: a cost-effectiveness analysis.

BACKGROUND: Topical therapies are a mainstay of psoriasis treatment, but they vary substantially in terms of cost. OBJECTIVES: To determine the cost-effectiveness and optimal treatment sequence for psoriasis of the trunk, limbs and scalp. METHODS: Probabilities of response from a network meta-analysis were used to determine the short-term efficacy of topical therapies. Longer-term outcomes, including relapse, were informed by published evidence and clinical opinion. Benefits of treatment were measured as quality-adjusted life years (QALYs). Direct costs included topical agents, primary and secondary care visits and second-line therapies for treatment failures. RESULTS: For the trunk and limbs, initial treatment with a two-compound formulation (TCF) product containing vitamin D and potent corticosteroid provided the most QALYs, followed by separate morning and evening application of vitamin D and potent corticosteroid [two-compound application, TCA (am/pm)], and then twice-daily potent corticosteroids. The use of twice-daily potent corticosteroids was the most cost-effective first-line strategy (incremental cost-effectiveness ratio £ 20,000 per QALY), followed by TCA (am/pm) (£ 22,658 per QALY) and TCF product (£ 179,439 per QALY). For scalp psoriasis, initial treatment with very potent corticosteroids generated the most QALYs, followed by TCF product and then potent corticosteroids. Very potent corticosteroids were the most cost-effective treatment but, if too aggressive, potent corticosteroids were optimal followed by TCF product (£ 219,846 per QALY). The cost-effectiveness of second- and third-line topical agents varied with the assumptions made. CONCLUSIONS: Potent corticosteroids, used alone or in combination with vitamin D, are the most cost-effective treatment for patients with psoriasis of the trunk and limbs. Potent or very potent corticosteroids are the most cost-effective treatment for patients with scalp psoriasis.

Practical experience of ustekinumab in the treatment of psoriasis: experience from a multicentre, retrospective case cohort study across the U.K. and Ireland.

BACKGROUND: There are limited data on the use of ustekinumab outside of clinical trials. OBJECTIVES: To assess the efficacy and safety of ustekinumab in patients with severe psoriasis attending 10 dermatology centres in the U.K. and Ireland. METHODS: A retrospective case-note review of 129 patients with psoriasis treated with ustekinumab. RESULTS: Baseline Psoriasis Area and Severity Index (PASI) was 22·9±10·1 (mean±SD). After 16weeks of treatment with ustekinumab PASI 75 (75% reduction in PASI) was observed in 63·0% (n=80/127) of patients, although four patients required concomitant therapy at the 16-week time point. Previous biologic use did show a small, non-significant trend towards treatment failure. A PASI 75 response was seen in 29·4% (n=5/17) of individuals weighing 90-100kg and treated with the standard 45mg ustekinumab dose compared with PASI 75 of 70·3%, 71·4%, 75·0% and 55·6% for weight groups <80, 80-90, 100-110 and >110kg, respectively (P=0·024). Ustekinumab therapy was well tolerated; serious adverse events were observed in 2·3% (n=3/129) of patients. CONCLUSIONS: Ustekinumab is a novel biologic agent for psoriasis. When used in everyday clinical practice it demonstrates high levels of short-term therapeutic efficacy with an acceptable short-term safety profile.

A retrospective cohort study of the impact of biologic therapy initiation on medical resource use and costs in patients with moderate to severe psoriasis.

BACKGROUND: Biologic therapy has become established as an important treatment option in patients with severe psoriasis, but is significantly more expensive in terms of drug costs than traditional treatment options. Relatively little is known about the total healthcare cost of treating severe psoriasis in daily clinical practice and what the budgetary impacts of such high-cost drugs are when compared with standard systemic therapy. OBJECTIVES: To describe the impact of biologic therapy introduction on the use of medical resources, costs and where available, outcomes in patients with moderate to severe psoriasis. METHODS: Data were extracted from case notes of a sequential patient cohort with psoriasis attending a tertiary referral severe psoriasis service and initiated on biologics (adalimumab, efalizumab, etanercept or infliximab) for treatment of their psoriasis. Data on hospital resource use (inpatient, outpatient, day ward, accident and emergency visits and phototherapy sessions) and drug usage (systemic nonbiologic and biologic psoriasis therapies and supportive drugs) were collected for 12 months prior to, and at least 6 months following initiation of biologic therapy. Outcome was measured using the Psoriasis Area and Severity Index (PASI). Differences in resource use and associated costs and outcomes, between 12 months before and after initiation of biologic therapy, were tested using Wilcoxon paired sign tests for continuous data and the McNemar test for categorical data. Confidence intervals (CI) around treatment costs were constructed using a 5000-sample bootstrap analysis. RESULTS: The primary analysis population comprised 76 patients completing 12 months of biologic therapy: 71% males; mean age at time of study 47·3 years (range 23-74); mean duration of psoriasis 24·7 years (range 5·3-45·5). Significant reductions (P < 0·05) in the year following initiation of biologic therapy were observed for all hospital resource use categories, with mean annual costs reduced by £1682 (95% CI -3182 to -182·2; P = 0·05). Mean annual drug costs increased by £9456 (95% CI 8732-10,182; P < 0·001). Mean PASI fell by 8·9 points from 18·7 to 9·8 (95% CI -10·8 to -7·1; P < 0·001). CONCLUSIONS: Total healthcare costs associated with treatment of severe psoriasis with biologic therapy are significantly greater than with traditional systemic therapy. However, some of these are offset by substantial reductions in the number and length of hospital admissions and use of photo- and systemic therapy, and result in significantly improved patient outcome (as inferred by improvement in PASI).

Care of patients with psoriasis: an audit of U.K. services in secondary care.

BACKGROUND: Medical professionals require data about the structure and delivery of dermatological services in primary and secondary care in order to identify and tackle variations in standards and monitor the impact of healthcare reforms. The British Association of Dermatologists (BAD) commissioned an audit of the provision of care for patients with psoriasis. OBJECTIVES: To assess the staffing and facilities in dermatology units in the U.K. with a focus on the provision of care for patients with psoriasis. METHODS: Data were collected from 100 dermatology units in the U.K. for 1 year using a questionnaire and a web-based collection system. RESULTS: Key results are as follows. Eighteen per cent (18/98) of units had fewer than 2.0 whole-time equivalent consultants and 20% had no specialist dermatology nurse. Only 23% of units collected diagnostic data on outpatients, and half were unable to supply details about the number of attendances for psoriasis. Seventy-seven units reported admitting patients to dedicated dermatology beds, general medical beds, or both; three-quarters of units had access to dedicated adult dermatology beds. Pharmacy services were not always available for dermatology patients. Only 21 units (21%) had dedicated clinics for patients with psoriasis and 56% of units lacked a clinical psychology service willing to accept adult dermatology patients; 59% (55/93) lacked psychological services for children. Fifty-five per cent had no systemic drug monitoring clinic. Phototherapy was run by dermatology nurses in 93% (88/95) of the units and by physiotherapists in 11% (10/94). Biologics for psoriasis were prescribed in 75% (73/97) of units and in 88% (64/73) of these the BAD guidelines for the use of biologics were known to be followed. Of the seventy-three units prescribing biologic therapies, 64% had a nurse trained in the assessment and administration of biologics, 71% had facilities for outpatient infusions (e.g. for infliximab) and 39% were restricted in prescribing biologic agents because of financial constraints. A quality-of-life score was either inadequately or never recorded in outpatient records in 81% of units, increasing to 88% for inpatient records. The Psoriasis Area and Severity Index score was inadequately or never recorded in 79% of outpatient records and 82% of inpatient records. CONCLUSIONS: Units varied in their capacity to meet BAD guidelines and standards. Among the most significant deficiencies identified were a shortage of specialist dermatology nurses, treatment delivery by untrained nurses and financial constraints on the prescription of biologics for psoriasis. Gaps in data collection and record keeping jeopardize efforts to improve standards of care.

Replacement of routine liver biopsy by procollagen III aminopeptide for monitoring patients with psoriasis receiving long-term methotrexate: a multicentre audit and health economic analysis.

BACKGROUND: Patients receiving long-term methotrexate for psoriasis are at risk of developing hepatic fibrosis. Repeated liver biopsy has long been regarded as the only reliable method of detecting this and it is still recommended by the American Academy of Dermatology (AAD). More recently, monitoring by serum procollagen III aminopeptide (PIIINP) measurement (Orion Diagnostica, Espoo, Finland) has been advocated as a means of significantly reducing the need for liver biopsy. OBJECTIVES: To assess the validity of guidelines developed in Manchester for the use of PIIINP to monitor patients with psoriasis receiving long-term methotrexate; to assess the anticipated benefits to patients of introducing this change in practice, including reduction in requirement for liver biopsy; and to determine the impact of its introduction on healthcare costs. METHODS: A multicentre audit was conducted over a 24-month period to compare the healthcare costs and outcomes of two intervention groups from centres where serial PIIINP measurement was employed with those of two control groups from centres in which AAD guidelines were followed. RESULTS: A sevenfold reduction in the need for liver biopsy was observed in the two intervention groups (n = 166; 0.04 and 0.02 biopsies/patient/year, respectively) compared with the two control groups (n = 87; 0.26 and 0.30 biopsies/patient/year, respectively). Abnormalities of sufficient severity to influence management were identified in one in five patients biopsied in the main intervention group compared with one in 16 in the control groups. The overwhelming majority of patients surveyed expressed a preference for being monitored by methods that would minimize the need for liver biopsy. The adoption of PIIINP for monitoring would result in significant cost savings. CONCLUSIONS: This audit has shown that patients managed by the Manchester protocol using serial PIIINP measurement and selective liver biopsy were not disadvantaged in comparison with those managed according to AAD guidelines; they were subjected to sevenfold fewer liver biopsies without evidence that important liver toxicity was missed in the process. If PIIINP monitoring were widely adopted, methotrexate would become a more acceptable option for many patients who are dissuaded from considering it because of the threat of repeated liver biopsy; it would also result in significant savings to the healthcare budget.

Preliminary results of bedside inferior vena cava filter placement: safe and cost-effective.

The use of inferior vena cava filters (IVCFs) is increasing in patients at high risk for venous thromboembolism; however, there is considerable controversy related to their cost. We inserted eight percutaneous IVCFs at the bedside. The hospital charges for bedside IVCF insertion were substantially lower compared with those for IVCF insertion performed in the Radiology Department or operating room. There was one death (unrelated to the procedure) and one asymptomatic caval occlusion believed to be caused by thrombus trapping. Bedside IVCF insertion is safe and cost-effective in selected patients. This practice averts the potential complications associated with transporting critically ill patients.