Randomised control trial of the effectiveness of an integrated psychosocial health promotion intervention aimed at improving health and reducing substance use in established psychosis (IMPaCT).

BACKGROUND: People with psychosis have a reduced life expectancy of 10-20 years, largely due to cardiovascular disease. This trial aimed to determine the effectiveness of a modular health promotion intervention (IMPaCT Therapy) in improving health and reducing cardiovascular risk in psychosis. METHODS: A multicentre, two arm, parallel cluster RCT was conducted across five UK mental health NHS trusts. Community care coordinators (CC) were randomly assigned to training and supervision in delivering IMPaCT Therapy or treatment as usual (TAU) to current patients with psychosis (cluster). The primary outcome was the physical and mental health subscales of the Short form-36 (SF-36) questionnaire. RESULTS: Of 104 care coordinators recruited, 52 (with 213 patients) were randomised to deliver IMPaCT therapy and 52 (with 193 patients) randomised to TAU. Of 406 patients, 318 (78%) and 301 (74%) attended 12- and 15-month follow-up respectively. IMPaCT therapy showed no significant effect on the physical or mental health component SF-36 scores versus TAU at 12 or 15 months. No effect was observed for cardiovascular risk indicators, except for HDL cholesterol, which improved more with IMPACT therapy than TAU (Treatment effect (95% CI); 0.085 (0.007 to 0.16); p = 0.034). The 22% of patients who received >180 min of IMPACT Therapy in addition to usual care achieved a greater reduction in waist circumference than did controls, which was clinically significant. CONCLUSION: Training and supervising community care coordinators to use IMPaCT therapy in patients with psychosis is insufficient to significantly improve physical or mental health quality of life. The search for effective, pragmatic interventions deliverable in health care services continues. TRIAL REGISTRATION: The trial was retrospectively registered with ISRCTN registry on 23/4/2010 at ISRCTN58667926 ; recruitment started on 01/03/2010 with first randomization on 09.08.2010 ISRCTN58667926 .

Randomised controlled trial to improve health and reduce substance use in established psychosis (IMPaCT): cost-effectiveness of integrated psychosocial health promotion.

BACKGROUND: There is mounting evidence that people with severe mental illness have unhealthy lifestyles, high rates of cardiovascular and metabolic diseases, and greater risk of early mortality. This study aimed to assess the cost-effectiveness of a health promotion intervention seeking to improve physical health and reduce substance use in people with psychosis. METHODS: Participants with a psychotic disorder, aged 18-65 years old and registered on an enhanced care approach programme or equivalent were recruited from community mental health teams in six mental health trusts in England. Participants were randomisation to either standard community mental health team care (treatment as usual) or treatment as usual with an integrated health promotion intervention (IMPaCT). Cost-effectiveness and cost-utility analyses from health and social care and societal perspectives were conducted alongside a cluster randomised controlled trial. Total health and social care costs and total societal costs at 12 and 15 months were calculated as well as cost-effectiveness (incremental cost-effectiveness ratios and cost-effectiveness acceptability curves) at 15 months based on quality of life (SF-36 mental and physical health components, primary outcome measures) and quality adjusted life years (QALYs) using two measures, EQ-5D-3 L and SF-36. Data were analysed using bootstrapped regressions with covariates for relevant baseline variables. RESULTS: At 12-15 months 301 participants had full data needed to be included in the economic evaluation. There were no differences in adjusted health and social care costs (£95, 95% CI -£1410 to £1599) or societal costs (£675, 95% CI -£1039 to £2388) between the intervention and control arms. Similarly, there were no differences between the groups in the SF-36 mental component (-0.80, 95% CI -3.66 to 2.06), SF-36 physical component (-0.68, 95% CI -3.01 to 1.65), QALYs estimated from the SF-36 (-0.00, -0.01 to 0.00) or QALYs estimated from the EQ-5D-3 L (0.00, 95% CI -0.01 to 0.02). Cost-effectiveness acceptability curves for all four outcomes and from both cost perspectives indicate that the probability of the health promotion intervention being cost-effective does not exceed 0.4 for willingness to pay thresholds ranging from £0-£50,000. CONCLUSIONS: Alongside no evidence of additional quality of life/clinical benefit, there is also no evidence of cost-effectiveness. TRIAL REGISTRATION: ISRCTN58667926 . Date retrospectively registered: 23/04/2010. Recruitment start date: 01/03/2010.

Botulinum toxin type B: pH change reduces injection pain, retains efficacy.

BACKGROUND: Injection of botulinum toxin Type B (BTX-B) is substantially more painful than injection of botulinum toxin Type A (BTX-A). OBJECTIVE: A method of reducing pain with BTX-B injection without reducing efficacy. This was evaluated in 2 BTX-A-resistant subjects and another BTX-B-naive subject. METHODS: Clinical evaluation and computer analysis of photographs were used to confirm efficacy to different dilutions of Type B toxin and confirm BTX-A resistance. A pilot study of 3 subjects involves BTX-B (usually pH 5.6) that was diluted with sodium bicarbonate to normalize the pH to 7.5 in the syringe immediately before injection. Pain assessment compared the different pH BTX-B solutions. RESULTS: Two patients with acquired resistance to 3 BTX-As in upper facial muscles responded to BTX-B. Injection pain of BTX-B changed to pH 7.5 was significantly reduced and retained efficacy over 10 weeks. CONCLUSION: Botulinum toxin Type A resistance is documented to 3 BTX-A brands in 2 patients. They had received low doses of Type A toxin, they responded to Type B toxin. Injection pain of the acidic solution of BTX-B neurotoxin was reduced and efficacy not compromised by changing pH of BTX-B solution to pH 7.5. This method improved patient tolerance to BTX-B injections.

Improving physical health and reducing substance use in psychosis--randomised control trial (IMPACT RCT): study protocol for a cluster randomised controlled trial.

BACKGROUND: Cardiovascular morbidity and mortality is increased in individuals with severe mental illnesses.We set out to establish a multicentre, two arm, parallel cluster randomized controlled trial (RCT) of a health promotion intervention (HPI), IMPACT Therapy. The patient-tailored IMPACT Therapy aims to target one or more health behaviours from a pre-defined list that includes cannabis use; alcohol use; other substance use; cigarette smoking; exercise; diet and diabetic control, prioritising those identified as problematic by the patient, taking a motivational interviewing and CBT approach. METHODS: Impact therapy will be delivered by care coordinators in the community to the treatment group and will be compared to treatment as usual (TAU). The main hypothesis is that the addition of IMPACT Therapy (HPI) to TAU will be more effective than TAU alone in improving patients' quality of life as measured by the Short Form-36, including mental health and physical health subscales on completion of the intervention at 12 months post randomisation. A subsidiary hypothesis will be that addition of IMPACT Therapy (HPI) will be more cost-effective than TAU alone in improving health in people with SMI 12 months from baseline. The IMPACT therapy patient groups' improvement in quality of life, as well as its cost effectiveness, is hypothesised to be maintained at 15 months. Outcomes will be analyzed on an intention-to-treat (ITT) basis. DISCUSSION: The results of the trial will provide information about the effectiveness of the IMPACT therapy programme in supporting community mental health teams to address physical comorbidity in severe mental illness. TRIAL REGISTRATION: ISRCTN58667926.

Three-dimensional digital surface imaging measurement of the volumizing effect of injectable poly-L-lactic acid for nasolabial folds.

INTRODUCTION: Injectable poly-l-lactic acid (PLLA) is a biocompatible and biodegradable polymer device indicated in Europe for correction of facial contour deficiencies, with a gradual onset of effect that is maintained for up to 25 months. METHODS: In this single-centre, open-label study, 20 adult subjects seeking treatment for facial contour deficiencies were treated with injectable PLLA every 4-6 weeks for ≤6 months or until optimal correction (0 or 1 on nasolabial photonumeric wrinkle assessment scale [0 = no wrinkles; 5 = very deep wrinkles, redundant fold]). 3-D digital surface imaging and standardized 2-D photography were used to assess mid-face and nasolabial volumetric correction and clinical improvement, respectively. RESULTS: Based on 3-D digital surface imaging, statistically significant increases in average mid-facial volume occurred with injectable PLLA after the first injection session and persisted through to the end of treatment. Investigator and subject ratings of 'much improved' or 'excellent' improvement were reported using 2-D photographs as a visual aid. Subjects reported high levels of satisfaction. No serious adverse events were reported. DISCUSSION: In this study, injectable PLLA was found to be safe and effective for mid-face and nasolabial fold volumetric correction.

A phase IIa open-label dose-escalation pilot study using allogeneic human dermal fibroblasts for nasolabial folds.

BACKGROUND AND OBJECTIVE: The correction of soft tissue contour defects and dermal atrophy is a growing area driven by medical and aesthetic need. Deterioration of the skin's appearance occurs as a result of age and trauma, such as surgery, infections, and acne. Typically, imperfections are treated with volume-correcting fillers. This study evaluated allogeneic human dermal fibroblasts (HDFs) for the treatment of nasolabial folds as an alternative strategy to improve the structure, texture, and quality of the skin. METHODS AND MATERIALS: In this phase IIa study, a suspension of allogeneic HDF (2 × 10(6) cells/mL or 2 × 10(7) cells/mL) was injected intradermally along the nasolabial fold; line severity was assessed using a photographic scale. RESULTS: Mean investigator satisfaction was 7.4 (range 4.7-9.5) at 12 weeks and 7.6 (range 4.4-9.8) at 24 weeks. Subject satisfaction scores were 7.0 (range 0.1-10.0) at 12 weeks and 7.8 (range 1.5-10.0) at 24 weeks. All patients experienced adverse events, the majority of which were deemed treatment related. Most were mild to moderate in severity and resolved completely. CONCLUSION: This study demonstrated that allogeneic HDF can produce an improvement in aesthetic appearance with minimal adverse events and warrants further investigation and development. Intercytex provided financial support for this study. John Roberts is an employee of Intercytex.

Dosing, efficacy and safety plus the use of computerized photography for botulinum toxins type A for upper facial lines.

INTRODUCTION: Several studies confirm that botulinum toxins type A (BTX-A) are effective for reducing facial lines caused by hyperactive muscles. Two different commercial types of BTX-A currently available are BTX-A-1 (Botox) and BTX-A-2 (Dysport). This paper reports further comparison of dosing, efficacy and safety. METHODS: Sites treated: glabellar, horizontal forehead lines and crow's feet. Different dilutions and dosages were studied with BTX-A-1 and BTX-A-2. The reduction of facial lines was evaluated by investigators and patients. Computerized photographic numerical assessment was also studied in determining the efficacy of BTX-A for crow's feet lines. RESULTS: Study 1: Injecting glabellar lines at doses of BTX-A-1 (30 units) and BTX-A-2 (75 units) (2.5:1 ratio BTX-A2:BTX-A1) showed similar efficacy. Study 2: BTX-A-2 (256 units total) was significantly more effective than BTX-A-1 (64 units total) (i.e. a dose ratio of 4:1) for upper face lines. No differences in the side-effect profiles between the two toxins were observed in either study. Study 3: A computerized photographic numerical assay was an objective assessment of crow's feet severity. Using a dose ratio of BTX-A-2 to BTX-A-1 of 3:1 showed a trend towards BTX-A-2 superiority. CONCLUSION: Two different botulinum toxins type A were shown to be effective and safe for hyperfunctional facial lines. The choice of dose, dilution and placement is critical for each individual toxin. Computerized photography gave numerical severity scores of crow's feet severity.

Vitamin D supplementation compared to placebo in people with First Episode psychosis - Neuroprotection Design (DFEND): a protocol for a randomised, double-blind, placebo-controlled, parallel-group trial.

BACKGROUND: People experiencing their first episode of psychosis are often deficient in vitamin D. Observational studies have reported an association between low vitamin D concentrations and poorer subsequent health outcomes in psychosis. A vitamin D deficiency in neonates and children has been linked to a later increased risk of schizophrenia and psychotic-like experiences. This trial aims to examine the effect of high-dose vitamin D supplementation on outcomes in early psychosis. We hypothesise that vitamin D supplementation will be associated with better mental health outcomes. METHODS/DESIGN: The DFEND study is a multicentre double-blind placebo-controlled parallel-group trial of vitamin D supplementation in people with early psychosis. Patients with an ICD-10 diagnosis of functional psychosis will be randomised in a 1:1 ratio to receive either 120,000 IU/month of vitamin D (cholecalciferol) or a matched placebo for 6 months. The primary outcome is the total Positive and Negative Syndrome Scale (PANSS) score at the 6-month follow-up for all patients. Secondary outcomes include assessment of mood (Calgary Depression Scale), general function (Global Assessment of Functioning), cardiovascular risk (body mass index, waist circumference, C-reactive protein, cholesterol and HbA1c) and vitamin D levels at the 6-month follow-up. Additionally, 3- and 6-month total PANSS scores will be analysed for those with inadequate vitamin D levels at the baseline. DISCUSSION: The DFEND study is the first trial to examine whether vitamin D supplementation in early psychosis is associated with better mental health outcomes. The findings of this study may help to resolve the clinical equipoise regarding the benefits and cost-effectiveness of routine vitamin D supplementation in people with psychosis. TRIAL REGISTRATION: ISRCTN, ISRCTN12424842. Registered on 25 February 2015.

Injectable poly-l-lactic acid: 3 years of aesthetic experience.

BACKGROUND: Injectable poly-l-lactic acid (PLLA) has been used to correct age- or disease-related facial volume deficits. OBJECTIVE: This single-center, retrospective survey evaluated PLLA for cosmetic use. METHODS AND MATERIALS: A questionnaire was mailed to 281 patients treated with PLLA 6 months or more previously. PLLA was reconstituted 4 hours or more before injection with 5 mL of sterile water plus 1 mL of 1% xylocaine added before injection. RESULTS: Two hundred twenty-one patients responded (210 female; average age 54.3; average treatments 3.3 per patient); the majority had received facial injections. Transient side effects included bruising, swelling, and discomfort. After treatment (1-6 months), 14/41 patients developed Grade 1 papules or nodules (slightly palpable, nonvisible; clinically nonrelevant; all resolved spontaneously), 15/41 developed Grade 2 papules or nodules (palpable, slightly visible; clinically nonrelevant; all resolved spontaneously), and 12/41 developed Grade 3 nodules (easily palpable, obviously visible [9 perioral; 3 periorbital or temple]; 5 resolved spontaneously; 7 were treated [5 intralesional corticosteroids; 2 surgery]). CONCLUSION: Patients treated with PLLA experienced duration of improvement of up to 24 months. Maximum improvement took several treatment sessions. Nodules occurred in perioral and periorbital regions, so incidence is reduced by avoiding these areas.

Comparison of two formulations of botulinum toxin type A for the treatment of glabellar lines: a double-blind, randomized study.

BACKGROUND: Different formulations of botulinum toxin type A can behave differently. There has been little clinical research directly comparing formulations. OBJECTIVE: We sought to compare the efficacy and tolerability of two botulinum toxin type A formulations-BoNTA1 and BoNTA2-in the treatment of moderate and severe glabellar lines. METHODS: Sixty-two patients with moderate or severe glabellar lines at maximum contraction were randomly assigned to receive 20 U of BoNTA1 or 50 U of BoNTA2 (20% in the procerus muscle, 80% in the corrugator muscles). RESULTS: The incidence of 1-grade improvement or greater in glabellar line severity at maximum contraction was as follows: 77% (BoNTA1) versus 59% (BoNTA2) at week 12, 53% versus 28% at week 16. The estimated incidence of relapse was 23% (BoNTA1) versus 40% (BoNTA2) at week 16. Both formulations were similarly well tolerated. LIMITATIONS: Few male and non-Caucasian subjects were studied. CONCLUSION: BoNTA(1) offered more prolonged efficacy than BoNTA2 in the treatment of glabellar lines at the dose ratio of 2.5:1 (BoNTA2:BoNTA1) used in this study.

Botulinum toxins for facial lines: a concise review.

This is a concise review of the uses of botulinum toxins (BTXs) in dermatology and cosmetic procedures. It is a clinical rather than a basic science, pharmacological review. BTX had been initially used for selectively reducing and balancing periorbital muscle activity; thereby, reducing childhood strabismus and blepharospasm. This clinical research was initiated by Dr. Alan Scott over 40 years ago. BTX type A (BTX-A) was serendipitously observed to reduce forehead frown lines in patients being treated for blepharospasm. Extensive clinical research and development resulted in widespread aesthetic uses for BTX-A by reduction of selected hyperfunctional facial muscles. BTXs are also used for reduced localized hyperhidrosis. A topical BTX-A is being developed as a potential alternative to injected BTX.

3D photography and lip filler: a novel assay.

BACKGROUND: Injectable fillers have been used for a considerable number of years in aesthetic dermatology, including the use of lip augmentation. There has been little attempt to scientifically measure the degree of filler augmentation. METHODS: We report the use of novel photography utilising three-dimensional imagery (Surface Imaging Ltd and Canfield Scientific Vectra 3D Volumetric Analysis System) for evaluating the change in lip volume before and after injection of filler. RESULTS: This is a single-patient case report where computerised three-dimensional photography was taken and subsequently analysed. The increased volume was then measured following lip augmentation with a hyaluronic acid filler (Restylane). CONCLUSIONS: This system would seem to have the potential for analysing the change of volume both for different parts of the face and, in this instance, for lips. Further studies are required and are ongoing to examine its accuracy to measure volume enhancement with other fillers.

Pilot study to determine the efficacy of ALA-PDT photo-rejuvenation for the treatment of facial ageing.

OBJECTIVE: The study was divided into two parts. The objective of the preliminary study was to evaluate the optimum dose and tolerance of 5-aminolaevulinic acid (5-ALA) compared to a placebo cream with a 633-nm LED light in normal, healthy, volunteer forearm skin. The second study was to establish if ALA-PDT treatments improve the signs of ageing. RESULTS: Threshold photosensitization was observed using 5% 5-ALA under plastic occlusion for 30 minutes following a dose response study of forearm skin. Mild improvement was observed, using this concentration and time, for periorbital skin aging. Other anecdotal positive results of photo-rejuvenation are reported for facial and chest areas.

A comparison of two botulinum type a toxin preparations for the treatment of glabellar lines: double-blind, randomized, pilot study.

BACKGROUND: Botulinum toxins have been proven effective for reducing facial lines. There are two commercial types of botulinum toxin type A available in many countries but no published comparison studies. OBJECTIVE: To compare the efficacy and tolerability of Botox Cosmetic and Dysport 50 U in the treatment of glabellar lines (using 20 U of Botox Cosmetic, which is the dose approved by the US Food and Drug Administration for the treatment of glabellar lines, and 50 U of Dysport, which has been reported to be the optimal dose for this formulation). STUDY DESIGN: Parallel-group double-blind pilot study. Evaluation by observing physician, photographic, and patient evaluations. CONCLUSION: Botox 20 U provided better and more prolonged efficacy than Dysport 50 U in the treatment of glabellar lines.