Jack Wilkinson

Sun Exposure Behavior, Seasonal Vitamin D Deficiency, and Relationship to Bone Health in Adolescents

CONTEXT Vitamin D is essential for bone health in adolescence, when there is rapid bone mineral content accrual. Because cutaneous sun exposure provides vitamin D, there is no recommended oral intake for UK adolescents. OBJECTIVE Our objective was to assess seasonal vitamin D status and its contributors in white Caucasian adolescents and examine bone health in those found deficient. DESIGN Prospective cohort study was undertaken. SETTING Six schools in Greater Manchester, UK, were included. PARTICIPANTS Participants were 131 adolescents between 12 and 15 years of age. INTERVENTION(S) Seasonal assessment of circulating 25-hydroxyvitamin D (25OHD), personal sun exposure, and dietary vitamin D. Adolescents deficient (25OHD <10 ng/ml/25 nmol/liter) in at least one season underwent dual-energy X-ray absorptiometry (lumbar spine, femoral neck), with bone mineral apparent density correction for size, and peripheral quantitative computed tomography (distal radius) for volumetric bone mineral density (BMD). MAIN OUTCOME MEASURE Serum 25OHD and BMD measurements. RESULTS Mean 25OHD was highest in September: 24.1 (SD, 6.9) ng/ml and lowest in January: 15.5 (5.9) ng/ml. Over the year, 16% were deficient in ≥ one season and 79% insufficient (25OHD <20 ng/ml/50 nmol/liter) including 28% in September. Dietary vitamin D was low year-round, whereas personal sun exposure was seasonal and predominantly across the school week. Holidays accounted for 17% variation in peak 25OHD (P < .001). Nineteen adolescents underwent bone assessment, which showed low femoral neck bone mineral apparent density vs matched reference data (P = .0002), three with Z less than or equal to -2.0 distal radius trabecular volumetric BMD. CONCLUSIONS Sun exposure levels failed to provide adequate vitamin D, with approximately one-quarter of adolescents insufficient even at summer peak. Seasonal vitamin D deficiency was prevalent and those affected had low BMD. Recommendations on vitamin D acquisition are indicated in this age-group.

Sunlight exposure behaviour and vitamin D status in photosensitive patients: longitudinal comparative study with healthy individuals at U.K. latitude.

Low vitamin D status is prevalent in wintertime in populations at northerly latitudes. Photosensitive patients are advised to practise sun avoidance, but their sunlight exposure levels, photoprotective measures and resulting vitamin D status are unknown.

A comparison of intense pulsed light and laser treatment of telangiectases in patients with systemic sclerosis: a within-subject randomized trial

OBJECTIVE Cutaneous telangiectases are a characteristic and psychologically distressing feature of SSc. Our aim was to assess the efficacy of two light-based treatments: pulsed dye laser (PDL) and intense pulsed light (IPL). METHODS Nineteen patients with facial or upper limb telangiectases underwent three treatments with PDL and IPL (randomly assigned to left- and right-sided lesions). Outcome measures were clinical photography (assessed by two clinicians), dermoscopy (assessed by two observers), laser Doppler imaging (LDI) and observer and patient opinion, including patient self-assessment psychological questionnaires [Hospital Anxiety and Depression Scale (HADS), Adapted Satisfaction with Appearance Scale (ASWAP)]. RESULTS Comparison between 16-week follow-up and baseline photography scores (from -2 to +2 on a Likert scale, with >0 being improvement) were a mean score for PDL of 1.7 (95% CI 1.4, 2.0) and for IPL 1.4 (0.9, 1.8), with a mean difference between PDL and IPL of -0.3 (-0.5, -0.1) (P = 0.01). Dermoscopy scores also improved with both therapies: PDL 1.3 (1.1, 1.5) and IPL 0.8 (0.5, 1.1), again greater with PDL (P = 0.01). LDI showed decreases in blood flow at 16 weeks, indicating a response to both therapies. All patients reported benefit from treatment (more preferred PDL at 16 weeks). Psychological questionnaires also indicated improvement after therapy with mean change in ASWAP of -13.9 (95% CI -20.5, -7.4). No side effects were reported for IPL; PDL caused transient bruising in most cases. CONCLUSION Both PDL and IPL are effective treatments for SSc-related telangiectases. Outcome measures indicate that PDL has better outcomes in terms of appearance, although IPL had fewer side effects.

Reducing research waste in benign gynaecology and fertility research

and fertility research JMN Duffy, S Bhattacharya, M Herman, B Mol, A Vail, J Wilkinson, C Farquhar, on behalf of the Cochrane Gynaecology and Fertility Group a Balliol College, University of Oxford, Oxford, UK b Primary Care Health Sciences, University of Oxford, Oxford, UK c The Institute of Applied Health Sciences, University of Aberdeen, Aberdeen, UK d Department of Obstetrics and Gynaecology, M axima Medical Centre, Veldhoven, the Netherlands e Robinson Research Institute, University of Adelaide, Adelaide, SA, Australia f Centre for Biostatistics, University of Manchester, Manchester, UK g Cochrane Gynecology and Fertility Group, University of Auckland, Auckland, New Zealand Correspondence: C Farquhar, Cochrane Gynecology and Fertility Group, University of Auckland, PO Box 92019, Auckland 1142, New Zealand. Email c.farquhar@auckland.ac.nz

Reduced perfusion in systemic sclerosis digital ulcers (both fingertip and extensor) can be increased by topical application of glyceryl trinitrate

Objectives In patients with systemic sclerosis (SSc), fingertip digital ulcers (DUs) are believed to be ischaemic, and extensor surface DUs a result of mechanical factors/microtrauma. Our aim was to assess blood flow response to topical glyceryl trinitrate (GTN) compared to placebo in SSc DUs, looking for differences in pathophysiology between fingertip and extensor lesions. Method This was a double-blind, randomised, crossover, placebo-controlled study. Sixteen (6 fingertip, 10 extensor) DUs were each studied twice (one day apart): once with GTN and once with placebo ointment. Perfusion at the DU centre (‘DUCore’) and periphery (‘DUPeriphery’), as measured by laser Doppler imaging was performed before and immediately after ointment application, then every 10 min, up to 90 min post-application. We calculated the area under the response curve (AUC) and the ratio of peak perfusion to baseline, then compared these between GTN and placebo. Results Perfusion was lower in the DUCore compared to the DUPeriphery (ratio of 0.52). The microvessels of the DUCore were responsive to GTN, with an increase in perfusion, with a similar effect in both fingertip and extensor DUs. The AUC and peak/baseline perfusion difference in means (ratio, 95% confidence interval) between GTN and placebo at the DUCore were 1.2 (1.0–1.6) and 1.2 (1.0–1.5) respectively, and at the DUPeriphery were 1.1 (0.8–1.6) and 1.0 (0.9–1.2) respectively. Conclusion DUs (both fingertip and extensor) were responsive to topical GTN, with an increase in perfusion to the ischaemic DU centre. If both fingertip and extensor DUs have a (potentially reversible) ischaemic aetiology, this has important treatment implications.

Developments in IVF warrant the adoption of new performance indicators for ART clinics, but do not justify the abandonment of patient-centred measures

Recent advances in embryo freezing technology together with growing concerns over multiple births have shifted the paradigm of appropriate IVF. This has led to the adoption of new performance indicators for ART clinics by national reporting schemes, such as those curated by the Society for Assisted Reproductive Technology (SART) and the Human Fertilization and Embryology Authority (HFEA). Using these organizations as case studies, we review several outcome measures from a statistical perspective. We describe several denominators that are used to calculate live birth rates. These include cumulative birth rates calculated from all fresh and frozen transfer procedures arising from a particular egg collection or cycle initiation, and live birth rates calculated per embryo transferred. Using data from both schemes, we argue that all cycles should be included in the denominator, regardless of whether or not egg collection and fertilization were successful. Excluding cancelled cycles reduces the impact of confounding due to patient characteristics but also removes policy and performance differences which we argue represent relevant sources of variation. It may be misleading to present prospective patients with essentially hypothetical measures of performance predicated on parity of ovarian stimulation and transfer policies. Although live birth per embryo has the advantage of encouraging single embryo transfer, we argue that it is prone to misinterpretation. This is because the likelihood of live birth is not proportional to the number of embryos transferred. We conclude that it is not possible to present a single measure that encompasses both effectiveness and safety. Instead, we propose that a set of clear, relevant outcome indicators is necessary to enable subfertile patients to make informed choices regarding whether and where to be treated.

Direct-to-consumer advertising of success rates for medically assisted reproduction: a review of national clinic websites

Objectives To establish how medically assisted reproduction (MAR) clinics report success rates on their websites. Setting Websites of private and NHS clinics offering in vitro fertilisation (IVF) in the UK. Participants We identified clinics offering IVF using the Choose a Fertility Clinic facility on the website of the Human Fertilisation and Embryology Authority (HFEA). Of 81 clinics identified, a website could not be found for 2, leaving 79 for inclusion in the analysis. Primary and secondary outcome measures Outcome measures reported by clinic websites. The numerator and denominator included in the outcome measure were of interest. Results 53 (67%) websites reported their performance using 51 different outcome measures. It was most common to report pregnancy (83% of these clinics) or live birth rates (51%). 31 different ways of reporting pregnancy and 9 different ways of reporting live birth were identified. 11 (21%) reported multiple birth or pregnancy rates. 1 clinic provided information on adverse events. It was usual for clinics to present results without relevant contextual information such as sample size, reporting period, the characteristics of patients and particular details of treatments. Conclusions Many combinations of numerator and denominator are available for the purpose of reporting success rates for MAR. The range of reporting options available to clinics is further increased by the possibility of presenting results for subgroups of patients and for different time periods. Given the status of these websites as advertisements to patients, the risk of selective reporting is considerable. Binding guidance is required to ensure consistent, informative reporting.

Phase II Pragmatic Randomized Controlled Trial of Patient-Led Therapies (Mirror Therapy and Lower-Limb Exercises) During Inpatient Stroke Rehabilitation:

Background and objective. Patient-led therapy has the potential to increase the amount of therapy patients undertake during stroke rehabilitation and to enhance recovery. Our objective was to assess the feasibility and acceptability of 2 patient-led therapies during the acute stages of stroke care: mirror therapy for the upper limb and lower-limb exercises for the lower limb. Methods. This was a blind assessed, multicenter, pragmatic randomized controlled trial of patient-led upper-limb mirror therapy and patient-led lower leg exercises. Stroke survivors with upper and lower limb limitations, undergoing inpatient rehabilitation and able to consent were recruited at least 1 week poststroke. Results. Both interventions proved feasible, with >90% retention. No serious adverse events were reported. Both groups did less therapy than recommended; typically 5 to 15 minutes for 7 days or less. Participants receiving mirror therapy (n = 63) tended to do less practice than those doing lower-limb exercises (n = 31). Those with neglect did 69% less mirror therapy than those without (P = .02), which was not observed in the exercise group. Observed between-group differences were modest but neglect, upper-limb strength, and dexterity showed some improvement in the mirror therapy group. No changes were seen in the lower-limb group. Conclusions. Both patient-led mirror therapy and lower-limb exercises during inpatient stroke care are safe, feasible, and acceptable and warrant further investigation. Practice for 5 to 15 minutes for 7 days is a realistic prescription unless strategies to enhance adherence are included.

Thermographic Abnormalities are Associated with Future Digital Ulcers and Death in Patients with Systemic Sclerosis

Objective. Capillaroscopic abnormalities are predictive of future digital ulcers (DU). Our aim was to investigate whether functional digital vascular disease (thermographically assessed) is also associated with future DU. Methods. A retrospective case note review of patients with systemic sclerosis (SSc) undergoing thermography and who were followed for up to about 3 years. Results. There were 138 patients (equal mixture of normal/abnormal thermography). Patients with abnormal thermography were more likely to develop DU (clinician-observed and/or patient-reported, OR 2.84, p = 0.021), including multiple episodes, and more likely to die (OR 5.42, p = 0.050). Conclusion. Abnormal thermography is associated with DU and disease severity in patients with SSc.

Colour Counts: Sunlight and Skin Type as Drivers of Vitamin D Deficiency at UK Latitudes

Sunlight exposure, with resulting cutaneous synthesis, is a major source of vitamin D for many, while dietary intake is low in modern diets. The constitutive pigment in skin determines skin type, observed as white, brown, or black skin. The melanin pigment absorbs ultraviolet radiation (UVR) and protects underlying skin from damage caused by UVR. It also reduces the UVR available for vitamin D synthesis in the skin. It has been shown that the white-skinned population of the UK are able to meet their vitamin D needs with short, daily lunchtime exposures to sunlight. We have followed the same methodology, based on a 10-year UK all-weather UVR climatology, observation (sun exposure, diet, vitamin D status), and UVR intervention studies with Fitzpatrick skin type V (brown) adults, to determine whether sunlight at UK latitudes could provide an adequate source of vitamin D for this section of the population. Results show that to meet vitamin D requirements, skin type V individuals in the UK need ~25 min daily sunlight at lunchtime, from March to September. This makes several assumptions, including that forearms and lower legs are exposed June–August; only exposing hands and face at this time is inadequate. For practical and cultural reasons, enhanced oral intake of vitamin D should be considered for this population.