Vitamin D and the hepatitis B vaccine response: a prospective cohort study and a randomized, placebo-controlled oral vitamin D3 and simulated sunlight supplementation trial in healthy adults.

PURPOSE: To determine serum 25(OH)D and 1,25(OH)2D relationship with hepatitis B vaccination (study 1). Then, to investigate the effects on hepatitis B vaccination of achieving vitamin D sufficiency (serum 25(OH)D ≥ 50 nmol/L) by a unique comparison of simulated sunlight and oral vitamin D3 supplementation in wintertime (study 2). METHODS: Study 1 involved 447 adults. In study 2, 3 days after the initial hepatitis B vaccination, 119 men received either placebo, simulated sunlight (1.3 × standard-erythema dose, 3 × /week for 4 weeks and then 1 × /week for 8 weeks) or oral vitamin D3 (1000 IU/day for 4 weeks and 400 IU/day for 8 weeks). We measured hepatitis B vaccination efficacy as percentage of responders with anti-hepatitis B surface antigen immunoglobulin G ≥ 10 mIU/mL. RESULTS: In study 1, vaccine response was poorer in persons with low vitamin D status (25(OH)D ≤ 40 vs 41-71 nmol/L mean difference [95% confidence interval] - 15% [- 26, - 3%]; 1,25(OH)2D ≤ 120 vs ≥ 157 pmol/L - 12% [- 24%, - 1%]). Vaccine response was also poorer in winter than summer (- 18% [- 31%, - 3%]), when serum 25(OH)D and 1,25(OH)2D were at seasonal nadirs, and 81% of persons had serum 25(OH)D < 50 nmol/L. In study 2, vitamin D supplementation strategies were similarly effective in achieving vitamin D sufficiency from the winter vitamin D nadir in almost all (~ 95%); however, the supplementation beginning 3 days after the initial vaccination did not effect the vaccine response (vitamin D vs placebo 4% [- 21%, 14%]). CONCLUSION: Low vitamin D status at initial vaccination was associated with poorer hepatitis B vaccine response (study 1); however, vitamin D supplementation commencing 3 days after vaccination (study 2) did not influence the vaccination response. CLINICAL TRIAL REGISTRY NUMBER: Study 1 NCT02416895; https://clinicaltrials.gov/ct2/show/study/NCT02416895 ; Study 2 NCT03132103; https://clinicaltrials.gov/ct2/show/NCT03132103 .

Catchments of general practice in different countries--a literature review.

The purpose of this paper is to review the current research on catchment areas of private general practices in different developed countries because healthcare reform, including primary health care, has featured prominently as an important political issue in a number of developed countries. The debates around health reform have had a significant health geographic focus. Conceptually, GP catchments describe the distribution, composition and profile of patients who access a general practitioner or a general practice (i.e. a site or facility comprising one or more general practitioners). Therefore, GP catchments provide important information into the geographic variation of access rates, utilisation of services and health outcomes by all of the population or different population groups in a defined area or aggregated area.This review highlights a wide range of diversity in the literature as to how GP catchments can be described, the indicators and measures used to frame the scale of catchments. Patient access to general practice health care services should be considered from a range of locational concepts, and not necessarily constrained by their place of residence. An analysis of catchment patterns of general practitioners should be considered as dynamic and multi-perspective. Geographic information systems provide opportunities to contribute valuable methodologies to study these relationships. However, researchers acknowledge that a conceptual framework for the analysis of GP catchments requires access to real world data. Recent studies have shown promising developments in the use of real world data, especially from studies in the UK. Understanding the catchment profiles of individual GP surgeries is important if governments are serious about patient choice being a key part of proposed primary health reforms. Future health planning should incorporate models of GP catchments as planning tools, at the micro level as well as the macro level, to assist policies on the allocation of resources so that opportunities for good health outcomes for all groups within society, especially those who have been systematically denied equitable access, are maximised.

The Student You Know: Orthopedic Surgery Home Program Match Rates and Geographic Relationships Before and After COVID-19.

OBJECTIVE: In March 2020, COVID-19 was declared a pandemic by the World Health Organization. This led to the outright cancellation of away rotations and in person residency interviews for the class of 2021. This study aims to identify the geographic relationships in the orthopedic match and further explore COVID-19's effect on these geographic relationships. Furthermore, we aim to compare the home program match rates before and after COVID-19. SETTING: Southern Illinois University School of Medicine, Department of Orthopedic Surgery (tertiary, university-based). DESIGN AND PARTICIPANTS: Residency websites and social media sites were used to record basic residency information as well as each resident's year, matriculated medical school, and matriculated medical school geographic data. This information was used to evaluate the proportion of orthopedic residents from "home program" medical schools and evaluate the geographic relationship of matched orthopedic residents. 202 Orthopedic residencies were initially identified and 134 allopathic and nonmilitary residency programs met the inclusion criteria. In all, 3253 of the 3931 (82.7%) current U.S orthopedic residents were included in the analysis. RESULTS: In the 4 orthopedic surgery residency classes before the pandemic (2017-2020), 21.8% of residency slots were filled by home program students. During the pandemic match cycle (2021), this number jumped to 28.2% (p < 0.0006). The increase was observed consistently across residency subgroup analysis: class size, doximity rank, and doximity research rank. Correspondingly, there was a statistically significant increase from 34.7% (2017-2020) to 39.3% (2021) (p = 0.0318) in residencies matching with same state medical students. Regional trends stayed consistent. Our study showed that residency programs matched applicants who went to same region medical schools during the 2020 to 2021 cycle at nearly the exact same rate as they did pre-pandemic (63.6%, up from 63.3%). CONCLUSIONS: Our study demonstrates that despite widespread virtual away rotations and virtual open houses, residency programs showed an increased preference for their home program students. This trend was significant and widespread, highlighting the generalized nationwide hesitation of both residency programs and students on the virtual interview process.

Influence of Vitamin D Supplementation by Simulated Sunlight or Oral D3 on Respiratory Infection during Military Training.

PURPOSE: This study aimed to determine the relationship between vitamin D status and upper respiratory tract infection (URTI) of physically active men and women across seasons (study 1) and then to investigate the effects on URTI and mucosal immunity of achieving vitamin D sufficiency (25(OH)D ≥50 nmol·L-1) by a unique comparison of safe, simulated sunlight or oral D3 supplementation in winter (study 2). METHODS: In study 1, 1644 military recruits were observed across basic military training. In study 2, a randomized controlled trial, 250 men undertaking military training received placebo, simulated sunlight (1.3× standard erythemal dose, three times per week for 4 wk and then once per week for 8 wk), or oral vitamin D3 (1000 IU·d-1 for 4 wk and then 400 IU·d-1 for 8 wk). URTI was diagnosed by a physician (study 1) and by using the Jackson common cold questionnaire (study 2). Serum 25(OH)D, salivary secretory immunoglobulin A (SIgA), and cathelicidin were assessed by liquid chromatography-mass spectrometry LC-MS/MS and enzyme-linked immunosorbent assay. RESULTS: In study 1, only 21% of recruits were vitamin D sufficient during winter. Vitamin D-sufficient recruits were 40% less likely to suffer URTI than recruits with 25(OH)D <50 nmol·L-1 (OR = 0.6, 95% confidence interval = 0.4-0.9), an association that remained after accounting for sex and smoking. Each URTI caused, on average, three missed training days. In study 2, vitamin D supplementation strategies were similarly effective to achieve vitamin D sufficiency in almost all (≥95%). Compared with placebo, vitamin D supplementation reduced the severity of peak URTI symptoms by 15% and days with URTI by 36% (P < 0.05). These reductions were similar with both vitamin D strategies (P > 0.05). Supplementation did not affect salivary secretory immunoglobulin A or cathelicidin. CONCLUSION: Vitamin D sufficiency reduced the URTI burden during military training.

Reappraisal of giant basal cell carcinoma: Clinical features and outcomes.

BACKGROUND: Giant basal cell carcinoma (GBCC) is a rare subgroup of basal cell carcinomas with a diameter of >5 cm. Current evidence about determining factors is conflicting, suggesting patient neglect, on the one hand, and biologically aggressive behaviour, on the other, with outcomes varying from clearance to death. We aimed to clarify the natural history of GBCC and its response to treatment. METHODS: We extracted information from clinical records of all patients with GBCC treated from 1998 to 2017 in a tertiary oncology hospital in northwest England. Associations between patient and tumour characteristics were investigated, and modes of treatment and outcomes were assessed. RESULTS: In the 20-year study period, 43 patients (median age 76 years; 23 (53%) female), 3 of whom had Gorlin syndrome, were treated for GBCCs. Median diameter was 6.3 cm, and median time to presentation was 5 years. Seven (16%) GBCCs arose from recurrent BCC, while the majority (84%) presented de novo. The size of GBCC was significantly correlated with delay in presentation (p = 0.03) but not with age or sex. Of 41 patients receiving definitive treatment, 19 GBCCs were treated by excision with ≤1 cm margin and none recurred during follow-up, compared with 10 recurrences of 23 treated with photodynamic therapy (PDT), and 1 of 7 recurred after radiotherapy. Two of 43 patients with GBCC (<5%) presented with extensive local invasion, one of whom also had distant metastases, and both died of the disease. CONCLUSION: The majority of GBCCs are not clinically aggressive and respond to conservative surgical treatment with a low risk of recurrence.

Influence of skin melanisation and ultraviolet radiation on biomarkers of systemic oxidative stress.

Skin melanisation ranges widely across human populations. Melanin has antioxidant properties and also acts as a filter to solar ultraviolet radiation (UVR) incident upon the skin. In this study we firstly examined whether melanin level might influence baseline levels of systemic oxidative stress, in 65 humans in vivo from the same geographical area ranging from the lightest to darkest skin type (phototype I-VI). This was examined in winter-time (latitude 53.5°N). Remarkably, we found that urinary biomarkers of oxidatively-generated DNA damage (8-oxodG) and RNA damage (8-oxoGuo) were significantly correlated with skin lightness (L*), such that 14-15% of the variation in their baseline levels could be explained by skin colour. Next we exposed 15 humans at the extremes of skin melanisation to a simulated summer-time exposure of solar UVR (95% UVA, 5% UVB; dose standardised to sunburn threshold), following which they provided a sample of every urine void over the next five days. We found that UVR induced a small but significant increase in urinary 8-oxodG and 8-oxoGuo, with differing kinetics between skin types. Thus greater melanisation is associated with protection against systemic oxidative stress, which may reflect melanin's antioxidant properties, and solar UVR exposure also influences systemic oxidative stress levels in humans. These novel findings may have profound implications for human physiology and health.

Ultraviolet radiation-induced DNA damage is prognostic for outcome in melanoma.

The melanoma genome is dominated by ultraviolet radiation (UVR)-induced mutations. Their relevance in disease progression is unknown. Here we classify melanomas by mutation signatures and identify ten recurrently mutated UVR signature genes that predict patient survival. We validate these findings in primary human melanomas; in mice we show that this signature is imprinted by short-wavelength UVR and that four exposures to UVR are sufficient to accelerate melanomagenesis.

Publisher Correction: Ultraviolet radiation-induced DNA damage is prognostic for outcome in melanoma.

In the version of this article originally published, Extended Data Fig. 3 was incorrect. A duplicate of Extended Data Fig. 4 was uploaded in place of Extended Data Fig. 3. Extended Data Fig. 3 has now been uploaded. The error has been fixed in the PDF and HTML versions of this article.

Influence of Vitamin D Supplementation by Sunlight or Oral D3 on Exercise Performance.

PURPOSE: To determine the relationship between vitamin D status and exercise performance in a large, prospective cohort study of young men and women across seasons (study 1). Then, in a randomized, placebo-controlled trial, to investigate the effects on exercise performance of achieving vitamin D sufficiency (serum 25(OH)D ≥ 50 nmol·L) by a unique comparison of safe, simulated-sunlight and oral vitamin D3 supplementation in wintertime (study 2). METHODS: In study 1, we determined 25(OH)D relationship with exercise performance in 967 military recruits. In study 2, 137 men received either placebo, simulated sunlight (1.3× standard erythemal dose in T-shirt and shorts, three times per week for 4 wk and then once per week for 8 wk) or oral vitamin D3 (1000 IU·d for 4 wk and then 400 IU·d for 8 wk). We measured serum 25(OH)D by high-pressure liquid chromatography tandem mass spectrometry and endurance, strength and power by 1.5-mile run, maximum dynamic lift and vertical jump, respectively. RESULTS: In study 1, only 9% of men and 36% of women were vitamin D sufficient during wintertime. After controlling for body composition, smoking, and season, 25(OH)D was positively associated with endurance performance (P ≤ 0.01, ΔR = 0.03-0.06, small f effect sizes): 1.5-mile run time was ~half a second faster for every 1 nmol·L increase in 25(OH)D. No significant effects on strength or power emerged (P > 0.05). In study 2, safe simulated sunlight and oral vitamin D3 supplementation were similarly effective in achieving vitamin D sufficiency in almost all (97%); however, this did not improve exercise performance (P > 0.05). CONCLUSIONS: Vitamin D status was associated with endurance performance but not strength or power in a prospective cohort study. Achieving vitamin D sufficiency via safe, simulated summer sunlight, or oral vitamin D3 supplementation did not improve exercise performance in a randomized-controlled trial.

Nodular basal cell carcinoma in Gorlin's syndrome treated with systemic photodynamic therapy and interstitial optical fiber diffuser laser.

Nodular basal cell carcinomas resistant to multiple forms of treatment in two patients with nevoid basal cell carcinoma syndrome (Gorlin's syndrome) were treated with systemic porfimer sodium-based photodynamic therapy. Interstitially placed optical diffuser fibers were used to deliver light. Good response to treatment was seen on clinical evaluation and on measurement by a 20-MHz high-resolution ultrasound.

Functional comparison of annexin V analogues labeled indirectly and directly with iodine-124.

We are interested in imaging cell death in vivo using annexin V radiolabeled with (124)I. In this study, [(124)I]4IB-annexin V and [(124)I]4IB-ovalbumin were made using [(124)I]N-hydroxysuccinimidyl-4-iodobenzoate prepared by iododestannylation of N-hydroxysuccinimidyl-4-(tributylstannyl)benzoate. [(124)I]4IB-annexin V binds to phosphatidylserine-coated microtiter plates and apoptotic Jurkat cells and accumulates in hepatic apoptotic lesions in mice treated with anti-Fas antibody, while [(124)I]4IB-ovalbumin does not. In comparison with (124)I-annexin V, [(124)I]4IB-annexin V has a higher rate of binding to phosphatidylserine in vitro, a higher kidney and urine uptake, a lower thyroid and stomach content uptake, greater plasma stability and a lower rate of plasma clearance. Binding of radioactivity to apoptotic cells relative to normal cells in vitro and in vivo appears to be lower for [(124)I]4IB-annexin V than for (124)I-annexin V.

An ultrasound analysis of the response of Gorlin syndrome-related and sporadic basal cell carcinomas to aminolaevulinic acid photodynamic therapy.

BACKGROUND: Gorlin Syndrome (naevoid basal cell carcinoma syndrome, NBCCS) predisposes the patient to the development of basal cell carcinomas (BCCs) throughout their life. The standard treatment for isolated lesions is surgical excision. However, when numerous surgical procedures are required over time, the patient can be left with multiple disfiguring scars. Photodynamic therapy (PDT) offers a non-invasive treatment option for patients with this condition, in which ionizing radiation is contraindicated. This study evaluates PDT as a treatment modality for Gorlin Syndrome and compares the treatment response of Gorlin-related basal cell carcinomas with that of the sporadic lesions. METHODS: In this un-randomized study, basal cell carcinomas in 25 Gorlin syndrome patients (with 36 lesions) and 145 sporadic patients (with 189 lesions) were treated by photodynamic therapy, using δ-5-aminolaevulinic acid (ALA) as a photosensitizer and 100Jcm(-2) of red light (630±15nm). The maximum thickness of the BCC was measured by 20MHz pulsed ultrasound prior to treatment and again 4-6 weeks and 12 months following treatment. The response of Gorlin syndrome lesions was compared to those in the overall sporadic population and then to a subpopulation matched as closely as possible for age, lesion thickness and site. RESULTS: For both populations, the average pre-treatment BCC thickness by US was 1.5mm (overall range 0.3-5.3), and the average thickness at 4-6 weeks post-treatment was 0.5mm (overall range 0-4.3). Those BCC less than 1.5mm thick prior to treatment were significantly more likely to have no US evidence of disease at 4-6 weeks than and were more likely to be controlled at 12 months. CONCLUSIONS: The average response to ALA PDT of Gorlin syndrome-related BCC closely resembles that for the sporadic population, with the same wide range of responses for a given dose. Ultrasound parameters measured at treatment and at 4-6 weeks post-treatment aid prediction of outcome and necessity for further treatment.

Efficacy of a dose range of simulated sunlight exposures in raising vitamin D status in South Asian adults: implications for targeted guidance on sun exposure.

BACKGROUND: Vitamin D is essential for bone health, and cutaneous synthesis is an important source. South Asians cannot attain adequate amounts of vitamin D by following general recommendations on summer sunlight exposure at northerly latitudes, and increased exposure may be appropriate for improving their vitamin D status. OBJECTIVE: We examined the efficacy of a dose range of simulated summer sunlight exposures in raising vitamin D status in UK adults of South Asian ethnicity. DESIGN: In a dose-response study, healthy adults of South Asian ethnicity (n = 60; 20-60 y old) received 1 of 6 ultraviolet exposures ranging from 0.65 to 3.9 standard erythema doses (SEDs), which were equivalent to 15-90 min unshaded noontime summer sunlight at 53.5°N (Manchester, United Kingdom), 3 times/wk for 6 wk, while wearing casual clothes that revealed a 35% skin area. Serum 25-hydroxyvitamin D [25(OH)D] was measured weekly, and dietary vitamin D was estimated. RESULTS: At baseline, all completing participants (n = 51) were vitamin D insufficient [25(OH)D concentrations <20 ng/mL], and a high proportion of participants were deficient [35% of subjects had 25(OH)D concentrations <5 ng/mL, and 90% of subjects had 25(OH)D concentrations <10 ng/mL, which are concentrations at which osteomalacia and rickets occur). The 25(OH)D concentration rose significantly in all dose groups. Postcourse, all participants achieved 25(OH)D concentrations ≥5 ng/mL, whereas only 6 subjects attained 25(OH)D concentrations ≥20 ng/mL. Participants who received exposures ≥1.95 SEDs (equivalent to 45 min unshaded sunlight; n = 33) attained a mean (±SD) 25(OH)D concentration of 15.7 ± 5 ng/mL (mean rise: 8.7 ± 5.7 ng/mL; 95% CI: 6.8, 10.6 ng/mL; P < 0.001), and 94% of subjects achieved concentrations >10 ng/mL. CONCLUSIONS: Targeted guidance on sunlight exposure could usefully enhance vitamin D status to avoid deficiency [25(OH)D concentration >10 ng/mL] in South Asians living at latitudes distant from the equator. This trial was registered at the ISRCTN Register (www.isrctn.org) as 07565297.

Differential cytotoxic response in keloid fibroblasts exposed to photodynamic therapy is dependent on photosensitiser precursor, fluence and location of fibroblasts within the lesion.

Treatment of keloid disease (KD) is ill-defined and remains challenging. We previously reported successful clinical application of photodynamic therapy (PDT) in KD. The aim here was to evaluate cytotoxic effect of PDT using methyl aminolevulinate (M-ALA) and 5-aminolevulinic acid (5-ALA) on keloid fibroblasts (KF) (n = 8) from different lesional sites (top, middle and margin) as compared to normal skin fibroblasts (n = 3). The effect of protoporphyrin IX (PpIX) precursors was evaluated by fluorescence emission, LDH and WST-1 assay, reactive oxygen species (ROS) generation and qRT-PCR analysis. Apoptosis/necrosis differentiation and senescence were studied by fluorometric staining with Hoechst 33258/propidium iodide and ß-galactosidase activity, respectively. Three hours post incubation with 4 mM precursors of photosensitisers, PpIX accumulation was site specific and higher with M-ALA. Cytotoxicity was also site specific (higher in fibroblasts from middle of the keloid as compared to cells from other sites) and increased proportionately to fluence rates post-PDT. Additionally, cytoproliferation was significantly decreased post-PDT depending on the light energy. Fluorescence analysis revealed that M-ALA instigated higher KF cytotoxicity at lower fluence (≤20 J/cm(2)) while 5-ALA instigated higher KF cytotoxicity at higher fluence, except in cells derived from middle of the keloid. ROS-mediated cytotoxicity was light energy dependent. Senescence was not observed at higher light energies (>10 J/cm(2)). Compared to other sites, fibroblasts from the middle were more prone to cell death post 5-ALA treatment. We conclude that cytotoxicity post-PDT in KD fibroblasts is dependent on the lesional site, precursor of intracellular photosensitiser and fluence. Thus, PDT may be used for site-targeted therapy of KD.

Addition of novel degenerate electrical waveform stimulation with photodynamic therapy significantly enhances its cytotoxic effect in keloid fibroblasts: first report of a potential combination therapy.

BACKGROUND: We recently reported use of photodynamic therapy (PDT) for treating keloid disease (KD). However, in view of high recurrence rates post any treatment modality, adjuvant therapies should be considered. Additionally, we previously demonstrated the effect of a novel electrical waveform, the degenerate wave (DW) on differential gene expression in keloid fibroblasts. OBJECTIVE: In this study, we evaluated the in vitro cytotoxic effect of PDT at 5J/cm(2) and 10J/cm(2) of red light (633 ± 3nm) using 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) with and without DW, on keloid fibroblasts compared to normal skin fibroblasts. METHODS: The rate of intracellular photosensitizer (protoporphyrin IX, PPIX) generation and disintegration, reactive oxygen species (ROS) generation, LDH cytotoxicity, WST-1 cytoproliferation, apoptosis by Caspase-3 activation, mitochondrial membrane potential assessment by JC-1 aggregates, qRT-PCR, flow cytometry and In-Cell Western Blotting were performed. RESULTS: PPIX accumulation and disintegration rate was higher in keloid than normal fibroblasts after incubation with MAL compared to ALA. Increased cytotoxicity and decreased cytoproliferation were observed for keloid fibroblasts after PDT+DW treatment compared to PDT alone. ROS generation, mitochondrial membrane depolarization, apoptosis (Caspase-3 activation) and collagens I and III gene down-regulation were higher in keloid compared to normal skin fibroblasts after MAL-PDT+DW treatment. An increase in the number of cells entering apoptosis and necrosis was observed after PDT+DW treatment by flow cytometry analysis. All positive findings were statistically significant (P<0.05). CONCLUSION: The cytotoxic effect of PDT on keloid fibroblasts can be enhanced significantly with addition of DW stimulation, indicating for the first time the utility of this potential combinational therapy.

Recommended summer sunlight exposure amounts fail to produce sufficient vitamin D status in UK adults of South Asian origin.

BACKGROUND: The cutaneous synthesis of vitamin D is dependent on UVB from sunlight, but melanin reduces the penetration of UVB and thus contributes to vitamin D insufficiency in individuals with darker skin. The national guidance provided on amounts of sunlight exposure in the United Kingdom is for the light-skinned population, and in the absence of dedicated information, darker-skinned people may attempt to follow this guidance. OBJECTIVES: We determined the relative effect of a simulation of UK recommendations of summer sunlight exposure on the vitamin D status of individuals of South Asian ethnicity compared with that of whites. DESIGN: In a prospective cohort study, simulated summer sunlight exposures were provided under rigorous dosimetric conditions to 15 adults (aged 20-60 y) of South Asian ethnicity, and serum 25-hydroxyvitamin D [25(OH)D] was measured weekly. Dietary vitamin D intake was estimated. Outcomes were compared with those of 109 whites (aged 20-60 y) treated with the identical UV-radiation exposure protocol. RESULTS: At baseline (winter trough), all South Asians were vitamin D-insufficient [25(OH)D concentrations <20 ng/mL], and 27% of South Asians were vitamin D-deficient [25(OH)D concentrations <5 ng/mL]; although 25(OH)D concentrations increased postcourse (P < 0.0001), all South Asians remained vitamin D-insufficient. The mean increase in 25(OH)D was 4.3 compared with 10.5 ng/mL in the South Asian and white groups, respectively (P < 0.0001), and 90% of the white group reached vitamin D sufficiency postcourse. The median dietary vitamin D intake was very low in both groups. CONCLUSIONS: Sunlight-exposure recommendations are inappropriate for individuals of South Asian ethnicity who live at the UK latitude. More guidance is required to meet the vitamin D requirements of this sector of the population. This study was registered at www.isrctn.org as ISRCTN 07565297.

Recommended summer sunlight exposure levels can produce sufficient (> or =20 ng ml(-1)) but not the proposed optimal (> or =32 ng ml(-1)) 25(OH)D levels at UK latitudes.

Recommendations on limitation of summer sunlight exposure to prevent skin cancer may conflict with requirements to protect bone health through adequate vitamin D levels, the principal source being UVB in summer sunlight. We determined whether sufficient (> or =20 ng ml(-1)) and proposed optimal (> or =32 ng ml(-1)) 25(OH)D levels are attained by following UK guidance advising casual short exposures to UVB in summer sunlight, and performed the study under known conditions to enhance the specificity of future recommendations. During wintertime, when ambient UVB is negligible, 120 white Caucasians, aged 20-60 years, from Greater Manchester, UK (53.5 degrees N) received a simulated summer's sunlight exposures, specifically 1.3 standard erythemal dose, three times weekly for 6 weeks, while wearing T-shirt and shorts. The baseline winter data predict that 5% (confidence interval (CI): 2.7-8.6) of Greater Manchester white Caucasians have deficient (<5 ng ml(-1)) 25(OH)D, 62.5% (CI: 55.2-69.4) have insufficient, and only 2.9% (CI: 1.4-5.6) have proposed optimal levels. After the simulated summer exposures, 90 (CI: 84.9-93.7) and 26.2% (CI: 20.1-33.2) reached 20 and 32 ng ml(-1) 25(OH)D, respectively. Assuming midday UVB levels, sufficient but suboptimal vitamin D status is attained after a summer's short (13 minutes) sunlight exposures to 35% skin surface area; these findings will assist future public health guidance on vitamin D acquisition.

Impact of Levovist ultrasonographic contrast agent on the diagnosis and management of hypertensive patients with suspected renal artery stenosis: a Canadian multicentre pilot study.

OBJECTIVES: To compare the diagnoses obtained with unenhanced ultrasonography (US), contrast-enhanced US and captopril-enhanced renal scintigraphy and to determine whether use of a contrast agent improves ability to assess the renal arteries with duplex Doppler US. SUBJECTS AND METHODS: The study was an open-label controlled trial involving 78 patients with hypertension suspected to have a renovascular cause. The patients underwent captopril-enhanced scintigraphy or routine unenhanced US (the usual diagnostic methods at the centres where the study was conducted) and contrast-enhanced US (with Levovist, Berlex Canada, Lachine, Que.). The patients were followed for 3 months after the diagnostic tests were performed. RESULTS: Enhanced US yielded a diagnosis for a significantly greater proportion of patients than did unenhanced US (77 [99%] v. 64 [82%] of 78 patients; p = 0.002) or captopril-enhanced scintigraphy (71 [99%] v. 58 [81%] of 72 patients; p = 0.002). Diagnosis was possible with both enhanced and unenhanced duplex Doppler US in only 64 (82%) of the 78 patients, and the diagnosis was the same with both methods for 63 (98%) of these 64 patients. In contrast, diagnosis was possible for only 58 (81%) of the 72 patients who underwent both enhanced US and captopril-enhanced scintigraphy; the same diagnosis was reported in 53 (91%) of these 58 cases. During follow-up, 11 patients (21 kidneys) underwent angiography. Significant stenosis was detected in 6 (55%) of the patients (8 [38%] of the kidneys). Both the enhanced and unenhanced US results agreed more often with angiography than did captopril-enhanced scintigraphy (9 [82%] v. 8 [73%] of the 11 patients). The proportion of patients in whom the left and right renal artery could be assessed by duplex Doppler US increased significantly (by 58% and 43%, respectively) with use of the contrast agent. CONCLUSION: Enhanced US had a higher rate of successful diagnosis than unenhanced US and captopril-enhanced renal scintigraphy. Enhanced US might therefore be suitable as a screening method for hypertensive patients with suspected renal artery stenosis.

Economic impact of an ultrasonographic contrast agent on the diagnosis and initial management of patients with suspected renal artery stenosis.

OBJECTIVES: To determine resource use in the diagnosis and management of Canadian hypertensive patients with suspected renal artery stenosis and to estimate the impact of diagnosis with contrast-enhanced duplex Doppler ultrasonography (US) on resource use. SUBJECTS AND METHODS: Seventy-eight patients with suspected renal artery stenosis underwent usual diagnostic tests (captopril-enhanced renal scintigraphy or duplex Doppler US) and contrast-enhanced US. A management pathway ("planned") describing the medical resources required for further patient care was outlined on the basis of results from each test (separately), and a modified management pathway ("recommended"), which considered data from both diagnostic methods, was also outlined. Medical resources and productivity losses were assessed prospectively for a 3-month period after patients underwent both tests ("actual" management pathway). RESULTS: With usual diagnostic methods, 14 (18%) of the tests were inconclusive, whereas only 1 (1%) of the enhanced US examinations was inconclusive; the cost-efficacy ratio was $422 and $343 per successful diagnosis, respectively. Further management costs for patients with an inconclusive diagnosis were estimated at $6370 after the usual diagnostic tests, but only $1278 with enhanced US. Although the costs of the planned and recommended management pathways were similar ($227 and $294 per patient respectively), the proportion of patients requiring further resources was lower with enhanced US (56% v. 46%). Three-month actual management costs ranged from $121 to $1605 per patient (mean $360). Diagnostic tests and surgical procedures were the major cost drivers in all pathways, and costs were highest for patients in whom stenosis was diagnosed. CONCLUSIONS: For patients with suspected renal artery stenosis, contrast-enhanced US had a higher diagnostic success rate than usual diagnostic methods and afforded savings through lower administrative costs and lower medical resource consumption for patients whose diagnosis was unclear after usual diagnostic tests.