Effect of Monthly High-Dose Vitamin D Supplementation on Acute Respiratory Infections in Older Adults: A Randomized Controlled Trial.

BACKGROUND: Although adults with low vitamin D status are at increased risk of acute respiratory infection (ARI), randomized controlled trials of vitamin D supplementation have provided inconsistent results. METHODS: We performed a randomized, double-blinded, placebo-controlled trial of 5110 adults aged 50-84 years. In 2011-2012, participants were randomized to an initial oral dose of 200 000 IU vitamin D3 followed by 100 000 IU monthly (n = 2558) or placebo (n = 2552) until late 2013 (median follow-up, 1.6 years). Participants reported upper and lower ARIs on monthly questionnaires. Cox models analyzed time to first ARI (upper or lower) by treatment group. RESULTS: Participants' mean age was 66 years and 58% were male; 83% were of European/other ethnicity, with the rest Maori, Polynesian, or South Asian. Mean (SD) baseline blood 25-hydroxyvitamin D [25(OH)D] level was 63 (24) nmol/L; 25% were <50 nmol/L. In a random sample (n = 441), vitamin D supplementation increased mean 25(OH)D to 135 nmol/L at 3 years, while those on placebo remained at 63 nmol/L. During follow-up, 3737 participants reported ≥1 ARI: 74.1% in the vitamin D group versus 73.7% in the placebo group. The hazard ratio for vitamin D compared with placebo was 1.01 (95% CI, 0.94, 1.07). Similar results were seen in most subgroups, including those with baseline 25(OH)D <50 nmol/L and in analyses of the upper/lower components of the ARI outcome. CONCLUSIONS: Monthly high-dose vitamin D supplementation does not prevent ARI in older adults with a low prevalence of profound vitamin D deficiency at baseline. Whether effects of daily or weekly dosing differ requires further study. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry, identifier ACTRN12611000402943.

Effect of Monthly, High-Dose, Long-Term Vitamin D Supplementation on Central Blood Pressure Parameters: A Randomized Controlled Trial Substudy.

BACKGROUND: The effects of monthly, high-dose, long-term (≥1-year) vitamin D supplementation on central blood pressure (BP) parameters are unknown. METHODS AND RESULTS: A total of 517 adults (58% male, aged 50-84 years) were recruited into a double-blinded, placebo-controlled trial substudy and randomized to receive, for 1.1 years (median; range: 0.9-1.5 years), either (1) vitamin D3 200 000 IU (initial dose) followed 1 month later by monthly 100 000-IU doses (n=256) or (2) placebo monthly (n=261). At baseline (n=517) and follow-up (n=380), suprasystolic oscillometry was undertaken, yielding aortic BP waveforms and hemodynamic parameters. Mean deseasonalized 25-hydroxyvitamin D increased from 66 nmol/L (SD: 24) at baseline to 122 nmol/L (SD: 42) at follow-up in the vitamin D group, with no change in the placebo group. Despite small, nonsignificant changes in hemodynamic parameters in the total sample (primary outcome), we observed consistently favorable changes among the 150 participants with vitamin D deficiency (<50 nmol/L) at baseline. In this subgroup, mean changes in the vitamin D group (n=71) versus placebo group (n=79) were -5.3 mm Hg (95% confidence interval [CI], -11.8 to 1.3) for brachial systolic BP (P=0.11), -2.8 mm Hg (95% CI, -6.2 to 0.7) for brachial diastolic BP (P=0.12), -7.5 mm Hg (95% CI, -14.4 to -0.6) for aortic systolic BP (P=0.03), -5.7 mm Hg (95% CI, -10.8 to -0.6) for augmentation index (P=0.03), -0.3 m/s (95% CI, -0.6 to -0.1) for pulse wave velocity (P=0.02), -8.6 mm Hg (95% CI, -15.4 to -1.9) for peak reservoir pressure (P=0.01), and -3.6 mm Hg (95% CI, -6.3 to -0.8) for backward pressure amplitude (P=0.01). CONCLUSIONS: Monthly, high-dose, 1-year vitamin D supplementation lowered central BP parameters among adults with vitamin D deficiency but not in the total sample. CLINICAL TRIAL REGISTRATION: URL: http://www.anzctr.org.au. Unique identifier: ACTRN12611000402943.

Effect of monthly high-dose vitamin D supplementation on falls and non-vertebral fractures: secondary and post-hoc outcomes from the randomised, double-blind, placebo-controlled ViDA trial.

BACKGROUND: Adults with low concentrations of 25-hydroxyvitamin D (25[OH]D) in blood have an increased risk of falls and fractures, but randomised trials of vitamin D supplementation have had inconsistent results. We aimed to assess the effect of high-dose vitamin D supplementation on fractures and falls. METHODS: The Vitamin D Assessment (ViDA) Study was a randomised, double-blind, placebo-controlled trial of healthy volunteers aged 50-84 years conducted at one centre in Auckland, New Zealand. Participants were randomly assigned to receive either an initial oral dose of 200 000 IU (5·0 mg) colecalciferol (vitamin D3) followed by monthly 100 000 IU (2·5 mg) colecalciferol or equivalent placebo dosing. The prespecified primary outcome was cardiovascular disease and secondary outcomes were respiratory illness and fractures. Here, we report secondary outcome data for fractures and post-hoc outcome data for falls. Cox proportional hazards models were used to estimate hazard ratios (HRs) for time to first fracture or time to first fall in individuals allocated vitamin D compared with placebo. The analysis of fractures included all participants who gave consent and was by intention-to-treat; the analysis of falls included all individuals who returned one or more questionnaires. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12611000402943. FINDINGS: Between April 5, 2011, and Nov 6, 2012, 5110 participants were recruited and randomly assigned either colecalciferol (n=2558) or placebo (n=2552). Two participants allocated placebo withdrew consent after randomisation; thus, a total of 5108 individuals were included in the analysis of fractures. The mean age of participants was 65·9 years (SD 8·3) and 2971 (58%) were men. The mean concentration of 25(OH)D in blood was 63 nmol/L (SD 24) at baseline, with 1534 (30%) having 25(OH)D concentrations lower than 50 nmol/L. Follow-up was until July 31, 2015, with a mean treatment duration of 3·4 years (SD 0·4, range 2·5-4·2). During follow-up, 2638 participants reported having a fall, 1312 (52%) of 2539 in the vitamin D group compared with 1326 (53%) of 2517 in the placebo group. The HR for falls-adjusted for age, sex, ethnic origin, history of recent fall, physical activity, and baseline 25(OH)D-was 0·99 (95% CI 0·92-1·07; p=0·82) for vitamin D compared with placebo. Non-vertebral fractures were reported in 292 individuals, 156 (6%) of 2558 in the vitamin D group and 136 (5%) of 2550 in the placebo group. The adjusted HR for fractures was 1·19 (95% CI 0·94-1·50; p=0·15) for vitamin D compared with placebo. 123 (2%) people died during the trial, 65 assigned vitamin D and 58 allocated placebo; the difference between treatment groups was not significant. INTERPRETATION: High-dose bolus vitamin D supplementation of 100 000 IU colecalciferol monthly over 2·5-4·2 years did not prevent falls or fractures in this healthy, ambulatory, adult population. Further research is needed to ascertain the effects of daily vitamin D dosing, with or without calcium. FUNDING: Health Research Council of New Zealand and Accident Compensation Corporation of New Zealand.

Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study : A Randomized Clinical Trial.

Importance: Cohort studies have reported increased incidence of cardiovascular disease (CVD) among individuals with low vitamin D status. To date, randomized clinical trials of vitamin D supplementation have not found an effect, possibly because of using too low a dose of vitamin D. Objective: To examine whether monthly high-dose vitamin D supplementation prevents CVD in the general population. Design, Setting, and Participants: The Vitamin D Assessment Study is a randomized, double-blind, placebo-controlled trial that recruited participants mostly from family practices in Auckland, New Zealand, from April 5, 2011, through November 6, 2012, with follow-up until July 2015. Participants were community-resident adults aged 50 to 84 years. Of 47 905 adults invited from family practices and 163 from community groups, 5110 participants were randomized to receive vitamin D3 (n = 2558) or placebo (n = 2552). Two participants retracted consent, and all others (n = 5108) were included in the primary analysis. Interventions: Oral vitamin D3 in an initial dose of 200 000 IU, followed a month later by monthly doses of 100 000 IU, or placebo for a median of 3.3 years (range, 2.5-4.2 years). Main Outcomes and Measures: The primary outcome was the number of participants with incident CVD and death, including a prespecified subgroup analysis in participants with vitamin D deficiency (baseline deseasonalized 25-hydroxyvitamin D [25(OH)D] levels <20 ng/mL). Secondary outcomes were myocardial infarction, angina, heart failure, hypertension, arrhythmias, arteriosclerosis, stroke, and venous thrombosis. Results: Of the 5108 participants included in the analysis, the mean (SD) age was 65.9 (8.3) years, 2969 (58.1%) were male, and 4253 (83.3%) were of European or other ethnicity, with the remainder being Polynesian or South Asian. Mean (SD) baseline deseasonalized 25(OH)D concentration was 26.5 (9.0) ng/mL, with 1270 participants (24.9%) being vitamin D deficient. In a random sample of 438 participants, the mean follow-up 25(OH)D level was greater than 20 ng/mL higher in the vitamin D group than in the placebo group. The primary outcome of CVD occurred in 303 participants (11.8%) in the vitamin D group and 293 participants (11.5%) in the placebo group, yielding an adjusted hazard ratio of 1.02 (95% CI, 0.87-1.20). Similar results were seen for participants with baseline vitamin D deficiency and for secondary outcomes. Conclusions and Relevance: Monthly high-dose vitamin D supplementation does not prevent CVD. This result does not support the use of monthly vitamin D supplementation for this purpose. The effects of daily or weekly dosing require further study. Trial Registration: clinicaltrials.gov Identifier: ACTRN12611000402943.

Effect of Vitamin D Supplementation on Pain: A Systematic Review and Meta-analysis.

BACKGROUND: There is conflicting evidence from previous qualitative reviews on the effect of vitamin D supplementation on pain. OBJECTIVE: To determine with quantitative methods if vitamin D supplementation lowers pain levels. STUDY DESIGN: Quantitative meta-analysis of published randomized controlled trials (RCTs). SETTING: This meta-analysis examined all studies involving the effect of vitamin D supplementation on pain score. METHOD: Electronic sources (Medline, Embase, Cochrane Central Register of Controlled Trials, clinical trials website, and Google scholar) were systematically searched for RCTs of vitamin D supplementation and pain from inception of each database to October 2015. RESULTS: Nineteen RCTs with 3,436 participants (1,780 on vitamin D supplementation and 1,656 on placebo) were included in the meta-analysis. For the primary outcome (mean change in pain score from baseline to final follow-up), 8 trials with 1,222 participants on vitamin D and 1,235 on placebo reported a significantly greater mean decrease in pain score for the vitamin D group compared to placebo (mean difference -0.57, 95% CI: -1.00 to -0.15, P = 0.007). The effect from vitamin D was greater in patients recruited with pre-existing pain (P-value for interaction = 0.03). Fourteen studies (1,548 on vitamin D, 1,430 on placebo) reported the mean pain score at final follow-up outcome, and no statistical difference was observed (mean difference -0.06, 95%CI: -0.44 to 0.33, P = 0.78). In 4 studies which reported pain improvement (209 on vitamin D, 146 on placebo), the effect size although not significant, shows participants in the vitamin D supplementation group were more likely to report pain improvement compared with the placebo group (relative risk 1.38, 95%CI: 0.93 to 2.05, P = 0.11). LIMITATIONS: Only a few studies reported the mean score change from baseline to final follow-up, and we do not have enough data to determine any modifying effect of baseline vitamin D status and different doses of vitamin D supplementation on pain. CONCLUSION: A significantly greater mean decrease in pain score (primary outcome) was observed with vitamin D supplementation compared with placebo in people with chronic pain. These results suggest that vitamin D supplementation could have a role in the management of chronic pain. KEY WORDS: Meta-analysis, pain, randomized controlled trials, vitamin D supplementation.

Hypercalcemia, hypercalciuria, and kidney stones in long-term studies of vitamin D supplementation: a systematic review and meta-analysis.

BACKGROUND: Vitamin D supplementation is increasingly being used in higher doses in randomized controlled trials (RCTs). However, adverse events from very large annual doses of vitamin D have been shown in 2 RCTs, whereas in a third RCT, low-dose vitamin D, with calcium supplements, was shown to increase kidney stone risk. OBJECTIVE: We analyzed the side effects related to calcium metabolism in RCTs, specifically hypercalcemia, hypercalciuria, and kidney stones, in participants who were given vitamin D supplements for ≥24 wk compared with in subjects in the placebo arm. DESIGN: The following 3 main online databases were searched: Ovid Medline (PubMed), EMBASE, and the Cochrane Library. Software was used for the meta-analysis. RESULTS: A total of 48 studies with 19,833 participants were identified, which reported ≥1 of the following side effects: hypercalcemia, hypercalciuria, or kidney stones. Of these studies, kidney stones were reported in only 9 trials with a tendency for fewer subjects reporting stones in the vitamin D arm than in the placebo arm (RR: 0.66, 95% CI: 0.41, 1.09; P = 0.10). In 37 studies, hypercalcemia was shown with increased risk shown for the vitamin D group (RR: 1.54; 95% CI: 1.09, 2.18; P = 0.01). Similar increased risk of hypercalciuria was shown in 14 studies for the vitamin D group (RR: 1.64; 95% CI: 1.06, 2.53; P = 0.03). In subgroup analyses, it was shown that the effect of vitamin D supplementation on risk of hypercalcemia, hypercalciuria, or kidney stones was not modified by baseline 25-hydroxyvitamin D, vitamin D dose and duration, or calcium co-supplementation. CONCLUSIONS: Long-term vitamin D supplementation resulted in increased risks of hypercalcemia and hypercalciuria, which were not dose related. However, vitamin D supplementation did not increase risk of kidney stones. Additional large RCTs of long-term vitamin D supplementation are required to confirm these findings.

The Vitamin D Assessment (ViDA) Study: design of a randomized controlled trial of vitamin D supplementation for the prevention of cardiovascular disease, acute respiratory infection, falls and non-vertebral fractures.

Observational studies have shown that low vitamin D status is associated with an increased risk of cardiovascular disease, acute respiratory infection, falls and non-vertebral fractures. We recruited 5110 Auckland adults, aged 50-84 years, into a randomized, double-blind, placebo-controlled trial to test whether vitamin D supplementation protects against these four major outcomes. The intervention is a monthly cholecalciferol dose of 100,000IU (2.5mg) for an estimated median 3.3 years (range 2.5-4.2) during 2011-2015. Participants were recruited primarily from family practices, plus community groups with a high proportion of Maori, Pacific, or South Asian individuals. The baseline evaluation included medical history, lifestyle, physical measurements (e.g. blood pressure, arterial waveform, lung function, muscle function), and a blood sample (stored at -80°C for later testing). Capsules are being mailed to home addresses with a questionnaire to collect data on non-hospitalized outcomes and to monitor adherence and potential adverse effects. Other data sources include New Zealand Ministry of Health data on mortality, hospitalization, cancer registrations and dispensed pharmaceuticals. A random sample of 438 participants returned for annual collection of blood samples to monitor adherence and safety (hypercalcemia), including repeat physical measurements at 12 months follow-up. The trial will allow testing of a priori hypotheses on several other endpoints including: weight, blood pressure, arterial waveform parameters, heart rate variability, lung function, muscle strength, gait and balance, mood, psoriasis, bone density, and chronic pain.

Vitamin D activity of breast milk in women randomly assigned to vitamin D3 supplementation during pregnancy.

BACKGROUND: Human milk is typically low in vitamin D activity (VDA). Whether the vitamin D content of breast milk at birth can be increased by supplementing the mother during pregnancy has not been reported to the best of our knowledge. OBJECTIVE: We examined the effect of vitamin D supplementation during pregnancy on breast-milk VDA in the first 2 mo of lactation. DESIGN: Breast-milk samples were obtained from women who were enrolled in a randomized, double-blinded, placebo-controlled trial of vitamin D supplementation during pregnancy. Pregnant women were enrolled at 27 wk of gestation and randomly assigned to the following 3 groups: a placebo group, a group who received one dosage of daily oral vitamin D3 (1000 IU), or a group who received 2 dosages of daily oral vitamin D3 (2000 IU). Serum 25-hydroxyvitamin D [25(OH)D] was measured at enrollment, at 36 wk of gestation, and in cord blood at birth. Study participants who were breastfeeding were invited to provide breast-milk samples for VDA measurement [concentration of vitamin D2, vitamin D3, 25(OH)D2, and 25(OH)D3] at 2 wk and 2 mo postpartum. A linear mixed model was used to compare breast-milk VDA between the 3 study groups. RESULTS: A total of 75 women provided breast-milk samples (44 women provided breast-milk samples at both 2 wk and 2 mo postpartum). The mean (95% CI) VDA at age 2 wk was 52 IU/L (12, 217 IU/L) in the placebo group, 51 IU/L (17, 151 IU/L) in the 1000-IU group, and 74 IU/L (25, 221 IU/L) in the 2000-IU group; and at age 2 mo, the mean (95% CI) VDA was 45 IU/L (16, 124 IU/L), 43 IU/L (18, 103 IU/L), and 58 IU/L (15, 224 IU/L), respectively. There was no significant interaction in VDA between the sample-collection time and treatment (P = 0.61), but there was a difference between lower- and higher-dosage treatment groups (P = 0.04). CONCLUSION: Maternal vitamin D supplementation during pregnancy of 2000 IU/d (compared with 1000 IU/d and with a placebo) results in a higher VDA of breast milk ≥2 mo postpartum. This trial was registered at the Australian New Zealand Clinical Trials Registry as ACTRN12610000483055.

Effect of monthly vitamin D3 supplementation in healthy adults on adverse effects of earthquakes: randomised controlled trial.

OBJECTIVE: To determine whether supplementation with vitamin D improves resilience to the adverse effects of earthquakes. DESIGN: Opportunistic addition to an established randomised double blind placebo controlled trial. SETTING: Christchurch, New Zealand, where a prolonged series of catastrophic earthquakes beginning on 4 September 2010 occurred, which caused widespread destruction, fatalities, and extensive psychological damage. PARTICIPANTS: 322 healthy adults (241 women; 81 men) aged 18-67 who were already participating in the vitamin D and acute respiratory infections study (VIDARIS) between February 2010 and November 2011. INTERVENTION: Participants were randomised to receive an oral dose of either 200,000 IU vitamin D3 monthly for two months then 100,000 IU monthly (n=161) or placebo (n=161) for a total of 18 months. MAIN OUTCOME MEASURE: This is a post hoc analysis from the previously published VIDARIS trial. The primary endpoint in the current analysis was the self reported effects and overall adverse impact of the Christchurch earthquakes as assessed by questionnaire four months after the most destructive earthquake on 22 February 2011, which was used as the index event. The secondary end point was the number of "psychological" adverse events that participants reported at their usual monthly appointments as part of the original VIDARIS trial. RESULTS: 308 participants completed the earthquake impact questionnaire (n=152 in the vitamin D group and 156 in the placebo group). There was no significant difference in the number of self reported adverse effects between those receiving vitamin D supplementation and those receiving placebo. There was also no difference in the overall adverse impact score between treatment groups (χ(2) P=0.44). The exception was that those in the vitamin D group experienced more adverse effects on family relationships (22% v 13%; χ(2) P=0.03). The number of psychological adverse events-such as fatigue, stress, anxiety, and insomnia-that participants reported at their usual monthly appointments was significantly higher after the earthquake (χ(2) P=0.007) but did not differ between treatment groups. CONCLUSION: In this trial, vitamin D supplementation did not reduce the adverse impact of earthquakes in healthy adults. Trial registration Australian New Zealand Clinical Trials Registry (anzctr.org.au) ACTRN12609000486224.

Long-term high-dose vitamin D3 supplementation and blood pressure in healthy adults: a randomized controlled trial.

Previous randomized controlled trials of vitamin D supplementation and blood pressure (BP) mainly have given vitamin D for short periods (<6 months) or at low doses (400 IU per day). This study aims to determine whether long-term high-dose vitamin D taken for 18 months lowers BP. Adults were recruited from a healthcare organization or university into a double-blind controlled trial and randomized to receive either vitamin D3 200 000 IU for 2 months followed by 100 000 IU monthly up to 18 months (n=161) or placebo (n=161). BP was measured at baseline, 5, and 18 months. Subjects had a mean (SD) age of 47.6 (9.7) years, 75% were women, and 94% were of European ancestry (white). Mean (SD) 25-hydroxyvitamin D3 changed from 73 (22) nmol/L at baseline to 124 (28) nmol/L at 18 months in the vitamin D group, and from 71 (22) nmol/L to 56 (22) nmol/L in the placebo group. Mean BP was similar for the vitamin D and placebo groups at baseline (123.4/76.3 versus 122.6/75.6 mm Hg; respectively). The mean change (95% confidence interval) in BP at 18 months minus baseline in the vitamin D group compared with placebo group was -0.6 (-2.8 to 1.6) mm Hg for systolic (P=0.61) and 0.5 (-1.1, 2.2) mm Hg for diastolic (P=0.53). Long-term vitamin D supplementation, which increased mean 25-hydroxyvitamin D3 concentration >100 nmol/L for 18 months, had no effect on systolic or diastolic BP in predominantly white, healthy adults without severe vitamin D deficiency. Beneficial effects on BP cannot be ruled out for other populations.

Vitamin D during pregnancy and infancy and infant serum 25-hydroxyvitamin D concentration.

OBJECTIVE: To determine the vitamin D dose necessary to achieve serum 25-hydroxyvitamin D (25(OH)D) concentration ≥ 20 ng/mL during infancy. METHODS: A randomized, double-blind, placebo-controlled trial in New Zealand. Pregnant mothers, from 27 weeks' gestation to birth, and then their infants, from birth to age 6 months, were randomly assigned to 1 of 3 mother/infant groups: placebo/placebo, vitamin D3 1000/400 IU, or vitamin D3 2000/800 IU. Serum 25(OH)D and calcium concentrations were measured at enrollment, 36 weeks' gestation, in cord blood, and in infants at 2, 4, and 6 months of age. RESULTS: Two-hundred-and-sixty pregnant women were randomized. At enrollment, the proportions with serum 25(OH)D ≥ 20 ng/mL for placebo, lower-dose, and higher-dose groups were 54%, 64%, and 55%, respectively. The proportion with 25(OH)D ≥ 20 ng/mL was larger in both intervention groups at 36 weeks' gestation (50%, 91%, 89%, P < .001). In comparison with placebo, the proportion of infants with 25(OH)D ≥ 20 ng/mL was larger in both intervention groups to age 4 months: cord blood (22%, 72%, 71%, P < .001), 2 months (50%, 82%, 92%, P < .001), and 4 months (66%, 87%, 87%, P = .004), but only in the higher-dose group at age 6 months (74%, 82%, 89%, P = .07; higher dose versus placebo P = .03, lower dose versus placebo P = .21). CONCLUSIONS: Daily vitamin D supplementation during pregnancy and then infancy with 1000/400 IU or 2000/800 IU increases the proportion of infants with 25(OH)D ≥ 20 ng/mL, with the higher dose sustaining this increase for longer.

Effect of vitamin D3 supplementation on upper respiratory tract infections in healthy adults: the VIDARIS randomized controlled trial.

CONTEXT: Observational studies have reported an inverse association between serum 25-hydroxyvitamin D (25-OHD) levels and incidence of upper respiratory tract infections (URTIs). However, results of clinical trials of vitamin D supplementation have been inconclusive. OBJECTIVE: To determine the effect of vitamin D supplementation on incidence and severity of URTIs in healthy adults. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial conducted among 322 healthy adults between February 2010 and November 2011 in Christchurch, New Zealand. INTERVENTION: Participants were randomly assigned to receive an initial dose of 200,000 IU oral vitamin D3, then 200,000 IU 1 month later, then 100,000 IU monthly (n = 161), or placebo administered in an identical dosing regimen (n = 161), for a total of 18 months. MAIN OUTCOME MEASURES: The primary end point was number of URTI episodes. Secondary end points were duration of URTI episodes, severity of URTI episodes, and number of days of missed work due to URTI episodes. RESULTS: The mean baseline 25-OHD level of participants was 29 (SD, 9) ng/mL. Vitamin D supplementation resulted in an increase in serum 25-OHD levels that was maintained at greater than 48 ng/mL throughout the study. There were 593 URTI episodes in the vitamin D group and 611 in the placebo group, with no statistically significant differences in the number of URTIs per participant (mean, 3.7 per person in the vitamin D group and 3.8 per person in the placebo group; risk ratio, 0.97; 95% CI, 0.85-1.11), number of days of missed work as a result of URTIs (mean, 0.76 days in each group; risk ratio, 1.03; 95% CI, 0.81-1.30), duration of symptoms per episode (mean, 12 days in each group; risk ratio, 0.96; 95% CI, 0.73-1.25), or severity of URTI episodes. These findings remained unchanged when the analysis was repeated by season and by baseline 25-OHD levels. CONCLUSION: In this trial, monthly administration of 100,000 IU of vitamin D did not reduce the incidence or severity of URTIs in healthy adults. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12609000486224.

Cross-sectional survey of risk factors for asthma in 6-7-year-old children in New Zealand: International Study of Asthma and Allergy in Childhood Phase Three.

AIM: To identify risk factors for asthma in primary school-aged children in New Zealand. METHODS: A cross-sectional survey of 10,873 6-7-year-old children in Auckland, Bay of Plenty, Nelson and Christchurch (a response rate of 85.2%). A questionnaire was completed by the parent or care giver. RESULTS: 22.2% of children wheezed in the last 12 months (current wheeze). Maori children were at greater risk of current wheeze compared with European children (adjusted odds ratio (adjOR) = 1.37; 95% confidence interval = 1.18-1.59). Antibiotics and paracetamol used in the first year of life were associated with an increased risk of current wheeze (adjOR = 1.78 (1.56-2.04) and adjOR = 1.31 (1.06-1.61), respectively). Watching television for 5 or more hours per day was associated with an increased risk of current wheeze (adjOR = 1.44 (1.13-1.83)). Milk and egg consumption in the last 12 months was associated with a reduced risk of current wheeze. CONCLUSIONS: This study has identified risk factors for asthma in children aged 6-7 years, although causal pathways cannot be established. These associations have important public health implications if causal.

Large-spot subthreshold infrared laser to treat diabetic macular edema.

PURPOSE: To evaluate the efficacy of a large-spot subthreshold infrared laser protocol to treat diabetic maculopathy. METHODS: In a prospective, fellow eye, controlled case series, all patients had clinically significant diabetic macular edema (DME) treated with a single application of subthreshold infrared (810 nm) laser. If bilateral disease was present, the fellow eye was treated with conventional macular laser. The study was to include 20 patients. Visual acuity and central macular thickness (CMT) measured by optical coherence tomography (OCT) were assessed in the study and fellow eyes at baseline and 6 months, and any changes were compared. RESULTS: The 11th patient developed a choroidal infarct with subsequent profound loss of vision immediately after treatment. The study was terminated prematurely at this point. For the remaining 10 patients, there was a trend toward improvement in visual acuity in the study eye compared with the fellow eye at the 6-month follow-up (median change: +1.5 letters for study eye vs -6.5 letters for fellow eye; P = 0.08). There was also significant improvement in OCT-measured CMT in the study eye (mean decrease, 117 microm) compared with deterioration in OCT-measured CMT in the fellow eye (mean increase, 24 microm; P = 0.02). CONCLUSION: This subthreshold infrared laser protocol led to improvement in OCT-measured CMT and stabilization of vision in most subjects. The current protocol is however unpredictable and should not be used in the treatment of DME without further modification.