Temporal dynamics in the composition of bird communities along a gradient of farmland restoration.

Revegetation plantings are a key activity in farmland restoration and are commonly assumed to support biotic communities that, with time, replicate those of reference habitats. Restoration outcomes, however, can be highly variable and difficult to predict; hence there is value in quantifying restoration success to improve future efforts. We test the expectation that, over time, revegetation will restore bird communities to match those in reference habitats; and assess whether specific planting attributes enhance restoration success. We surveyed birds in 255 sites in south-east Australia, arranged along a restoration gradient encompassing three habitat types: unrestored farmland (paddocks), revegetation plantings (comprising a chronosequence up to 52 years old) and reference habitats (remnant native vegetation). Surveys were undertaken in 2006/2007 and again in 2019, with data used to compare bird assemblages between habitat types. We also determined whether, in the intervening 12 years, bird communities in revegetation had shifted toward reference habitats on the restoration gradient. Our results showed that each habitat contained a unique bird community and that, over time, assemblages in revegetation diverged away from those in unrestored farmland and converged toward those in reference habitats. Two planting attributes influenced this transition: the bird assemblages of revegetation were more likely to have diverged away from those of unrestored farmland (with scattered mature trees) 12 years later if they were located in areas with more surrounding tree cover, and were mostly ungrazed by livestock (compared with grazed plantings). Our results highlight three key ways in which revegetation contributes to farmland restoration: (1) by supporting richer and more diverse bird assemblages than unrestored farmland, (2) by enhancing beta diversity in rural landscapes through the addition of a unique bird community, and (3) by shifting bird assemblages toward those found in reference habitats over time. However, revegetation plantings did not replicate reference habitats by ~40-50 years in our region, and complete convergence may take centuries. These findings have implications for environmental offset programs and mean that effective conservation in farmland environments depends on the retention and protection of natural and seminatural habitats as a parallel management strategy to complement restoration.

Randomised controlled trial of nebulised gentamicin in children with bronchiectasis.

AIM: Following trials of inhaled antibiotics in adults, this study investigates the efficacy of nebulised gentamicin to improve respiratory function in children with bronchiectasis. METHODS: This is a randomised, double-blind, placebo-controlled, crossover trial of 12-week nebulised placebo/gentamicin, 6-week washout, 12-week gentamicin/placebo. Participants were children (5-15 years) with bronchiectasis, chronic infection (any pathogen), and able to perform spirometry from a hospital bronchiectasis clinic. Primary outcomes were change in forced expiratory volume in 1 s (FEV1 ) and hospitalisation days. Secondary outcomes included sputum bacterial density, sputum inflammatory markers, additional antibiotics and symptom severity. Analyses were on an intention-to-treat basis. RESULTS: Fifteen children (mean 11.7-years-old) completed the study. There was no significant change in mean FEV1 (56%/55%, P = 0.38) or annual rate of hospital admissions (1.1/0, P = 0.12) between gentamicin and placebo, respectively. However, Haemophilus influenzae sputum growth (27% vs. 80%, P = 0.002) and bacterial density (2.4 log10 cfu/mL lower P < 0.001) improved with gentamicin. Sputum inflammatory markers interleukin-1ß (P < 0.001), interleukin-8 (P < 0.001) and tumour necrosis factor-α (P = 0.003) were lower with gentamicin. Poor recruitment limited study power and treatment adherence was challenging for this cohort. CONCLUSIONS: In this crossover study of nebulised gentamicin in children with bronchiectasis, there was a reduction in sputum bacterial density and inflammation. However, there were no major improvements in clinical outcomes and adherence was a challenge.

Assessment of Age and Duration of Symptoms on Outcomes of Emergency Scrotal Exploration for Acute Scrotal Pain.

OBJECTIVE: To study the effects of age and duration of symptoms on the outcomes of scrotal explorations for acute scrotal pain at our institution. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Bradford Teaching Hospital NHS Trust, from January 2006 to December 2017. METHODOLOGY: Retrospective data was collected from electronic case records of the patients who required scrotal exploration for suspected torsion of the testis. Group difference between continuous variables (age and duration of symptoms) were assessed by Kruskal Wallis and independent samples Mann-Whitney U-tests. The Fisher Exact and Chisquare tests were used to analyse relationships between categorical data. RESULTS: In total, 502 patients required scrotal exploration. The median age (years) and duration of symptoms (hours) were 16.4 years (1.3 - 77) and 4 hours (1 - 336), respectively. Torsion of the testis was found in 231 (46%), torsion of the testicular appendix in 126 (25%), epididymal inflammation in 46 (9.2%), and no cause identified in 99 (19.7%). Immediate orchidectomy for non-viable testis performed in 34 (14.7% of TT group and 6.8% of the overall cohort). Duration of symptoms was significantly associated with risk of orchidectomy in torsion patients 4 vs. 27 hours (p <0.0001). Overall 47 (9.3%) patients presented after 12 hours, 22 (46.8%) had TT. There were 13 (2.6%) patients older than 40 years and 8 (61.5%) of these had torsion. CONCLUSION: The most commonest diagnosis for patients presenting with acute scrotal pain was torsion of the testis followed by torsion of appendix testis. Testicular salvage was inversely related to the duration of symptoms. Patient's age did not predict the need for orchidectomy. This data supports the practice of urgent scrotal exploration for acute scrotal pain with a clinical suspicion of torsion regardless of age and duration of symptoms.

Sensitivity of RT-PCR testing of upper respiratory tract samples for SARS-CoV-2 in hospitalised patients: a retrospective cohort study.

Background: This study aimed to determine the sensitivity and specificity of reverse transcription PCR (RT-PCR) testing of upper respiratory tract (URT) samples from hospitalised patients with coronavirus disease 2019 (COVID-19), compared to the gold standard of a clinical diagnosis. Methods: All URT RT-PCR testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in NHS Lothian, Scotland, United Kingdom between the 7 th of February and 19 th April 2020 (inclusive) was reviewed, and hospitalised patients were identified. All URT RT-PCR tests were analysed for each patient to determine the sequence of negative and positive results. For those who were tested twice or more but never received a positive result, case records were reviewed, and a clinical diagnosis of COVID-19 allocated based on clinical features, discharge diagnosis, and radiology and haematology results. For those who had a negative RT-PCR test but a clinical diagnosis of COVID-19, respiratory samples were retested using a multiplex respiratory panel, a second SARS-CoV-2 RT-PCR assay, and a human RNase P control. Results: Compared to the gold standard of a clinical diagnosis of COVID-19, the sensitivity of a single upper respiratory tract RT-PCR for COVID-19 was 82.2% (95% confidence interval 79.0-85.1%).   The sensitivity of two upper respiratory tract RT-PCR tests increased sensitivity to 90.6% (CI 88.0-92.7%). A further 2.2% and 0.9% of patients who received a clinical diagnosis of COVID-19 were positive on a third and fourth test; this may be an underestimate of the value of further testing as the majority of patients 93.0% (2999/3226) only had one or two URT RT-PCR tests. Conclusions: The sensitivity of a single RT-PCR test of URT samples in hospitalised patients is 82.2%. Sensitivity increases to 90.6% when patients are tested twice.  A proportion of cases with clinically defined COVID-19 never test positive on URT RT-PCR despite repeat testing.

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.

Factors associated with body mass index in children and adolescents: An international cross-sectional study.

BACKGROUND: The increasing prevalence of overweight and obesity in childhood has implications for their future health. There are many potential contributors to overweight and obesity in childhood. The aim was to investigate the association between postulated risk factors and body mass index (BMI) in children and adolescents. METHODS: Secondary analysis of data from a multi-centre, multi-country, cross-sectional study (ISAAC Phase Three). Parents/guardians of children aged 6-7 years completed a questionnaire about their child's current height and weight, and the postulated risk factors. Adolescents aged 13-14 years reported their own height and weight and answered questions about the postulated risk factors. A general linear mixed model was used to determine the association between BMI and the postulated risk factors. Imputation was used if there were missing responses for 3 or fewer explanatory variables. RESULTS: 65,721 children (27 centres, 15 countries) and 189,282 adolescents (70 centres, 35 countries) were included in the final analyses. Many statistically significant associations were identified, although for most variables the effect sizes were small. In children birth weight (for each kg increase in birth weight the BMI increased by +0.43 kg/m2, p<0.001), television viewing (5+ hours/day +0.33 kg/m2 vs. <1 hour/day, p<0.001), fast food (≥3 times/week +0.16 kg/m2 vs. never, p<0.001) vigorous physical activity (3+ hours/week 0.071 kg/m2 vs. never, p = 0.023) and maternal smoking in the first year of life (+0.13 kg/m2, p<0.001) were associated with a higher BMI in the adjusted model. Nut consumption (≥3 times/week -0.11 kg/m2 vs. never, p = 0.002) was associated with a lower BMI. Early life exposures (antibiotics, paracetamol and breast feeding) were also associated with BMI. For adolescents statistically significant associations with BMI and were seen with maternal smoking (+0.25 kg/m2, p<0.001), television viewing (5+ hours/day +0.23 kg/m2 vs. <1 hour/day, p<0.001), fast food (≥3 times/week -0.19 kg/m2 vs. never, p<0.001), vigorous physical activity (3+ hours/week 0.047 kg/m2 vs. never, p<0.001) and nuts (≥3 times/week -0.22 kg/m2 vs. never, p<0.001). CONCLUSIONS: Although several early life exposures were associated with small differences in BMI, most effect sizes were small. Larger effect sizes were seen with current maternal smoking, television viewing (both with higher BMI) and frequent nut consumption (lower BMI) in both children and adolescents, suggesting that current behaviours are more important than early exposures. Although many variables may influence BMI in childhood, the putative factors studied are not of sufficient magnitude to support major public health interventions.

The association between vitamin D concentration and pain: a systematic review and meta-analysis.

OBJECTIVE: Pain-related conditions, such as chronic widespread pain and fibromyalgia, are major burdens for individuals and the health system. Evidence from previous research on the association between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and pain is conflicting. Thus, we aimed to determine if there is an association between mean 25(OH)D concentration (primary aim), or proportion of hypovitaminosis D (secondary aim), and pain conditions in observational studies. DESIGN: Published observational research on 25(OH)D concentration and pain-related conditions was systematically searched for in electronic sources (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) and a random-effects meta-analysis was conducted on included studies. RESULTS: Eighty-one observational studies with a total of 50 834 participants were identified. Compared with controls, mean 25(OH)D concentration was significantly lower in patients with arthritis (mean difference (MD): -12·34 nmol/l; P<0·001), muscle pain (MD: -8·97 nmol/l; P=0·003) and chronic widespread pain (MD: -7·77 nmol/l; P<0·001), but not in patients with headache or migraine (MD: -2·53 nmol/l; P=0·06). The odds of vitamin D deficiency was increased for arthritis, muscle pain and chronic widespread pain, but not for headache or migraine, compared with controls. Sensitivity analyses revealed similar results. CONCLUSIONS: A significantly lower 25(OH)D concentration was observed in patients with arthritis, muscle pain and chronic widespread pain, compared with those without. These results suggest that low 25(OH)D concentrations may be associated with pain conditions.

Association between Frequency of Consumption of Fruit, Vegetables, Nuts and Pulses and BMI: Analyses of the International Study of Asthma and Allergies in Childhood (ISAAC).

Diets which emphasize intakes of plant-based foods are recommended to reduce disease risk and for promoting healthy weight. The aim of this study was to examine the association between fruit, vegetables, pulses and nut intake and body mass index (BMI) across countries in adolescents (13-14 years) and children (6-7 years). Data from the International Study of Asthma and Allergies in Childhood; 77,243 children's parents and 201,871 adolescents was used to examine the association between dietary intake (Food Frequency Questionnaire) and BMI using general linear models, adjusting for country gross national index. Adolescents who consumed fruit, vegetables, pulses and nuts three or more times a week had a lower BMI than the never or occasional group; eating nuts three or more times a week, was associated with a BMI value of 0.274 kg/m² lower than the never group (p < 0.001). Compared to children who never or occasionally reported eating vegetables, those reporting that they ate vegetables three or more times per week had a lower BMI of -0.079 kg/m². In this large global study, an inverse association was observed between BMI and the reported increasing intake of vegetables in 6-7 years old and fruit, vegetables, pulses and nuts in adolescents. This study supports current dietary recommendations which emphasize the consumption of vegetables, nut and pulses, although the effect sizes were small.

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.

The combination of bed sharing and maternal smoking leads to a greatly increased risk of sudden unexpected death in infancy: the New Zealand SUDI Nationwide Case Control Study.

BACKGROUND: Despite a major reduction in overall infant mortality, sudden unexpected death in infancy (SUDI) continues to be of concern in New Zealand, as the rate is high by international standards, and is even higher in indigenous Maori. AIM: To identify modifiable risk factors for SUDI. METHODS: A three-year (1 March 2012-28 February 2015) nationwide case-control study was conducted in New Zealand. RESULTS: There were 137 SUDI cases, giving a SUDI mortality rate of 0.76/1,000 live births. The rate for Maori was 1.41/1,000, Pacific 1.01/1,000 and non-Maori non-Pacific (predominantly European) 0.50/1,000. The parent(s) of 97% of the SUDI cases were interviewed. Six hundred and forty-nine controls were selected and 258 (40%) were interviewed. The two major risk factors for SUDI were: maternal smoking in pregnancy (adjusted OR=6.01, 95% CI=2.97, 12.15) and bed sharing (aOR=4.96, 95% CI=2.55, 9.64). There was a significant interaction (p=0.002) between bed sharing and antenatal maternal smoking. Infants exposed to both risk factors had a markedly increased risk of SUDI (aOR=32.8, 95% CI=11.2, 95.8) compared with infants not exposed to either risk factor. Infants not sharing the parental bedroom were also at increased risk of SUDI (aOR=2.77, 95% CI=1.45, 5.30). Just 21 cases over the three-year study were not exposed to smoking in pregnancy, bed sharing or front or side sleeping position. CONCLUSIONS: This study has shown that many of the risk factors that were identified in the original New Zealand Cot Death Study (1987-1989) are still relevant today. The combination of maternal smoking in pregnancy and bed sharing is extremely hazardous for infants. Furthermore, our findings indicate that the SUDI prevention messages are still applicable today and should be reinforced. SUDI mortality could be reduced to just seven p.a. in New Zealand (approximately one in 10,000 live births).

Body mass index and vigorous physical activity in children and adolescents: an international cross-sectional study.

AIM: To examine the relationship between reported vigorous physical activity (VPA) and body mass index (BMI) in children (6-7 years) and adolescents (13-14 years). METHODS: In the International Study of Asthma and Allergies in Childhood Phase Three, 75 895 children's parents and 199 502 adolescents answered questions relating to VPA, height and weight. The association between VPA and BMI was analysed using general linear models, adjusting for country gross national index. RESULTS: Compared to children who undertook no VPA, those in the infrequent group (once or twice per week) and those in the frequent group (three or more times per week) had mean (95% CI) BMI values 0.07 kg/m2 (0.03-0.11) and 0.09 kg/m2 (0.03-0.15) greater, respectively (p = 0.001). Compared to adolescents reporting no VPA, those in the infrequent group had a BMI 0.19 kg/m2 (0.15-0.23) greater while those in the frequent group had a BMI 0.01 kg/m2 (-0.03-0.05) greater (p < 0.0001). CONCLUSION: Reported VPA is not associated with lower BMI among children and adolescents. Investigation of VPA and BMI may be best undertaken in conjunction with other variables in the energy expenditure equation. A focus on VPA alone may be an inefficient way to manage BMI.

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.

Electronic adherence monitoring device performance and patient acceptability: a randomized control trial.

BACKGROUND: To investigate the performance and patient acceptability of an inhaler electronic monitoring device in a real-world childhood asthma population. METHODS: Children 6 to 15 years presenting with asthma to the hospital emergency department and prescribed inhaled corticosteroids were included. Participants were randomized to receive a device with reminder features enabled or disabled for use with their preventer. Device quality control tests were conducted. Questionnaires on device acceptability, utility and ergonomics were completed at six months. RESULTS: A total of 1306 quality control tests were conducted; 84% passed pre-issue and 87% return testing. The most common failure reason was actuation under-recording. Acceptability scores were high, with higher scores in the reminder than non-reminder group (median, 5th-95th percentile: 4.1, 3.1-5.0 versus 3.7, 2.3-4.8; p < 0.001). Most (>90%) rated the device easy to use. Feedback was positive across five themes: device acceptability, ringtone acceptability, suggestions for improvement, effect on medication use, and effect on asthma control. CONCLUSIONS: This study investigates electronic monitoring device performance and acceptability in children using quantitative and qualitative measures. Results indicate satisfactory reliability, although failure rates of 13-16% indicate the importance of quality control. Favorable acceptability ratings support the use of these devices in children.

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.

Habitat as a mediator of mesopredator-driven mammal extinction.

A prevailing view in dryland systems is that mammals are constrained by the scarcity of fertile soils and primary productivity. An alternative view is that predation is a primary driver of mammal assemblages, especially in Australia, where 2 introduced mesopredators-feral cat (Felis catus) and red fox (Vulpes vulpes)-are responsible for severe declines of dryland mammals. We evaluated productivity and predation as drivers of native mammal assemblage structure in dryland Australia. We used new data from 90 sites to examine the divers of extant mammal species richness and reconstructed historic mammal assemblages to determine proportional loss of mammal species across broad habitat types (landform and vegetation communities). Predation was supported as a major driver of extant mammal richness, but its effect was strongly mediated by habitat. Areas that were rugged or had dense grass cover supported more mammal species than the more productive and topographically simple areas. Twelve species in the critical weight range (CWR) (35-5500 g) that is most vulnerable to mesopredator predation were extirpated from the continent's central region, and the severity of loss of species correlated negatively with ruggedness and positively with productivity. Based on previous studies, we expect that habitat mediates predation from red foxes and feral cats because it affects these species' densities and foraging efficiency. Large areas of rugged terrain provided vital refuge for Australian dryland mammals, and we predict such areas will support the persistence of CWR species in the face of ongoing mammal declines elsewhere in Australia.

Sun exposure and 25-hydroxyvitamin D3 levels in a community sample: Quantifying the association with electronic dosimeters.

There is uncertainty about the amount of sun exposure required to increase low blood 25-hydroxyvitamin D (25(OH)D3) levels, a possible disease risk factor. The study aimed to quantify the association between sun exposure and serum 25(OH)D3 concentrations in a multiethnic community sample (n=502) living in Auckland (37°S) and Dunedin (46°S), New Zealand, aged 18-85 years. They wore electronic ultraviolet dosimeters between March and November (autumn, winter and spring) for 8 weeks to record their sun exposure. This was converted to standard erythemal doses (SEDs), corrected for clothing to generate equivalent full-body exposures, SEDEFB. Blood samples were collected at the end of weeks 4 and 8 to measure 25(OH)D3. Median weekly SEDEFB was 0.33 during weeks 1-4 and 0.34 during weeks 5-8. Weekly exposures <0.5 SEDEFB during weeks 5-8 were associated with decreasing 25(OH)D3 concentrations at the end of week 8. There was a non-linear association between sun exposure and 25(OH)D3, with most of the increase in 25(OH)D3 being at exposures <2 SEDEFB per week. This finding suggests that vitamin D status is increased by regular small sun exposures (<2 SEDEFB per week), and that greater exposures result in only small additional increases in 25(OH)D3.

Factors associated with medication adherence in school-aged children with asthma.

Adherence to preventive asthma treatment is poor, particularly in children, yet the factors associated with adherence in this age group are not well understood. Adherence was monitored electronically over 6 months in school-aged children who attended a regional emergency department in New Zealand for an asthma exacerbation and were prescribed twice-daily inhaled corticosteroids. Participants completed questionnaires including assessment of family demographics, asthma responsibility and learning style. Multivariable analysis of factors associated with adherence was conducted. 101 children (mean (range) age 8.9 (6-15) years, 51% male) participated. Median (interquartile range) preventer adherence was 30% (17-48%) of prescribed. Four explanatory factors were identified: female sex (+12% adherence), Asian ethnicity (+19% adherence), living in a smaller household (-3.0% adherence per person in the household), and younger age at diagnosis (+2.7% for every younger year of diagnosis) (all p<0.02). In school-aged children attending the emergency department for asthma, males and non-Asian ethnic groups were at high risk for poor inhaled corticosteroid adherence and may benefit most from intervention. Four factors explained a small proportion of adherence behaviour indicating the difficulty in identifying adherence barriers. Further research is recommended in other similar populations.

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.

Does urban extent from satellite images relate to symptoms of asthma, rhinoconjunctivitis and eczema in children? A cross-sectional study from ISAAC Phase Three.

OBJECTIVE: The relationship between urbanisation and the symptom prevalence of asthma, rhinoconjunctivitis and eczema is not clear, and varying definitions of urban extent have been used. Furthermore, a global analysis has not been undertaken. This study aimed to determine whether the symptom prevalence of asthma, rhinoconjunctivitis and eczema in centres involved in the International Study of Asthma and Allergies in Childhood (ISAAC) were higher in urban than rural centres, using a definition of urban extent as land cover from satellite data. METHODS: A global map of urban extent from satellite images (MOD500 map) was used to define the urban extent criterion. Maps from the ISAAC centres were digitised and merged with the MOD500 map to describe the urban percentage of each centre. We investigated the association between the symptom prevalence of asthma, rhinoconjunctivitis and eczema and the percentage of urban extent by centre. RESULTS: A weak negative relationship was found between the percentage of urban extent of each ISAAC centre and current wheeze in the 13-14-year age group. This association was not statistically significant after adjusting for region of the world and gross national income. No other relationship was found between urban extent and symptoms of asthma, rhinoconjunctivitis and eczema. CONCLUSIONS: In this study, the prevalence of symptoms of asthma, rhinoconjunctivitis and eczema in children were not associated with urbanisation, according to the land cover definition of urban extent from satellite data. Comparable standardised definitions of urbanisation need to be developed so that global comparisons can be made.