Cameron Grant

Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data

Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect. Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials. Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015. Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome. Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality. Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit. Systematic review registration PROSPERO CRD42014013953.

Whooping cough in school age children with persistent cough: prospective cohort study in primary care

Abstract Objective To estimate the proportion of school age children with a persistent cough who have evidence of a recent Bordetella pertussis infection. Design Prospective cohort study (October 2001 to March 2005). Setting General practices in Oxfordshire, England. Participants 172 children aged 5-16 years who presented to their general practitioner with a cough lasting 14 days or more who consented to have a blood test. Main outcome measures Serological evidence of a recent Bordetella pertussis infection; symptoms at presentation; duration and severity of cough; sleep disturbance (parents and child). Results 64 (37.2%, 95% confidence interval 30.0% to 44.4%) children had serological evidence of a recent Bordetella pertussis infection; 55 (85.9%) of these children had been fully immunised. At presentation, children with whooping cough were more likely than others to have whooping (odds ratio 2.85, 95% confidence interval 1.39 to 5.82), vomiting (4.35, 2.04 to 9.25), and sputum production (2.39, 1.14 to 5.02). Children with whooping cough were also more likely to still be coughing two months after the start of their illness (85% v 48%; P = 0.001), continue to have more than five coughing episodes a day (P = 0.049), and cause sleep disturbance for their parents (P = 0.003). Conclusions For school age children presenting to primary care with a cough lasting two weeks or more, a diagnosis of whooping cough should be considered even if the child has been immunised. Making a secure diagnosis of whooping cough may prevent inappropriate investigations and treatment.

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.

Delayed immunisation and risk of pertussis in infants: unmatched case-control study

Pertussis remains a severe disease in infants. As about two thirds of infants with pertussis are admitted to hospital, factors that seem to be associated with an increased risk of pertussis may in fact be associated with an increased risk of hospital admission. 1 2 The admission rate for pertussis in New Zealand is five to 10 times higher than in England and Wales and the United States.3 We determined whether immunisation reduced the risk of admission to hospital for pertussis by comparing infants admitted with pertussis and infants admitted with other acute respiratory illnesses. View this table: Odds ratios (95% confidence intervals) of catching pertussis associated with delays in giving pertussis vaccine We performed an unmatched case-control study during the 1995-7 pertussis epidemic in Auckland, New Zealand. Pertussis was defined as cough lasting at least two weeks, with coughing paroxysms, inspiratory “whoop,” or vomiting after coughing. The control group consisted of 98 infants admitted to hospital with a coughing illness who were …

Use of complementary treatment by those hospitalised with acute illness

AIM To determine the frequency of use of complementary treatment and measure its impact on clinical outcomes in a hospitalised general paediatric population. METHODS A population based random sample of children admitted to the general paediatric service at a metropolitan children’s hospital in Auckland, New Zealand from February to July 1998. Children with asthma, pneumonia, bronchiolitis, gastroenteritis, or fever were eligible. Data collected by personal interview with parents and by review of the medical records of these children. RESULTS 251 of 511 eligible children admitted during the study period were enrolled. Forty four children (18%) had received complementary treatment during the hospitalising illness. Most children (77%) had been seen in primary care before hospitalisation. The proportion that were seen in primary care and the number of primary care visits before hospitalisation did not vary with receipt of complementary treatment. The proportion of children who were prescribed medications before hospitalisation was significantly greater for those who had received complementary treatment compared with those who had not (59%v 39%). There was no significant difference between users and non-users of complementary treatment in the severity of the illness at presentation, investigations performed, treatment administered, or length of inpatient stay. CONCLUSION A substantial proportion of children hospitalised with acute medical illnesses have received complementary treatment. Alternative health care is used as an adjunct rather than an alternative to conventional health care. Receipt of complementary treatment has no significant effect on clinical outcomes for children hospitalised with common acute medical illnesses.

Global summary of maternal and newborn vitamin D status – a systematic review

Pregnant women and newborns are at increased risk of vitamin D deficiency. Our objective was to create a global summary of maternal and newborn vitamin D status. We completed a systematic review (1959-2014) and meta-analysis of studies reporting serum 25-hydroxyvitamin D [25(OH)D] concentration in maternal and newborn populations. The 95 identified studies were unevenly distributed by World Health Organization (WHO) region: Americas (24), European (33), Eastern Mediterranean (13), South-East Asian (7), Western Pacific (16) and African (2). Average maternal 25(OH)D concentrations (nmol L(-1) ) by region were 47-65 (Americas), 15-72 (European), 13-60 (Eastern Mediterranean), 20-52 (South-East Asian), 42-72 (Western Pacific) and 92 (African). Average newborn 25(OH)D concentrations (nmol L(-1) ) were 35-77 (Americas), 20-50 (European), 5-50 (Eastern Mediterranean), 20-22 (South-East Asian), 32-67 (Western Pacific) and 27-35 (African). The prevalences of 25(OH)D <50 and <25 nmol L(-1) by WHO region in pregnant women were: Americas (64%, 9%), European (57%, 23%), Eastern Mediterranean (46%, 79%), South-East Asian (87%, not available) and Western Pacific (83%, 13%). Among newborns these values were: Americas (30%, 14%), European (73%, 39%), Eastern Mediterranean (60%, not available), South-East Asian (96%, 45%) and Western Pacific (54%, 14%). By global region, average 25(OH)D concentration varies threefold in pregnant women and newborns, and prevalence of 25(OH)D <25 nmol L(-1) varies eightfold in pregnant women and threefold in newborns. Maternal and newborn 25(OH)D concentrations are highly correlated. Addressing vitamin D deficiency in pregnant women and newborns should be a global priority. To protect children from the adverse effects of vitamin D deficiency requires appropriate interventions during both pregnancy and childhood.

Pertussis requiring intensive care

Objectives: To describe children with pertussis who require intensive care. Design, setting and patients: An audit in Auckland, New Zealand, of pertussis admissions to the national paediatric intensive care unit (PICU) from 1991 to 2003. Results: 72 children, 97% of whom were <12 months old. The annual number of cases increased with time (p = 0.04). Forty patients (56%) were coughing for less than 8 days before admission. Apnoea or paroxysmal cough was present in 33 (83%) of these children. Thirty five (49%) received assisted ventilation. Four died. 19% were readmitted to PICU. Those readmitted presented with more atypical disease and had a shorter first admission but longer total PICU admission (9 vs 5 days, p = 0.009). Of the 58 children from Auckland, nine either died (three) or had subsequent respiratory or neurodevelopmental problems (six). There was an increased risk (relative risk, 95% CI) of death or disability associated with having a co-morbidity (RR = 5.56, 1.50 to 8.15), an elevated lymphocyte count (RR = 5.75, 1.54 to 13.65), presenting with seizures/encephalopathy (4.87, 1.18 to 8.34) or shock (6.50, 1.89 to 8.94), having a PIM score of 1% or more (RR = 6.20, 1.22 to 21.72), any abnormal neurological signs (RR = 9.65, 3.32 to 15.23) or being readmitted to PICU (RR = 4.63, 1.44 to 8.82). Conclusions: Apnoea and paroxysmal cough are key symptoms of pertussis in those with shorter cough duration. Death or disability are frequent. Clinical factors define children at increased risk of these poor outcomes. Early discharge from PICU is associated with an increased risk of readmission and poor outcome.

Tools for Assessing Outcomes in Studies of Chronic Cough: CHEST Guideline and Expert Panel Report

BACKGROUND Since the publication of the 2006 American College of Chest Physicians (CHEST) cough guidelines, a variety of tools has been developed or further refined for assessing cough. The purpose of the present committee was to evaluate instruments used by investigators performing clinical research on chronic cough. The specific aims were to (1) assess the performance of tools designed to measure cough frequency, severity, and impact in adults, adolescents, and children with chronic cough and (2) make recommendations or suggestions related to these findings. METHODS By following the CHEST methodologic guidelines, the CHEST Expert Cough Panel based its recommendations and suggestions on a recently published comparative effectiveness review commissioned by the US Agency for Healthcare Research and Quality, a corresponding summary published in CHEST, and an updated systematic review through November 2013. Recommendations or suggestions based on these data were discussed, graded, and voted on during a meeting of the Expert Cough Panel. RESULTS We recommend for adults, adolescents (≥ 14 years of age), and children complaining of chronic cough that validated and reliable health-related quality-of-life (QoL) questionnaires be used as the measurement of choice to assess the impact of cough, such as the Leicester Cough Questionnaire and the Cough-Specific Quality-of-Life Questionnaire in adult and adolescent patients and the Parent Cough-Specific Quality of Life Questionnaire in children. We recommend acoustic cough counting to assess cough frequency but not cough severity. Limited data exist regarding the performance of visual analog scales, numeric rating scales, and tussigenic challenges. CONCLUSIONS Validated and reliable cough-specific health-related QoL questionnaires are recommended as the measurement of choice to assess the impact of cough on patients. How they compare is yet to be determined. When used, the reporting of cough severity by visual analog or numeric rating scales should be standardized. Previously validated QoL questionnaires or other cough assessments should not be modified unless the new version has been shown to be reliable and valid. Finally, in research settings, tussigenic challenges play a role in understanding mechanisms of cough.

Randomized, double-blind comparison of growth in infants receiving goat milk formula versus cow milk infant formula.

Objective: To compare growth of infants fed goat milk infant formula (GMF) or cow milk infant formula (CMF) and to compare tolerability and safety of the two formulas.

Recruitment of practices in primary care research: the long and the short of it

OBJECTIVE To determine factors that facilitated or hindered recruitment of general practices into a large New Zealand primary care project that aimed to determine general practice characteristics of immunization coverage. METHODS The project had a multi-level recruitment strategy requiring recruitment of randomly selected practices before randomly selecting GPs, practice nurses and caregivers of children enrolled at those practices. Detailed quantitative and qualitative recruitment data were recorded on an access database. Post-recruitment, recruiters underwent semi-structured interviews. Analysis was mixed method, with triangulation of descriptive statistics of the number of calls and time course to recruitment and general inductive thematic analysis of qualitative data. RESULTS Identifying key decision makers and how individual practice processes work can save significant recruitment time. Factors identified as assisting practice recruitment included using a personal approach from doctor to doctor, getting buy-in from all practice staff, streamlining the research process to minimize disruption to the practice and flexibility to accommodate practices. CONCLUSIONS The task of recruiting should not be underestimated. Adequate time and resource need to be allocated from the onset. Long periods where practices have no added burdens such as audits, mass vaccination programmes or influenza season are unlikely, therefore there are always considerable challenges in recruiting practices for research. Remaining flexible to individual practice styles and influences and acknowledging the commitment of participants is important.