Risk factors for reporting adverse events and for study withdrawal in a population-based trial of vitamin D supplementation.

With increasing numbers of randomized controlled trials (RCTs) investigating potential health events of vitamin D supplementation, a better understanding is required of the risk factors for adverse events and for study withdrawals. This analysis aimed to identify baseline risk factors of reporting an adverse event in a multi-year randomized double-blinded placebo-controlled trial of vitamin D supplementation. The secondary aim was to investigate if adverse events were associated with study withdrawals. We analyzed data from the Vitamin D Assessment (ViDA) study: 5110 adults, aged 50-84 years, living in Auckland, New Zealand. Monthly doses of 100,000 IU vitamin D3 or placebo were mailed to participants homes, with a questionnaire to collect data on adverse events and adherence to the study capsule (initially monthly, then 4-monthly). Median follow-up was 3.3 years. Data were analysed using multivariable log-binomial regression and Cox-regression. During the follow-up period, 818 people reported adverse events and 412 withdrew or stopped returning questionnaires. Vitamin D was not associated with reporting of adverse events. Of sociodemographic factors, ethnicity was associated with reporting adverse events: compared to European participants, Maori and Pacific Islander people were more likely to report an adverse event. Non-smokers were more likely to report an adverse event, compared to smokers (adjusted hazard ratio (HR) = 1.80; 95%CI = 1.24, 2.62); as were those who had reported a history of depression (adjusted HR = 1.27; 95%CI = 1.01, 1.60) or a recent cough or cold (adjusted HR = 1.22; 95%CI = 1.03, 1.44) at baseline. Reporting of adverse events was not associated with withdrawals (adjusted HR = 1.12; 95%CI = 0.86, 1.46). These data did not identify any clear pattern in the factors associated with self-reported adverse events, which themselves did not increase risk of withdrawals.

Monthly high-dose vitamin D3 supplementation and self-reported adverse events in a 4-year randomized controlled trial.

BACKGROUND: The use of high-dose vitamin D supplementation has increased in recent years. However, relatively little is known about the safety of long-term high doses. AIMS: To investigate the safety of a monthly high-dose of vitamin D3 supplementation taken for up to 4 years. METHODS: Data were collected in a randomized, double blind, placebo-controlled trial of 5108 adults aged 50-84 years old from Auckland, New Zealand. Participants were given monthly doses of 100,000 IU vitamin D3 or placebo, for a median of 3.3 years (range 2.5-4.2 years). They answered an open-ended question in a monthly questionnaire about any adverse events they attributed to the study capsules, which were coded blindly. Incidence rates per person months were calculated for categories of adverse events. Cox regression model used to calculate hazard ratio of time to first adverse-event. RESULTS: In total, 419 (16.5%) participants taking vitamin D and 399 (15.8%) taking placebo reported ≥1 adverse event. Compared to placebo, the hazard ratio (HR) of reporting first adverse event in the vitamin D group was 1.03 (95% CI: 0.90, 1.18; p = 0.63). Despite a slightly higher incidence of recurrent adverse events in vitamin D arm, the incidence rate ratio (1.17) was not significantly higher in vitamin D (95% CI: 0.97, 1.41; p = 0.10). All regression results were adjusted for age, sex, and ethnicity. There was no difference between study arms in terms of participants' allocation perception (p = 0.52). CONCLUSION: Monthly supplementation of 100,000 IU vitamin D3 for a median of 3.3 years did not affect participant-reported adverse events. TRIAL REGISTRATION: clinicaltrials.gov Identifier: ACTRN12611000402943; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=ACTRN12611000402943.

Provision of information on regulatory authorities' websites.

BACKGROUND: Several organizations have raised concerns about the excessive secrecy maintained by regulatory authorities around the world, in particular in the European Union, France, UK, Canada and Australia. However, limited research has assessed the provision of information by regulatory authorities. This study aimed to assess the type and availability of information provided on the regulatory authorities' websites. METHODS: Regulatory authorities' websites in six countries (USA, Canada, UK, France, Australia and New Zealand) and at the European level (European Medicines Evaluation Agency) were surveyed by two reviewers between October 2005 and March 2006. The survey instrument included 16 criteria organized in 3 domains: information on marketed drugs, information on assessment of drugs and information on drug safety. RESULTS: There was a great variability in the level of information provided. Several medicine agencies did not provide basic information on marketed drugs, such as the summary of products' characteristics. Information on registration dossiers was scant on most websites except that of the US Food and Drug Administration. The European Medicines Evaluation Agency, the French agency and the Canadian agency released public assessment reports that contained only summarized information of registration data. Only one country, Canada, provided full access to pharmacovigilance data. The periodic safety update reports that companies have to provide regularly to regulatory authorities were not available in any country. CONCLUSION: Information on which regulatory authorities base their decisions for licensing new drugs and the rationales behind these decisions were often not publicly available.

Preventive care in Canterbury general practice.

AIMS: To describe the preventive care attitudes, beliefs, priorities and systems of Canterbury general practitioners, to compare their beliefs about appropriate care with evidence-based guidelines and to investigate possible associations between preventive care beliefs and attitudes, and selected practitioner variables. METHOD: A questionnaire was mailed to all 375 general practitioners in Canterbury, with a response rate of 70%. RESULTS: Respondents expressed positive attitudes to preventive care, their views about appropriate care corresponding well to United States Preventive Services Task Force recommendations. The responses of practitioners who had qualified more recently were closer to the recommendations, with these practitioners more likely to want to carry out more preventive care. Membership of an independent practice association or the Royal New Zealand College of General Practitioners was associated with more positive attitudes to preventive care and with believing more interventions to be appropriate. Relatively few preventive interventions appeared to be offered to patients in a systematic way. CONCLUSIONS: Canterbury general practitioners were well-informed about, and interested in carrying out, more preventive care. Preventive care delivery could be enhanced in many practices by the adoption of a more systematic approach.

Evaluation of a self-management plan for chronic obstructive pulmonary disease.

We hypothesized that the use of an Action Plan might assist self-management for patients with chronic obstructive pulmonary disease (COPD). A pilot process and randomized, controlled study were undertaken to evaluate an Action Plan that provided advice on management of usual care and exacerbations, together with a booklet on self-management. Fifty six subjects with COPD recruited through general practitioners (GPs) completed the 6 month study, 27 in the control group and 29 in the intervention group. The control group received usual care from their GP, and the intervention group received a booklet and Action Plan from their practice nurse plus a supply of prednisone and antibiotic from their GP. The two groups were demographically similar with a mean age of 68 yrs. The resources were well received by GPs, practice nurses and intervention group subjects. After 6 months, there were no differences in quality of life scores or pulmonary function. There were significant changes in self-management behaviour in the intervention group compared to controls. In response to deteriorating symptoms, 34 versus 7% (p=0.014) initiated prednisone treatment and 44 versus 7% (p=0.002) initiated antibiotics. Subjects in the intervention group readily adopted self-management skills but did not show any difference in quality of life or lung function parameters. A larger, prospective, controlled, clinical trial of this approach is warranted.

Respiratory effects of air pollution in chronic obstructive pulmonary disease: a three month prospective study.

BACKGROUND: A study was undertaken to investigate the relationship between air pollution levels and respiratory symptoms and peak expiratory flow rate (PEFR) in subjects with chronic obstructive pulmonary disease (COPD) living in Christchurch, New Zealand. METHODS: Forty subjects aged over 55 years with COPD completed twice daily diaries for three months during the winter of 1994. Subjects recorded respiratory symptoms, PEFR, outdoor activity, visits to doctor or hospital, and medication use. All were resident within a 5 km radius of the regional council's air pollution monitoring site. Daily and hourly mean pollutant levels (particulates (PM10, nitrogen dioxide (NO2), sulphur dioxide (SO2) and carbon monoxide (CO)) were measured at the monitoring site. RESULTS: Pollution levels were generally low relative to those recorded in previous years. The New Zealand Ministry for the Environment guidelines for PM10 were exceeded on five occasions, and for CO six times. No association was found between PEFR and any of the pollution variables. A rise in the PM10 concentration equivalent to the interquartile range was associated with an increase in night time chest symptoms (relative risk 1.38, 95% CI 1.07 to 1.78). A rise in NO2 concentrations equivalent to the interquartile range was associated with increased reliever inhaler use (relative risk 1.42, 95% CI 1.13 to 1.79) and for 24 hour lag analysis with increased nebuliser use (relative risk 2.81, 95% CI 1.81 to 4.39). There was no increase in the relative risk of other symptoms in relation to pollution levels. CONCLUSIONS: These effects, demonstrated in a small susceptible group of subjects with COPD, indicate that adverse outcomes can be measured in response to pollution levels that are within current guidelines.

A community trial of a written self management plan for children with asthma. Asthma Foundation of NZ Children's Action.

AIMS: To determine the effect of introducing an action plan to children with mild to moderate asthma, who have never used a plan before. METHODS: Children were recruited from general practitioner records with a diagnosis of asthma, and who agreed to participate, having identified that they had not used an action plan before and that they had mild or moderate asthma based upon symptoms, acute episodes and the need for preventative medication. The families were given a plan, and its use was explained to them by their general practitioner. A symptom diary was kept, and, where appropriate, peak flow measurements were recorded. A number of outcomes were measured to determine changes that could be attributed to the introduction of the plan. RESULTS: Following the introduction of the plan, the percentage of nights woken for asthma fell from 18.2% to 12.2% (P<0.001) and the number of days out of action fell from 6.4 to 4.1 (P<0.001). The requirement for acute medical treatment also fell during the intervention period with general practitioner visits falling from 129 to 42 (p<0.001). Most participants commented favourably about the usefulness of the plan in giving them a better idea of the state of their asthma at any time, and in knowing what to do about it. CONCLUSIONS: The children's action plan, when introduced into a group of asthmatic children was effective and acceptable in the self management of asthma.

A community-wide promotion of asthma self-management in New Zealand.

Asthma affects approximately 9% of young adults in New Zealand, with evidence of an increase in prevalence over recent years. Morbidity and mortality from this condition have caused widespread concern. In response to identified deficiencies in asthma management, initiatives to promote self-management using an asthma action plan were promoted throughout the Canterbury region in 1991 as part of a regional pilot study. A resource kit was prepared and self-management principles were promoted to general practitioners in discussion workshops. A community-wide promotion of the action plan was followed by a process and outcome evaluation. The plan and associated resources were well received by doctors and patients. Seventy-seven percent of doctors responding to a questionnaire had used the plan, and of these, 94% indicated that they would continue to use the plan in the future. Patients who obtained a completed plan experienced a greater reduction in nocturnal waking with asthma and improved self-management skills.

A community wide promotion of asthma self management: process evaluation.

AIMS: During the months February through July 1991, a community wide promotion of asthma self-management was undertaken as a pilot study for the national launch of an asthma action plan developed by the Asthma Foundation of New Zealand in conjunction with the Royal New Zealand College of General Practitioners. METHODS: A multidisciplinary team of hospital and community-based health workers was established, with the aim of educating and resourcing general practitioners, practice nurses and retail pharmacists to enable them to effectively promote and distribute the asthma action plan. 332 general practitioners and 148 retail pharmacists were surveyed through postal and telephone questionnaires at the completion of the promotion, to assess its impact on health professionals and to obtain feedback for the national promotion of the asthma action plan. RESULTS: 108 (73%) of pharmacists who responded and were involved with the promotion found their participation to be worthwhile, although some had difficulty allocating sufficient time to give detailed advice to patients. Of the 240 general practitioners who responded, 77% indicated that they had used the asthma action plan with their patients. They were positive about the use of the workshop format that had provided education and resources for the plan, and of those that had used the plan, 94% indicated that they would continue to promote the plan, or one similar. CONCLUSIONS: The promotion of the asthma action plan in Canterbury had a major impact on health professionals. The community-wide promotion might have had a greater impact on people with asthma had television advertising been used. The pilot project provided useful feedback for the Asthma Foundation in their preparation for the national launch.

Towards a quantitative description of asthmatic cough sounds.

This study describes a method of quantitatively characterizing cough sounds using digital signal processing techniques. Differences between asthmatic and non-asthmatic cough sounds are presented. Coughs from 12 asthmatic and 5 non-asthmatic subjects were analysed. Cough sounds and flows were digitized, at a sampling rate of 5 kHz, before and after a free-running exercise test. Individual coughs were divided into two or three phases, corresponding to the initial glottal opening burst, the quieter middle phase, and (sometimes) the final closing burst. Standard signal processing techniques were then invoked to characterize the spectral and temporal shapes of the first two phases. Factor analysis indicated that the spectral shapes of the two phases are independent, with each being largely described by the degree of "peakedness" in the spectrum, and by the balance of energy between low and high frequencies. Both the duration of the initial burst and zero-crossing rates of the cough waveform (which indicates the "spectral balance") during each of the first two phases were smaller for asthmatic than for non-asthmatic coughs. Fewer asthmatic coughs contained a final burst. Discriminant analysis between the two groups gave classification error rates of 20-30%. The peak flow recorded during the cough was significantly smaller for asthmatics, and correlated very well with the peak flow recorded during forced expiration. Thus, significant differences exist between asthmatic and non-asthmatic cough sounds. An effective representation of the temporal structure of the cough sound is required to successfully characterize the cough.

A microcomputer-based interactive cough sound analysis system.

The occurrence and nature of cough sounds, especially those occurring in asthma in young children, is of considerable interest to workers in paediatrics and general practice. To facilitate our research into the characteristics of such sounds, we have developed a microcomputer-based analysis system, which we call COFF. In this paper we discuss the design and implementation of the system, emphasising its user-friendly, interactive features, and the manner in which it efficiently manages the large amounts of data that research into sounds incurs. We illustrate the operation of the system with examples of spectrograms computed from cough sounds recorded simultaneously at the mouth and through the chest wall.

A portable system for the spectral analysis of cough sounds in asthma.

A practical and portable method is described to analyze the sound spectra of coughs. The system is based upon a personal computer and simultaneously collects the sounds of cough heard both at the mouth and through the chest wall together with the airflow at the mouth produced during the cough. Subsequent analysis produce spectrographs of the cough sound linked to the corresponding airflow. The system will be used initially to examine the effects of exercise on the sound of cough in asthma. Further study of cough spectra in this way may be useful in the management of asthma either diagnostically or in the assessment of therapeutic interventions.

Cough sound analysis: a new tool for the diagnosis of asthma?

A method of computerized cough sound analysis is described. The sounds of nocturnal and post-exercise coughs from a child with asthma were compared with those from a child without asthma. The spectrographic patterns of voluntary cough at rest from the two children were similar. The pattern seen after exercise from the asthmatic child was different from the resting cough but similar to that seen during recorded nocturnal cough. In contrast the post-exercise cough from the non-asthmatic child was similar to the cough seen at rest. Refinement of this method of cough sound analysis may be useful in the diagnosis of asthma in young children.