Seasonality of medical contacts in school-aged children with asthma: association with school holidays.

OBJECTIVES: To assess the seasonality of medical contacts in children with asthma, to compare England with Scotland, and to assess the impact of medication compliance on the frequency of medical contacts. STUDY DESIGN: A retrospective study taken from the General Practice Research Database of daily medical contacts from 1999 to 2005 in a population of school-aged (5-16 years) children with a diagnosis of asthma, and age- and gender-matched controls. PRIMARY OUTCOME MEASURE: All unscheduled medical contacts. Prescription frequency for inhaled corticosteroids over the same period was also assessed. RESULTS: Data from 76,924 children were analyzed. There was an increase in unscheduled medical contacts for all children on return to school in September. Unscheduled medical contacts occurred almost twice as frequently in children with asthma compared with non-asthmatic children. The frequency of medical contacts in children with asthma could be predicted from the frequency of medical contacts in non-asthmatic children. In the 3 months from September to December, unscheduled medical contacts were disproportionately greater than would be predicted for children with asthma relative to non-asthmatic children in both England and Scotland. The rise in medical contacts in Scotland preceded that in England by approximately 14 days, reflecting the earlier date for returning to school. The number of prescriptions for inhaled corticosteroids decreased in August. A higher incidence of unscheduled medical contacts was noted during September in those not receiving a prescription in August. CONCLUSIONS: Returning to school after the summer break is associated with a sharp increase in unscheduled medical contacts in school-aged children, particularly in those with asthma. This follows a decrease in the number of prescriptions for inhaled corticosteroids. It is suggested that at least part of the excess numbers of unscheduled contacts in children with asthma is because they do not maintain their inhaled corticosteroids over the summer holidays.

The relationship between administered radiopharmaceutical activity in myocardial perfusion scintigraphy and imaging outcome.

INTRODUCTION: Lower radiopharmaceutical activities are used for myocardial perfusion scintigraphy (MPS) in the UK than in other countries. There is no evidence to suggest that higher activities improve imaging or clinical outcome. MATERIALS AND METHODS: We undertook a multicentre study of the relationship between radiopharmaceutical activity and imaging outcome. Fifty-one patients with clinical referrals for MPS followed a 2-day protocol with an injection of 1,000 MBq (99m)Tc-tetrofosmin for each of the stress and rest images. ECG-gated acquisition was performed in three rotations occupying 25, 35 and 40% of a standard acquisition, and rotations were summed to simulate administered activities of 250, 400, 750 and 1,000 MBq. Each set of images was reported by an experienced physician who was blinded to all clinical information and to the simulated activity. Scores were assigned for image quality, low count, attenuation and reconstruction artefact, segmental tracer uptake, segmental and global defect classification, and confidence in the global classification. The images were reported twice to assess intra-observer variability. RESULTS: Positive relationships were found between administered activity and overall image quality, observer confidence and intra-observer agreement of uptake score, and a negative relationship was found with low-count artefact. For the majority of comparisons, there was no additional improvement with increasing activity from 750 to 1,000 MBq. Intra-observer agreement was found to be better in female patients and in those below average body mass index. DISCUSSION: We conclude that higher administered radiopharmaceutical activities lead to better quality images and improved surrogate parameters for clinical outcome, but that activities above 750 MBq may be unnecessary in average patients.

Increases in asthma hospital admissions associated with the end of the summer vacation for school-age children with asthma in two cities from England and Scotland.

In school-age asthmatics, an increase in hospitalizations has been reported in early autumn. This increase in admissions is conjectured to be associated with the return back to school. In the UK schools in England complete their summer vacations 2 weeks later than in Scotland and so there should be a lag between the two countries in the increase in asthma episode. Daily hospital asthma admission data from Aberdeen (in Scotland) and Doncaster (in England) for the period July 23rd to October 8th for years 1999-2004 were included in the analysis. There are peaks in hospitalization after the return back to school for both Aberdeen and Doncaster with the peak for Doncaster appearing 2 weeks after Aberdeen. This study has demonstrated peaks in admissions in school-age children around the return back to school in two cities where different school return dates were reflected in a 2-week lag effect. These data therefore provide strong evidence that peaks in admissions are associated with the end of the summer holidays.

Atmospheric pressure and sudden infant death syndrome in Cook County, Chicago.

We investigated daily deaths from sudden infant death syndrome (SIDS) in Cook County, Chicago, from 1 January 1986 to 31 December 1990. The daily SIDS rate was 0.54 deaths/day. Mean daily atmospheric pressure ranged from 952 to 1007 mb. We found a weak link with barometric pressure, whereby an increase of 10 mb was associated with an increased risk of 12% [95% CI 0.1%, 24%]. Cross-tabulation revealed that the highest SIDS rates were associated with a drop from high to low pressure. Possible reasons for this are discussed.

Why do we continue to use standardized mortality ratios for small area comparisons?

Public health practitioners are often faced with the necessity to compare the mortality experience of different geographical areas. Indirect standardization, producing a 'standardized mortality ratio' (SMR) is the most commonly used technique for doing this. However, as we show, indirect standardization is inappropriate for such comparisons, as SMRs for different geographical areas have different denominators. The fact that indirect standardization is usually chosen for this type of comparison is probably based on two beliefs: (1) that direct standardization yields only a rate rather than a more easily interpreted ratio or index; (2) that direct standardization cannot be carried out in many cases because the sub-group specific mortality rates in the groups to be compared are not available or, in at least some age classes, are based upon such small numbers as to be completely unreliable. In this paper we show that a simple index (the comparative mortality figure) can be calculated from the directly standardized rate in most cases. Using a comparison of the overall mortality experience of electoral wards in Sheffield between 1980 and 1987 we demonstrate also that the advantage gained by the smaller standard error of the SMR is outweighed by the bias inherent in its construction. We recommend that the SMR is used only when absolutely necessary, that is, in the rare circumstance when data are not available for the calculation of age- and sex-specific subgroup rates in the study population.

Problems with the performance of the SF-36 among people with type 2 diabetes in general practice.

OBJECTIVE: To validate the short form-36 (SF-36) among people with type 2 diabetes in general practice, and to make comparisons with the Audit of Diabetes Dependent Quality of Life (ADDQoL). DESIGN: Postal survey with one reminder. SETTING: Four general practices. PATIENTS: One hundred and eighty-four eligible patients (30-70 years) with type 2 diabetes on 14 general practitioner lists. MEASURES: SF-36 response rates, distribution of dimension scores and internal consistency. Median scores in relation to sociodemography and self-reported health. Comparisons with ADDQoL scores. RESULTS: One hundred and thirty-one patients responded (71%). Distributions of SF-36 dimension scores were mostly skewed. Internal consistency and construct validity were acceptable, with predictable sociodemographic trends. People with illness related to or unrelated to diabetes scored significantly lower on most dimensions. SF-36 dimension scores correlated best with relevant diabetes-specific ADDQoL scores amongst respondents reporting no comorbidity. CONCLUSIONS: Although valid and reliable, SF-36 scores are strongly affected by non-diabetic comorbidity in type 2 diabetes, supporting the complementary use of a diabetes-specific measure, providing information about the impact of diabetes specifically.

Sample sizes for cancer trials where Health Related Quality of Life is the primary outcome.

Health Related Quality of Life (HRQoL) instruments are increasingly important in evaluating health care, especially in cancer trials. When planning a trial, one essential step is the calculation of a sample size, which will allow a reasonable chance (power) of detecting a pre-specified difference (effect size) at a given level of statistical significance. It is almost mandatory to include this calculation in research protocols. Many researchers quote means and standard deviations to determine effect sizes, and assume the data will have a Normal distribution to calculate their required sample size. We have investigated the distribution of scores for two commonly used HRQoL instruments completed by lung cancer patients, and have established that scores do not have the Normal distribution form. We demonstrate that an assumption of Normality can lead to unrealistically sized studies. Our recommendation is to use a technique that is based on the fact that the HRQoL data are ordinal and makes minimal but realistic assumptions.

Why are pharmacokinetic data summarized by arithmetic means?

The main aim of many studies in clinical pharmacology is to describe the pharmacokinetic activity of a given compound. This pharmacokinetic activity for an individual is then evaluated through a series of summary parameters, such as area under the concentration-time curve (AUC), maximum concentration (Cmax) and the rate constant lambda, and it is evaluated across individuals by descriptive statistics of these parameters, such as the mean and range and a measure of spread such as the standard deviation. How the pharmacokinetic parameters are derived is described here. It is demonstrated that the assumption of an exponential half-life is often fundamental to the derivation of pharmacokinetic parameters. Given this fact, one would think it logical that data are analyzed with the appropriate statistics on the log-scale and not by summary statistics, such as arithmetic means, on the original scale. Why arithmetic means are used to describe the data is explored and the special nature of the log-transformation highlighted.

Estimating sample sizes for continuous, binary, and ordinal outcomes in paired comparisons: practical hints.

Paired data occur in crossover trials and matched case-control studies, and it is rare to find studies reporting sample size calculations associated with these types of studies, despite recommendations from editors that sample size calculations should be justified. In this article we describe some simple formulas and strategies for calculating the number of patients that should be entered into a matched or paired study when the outcome measures are continuous, binary, or ordinal.

Sample size calculations for paired or matched ordinal data.

The problem of calculating the number of subjects in a paired or matched study in which the outcome variable is ordinal is discussed. A common approach in the case of a two category variable is to calculate the required number of discordant pairs, and then divide this by the expected proportion of discordant pairs to obtain the total sample size. An approximate solution for the number of discordant pairs is proposed for ordinal data and compared to sample sizes estimated through simulation. It is shown that the sample sizes are underestimated when the number of categories is two, but that the approximation improves as the number of categories increases. Comparison of the required discordant sample size when there are two categories with the required sample size for more than two categories would suggest that the loss of power is not great if a categorical variable is collapsed into only two categories. However, the total sample size required is likely to be greater with only two categories, since the expected proportion of discordant to concordant pairs increases. Since the expected number of discordant pairs is likely to decrease as the number of categories increases, this suggests that as a rule of thumb the required discordant sample size for the two category case be used as an approximation to the total required sample size when the number of categories is greater than two.

Chronic Chlamydia pneumoniae infection and asthma exacerbations in children.

This study was undertaken to investigate the reported association between Chlamydia pneumoniae and Mycoplasma pneumoniae infection and the expression of asthma-related symptoms. One hundred and eight children with asthma symptoms, aged 9-11 yrs, completed a 13 month longitudinal study. The children maintained a daily diary of respiratory symptoms and peak flow rates. When respiratory symptoms were reported an investigator was called and a nasal aspirate obtained. In total 292 episodes were reported. After the study 65 children provided samples when asymptomatic. The presence of infection was investigated by the polymerase chain reaction for C. pneumoniae and M. pneumoniae and C. pneumoniae secretory immunoglobulin A (IgA) was detected by amplified enzyme immunoassay. C. pneumoniae detections were similar between the symptomatic and asymptomatic episodes (23 versus 28%, respectively). Children who reported multiple episodes also tended to remain PCR positive for C. pneumoniae suggesting chronic infection (p< 0.02). C. pneumoniae-specific secretory-IgA antibodies were more than seven times greater in subjects who reported four or more exacerbations in the study compared to those who reported just one (p<0.02). M. pneumoniae was found in two of 292 reports and in two of 65 asymptomatic samples. In conclusion, chronic Chlamydia pneumoniae infection is common in schoolage children and immune responses to C. pneumoniae are positively associated with frequency of asthma exacerbations. We suggest that the immune response to chronic C. pneumoniae infection may interact with allergic inflammation to increase asthma symptoms. In contrast Mycoplasma pneumoniae was not found to be important in this study.

Acupuncture in the prevention of postoperative nausea and vomiting.

The efficacy of intra-operative acupuncture at the PC6 point in the prevention of postoperative nausea or vomiting was studied. A double-blind randomised controlled study of acupuncture versus placebo was performed in 81 patients scheduled for day case gynaecological laparoscopic surgery. Failure of treatment was defined as the occurrence of nausea or vomiting prior to or within 24 h of discharge. The use of acupuncture reduced the incidence of postoperative nausea or vomiting in hospital from 65% to 35% compared with placebo and after discharge from 69% to 31% compared with placebo.

Sample sizes for randomized trials measuring quality of life in cancer patients.

This paper describes the methods appropriate for calculating sample sizes for clinical trials assessing quality of life (QOL). An example from a randomized trial of patients with small cell lung cancer completing the Hospital Anxiety and Depression Scale (HADS) is used for illustration. Sample size estimates calculated assuming that the data are either of the Normal form or binary are compared to estimates derived using an ordered categorical approach. In our example, since the data are very skewed, the Normal and binary approaches are shown to be unsatisfactory: binary methods may lead to substantial over estimates of sample size and Normal methods take no account of the asymmetric nature of the distribution. When summarizing normative data for QOL scores the frequency distributions should always be given so that one can assess if non-parametric methods should be used for sample size calculations and analysis. Further work is needed to discover what changes in QOL scores represent clinical importance for health technology interventions.

Diazepam for relief of irrigation pain after transurethral resection of the prostate.

Irrigation of the bladder after transurethral resection of the prostate is often distressing because of pain arising from detrusor muscle spasm. The effect of post-operative oral diazepam was compared with sacral epidural (caudal) block at the time of surgery, both treatments together and a control group, assessed by three-point rank scoring. Either treatment significantly reduced the incidence of pain reported by patients, P < 0.001. No patient experienced pain after both treatments.

The flow cytometric analysis of total p53 protein content and proliferation indices in colorectal cancer, in relation to clinical outcome.

This study was undertaken to assess the value of flow cytometric measurements of total p53 protein content and proliferation indices derived from in vivo halogenated pyrimidine labelling. Two series of colorectal cancer specimens were studied for which clinical outcome data were recorded. A series of 84 archival, ethanol-fixed, bromodeoxyuridine (BrdUrd) labelled colorectal tumours were analysed by flow cytometry for their total and cell cycle phase p53 protein content using the pAb1801 monoclonal antibody. A second series of 33 freshly obtained tumours was used for assay evaluation and for comparison with the archival material. In the archival series (n=84), the median p53-pAb1801 LI was 81.9% (range: 11.1-99.8%). In only three tumours could significant amounts of p53 protein not be detected. The median phase specific p53-pAb1801 LI in G0/G1 was 71.6%, in S was 95.5%, and in G2/M was 98.5%. In the series of fresh tumours (n=33), the median p53-pAb1801 labelling index (LI) was 94.6% (range: 17.9-99.9%). Only two tumours failed to express significant amounts of p53 protein. There was no significant difference in the generally high levels of p53 protein content between the fresh and archival series. Life-table analysis of the patients in the archival series failed to demonstrate a statistical difference in life expectancy in relation to Dukes' stage when tumours were stratified by the median total p53 labelling index. In this study, p53 content and proliferative indices measured by flow cytometry do not have independent predictive value over Dukes' grading in determining the outcome of colorectal cancer. Flow cytometry is confirmed as a practical tool for multi-parametric and cell cycle analysis of oncoprotein expression in human tumour biopsies.

Estimating sample sizes for binary, ordered categorical, and continuous outcomes in two group comparisons.

Sample size calculations are now mandatory for many research protocols, but the ones useful in common situations are not all easily accessible. This paper outlines the ways of calculating sample sizes in two group studies for binary, ordered categorical, and continuous outcomes. Formulas and worked examples are given. Maximum power is usually achieved by having equal numbers in the two groups. However, this is not always possible and calculations for unequal group sizes are given.