Responsiveness of quality of life instruments : a thesis presented in partial fulfilment of the requirements for the degree of Master of Applied Statistics in Statistics at Massey University

Quality of life (QoL) is a phrase that is intuitively meaningful. As a concept it distinguishes between the mere duration of life and a life that is in some sense 'worthwhile'. QoL measurement is thought to be important in the assessment of chronic health conditions and their treatment. It is difficult to create an operational definition of QoL that takes into account different concepts of QoL as well as the heterogeneity of subjects and diseases. Responsiveness is one aspect of instruments which measure QoL. A responsive instrument captures the change in QoL in response to interventions which change underlying health conditions. Internal responsiveness, measured by a variety of standardised mean changes, reflects change in a QoL instrument score measured on subjects who 'should have' changed. External responsiveness relates change in a QoL instrument score to a change in external criteria. Methods of determining external responsiveness include receiver operating characteristic curves, correlation and simple regression. Simple linear regression can be extended using linear mixed models which can estimate parameters either by maximum likelihood or by Markov Chain Monte Carlo methods. This thesis critically examines methods of assessing responsiveness and demonstrates the methodology, including the extension to linear mixed models. The data set used for illustration is based on a study of subjects with rheumatoid arthritis who are assessed before and after a period of inpatient hospital treatment for their condition. Three new QoL instruments, the EuroQol, the Quality of Life Profile and the WHOQoL-Bref were found to be moderately responsive. However the available methodology and the extensions described in this thesis were unable to find any difference in responsiveness. Reasons for this could include that QoL instruments are relatively blunt instruments for the detection of change. The external criteria for change used may not have been ideal. The reasons for a choice of instrument for QoL assessment may be better related to ease of completion, interpretation and analysis, than on sophisticated assessment of responsiveness

The 24h duration of bronchodilator action of the salmeterol/fluticasone combination inhaler

SummaryIntroduction: The duration of bronchodilator action of the long-acting beta agonist salmeterol when administered in the evening has not been investigated. In this study we have investigated whether a single evening dose of salmeterol, administered from the combination salmeterol/fluticasone (SFC) Accuhaler significantly attenuates the circadian rhythm in airway tone over 24h.Methods: Eighteen subjects with mild to moderate asthma (mean FEV1 84% predicted) participated in a double-blind, double dummy, placebo controlled, cross-over study. Subjects inhaled, in random order, placebo, salbutamol (200μg) or SFC (50/100μg) administered in the evening (2000h) on three separate occasions. Lung function measurements including FEV1, specific airways conductance (sGaw) and maximum expiratory flow at 25–75% of vital capacity (MEF25−75%) were assessed at baseline, at 1h and subsequently every 4h post-dose for 24h.Results: Compared with placebo, SFC significantly improved the three measures of airways function throughout the 24h period, with a difference in FEV1 at 24h of 0.24l (0.00–0.47l). SFC abolished the biphasic pattern of the circadian rhythm in airway tone. In contrast, salbutamol had a significant bronchodilator action of 4–8h, depending on the lung function parameter measured.Conclusion: The single evening administration of SFC via the Accuhaler resulted in a duration of bronchodilation of at least 24h, with the abolition of the accentuated biphasic circadian variation in airway tone observed in asthma

Randomised controlled trial of rhinothermy for treatment of the common cold: a feasibility study

OBJECTIVE: To determine the feasibility of a randomised controlled trial (RCT) of rhinothermy for the common cold. DESIGN: Open label, randomised, controlled feasibility study. SETTING: Single-centre research institute in New Zealand recruiting participants from the community. PARTICIPANTS: 30 adult participants with symptoms of a common cold, presenting within 48 hours of the onset of symptoms. INTERVENTIONS: Participants were randomly assigned 2:1 to receive either 35 L/min of 100% humidified air at 41°C via high flow nasal cannulae, 2 hours per day for up to 5 days (rhinothermy), or vitamin C 250 mg daily for 5 days (control). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the proportion of screened candidates who were randomised. Secondary outcomes included: proportion of randomised participants who completed the study; modified Jackson scores from randomisation to 10 days after initiation of randomised regimen; time until feeling 'a lot better' compared with study entry; time until resolution of symptoms or symptom score at 10 days postrandomisation; proportion of organisms identified by PCR analysis of nasal swabs taken at baseline; the patterns of use of the rhinothermy device; estimated adherence of the control group; and rhinothermy device tolerability. RESULTS: In all 30/79 (38%, 95% CI 27% to 50%) of potential participants screened for eligibility were randomised. Rhinothermy was well tolerated, and all randomised participants completed the study (100%, 95% CI 88% to 100%). The reduction from baseline in the modified Jackson score was greater with rhinothermy compared with control at days 2, 3, 4, 5 and 6, with the maximum difference at day 4 (-6.4, 95% CI -9.4 to -3.3). The substantial clinical benefit threshold for modified Jackson score was a 5-unit change. CONCLUSIONS: This study shows that an RCT of rhinothermy compared with low-dose vitamin C in the treatment of the common cold is feasible. TRIAL REGISTRATION NUMBER: ACTRN12616000470493; Results

Combinatorics of compactified universal Jacobians

We use orientations on stable graphs to express the combinatorial structure of the compactified universal Jacobians in degrees g-1 and g over the moduli space of stable curves, \Mgb, and construct for them graded stratifications compatible with the one of \Mgb. In particular, for a stable curve we exhibit graded stratifications of the compactified Jacobians in terms of totally cyclic, respectively rooted, orientations on subgraphs of its dual graph.Comment: Final version, to appear in Advances in Mathematics. 41 page

How big is your bubble? : characteristics of self-isolating household units ('bubbles') during the COVID-19 Alert Level 4 period in New Zealand : a cross-sectional survey

Objective To characterise the self-isolating household units (bubbles) during the COVID-19 Alert Level 4 lockdown in New Zealand. Design, setting and participants In this cross-sectional study, an online survey was distributed to a convenience sample via Facebook advertising and the Medical Research Institute of New Zealand's social media platforms and mailing list. Respondents were able to share a link to the survey via their own social media platforms and by email. Results were collected over 6 days during Alert Level 4 from respondents living in New Zealand, aged 16 years and over. Main outcomes measures The primary outcome was the mean size of a self-isolating household unit or bubble. Secondary outcomes included the mean number of households in each bubble, the proportion of bubbles containing essential workers and/or vulnerable people, and the mean number of times the home was left each week. Results 14 876 surveys were included in the analysis. The mean (SD) bubble size was 3.58 (4.63) people, with mean (SD) number of households 1.26 (0.77). The proportion of bubbles containing one or more essential workers, or one or more vulnerable persons was 45.3% and 42.1%, respectively. The mean number of times individual bubble members left their home in the previous week was 12.9 (12.4). Bubbles that contained at least one vulnerable individual had fewer outings over the previous week compared with bubbles that did not contain a vulnerable person. The bubble sizes were similar by respondent ethnicity. Conclusion In this New Zealand convenience sample, bubble sizes were small, mostly limited to one household, and a high proportion contained essential workers and/or vulnerable people. Understanding these characteristics from a country which achieved a low COVID-19 infection rate may help inform public health interventions during this and future pandemics

Kanuka honey versus aciclovir for the topical treatment of herpes simplex labialis : a randomised controlled trial

Objective To compare New Zealand medical grade kanuka honey with topical aciclovir for the treatment of herpes simplex labialis. Design Prospective parallel randomised controlled open-label superiority trial. Setting 76 community pharmacies across New Zealand between 10 September 2015 and 13 December 2017. Participants 952 adults randomised within the first 72 hours of a herpes simplex labialis episode. Interventions Random assignment 1:1 to either 5% aciclovir cream or medical grade kanuka honey (90%)/glycerine (10%) cream, both applied five times daily. Outcome measures The primary outcome was time from randomisation to return to normal skin (stage 7). Secondary outcomes included time from randomisation to stage 4 (open wound), time from stage 4 to 7, maximal pain, time to pain resolution and treatment acceptability. Results Primary outcome variable: Kaplan-Meier-based estimates (95% CI) for the median time in days for return to normal skin were 8 (8 to 9) days for aciclovir and 9 (8 to 9) for honey; HR (95% CI) 1.06 (0.92 to 1.22), p=0.56. There were no statistically significant differences between treatments for all secondary outcome variables. No related serious adverse events were reported. Conclusion There was no evidence of a difference in efficacy between topical medical grade kanuka honey and 5% aciclovir in the pharmacy-based treatment of herpes simplex labialis

ICS-formoterol reliever therapy stepwise treatment algorithm for adult asthma

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