Investigating the missing data mechanism in quality of life outcomes: a comparison of approaches

Background: Missing data is classified as missing completely at random (MCAR), missing at random (MAR) or missing not at random (MNAR). Knowing the mechanism is useful in identifying the most appropriate analysis. The first aim was to compare different methods for identifying this missing data mechanism to determine if they gave consistent conclusions. Secondly, to investigate whether the reminder-response data can be utilised to help identify the missing data mechanism. Methods: Five clinical trial datasets that employed a reminder system at follow-up were used. Some quality of life questionnaires were initially missing, but later recovered through reminders. Four methods of determining the missing data mechanism were applied. Two response data scenarios were considered. Firstly, immediate data only; secondly, all observed responses (including reminder-response). Results: In three of five trials the hypothesis tests found evidence against the MCAR assumption. Logistic regression suggested MAR, but was able to use the reminder-collected data to highlight potential MNAR data in two trials. Conclusion: The four methods were consistent in determining the missingness mechanism. One hypothesis test was preferred as it is applicable with intermittent missingness. Some inconsistencies between the two data scenarios were found. Ignoring the reminder data could potentially give a distorted view of the missingness mechanism. Utilising reminder data allowed the possibility of MNAR to be considered.The Chief Scientist Office of the Scottish Government Health Directorate. Research Training Fellowship (CZF/1/31

A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes

Background: Randomised controlled trials (RCTs) are perceived as the gold-standard method for evaluating healthcare interventions, and increasingly include quality of life (QoL) measures. The observed results are susceptible to bias if a substantial proportion of outcome data are missing. The review aimed to determine whether imputation was used to deal with missing QoL outcomes. Methods: A random selection of 285 RCTs published during 2005/6 in the British Medical Journal, Lancet, New England Journal of Medicine and Journal of American Medical Association were identified. Results: QoL outcomes were reported in 61 (21%) trials. Six (10%) reported having no missing data, 20 (33%) reported ≤ 10% missing, eleven (18%) 11%–20% missing, and eleven (18%) reported >20% missing. Missingness was unclear in 13 (21%). Missing data were imputed in 19 (31%) of the 61 trials. Imputation was part of the primary analysis in 13 trials, but a sensitivity analysis in six. Last value carried forward was used in 12 trials and multiple imputation in two. Following imputation, the most common analysis method was analysis of covariance (10 trials). Conclusion: The majority of studies did not impute missing data and carried out a complete-case analysis. For those studies that did impute missing data, researchers tended to prefer simpler methods of imputation, despite more sophisticated methods being available.The Health Services Research Unit is funded by the Chief Scientist Office of the Scottish Government Health Directorate. Shona Fielding is also currently funded by the Chief Scientist Office on a Research Training Fellowship (CZF/1/31)

A review of RCTs in four medical journals to assess the use of imputation to overcome missing data in quality of life outcomes

Peer reviewedPublisher PD

An assessment of validity and responsiveness of generic measures of health-related quality of life in hearing impairment

This article is made available through the Brunel Open Access Publishing Fund. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Purpose: This review examines psychometric performance of three widely used generic preference-based measures, that is, EuroQol 5 dimensions (EQ-5D), Health Utility Index 3 (HUI3) and Short-form 6 dimensions (SF-6D) in patients with hearing impairments. Methods: A systematic search was undertaken to identify studies of patients with hearing impairments where health state utility values were measured and reported. Data were extracted and analysed to assess the reliability, validity (known group differences and convergent validity) and responsiveness of the measures across hearing impairments. Results: Fourteen studies (18 papers) were included in the review. HUI3 was the most commonly used utility measures in hearing impairment. In all six studies, the HUI3 detected difference between groups defined by the severity of impairment, and four out of five studies detected statistically significant changes as a result of intervention. The only study available suggested that EQ-5D only had weak ability to discriminate difference between severity groups, and in four out of five studies, EQ-5D failed to detected changes. Only one study involved the SF-6D; thus, the information is too limited to conclude on its performance. Also evidence for the reliability of these measures was not found. Conclusion: Overall, the validity and responsiveness of the HUI3 in hearing impairment was good. The responsiveness of EQ-5D was relatively poor and weak validity was suggested by limited evidence. The evidence on SF-6D was too limited to make any judgment. More head-to-head comparisons of these and other preference measures of health are required.Medical Research Counci

Inspiratory muscle training reduces blood lactate concentration during volitional hyperpnoea

Although reduced blood lactate concentrations ([lac−]B) have been observed during whole-body exercise following inspiratory muscle training (IMT), it remains unknown whether the inspiratory muscles are the source of at least part of this reduction. To investigate this, we tested the hypothesis that IMT would attenuate the increase in [lac−]B caused by mimicking, at rest, the breathing pattern observed during high-intensity exercise. Twenty-two physically active males were matched for 85% maximal exercise minute ventilation (V˙Emax) and divided equally into an IMT or a control group. Prior to and following a 6 week intervention, participants performed 10 min of volitional hyperpnoea at the breathing pattern commensurate with 85% V˙Emax

Phenotypic redshifts with self-organizing maps: A novel method to characterize redshift distributions of source galaxies for weak lensing

Wide-field imaging surveys such as the Dark Energy Survey (DES) rely on coarse measurements of spectral energy distributions in a few filters to estimate the redshift distribution of source galaxies. In this regime, sample variance, shot noise, and selection effects limit the attainable accuracy of redshift calibration and thus of cosmological constraints. We present a new method to combine wide-field, few-filter measurements with catalogs from deep fields with additional filters and sufficiently low photometric noise to break degeneracies in photometric redshifts. The multi-band deep field is used as an intermediary between wide-field observations and accurate redshifts, greatly reducing sample variance, shot noise, and selection effects. Our implementation of the method uses self-organizing maps to group galaxies into phenotypes based on their observed fluxes, and is tested using a mock DES catalog created from N-body simulations. It yields a typical uncertainty on the mean redshift in each of five tomographic bins for an idealized simulation of the DES Year 3 weak-lensing tomographic analysis of $\sigma_{\Delta z} = 0.007$, which is a 60% improvement compared to the Year 1 analysis. Although the implementation of the method is tailored to DES, its formalism can be applied to other large photometric surveys with a similar observing strategy.Comment: 24 pages, 11 figures; matches version accepted to MNRA

Radiation management and credentialing of fluoroscopy users

During the last 15 years, developments in X-ray technologies have substantially improved the ability of practitioners to treat patients using fluoroscopically guided interventional techniques. Many of these procedures require a greater use of fluoroscopy and more recording of images. This increases the potential for radiation-induced dermatitis and epilation, as well as severe radiation-induced burns to patients. Many fluoroscope operators are untrained in radiation management and do not realize that these procedures increase the risk of radiation injury and radiation-induced cancer in personnel as well as patients. The hands of long-time fluoroscope operators in some cases exhibit radiation damage—especially when sound radiation protection practices have not been followed. In response, the Center for Devices and Radiological Health of the United States Food and Drug Administration has issued an Advisory calling for proper training of operators. Hospitals and administrators need to support and enforce the need for this training by requiring documentation of credentials in radiation management as a prerequisite for obtaining fluoroscopy privileges. A concerted effort on the part of professional medical organizations and regulatory agencies will be required to train fluoroscopy users to prevent physicians from unwittingly imparting serious radiation injuries to their patients

The preference for water nipples vs. water bowls in dairy goats

<p>Abstract</p> <p>Background</p> <p>Previous studies have reported that the design of the water dispensers can influence the water intake in farm animals. Horses and dairy cows seem to prefer to drink from an open surface whereas sheep and pigs apparently prefer water nipples, probably because of the worse water quality in water bowls. The aim of the present study was to examine the preference of dairy goats for water nipples or water bowls.</p> <p>Methods</p> <p>In each of the two experiments (exp. 1, dry goats, exp. 2 lactating goats), 42 dairy goats were allotted into 6 groups of 7 goats. In period 1, the goats had access to a water nipple. In period 2, they had access to a water bowl and in period 3 (preference test) they had access to both a water nipple and a water bowl. Water usage and wastage was recorded and water intake (water usage - water wastage) was calculated for each group for the two last days of each period. In experiment 2, water samples from each dispenser were analyzed for heterotrophy germs at 22°C, <it>Escherichia coli </it>and turbidity.</p> <p>Results</p> <p>Water usage was higher from water nipples than from water bowls both in experiment 1 (dry goats) and experiment 2 (lactating goats). There was however, no difference in water intake from water nipples and water bowls. In the preference test (period 3), the water intake tended to be higher from the water nipple than from the water bowl both for the dry goats (exp. 1) and lactating goats (exp. 2). Especially for the dry goats, the differences between groups were large. Turbidity and heterotrophy germs were much higher in the samples from the water bowls than from the water nipples.</p> <p>Water wastage from the water bowls was negligible compared to the water nipples. From the water nipples the water wastage was 30% and 23% of water usage for the dry and lactating goats respectively.</p> <p>Conclusions</p> <p>We conclude that type of water dispenser (nipple or bowl) was probably of minor importance for water intake in goats, but water bowls had a lower water quality.</p

Mutations in MITF and PAX3 Cause “Splashed White” and Other White Spotting Phenotypes in Horses

During fetal development neural-crest-derived melanoblasts migrate across the entire body surface and differentiate into melanocytes, the pigment-producing cells. Alterations in this precisely regulated process can lead to white spotting patterns. White spotting patterns in horses are a complex trait with a large phenotypic variance ranging from minimal white markings up to completely white horses. The “splashed white” pattern is primarily characterized by an extremely large blaze, often accompanied by extended white markings at the distal limbs and blue eyes. Some, but not all, splashed white horses are deaf. We analyzed a Quarter Horse family segregating for the splashed white coat color. Genome-wide linkage analysis in 31 horses gave a positive LOD score of 1.6 in a region on chromosome 6 containing the PAX3 gene. However, the linkage data were not in agreement with a monogenic inheritance of a single fully penetrant mutation. We sequenced the PAX3 gene and identified a missense mutation in some, but not all, splashed white Quarter Horses. Genome-wide association analysis indicated a potential second signal near MITF. We therefore sequenced the MITF gene and found a 10 bp insertion in the melanocyte-specific promoter. The MITF promoter variant was present in some splashed white Quarter Horses from the studied family, but also in splashed white horses from other horse breeds. Finally, we identified two additional non-synonymous mutations in the MITF gene in unrelated horses with white spotting phenotypes. Thus, several independent mutations in MITF and PAX3 together with known variants in the EDNRB and KIT genes explain a large proportion of horses with the more extreme white spotting phenotypes