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PubMed2006

Cholinesterase inhibitors for Alzheimer's disease: variations in clinical practice in the north-west of England.

BACKGROUND: In the UK, the National Institute for Health and Clinical Excellence (NICE) is currently reviewing cost-effectiveness of cholinesterase inhibitors (ChEIs) for Alzheimer's disease (AD) in the NHS. The implementation of the original NICE (2001) guidance that made these drugs available in the UK was not examined in this review process, and was the objective of this study. METHOD: Ten hospitals in and around Manchester participated in the audit. Case records of all patients who were started on ChEIs between January 2002 and the date of the audit (November 2003 to December 2004) were examined to assess adherence to the NICE (2001) guidance. Information about available resources was gathered from lead clinicians of each hospital. RESULTS: A total of 1,092 case records were examined. The treatment of AD with ChEIs varied considerably with regard to pre-treatment investigations, waiting period for treatment, scales used to assess efficacy, adherence to the NICE (2001) guidance, and available resources. The actual number of patients with mild to moderate AD receiving ChEIs was much lower than that expected from known prevalence rates. Non-uniformity of clinical practice and missing data were the main limitations of the audit. CONCLUSION: There is a need to harmonise the use and monitoring of ChEIs for AD in the NHS so that the data from routine clinical practice could feed into future clinical and cost-effectiveness analyses.

Aged↗

PubMed2001

The performance of sample selection estimators to control for attrition bias.

Sample attrition is a potential source of selection bias in experimental, as well as non-experimental programme evaluation. For labour market outcomes, such as employment status and earnings, missing data problems caused by attrition can be circumvented by the collection of follow-up data from administrative registers. For most non-labour market outcomes, however, investigators must rely on participants' willingness to co-operate in keeping detailed follow-up records and statistical correction procedures to identify and adjust for attrition bias. This paper combines survey and register data from a Norwegian randomized field trial to evaluate the performance of parametric and semi-parametric sample selection estimators commonly used to correct for attrition bias. The considered estimators work well in terms of producing point estimates of treatment effects close to the experimental benchmark estimates. Results are sensitive to exclusion restrictions. The analysis also demonstrates an inherent paradox in the 'common support' approach, which prescribes exclusion from the analysis of observations outside of common support for the selection probability. The more important treatment status is as a determinant of attrition, the larger is the proportion of treated with support for the selection probability outside the range, for which comparison with untreated counterparts is possible.

Adult↗

PubMed2002

Testing the convergent validity of the contingent valuation and travel cost methods in valuing the benefits of health care.

In this study, the convergent validity of the contingent valuation method (CVM) and travel cost method (TCM) is tested by comparing estimates of the willingness to pay (WTP) for improving access to mammographic screening in rural areas of Australia. It is based on a telephone survey of 458 women in 19 towns, in which they were asked about their recent screening behaviour and their WTP to have a mobile screening unit visit their nearest town. After eliminating missing data and other non-usable responses the contingent valuation experiment and travel cost model were based on information from 372 and 319 women, respectively. Estimates of the maximum WTP for the use of mobile screening units were derived using both methods and compared. The highest mean WTP estimated using the TCM was $83.10 (95% C.I. $99.06-$68.53), which is significantly less than the estimate of $148.09 ($131.13-$166.60) using the CVM. This could be due to the CVM estimates also reflecting non-use values such as altruism, or a range of potential biases that are known to affect both methods. Further tests of validity are required in order to gain a greater understanding of the relationship between these two methods of estimating WTP.

Bias↗

PubMed2003

Demand for private health insurance: how important is the quality gap?

Perceived quality of private and public health care, income and insurance premium are among the determinants of demand for private health insurance (PHI). In the context of a model in which individuals are expected utility maximizers, the non purchasing choice can result in consuming either public health care or private health care with full cost paid out-of-pocket. This paper empirically analyses the effect of the determinants of the demand for PHI on the probability of purchasing PHI by estimating a pseudo-structural model to deal with missing data and endogeneity issues. Our findings support the hypothesis that the demand for PHI is indeed driven by the quality gap between private and public health care. As expected, PHI is a normal good and a rise in the insurance premium reduces the probability of purchasing PHI albeit displaying price elasticities smaller than one in absolute value for different groups of individuals.

Adult↗

PubMed2004

Verrucous carcinoma of the paranasal sinuses: case report and clinical update.

BACKGROUND: Verrucous carcinoma is a low-grade malignancy that has been reported to occur in all anatomic sites of the head and neck. Fourteen cases of verrucous carcinoma of paranasal sinus origin have been reported to date in the English literature. METHODS: Case report and retrospective review of all cases of verrucous carcinoma of the paranasal sinuses in the English literature. All authors were contacted to provide missing data and long-term follow-up. RESULTS: Five of the eight authors contacted responded, and the most current data from all 15 cases was compiled. Eleven of the 15 patients (73%) were men and ranged in age from 35 to 81 years (median, 68 years). The maxillary sinus is the most common paranasal sinus involved (93%). Presentation often occurred late, with 12 of 15 (80%) initially being seen at stage T3 or higher. Surgical excision was the treatment of choice, and median disease-free survival was 54 months. CONCLUSIONS: Verrucous carcinoma of the paranasal sinuses is a rare but potentially curable disease. Treatment is surgical, and prognosis is good with early intervention.

Aged↗

PubMedDate not supplied

Correspondence of closest gradient voxels--a robust registration algorithm.

A robust, automatic volume registration algorithm based on intensity gradients is presented. This algorithm can successfully perform registrations under conditions of unrelated intervolume voxel intensities, significant object displacements, and/or significant amounts of missing data. It also allows the user to visualize the registration convergence, clearly illustrating any source of registration errors. This algorithm consists of a matching algorithm based on iteratively finding the correspondence of the closest voxels containing a high three-dimensional intensity gradient magnitude. This algorithm was tested by registering T2-weighted MR volumes that had undergone varying displacement transformations to simultaneously acquired proton-density volumes. These transformations involved rotations of up to 25 degrees followed by translations of up to 25 mm along the axis of rotation. For all registrations, the mean registration error was less than one-fifth of a voxel and the mean registration time was less than 30 minutes. In conclusion, this algorithm is shown to be a powerful method of sequence-independent MR volume registration that is simple to both use and understand.

Algorithms↗

PubMed2006

Metric attributes of the unified Parkinson's disease rating scale 3.0 battery: Part I, feasibility, scaling assumptions, reliability, and precision.

This article sought to assess the feasibility, scaling assumptions, reliability, precision, and factor analysis of the three most widely used rating scales in Parkinson's disease (PD): modified Hoehn and Yahr (HY), Schwab and England (SE), and Unified Parkinson's Disease Rating Scale (UPDRS). A multicenter sample of 1,136 PD patients was assessed. The percentage of missing data was 8% for SE, HY, and UPDRS mentation, and almost negligible (<2%) for the other UPDRS subscales. A high floor effect was found for UPDRS mentation (23%) and complications scales (36%). Item content validity, measured by multitrait scaling analysis, was adequate for all UPDRS subscales (scaling successes > 90%). Internal consistency coefficients for the UPDRS scales ranged from 0.79 (mentation) to 0.92 (activities of daily living and motor). Factor structure of the UPDRS mentation, activities of daily living, and complications subscales was replicated. As a whole, the HY, SE, and UPDRS are acceptable, consistent, and potentially sensitive rating scales.

Aged↗

PubMed2004

Use of resampling to select among alternative error structure specifications for GLMM analyses of repeated measurements.

Autocorrelated error and missing data due to dropouts have fostered interest in the flexible general linear mixed model (GLMM) procedures for analysis of data from controlled clinical trials. The user of these adaptable statistical tools must, however, choose among alternative structural models to represent the correlated repeated measurements. The fit of the error structure model specification is important for validity of tests for differences in patterns of treatment effects across time, particularly when maximum likelihood procedures are relied upon. Results can be affected significantly by the error specification that is selected, so a principled basis for selecting the specification is important. As no theoretical grounds are usually available to guide this decision, empirical criteria have been developed that focus on mode fit. The current report proposes alternative empirical criteria that focus on bootstrap estimates of actual type I error an power of tests for treatment effects. Results for model selection before and after the blind is broken are compared. Goodness-of-fit statistics also compare favourably for models fitted to the blinded or unblinded data, although the correspondence to actual type I error and power depends on the particular fit statistic that is considered.

Antidepressive Agents↗

PubMed2006

Rule-of-thumb adjustment of sample sizes to accommodate dropouts in a two-stage analysis of repeated measurements.

Recent contributions to the statistical literature have provided elegant model-based solutions to the problem of estimating sample sizes for testing the significance of differences in mean rates of change across repeated measures in controlled longitudinal studies with differentially correlated error and missing data due to dropouts. However, the mathematical complexity and model specificity of these solutions make them generally inaccessible to most applied researchers who actually design and undertake treatment evaluation research in psychiatry. In contrast, this article relies on a simple two-stage analysis in which dropout-weighted slope coefficients fitted to the available repeated measurements for each subject separately serve as the dependent variable for a familiar ANCOVA test of significance for differences in mean rates of change. This article is about how a sample of size that is estimated or calculated to provide desired power for testing that hypothesis without considering dropouts can be adjusted appropriately to take dropouts into account. Empirical results support the conclusion that, whatever reasonable level of power would be provided by a given sample size in the absence of dropouts, essentially the same power can be realized in the presence of dropouts simply by adding to the original dropout-free sample size the number of subjects who would be expected to drop from a sample of that original size under conditions of the proposed study.

Analysis of Variance↗

PubMed2003

Reconstruction after rotational motion.

Patient rotational motion during a scan causes the k-space sampling to be both irregular and undersampled. Conventional regridding requires an estimate of the sampling density at each measured point and is not strictly consistent with sampling theory. Here, a 2D problem is converted to a series of 1D regriddings by exact interpolation along the measured readouts. Each 1D regridding, expressed in matrix form, requires a matrix inversion to gain an exact solution. Undersampled regions make the matrix ill-conditioned but summing the matrix columns (without inversion) indicates the undersampled regions. The missing data could be reacquired, but in this study it is estimated using a Delaunay triangle-based linear interpolation on the original 2D data. The matrix conditioning is improved, leading to images with reduced artifacts compared to other regridding schemes. Furthermore, there is no requirement to estimate a density compensation function at each of the measured points.

Head↗

PubMed2001

Modeling in vivo recovery of intracellular pH in muscle to provide a novel index of proton handling: application to the diagnosis of mitochondrial myopathy.

Post-exercise recovery of intracellular pH (pH(i)) assessed using phosphorus magnetic resonance spectroscopy has not been previously evaluated in its entirety due to its complex time-course and missing data points resulting from a transient loss of inorganic phosphate signal. By considering the transition from exercise to recovery as a step function input, pH(i) recovery was modeled based on the creatine-kinase equilibrium, and the entire pH(i) recovery was characterized by calculating the time required for pH(i) recovery (t(pHrec)). Applying this methodology, normal subjects showed a strong linear correlation between phosphocreatine (PCr) half-time and t(pHrec) (r = 0.90, P < 0.001). In mitochondrial myopathy (MM) patients with weakness in the limb examined, 9/10 had faster pH(i) recovery relative to PCr recovery; wide normal ranges from a control group which included deconditioned subjects resulted in 7 of those 10 patients having otherwise normal recovery indices. Therefore, modeling pH(i) recovery allows characterization of the entire pH(i) recovery and detects altered proton handling in MM patients, including those with otherwise normal recovery indices.

Adult↗

PubMed1998

Versatile frequency domain fitting using time domain models and prior knowledge.

An iterative nonlinear least-squares fitting algorithm in the frequency domain using time domain models for quantification of complex frequency domain MR spectra is presented. The algorithm allows incorporation of prior knowledge and has both the advantage of time-domain fitting with respect to handling the problem of missing data points and truncated data sets and of frequency-domain fitting with respect to multiple frequency-selective fitting. The described algorithm can handle, in addition to Lorentzian and Gaussian lineshapes, Voigt and nonanalytic lineshapes. The program allows the user the design of his own fitting strategy to optimize the probability of reaching the global least-squares minimum. The application of the fitting program is illustrated with examples from in vivo 1H-, 31P-, and 13C-MR spectroscopy.

Algorithms↗

PubMed2004

ICIQ: a brief and robust measure for evaluating the symptoms and impact of urinary incontinence.

AIMS: To develop and evaluate the International Consultation on Incontinence Questionnaire (ICIQ), a new questionnaire to assess urinary incontinence and its impact on quality of life (QoL). METHODS: A developmental version of the questionnaire was produced following systematic literature review and views of an expert committee and patients. Several studies were undertaken to evaluate the psychometric properties of the questionnaire, including content, construct and convergent validity, reliability and sensitivity to change. RESULTS: The ICIQ was easily completed, with low levels of missing data (mean 1.6%). It was able to discriminate among different groups of individuals, indicating good construct validity. Convergent validity was acceptable, with most items demonstrating 'moderate' to 'strong' agreement with other questionnaires. Reliability was good, with 'moderate' to 'very good' stability in test-retest analysis and a Cronbach's alpha of 0.95. Items identified statistically significant reductions in symptoms from baseline following surgical and conservative treatment. Item reduction techniques were used to determine the final version and scoring scheme, which also demonstrated good psychometric properties. CONCLUSIONS: The final ICIQ comprises three scored items and an unscored self-diagnostic item. It allows the assessment of the prevalence, frequency, and perceived cause of urinary incontinence, and its impact on everyday life. The ICIQ is a brief and robust questionnaire that will be of use in outcomes and epidemiological research as well as routine clinical practice.

Adult↗

PubMed2026

Effects of Dynamic Neck Sensorimotor Biofeedback Training in Individuals With Mechanical Neck Pain: A Pilot Randomized Controlled Trial.

Mechanical neck pain (MNP) is commonly accompanied by pain-related functional limitations, sensorimotor disturbances, and fear of movement, which together may contribute to persistent disability. This preliminary randomized controlled trial study investigated the short-term effects of dynamic neck sensorimotor-based biofeedback training in individuals with MNP. 20 MNP patients from outpatient clinics were assigned to a biofeedback training group or a control group. The training group underwent dynamic biofeedback exercises twice weekly for 2 weeks, whereas the control group performed repeated cervical movements without biofeedback. Outcomes included cervical kinematics as repositioning errors (RPE), movement units (MU), maximal range of motion (ROM), and subjective measures, including pain intensity, Neck Disability Index (NDI), and Fear-Avoidance Beliefs Questionnaire (FABQ). All participants completed post-intervention assessments; adherence in the training group was 100%, with no missing data and no adverse events reported. Within the biofeedback training group, participants receiving biofeedback training demonstrated greater improvements in cervical repositioning accuracy during flexion (51.95%, p = 0.04) and extension (46.67%, p = 0.02), along with reductions in fear-avoidance beliefs related to physical activity and work (p < 0.05); these changes were less apparent in the active control group. Exploratory regression analyses suggested associations between improvements in repositioning accuracy and pain reduction, and between increased cervical range of motion and improvements in fear-avoidance beliefs related to physical activity. These pilot findings suggest that dynamic sensorimotor biofeedback training may improve proprioceptive acuity and fear-avoidance beliefs in individuals with MNP, supporting further evaluation in an adequately powered randomized trial.

Humans↗

PubMed2002

Use of the mean, hot deck and multiple imputation techniques to predict outcome in intensive care unit patients in Colombia.

A cohort of intensive care unit (ICU) patients in 20 Colombian ICUs is used to describe the application of three imputation techniques: single, hot deck and multiple imputation. These strategies were used to impute the missing data in the variables used to construct APACHE II scores, a scoring system for the ICU patients that provides an unbiased standardized estimate of the probability of hospital death. Imputed APACHE II scores were then used in the APACHE II model to estimate adjusted hospital mortality rates. The area under the receiver operating characteristic (ROC) curve was used to compare imputation strategies with respect to predictive power. While statistically significant differences were found for the area under the ROC curve, these differences were not clinically significant.

APACHE↗

PubMed2004

A log-normal distribution model of the effect of bacteria and ear fenestration on hearing loss: a Bayesian approach.

Chronic ear infection is a potentially life-threatening illness that medical doctors typically treat with ear surgery. Despite the success of this treatment, complications can occur due to bacteria infection. Surgeons believe that this infection causes the patient to have clinically significant hearing damage. In order to understand such complications, surgeons must quantify the effect of bacteria, their toxins and ear surgery on hearing loss. To this end, the other two authors of this paper performed two experiments on guinea pigs to measure hearing thresholds following a bacterial infection and surgery of the inner ear. The response variable in these experiments is hearing thresholds measured in decibels (dB). The problem in analysing such experiments is that the hearing threshold observations often suffer from missing data and censoring mechanisms of various types. Additionally, the distribution of hearing thresholds has heavy tails and is peaked. In order to account for the above statistical issues, we present a Bayesian method with a location-shifted log-normal distribution. The method accounts for the uncertainty in the data collection mechanism and the parameters associated with a location-shifted log-normal distribution. We refer to one of the parameters as the "location-shift" parameter. The Bayesian approach provides a posterior distribution of the location-shift parameter that we compare with values estimated in previously published studies. The immediate goal of our proposed method was to quantify the effects of ear surgery and bacteria infection on hearing loss. Thus, we present the merits of the method in the form of a case study, and report posterior distributions of mean hearing loss, probability of clinically significant hearing loss and relative risk. The results show that surgeon 2, using the surgical procedure "oval window", poses a greater than 40 per cent chance of a 15dB hearing loss regardless of injection of bacteria or not. However, surgeon 1, using the surgical procedure "semicircular canal", does not pose a significantly greater than 40 per cent chance of a 15dB hearing loss unless there is a Pseudomonas aeruginosa-induced infection.

Aged↗

PubMed2005

Sense and sensitivity when correcting for observed exposures in randomized clinical trials.

Standard intent-to-treat analyses of randomized clinical trials can yield biased estimates of treatment efficacy and toxicity when not all patients comply with their assigned treatment. Flexible methods have been proposed which correct for this by modelling expected contrasts between an individual's observed outcome and his/her potential outcome in the absence of exposure. Because such comparisons often require untestable assumptions, a sensitivity analysis is warranted. We show how this can be performed in a meaningful and practically useful way. Following the approach of Molenberghs, Kenward and Goetghebeur in a missing data context, we evaluate the separate contributions of structural uninformativeness and sampling variation to uncertainty about the population parameters. This leads us to consider Honestly Estimated Ignorance Regions (HEIRs) and Estimated Uncertainty RegiOns (EUROs), respectively. We use the results to estimate the causal effect of observed exposure on successful blood pressure reduction in a randomized controlled clinical trial with partial non-compliance.

Antihypertensive Agents↗

PubMed2006

Multiple imputation techniques in small sample clinical trials.

Clinical trials allow researchers to draw conclusions about the effectiveness of a treatment. However, the statistical analysis used to draw these conclusions will inevitably be complicated by the common problem of attrition. Resorting to ad hoc methods such as case deletion or mean imputation can lead to biased results, especially if the amount of missing data is high. Multiple imputation, on the other hand, provides the researcher with an approximate solution that can be generalized to a number of different data sets and statistical problems. Multiple imputation is known to be statistically valid when n is large. However, questions still remain about the validity of multiple imputation for small samples in clinical trials. In this paper we investigate the small-sample performance of several multiple imputation methods, as well as the last observation carried forward method.

Bayes Theorem↗