Estimating the number needed to treat from continuous outcomes in randomised controlled trials: methodological challenges and worked example using data from the UK Back Pain Exercise and Manipulation (BEAM) trial

Background Reporting numbers needed to treat (NNT) improves interpretability of trial results. It is unusual that continuous outcomes are converted to numbers of individual responders to treatment (i.e., those who reach a particular threshold of change); and deteriorations prevented are only rarely considered. We consider how numbers needed to treat can be derived from continuous outcomes; illustrated with a worked example showing the methods and challenges. Methods We used data from the UK BEAM trial (n = 1, 334) of physical treatments for back pain; originally reported as showing, at best, small to moderate benefits. Participants were randomised to receive 'best care' in general practice, the comparator treatment, or one of three manual and/or exercise treatments: 'best care' plus manipulation, exercise, or manipulation followed by exercise. We used established consensus thresholds for improvement in Roland-Morris disability questionnaire scores at three and twelve months to derive NNTs for improvements and for benefits (improvements gained+deteriorations prevented). Results At three months, NNT estimates ranged from 5.1 (95% CI 3.4 to 10.7) to 9.0 (5.0 to 45.5) for exercise, 5.0 (3.4 to 9.8) to 5.4 (3.8 to 9.9) for manipulation, and 3.3 (2.5 to 4.9) to 4.8 (3.5 to 7.8) for manipulation followed by exercise. Corresponding between-group mean differences in the Roland-Morris disability questionnaire were 1.6 (0.8 to 2.3), 1.4 (0.6 to 2.1), and 1.9 (1.2 to 2.6) points. Conclusion In contrast to small mean differences originally reported, NNTs were small and could be attractive to clinicians, patients, and purchasers. NNTs can aid the interpretation of results of trials using continuous outcomes. Where possible, these should be reported alongside mean differences. Challenges remain in calculating NNTs for some continuous outcomes

Clinimetric properties of the motor activity log for the assessment of arm use in hemiparetic patients

Background and Purpose - The Motor Activity Log (MAL) is a semistructured interview for hemiparetic stroke patients to assess the use of their paretic arm and hand (amount of use [AOU]) and quality of movement [QOM]) during activities of daily living. Scores range from 0 to 5. The following clinimetric properties of the MAL were quantified: internal consistency (Cronbach α), test-retest agreement (Bland and Altman method), cross-sectional construct validity (correlation between AOU and QOM and with the Action Research Arm (ARA] test), longitudinal construct validity (correlation of change on the MAL during the intervention with a global change rating [GCR] and with change on the ARA), and responsiveness (effect size). Methods - Two baseline measurements 2 weeks apart and 1 follow-up measurement immediately after 2 weeks of intensive exercise therapy either with or without immobilization of the unimpaired arm (forced use) were performed in 56 chronic stroke patients. Results - Internal consistency was high (AOU: a=0.88; QOM: a=0.91). The limits of agreement were -0.70 to 0.85 and -0.61 to 0.71 for AOU and QOM, respectively. The correlation with the ARA score (Spearman p) was 0.63 (AOU and QOM). However, the improvement on the MAL during the intervention was only weakly related to the GCR and to the improvement on the ARA, Spearman p was between 0.16 and 0.22. The responsiveness ratio was 1.9 (AOU) and 2.0 (QOM). Conclusion - The MAL is internally consistent and relatively stable in chronic stroke patients not undergoing an intervention. The cross-sectional construct validity of the MAL is reasonable, but the results raise doubt about its longitudinal construct validity

The usefulness of evaluative outcome measures in patients with multiple sclerosis

To select the most useful evaluative outcome measures for early multiple sclerosis, we included 156 recently diagnosed patients in a 3-year follow-up study, and assessed them on 23 outcome measures in the domains of disease-specific outcomes, physical functioning, mental health, social functioning and general health. A global rating scale (GRS) and the Expanded Disability Status Scale (EDSS) were used as external criteria to determine the minimally important change (MIC) for each outcome measure. Subsequently, we determined whether the outcome measures could detect their MIC reliably. From these, per domain the outcome measure that was found to be most sensitive to changes (responsive) was identified. At group level, 11 outcomes of the domains of physical functioning, mental health, social functioning and general health could reliably detect the MIC. Of these 11, the most responsive measures per domain were the Medical Outcome Study 36 Short Form sub-scale physical functioning (SF36pf), the Disability and Impact Profile (DIP) sub-scale psychological, the Rehabilitation Activities Profile sub-scale occupation (RAPocc) and the SF36 sub-scale health, respectively. Overall, the most responsive measures were the SF36pf and the RAPocc. In individual patients, none of the measures could reliably detect the MIC. In sum, in the early stages of multiple sclerosis the most useful evaluative outcome measures for research are the SF36pf (physical functioning) and the RAPocc (social functioning). © The Author (2006). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved

Streamwise turbulence modulation in non-uniform open-channel clay suspension flows

Cohesive sediment particles are ubiquitous in environmental flows. The cohesive properties of clay promote the formation of clay flocs and gels and relatively small suspended clay concentrations can enhance or suppress turbulence in a flow. Furthermore, flows are naturally non-uniform, varying in space and time, yet the dynamics of non-uniform open-channel clay suspension flows is poorly understood. For the first time, the adaptation time and length scales of non-uniform clay suspension flows were quantified using novel experiments with spatially varying but temporally uniform flow. Different levels of turbulence enhancement and attenuation were identified as the flow decelerates or accelerates. Results highlight that decelerating clay suspension flows crucially have a longer adaptation time than accelerating clay suspension flows. This is explained by the longer timescale required for the formation of bonds between cohesive particles in turbulence attenuated flows after deceleration than the rapid breakdown of bonds in turbulent flows after acceleration of clay suspension flows. This hysteresis is more pronounced for higher concentration decelerating flows that pass through a larger variety of clay flow types of turbulence enhancement and attenuation. These different adaptation time scales and associated clay flow type transitions are likely to affect clay flow dynamics in a variety of fluvial and submarine settings

The cost-effectiveness of a treatment based classification system for low back pain: design of a randomised controlled trial and economic evaluation

<p>Abstract</p> <p>Background</p> <p>Systematic reviews have shown that exercise therapy and spinal manipulation are both more effective for low back pain (LBP) than no treatment at all. However, the effects are at best modest. To enhance the clinical outcomes, recommendations are to improve the patient selection process, and to identify relevant subgroups to guide clinical decision-making. One of the systems that has potentials to improve clinical decision-making is a treatment-based classification system that is intended to identify those patients who are most likely to respond to direction-specific exercises, manipulation, or stabilisation exercises.</p> <p>Methods/Design</p> <p>The primary aim of this randomised controlled trial will be to assess the effectiveness of a classification-based system. A sample of 150 patients with subacute and chronic LBP who attend a private physical therapy clinic for treatment will be recruited. At baseline, all participants will undergo a standard evaluation by trained research physical therapists and will be classified into one of the following subgroups: direction-specific exercises, manipulation, or stabilisation. The patient will not be informed about the results of the examination. Patients will be randomly assigned to classification-based treatment or usual care according to the Dutch LBP guidelines, and will complete questionnaires at baseline, and 8, 26, and 52 weeks after the start of the treatment. The primary outcomes will be general perceived recovery, functional status, and pain intensity. Alongside this trial, an economic evaluation of cost-effectiveness and cost-utility will be conducted from a societal perspective.</p> <p>Discussion</p> <p>The present study will contribute to our knowledge about the effectiveness and cost-effectiveness of classification-based treatment in patients with LBP.</p> <p>Trial registration</p> <p>Trial registration number: NTR1176</p

Personal dignity in the terminally ill from the perspective of caregivers : a survey among trained volunteers and physicians

Background: Although dignity is increasingly considered a goal of palliative care, little research has evaluated the understanding of dignity at the end of life from a caregiver's perspective. Objective: The study objective was to investigate and compare the views of trained volunteers and SCEN physicians on maintaining dignity for patients reaching the end of life. Design: The study is a survey questionnaire study. Subjects: Subjects were two groups of caregivers involved in care for dying patients: trained volunteers (n=236) and end-of-life consultants (SCEN physicians; n=427). Measurements: Measurement was done via the Dutch version of the 22-item Patient Dignity Inventory on symptoms and experiences that have been shown to influence the sense of dignity in terminally ill patients. Respondents were asked to rate on a five-point scale the extent to which they considered the items as influential on dignity in terminally ill patients, and as problematic in practice in maintaining dignity for patients in the last phase of life. Results: Overall, volunteers indicated items more frequently as influential to dignity and as problematic in maintaining dignity at the end of life, compared to SCEN physicians. Volunteers gave significantly higher ratings than SCEN physicians to most of the social items, and to half of the psychological and existential items. Conclusions: It seems that SCEN physicians consider the physical aspects of suffering to be most influential and problematic in practice in preserving dignity, while volunteers think psychosocial aspects are most important in preserving dignity at the end of life. These findings suggest that the role and responsibilities of caregivers involved in care for terminally ill patients affect the factors that they think influence dignity

Analysis of the construct of dignity and content validity of the patient dignity inventory

<p>Abstract</p> <p>Background</p> <p>Maintaining dignity, the quality of being worthy of esteem or respect, is considered as a goal of palliative care. The aim of this study was to analyse the construct of personal dignity and to assess the content validity of the Patient Dignity Inventory (PDI) in people with an advance directive in the Netherlands.</p> <p>Methods</p> <p>Data were collected within the framework of an advance directives cohort study. This cohort study is aiming to get a better insight into how decisions are made at the end of life with regard to advance directives in the Netherlands. One half of the cohort (n = 2404) received an open-ended question concerning factors relevant to dignity. Content labels were assigned to issues mentioned in the responses to the open-ended question. The other half of the cohort (n = 2537) received a written questionnaire including the PDI. The relevance and comprehensiveness of the PDI items were assessed with the COSMIN checklist ('COnsensus-based Standards for the selection of health status Measurement INstruments').</p> <p>Results</p> <p>The majority of the PDI items were found to be relevant for the construct to be measured, the study population, and the purpose of the study but the items were not completely comprehensive. The responses to the open-ended question indicated that communication and care-related aspects were also important for dignity.</p> <p>Conclusions</p> <p>This study demonstrated that the PDI items were relevant for people with an advance directive in the Netherlands. The comprehensiveness of the items can be improved by including items concerning communication and care.</p

Reproducibility of cervical range of motion in patients with neck pain

OBJECTIVE: To assess the intra-rater and inter-rater reproducibility of the measurement of active Range of Motion (ROM) in patients with neck pain using the Cybex Electronic Digital Inclinometer-320 (EDI-320). DESIGN: In an outpatient clinic in a primary care setting 32 patients with at least 2 weeks of pain and/or stiffness in the neck were randomly assessed, in a test- retest design with blinded raters using a standardized measurement protocol. Main outcome measure: Cervical flexion-extension, lateral flexion and rotation was assessed. RESULTS: Reliability expressed by the Intraclass Correlation Coefficient (ICC) was 0.93 (lateral flexion) or higher for intra-rater reliability and 0.89 (lateral flexion) or higher for inter-rater reliability. The 95% limits of agreement for intra-rater agreement, expressing the range of the differences between two ratings were -2.5 +/- 11.1 degrees for flexion-extension, -0.1 +/- 10.4degrees for lateral flexion and -5.9 +/- 13.5 degrees for rotation. For inter-rater agreement the limits of agreement were 3.3 +/- 17.0 degrees for flexion-extension, 0.5 +/- 17.0degrees for lateral flexion and -1.3 +/- 24.6 degrees for rotation. CONCLUSIONS: In general, the intra-rater reproducibility and the inter-rater reproducibility were good. We recommend to compare the reproducibility and clinical applicability of the EDI-320 inclinometer with other cervical ROM measures in symptomatic patients. (aut.ref.