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PubMedDate not supplied

The prediction of height by armspan in older Chinese people.

OBJECTIVE: To compare the accuracy of the predictive equations derived from older Chinese people without vertebral deformity with those derived from unselected older people, in estimating height from armspan. METHODOLOGY: Height and armspan were measured in 789 older Chinese and 885 young Chinese in Hong Kong. All the older subjects had spinal X-ray (T4 to L4). Vertebral deformity was determined by a trained technician using a translucent digital analyser. Definite deformity was defined by a greater than 3 standard deviation increase in one of the three vertebral height ratios (anterior/posterior, middle/posterior and posterior/posterior). Eighty of the older subjects without vertebral deformity were randomly selected from the studied population for internal validation of predictive equations. The remaining subjects were used to derive sex-specific predictive equations for height by linear regression against armspan. The accuracy of these equations was analysed by the Bland and Altman method. RESULTS: Vertebral deformity was present in 30.7% and 15.6% of older female and male subjects, respectively. Older women without vertebral deformity had significantly greater armspan: height ratio when compared with the young (1.04 versus 1.02), but the corresponding ratios were the same in older and young men (both 1.04). The predictive equation derived from older females without vertebral deformity had lower standard error of estimation and gave estimates closer to measured height than those derived from unselected older women. But this was not the case in older men. CONCLUSION: In deriving predictive equation to estimate height by armspan in older Chinese women, selecting out older women without vertebral deformity increased accuracy of the equation. This was, however, not the case in older men.

Adolescent↗

PubMed2003

Effect of the angiotensin II antagonist valsartan on sexual function in hypertensive men.

The present open and prospective study was performed to investigate the effect of the angiotensin II receptor blocker (ARB) valsartan on sexual function in hypertensive males. Patients who were either newly treated or who were switched from other treatment regimens received valsartan 80-160 mg/day. Blood pressure decreased from an average of 158/94 mmHg to 136/82 mmHg during the 6 months of treatment (p < 0.001). The patients' sexual function was assessed before valsartan and after 6 months of treatment using the International Index of Erectile Function (IIEF), an internationally validated 15-item questionnaire. The IIEF addresses the relevant domains of male sexual function, i.e. erectile function, orgasmic function, sexual desire, intercourse satisfaction and overall satisfaction. At baseline, 75.4% of the total group of 3502 patients investigated and 65.0% of the subgroup of patients without previous antihypertensive treatment (n = 952) could be diagnosed as having erectile dysfunction (ED) according to the IIEF. Valsartan therapy markedly reduced ED in these groups to 53% and 45% (p < 0.0001), respectively. Improved ED was associated with highly significant improvements in orgasmic function, intercourse and overall satisfaction both in the total and previously untreated groups. In addition, sexual desire averaged 5.64 +/- 1.99 IIEF units in the total and 5.99 +/- 2.03 in the group without antihypertensive treatment at baseline. Valsartan markedly increased these numbers to 6.82 +/- 1.72 and 7.06 +/- 1.68 (p < 0.0001), respectively. The results of our open study suggest that the ARB valsartan improves sexual function in hypertensive males.

Adolescent↗

PubMedDate not supplied

Rating methodological quality: toward improved assessment and investigation.

Assessing methodological quality is considered essential in deciding what investigations to include in research syntheses and in detecting potential sources of bias in meta-analytic results. Quality assessment is also useful in characterizing the strengths and limitations of the research in an area of study. Although numerous instruments to measure research quality have been developed, they have lacked empirically-supported components. In addition, different summary quality scales have yielded different findings when they were used to weight treatment effect estimates for the same body of research. Suggestions for developing improved quality instruments include: distinguishing distinct domains of quality, such as internal validity, external validity, the completeness of the study report, and adherence to ethical practices; focusing on individual aspects, rather than domains of quality; and focusing on empirically-verified criteria. Other ways to facilitate the constructive use of quality assessment are to improve and standardize the reporting of research investigations, so that the quality of studies can be more equitably and thoroughly compared, and to identify optimal methods for incorporating study quality ratings into meta-analyses.

Bias↗

PubMed2006

The association of physical deconditioning and chronic low back pain: a hypothesis-oriented systematic review.

PURPOSE: Does physical deconditioning (loss of cardiovascular capacity and strength/endurance of paraspinal muscles) exist in patients with chronic low back pain (CLBP) and are treatments specifically aimed to reduce these signs effective? METHOD: Systematic literature search in PUBMED, MEDLINE, EMBASE and PsycINFO until December 2004 to identify observational studies regarding deconditioning signs and high quality RCTs regarding the effectiveness of cardiovascular and/or muscle strengthening exercises. Internal validity of the RCTs was assessed by using a checklist of nine methodology criteria in accordance with the Cochrane Collaboration. RESULTS: There is conflicting evidence that cardiovascular deconditioning is present in CLBP and limited evidence for wasting of the multifidus muscle. No study examined the effectiveness of cardiovascular training specifically. General and lumbar muscle strengthening are equally effective as other active treatments. Only moderate evidence is available for the effectiveness of intensive low back extensor muscle strengthening compared to less intensive strengthening. CONCLUSION: Probably reactivation caused by active treatment and not the reconditioning itself is the important factor in the reduction of disability. Further prospective and evaluative research into the role of physical deconditioning is necessary. It seems more promising to further explore the interplay between biological, social and psychological factors.

Cardiovascular Deconditioning↗

PubMed1993

Confidence intervals versus p-values for interpretation of clinical trial results: introduction.

The following three papers summarize the presentations at a Society for Clinical Trials annual meeting session on the relative merits of estimation versus testing for analysis of randomized clinical trials. By design, randomized clinical trials have internal validity. Whether they also possess quantitative external validity--generalizability of effect size to some population represented by the trial subjects--is one of the main points of disagreement among the three authors. It may be unrealistic to expect a resolution that applies across the wide variety of therapeutic areas and clinical trial goals. Extrapolation from clinical trial to clinical practice is often endorsed in connection with large trials having loose entry criteria and focusing on an objective, clearly meaningful clinical endpoint. By contrast, the relevance of estimates of effect size is less clear in the case of many clinical trials conducted in the course of drug development.

Clinical Trials as Topic↗

PubMed1993

Confidence intervals and controlled clinical trials: incompatible tools for medical research.

The probabilistic rationale for statistical design and analysis of clinical trials is random assignment. While arithmetic and mathematical formulations may be identical to those used with random samples, we should not indiscriminately borrow tools from survey sample methods. Specifically, the confidence interval should be used sparingly, if at all. Observations have an internal validity, within the clinical trial, with no basis for claims of quantitative external generalizability. Confidence intervals encourage an unnecessary dependence on statistical analysis when the careful design should allow the data to speak for itself. Confidence intervals encourage a statistical focus and statistical conclusions that ignore scientific context and misrepresent relationships among results from related research. The clinician is presented with information about population parameters when facing confidence intervals. These do not address questions about treatment and prognosis of an individual patient. Confidence intervals are particularly distracting when a clinical trial has failed to produce anticipated results. The clinical trial is the model research tool for clinical medical research, founded on randomization. The confidence interval is a statistical tool for parameter estimation based on population sampling concepts. These tools are incompatible.

Clinical Trials as Topic↗

PubMed1999

Options for managing psychotropic medications in drug-abusing patients participating in behavioral therapies clinical trials.

This manuscript reviews strengths and weaknesses of common design options for managing non-study medications in randomized clinical trials of behavioral treatments for drug abusers. While the principal focus of these trials is on the relative efficacy of different behavioral interventions, drug abusers entering these trials are often either using or in need of prescribed psychotropic medications, which can have a major independent impact on treatment outcome. Options reviewed range from tight to minimal restriction on use of ancillary medications. Generally, major tradeoffs pertain to the balance between internal validity and generalizability. However, experimental rigor can be maintained while allowing subjects to use ancillary medications if steps are taken to monitor and minimize the variability in treatment delivery.

Behavior Therapy↗

PubMed2005

Psychometric characteristics of the child occupational self-assessment (COSA), part two: refining the psychometric properties.

Self-assessment is an appropriate way to support client-centered practice and promote personal development in young occupational therapy clients. This study, the second study in a series of two, sought to refine the psychometric properties based on previous analysis of the Child Occupational Self-Assessment (COSA), a self-report tool based on the Model of Human Occupation. The COSA comprises 24 statements, which the child rates in terms of personal competence and importance. The Rasch Rating Scale Model was used to evaluate the measurement properties of the Competence and Values scales that result from these self-ratings. The original three-point rating scale was expanded to four response categories in this study, which resulted in improved reliability and sensitivity. In this second study, the items once again coalesced to form measures of competence and values, and the order of items from less to more competence and value was similar to that in the first study, supporting the internal validity of the COSA scales. The results provide evidence that the COSA can be used as meaningful and reliable client-directed assessment tool as well as an outcome measure.

Activities of Daily Living↗

PubMed1990

Endotoxin measurement: aerosol sampling and application of a new Limulus method.

A new Limulus test was designed specifically for measuring endotoxin in environmental aerosols. The new Limulus method has a detection limit for airborne endotoxin of 2.2 pg (NP-1 activity)/m3 and can precisely quantitate aerosols containing 14 or more pg/m3 from samples representing 6.5 m3 of air. Aerosols in the range 100 to 500 pg/m3 were measured with 95% confidence of +/- 32% and an aerosol of 10 pg/m3 with 95% confidence of +/- 50%. Qualitative information about airborne endotoxin was also obtained from the assay. A wide variety of filter media were found to inactivate lipopolysaccharide in solution. This implies that airborne endotoxin can be measured only relative to the conditions of a particular study and that comparison of endotoxin aerosol measurements made under different circumstances are invalid. The research and policy implications of this observation are discussed. The need for improved collection and extraction methods notwithstanding, it was proposed that a buffered, parallel-line Limulus assay method be adopted as the standard method for measuring environmental endotoxin. The kinetic-turbidimetric Limulus assay with resistant-parallel-line estimates (KLARE), rate response method, should be considered a prime candidate for the standard method because of its precision, sensitivity, resistance to interference by pH, internal validation of estimates, and ability to provide qualitative as well as quantitative information about airborne endotoxin.

Aerosols↗

PubMedDate not supplied

Task-based assessment of occupational vibration and noise exposures in forestry workers.

Forty-two noise exposures and 164 whole-body (WBV) and hand-arm (HAV) vibration exposures were collected from 43 forestry workers in six trades employed by two forestry companies. Data were collected on 10 days over 8 weeks during various felling, logging, and log handling operations. Up to 5 volunteers were monitored for noise and vibration daily using datalogging noise dosimeters, which provided daily time-weighted averages (TWAs) and 1-min averages; and a precision sound level meter equipped to measure human vibration, which provided triaxial HAV and WBV event-weighted averages (AEQS). Workers completed a short questionnaire throughout the workday detailing the timing and number of tasks performed and equipment used. Substantial overexposures to noise and vibration were seen; for example, 60% of Occupational Safety and Health Administration (OSHA) TWAs and 83% of National Institute for Occupational Safety and Health (NIOSH) noise TWAs exceeded 85 dBA, 33-53% of the axis-specific HAV AEQS exceeded the 8-hour American Conference of Governmental Industrial Hygienists' HAV threshold limit value, and 34% of all summary weighted WBV AEQS exceeded the Commission of the European Communities' 8-hour exposure limit. The mean for 99 WBV summary weighted AEQ was 3.53 +/- 7.12 m/sec2, whereas the mean for 65 HAV summary weighted AEQ was 5.45 +/- 5.25 m/sec2. The mean OSHA TWA was 86.1 +/- 6.2 dBA, whereas the mean NIOSH TWA was 90.2 +/- 5.1 dBA. The task and tool with the highest exposure levels were unbelling chokers on landings and chain saws (noise), log processing and frontend loaders (WBV), and notching stumps and chain saws (HAV). An internal validation substudy indicated excellent agreement between worker-reported and researcher-documented tasks and tools.

Adult↗

PubMed2005

Evaluation of community-based injury prevention programmes: methodological issues and challenges.

The evaluation of comprehensive community-based injury prevention programmes is complex and poses many methodological challenges. There is little consensus in contemporary literature about the most appropriate methods of evaluating these programmes. This study employed a systematic literature review to examine evaluations of 16 community-based injury prevention programmes with regard to key methodological issues and challenges. Three aspects of the evaluated programmes were analysed: assessed elements (context, structure, process, impact, and outcome); study design; and methodological issues addressed. The results showed that context, structure and process assessments were the most neglected aspects of the evaluation studies. The programmes were typically described with minimal discussion of how the context may have influenced the effectiveness. The process (activities) was described rather than evaluated against appropriate standards of comparisons. Impact evaluations adhered more closely to documented guidelines, but half of the evaluations did not include impact variables. Outcome evaluations focused on injury incidence. Most evaluations employed some qualitative methods, but the vast majority of methods used were quantitative. This study indicated that the quasi-experimental study design has become an accepted norm for the evaluation of community-based injury prevention programmes. Most of the evaluations contained explicit details of the methodology used and of the choices related to the methodology. While threats to internal validity were identified in most studies, problems related to external validity and construct validity were largely overlooked by the evaluators.

Community Health Planning↗

PubMed2003

A group sequential approach to evaluation of bridging studies.

The International Conference on Harmonization (ICH) E5 guideline defines a bridging study as a supplementary study conducted in the new region to provide pharmacodynamic or clinical data on efficacy, safety, dosage, and dose regimen to allow extrapolation of the foreign clinical data to the population of the new region. Therefore, a bridging study is usually conducted in the new region only after the test product has been approved for commercial marketing in the original region due to its proven efficacy and safety. The issue of analysis of clinical data generated by the bridging study conducted in the new region to evaluate the similarity for extrapolation of the foreign clinical data to the population of the new region is the information on efficacy, safety, dosage, and dose regimen of the original region that cannot be concurrently obtained from the local bridging studies but is available in the trials conducted in the original region. A group sequential approach is therefore proposed to overcome the issue of internal validity. In particular, we use the region as a group sequence to enroll the patients from the original region first and then to enroll patients from the new region subsequently. Methods for sample size determination for the bridging study in the new region are also proposed.

Biopharmaceutics↗

PubMed2004

Design and analytic considerations for single-armed studies with misclassification of a repeated binary outcome.

Due to logistics or prohibitive costs, clinical studies often rely upon a potentially misclassified binary outcome variable for assessing an intervention effect. We consider noncomparative single-armed studies that are sometimes necessary for ethical reasons, and we focus on the situation in which subjects are selected to receive the intervention contingent upon a positive screening test. Both initial misclassification at screening and a regression phenomenon impacting the error-prone follow-up outcome measure contribute to bias in the typical treatment effect estimate. We propose a study design involving the collection of internal validation data assuming the availability of a more demanding gold standard outcome measure. We pursue likelihood-based analysis and describe efficiency considerations relevant to two different treatment effect definitions. We identify four possible types of validation study observations, and discuss finding the optimal allocation into these four types in order to minimize the variance of the estimated treatment effect. The optimal allocation can be highly dependent upon whether a ratio or a difference measure is adopted to evaluate the intervention. The methods are illustrated numerically, and a real-life example motivating the proposed optimal design is provided.

Clinical Trials as Topic↗

PubMed2004

Tests of noninferiority via rate difference for three-arm clinical trials with placebo.

In assessing a noninferiority trial, the investigator intends to show efficacy by demonstrating that a new experimental drug/treatment is not worse than a known active control/reference by a small predefined margin. If it is ethically justifiable, it may be advisable to include an additional placebo group for internal validation purpose. This constitutes the well-known three-arm clinical trial with placebo. In this paper, we study two asymptotic statistical methods for testing of noninferiority in three-arm clinical trials with placebo for binary outcomes based on rate difference. They are sample-based estimation method and restricted maximum likelihood estimation method, respectively. We investigate the performance of the proposed test procedures under different sample size allocation settings via a simulation study. Both methods perform satisfactorily under moderate to large sample settings. However, the restricted maximum likelihood estimation method usually possesses slightly smaller actual type I error rates, which are relatively close to the prespecified nominal level, while the sample-based method can be expressed in a simple closed-form format. Real examples from a pharmacological study of patients with functional dyspepsia and a placebo-controlled trial of subjects with acute migraine are used to demonstrate our methodologies.

Humans↗

PubMed2002

Use of family proxies in quality of life research for cancer patients at the end of life: a literature review.

One of the main goals of end-of-life care is to achieve the best quality of life (QOL) for patients and their families. Quality of life, therefore, represents a significant outcome indicator to evaluate end-of-life care interventions. However, nonresponse bias and nonrandom missing data in QOL research at the end-of-life limits the generalizability and threatens the internal validity of the study findings. The use of family proxy of patients' QOL has been suggested as a solution. Demonstration of satisfactory levels of agreement between proxies and patients is warranted before family caregivers' or other proxies' assessments can be employed when patients cannot provide their own information. Contrary to the conclusion made by Sprangers and Aaronson [The Role of Health Care Providers and Significant Others in Evaluating the Quality of Life of Patients with Chronic Disease: A Review. J. Clin. Epidemiol. 1992, 45, 743-760], it is suggested from this review of literature that terminal cancer patients and their family caregivers agreed at least moderately well on the patients' QOL. The bias introduced by the use of family informants is generally of a modest magnitude. When discrepancies existed, without exception, family caregivers held a more negative view of patients' QOL than did patients. When using family proxies, this is important to remember. The degree of agreement between terminal cancer patients' and their family caregivers' assessments varies as a function of the dimensions of QOL being measured and the patient's health status. However, the accuracy of family caregivers' assessments can be improved by assessing both patients and family caregivers concurrently over time. Several suggestions for future research are provided to better understand the influencing factors of agreement between patients and family assessments and to enhance the quality of statistical analyses on this topic.

Attitude to Health↗

PubMed2004

Appropriate methods to assess the effectiveness and efficacy of treatments or interventions to control cancer pain.

Pain is common in cancer patients. To ensure optimal pain management efficacy and effectiveness of new drugs and treatments have to be investigated in clinical trials. Efficacy trials such as randomised controlled trials (RCT) are experimental studies and estimate the maximum potential benefit to be derived from an intervention in ideal circumstances and under a controlled environment. RCTs are the only trial design to establish causal effects. A crossover study is a special type of RCT where patients serve as own controls. In efficacy studies the intervention and the control group should be as homogeneous as possible, confounding variables are controlled, bias is reduced, internal validity is high whereas external validity is low. Studies looking at effectiveness assess clinical practice and reflect real life circumstances. They rely high on external validity at the expense of careful controls, the study population is heterogeneous, confounding variables are examined. Cohort studies follow a group or groups of individuals with a common characteristic over a period of time to measure outcomes. Case-control studies start with the outcome and compare the characteristics of two groups of interest, those with the outcome and those without to identify factors which occur more or less often in the poor outcome group. Definition of outcome criteria is crucial both for efficacy and effectiveness studies and is often a primary problem. All clinical studies must use valid and reliable outcome measures.

Cross-Over Studies↗

PubMed2006

Devil's Claw (Harpagophytum procumbens) as a treatment for osteoarthritis: a review of efficacy and safety.

BACKGROUND: Osteoarthritis (OA) is a highly prevalent musculoskeletal disorder. Conventional treatment (i.e., the use of nonsteroidal anti-inflammatory drugs-NSAIDs) is associated with well-documented adverse effects. Devil's Claw (Harpagophytum procumbens) a traditional South African herbal remedy used for rheumatic conditions, may be a safer treatment option. To date, 14 clinical trials have assessed its efficacy/ effectiveness in OA. AIM: To address the two main questions of importance to clinicians: (1) Does Devil's Claw work for the treatment of OA, and (2) Is it safe? METHODS: A review of the literature on Devil's Claw and OA from 1966 to 2006 was performed using multiple search databases, monographs, and citation tracking. Relevant trials in all languages were identified and included. Both internal validity (i.e., adequacy of the dosage and period of treatment for this condition, reporting of randomization, rates of dropout, blinding, and statistical analysis) and external validity (i.e., inclusion/ exclusion criteria, baseline characteristics of the study populations, trial setting, and the appropriateness of the outcome measures of the trials) were assessed. RESULTS: Fourteen studies were identified: eight observational studies; 2 comparator trials (1 open, the other randomized to assess clinical effectiveness); and 4 double-blinded, placebo-controlled, randomized controlled trials to assess efficacy. Many of the published trials lacked certain important methodological quality criteria. However, the data from the higher quality studies suggest that Devil's Claw appeared effective in the reduction of the main clinical symptom of pain. The assessment of safety is limited by the small populations generally evaluated in the clinical studies. From the current data, Devil's Claw appears to be associated with minor risk (relative to NSAIDs), but further long-term assessment is required. CONCLUSIONS: The methodological quality of the existing clinical trials is generally poor, and although they provide some support, there are a considerable number of methodologic caveats that make further clinical investigations warranted. The clinical evidence to date cannot provide a definitive answer to the two questions posed: (1) Does it work? And (2) is it safe? A definitive high-quality trial that addresses the necessary methodologic improvements noted is needed to answer these important clinical questions.

Analgesics↗

PubMed1997

Treatment algorithms in child psychopharmacology research.

Clinical trials in child psychiatry research have increased in complexity. Several factors have contributed to this change, including the need to compare multiple therapies, to re-create clinically relevant situations in research, to standardize treatment approaches, to account for the impact of comorbidity, to respond to the needs of individual patients, and to optimize treatment accordingly. To preserve the clinical and internal validity of the experimental interventions vis-à-vis their increasing complexity, researchers have started developing treatment algorithms. These deductive systems for handling data allow us to standardize and incorporate clinical judgment into study designs through the adoption of a stepwise decision making process. Treatment algorithms are different from treatment guidelines. Guidelines are general recommendations that apply to groups of patients with certain characteristics; they are not fully detailed and are created with the expectation that clinical judgment will be applied in individual cases. Algorithms are patient specific, are intended to capture all the relevant details of the clinical situation, and require minimal clinical judgment for their clinical application; they are designed to minimize the role of clinical judgment in research protocols. The entire multistep algorithm is tested in a clinical trial, not the single steps that constitute the algorithm, so proving the efficacy of an algorithm cannot replace a controlled assessment of the individual treatments embedded in the algorithm. Some characteristics, properties, and limitations of algorithms in child psychiatry and psychopharmacology research are presented along with two examples of algorithms currently used in child and adolescent psychopharmacology. Although treatment algorithms seldom have been used in pediatric psychiatry and psychopharmacology, there are indications that their use will increase in the near future and will allow the standardized introduction of clinical judgment into research design.

Adolescent↗