Validity and Reliability of POM-Checker for Measuring Shoulder Range of Motion in Healthy Participants: A Pilot Single-Center Comparative Study.

BACKGROUND: The aim of this study was to compare shoulder movement measurements between a Kinect-based markerless ROM assessment device (POM-Checker) and a 3D motion capture analysis system (BTS SMART DX-400). METHODS: This was a single-visit clinical trial designed to evaluate the validity and reliability of the POM-Checker. The primary outcome was to assess the equivalence between two measurement devices within the same set of participants, aiming to evaluate the validity of the POM-Checker compared to the gold standard device (3D Motion Analysis System). As this was a pilot study, six participants were included. RESULTS: The intraclass correlation coefficient (ICC) and the corresponding 95% confidence intervals (CIs) were used to assess the reproducibility of the measurements. Among the 18 movements analyzed, 16 exhibited ICC values of >0.75, indicating excellent reproducibility. CONCLUSION: The results showed that the POM-checker is reliable and validated to measure the range of motion of the shoulder joint.

Quality Characteristics and Acceptance Intention for Healthcare Kiosks: Perception of Elders from South Korea Based on the Extended Technology Acceptance Model.

This study aimed to perform a path analysis to understand the effects of quality characteristics on perceived usefulness, perceived ease to use, involvement, and acceptance intention of healthcare kiosks in elderly using the extended technology acceptance model. We performed structural equation modeling (SEM) with data from 300 elderly. The following results were obtained. Firstly, elderly's perceived quality characteristics of healthcare kiosks had a partial positive effect on perceived usefulness. Secondly, elderly's perceived quality characteristics of healthcare kiosks had a partial positive effect on perceived ease to use. Thirdly, elderly's perceived ease to use healthcare kiosks had a partial positive effect on perceived usefulness. In addition, elderly's perceived usefulness of healthcare kiosks had a positive effect on acceptance intention. Lastly, elderly's perceived ease to use healthcare kiosks had a positive effect on acceptance intention.

Deep CT to MR Synthesis Using Paired and Unpaired Data.

Magnetic resonance (MR) imaging plays a highly important role in radiotherapy treatment planning for the segmentation of tumor volumes and organs. However, the use of MR is limited, owing to its high cost and the increased use of metal implants for patients. This study is aimed towards patients who are contraindicated owing to claustrophobia and cardiac pacemakers, and many scenarios in which only computed tomography (CT) images are available, such as emergencies, situations lacking an MR scanner, and situations in which the cost of obtaining an MR scan is prohibitive. From medical practice, our approach can be adopted as a screening method by radiologists to observe abnormal anatomical lesions in certain diseases that are difficult to diagnose by CT. The proposed approach can estimate an MR image based on a CT image using paired and unpaired training data. In contrast to existing synthetic methods for medical imaging, which depend on sparse pairwise-aligned data or plentiful unpaired data, the proposed approach alleviates the rigid registration of paired training, and overcomes the context-misalignment problem of unpaired training. A generative adversarial network was trained to transform two-dimensional (2D) brain CT image slices into 2D brain MR image slices, combining the adversarial, dual cycle-consistent, and voxel-wise losses. Qualitative and quantitative comparisons against independent paired and unpaired training methods demonstrated the superiority of our approach.

On a class of optimal covariate-adjusted response adaptive designs for survival outcomes.

A class of optimal covariate-adjusted response adaptive procedures is developed for phase III clinical trials when the treatment response is a survival time and there is random censoring. The basic aim is to develop an allocation design by combining the ethical aspects with statistical precision in a reasonable way under the presence of covariate information. Considering minimisation of total hazards as the ethical requirement, the proposed procedure is assessed in terms of the assignment to the better treatment and the efficiency (i.e. power) to detect a small departure in treatment effectiveness. The applicability of the proposed methodology is also illustrated using a real data set.

Multiple-stage sampling procedure for covariate-adjusted response-adaptive designs.

Covariate-adjusted response-adaptive (CARA) design becomes an important statistical tool for evaluating and comparing the performance of treatments when targeted medicine and adaptive therapy become important medical innovations. Due to the nature of the adaptive therapies of interest and how subjects accrue to a sampling procedure, it is of interest how to control the sample size sequentially such that the estimates of treatment effects have satisfactory precision in addition to its asymptotic properties. In this paper, we apply a multiple-stage sequential sampling method to CARA design in such a way that the control of the sample size is more feasible. The theoretical properties of the proposed method, including the estimates of regression parameters and the allocation probabilities under this randomly stopped sampling procedure, are discussed. The numerical results based on synthesized data and a real example are presented.

Is tolvaptan indicated for refractory oedema in nephrotic syndrome?

Tolvaptan is useful for correcting dilutional hyponatraemia because of its aquaretic effect. On the other hand, there is a distinct lack of data regarding tolvaptan-induced natriuresis, although previous studies have demonstrated improvement of congestive symptoms and signs in heart failure patients following tolvaptan treatment. Here, we report the case of a 47-year-old man diagnosed with minimal change nephrotic syndrome and whose refractory oedema was immediately controlled by tolvaptan before steroid response was induced. With tolvaptan treatment, patient urine output increased dramatically to approximately 5.5 L/day and body weight decreased by 9 kg over 5 days. Interestingly, urine sodium concentration, fractional excretion of sodium and urine osmolality all increased in response to tolvaptan administration. However, serum sodium concentration was maintained within the normal range, and mild azotaemia was corrected. Tolvaptan was discontinued after 11 days when heavy proteinuria and generalized oedema had been resolved. We discuss the potential mechanisms by which V2 receptor antagonists may stimulate natriuresis in the kidney. In conclusion, tolvaptan may be useful as an adjunctive treatment for oedematous disorders.

Comparison of Paired ROC Curves through a Two-Stage Test.

The area under the receiver operating characteristic (ROC) curve (AUC) is a popularly used index when comparing two ROC curves. Statistical tests based on it for analyzing the difference have been well developed. However, this index is less informative when two ROC curves cross and have similar AUCs. In order to detect differences between ROC curves in such situations, a two-stage nonparametric test that uses a shifted area under the ROC curve (sAUC), along with AUCs, is proposed for paired designs. The new procedure is shown, numerically, to be effective in terms of power under a wide range of scenarios; additionally, it outperforms two conventional ROC-type tests, especially when two ROC curves cross each other and have similar AUCs. Larger sAUC implies larger partial AUC at the range of low false-positive rates in this case. Because high specificity is important in many classification tasks, such as medical diagnosis, this is an appealing characteristic. The test also implicitly analyzes the equality of two commonly used binormal ROC curves at every operating point. We also apply the proposed method to synthesized data and two real examples to illustrate its usefulness in practice.

Covariate-adjusted response-adaptive designs for longitudinal treatment responses: PEMF trial revisited.

Response-adaptive designs have become popular for allocation of the entering patients among two or more competing treatments in a phase III clinical trial. Although there are a lot of designs for binary treatment responses, the number of designs involving covariates is very small. Sometimes the patients give repeated responses. The only available response-adaptive allocation design for repeated binary responses is the urn design by Biswas and Dewanji [Biswas A and Dewanji AA. Randomized longitudinal play-the-winner design for repeated binary data. ANZJS 2004; 46: 675-684; Biswas A and Dewanji A. Inference for a RPW-type clinical trial with repeated monitoring for the treatment of rheumatoid arthritis. Biometr J 2004; 46: 769-779.], although it does not take care of the covariates of the patients in the allocation design. In this article, a covariate-adjusted response-adaptive randomisation procedure is developed using the log-odds ratio within the Bayesian framework for longitudinal binary responses. The small sample performance of the proposed allocation procedure is assessed through a simulation study. The proposed procedure is illustrated using some real data set.

Gemcitabine and oxaliplatin in patients with unresectable biliary cancer including gall bladder cancer: a Korean Cancer Study Group phase II trial.

PURPOSE: Chemotherapy represents a palliative treatment, with poor response rates and a median survival of less than 6 months in patients with biliary tract cancers (BTCs). The aim of this study was to evaluate the efficacy and safety of the combination chemotherapy with gemcitabine and oxaliplatin (GEMOX) in patients with BTCs including gall bladder cancer. METHODS: We carried out a nationwide multicenter phase II study evaluated the efficacy and safety of GEMOX as first-line therapy in patients with advanced BTCs. Eligible patients with previously untreated locally advanced or metastatic BTCs received gemcitabine 1,000 mg/m(2) (day 1 and 8) and oxaliplatin 100 mg/m(2) (day 1), every 3 weeks. RESULTS: Fifty-three patients were evaluated, 60% had cholangiocarcinoma and the remaining 40% gall bladder cancer; the objective response rate was 18.9% (10/53 patients including 1 Complete response) [14.9%; 95% confidence interval (CI), 7.4-25.7%] in the treated population. Stable disease were observed in 27/53 (50.9%) patients, disease control rate was achieved in 69.8% of all patients. Median progression-free survival was 4.8 months (3.1-6.5, 95% CI) and median overall survival was 8.3 months (5.8-10.8, 95% CI). Grade 3/4 toxicities included neutropenia (33.9% of patients) and thrombocytopenia (7.6%). CONCLUSIONS: The GEMOX regimen demonstrated a modest antitumor activity and is well tolerated in patients with advanced BTCs.

Sequential analysis of longitudinal data in a prospective nested case-control study.

The nested case-control design is a relatively new type of observational study whereby a case-control approach is employed within an established cohort. In this design, we observe cases and controls longitudinally by sampling all cases whenever they occur but controls at certain time points. Controls can be obtained at time points randomly scheduled or prefixed for operational convenience. This design with longitudinal observations is efficient in terms of cost and duration, especially when the disease is rare and the assessment of exposure levels is difficult. In our design, we propose sequential sampling methods and study both (group) sequential testing and estimation methods so that the study can be stopped as soon as the stopping rule is satisfied. To make such a longitudinal sampling more efficient in terms of both numbers of subjects and replications, we propose applying sequential sampling methods to subjects and replications, simultaneously, until the information criterion is fulfilled. This simultaneous sequential sampling on subjects and replicates is more flexible for practitioners designing their sampling schemes, and is different from the classical approaches used in longitudinal studies. We newly define the σ-field to accommodate our proposed sampling scheme, which contains mixtures of independent and correlated observations, and prove the asymptotic optimality of sequential estimation based on the martingale theories. We also prove that the independent increment structure is retained so that the group sequential method is applicable. Finally, we present results by employing sequential estimation and group sequential testing on both simulated data and real data on children's diarrhea.

Correct use of repeated measures analysis of variance.

In biomedical research, researchers frequently use statistical procedures such as the t-test, standard analysis of variance (ANOVA), or the repeated measures ANOVA to compare means between the groups of interest. There are frequently some misuses in applying these procedures since the conditions of the experiments or statistical assumptions necessary to apply these procedures are not fully taken into consideration. In this paper, we demonstrate the correct use of repeated measures ANOVA to prevent or minimize ethical or scientific problems due to its misuse. We also describe the appropriate use of multiple comparison tests for follow-up analysis in repeated measures ANOVA. Finally, we demonstrate the use of repeated measures ANOVA by using real data and the statistical software package SPSS (SPSS Inc., USA).

Peru-15, a live attenuated oral cholera vaccine, is safe and immunogenic in Bangladeshi toddlers and infants.

A live oral Vibrio cholerae O1 El Tor vaccine, Peru-15 was tested in a double-blind, randomized placebo controlled study for safety and immunogenicity in Phase I and Phase II studies in 240 Bangladeshi children aged 9 months-5 years of age. Two different doses (2x10(7) and 2x10(8)cfu) were tested. Vaccination did not elicit adverse events and the strain was genetically stable. Vibriocidal antibody responses developed in 42/50 (84%) toddlers (2-5 years) and 35/50 (70%) of younger children (9-23 months) and overall 77/100 (77%) who received the high dose. LPS-IgA-antibody responses were seen in 60% of toddlers and 34% of infants; 40% responded with IgA antibodies to cholera toxin. The responses to the reduced dose was lower. These studies demonstrate that Peru-15 at a dose of 2x10(8)cfu is safe and immunogenic in children in Bangladesh.

Randomized, controlled study of the safety and immunogenicity of Peru-15, a live attenuated oral vaccine candidate for cholera, in adult volunteers in Bangladesh.

BACKGROUND: A live oral Vibrio cholerae O1 El Tor vaccine candidate, Peru-15, was studied for safety, immunogenicity, and excretion in phase 1 (inpatient) and phase 2 (outpatient) studies of Bangladeshi adults.METHODs. The study was conducted among adults, by use of a double-blind, randomized, placebo-controlled design. A single dose of Peru-15 (approximately 2 x 108 cfu) or placebo (buffer only) was given in standard bicarbonate and ascorbic acid buffer.RESULTS. Study treatment did not elicit any major adverse events in the volunteers, during either the inpatient or the outpatient phases, and there were no reports of diarrhea. V. cholerae was isolated from the stool of only 1 volunteer and was found to be genetically identical to the vaccine strain. Vibriocidal antibody responses were seen in 30 (75%) of 40 vaccine recipients and in 3 (10%) of 30 placebo recipients. Peripheral blood immunoglobulin (Ig) A and IgM antibody-secreting cell responses to lipopolysaccharide were seen in the majority of vaccine recipients (response rate, 78%--88%). Seroconversion for lipopolysaccharide-specific IgA antibodies was seen in 88% of vaccine recipients. The response in vaccine recipients was significantly higher than that in placebo recipients, in all of the immunological assays (P=.036 to <.001). A lower immunological response against cholera toxin B subunit was detected.CONCLUSIONS. The safety and immunogenicity of this Peru-15 vaccine candidate indicates the usefulness of future studies in Bangladesh, where cholera is endemic.

The role of epidemiology in the introduction of vi polysaccharide typhoid fever vaccines in Asia.

Despite the availability of at least two licensed typhoid fever vaccines--injectable sub-unit Vi polysaccharide vaccine and live, oral Ty21a vaccine--for the last decade, these vaccines have not been widely introduced in public-health programmes in countries endemic for typhoid fever. The goal of the multidisciplinary DOMI (Diseases of the Most Impoverished) typhoid fever programme is to generate policy-relevant data to support public decision-making regarding the introduction of Vi polysaccharide typhoid fever immunization programmes in China, Viet Nam, Pakistan, India, Bangladesh, and Indonesia. Through epidemiological studies, the DOMI Programme is generating these data and is offering a model for the accelerated, rational introduction of new vaccines into health programmes in low-income countries. Practical and specific examples of the role of epidemiology are described in this paper. These examples cover: (a) selection of available typhoid fever vaccines to be introduced in the programme, (b) generation of policy-relevant data, (c) providing the 'backbone' for the implementation of other multidisciplinary projects, and (d) generation of unexpected but useful information relevant for the introduction of vaccines. Epidemiological studies contribute to all stages of development of vaccine evaluation and introduction.

Development of pathogenicity-driven definitions of outcomes for a field trial of a killed oral vaccine against enterotoxigenic Escherichia coli in Egypt: application of an evidence-based method.

BACKGROUND: To design an efficacy trial of a killed oral vaccine against enterotoxigenic Escherichia coli (ETEC) diarrhea in Egyptian children, we derived for ETEC diarrhea an empirical definition that increased the probability that diarrhea associated with excretion of ETEC was caused by the detected ETEC. METHODS: We conducted a cohort study of 397 Egyptian children <24 months old and monitored them until they were 3 years old. Vaccine-preventable (VP) ETEC was defined as ETEC expressing >/=1 of the toxin- (heat-labile [LT] toxin) and colonization-factor antigens (CFA I, II, and IV) in the vaccine. RESULTS: Although fecal excretion of VP-ETEC was highly associated with diarrhea, excretion of LT-ETEC per se was not related to diarrhea (adjusted odds ratio [OR(A)], 1.16 [95% confidence interval [CI], 0.90-1.49]). The fecal excretion of antigenic types of VP-ETEC other than LT-ETEC (non-LT VP-ETEC) was highly associated with diarrheal symptoms (OR(A), 3.91 [95% CI, 2.78-5.49]; P<.001), and this association was greater for nonbloody than for bloody diarrhea. CONCLUSIONS: Because the vaccine had been anticipated to protect primarily against symptomatic ETEC diarrhea, these results indicate that the primary-outcome definition of ETEC diarrhea for the trial should be restricted to nonbloody diarrheal episodes associated with fecal excretion of non-LT VP-ETEC.

Clinical, epidemiological, and socioeconomic analysis of an outbreak of Vibrio parahaemolyticus in Khanh Hoa Province, Vietnam.

From 1996 onward, a pandemic spread of Vibrio parahaemolyticus infections due to one clone has been reported in several Asian countries. During a population-based study that relied on passive surveillance, 548 cases of V. parahaemolyticus infection were detected between 1997 and 1999 in the Khanh Hoa province of Vietnam. Detection of cases of V. parahaemolyticus infection abruptly stopped in November 1999, although Vibrio species other than V. parahaemolyticus continued to be isolated throughout 2000. Of the infections, 90% occurred in individuals >5 years old; 53% of the patients presented with watery stools, and 6% reported blood in their stools. All patients had recovered by the time of discharge. A surprising risk factor for V. parahaemolyticus infections was high socioeconomic status. Like the interruption of the transmission of V. cholerae infections that had been observed earlier, the transmission of V. parahaemolyticus came to a halt without meteorological changes or changes in water supply and sanitation.