Analysis and reporting of stratified cluster randomized trials—a systematic survey

Background In order to correctly assess the effect of intervention from stratified cluster randomized trials (CRTs), it is necessary to adjust for both clustering and stratification, as failure to do so leads to misleading conclusions about the intervention effect. We have conducted a systematic survey to examine the current practices about analysis and reporting of stratified CRTs. Method We used the search terms to identify the stratified CRTs from MEDLINE since the inception to July 2019. In phase 1, we screened the title and abstract for English-only studies and selected, including the main results paper of the identified protocols, for the next phase. In phase 2, we screened the full text and selected studies for data abstraction. The data abstraction form was piloted and developed using the REDCap. We abstracted data on multiple design and methodological aspects of the study including whether the primary method adjusted for both clustering and stratification, reporting of sample size, randomization, and results. Results We screened 2686 studies in the phase 1 and selected 286 studies for phase 2—among them 185 studies were selected for data abstraction. Most of the selected studies were two-arm 140/185 (76%) and parallel-group 165/185 (89%) trials. Among these 185 studies, 27 (15%) of them did not provide any sample size or power calculation, while 105 (57%) studies did not mention any method used for randomization within each stratum. Further, 43 (23%) and 150 (81%) of 185 studies did not provide the definition of all the strata, while more than 60% of the studies did not include all the stratification variable(s) in the flow chart or baseline characteristics table. More than half 114/185 (62%) of the studies did not adjust the primary method for both clustering and stratification. Conclusion Stratification helps to achieve the balance among intervention groups. However, to correctly assess the intervention effect from stratified CRTs, it is important to adjust the primary analysis for both stratification and clustering. There are significant deficiencies in the reporting of methodological aspects of stratified CRTs, which require substantial improvements in several areas including definition of strata, inclusion of stratification variable(s) in the flow chart or baseline characteristics table, and reporting the stratum-specific number of clusters and individuals in the intervention groups.

PENGARUH STRATIFIKASI SOSIAL TERHADAP PELAYANAN PUBLIK DI KANTOR DESA KALOSI KECAMATAN DUA PITUE KABUPATEN SIDENRENG RAPPANG

The purpose of this study is to determine the effect of social stratification at the Kalosi Village Office in Duapitue Sub-district, Sidenreng Rappang Regency and to determine the factors that influence social stratification on public services at the Kalosi Village Office in Duapitue Sub-District, Sidenreng Rappang District.The population in this study is the total number of family heads in the village of Kalosi, amounting to 1,471 consisting of two hamlets. The sampling technique uses the Slovin formula with 93.63 results rounded up to 94, including 94 respondents, taken based on the Probability sampling technique, more precisely Random sampling. This type of research is quantitative descriptive. Data collection techniques used in this study were observation, questionnaire, literature study and documentation. The collected data is then analyzed using data analysis techniques using validity, reliability and regression tests with the help of the SPSS 16.0 program. Based on the results of the questionnaire, the influence of social stratification on public services has a significant effect on the results of the processed data in the ANOVA table. The value of t arithmetic = 9.340> t table = 3.179 with a significant value of 0,000 <0.05, then Ho is rejected and Ha is accepted, which means there is a significant (significant) social stratification variable (X) on public service variables (Y) and based on From the results of the questionnaire, the factors influencing social stratification can be seen from the first factor differences in race and culture have an influence of 50.2%, the second factor is the existence of specifications in the field of work, 19.2% and the third factor is the scarcity in society regarding the distribution of rights. and a liability of 13%. Keywords: Startification and service public

RADI-31. MULTI-INSTITUTIONAL VALIDATION OF BRAIN METASTASIS VELOCITY, A RECENTLY DEFINED PREDICTOR OF OUTCOMES FOLLOWING STEREOTACTIC RADIOSURGERY

INTRODUCTION: Brain metastasis velocity (BMV) is a prognostic metric that describes the recurrence rate of new brain metastases after initial treatment with radiosurgery (SRS). We have previously risk stratified patients into high, intermediate, and low-risk BMV groups, which correlates with overall survival (OS). We sought to externally validate BMV in a multi-institutional setting. METHODS: Patients from nine academic centers were treated with upfront SRS; the validation cohort consisted of data from eight institutions not previously used to define BMV. Patients were classified by BMV into low (&lt; 4 BMV), intermediate (4–13 BMV), and high-risk groups (&gt;13 BMV). Time-to-event outcomes were estimated using the Kaplan-Meier method. Cox proportional hazards methods were used to estimate the effect of BMV and salvage modality on OS. RESULTS: Of 2829 patients, 2092 patients were included in the validation dataset. Of these, 921 (44.0%) experienced distant brain failure (DBF). Median OS from initial SRS was 11.2 mo. Median OS for BMV &lt; 4, BMV 4–13, and BMV &gt; 13 were 12.5 mo, 7.0 mo, and 4.6 mo (p &lt; 0.0001). Compared to initial salvage with WBRT, salvage SRS was associated with improved OS following DBF for BMV &lt; 4 (p = 0.05), BMV 4–13 (p = 0.002) and BMV &gt; 13 (p = 0.0001). CONCLUSIONS: This multi-institutional dataset validates BMV as a predictor of OS following initial SRS. BMV is being utilized in upcoming multi-institutional randomized controlled trials as a stratification variable for salvage whole brain radiation vs salvage SRS after DBF.

Teaching Vocabulary Using Multimedia: The Case of U.S. International Students.

The study examined the use of Multimedia in teaching of vocabulary. For the past decades, the use of technology in the language classrooms has been an important aspect of language instruction. Most research in language teaching has focused on the efficacy of teaching using computers. Sixty participants (40 females and 20 males), studying in the United States, participated in this study. Stratified sampling using nationality as a stratification variable was used to select participants. In this study, there were two independent variables, with each variable having two levels. The first independent variable was “use of pictures,” with two levels: still versus animation, and the second independent variable was “knowledge type”, with two levels: receptive versus productive. The dependent variables were participants’ scores derived from vocabulary tests obtained from pre-test and post-test. Data were analyzed using dependent t–tests and Pearson r correlation efficient. The results revealed that there was a positive correlation between the use of still and animated pictures in teaching vocabulary, while the dependent t-tests revealed that there was a significant difference between retention of still receptive knowledge and still productive knowledge, also between animated receptive knowledge and animated productive knowledge. The results have implications for teaching vocabulary using Multimedia.

Defibrotide for Prophylaxis of Hepatic Veno-Occlusive Disease in Pediatric Hematopoietic Stem Cell Transplantation: Subanalysis Data from an Open-Label, Phase III, Randomized Trial

Introduction Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (VOD/SOS), is a potentially life-threatening complication of conditioning for hematopoietic stem cell transplantation (HSCT) and is associated with patient and transplant-related risk factors, such as prior therapies, underlying diagnoses, and conditioning regimen. Unpredictable in its occurrence and severity, VOD/SOS is clinically characterized by painful hepatomegaly, hyperbilirubinemia, ascites, and weight gain. Overall estimated prevalence is 14% post-HSCT, while rates in some high-risk populations (eg, osteopetrosis or prior gemtuzumab ozogamicin) are >60% (Wadleigh M et al. Blood. 2003;102:1578-82; Corbacioglu S et al. Bone Marrow Transplant. 2006;38:547-53). Evidence suggests that defibrotide stabilizes endothelial cells, with direct and endothelial-cell mediated restoration of the thrombo-fibrinolytic balance. Defibrotide is approved in the European Union for the treatment of severe hepatic VOD/SOS in patients receiving HSCT, and is available in the United States through an expanded-access study. In a previously reported randomized clinical trial, defibrotide prophylaxis for VOD/SOS in high-risk pediatric patients undergoing HSCT reduced the overall incidence of VOD/SOS by day +30 post-HSCT. Here we report novel subgroup analyses of VOD/SOS incidence from this trial in patients with specific VOD/SOS risk factors at baseline. Methods This was a phase 3, multicenter, open-label, randomized, controlled trial in patients aged <18 years, undergoing myeloablative conditioning before allogeneic or autologous HSCT, with ≥1 risk factor for VOD/SOS. VOD/SOS was diagnosed according to modified Seattle criteria plus >5% weight gain. Patients were randomized to standard care with or without defibrotide prophylaxis dosed at 25 mg/kg/day in 4 divided infusions of 6.25 mg/kg. Osteopetrosis was a stratification variable. Defibrotide began the same day as HSCT conditioning and continued for 30 days post-HSCT, or ≥14 days for patients discharged from hospital before day +30 post-HSCT. Control patients who developed VOD/SOS received defibrotide treatment. The primary endpoint was incidence of VOD/SOS at day +30 post-HSCT. Results The intent-to-treat population included 356 patients: 180 randomized to defibrotide prophylaxis and 176 in the control group. Mean (SD) age was 6.6 (5.3) years, and 40.7% of patients were female. Demographic and clinical characteristics, including VOD/SOS risk factors (Table), were well-matched in the defibrotide and control groups. The most common risk factors among all patients were conditioning with busulfan and melphalan (58%), preexisting liver disease (27%), and second myeloablative transplantation (13%). VOD/SOS occurred by day +30 post-HSCT in 22 (12%) patients in the defibrotide prophylaxis group vs 35 (20%) patients in the control group. For the stratification variable, osteopetrosis, rates of VOD/SOS were 14% in the defibrotide prophylaxis arm and 67% in the control arm (Table). Differences in rates of VOD/SOS were lowest for adrenoleukodystrophy (no cases) and prior abdominal irradiation (11% vs 13%, respectively) (Table). Conclusions Across risk-factor subgroups, the rate of VOD/SOS was lower in patients receiving defibrotide compared with controls (except adrenoleukodystrophy: no VOD/SOS in either group). In particular, rates of VOD/SOS by day +30 were reduced by ≥50% in the defibrotide arm vs the control arm among patients with osteopetrosis, hemophagocytic lymphohistiocytosis, second myeloablative transplantation, and prior gemtuzumab treatment. Although the total numbers of patients with these risk factors were small, these between-group differences are of clinical interest and should be further explored. Table. Risk Factor Defibrotide (n=180) Control (n=176) Total n VOD/SOS incidence (n=22; 12.2%) n (%*) Total n VOD/SOS incidence (n=35; 20.0%) n (%*) Adrenoleukodystrophy 1 0 (0) 1 0 (0) Osteopetrosis 7 1 (14) 6 4 (67) Prior abdominal irradiation 9 1 (11) 8 1 (13) Hemophagocytic lymphohistiocytosis 10 0 (0) 15 6 (40) Prior gemtuzumab 11 2 (18) 5 2 (40) Allogeneic HSCT for leukemia 17 2 (12) 11 2 (18) Second myeloablative transplantation 25 2 (8) 23 4 (17) Pre-existing liver disease 41 6 (15) 54 12 (22) Busulfan/melphalan conditioning 106 15 (14) 99 17 (17) *Percent of patients with VOD/SOS. Support: Jazz Pharmaceuticals Disclosures Corbacioglu: Gentium S.p.A.: Consultancy, Honoraria. Off Label Use: Defibrotide is an investigational treatment for hepatic veno-occlusive disease/sinusoidal obstruction syndrome in the United States.. Bader:Amgen: Consultancy; Medac: Other: Institutional grants; Neovii: Other: Institutional grants; Riemser: Other: Institutional grants; Novartis: Consultancy; Jazz Pharmaceuticals: Consultancy.

Relationships between Smoking Behavior and Readiness to Change Physical Activity Patterns in a Community in Japan

Purpose. To examine the relationship between readiness to change exercise behavior and smoking behavior, stratified by gender. Methods. A cross-sectional survey of those inhabitants of Hikami, Japan, who were 30 years of age or older (n = 11,708). The response rate was 82.1%. Chi-squared tests and analysis of variance were used to evaluate differences in characteristics by smoking behavior, and the odds ratio (OR) was calculated to examine the relationship while controlling for possible confounding factors such as age, body mass index, and health consciousness. Results. Even when controlling for confounding factors, the relationship between the two behaviors differed according to gender. Among males, ex-smokers were more likely to be motivated to exercise (OR, 1.14; 95% confidence interval [CI], .95–1.36), whereas among females, smokers were more likely to be motivated to exercise (OR, .40; 95% CI, .34–.48). Discussion. Despite some limitations, the findings suggest that gender should be used as a stratification variable when discussing the relationship between smoking and exercise behaviors.

Caffeine intake and pregnancy outcomes: a meta-analytic review

Epidemiological publications on the relationship of caffeine to birth weight and duration of human pregnancy, from 1966 to 1995, were searched through Medline. Each study was treated as the stratification variable, and its weight in the weighted average was proportional to the inverse of its variance. Twenty-six studies were located. Among the twenty-two studies on birth weight, eleven were on mean birth weight, nine on low birth weight (LBW), and four on intrauterine growth retardation (IUGR). Combined analysis of mean birth weigh study results showed a significant decrease in birth weight of nearly 43g among newborns of the heaviest caffeine-consuming mothers. LBW, IUGR, and preterm delivery displayed significant homogeneity in the test results, indicating that a pooled estimate should not be taken as an adequate measure. The high heterogeneity of the available literature on the effects of caffeine on LBW, IUGR, and preterm delivery prevents estimation of reliable pooled estimates through meta-analysis. Further assessment of caffeine intake during pregnancy is needed in future research.