Target and actual sample sizes for studies from two trial registries from 1999 to 2020: an observational study

ObjectivesTo investigate differences between target and actual sample sizes, and what study characteristics were associated with sample sizes.DesignObservational study.SettingThe large trial registries of clinicaltrials.gov (starting in 1999) and ANZCTR (starting in 2005) through to 2021.ParticipantsOver 280 000 interventional studies excluding studies that were withheld, terminated for safety reasons or were expanded access.Main outcome measuresThe actual and target sample sizes, and the within-study ratio of the actual to target sample size.ResultsMost studies were small: the median actual sample sizes in the two databases were 60 and 52. There was a decrease over time in the target sample size of 9%–10% per 5 years, and a larger decrease of 18%–21% per 5 years for the actual sample size. The actual-to-target sample size ratio was 4.1% lower per 5 years, meaning more studies (on average) failed to hit their target sample size.ConclusionRegistered studies are more often under-recruited than over-recruited and worryingly both target and actual sample sizes appear to have decreased over time, as has the within-study gap between the target and actual sample size. Declining sample sizes and ongoing concerns about underpowered studies mean more research is needed into barriers and facilitators for improving recruitment and accessing data.

O-L06 The use of tumour marker Ca19.9 in the follow up of patients with resected biliary tract cancer: Results from the BILCAP randomised clinical trial

Background Even after resection biliary tract cancer has a poor outlook. Follow-up is commonly utalises and the sialyl-Lewis tetra saccharide antigen Ca19.9, a known tumour marker in pancreatic and biliary malignancy (upper limit of normal (ULN) 37U/ml). However, the evidence base for the utility of Ca19.9 is limited. The UK BILCAP trial examined the use of adjuvant capecitabine chemotherapy in resected biliary tract cancer and establishing a new global standard of care. Ca19.9 was regularly measured as part of the BILCAP protocol, this provides an opportunity to assess the use of this marker in a large trial with complete patient follow-up. Methods Between March 2006 and December 2014 447 patients underwent resectional surgery (R0 or R1) then were randomised to receive capecitabine chemotherapy or observation. CT imaging and Ca19.9 were performed 3 monthly in year 1, 6 monthly in year 2, and annually thereafter up to 5 years. Follow up was continued until all patients had 5 years follow-up. Recurrence was based mainly on imaging criteria combined with the clinical presentation. The cohort was divided into progression and non- progression groups and the Ca19. 9 values recorded were investigated using descriptive analyses with cut-off of 37 (ULN), 100 and 400U/ml. Results Of 447 study patients 440 had at least one Ca19.9 measurement from either post-operative baseline (394) or a follow-up visit (422). Baseline Ca19-9 was elevated above 37U/ml in 96 patients and 82 (85%) went on to develop recurrence. The sensitivity, specificity, positive predictive value (PPV) and negative predictive values (NPV) of the Ca19.9 on follow up are shown in the table. Conclusions Although high Ca19.9 levels predict recurrence as shown by acceptable positive predictive values at cut-offs of 100 and 400U/ml the negative predictive values are very poor as most patients develop recurrence without elevation of Ca19.9. Ca19.9 measurement is of very limited value in the follow up of patients with resected biliary cancer.

Mechanisms of cognitive-behavioral therapy effects on symptoms of body dysmorphic disorder: a network intervention analysis

Background Body dysmorphic disorder (BDD) is a severe and undertreated condition. Although cognitive-behavioral therapy (CBT) is the first-line psychosocial treatment for this common disorder, how the intervention works is insufficiently understood. Specific pathways have been hypothesized, but only one small study has examined the precise nature of treatment effects of CBT, and no prior study has examined the effects of supportive psychotherapy (SPT). Methods This study re-examined a large trial (n = 120) comparing CBT to SPT for BDD. Network intervention analyses were used to explore symptom-level data across time. We computed mixed graphical models at multiple time points to examine relative differences in direct and indirect effects of the two interventions. Results In the resulting networks, CBT and SPT appeared to differentially target certain symptoms. The largest differences included CBT increasing efforts to disengage from and restructure unhelpful thoughts and resist BDD rituals, while SPT was directly related to improvement in BDD-related insight. Additionally, the time course of differences aligned with the intended targets of CBT; cognitive effects emerged first and behavioral effects second, paralleling cognitive restructuring in earlier sessions and the emphasis on exposure and ritual prevention in later sessions. Differences in favor of CBT were most consistent for behavioral targets. Conclusions CBT and SPT primarily affected different symptoms. To improve patient care, the field needs a better understanding of how and when BDD treatments and treatment components succeed. Considering patient experiences at the symptom level and over time can aid in refining or reorganizing treatments to better fit patient needs.

Highlights from ASCO-GI 2021 from EORTC Gastrointestinal tract cancer group

Last year the field of immunotherapy was finally introduced to GI oncology, with several changes in clinical practice such as advanced hepatocellular carcinoma or metastatic colorectal MSI-H. At the virtual ASCO-GI symposium 2021, several large trial results have been reported, some leading to a change of practice. Furthermore, during ASCO-GI 2021, results from early phase trials have been presented, some with potential important implications for future treatments. We provide here an overview of these important results and their integration into routine clinical practice.

Benefits and Risks of Dexamethasone in Noncardiac Surgery

Dexamethasone is an effective antiemetic and improves patient quality of recovery. Meta-analyses and a recent large trial found no increase in risk of surgical site infection. Dexamethasone should be more widely used in perioperative practice.

Developing learning supplement book of Cell Mitotic Division material for Junior High School students

Cell division is an abstract material for middle school students in which learning resources and supporting learning media are compulsory to use. This research and development aimed at developing learning supplement book of mitotic cell material for IX graders which eases them to identify cell division, particularly in mitotic phase. This study was developed based on ADDIE model which comprised of four stages (i.e. Analysis, Design, Development, Implementation, and Evaluation). The validation test was conducted by teaching and learning material experts. The two stage tests were conducted in small and large trial groups. The qualitative and quantitative data gained were analyzed using percentage. The results showed that the percentage values were 86.2% (very feasible) for teaching material, 99.4% (very feasible) for learning material. The small-scale trial gained 87.8% (very feasible), meanwhile the large-scale test gained 88.3% (very feasible). In conclusion, the mitotic learning supplement book of cell division material for junior high school can be used as teaching material in classroom learning activities.

Ultrasound Assessment of the Inferior Vena Cava for Fluid Responsiveness: Making the Case for Skepticism

Determining whether a patient in shock is in a state of fluid responsiveness (FR) has long been the Holy Grail for clinicians who care for acutely ill patients. While various tools have been put forth as solutions to this important problem, ultrasound assessment of the inferior vena cava has received particular attention of late. Dozens of studies have examined its ability to determine whether a patient should receive volume expansion, and general enthusiasm has been strengthened by the fact that it is easy to perform and non-invasive, unlike many competing FR tests. A deeper examination of the technique, however, reveals important concerns regarding inaccuracies in measurement and a high prevalence of confounding factors. Furthermore, a detailed review of the evidence (small individual studies, multiple meta-analyses, and a single large trial) reveals that the tool performs poorly in general and is unlikely to be helpful at the bedside in circumstances where genuine clinical uncertainty exists.

Late Thrombectomy in Clinical Practice

Background and Purpose To provide real-world data on outcome and procedural factors of late thrombectomy patients. Methods We retrospectively analyzed patients from the multicenter German Stroke Registry. The primary endpoint was clinical outcome on the modified Rankin scale (mRS) at 3 months. Trial-eligible patients and the subgroups were compared to the ineligible group. Secondary analyses included multivariate logistic regression to identify predictors of good outcome (mRS ≤ 2). Results Of 1917 patients who underwent thrombectomy, 208 (11%) were treated within a time window ≥ 6–24 h and met the baseline trial criteria. Of these, 27 patients (13%) were eligible for DAWN and 39 (19%) for DEFUSE3 and 156 patients were not eligible for DAWN or DEFUSE3 (75%), mainly because there was no perfusion imaging (62%; n = 129). Good outcome was not significantly higher in trial-ineligible (27%) than in trial-eligible (20%) patients (p = 0.343). Patients with large trial-ineligible CT perfusion imaging (CTP) lesions had significantly more hemorrhagic complications (33%) as well as unfavorable outcomes. Conclusion In clinical practice, the high number of patients with a good clinical outcome after endovascular therapy ≥ 6–24 h as in DAWN/DEFUSE3 could not be achieved. Similar outcomes are seen in patients selected for EVT ≥ 6 h based on factors other than CTP. Patients triaged without CTP showed trends for shorter arrival to reperfusion times and higher rates of independence.