The learning curve for ultrasound-guided peripheral intravenous cannulation in adults: a multicenter study

Aims: To lower the threshold for applying ultrasound (US) guidance during peripheral intravenous cannulation, nurses need to be trained and gain experience in using this technique. The primary outcome was to quantify the number of procedures novices require to perform before competency in US-guided peripheral intravenous cannulation was achieved. Materials and methods: A multicenter prospective observational study, divided into two phases after a theoretical training session: a hands-on training session and a supervised life-case training session. The number of US-guided peripheral intravenous cannulations a participant needed to perform in the life-case setting to become competent was the outcome of interest. Cusum analysis was used to determine the learning curve of each individual participant. Results: Forty-nine practitioners participated and performed 1855 procedures. First attempt cannulation success was 73% during the first procedure, but increased to 98% on the fortieth attempt (p<0.001). The overall first attempt success rate during this study was 93%. The cusum learning curve for each practitioner showed that a mean number of 34 procedures was required to achieve competency. Time needed to perform a procedure successfully decreased when more experience was achieved by the practitioner, from 14±3 minutes on first proce-dure to 3±1 minutes during the fortieth procedure (p<0.001). Conclusions: Competency in US-guided peripheral intravenous cannulation can be gained after following a fixed educational curriculum, resulting in an increased first attempt cannulation success as the number of performed procedures increased.

The Contribution of “Individual Participant Data” Meta-Analyses of Psychotherapies for Depression to the Development of Personalized Treatments: A Systematic Review

While randomized trials typically lack sufficient statistical power to identify predictors and moderators of outcome, “individual participant data” (IPD) meta-analyses, which combine primary data of multiple randomized trials, can increase the statistical power to identify predictors and moderators of outcome. We conducted a systematic review of IPD meta-analyses on psychological treatments of depression to provide an overview of predictors and moderators identified. We included 10 (eight pairwise and two network) IPD meta-analyses. Six meta-analyses showed that higher baseline depression severity was associated with better outcomes, and two found that older age was associated with better outcomes. Because power was high in most IPD meta-analyses, non-significant findings are also of interest because they indicate that these variables are probably not relevant as predictors and moderators. We did not find in any IPD meta-analysis that gender, education level, or relationship status were significant predictors or moderators. This review shows that IPD meta-analyses on psychological treatments can identify predictors and moderators of treatment effects and thereby contribute considerably to the development of personalized treatments of depression.

Hydroxychloroquine/Chloroquine for the Treatment of Hospitalized Patients with COVID-19: An Individual Participant Data Meta-Analysis

Importance: Results from observational studies and randomized clinical trials (RCTs) have led to the consensus that hydroxychloroquine (HCQ) and chloroquine (CQ) are not effective for COVID-19 prevention or treatment. Pooling individual participant data (IPD), including unanalyzed data from trials terminated early, enables further investigation of the efficacy and safety of HCQ/CQ. Objective: To assess efficacy of HCQ/CQ in patients hospitalized with COVID-19, both overall and in prespecified subgroups. Data Sources: ClinicalTrials.gov was searched multiple times in May-June 2020. Principal investigators of US-based RCTs evaluating HCQ/CQ in hospitalized COVID-19 patients were invited to collaborate in this IPD meta-analysis. Study Selection: RCTs in which: (1) HCQ/CQ was a treatment arm; (2) patient informed consent and/or individual study IRB approval allowed for data sharing; (3) principal investigators/their institutions signed a data use agreement for the present study; and (4) the outcomes defined in this study were recorded or could be extrapolated. Data Extraction and Synthesis: Wherever possible, harmonized de-identified data were collected via a common template spreadsheet sent to each principal investigator, then shared via a secure online data sharing platform to create a pooled data set. When this was not possible, individual study data were harmonized and merged manually. Data were analyzed by fitting a prespecified Bayesian ordinal regression model and standardizing the resulting predictions. Main Outcome(s) and Measure(s): 7-point ordinal scale, measured between day 28 and 35 post-enrollment. Results: Eight of 19 trials met eligibility criteria and agreed to participate. Patient-level data were available from 770 participants (412 HCQ/CQ vs 358 control). Baseline characteristics were similar between groups. We found no evidence of a difference in ordinal scores between days 28 and 35 post-enrollment in the pooled patient population (odds ratio, 0.97; 95% credible interval, 0.76-1.24; higher favors HCQ/CQ), and no convincing evidence of meaningful treatment effect heterogeneity among prespecified subgroups. Adverse event and serious adverse event rates were numerically higher with HCQ/CQ vs control (0.39 vs 0.29 and 0.13 vs 0.09 per patient, respectively). Conclusions and Relevance: The findings of this IPD meta-analysis reinforce those of individual RCTs that HCQ/CQ is not efficacious for treatment of COVID-19 in hospitalized patients.

Concurrent chemoradiotherapy with cisplatin + S-1 versus cisplatin + other third-generation agents for locally advanced non-small-cell lung cancer: a meta-analysis of individual participant data

Background For decades, concurrent chemo-radiotherapy with cisplatin-based regimen has been a standard therapy for locally advanced stage III non-small-cell lung cancer (NSCLC). We conducted individual-participant-data (IPD) meta-analyses to compare S-1/cisplatin versus other third-generation anti-cancer medications plus cisplatin regimens with the goal of determining whether or not S-1/cisplatin was the ideal choice for treatment accompanied by radiotherapy (RT). Methods A thorough search was performed using multiple electronic databases. We integrated the IPD of each trial and analyzed the resulting meta-database. The primary endpoint was the overall survival (OS), and the secondary endpoints included the progression-free survival (PFS), objective response rate (ORR), toxicities, and treatment delivery. Subgroup analyses were conducted based on baseline characteristics. Statistical analyses were stratified by trials. Results Three randomized control trials (WJOG5008L study, SPECTRA study, and TORG1018 study) were found. Of the 316 patients enrolled in those studies, 159 received S-1/cisplatin (SP), and 157 were assigned to other combination chemotherapy. The median OS for the SP arm was 48.2 months, and that of the non-SP arm was 42.4 months. The combined hazard ratio (HR) for the OS was 0.895 (95% confidence interval [CI] 0.638–1.256), and no heterogeneity was noted among the trials (test for heterogeneity, p = 0.87; I2 = 0). The median PFS for the SP and non-SP arms was 12.8 and 14.0 months, respectively. The corresponding HR for the PFS was 1.022 (95% CI 0.776–1.347), and there was evidence of moderate heterogeneity among the trials (test for heterogeneity, p = 0.16; I2 = 0.46). The ORRs were 69.7% (95% CI 62.1–76.7%) and 70.9% (95% CI 63.7–78.1%) in the SP and non-SP arms, respectively. The toxicity profile showed that SP caused significantly fewer instances of grade 3–4 leukopenia and neutropenia than non-SP regimens. Conclusion No marked differences were detected in the OS, PFS, or ORR between the SP and non-SP arms. SP had significantly less myelosuppression and better treatment compliance as a chemotherapy regimen for concurrent chemoradiation in locally advanced NSCLC than non-SP regimens.

Effect of daily Vitamin D3 Supplementation on Muscle Health: An Individual Participant Meta-Analysis

Background The role of vitamin D on muscle health is debated. Methods An individual participant metanalysis of four randomized placebo-controlled trials, investigating short term (three to nine months) effects of vitamin D3 in moderate (2800 IU) to high (7000 IU) daily oral doses on muscle health and quality of life (QoL). Inclusion criteria were either obesity (N=52), newly diagnosed primary hyperparathyroidism (N=41), Graves’ disease (N=86) or secondary hyperparathyroidism (N=81). Results Overall (N=260) as well as in a subgroup analysis including only vitamin D insufficient (25(OH)D&lt; 50 nmol/L) individuals (N=176), vitamin D supplementation did not affect measures of muscle health (isometric muscle strength, Timed Up and Go test, Chair Rising Test, body composition, and balance) or QoL. However, a beneficial effect was present on QoL (physical component score) in vitamin D deficient (25(OH)D≤ 25 nmol/L) individuals (N=34). Overall, relative changes in 25(OH)D inversely affected maximum muscle strength in a dose response manner. Stratified into BMI &lt;/≥ 30 kg/m 2, vitamin D supplementation had divergent effects on isometric muscle strength, with beneficial effects in obese individuals (N=93) at knee flexion 90° (p=0.04), and adverse effects in non-obese individuals (N=167) at handgrip (p=0.02), knee extension 60° (p=0.03) and knee flexion 60° (p&lt;0.01). Conclusion Overall, short-term treatment with moderate to high daily doses of vitamin D did not affect muscle health or QoL. A potential beneficial effect was present on muscle strength in severe obese individuals and on QoL in vitamin D deficient individuals. Subgroup analyses however suggested negative effects of large relative increases in p-25(OH)D.