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Background: Our study aimed to systematically summarize the dentoskeletal effects of Herbst appliance; Forsus fatigue resistance device; and Class II elastics in adolescent Class II malocclusion. Methods: Five databases; unpublished literature; and reference lists were last searched in August 2022. Randomized clinical trials and observational studies of at least 10 Class II growing patients that assessed dentoskeletal effects through cephalometric/CBCT superimpositions were eligible. The included studies quality was assessed with the RoB 2 and ROBINS-I tools. A random-effects model meta-analysis was performed. Heterogeneity was explored with subgroup and sensitivity analyses. Results: Among nine studies (298 patients); two-to-three studies were included in each meta-analysis. Less post-treatment upper incisor retroclination (<2) and no overbite; overjet; SNA; SNB; and lower incisor inclination differences were found between Herbst/Forsus and Class II elastics. No differences in maxilla; condyle; glenoid fossa; and most mandibular changes were found between Herbst and Class II elastics; except for a greater 1.5 mm increase in mandibular length and right mandibular ramus height (1.6 mm) with Herbst. Conclusions: Herbst and Class II elastics corrected the molar relationship; but Herbst moved the lower molars more mesially. Apart from an additional mandibular length increase; no other dental and anteroposterior skeletal difference was found. Forsus was more effective in molar correction; overjet reduction; and upper incisor control than Class II elastics. Trial registration number OSF: 10.17605/OSF.IO/8TK3R. [ABSTRACT FROM AUTHOR]

Aim of this systematic review was to assess the efficacy of preventive interventions against the development of white spot lesions (WSLs) during fixed appliance orthodontic treatment. Nine databases were searched without limitations in September 2018 for randomized trials. Study selection, data extraction and risk of bias assessment were done independently in duplicate. Random-effects meta-analyses of mean differences (MDs) or relative risks (RRs) with their 95% confidence intervals (CIs) were conducted, followed by sensitivity analyses, and the GRADE analysis of the evidence quality. A total of 24 papers (23 trials) were included, assessing preventive measures applied either around orthodontic brackets (21 trials; 1427 patients; mean age 14.4 years) or molar bands (2 trials; 46 patients; age/sex not reported). Active patient reminders were associated with reduced WSL incidence on patient level compared to no reminder (3 trials; 190 patients; RR: 0.4; 95% CI: 0.31-0.64; Number Needed to Treat [NNT]: 3 patients), flat surface sealants were associated with reduced WSL incidence on tooth level than no sealant (5 trials; 2784 teeth; RR: 0.8; 95% CI: 0.63-0.95; NNT: 33 teeth), and fluoride varnish was associated with reduced WSL severity on tooth level (2 trials; 1160 teeth; MD: -0.32 points; 95% CI: -0.44 to -0.21 points). However, the quality of evidence was low according to GRADE, due to risk of bias. Some evidence indicates that active patient reminders and flat surface sealants or fluoride varnish around orthodontic brackets might be associated with reduced WSL burden, but further research is needed. [ABSTRACT FROM AUTHOR]

In this overview we present a summary of evidence from systematic reviews (SRs) on the safety and efficacy of carfilzomib in multiple myeloma (MM). Our search in electronic databases and conference proceedings yielded 14 eligible SRs, graded as of low overall quality with the AMSTAR-2 tool. The Corrected Covered Area index was 52.3% which shows very high overlap among studies. Carfilzomib was shown to increase progression free survival (HR=0.61, 95%CI=0.47–0.78, p = 0.01, I2 =73%), overall survival (HR=0.79,95%CI=0.66–0.95, p = 0.01, I2 =0) and overall response rate (OR=2.4,95% CI=1.6–3.4, p < 0.001, I2 =99%) in relapsed/refractory MM (RRMM); all with moderate quality of evidence assessed with the GRADE approach. Carfilzomib was associated with cardiovascular adverse events (AEs) (RR=2.2, 95%CI=1.6–2.9, p < 0.001, I2 =0), nephrotoxicity (RR=1.79, 95% CI=1.43–2.23, p < 0.001, I2 =39%) and serious infections (RR=1.40, 95%CI=1.17–1.69, p < 0.001, I2 =57%). Concluding, carfilzomib is effective in RRMM, but associated with certain AEs. More randomized clinical trials and high-quality SRs, especially on newly diagnosed patients are needed. [Display omitted] • Carfilzomib improves survival in relapsed/ refractory multiple myeloma. • Carfilzomib increases cardiotoxicity, nephrotoxicity and serious infections. • The quality of systematic reviews for carfilzomib is generally low. • More randomized controlled trials with carfilzomib are needed for safe conclusions. • Carfilzomib needs further investigation in newly diagnosed myeloma patients. [ABSTRACT FROM AUTHOR]

Objective: Clinical sites participating in multicenter trials may have unequal performance in recruiting subjects. We propose using the Gini coefficient as a quantitative measure of site accrual inequalities.Study design and setting: We evaluated the relationship of this metric to other study characteristics across 166 clinical studies (27,865 subjects) conducted by the AIDS Clinical Trials Group between 1986 and 1999.Results: Overall there was a modest recruitment inequality among clinical centers (mean Gini = 0.33). In multivariate modeling, site accrual inequalities were higher when there was more protracted enrollment, and a larger number of sites and were lower in antiretroviral studies than other studies. In long-term studies, the site accrual inequality increased significantly over time (P = 0.004). In efficacy trials, a higher Gini coefficient was associated with higher likelihood of the study results being statistically significant (P = 0.010).Conclusion: The Gini coefficient may be easily and routinely incorporated in the description of the characteristics of a clinical study and may provide insights about its enrollment pattern. [Copyright &y& Elsevier]

In a cohort of 14 randomized controlled trials conducted by the Adult AIDS Clinical Trials Group between 1986 and 1999 with a target sample size of >400 (total enrollment 15,531 patients), we evaluated whether “late-starter” sites can make a meaningful contribution to eventual trial accrual. The sites that started recruiting within 5 months from the time the first patient entered the trial were eventually responsible for over 90% of the total enrollment in 11 of the 14 trials. Across the 14 trials, some sites were consistently among the first to start enrollment, whereas others were routinely among the last. The late-starter sites are unlikely to make important contributions to eventual trial enrollment in large clinical trials conducted by groups with a fixed number of sites. Protracting administrative efforts to add more sites many months after a multicenter trial has started may not be useful to trial accrual. [Copyright &y& Elsevier]

Guideline statements may be supported by evidence obtained from various study designs, but randomized trials are usually considered most important for making recommendations about therapeutic and preventive interventions. This study evaluated the extent to which randomized trials are cited in guidelines published in major journals. The references of 191guidelines of therapeutic and/or preventive interventions published in Annals of Internal Medicine, BMJ, JAMA, Lancet, NEJM and Pediatrics in 1979, 1984, 1989, 1994, and 1999, were analyzed. The percentage of guidelines not citing any randomized controlled trials (RCTs) decreased gradually from 95% in 1979 to 53% in 1999. Among 4,853 references of the guidelines, there were 393 RCTs (8.1% of total), 19 systematic reviews (0.4%), and 23 meta-analyses of RCTs (0.5%). Among 19 guidelines published in 1999 or 1994 with <2 RCTs cited, in eight cases additional pertinent RCTs were identified that had not been cited by the guideline. There is a clear increase in the use of randomized evidence by guidelines over time. However, several guidelines in major journals still cite few or no RCTs. [Copyright &y& Elsevier]

The authors evaluated whether early enrollment affects the significance of the results and the time to completion and publication of randomized controlled trials. Seventy-seven efficacy randomized controlled trials (total enrollment, 28,992 patients) initiated by the Acquired Immunodeficiency Syndrome Clinical Trials Group between 1986 and 1996 were evaluated. After adjustment for target sample size, for each 10-fold increase in the first-month accrual, the odds of a trial reaching statistically significant results increased 2.8-fold (p = 0.040). The relative enrollment during the first month over target sample size (hazard ratio (HR) = 1.40 per 10 percent increase, p = 0.004) and masking (HR = 1.78 for double-blind vs. single or unblinded studies, p = 0.031) were the major predictors of faster completion. Rapid early accrual (HR = 1.09 per 10 additional patients accrued the first month, p = 0.011) and statistical significance in favor of an experimental arm (HR = 2.47, p = 0.004) independently predicted faster publication. Early enrollment is a strong predictor of whether a study will reach formal statistical significance, and it can offer predictive information on the time needed to complete the study and publish its findings. Ongoing unpublished studies and their enrollment rates may need to be considered when interpreting the accumulated evidence. [ABSTRACT FROM PUBLISHER]

Background: We examined whether quarterly patient enrollment in a large multicenter clinical trials group could be modeled in terms of predictors including time parameters (such as long-term trends and seasonality), the effect of large trials and the number of new studies launched each quarter. We used the database of all clinical studies launched by the AIDS Clinical Trials Group (ACTG) between October 1986 and November 1999. Analyses were performed in two datasets: one included all studies and substudies (n = 475, total enrollment 69,992 patients) and the other included only main studies (n = 352, total enrollment 57,563 patients).Results: Enrollment differed across different months of the year with peaks in spring and late fall. Enrollment accelerated over time (+27 patients per quarter for all studies and +16 patients per quarter for the main studies, p < 0.001) and was affected by the performance of large studies with target sample size > 1,000 (p < 0.001). These relationships remained significant in multivariate autoregressive modeling. A time series based on enrollment during the first 32 quarters could forecast adequately the remaining 21 quarters.Conclusions: The fate and popularity of large trials may determine the overall recruitment of multicenter groups. Modeling of enrollment rates may be used to comprehend long-term patterns and to perform future strategic planning. [ABSTRACT FROM AUTHOR]

Aims: To compare the safety and efficacy of insulin detemir versus neutral protamine Hagedorn (NPH) in pregnant women with diabetes.Methods: MEDLINE, CENTRAL, Google Scholar databases, and ClinicalTrials.gov registry were searched from inception to December 2021 to identify randomized controlled trials (RCTs) concerning adult women with singleton pregnancies, gestational or pregestational diabetes, and the need for insulin therapy. A systematic review and a meta-analysis (weighted data, random-effects model) were performed. Continuous outcomes were expressed as mean difference (MD) with 95% confidence interval (CI) (inverse variance method); dichotomous outcomes were expressed as risk ratio (RR) with 95% CI (Mantel-Haenszel method). Heterogeneity was quantified using the I2 index.Results: Five RCTs involving 1450 participants met the inclusion criteria. Outcomes that showed significant results in favor of insulin detemir over NPH were maternal hypoglycemic events (RR 0.64, 95% CI 0.48-0.86, p = 0.003; I2 = 0%) and gestational age at delivery (MD 0.48, 95% CI 0.16-0.81, p = 0.003; I2 = 0%).Conclusions: Insulin detemir was associated with less maternal hypoglycemic events and decreased risk for prematurity compared with NPH insulin. More research should be conducted to reach a safe conclusion about the optimal insulin regimen for women with diabetes in pregnancy. [ABSTRACT FROM AUTHOR]