Tag: nevin manimala

Eur J Cancer. 2021 Apr 3;149:49-60. doi: 10.1016/j.ejca.2021.03.007. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: Trial designs using multiple primary endpoints (MPEs) are increasing in phase III cancer trials. Our objectives were to describe the incidence of MPEs in recently published phase III trials testing systemic treatments in patients with advanced cancer; the main characteristics of trials adopting MPEs; the presence of mature results for all endpoints in the primary publication; consistency between results of each endpoint and authors’ conclusions.

METHODS: Articles of randomised phase III trials conducted in patients with advanced cancer, published between 2017 and 2020, were retrieved from PubMed. The main outcome was the proportion of trials with MPEs. In principle, according to regulatory agencies, we considered two distinct cases: (i) MPEs correspond to ‘multiple chances’ for the success of experimental treatment, needing adjustment for multiplicity, and (ii) a positive result depends on the success in all MPEs (‘co-primary’ endpoints).

RESULTS: Out of 235 eligible trials, 27 trials (12%) adopted MPE, mostly overall survival (OS) and progression-free survival (PFS). The proportion of trials with MPEs increased over time, from 6% in 2017 to 20% in 2020 (p = 0.025). MPEs were adopted in 16% of for-profit trials versus 4% of non-profit trials (p = 0.006). The proportion of trials adopting MPEs was particularly high with immunotherapy (53%, p < 0.00001). Out of 27 trials with MPEs, 10 (37%) adopted an explicit definition of ‘co-primary’ endpoints, but only 1/10 declared the positivity of both endpoints critical for interpretation. Most trials (23, 85%) planned correction for multiplicity. Of 21 publications with positive conclusions, only 12 had a statistically significant positive result in both primary endpoints. In four cases (15%), positive conclusions were based on PFS results alone.

CONCLUSIONS: Adoption of MPEs in randomised trials in oncology is quite common. Only a minority of trials respect recommendations by regulatory agencies about the adoption of MPEs, definition of ‘co-primary’ endpoints and correction for multiplicity.

PMID:33823362 | DOI:10.1016/j.ejca.2021.03.007

Pediatr Neurol. 2021 Mar 8;119:15-21. doi: 10.1016/j.pediatrneurol.2021.02.010. Online ahead of print.

ABSTRACT

BACKGROUND: Levetiracetam is a relatively new-generation antiseizure drug approved for the treatment of focal and generalized seizures. Despite its favorable side effect profile and minimal drug-drug interactions, neuropsychiatric side effects are reported in up to 13% of children. A few case series have suggested that supplementation of pyridoxine may mitigate these side effects, but controlled trials are lacking. To address this issue, a randomized interventional study was carried out in a pediatric tertiary hospital to qualify and quantify the potential beneficial effect of pyridoxine in attenuating the neuropsychiatric side effects of levetiracetam in children.

METHODS: A total of 105 children with epilepsy who were taking levetiracetam (as a monotherapy or an adjunct) who showed behavioral symptoms coinciding with the start of levetiracetam, were included. Patients randomly and blindly received either a therapeutic (pyridoxine group, 46 of 105, 44%) or a homeopathic dose of pyridoxine (placebo, 59 of 105, 56%). A 30-item behavioral checklist was used to qualify and quantify the behavioral side effects at baseline and at different time points following initiation of treatment.

RESULTS: Both placebo and pyridoxine groups experienced a statistical reduction in behavioral scores when compared with baseline. Our study indicated that although there was a placebo effect, the improvement in neuropsychiatric symptoms was more prominent in children who received therapeutic doses of pyridoxine.

CONCLUSIONS: These data provide clinicians with pertinent evidence-based information that suggests that a trial of pyridoxine in patients who experience behavioral side effects due to the use of levetiracetam may avoid unnecessary change of antiseizure medications.

PMID:33823377 | DOI:10.1016/j.pediatrneurol.2021.02.010

J Pediatr Nurs. 2021 Apr 3;61:102-108. doi: 10.1016/j.pedn.2021.03.024. Online ahead of print.

ABSTRACT

PURPOSE: This study was designed to evaluate the short- and long-term effects of a scenario simulation-based education intervention on parental anxiety about fever in their children.

DESIGN AND METHODS: This experimental research was conducted using a two-group pretest-posttest design. One hundred and sixty parents of 3-month to 5-year-old children enrolled in preschools and kindergartens with childcare services were recruited as participants using cluster random sampling. The participants were divided randomly into an experimental group (80) and a control group (80). The former participated in a scenario simulation-based education intervention and received a fever education booklet. The latter received the booklet only. Data were collected using the Children’s Fever Anxiety Inventory at three time points: before the intervention (pretest, T1) and at six-month (T2) and 12-month (T3) posttests.

RESULTS: Significant intergroup differences in fever anxiety were found at both T2 and T3 (p < .001). For both groups, the scores at T2 and T3 were significantly lower than at T1 (p < .001) and the difference between T2 and T3 did not attain statistical significance (p > .05). Although both groups experienced reduced fever anxiety over time, this reduction was significantly greater in the experimental group than in the control group (p < .001).

CONCLUSION: Simulation-based education may be used in conjunction with the traditional fever education booklet to further reduce parent fever anxiety over time.

PRACTICE IMPLICATIONS: This simulation-based education approach significantly and positively impacts parental anxiety about fever in their children. Furthermore, the approach may be generalizable to other childhood healthcare settings.

PMID:33823379 | DOI:10.1016/j.pedn.2021.03.024

Contemp Clin Trials. 2021 Apr 3:106378. doi: 10.1016/j.cct.2021.106378. Online ahead of print.

ABSTRACT

Efficient identification of the optimal dose and dosing scheme is one of the most critical and challenging tasks in early-phase oncology trials. The results are far-reaching because advancing a sub-optimal dose to late-stage development may not only jeopardize patients’ safety or fail to deliver desired efficacy, but also be costly to sponsors as refined doses must be evaluated further before seeking regulatory approval. A good dose-escalation design is anticipated to yield high accuracy of selecting the correct dose while using fewer patients and keeping the trial duration short. Recently, treating a single patient at each lower dose level until certain events are triggered to switch to larger cohorts has gained much popularity. We name this approach “Single Patient Acceleration” (SPA), which is essentially a variant of the Accelerated Titration Design (ATD) by Simon et al. [25]. Although literature on novel dose-escalation methods is abundant in the past decade, there is a surprisingly lack of research on evaluating the ATD/SPA framework. In this article, we conduct comprehensive simulations to evaluate the performance of dose-escalation designs with or without SPA, and show that SPA improves design efficiency with similar or better accuracy to those without the “single patient” component under certain circumstances (e.g., slow initial enrollment, or the true maximum tolerated dose is at higher candidate dose levels). Potential safety concerns as a cost of efficiency improvement are also investigated in a quantitative manner to illustrate a comprehensive benefit-risk profile of SPA. Practical considerations and recommendations in using SPA are also discussed.

PMID:33823296 | DOI:10.1016/j.cct.2021.106378

Mol Cell Proteomics. 2021 Apr 3:100076. doi: 10.1016/j.mcpro.2021.100076. Online ahead of print.

ABSTRACT

Proteogenomics approaches often struggle with the distinction between true and false peptide-to-spectrum matches as the database size enlarges. However, features extracted from tandem mass spectrometry intensity predictors can enhance the peptide identification rate and can provide extra confidence for peptide-to-spectrum matching in a proteogenomics context. To that end, features from the spectral intensity pattern predictors MS²PIP and Prosit were combined with the canonical scores from MaxQuant in the Percolator post-processing tool for protein sequence databases constructed out of ribosome profiling and nanopore RNA-seq analyses. The presented results provide evidence that this approach enhances both the identification rate as well as the validation stringency in a proteogenomic setting.

PMID:33823297 | DOI:10.1016/j.mcpro.2021.100076

Ann Vasc Surg. 2021 Apr 3:S0890-5096(21)00241-7. doi: 10.1016/j.avsg.2021.01.118. Online ahead of print.

ABSTRACT

INTRODUCTION: Persistent type II endoleaks (ELIIp) occur in 8% to 23% of patients submitted to endovascular aneurysm repair (EVAR) and may lead to aneurysm progression and rupture. Intraoperative embolization of the abdominal aortic aneurysm (AAA) sac is effective to prevent their occurrence, however a method to achieve complete sac thrombosis has not been standardized yet. Aim of our study was to identify factors associated with prevention of ELIIp after intraoperative embolization, in order to optimize technical details.

METHODS: Patients at high risk for ELIIp, who underwent EVAR with AAA – sac coil embolization were prospectively collected into a dedicated database from January 2012 to March 2015. The endoluminal residual sac volume (ERV), not occupied by the endograft [ERV= AAA total volume (TV) – (AAA-thrombus volume (THV) + endograft volume (EgV)] was calculated on preoperative computed tomography and the concentration of coils implanted (CCoil= n coils implanted/ERV) for each patient was evaluated. AAA volumetric evaluation was conducted by dedicated vessels analysis software (3Mensio). ELIIp presence was evaluated by contrast-enhanced ultrasound at 6 and 12-month. Patients with ELIIp at 12 months (Group 1) were clustered and compared to patients without ELIIp (Group 2), in order to evaluate the incidence of ELIIp in patients undergone to preventive AAA-sac embolization, and identify the predictors of ELIIp prevention. Morphological potential risk factors for ELIIp such as TV, THV, VR% and EgV were also considered in all patients. Statistical correlation was assessed by Fisher Exact Test.

RESULTS: Among 326 patients undergone to standard EVAR, 61 (19% – M: 96.7%, median age: 72 (IQR: 8) years, median AAA diameter: 57(IQR: 7) mm) were considered at high risk for ELIIp and were submitted to coil embolization. The median AAA total volume (TV) and median ERV were 156 (IQR: 59) cc and 46 (IQR: 26) cc, respectively. The median number and concentration of coils (IMWCE-38-16-45 Cook M-Ray) positioned in AAA-sac were 5 (IQR: 1) coils and 0.17 coil/cm³ (range 0.02-1.20). Among this high-risk population, the incidence of ELIIp was 29.5% and 23% at 6 and 12-month, respectively. Fourteen patients (23%) were clustered in Group1 and 47 (77%) in Group 2. Both groups were homogeneous for clinical characteristics and preoperative morphological risk factors. There were no differences in the preoperative median TV, AAA-thrombus volume (THV), %VR, EgV and number of implanted coils between Group1 and Group2. Patients in Group1 had a significantly higher ERV [59 (IQR: 13) cm³ vs 42 (IQR: 27) cm³, P = .002] and lower CCoil [0.09 (IQR: 0.03) vs 0.18 (IQR: 0.21), P = .006] than patients of Group2. ELIIp was significantly related to the presence of ERV > 49 cm³ (86 % vs 42 %, Group1 and Group2 respectively, P = .006) and CCoil < 0.17coil/ cm³ (100% vs 68%, Group1 e Group2 respectively, P = .014).

CONCLUSION: According with our results, Coil concentration and endoluminal residual volume can affect the efficacy of the AAA – sac embolization in the prevention of ELIIp, moreover CCoil ≥ 0.17coil/ cm³ maight be considered to determine the tailored number of coils.

PMID:33823259 | DOI:10.1016/j.avsg.2021.01.118

Contemp Clin Trials. 2021 Apr 3:106392. doi: 10.1016/j.cct.2021.106392. Online ahead of print.

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) screening (CRCS) facilitates early detection and lowers CRC mortality.

OBJECTIVES: To increase CRCS in a randomized trial of stepped interventions. Step 1 compared three modes of delivery of theory-informed minimal cue interventions. Step 2 was designed to more intensively engage those not completing CRCS after Step 1.

METHODS: Recruitment packets (60,332) were mailed to a random sample of individuals with a record of U.S. military service during the Vietnam-era. Respondents not up-to-date with CRCS were randomized to one of four Step 1 groups: automated telephone, telephone, letter, or survey-only control. Those not completing screening after Step 1 were randomized to one of three Step 2 groups: automated motivational interviewing (MI) call, counselor-delivered MI call, or Step 2 control. Intention-to-treat (ITT) analyses assessed CRCS on follow-up surveys mailed after each step.

RESULTS: After Step 1 (n = 1784), CRCS was higher in the letter, telephone, and automated telephone groups (by 1%, 5%, 7%) than in survey-only controls (43%), although differences were not statistically significant. After Step 2 (n = 516), there were nonsignificant increases in CRCS in the two intervention groups compared with the controls. CRCS following any combination of stepped interventions overall was 7% higher (P = 0.024) than in survey-only controls (55.6%).

CONCLUSIONS: In a nationwide study of veterans, CRCS after each of two stepped interventions of varying modes of delivery did not differ significantly from that in controls. However, combined overall, the sequence of stepped interventions significantly increased CRCS.

PMID:33823295 | DOI:10.1016/j.cct.2021.106392

J Pediatr Endocrinol Metab. 2021 Apr 7. doi: 10.1515/jpem-2020-0714. Online ahead of print.

ABSTRACT

OBJECTIVES: Childhood obesity is a public health concern worldwide, with rates continuing to rise, despite preventive measures. Lifestyle modification remains the mainstay in the treatment of patients with excessive weight, but unfortunately, this is not always successful. Options for medical management of obesity in the paediatric population are limited.

METHODS: Seven adolescents (all girls, mean age 14.9 years) with a body mass index (BMI) above 98th percentile and serious complications secondary to obesity were offered an intense weight management programme. The participants were reviewed by a multidisciplinary team every two weeks for advice and support, and treated with daily subcutaneous injections of liraglutide (dose range 1.2-3.0 mg). Scores for anxiety and depression were evaluated using the Revised Child Anxiety and Depression Scale.

RESULTS: The results showed a significant weight loss over the three months with an average reduction of 5.4 kg (4.2%; 95% CI 1.93-8.78; p=0.0087). The mean drop in BMI was 2.1 kg/m², which is statistically significant (95% CI 0.973-3.199; p=0.0037). Resolution of complications (raised intracranial pressure and steatohepatitis) was noted following weight loss. Anxiety and depressive symptoms improved over the three-month intervention course, especially features of separation anxiety disorder. Liraglutide was well tolerated by all patients.

CONCLUSIONS: Liraglutide medication, alongside a dedicated multidisciplinary team guided lifestyle therapy, is effective and safe in the treatment for excessive weight in adolescents, leading to the reversal of the complications related to obesity and improvement in the psychological symptoms.

PMID:33823101 | DOI:10.1515/jpem-2020-0714

J Pediatr Endocrinol Metab. 2021 Apr 7. doi: 10.1515/jpem-2021-0051. Online ahead of print.

ABSTRACT

OBJECTIVES: It is unclear whether body weight status (underweight/normal weight/overweight/obese) is associated with allergic disease. Our objective was to investigate the relationship between body weight status (body mass index; BMI) and atopic allergic disease in prepubertal children, and to compare children with atopic allergic diseases with non atopic healthy children.

METHODS: A prospective cross sectional study of 707 prepubertal children aged 3-10 years was performed; the participants were 278 atopic children with physician-diagnosed allergic disease (allergic rhinitis and asthma) (serum total IgE level >100 kU/l and eosinophilia >4%, or positivity to at least one allergen in skin test) and 429 non atopic healthy age- and sex-matched controls. Data were collected between December 2019 and November 2020 at the Pediatric General and Pediatric Allergy Outpatient Clinics of Bezmialem Vakıf University Hospital.

RESULTS: Underweight was observed in 11.6% of all participants (10.8% of atopic children, 12.2% of healthy controls), and obesity in 14.9% of all participants (18.0% of atopic children, 12.8% of controls). Obese (OR 1.71; 95% CI: 1.08-2.71, p=0.021), and overweight status (OR 1.62; 95% CI: 1.06-2.50, p=0.026) were associated with an increased risk of atopic allergic disease compared to normal weight in pre-pubertal children. This association did not differ by gender. There was no relationship between underweight status and atopic allergic disease (OR 1.03; 95% CI: 0.63-1.68, p=0.894).

CONCLUSIONS: Overweight and obesity were associated with an increased risk of atopic allergic disease compared to normal weight among middle-income and high-income pre pubertal children living in Istanbul.

PMID:33823105 | DOI:10.1515/jpem-2021-0051

J Pediatr Endocrinol Metab. 2021 Apr 7. doi: 10.1515/jpem-2020-0600. Online ahead of print.

ABSTRACT

OBJECTIVES: We validated a continuous cardiometabolic risk (CMR) measure among adolescents.

METHODS: Five metabolic syndrome (MetS) components including waist circumference, triglycerides, high-density lipoprotein cholesterol, fasting blood glucose, and mean arterial pressure were assessed in a national cohort of U.S. adolescents (n=560; 16.5 ± 0.5 y/o at baseline) in 10th grade (2010, Wave 1 (W1)), and follow-up assessments four (W4) and seven (W7) years later. Separately by wave, linear regressions were fitted to each MetS component controlling for age, sex, and race/ethnicity, and yielded standardized residuals (Z-scores). Wave-specific component Z-scores were summed to obtain composite CMR Z-scores. Four- and seven-year CMR change (CMR-diff W1-W4 and W1-W7). and average CMR risk (CMR-avg; (W1 + W4)/2 and (W1 + W7)/2) were calculated using the CMR Z-scores. W7 MetS was determined using adult criteria. Student’s t-test and receiver operating characteristic (ROC) curve were conducted.

RESULTS: Participants meeting the adult criteria for MetS at W7 (74 of 416, 17.8%) had statistically significant (p<0.01) higher values for W1 CMR Z-scores (0.92 vs. -0.21), W4 CMR Z-scores (1.69 vs. -0.28), W7 CMR Z-scores (2.21 vs. -0.55), W1-W4 CMR-avg (1.53 vs. -0.27), W1-W7 CMR-diff (1.29 vs. -0.21), and W1-W7 CMR-avg (1.46 vs. -0.48) than those not meeting MetS criteria. Most results were similar for males and females in the sex-stratified analyses. The areas under the ROC curve were 0.61, 0.71, and 0.75 for W1, W4 and W7 Z-scores.

CONCLUSIONS: Findings support the validity of the continuous CMR Z-scores calculated using linear regression in evaluating and monitoring CMR profiles from adolescence to early adulthood.

PMID:33823099 | DOI:10.1515/jpem-2020-0600