Confidence Interval For Difference Research Articles

The effect of Tai Chi lower extremity exercise on the balance control of older adults in assistant living communities

BackgroundAlthough Tai Chi (TC) is an evidence-based fall prevention training for older adults, its effective movements remain unclear, which may limit the practice of TC. The purpose of this study was to compare the effectiveness of TC lower extremity exercise (TC LEE), the 8-form Tai Chi (8-form TC), and a stretching control intervention for improving balance and functional mobility among older adults.MethodsThis was a randomized controlled trial. A total of 102 participants (79 ± 6 years old) were recruited from assisted living facilities. All participants were randomly assigned to the TC LEE (n = 40), 8-form TC (n = 31), and stretching (n = 31) groups in which they received the respective interventions for 16 weeks. The Berg Balance Scale (BBS), Timed Up and Go (TUG) test, and center of pressure (COP) measurements during quiet stance were collected prior to and following the 16-week interventions. Comparisons on all measurements were conducted among all groups.ResultsSignificant improvements were found in BBS (P = 0.002), TUG test (P = 0.001), root mean square amplitude of COP displacement in the anterior–posterior (P = 0.001) and medial–lateral (P = 0.001) directions, and average COP speed in the anterior–posterior (P = 0.001) and medial–lateral (P = 0.001) directions after training in the TC intervention groups compared with the stretching group. The upper limit of the 95% confidence interval (CI) of differences in change scores on the BBS (-0.8 – 1.3 points) between the TC LEE group and the 8-form TC group was within equivalence margins (1.8 points), while the upper limit of the 95% CI of differences in change scores on the TUG test (0.1 – 2.1 s) exceeded the equivalence margin (0.7 s) with the TC LEE group having the larger change scores.ConclusionTC LEE can improve balance and functional mobility in older adults, and may have greater effect than the 8-form TC on improving functional mobility as measured by the TUG test.Trial registrationChiCTR2300070600 retrospectively registered.

Safety and immunogenicity of a modified Omicron-adapted inactivated vaccine in healthy adults: a randomized, double-blind, active-controlled Phase III clinical trial.

Updated vaccine strategies are needed to protect against new SARS-CoV-2 variants with increased immune escape. Here, information on the safety and immunogenicity of an inactivated Omicron-adapted vaccine is presented, as compared with CoronaVac. A randomized, double-blind, active-controlled, phase III clinical trial was conducted to compare a modified Omicron-adapted vaccine (Omicron vaccine) with the authorized prototype vaccine (CoronaVac®) as a booster dose. Healthy adults aged ≥18 years, who have previously received 2 or 3 doses of CoronaVac (2C or 3C cohort) at least 6 months before, were enrolled to get a booster dose of Omicron vaccine or CoronaVac in a ratio of 2:1 (2C/3C+1O/1C). Back-up serums after two initial doses of CoronaVac (2C+0) for adults aged 26-45 years were collected from a previous study. Immunogenicity and safety data at 28 days after vaccination were collected and analyzed. One of the primary objectives was to evaluate the superiority of immunogenicity of Omicron vaccine booster against Omicron BA.1, compared with CoronaVac booster against BA.1. Another objective was to evaluate the non-inferiority of immunogenicity of Omicron vaccine booster against BA.1, compared with two initial doses of CoronaVac against ancestral strain. Between June 1st and July 21st, 2022, a total of 1,500 healthy adults were enrolled. Results show that all pre-specified superiority criteria for BA.1 neutralizing antibody were met. Specifically, within the 3C cohort (3C+1O vs. 3C+1C), the geometric mean titers' (GMT) ratio and 95% confidence interval (CI) was 1.64 (1.42, 1.89), with the lower 95%CI ≥1; a GMT ratio of 1.84 (1.57, 2.16) was observed for 2C+1O versus 3C+1C. For seroconversion rate, the lower 95%CIs of differences between immuno-comparative groups (2/3C+1O vs. 3C+1C) were all above the superiority criterion 0%. However, the non-inferiority criterion of the lower 95%CI of GMT ratio ≥2/3 was unfulfilled for 2C/3C+1O against BA.1 versus 2C+0 against ancestral strain. Safety profiles were similar between groups, with no safety concerns identified. The Omicron-adapted vaccine was well-tolerated and could elicit superior immune responses as compared with CoronaVac against Omicron, while it appeared inferior to CoronaVac against ancestral strain. https://classic.clinicaltrials.gov/ct2/show/NCT05381350?term=NCT05381350&draw=2&rank=1, identifier NCT05381350.

Comparison of Efficacy and Safety of Lupin’s Pegfilgrastim with Neulastim® as an Adjunct to Chemotherapy in Patients with Non Myeloid Malignancies: A Randomised Phase III Clinical Study

Introduction: Pegfilgrastim is indicated in patients receiving myelosuppressive anticancer drugs to reduce the Duration of Severe Neutropenia (DSN) and incidence of Febrile Neutropenia (FN). The efficacy and safety of a proposed pegfilgrastim biosimilar should be compared with an approved biologic drug to establish therapeutic equivalence. Aim: To compare the efficacy of Lupin’s biosimilar Pegfilgrastim versus Neulastim® (Amgen Inc.) as an adjunct to chemotherapy in patients with non-myeloid malignancies. Materials and Methods: The present prospective, open-label, randomised phase lll clinical study was conducted on a total of 170 patients with histologically or cytologically confirmed non-myeloid malignancies eligible to receive a myelosuppressive chemotherapy regimen. The participants were administered Lupin’s Pegfilgrastim (n=86) or Neulastim® (n=84) 6 mg by subcutaneous injection, once in each chemotherapy cycle for a maximum of three cycles. Patients were chemotherapy naive or had not received myelosuppressive chemotherapy within last 12 months of screening. The primary efficacy endpoint was DSN (number of days on which absolute neutrophil count <0.5×109 /L) in cycle 1 of chemotherapy. Equivalence was confirmed if 95% Confidence Intervals (CI) were within the equivalence margin of ±1 day. Safety evaluation included assessment of Adverse Events (AEs), rate of discontinuation due to AEs, vital signs, and laboratory parameters. Statistical analysis were done using SAS Enterprise guide 9.4 (SAS Institute Inc., Cary, 2000). Results: Of the 170 patients balanced for demographic characteristics, 161 patients completed cycle 1, 151 patients completed cycle 2, and 142 patients completed cycle 3. The mean±Standard Deviation (SD) DSN in cycle 1 was 0.127±0.5533 days with Pegfilgrastim (n=63) and 0.197±0.6615 days with Neulastim® (n=66) in the Per Protocol (PP) assessment; and 0.174±0.636 days with Pegfilgrastim and 0.193±0.671 days with Neulastim® in the modified Intent-to-Treat (mITT) assessment. The mean DSN between the groups did not differ significantly (PP: p=0.5167, mITT: p=0.8554). The 95% CI of difference in mean DSN in PP (-0.2796 to 0.1481) and mITT (-0.2103 to 0.1889) assessments was contained within the predefined equivalence margin of ±1 day. Secondary outcomes and safety profiles were also comparable between the two groups. Conclusion: The present study establishes Lupin’s Pegfilgrastim as a therapeutically equivalent biosimilar alternative to Neulastim® in patients with non-myeloid malignancies receiving myelosuppressive chemotherapy

Confidence interval of risk difference by different statistical methods and its impact on the study conclusion in antibiotic non-inferiority trials

BackgroundNumerous statistical methods can be used to calculate the confidence interval (CI) of risk differences. There is consensus in previous literature that the Wald method should be discouraged. We compared five statistical methods for estimating the CI of risk difference in terms of CI width and study conclusion in antibiotic non-inferiority trials.MethodsIn a secondary analysis of a systematic review, we included non-inferiority trials that compared different antibiotic regimens, reported risk differences for the primary outcome, and described the number of successes and/or failures as well as patients in each arm. For each study, we re-calculated the risk difference CI using the Wald, Agresti-Caffo, Newcombe, Miettinen-Nurminen, and skewness-corrected asymptotic score (SCAS) methods. The CIs by different statistical methods were compared in terms of CI width and conclusion on non-inferiority. A wider CI was considered to be more conservative.ResultsThe analysis included 224 comparisons from 213 studies. The statistical method used to calculate CI was not reported in 134 (59.8%) cases. The median (interquartile range IQR) for CI width by Wald, Agresti-Caffo, Newcombe, Miettinen-Nurminen, and SCAS methods was 13.0% (10.8%, 17.4%), 13.3% (10.9%, 18.5%), 13.6% (11.1%, 18.9%), 13.6% (11.1% and 19.0%), and 13.4% (11.1%, 18.9%), respectively. In 216 comparisons that reported a non-inferiority margin, the conclusion on non-inferiority was the same across the five statistical methods in 211 (97.7%) cases. The differences in CI width were more in trials with a sample size of 100 or less in each group and treatment success rate above 90%. Of the 18 trials in this subgroup with a specified non-inferiority margin, non-inferiority was shown in 17 (94.4%), 16 (88.9%), 14 (77.8%), 14 (77.8%), and 15 (83.3%) cases based on CI by Wald, Agresti-Caffo, Newcombe, Miettinen-Nurminen, and SCAS methods, respectively.ConclusionsThe statistical method used to calculate CI was not reported in the majority of antibiotic non-inferiority trials. Different statistical methods for CI resulted in different conclusions on non-inferiority in 2.3% cases. The differences in CI widths were highest in trials with a sample size of 100 or less in each group and a treatment success rate above 90%.Trial registrationPROSPERO CRD42020165040. April 28, 2020.

Colchicine protects against cartilage degeneration by inhibiting MMP13 expression via PLC-γ1 phosphorylation

Low molecular weight compounds that reduce the expression of MMP13 at the mRNA level might serve as disease-modifying osteoarthritis (OA) drugs (DMOADs). The objective of this study was to identify a candidate DMOAD that targets MMP13 expression. High-throughput screening was performed to identify compounds that suppress inflammatory cytokine-induced MMP13 expression. Ingenuity pathway analysis (IPA) using isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic analysis was conducted to identify signaling pathways related to cytokines. MMP13 expression in chondrocytes was evaluated through RT-qPCR and western blotting analyses. Additionally, 10-week-old mice were subjected to destabilization of the medial meniscus (DMM) surgery to induce OA and were sacrificed 12 weeks post-surgery for pathological examination. OA was evaluated using the OARSI scoring system. Colchicine was identified as a DMOAD candidate as it inhibited inflammatory cytokine-induced MMP13 expression in vitro, and the colchicine-administered mice with DMM presented significantly lower OARSI scores (adjusted P: 0.0242, mean difference: 1.6, 95% confidence interval (CI) of difference: 0.1651-3.035) and significantly lower synovial membrane inflammation scores (adjusted P: 0.0243, mean difference: 0.6, 95% CI of difference: 0.06158-1.138) than mice with DMM. IPA further revealed that components of the Rho signaling pathways are regulated by cytokines and colchicine. IL-1β and TNF-α activate RAC1 and SRC signals, respectively, leading to the phosphorylation of PLC-γ1 and synergistic induction of MMP13 expression. Most notably, colchicine abrogates inflammatory cytokine-induced phosphorylation of PLC-γ1, leading to the induction of MMP13 expression. Colchicine is a potential DMOAD candidate that inhibits MMP13 expression and consequent cartilage degradation by disrupting the SRC/RAC1-phospho-PLCγ1-Ca2+ signaling pathway.

Quality-adjusted Time Without Symptoms or Toxicity (Q-TWiST) for Lenvatinib plus Everolimus Versus Everolimus Monotherapy in Patients with Advanced Renal Cell Carcinoma

BackgroundThe lenvatinib (LEN) plus everolimus (EVE) combination demonstrated improved progression-free survival over everolimus alone in a phase 2 trial (Study-205). ObjectiveTo compare quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST) between LEN + EVE and EVE alone among patients with advanced renal cell carcinoma (RCC) following one prior antiangiogenic therapy. Design, setting, and participantsThis was a post hoc analysis of Study-205. Outcome measurements and statistical analysisSurvival time was partitioned into three mutually exclusive health states: time with grade 3/4 toxicity (TOX); time before disease progression and without grade 3/4 toxicity (TWiST); and time after disease progression (REL). The mean time in each state was weighted by utility measures and summed to calculate Q-TWiST. Nonparametric bootstrapping generated 95% confidence intervals (CIs). In the base case, utility for TWiST, TOX, and REL was assigned as 1.0, 0.5, and 0.5, respectively. Sensitivity analyses applied alternative utility values for REL, TOX, and TWiST. A relative gain in Q-TWiST of ≥10% and ≥15% has been established as clinically important and clearly clinically important, respectively. Results and limitationsPatients receiving LEN + EVE (n = 51) had a significant mean Q-TWiST gain of 3.7 mo (14.7 vs 11.0 mo; 95% CI for difference 1.3–6.3), with a relative gain of 24% compared to EVE alone. In a sensitivity analysis using alternative utility values for TWiST (varied from 0.55 to 0.9) with utility set to 0.5 for both TOX and REL, the relative Q-TWiST gain was maintained (ranging from 11.0% to 21.2%; all significant) across varying utility values. Limitations include the sample size, the absence of utility estimates, and the length of adverse events from the trial. ConclusionsLEN + EVE showed a significant and clearly clinically important improvement in quality-adjusted survival time versus EVE alone. Patient summaryPatients with advanced kidney cancer who had received other previous treatments experienced a clearly clinically important improvement in quality survival time when treated with lenvatinib plus everolimus compared to everolimus alone.

Academic Emergency Medicine Faculty Experiences with Racial and Sexual Orientation Discrimination.

IntroductionDespite the increasing diversity of individuals entering medicine, physicians from racial and sexual minority groups continue to experience bias and discrimination in the workplace. The objective of this study was to determine the current experiences and perceptions of discrimination on the basis of race and sexual orientation among academic emergency medicine (EM) faculty.MethodsWe conducted a cross-sectional survey of a convenience sample of EM faculty across six programs. Survey items included the Overt Gender Discrimination at Work (OGDW) Scale adapted for race and sexual orientation, and the frequency and source of experienced and observed discrimination. Group comparisons were made using t-tests or chi-square analyses, and relationships between race or sexual orientation, and we evaluated physicians’ experiences using correlation analyses.ResultsA total of 141 out of 352 (40.1%) subjects completed at least a portion of the survey. Non-White physicians reported higher mean racial OGDW scores than their White counterparts (13.4 vs 8.6; 95% confidence interval (CI) for difference, −7.7 – −2.9). Non-White EM faculty were also more likely to report having experienced discriminatory treatment based on race than were White EM faculty (48.0% vs 12.6%; CI for difference, 16.6% – 54.2%), although both groups were equally likely to report having observed race-based discrimination of another physician. EM faculty who identified as sexual minorities reported higher mean sexual minority OGDW scores than their heterosexual counterparts (11.1 vs 7.1; 95% CI for difference, −7.3 – −0.6). There were no significant differences between sexual minority and heterosexual faculty in their reports of experiencing or observing discrimination based on sexual orientation.ConclusionEM faculty from racial and sexual minority groups perceived more discrimination based on race or sexual orientation in their workplace than their majority counterparts. EM faculty regardless of race or sexual orientation were similar in their observations of discriminatory treatment of another physician based on race or sexual orientation.

Effectiveness and safety study of oral triamcinolone in patients with rheumatoid arthritis in India

INTRODUCTION: This study was conducted to assess the effectiveness and safety of low-dose oral triamcinolone (Kenacort®, Abbott Healthcare Pvt. Ltd) in combination with disease-modifying antirheumatic drugs (DMARDs) in Indian patients with rheumatoid arthritis (RA).MATERIALS AND METHODS: Patients with an established diagnosis of RA, on a stable dose of DMARDs for at least 6-weeks, with evidence of disease flare-up or insufficient response to DMARDs were enrolled. Effectiveness of triamcinolone (4 mg) on disease activity (Disease Activity Score-28 [DAS28]), severity (Visual Analog Scale) and duration of morning stiffness, tender joint count (TJC), swollen joint count (SJC), patient global assessment of disease activity (Health Assessment Questionnaire-Disability Index [HAQ-DI]), quality of life (RAND 36-Item Health Survey score [SF-36]), and safety at 6 and 12 weeks of treatment were assessed.RESULTS: About 98.3% of patients completed the study (119/121; female: 64.5%). A significant improvement in DAS28 score was evident at weeks 6 and 12 compared to baseline (baseline: mean [standard deviation (SD)]: 6.6 (0.9); week 6: mean (SD): 5.5 (0.9); 95% confidence interval difference (CI): −1.3 to −1.0; P < 0.001; week 12: mean [SD]:4.7 [0.7]; 95% CI difference: −2.1 to −1.8; P < 0.001). Severity and duration of morning stiffness also improved significantly at the end of 6 and 12 weeks of treatment (P < 0.001). Substantial improvement in TJC, SJC, HAQ-DI score, and RAND 36-Item score was also evident (P < 0.001). Commonly reported adverse events were gastroesophageal reflux disease (3.3%), headache (3.3%), and fever (2.5%), which were mild and resolved subsequently.CONCLUSION: Low-dose triamcinolone with DMARDs was effective and well-tolerated in Indian patients with RA and in those with evidence of disease flare-up or insufficient response to DMARDs.

Effect of sevoflurane-based or propofol-based anaesthesia on the incidence of postoperative acute kidney injury: A retrospective propensity score-matched analysis.

Propofol may help to protect against ischaemic acute kidney injury (AKI); however, research on this topic is sparse. The current study aimed to investigate whether there were differences in the incidence of postoperative AKI after lung resection surgery between patients who received propofol-based total intravenous anaesthesia (TIVA) and those who received sevoflurane-based inhalational anaesthesia. A retrospective observational study. A single tertiary care hospital. Medical records of patients aged 19 years or older who underwent curative lung resection surgery for nonsmall cell lung cancer between January 2005 and February 2018 were examined. After propensity score matching, the incidence of AKI in the first 3 postoperative days was compared between patients who received propofol and those who received sevoflurane. Logistic regression analyses were also used to investigate whether propofol-based TIVA lowered the risk of postoperative AKI. The analysis included 2872 patients (1477 in the sevoflurane group and 1395 in the propofol group). After propensity score matching, 661 patients were included in each group; 24 (3.6%) of the 661 patients in the sevoflurane group developed AKI compared with 23 (3.5%) of the 661 patients in the propofol group (95% confidence intervals of difference in incidence -0.019 to 0.022, P = 0.882). The logistic regression analyses revealed that the incidence of AKI was not different in the two groups (odds ratio 0.96, 95% confidence interval 0.53 to 1.71, P = 0.882). In this retrospective study, no significant difference was found in the incidence of postoperative AKI after lung resection surgery between patients who received propofol-based TIVA and those who received sevoflurane-based inhalational anaesthesia. Considering the methodological limitation of this retrospective study, further studies are required to confirm these results.

Effect and Safety of Meropenem-Vaborbactam versus Best-Available Therapy in Patients with Carbapenem-Resistant Enterobacteriaceae Infections: The TANGO II Randomized Clinical Trial.

IntroductionTreatment options for carbapenem-resistant Enterobacteriaceae (CRE) infections are limited and CRE infections remain associated with high clinical failure and mortality rates, particularly in vulnerable patient populations. A Phase 3, multinational, open-label, randomized controlled trial (TANGO II) was conducted from 2014 to 2017 to evaluate the efficacy/safety of meropenem–vaborbactam monotherapy versus best available therapy (BAT) for CRE.MethodsA total of 77 patients with confirmed/suspected CRE infection (bacteremia, hospital-acquired/ventilator-associated bacterial pneumonia, complicated intra-abdominal infection, complicated urinary tract infection/acute pyelonephritis) were randomized, and 47 with confirmed CRE infection formed the primary analysis population (microbiologic-CRE-modified intent-to-treat, mCRE-MITT). Eligible patients were randomized 2:1 to meropenem–vaborbactam (2 g/2 g over 3 h, q8h for 7–14 days) or BAT (mono/combination therapy with polymyxins, carbapenems, aminoglycosides, tigecycline; or ceftazidime-avibactam alone). Efficacy endpoints included clinical cure, Day-28 all-cause mortality, microbiologic cure, and overall success (clinical cure + microbiologic eradication). Safety endpoints included adverse events (AEs) and laboratory findings.ResultsWithin the mCRE-MITT population, cure rates were 65.6% (21/32) and 33.3% (5/15) [95% confidence interval (CI) of difference, 3.3% to 61.3%; P = 0.03)] at End of Treatment and 59.4% (19/32) and 26.7% (4/15) (95% CI of difference, 4.6% to 60.8%; P = 0.02) at Test of Cure;.Day-28 all-cause mortality was 15.6% (5/32) and 33.3% (5/15) (95% CI of difference, − 44.7% to 9.3%) for meropenem–vaborbactam versus BAT, respectively. Treatment-related AEs and renal-related AEs were 24.0% (12/50) and 4.0% (2/50) for meropenem–vaborbactam versus 44.0% (11/25) and 24.0% (6/25) for BAT. Exploratory risk–benefit analyses of composite clinical failure or nephrotoxicity favored meropenem–vaborbactam versus BAT (31.3% [10/32] versus 80.0% [12/15]; 95% CI of difference, − 74.6% to − 22.9%; P < 0.001).ConclusionsMonotherapy with meropenem–vaborbactam for CRE infection was associated with increased clinical cure, decreased mortality, and reduced nephrotoxicity compared with BAT.Clinical Trials RegistrationNCT02168946.FundingThe Medicines Company.Electronic supplementary materialThe online version of this article (10.1007/s40121-018-0214-1) contains supplementary material, which is available to authorized users.

“EVEN LISTENING IS GOOD”: COMPARING AN ACTIVE AND PASSIVE PARTICIPATION OF FAMILIES IN MULTIDISCIPLINARY ROUNDS

SESSION TITLE: Improving Patient Care Through System Change SESSION TYPE: Original Investigations PRESENTED ON: 10/10/2018 02:30 pm - 03:30 pm PURPOSE: Studies have shown that keeping open information with families not only improves satisfaction but also improves the overall performance outcome of an Intensive Care Unit (ICU) [1]. It was therefore hypothesized that if a patient’s family was given the chance to be either actively or passively involved in the multidisciplinary rounds (MDRs), their satisfaction can be measured objectively. Searching of literature shows that we are the first to compare between active (AP) and passive participation (PP) of families in MDRs. METHODS: This observational study was performed in a 40 bed Cardio-Vascular ICU of a tertiary care center. Data was collected from the each weekday morning’s formal MDRs involving an intensivist, a bedside nurse, unit manager, a pharmacist, a dietician, a social worker, a respiratory therapist, a physical therapist and a chaplain. No patient identifying data were collected or preserved. A patient’s case is discussed, with recent updates, by the bedside nurse or an intensivist. Families are allowed to observe this discussion and are provided the opportunity to actively ask any questions. A total of 266 beds were rounded with 121 families present. Out of the 121 families present during the rounds, 73 scores were retained after they satisfy all inclusion questions. A five point satisfaction score is developed depending on understanding of the plan of the care for the day as well as overall goal of the treatment, opportunity to ask questions, opportunity to raise concerns and on the doctors’ communication skills. RESULTS: Out of 73 scores, 34 were from families that were active in the rounds (AP group) and 39 were from families that only passively listened to the discussion of providers (PP group). STATA © biostatistic software is used to satisfy sample size in each arm to obtain mean, histogram, power of 80%, equal variance, level of significance of .05 (Type 1 error) with standard deviation estimated using sample T-distribution. Z for 95% Confidence Interval (CI) = 1.96, 95% CI of difference: -0.3393 <0.333< 1.0053 (Wald), t= 0.971; df= 33; p= 0.83066 (left p: 0.1693; two sided: 0.3386). CONCLUSIONS: As we failed to reject our null hypothesis, we concluded that even passive participation ensures significant family satisfaction. Structured and family-centered MDRs designed to address all aspects of patient care may answers all concerns family might have. The presence of entire ICU team reinforce families of the best care. CLINICAL IMPLICATIONS: Effective communication with patients' families is an important determinant of ICU outcome measures. Involvement of families either actively or passively in MDRs can be used as a key to obtain these parameters. Further studies are needed to objectively measure a family-centered patient care.Ref.: Roland P, et al - Visitation in critical care: process and outcomes of a performance improvement initiative. J Nurs Care Qual. 2001;15(2):18–26 DISCLOSURES: No relevant relationships by Samantha DeLuca, source=Web Response No relevant relationships by Sahar Fatima, source=Web Response No relevant relationships by Tina Lam, source=Web Response No relevant relationships by Iqbal Ratnani, source=Web Response Speaker/Speaker's Bureau relationship with Sunovian Please note: $5001 - $20000 Added 11/20/2017 by Salim Surani, source=Web Response, value=Honoraria Advisory Committee Member relationship with Astra Zeneca Please note: $5001 - $20000 Added 11/20/2017 by Salim Surani, source=Web Response, value=Consulting fee

Improving digital breast tomosynthesis reading time: A pilot multi-reader, multi-case study using concurrent Computer-Aided Detection (CAD)

PurposeEvaluate concurrent Computer-Aided Detection (CAD) with Digital Breast Tomosynthesis (DBT) to determine impact on radiologist performance and reading time. Materials and methodsThe CAD system detects and extracts suspicious masses, architectural distortions and asymmetries from DBT planes that are blended into corresponding synthetic images to form CAD-enhanced synthetic images. Review of CAD-enhanced images and navigation to corresponding planes to confirm or dismiss potential lesions allows radiologists to more quickly review DBT planes. A retrospective, crossover study with and without CAD was conducted with six radiologists who read an enriched sample of 80 DBT cases including 23 malignant lesions in 21 women. Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) compared the readings with and without CAD to determine the effect of CAD on overall interpretation performance. Sensitivity, specificity, recall rate and reading time were also assessed. Multi-reader, multi-case (MRMC) methods accounting for correlation and requiring correct lesion localization were used to analyze all endpoints. AUCs were based on a 0–100% probability of malignancy (POM) score. Sensitivity and specificity were based on BI-RADS scores, where 3 or higher was positive. ResultsAverage AUC across readers without CAD was 0.854 (range: 0.785-0.891, 95% confidence interval (CI): 0.769,0.939) and 0.850 (range: 0.746-0.905, 95% CI: 0.751,0.949) with CAD (95% CI for difference: −0.046,0.039), demonstrating non-inferiority of AUC. Average reduction in reading time with CAD was 23.5% (95% CI: 7.0–37.0% improvement), from an average 48.2 (95% CI: 39.1,59.6) seconds without CAD to 39.1 (95% CI: 26.2,54.5) seconds with CAD. Per-patient sensitivity was the same with and without CAD (0.865; 95% CI for difference: −0.070,0.070), and there was a small 0.022 improvement (95% CI for difference: ‐0.046,0.089) in per-lesion sensitivity from 0.790 without CAD to 0.812 with CAD. A slight reduction in specificity with a −0.014 difference (95% CI for difference: ‐0.079,0.050) and a small 0.025 increase (95% CI for difference: −0.036,0.087) in recall rate in non-cancer cases were observed with CAD. ConclusionsConcurrent CAD resulted in faster reading time with non-inferiority of radiologist interpretation performance. Radiologist sensitivity, specificity and recall rate were similar with and without CAD.

Prospective clinical evaluation of a novel anatomic cuff for forearm crutches in patients with osteoarthritis

BackgroundThe use of forearm crutches has been associated with pain and neuropraxia along the ulnar bone. Whilst anatomic grips have improved comfort of crutch walking, to date anatomic forearm cuffs have not been clinically evaluated. The aim of this clinical pilot study was to determine if the use of forearm crutches with anatomic cuffs reduces pain and increases comfort and function in long-term users of forearm crutches during a 4-week period.MethodProspective study in ten patients suffering from end-stage osteoarthritis of the lower extremity. All participants were long-term users of conventional forearm crutches. Participants used forearm crutches with an anatomically shaped cuff for 4-weeks. General health was assessed using the SF-36, and the crutches were evaluated using a newly developed questionnaire focusing on symptoms along the forearm.ResultsPain and paresthesia along the forearms decreased by 3.3 points (95% confidence interval difference (CI): [−5.0; −1.6], p = .004) and 3.5 points (95%CI: [−5.1; −1.9], p = .002), respectively, after using the crutches with the new anatomic cuff for 4 weeks. Comfort and sense of security of crutch use increased by 3.0 points (95%CI: [1.3; 4.7], p = .007) and 2.4 points (95%CI: [0.7; 4.1], p = .024). Cross-correlation analysis revealed correlations among items in the same item category and no correlations between items of different item categories of the new questionnaires.ConclusionAn anatomically shaped cuff increases comfort of forearm crutches. Further research should confirm long-term clinical improvement.Trial registrationThis study was registered retrospectively in ISRCTN (TRN: ISRCTN 11135150) on 14/02/2017.

Randomized phase II trial of fulvestrant alone or in combination with bortezomib in hormone receptor-positive metastatic breast cancer resistant to aromatase inhibitors: a New York Cancer Consortium trial.

The proteasome inhibitor bortezomib enhances the effect of the selective estrogen receptor (ER) downregulator (SERD) fulvestrant by causing accumulation of cytoplasmic ER aggregates in preclinical models. The purpose of this trial was to determine whether bortezomib enhanced the effectiveness of fulvestrant. One hundred eighteen postmenopausal women with ER-positive metastatic breast cancer resistant to aromatase inhibitors (AIs) were randomized to fulvestrant alone (Arm A—500 mg intramuscular (i.m.) day −14, 1, 15 in cycle 1, and day 1 of additional cycles) or in combination with bortezomib (Arm B—1.6 mg/m2 intravenous (i.v.) on days 1, 8, 15 of each cycle). The study was powered to show an improvement in median progression-free survival (PFS) from 5.4 to 9.0 months and compare PFS rates at 6 and 12 months (α=0.10, β=0.10). Patients with progression on fulvestrant could cross over to the combination (arm C). Although there was no difference in median PFS (2.7 months in both arms), the hazard ratio for PFS in Arm B versus Arm A (referent) was 0.73 (95% confidence interval (CI)=0.49, 1.09, P=0.06, 1-sided log-rank test, significant at the prespecified 1-sided 0.10 α level). At 12 months, the PFS proportion in Arm A and Arm B was 13.6% and 28.1% (P=0.03, 1-sided χ2-test; 95% CI for difference (14.5%)=−0.06, 29.1%). Of 27 patients on arm A who crossed over to the combination (arm C), 5 (18%) were progression-free for at least 24 weeks. Bortezomib likely enhances the effectiveness of fulvestrant in AI-resistant, ER-positive metastatic breast cancer by reducing acquired resistance, supporting additional evaluation of proteasome inhibitors in combination with SERDs.

Femoral arterial cannulation performed by residents: a comparison between ultrasound‐guided and palpation technique in infants and children undergoing cardiac surgery

Percutaneous cannulation of the femoral artery in the pediatric age group can be technically challenging, especially when performed by residents in training. We examined whether the use of real-time ultrasound guidance is superior to a palpation landmark technique for femoral artery catheterization in children undergoing heart surgery. Patients were prospectively randomized into two groups. In the palpation group, the femoral artery was cannulated using the traditional landmark method of palpation of arterial pulse. In the ultrasound group, cannulation was guided by real-time scanning with an ultrasound probe. Ten minutes were set as time limit for the resident's trials during which the time taken for attempted cannulation (primary outcome), number of attempts, number of successful cannulations on first attempt, and success rate were compared between the two groups. Adverse events were monitored on postoperative days 1 and 3. A total of 106 patients were included in the study. The time taken for attempted femoral artery cannulation was shorter (301 ± 234 vs 420 ± 248 s; difference in mean: 119; 95% confidence interval (CI) of difference: 26-212; P = 0.012) and the number of attempts was lower [1 (1-10) vs 2 (1-5); difference in median: 1, 95% CI of difference: 0.28-1.72; P = 0.003] in the ultrasound group compared with the palpation group. The number of successful cannulations on first attempt was higher in the ultrasound group compared with palpation group [24/53 (45%) vs 13/53 (25%); odds ratio (OR): 2.54, 95% CI: 1.11-5.82; P = 0.025]. The number of patients who had successful cannulation was 31 of 55 (58%) in the palpation group and 40 of 53 (75%) in the ultrasound group (OR: 2.18, 95% CI: 0.95-5.01; P = 0.06). None of the patients had adverse events at days 1 and 3. Ultrasound-guided femoral arterial cannulation in children when performed by anesthesia residents is superior to the palpation technique based on the reduction of the time taken for attempted cannulation and the number of attempts, and improvement in first attempt success.

Brachial artery diameter, but not flow-mediated dilation, is associated with sleep apnoea in the Multiethnic Study of Atherosclerosis.

The percentage flow-mediated dilation (FMD%) of the brachial artery is purported to be an early indicator of atherosclerosis and has been reported to be reduced in people with obstructive sleep apnoea. Nevertheless, FMD% scales poorly for, and is concomitantly dependent on, initial artery diameter, which may, itself, be higher in obstructive sleep apnoea patients. Therefore, for the first time, we aimed to quantify the differences in initial diameter and properly scaled flow-mediated dilation between people with and without sleep apnoea. The prevalence of physician-diagnosed sleep apnoea, as well as initial and peak diameters of the brachial artery were recorded for 3354 participants in the Multiethnic Study of Atherosclerosis (MESA). Arterial data were analysed using FMD% and an allometric approach, which scales the flow-mediated response properly for initial diameter. In the sex, race and age-adjusted model, initial diameter was 0.19 mm larger in sleep apnoea patients [95% confidence interval (CI): 0.07 to 0.32 mm, P = 0.003] and correlated negatively with FMD% (r = -0.43, 95% CI: -0.57 to -0.26, P < 0.0005). Using this same adjusted model, FMD% was 3.8 ± 2.7% for sleep apnoea patients (n = 104) versus 4.4 ± 2.7% for undiagnosed people (95% CI for difference: -1.12 to -0.07%, P = 0.028). Allometric scaling halved this FMD%-indicated sample difference in flow-mediated dilation (95% CI: -0.7 to 0.1%, P = 0.19). The initial diameter of the brachial artery is larger in MESA participants diagnosed with sleep apnoea compared with undiagnosed people. However, the difference in flow-mediated dilation between these two cohorts is trivial, when the flow-mediated response is scaled properly for resting diameter.

Calcium channel blockers for primary Raynaud's phenomenon.

Calcium channel blockers are the most commonly prescribed drugs for people with primary Raynaud's phenomenon. Primary Raynaud's phenomenon is a common condition characterised by an exaggerated vasospastic response to cold or emotion: classically the digits (fingers and toes) turn white, then blue, then red. This is an update of the review first published in 2014. To assess the effects of different calcium channel blockers for primary Raynaud's phenomenon as determined by attack rates, severity scores, participant-preference scores and physiological measurements. For this update the Cochrane Vascular Trial Search Co-ordinator searched the Specialised Register (last searched January 2016) and the Cochrane Register of Studies (CENTRAL) (2015, Issue 12). In addition the TSC searched clinical trials databases. Randomised controlled trials evaluating the effects of oral calcium channel blockers for the treatment of primary Raynaud's phenomenon. Three review authors independently assessed the trials for inclusion and their quality, and extracted the data. Data extraction included adverse events. We contacted trial authors for missing data. We included seven randomised trials with 296 participants. Four trials examined nifedipine and the remainder nicardipine. Comparisons were with placebo in six trials and with both dazoxiben and placebo in one trial (only the nifedipine versus placebo data were used within this review). Treatment with oral calcium channel blockers was minimally effective in primary Raynaud's phenomenon at decreasing the frequency of attacks (standardised mean difference of 0.23; 95% confidence interval (CI) 0.08 to 0.38, P = 0.003). This translates to 1.72 (95% CI 0.60 to 2.84) fewer attacks per week on calcium channel blockers compared to placebo. One trial provided details on duration of attacks reporting no statistically significant difference between the nicardipine and placebo groups (no P value reported). Only two trials provided any detail of statistical comparisons of (unvalidated) severity scores between treatment groups: one of these trials (60 participants) reported a mean severity score of 1.55 on placebo and 1.36 on nicardipine, difference 0.2 (95% CI of difference 0 to 0.4, no P value reported) and the other trial (three participants only with primary Raynaud's phenomenon) reported a median severity score of 2 on both nicardipine and placebo treatment (P > 0.999) suggesting little effect on severity. Participant-preference scores were included in four trials, but in only two were results specific to participants with primary Raynaud's phenomenon, and scoring systems differed between trials: scores differed between treatments in only one trial, in which 33% of participants on placebo and 73% on nifedipine reported improvement in symptoms (P < 0.001). Physiological measurements were included as outcome measures in five trials (different methodologies were used in each): none of these trials found any statistically significant between-treatment group differences. Treatment with calcium channel blockers appeared to be associated with a number of adverse reactions, including headaches, flushing and oedema (swelling). Overall, the trials were classed as being at low or unclear risk of bias; and the quality of the evidence presented was moderate for number of attacks, very low for duration of attacks, high for severity scores and low for patient preference scores. The randomised controlled trials included in this review provide moderate quality evidence that oral calcium channel blockers are minimally effective in the treatment of primary Raynaud's phenomenon as measured by the frequency of attacks and high-quality evidence that they have little effect on severity. We are unable to comment on duration of attacks or on patient preference due to the very low and low quality of evidence as a result of small sample sizes in the included studies and the variable data quality of outcome measures.

Canadian Agility and Movement Skill Assessment (CAMSA): Validity, objectivity, and reliability evidence for children 8–12 years of age

PurposeThe primary aim of this study was to develop an assessment of the fundamental, combined, and complex movement skills required to support childhood physical literacy. The secondary aim was to establish the feasibility, objectivity, and reliability evidence for the assessment. MethodsAn expert advisory group recommended a course format for the assessment that would require children to complete a series of dynamic movement skills. Criterion-referenced skill performance and completion time were the recommended forms of evaluation. Children, 8–12 years of age, self-reported their age and gender and then completed the study assessments while attending local schools or day camps. Face validity was previously established through a Delphi expert (n = 19, 21% female) review process. Convergent validity was evaluated by age and gender associations with assessment performance. Inter- and intra-rater (n = 53, 34% female) objectivity and test–retest (n = 60, 47% female) reliability were assessed through repeated test administration. ResultsMedian total score was 21 of 28 points (range 5–28). Median completion time was 17 s. Total scores were feasible for all 995 children who self-reported age and gender. Total score did not differ between inside and outside environments (95% confidence interval (CI) of difference: −0.7 to 0.6; p = 0.91) or with/without footwear (95%CI of difference: −2.5 to 1.9; p = 0.77). Older age (p < 0.001, η2 = 0.15) and male gender (p < 0.001, η2 = 0.02) were associated with a higher total score. Inter-rater objectivity evidence was excellent (intraclass correlation coefficient (ICC) = 0.99) for completion time and substantial for skill score (ICC = 0.69) for 104 attempts by 53 children (34% female). Intra-rater objectivity was moderate (ICC = 0.52) for skill score and excellent for completion time (ICC = 0.99). Reliability was excellent for completion time over a short (2–4 days; ICC = 0.84) or long (8–14 days; ICC = 0.82) interval. Skill score reliability was moderate (ICC = 0.46) over a short interval, and substantial (ICC = 0.74) over a long interval. ConclusionThe Canadian Agility and Movement Skill Assessment is a feasible measure of selected fundamental, complex and combined movement skills, which are an important building block for childhood physical literacy. Moderate-to-excellent objectivity was demonstrated for children 8–12 years of age. Test–retest reliability has been established over an interval of at least 1 week. The time and skill scores can be accurately estimated by 1 trained examiner.

Relation between reperfusion and hemorrhagic transformation in acute ischemic stroke.

IntroductionIntravenous recombinant tissue plasminogen activator (IV-rtPA) is given in acute ischemic stroke patients to achieve reperfusion. Hemorrhagic transformation (HT) is a serious complication of IV-rtPA treatment and related to blood–brain barrier (BBB) injury. It is unclear whether HT occurs secondary to reperfusion in combination with ischemic BBB injury or is caused by the negative effect of IV-rtPA on BBB integrity. The aim of this study was to establish the association between reperfusion and the occurrence of HT.MethodsFrom the DUST study, patients were selected with admission and follow-up non-contrast CT (NCCT) and CT perfusion (CTP) imaging, and a perfusion deficit in the middle cerebral artery territory on admission. Reperfusion was categorized qualitatively as reperfusion or no-reperfusion by visual comparison of admission and follow-up CTP. Occurrence of HT was assessed on follow-up NCCT. The association between reperfusion and occurrence of HT on follow-up was estimated by calculating odds ratios (ORs) and 95 % confidence intervals (CIs) with additional stratification for IV-rtPA treatment.ResultsInclusion criteria were met in 299 patients. There was no significant association between reperfusion and HT (OR 1.2 95%CI 0.5–3.1). In patients treated with IV-rtPA (n = 203), the OR was 1.3 (95%CI 0.4–4.0), and in patients not treated with IV-rtPA (n = 96), the OR was 0.8 (95%CI 0.1–4.5). HT occurred in 14 % of the IV-rtPA patients and in 7 % of patients without IV-rtPA (95%CI of difference −1 to 14 %).ConclusionOur results suggest that the increased risk of HT after acute ischemic stroke treatment is not dependent on the reperfusion status.

Stage 1 Treatment of Pediatric Overweight and Obesity: A Pilot and Feasibility Randomized Controlled Trial

Staged clinical treatment of pediatric obesity is recommended, but untested. Understanding the lowest intensity stage's effectiveness is necessary for future research. This was a randomized controlled trial of children ages 4 to <9 years. Participants were recruited after routine evaluations at a primary care pediatric clinic revealed a BMI ≥85th percentile. The intervention was patterned after the "Prevention plus, Stage 1" treatment recommended by an expert committee. Groups were compared for changes, over a 3-month time period, in BMI z-score and parental reports of behavioral issues related to childhood obesity using intent-to-treat (ITT) analysis. Seventy-two (30% of eligible) children were enrolled and 64 were remeasured at 3-month follow-up. ITT analysis revealed that both groups improved mean BMI z-score [adjusted change -0.07, control, and -0.04, intervention; 95% confidence interval (CI) of difference=-0.14-0.20]. Over half of the children in each group improved their BMI z-score (adjusted proportion decreasing=55% in control vs. 72% in intervention; 95% CI of difference=-0.07-0.42). The intervention group improved comparatively to the control group on numerous behavioral indicators. Implementation of the lowest intensity stage of current recommendations is feasible and possibly of benefit toward lifestyle changes. Results of this study can be used by future clinical researchers designing protocols to test the full multi-staged approach for the treatment of pediatric overweight and obesity in primary care clinical settings.