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Ticagrelor-Aspirin Versus Clopidogrel-Aspirin Among CYP2C19 Loss-of-Function Carriers With Minor Stroke or Transient Ischemic Attack in Relation to Renal Function: A Post Hoc Analysis of the CHANCE-2 Trial

Ann Intern Med. 2022 Nov 1. doi: 10.7326/M22-1667. Online ahead of print.

ABSTRACT

BACKGROUND: Evidence on the risk-benefit ratio of dual antiplatelet therapies among patients with stroke and impaired renal function is limited and inconsistent.

OBJECTIVE: To investigate the effect of renal function on the efficacy and safety of ticagrelor-aspirin versus clopidogrel-aspirin treatment.

DESIGN: Post hoc analysis of a multicenter, randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT04078737).

SETTING: 202 centers in China.

PATIENTS: CYP2C19 loss-of-function allele carriers with minor stroke or transient ischemic attack.

INTERVENTION: Ticagrelor-aspirin and clopidogrel-aspirin.

MEASUREMENTS: Renal function was evaluated by estimated glomerular filtration rate (eGFR) levels. The primary efficacy and safety outcomes were recurrent stroke and severe or moderate bleeding within 90 days, respectively.

RESULTS: Among 6378 patients, 4050 (63.5%) had normal (eGFR ≥90 mL/min/1.73 m2), 2010 (31.5%) had mildly decreased (eGFR 60 to 89 mL/min/1.73 m2), and 318 (5.0%) had moderately to severely decreased (eGFR <60 mL/min/1.73 m2) renal function. The corresponding differences in recurrent stroke between ticagrelor-aspirin and clopidogrel-aspirin for normal, mildly decreased, and moderately to severely decreased renal function was -2.8 percentage points (95% CI, -4.4 to -1.3 percentage points) (hazard ratio [HR], 0.63 [CI, 0.49 to 0.81]), -0.2 percentage point (CI, -2.4 to 2.0 percentage points) (HR, 0.98 [CI, 0.69 to 1.39]), and 3.7 percentage points (CI, -2.3 to 10.1 percentage points) (HR, 1.31 [CI, 0.48 to 3.55]), respectively. Rates of severe or moderate bleeding did not substantially differ by treatment assignments across eGFR categories.

LIMITATION: Renal function was only evaluated by using eGFR, and the proportion of patients with severely decreased renal function was low.

CONCLUSION: Patients with normal, rather than impaired, renal function received greater benefit from ticagrelor-aspirin versus clopidogrel-aspirin.

PRIMARY FUNDING SOURCE: Ministry of Science and Technology of the People’s Republic of China.

PMID:36315949 | DOI:10.7326/M22-1667

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Slow Uptake of an Effective Therapy: Patterns of Olanzapine Prescribing for Those Receiving Highly Emetogenic Chemotherapy

JCO Oncol Pract. 2022 Oct 31:OP2200389. doi: 10.1200/OP.22.00389. Online ahead of print.

ABSTRACT

PURPOSE: For the past 5 years, most major antiemesis guidelines have included olanzapine-containing regimens among the recommended options for prophylaxis with highly emetogenic chemotherapy (HEC). We analyzed the uptake of olanzapine in clinical practice and the changing composition of multidrug antiemetic regimens.

METHODS: A retrospective analysis was performed using an OptumLabs deidentified database of medical and pharmacy claims, which was filtered for patients starting HEC in the interval of 2006 to Q2 of 2021. Descriptive statistics were used to analyze patient characteristics and year-by-year antiemetic prescribing patterns, coinciding with cycles 1 and 2 of chemotherapy.

RESULTS: A total of 63,154 distinct patients were included. The median age was 58 years (range, 18-88). Breast (45.2%) and hematologic (20.8%) cancers were the most common diagnoses. In 2016, olanzapine was prescribed to 1.4% of patients with cycle 1 of HEC. Prescriptions increased modestly each year, and by 2021, 13.9% of patients received olanzapine with their first cycle of chemotherapy. An additional 5.7% of patients received olanzapine for breakthrough symptoms or enhanced prophylaxis during cycle 2. In 2021, more than three-quarters of patients were prescribed antiemetics in a guideline-concordant manner, with an olanzapine-containing quadruplet (12.2%), an NK1-receptor antagonist triplet (64.5%), or an olanzapine triplet (suppressed for small sample size).

CONCLUSION: Despite inclusion in major antiemesis guidelines, there has been relatively slow uptake of olanzapine for prophylaxis with HEC. This finding highlights the challenges of disseminating information and keeping prescribing systems updated with the newest evidence in supportive oncology.

PMID:36315918 | DOI:10.1200/OP.22.00389

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High-Fidelity Simulation Effects on Cardiopulmonary Resuscitation Self-Efficacy and Knowledge Retention in Undergraduate Nursing Students: A Two-Group, Experimental, Longitudinal Pilot Study

Nurs Educ Perspect. 2022 Nov-Dec 01;43(6):E118-E120. doi: 10.1097/01.NEP.0000000000000984.

ABSTRACT

This pilot study aimed to assess the effects of high-fidelity simulation on cardiopulmonary resuscitation (CPR) self-efficacy and knowledge retention compared to case-based learning. A two-group, experimental, longitudinal design was adopted. Fifty-two undergraduate nursing students were invited to participate in the study, which was conducted between March and May 2019. The results show statistically significant differences in favor of the experimental group on both CPR knowledge retention and self-efficacy one month after training. These findings may assist nurse educators to implement high-fidelity simulation in CPR education.

PMID:36315894 | DOI:10.1097/01.NEP.0000000000000984

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The Impact of a Cognitive Behavioral Intervention on Test Anxiety in a BSN Program

Nurs Educ Perspect. 2022 Nov-Dec 01;43(6):E97-E99. doi: 10.1097/01.NEP.0000000000000989. Epub 2022 May 13.

ABSTRACT

Test anxiety and attrition are prevalent in nursing programs. Efforts should be made to assist nursing students in obtaining coping mechanisms to reduce anxiety. The aim of this quantitative, quasi-experimental, before and after study was to determine the impact of a cognitive-behavioral intervention on test anxiety during first-semester nursing courses. Thirty bachelor of science in nursing students in a rural university participated in a cognitive-behavioral intervention and completed the Cognitive Test Anxiety Scale. A two-tailed, dependent-samples t-test determined a statistically significant decrease in test anxiety scores (p < .001), supporting interventions aimed at reducing both the physical and mental effects of test anxiety.

PMID:36315890 | DOI:10.1097/01.NEP.0000000000000989

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Observed Injury Rates Did Not Follow Theoretically Predicted Injury Risk Patterns in Professional Human Circus Artists

Clin J Sport Med. 2022 Nov 1;32(6):e627-e634. doi: 10.1097/JSM.0000000000001045. Epub 2022 May 20.

ABSTRACT

OBJECTIVE: Identifying which types of athletes have increased injury risk (ie, predictive risk factors) should help develop cost-effective selective injury prevention strategies. Our objective was to compare a theoretical injury risk classification system developed by coaches and rehabilitation therapists, with observed injury rates in human circus acts across dimensions of physical stressors, acrobatic complexity, qualifications, and residual risks.

DESIGN: Descriptive epidemiological study.

SETTING: professional circus company.

PATIENTS OR OTHER PARTICIPANTS: Human circus artists performing in routine roles between 2007 and 2017.

ASSESSMENT OF RISK FACTORS: Characteristics of circus acts categorized according to 4 different dimensions.

MAIN OUTCOME MEASURES: Medical attention injury rates (injury requiring a visit to the therapist), time-loss injury rates (TL-1; injury resulting in at least one missed performance), and time-loss 15 injury rates (TL-15; injury resulting in at least 15 missed performances).

RESULTS: Among 962 artists with 1 373 572 performances, 89.4% (860/962) incurred at least one medical attention injury, 74.2% (714/962) incurred at least one TL-1 injury, and 50.8% (489/962) incurred at least one TL-15 injury. There were important inconsistencies between theoretical and observed injury risk patterns in each of the 4 dimensions for all injury definitions (medical attention, TL-1, and TL-15).

CONCLUSIONS: Although theoretical classifications are the only option when no data are available, observed risk patterns based on injury surveillance programs can help identify artists who have a high (or low) theoretical risk but are nonetheless actually at low (or high) risk of injury, given their current roles. This will help develop more cost-effective selective injury prevention programs.

PMID:36315828 | DOI:10.1097/JSM.0000000000001045

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Does the Addition of Whole-Body Vibration Training Improve Postural Stability and Lower Limb Strength During Rehabilitation Following Anterior Cruciate Ligament Reconstruction: A Systematic Review With Meta-analysis

Clin J Sport Med. 2022 Nov 1;32(6):627-634. doi: 10.1097/JSM.0000000000001001. Epub 2022 Jan 25.

ABSTRACT

OBJECTIVES: To investigate whether the addition of whole-body vibration therapy to standard rehabilitation improves postural stability and lower limb strength following anterior cruciate ligament (ACL) reconstruction.

DATA SOURCES: A computer-based literature search of MEDLINE, AMED, SPORTDiscus, Embase, CINAHL, CENTRAL, and Physiotherapy Evidence Database (PEDro) included studies up to October 2019.

MAIN RESULTS: Seven randomised controlled trials of moderate-to-high methodological quality involving 244 participants were included. Meta-analysis found statistically significant improvements in medial-lateral stability [standardized mean difference (SMD) = 0.50; 95% confidence interval (CI), 0.12-0.88] and overall stability (SMD = 0.60; 95% CI, 0.14-1.06) favoring whole-body vibration therapy, but effects were not significant for quadriceps strength (SMD = 0.24; 95% CI, -0.65 to 1.13), hamstring strength (SMD = 0.84; 95% CI, -0.05 to 1.72), lower limb strength (SMD = 0.76; 95% CI, -0.16 to 1.67), or anterior-posterior stability (SMD = 0.19; 95% CI, -0.39 to 0.76).

CONCLUSIONS: The addition of whole-body vibration therapy to standard postoperative rehabilitation following ACL reconstruction does not appear to significantly improve lower limb strength and anterior-posterior stability but may improve medial-lateral and overall postural stability. We found small sample sizes in all included trials, statistical heterogeneity, and methodological quality concerns, including publication bias, suggesting that larger high-quality trials are likely to be influential in this field. Registration: PROSPERO 155531.

PMID:36315822 | DOI:10.1097/JSM.0000000000001001

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Preliminary Evaluation of a Novel Point of Care Diagnostic Device for Sports-Related Concussion

Clin J Sport Med. 2022 Nov 1;32(6):623-626. doi: 10.1097/JSM.0000000000001056. Epub 2022 Jul 6.

ABSTRACT

OBJECTIVE: Visinin-like protein 1 (VILIP-1) is a neuron-specific calcium sensor protein rapidly released into blood after mild traumatic brain injury (mTBI) and may be a suitable biomarker for identification of sports-related concussion (SRC). The objective of the study is to test if quantification of a specific post-translationally modified (ubiquitinated) form of VILIP-1 (ubVILIP-1) from a fingerstick blood sample using a point of care (POC) lateral flow device (LFD) can be used to rapidly identify athletes with SRC.

DESIGN: Prospective cohort study.

SETTING: Side-line blood collection at football, soccer, and volleyball games/practices.

PARTICIPANTS: Division I athletes with/without SRC.

MAIN OUTCOME MEASURES: Blood ubVILIP-1 concentrations.

RESULTS: Data collected over 2 athletic seasons from non-SRC athletes (controls) show a small but statistically significant elevation of ubVILIP-1 over an individual season for male athletes (P = 0.02) dependent on sport (P = 0.014) and no significant changes in ubVILIP-1 levels between seasons. For SRC athletes, the data show ubVILIP-1 levels substantially increase above baseline as soon as 30 minutes postdiagnosis with peak concentrations and times postinjury that vary based on injury severity.

CONCLUSION: Results of the study suggest quantification of blood ubVILIP-1 levels measured using an LFD may provide an objective identification of athletes with SRC, setting the stage for further study with a larger number of SRC patients.

PMID:36315821 | DOI:10.1097/JSM.0000000000001056

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Longitudinal Prediction of Ventricular Arrhythmic Risk in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy

Circ Arrhythm Electrophysiol. 2022 Oct 31:e011207. doi: 10.1161/CIRCEP.122.011207. Online ahead of print.

ABSTRACT

BACKGROUND: The arrhythmogenic right ventricular cardiomyopathy (ARVC) risk calculator stratifies risk for incident sustained ventricular arrhythmias (VA) at the time of ARVC diagnosis. However, included risk factors change over time, and how well the ARVC risk calculator performs at follow-up is unknown.

METHODS: This was a retrospective analysis of patients with definite ARVC and without prior sustained VA. Risk factors for VA including age, nonsustained ventricular tachycardia, premature ventricular complex burden, T-wave inversions on electrocardiogram, cardiac syncope, right ventricular function, therapeutic medication use, and exercise intensity were assessed at the time of 2010 Task Force Criteria based ARVC diagnosis and upon repeat evaluations. Changes in these risk factors were analyzed over 5-year follow-up. The 5-year risk of VA was predicted longitudinally using (1) the baseline ARVC risk calculator prediction, (2) the ARVC risk prediction calculated using updated risk factors, and (3) time-varying Cox regression. Discrimination and calibration were assessed in comparison to observed VA event rates.

RESULTS: Four hundred eight patients with ARVC experiencing 132 primary VA events were included. Matched comparison of risk factors at baseline versus at 5 years of follow-up revealed decreased burdens of premature ventricular complexes (-1200/day) and nonsustained ventricular tachycardia (-14%). Presence of significant right ventricular dysfunction and number of T-wave inversions on electrocardiogram were unchanged. Observed risk for VA decreased by 13% by 5 years follow-up. The baseline ARVC risk calculator’s ability to predict 5-year VA risk worsened during follow-up (C statistics, 0.83 at diagnosis versus 0.68 at 5 years). Both the updated ARVC risk calculator (C statistics of 0.77) and time-varying Cox regression model (C statistics, 0.77) had strong discrimination. The updated ARVC risk calculator overestimated 5-year VA risk by an average of +6%.

CONCLUSION: Risk factors for VA in ARVC are dynamic, and overall risk for incident sustained VA decreases during follow-up. Up-to-date risk factor assessment improves VA risk stratification.

PMID:36315818 | DOI:10.1161/CIRCEP.122.011207

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Advances and Applications of Polygenic Scores for Coronary Artery Disease

Annu Rev Med. 2022 Oct 31. doi: 10.1146/annurev-med-042921-112629. Online ahead of print.

ABSTRACT

Polygenic scores quantify inherited risk by integrating information from many common sites of DNA variation into a single number. Rapid increases in the scale of genetic association studies and new statistical algorithms have enabled development of polygenic scores that meaningfully measure-as early as birth-risk of coronary artery disease. These newer-generation polygenic scores identify up to 8% of the population with triple the normal risk based on genetic variation alone, and these individuals cannot be identified on the basis of family history or clinical risk factors alone. For those identified with increased genetic risk, evidence supports risk reduction with least two interventions, adherence to a healthy lifestyle and cholesterol-lowering therapies, that can substantially reduce risk. Alongside considerable enthusiasm for the potential of polygenic risk estimation to enable a new era of preventive clinical medicine is recognition of a need for ongoing research into how best to ensure equitable performance across diverse ancestries, how and in whom to assess the scores in clinical practice, as well as randomized trials to confirm clinical utility. Expected final online publication date for the Annual Review of Medicine, Volume 74 is January 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID:36315649 | DOI:10.1146/annurev-med-042921-112629

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Risk factors for the presence and persistence of posttraumatic stress symptoms following traumatic brain injury in U.S. service members and veterans

J Trauma Stress. 2022 Oct 31. doi: 10.1002/jts.22892. Online ahead of print.

ABSTRACT

This study aimed to identify risk factors predictive of the presence and persistence of posttraumatic stress disorder (PTSD) symptom reporting following traumatic brain injury (TBI). Participants were 1,301 U.S. service members and veterans (SMVs) divided into four groups: uncomplicated mild TBI (mTBI; n = 543); complicated mild, moderate, severe, and penetrating TBI (n = 230); injured controls (n = 340); and noninjured controls (n = 188). We examined 25 factors related to demographic, injury-related, military-specific, treatment/health care need, and mental health/social support variables. Seven factors were statistically associated with the presence of DSM-IV-TR symptom criteria for PTSD: premorbid IQ, combat exposure, depression, social participation, history of mTBI, need for managing mood and stress, and need for improving memory and attention, p < .001 (51.3% variance). When comparing the prevalence of these risk factors in a longitudinal cohort (n = 742) across four PTSD trajectory groups (i.e., asymptomatic, improved, developed, persistent), a higher proportion of participants in the persistent PTSD group reported worse depression, a lack of social participation, and history of mTBI. Additionally, a higher proportion of participants in the persistent and developed PTSD groups reported the need for managing mood/stress and improving memory/attention. When considered simultaneously, the presence of ≥ 1 or ≥ 2 risk factors was associated with a higher proportion of participants in the developed and persistent PTSD groups, ps < .001. These risk factors may be useful in identifying SMVs at risk for the development and/or persistence of PTSD symptoms who may need intervention.

PMID:36315642 | DOI:10.1002/jts.22892