Final Date Research Articles

Strengthening Addiction Care Continuum Through Community Consortium in Vietnam: Protocol for a Cluster-Randomized Controlled Trial.

A chronic condition, drug addiction, requires long-term multipronged health care and treatment services. Community-based approaches can offer the advantages of managing integrated care along the care continuum and improving clinical outcomes. However, scant rigorous research focuses on sustainable, community-based care and service delivery. This protocol describes a study aiming to develop and test an intervention that features the alliance of community health workers and family members to provide integrated support and individualized services and treatment for people who use drugs (PWUD) in community settings. Based on the National Institute on Drug Abuse's Seek-Test-Treat-Retain (STTR) framework, an intervention that provides training to community health workers will be developed and piloted before an intervention trial. Trained community health workers will conduct home visits and provide support for PWUD and their families. The intervention trial will be conducted in 3 regions in Vietnam, with 60 communities (named communes). These communes will be randomized to either an intervention or control condition. Intervention outcomes will be evaluated at baseline and at 3, 6, 9, and 12 months. The primary outcome measure is PWUD's STTR fulfillment, consisting of multiple individual fulfillment indicators across 5 domains: Seek, Test, Treat, Retain, and Health. The secondary outcomes of interest are the community health workers' service provision and family members' support. The primary analysis will follow an intention-to-treat approach. Generalized mixed-effects regression models will be used to compare changes in the outcome measures from baseline between intervention and control conditions. During the first year of the project, we conducted formative studies, including in-depth interviews and focus groups, to identify service barriers and intervention strategies. The intervention and assessment pilots are scheduled in 2023 before commencing the trial. Reports based on the baseline data will be distributed in early 2024. The intervention outcome results will be available within 6 months of the final data collection date, that is, the main study findings are expected to be available in early 2026. This study will inform the establishment of community health workers and family members alliance, a locally available infrastructure, to support addiction services and care for PWUD. The methodology, findings, and lessons learned are expected to shed light on the addiction service continuum's implementation and demonstrate a community-based addiction service delivery model that can be transferable to other countries. ClinicalTrials.gov NCT05315492; https://clinicaltrials.gov/ct2/show/NCT05315492. DERR1-10.2196/44219.

A Systematic Review of Abuse or Overprescription of Bupropion in American Prisons and a Synthesis of Case Reports on Bupropion Abuse in American Prison and Non-prison Systems.

Illicit drug use is a huge problem in the US prison system. The objectives of this study are (1) to systematically investigate the prevalence of bupropion abuse in American prisons along with associated problems, and (2) to synthesize available case reports on this topic in both prison and non-prison settings. Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses, we searched five databases (PubMed, Embase, Scopus, CINAHL, and PsycINFO) and used Covidence software for screening and reviewing identified articles. The final search date was February 21, 2023. Newcastle-Ottawa Scale and ROBINS-I tool were used for risk of bias assessment. We included original studies of populations aged 18 years and above in American prisons. We found 77 unique articles, none of which met our eligibility criteria. A synthesis of 22 case reports that we found showed bupropion abuse to be more common in young males, and intranasal administration was the most common method of abuse. More frequent desired and adverse effects were "cocaine-like highs" and seizures, respectively. Although several cases of bupropion abuse have been reported in US prisons, no study has been done to understand its prevalence and associated effects. The absence of original studies on bupropion abuse in US prisons and the observed patterns in this case report synthesis further highlight the need for a study to investigate the prevalence of bupropion abuse in US prisons. The limitations of this study include that it is an empty systematic review and the absence of all pertinent data in many of the included case reports. The authors did not receive any funding for this work. This systematic review was registered in PROSPERO with registration number CRD42021227561.

Comparison of Contrast-Enhanced Ultrasound vs Conventional Ultrasound-Guided Percutaneous Nephrolithotomy in Nondilated Collecting System: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: It has been demonstrated that ultrasound (US)-guided renal collecting system access during percutaneous nephrolithotomy (PCNL) is efficient and secure. The puncture success rate fell to 82%, and the total complication rate rose to 15% in kidneys with nondilated collecting systems. Contrast-enhanced ultrasonography (CEUS) has been used in PCNL techniques to address this issue. Methods: We did this meta-analysis following the preferred reporting criteria for systematic reviews and meta-analysis to combine the data of published studies to compare the CEUS-guided PCNL and the standard US-guided PCNL (PRISMA). For relevant literature, we searched PubMed, Embase, Web of Science, CKNI, and the Cochrane Library. The final inclusion date for this meta-analysis was May 1, 2022, and three randomized controlled trials (RCTs) were finally included. RevMan V5.4.1 was used in this work. Standard mean difference (SMD) with a 95% confidence interval (CI) was utilized as the major estimate in the synthesis of continuous data, while odds ratio (OR) with a 95% CI was synthesized as the main estimate in the synthesis of discontinuous data. Results: We found that compared with traditional US-guided PCNL, CEUS-guided PCNL could offer more benefits in terms of single-needle success rate (OR: 3.02, 95% CI: 1.62 to 5.61, p = 0.0005), shorter puncture time (SMD: -1.33, 95% CI: -2.06 to -0.60, p = 0.0004), shorter hospital stays (SMD: -0.37, 95% CI: -0.60 to -0.13, p = 0.002), and a better stone clearance rate (OR: 2.32, 95% CI: 1.15 to 4.68. p = 0.02). Although the PCNL complication rate after surgery was not significantly reduced by the CEUS technique (overall complication: OR = 0.70, 95% CI: 0.37 to 1.30, p = 0.25. Grade 1/2 complication: OR = 0.79, 95% CI: 0.41 to 1.53, p = 0.48; Grade 3/4 complication: OR = 0.44, 95% CI: 0.10 to 1.98, p = 0.28), it could reduce hemoglobin dropping compared with conventional US-guided PCNL (SMD: -0.82, 95% CI: -1.06 to -0.58, p < 0.001). Conclusion: The CEUS-guided PCNL technique is superior to the US-guided PCNL, according to almost all synthesized data. Additional randomized studies are still required.

Impact of NSAIDs on 8-year cumulative incidence of major cardiovascular events in patients with ankylosing spondylitis: a nationwide study.

The objectives of this study were to describe the incidence of major adverse cardiovascular events (MACEs) in French patients newly benefiting from the French Long-term Illness scheme (LTI) for AS and to evaluate the effect of various treatments on the risk of MACE occurrence. This national cohort study was based on the French national medico-administrative database SNDS containing data on hospitalization, the LTI, and outpatient care consumption. All French patients newly receiving LTI benefits for AS from 2010 to 2013 were included. The final follow-up date was 31 December 2018. The occurrences of MACEs [stroke and myocardial infarction (MI)] and comorbidities were identified from algorithms previously described in the literature. Competitive risk analysis using propensity score and inverse weighting was performed to calculate cumulative incidence functions and to determine subhazard ratios (SHRs) for the various treatments of interest. Between 2010 and 2013, 22 929 patients were included [mean age 43.0 (s.d. 13.9) years, 44.9% mal]. The 8-year cumulative incidences of MACE, stroke, and MI were 1.81% (1.61-2.05), 0.97% (0.83-1.14), and 0.85% (0.71-1.04), respectively. NSAIDs [SHR: 0.39 (0.32-0.50), P < 0.001] and anti-TNF [SHR 0.61 (0.46-0.80), P < 0.001], but not anti-IL17 [2.10 (0.79-5.57)] were associated with a lower risk of MACE occurrence. MACE incidence rates at 8 years are low in patients newly benefiting from LTI for AS. Our results support the hypothesis of a protective role of NSAIDs and anti-TNF in cardiovascular risk in these patients.

The risk of depressive and anxiety symptoms in women with premature ovarian insufficiency: a systematic review and meta-analysis

Premature ovarian insufficiency (POI) appears to be associated with depressive and anxiety symptoms. However, there is a lack of high-quality evidence relating to the risk of patients with POI developing depression or anxiety. Therefore, we conducted a systematic review and meta-analysis to quantify the risk of depressive and anxiety symptoms in women with POI. We searched English and Chinese databases to evaluate the risk of depression and anxiety disorders in patients with POI. The final search date was November 2021. The risk was quantified using meta-analysis, with an estimation of pooled odds ratio (OR) and 95% confidence interval (CI). Sources of heterogeneity were explored by subgroup analysis. A total of seven primary studies with 1316 individuals were included, five of which were related to depression and six to anxiety disorders. All included articles were case–control studies of high quality. Patients with POI were associated with a higher odds of depression and anxiety (depression: OR = 3.33, 95% CI = 2.31–4.81, P < 0.001; anxiety: OR = 4.89, 95% CI = 3.28–7.30, P < 0.001). Subgroup analysis also indicated that patients with POI are at a higher risk of anxiety and depression. POI appears to be associated with a high risk of depression and anxiety. Early psychosocial assessment and regular screening of patients with POI are also necessary. In addition, it is important to consider the mental health of patients with POI.

Effect of Torsemide vs Furosemide After Discharge on All-Cause Mortality in Patients Hospitalized With Heart Failure

Although furosemide is the most commonly used loop diuretic in patients with heart failure, some studies suggest a potential benefit for torsemide. To determine whether torsemide results in decreased mortality compared with furosemide among patients hospitalized for heart failure. TRANSFORM-HF was an open-label, pragmatic randomized trial that recruited 2859 participants hospitalized with heart failure (regardless of ejection fraction) at 60 hospitals in the United States. Recruitment occurred from June 2018 through March 2022, with follow-up through 30 months for death and 12 months for hospitalizations. The final date for follow-up data collection was July 2022. Loop diuretic strategy of torsemide (n = 1431) or furosemide (n = 1428) with investigator-selected dosage. The primary outcome was all-cause mortality in a time-to-event analysis. There were 5 secondary outcomes with all-cause mortality or all-cause hospitalization and total hospitalizations assessed over 12 months being highest in the hierarchy. The prespecified primary hypothesis was that torsemide would reduce all-cause mortality by 20% compared with furosemide. TRANSFORM-HF randomized 2859 participants with a median age of 65 years (IQR, 56-75), 36.9% were women, and 33.9% were Black. Over a median follow-up of 17.4 months, a total of 113 patients (53 [3.7%] in the torsemide group and 60 [4.2%] in the furosemide group) withdrew consent from the trial prior to completion. Death occurred in 373 of 1431 patients (26.1%) in the torsemide group and 374 of 1428 patients (26.2%) in the furosemide group (hazard ratio, 1.02 [95% CI, 0.89-1.18]). Over 12 months following randomization, all-cause mortality or all-cause hospitalization occurred in 677 patients (47.3%) in the torsemide group and 704 patients (49.3%) in the furosemide group (hazard ratio, 0.92 [95% CI, 0.83-1.02]). There were 940 total hospitalizations among 536 participants in the torsemide group and 987 total hospitalizations among 577 participants in the furosemide group (rate ratio, 0.94 [95% CI, 0.84-1.07]). Results were similar across prespecified subgroups, including among patients with reduced, mildly reduced, or preserved ejection fraction. Among patients discharged after hospitalization for heart failure, torsemide compared with furosemide did not result in a significant difference in all-cause mortality over 12 months. However, interpretation of these findings is limited by loss to follow-up and participant crossover and nonadherence. ClinicalTrials.gov Identifier: NCT03296813.

Clinical features of elderly patients with COVID-19 in Wuhan, China.

Elderly patients with coronavirus disease 2019 (COVID-19) who have comorbidities, frailty or profound disabilities experience poor outcomes. We analyzed the clinical characteristics of elderly patients from Wuhan who had COVID-19 during the early stages of the pandemic. To identify factors affecting the early mortality of elderly patients with COVID-19. The records of 234 patients who were 65-years-old or more and were hospitalized in Wuhan Huoshenshan Hospital from February 4 to March 4, 2020 were reviewed. All patients had confirmed COVID-19 and the final date of follow-up was April 4, 2020. There were 163 cases of mild disease (69.66%), 39 cases of severe disease (16.67%) and 32 cases of critical disease (13.68%). Twenty-nine patients died within 1 mo (12.40%), all of whom had critical disease. Surviving patients and deceased patients had no significant differences in age or chronic diseases. Overall, the most common symptoms were fever (65.4%), dry cough (57.3%), fatigue (47.4%) and shortness of breath (41%). The deceased patients had higher levels of multiple disease markers (C-reactive protein, D-dimer, lactate dehydrogenase, alanine amino transferase, aspartate aminotransferase, creatinine kinase and creatinine kinase-MB) and higher incidences of lymphocytopenia and hypoproteinemia. This single-center study of elderly patients from Wuhan, China who were hospitalized with COVID-19 indicated that age and chronic diseases were not associated with mortality. Hypertension, diabetes and cardiovascular disease were the most common comorbidities and the most common symptoms were fever, dry cough, fatigue and shortness of breath. Lymphocytopenia, increased levels of D-dimer and other markers indicative of damage to the heart, kidneys or liver were associated with an increased risk of death.

1115. Effect of polymerized type I collagen in hyperinflammation of adult outpatients with symptomatic COVID-19: a double blind, randomised, placebo-controlled clinical trial

Abstract Background Currently, therapeutic options for outpatients with COVID-19 are limited, in Mexico Polymerized Collagen type I (PCTI) has been tested as a useful option. Methods Double-blind, randomised, placebo-controlled clinical trial of PTIC vs placebo. To evaluate the safety, efficacy and effect of the intramuscular administration of polymerized type I collagen (PTIC) on hyperinflammation, oxygen saturation and symptom improvement in adult outpatients with symptomatic COVID-19. Eighty-nine adult participants with a confirmed COVID-19 diagnosis and symptom onset within the 7 days preceding recruitment were included from August 31, 2020 to November 7, 2020 and followed for 12 weeks. Final date of follow-up was February 4, 2021. Patients were randomly assigned to receive either 1.5 ml of PTIC intramuscularly every 12 h for 3 days and then every 24 h for 4 days (n=45), or matching placebo (n=44). Results Of 89 patients who were randomised, 87 (97.8%) were included in an intention-to-treat analysis; 37 (41.6%) were male and mean age was 48.5±14.0 years. The IP-10 levels decreased 75% in the PTIC group and 40% in the placebo group vs baseline. The comparison between treatment vs placebo was also statistically significant (P=0.0047). The IL-8 (44%, P=0.045), M-CSF (25%, P=0.041) and IL-1Ra (36%, P=0.05) levels were also decreased in the PTIC group vs baseline. Mean oxygen saturation ≥92% was achieved by 40/44 (90%), 41/42 (98%) and 40/40 (100%) of participants that received PTIC at 8, 15 and 97 days of follow-up vs 29/43 (67%), 31/39 (80%) and 33/37 (89%) of patients treated with placebo (P=0.001). The unadjusted accelerated failure time model showed that patients treated with PTIC achieved the primary outcome 2.70-fold faster (P&amp;lt; 0.0001) than placebo. In terms of risk, the group of patients treated with PTIC had a 63% lower risk of having a mean oxygen saturation &amp;lt; 92% vs placebo (P&amp;lt; 0.0001). Symptom duration in patients treated with PTIC was reduced by 6.1±3.2 days vs placebo. No differences in adverse effects were observed between the groups at 8, 15 and 97 days of follow-up. Conclusion Treatment with PTIC down-regulated IP-10, IL-8, M-CSF and IL-Ra levels, which could explain the PTIC effect on the higher proportion of patients with mean SaO2 ≥92% and a shorter duration of symptoms as compared with placebo. Serum cytokine and chemokine levels of SARS-CoV2-infected symptomatic outpatients at baseline and day 8 post-treatment with PTIC or placebo. Data are expressed as median with 95% confidence. (A) IP-10, IFN-γ inducible protein-10; (B) IL-8, Interleukin-8; (C) M-CSF, Macrophage colony-stimulating factor; (D) IL-1Ra, IL-1 receptor antagonist; (E) TRAIL, TNF-related apoptosis inducing ligand; and (F) Forest plot (95% confidence intervals). (A) Probability of oxygen saturation 92% or greater while breathing ambient air. (B) Accelerated time failure model for oxygen saturation 92% or greater while breathing ambient air among polymerised type I collagen and placebo. Disclosures All Authors: No reported disclosures.

Morphological, clinical, and functional efficacy in the short and medium-term after radiofrequency treatment of predominantly solid, large, and clinically relevant thyroid nodules in patients who are not candidates for surgery: The experience after 100 procedures

IntroductionThyroid nodules (TN) are a prevalent pathology that can generate morbidity, in which case the traditional treatment is usually surgery. ObjectiveTo analyse the efficacy of radiofrequency ablation (RFA) treatment as a therapeutic alternative in the combined clinical, morphological, and functional control of predominantly solid, benign and clinically relevant TNs in patients not subsidiary to surgery. Materials and methodsA descriptive, retrospective, case series study was carried out to assess the efficacy and safety of the use of RFA. According to medical criteria, the selected patients underwent a clinical, ultrasound, and biochemical assessment prior to the procedure and then after the procedure at 1, 3, 6, and 12 months and then every 6–12 months according to medical criteria. ResultsA total of 100 RFA were performed on 83 patients with 85 TNs of ≥2.5 cm with an initial volume (IV) of 21.48 ± 15.89 ml. After a mean of 1.17 RFA sessions per TN, the volume decreased progressively and significantly (p < 0.01 for all times compared to the initial value), with a mean volume reduction rate (VRR) in relation to the IV of 54.43 ± 19.56% at 1-month follow-up; 67.69 ± 17% at 3 months; 70.38 ± 15.46% at 6 months; 70.67 ± 17.27% at 12 months and 70.24 ± 17.7% at the last follow-up. 88% of the patients followed up >6 months achieved the combined objective of a volume reduction rate of more than 50% of the VI, thyroid normal function and absence of clinic; and in all of these, it was maintained until the final follow-up date. Acute complications (mostly mild and all transient) were reported in 9 of the 100 RFA performed. ConclusionOur findings validate in our setting the efficacy and safety of RFA in predominantly large and solid TNs, and add undescribed information to position the technique more favourably as a therapeutic alternative.

A Conversational, Virtual, Avatar-Led Cognitive Behavioral Therapy App Intervention for Improving the Quality of Life and Mental Health of People With Epilepsy: Protocol for a Randomized Controlled Trial.

Epilepsy is a common neurological disorder affecting about 1 in 100 people in the United Kingdom. Many individuals experience a lower quality of life as a result of their epilepsy diagnosis and are more likely to develop mental health problems, such as anxiety and depression. Medical interventions for this client group tend to focus on the treatment of seizures, whereas mental health disorders often remain undiagnosed and untreated. Early identification and treatment of mental health difficulties in people with epilepsy are vital to ensure better outcomes and improvements in quality of life. The aim of this exploratory randomized controlled trial is to evaluate whether an 8-week cognitive behavioral therapy-based intervention delivered through a mobile app-ThinkNinja for Epilepsy-is a clinically effective tool to improve quality of life, mental health, and emotional well-being in a large sample of people with epilepsy and anxiety or comorbid anxiety and depression. The study aims to recruit 184 individuals, 18 to 65 years of age, with a self-reported diagnosis of epilepsy and anxiety or comorbid anxiety and depression. Participants will be randomly assigned to the ThinkNinja for Epilepsy app condition (arm A) or the waiting-list control group (arm B). Participants in arm A will receive access to the ThinkNinja for Epilepsy app first. After 8 weeks, participants in arm B will receive the same full access to the ThinkNinja for Epilepsy app as the participants in arm A. This design will allow an initial between-subjects analysis between the two conditions as well as a within-subject analysis including all participants. The primary outcome is participants' quality of life, measured by the 10-item patient-weighted Quality of Life in Epilepsy questionnaire. The secondary outcomes include measures of anxiety, using the 7-item Generalized Anxiety Disorder assessment; depression, using the 9-item Patient Health Questionnaire; medication adherence, using the Medication Adherence Questionnaire; and impression of change, using the Patient Global Impression of Change questionnaire. Recruitment for this study began in March 2022 and was completed in October 2022. We expect data collection to be finalized by May 2023 and study results to be available within 12 months of the final data collection date. Results of the study will be written up as soon as possible thereafter, with the intention of publishing the outcomes in high-quality peer-reviewed journals. This study aims to determine the clinical efficacy and safety of the ThinkNinja for Epilepsy intervention at improving the quality of life, mental health, and emotional well-being of people with epilepsy. The findings from our study will hopefully contribute to addressing the critical gap in universal provision and accessibility of mental health and emotional well-being support for people with epilepsy. ISRCTN Registry 16270209 (04/03/2022); https://www.isrctn.com/ISRCTN16270209. DERR1-10.2196/40261.

Final Results of the Phase 1/2 Study of Acalabrutinib Monotherapy in Treatment-Naive Chronic Lymphocytic Leukemia with >6 Years of Follow-up

Background: Acalabrutinib is a next-generation, covalent Bruton tyrosine kinase inhibitor approved for the treatment of patients with treatment-naive (TN) or relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). A previous analysis of the phase 1/2, multicenter ACE-CL-001 study (NCT02029443) demonstrated durable responses and good long-term tolerability of acalabrutinib as first-line therapy in patients with CLL at a median follow-up of 53 months (Byrd et al. Blood. 2021;137:3327-38). Here, we report the final analysis in the TN cohort of that study, the longest running study of acalabrutinib, with over 6 years of follow-up. Methods: Patients included in the study were aged ≥18 years with TN CLL/SLL who met the 2008 iwCLL criteria for treatment, were inappropriate for or declined standard chemotherapy, and had ECOG performance status 0-2. All TN patients were treated in the phase 2 portion of the study and received acalabrutinib 100 mg twice daily (BID) or 200 mg once daily (QD), later switching to 100 mg BID, until progressive disease (PD) or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included investigator-assessed overall response rate (ORR), time to response (TTR), duration of response (DOR), and progression-free survival (PFS), with a post hoc analysis of event-free survival (EFS). Results: Ninety-nine patients (n=62 100 mg BID; n=37 200 mg QD) were treated. The median age was 64 years; 47% of patients had Rai stage 3-4 disease, 10% had del(17p), 14% had TP53 mutation, 17% had del(11q), 62% had unmutated IGHV, and 18% had complex karyotype. At the final data cut-off date of July 15, 2021, the median study follow-up was 73.7 months (range 0.92-82.4), and 70 (71%) patients remain on acalabrutinib treatment. The most common reasons for treatment discontinuation were adverse events (AEs) (10%) and PD (6%). The most common AEs (Table 1) were consistent with those reported in the prior update (53-month median follow-up). The only grade ≥3 AEs with a ≥50% increase in incidence since the prior update were pneumonia (4% [prior update] vs 8%) and syncope (4% [prior update] vs 6%). AEs that led to treatment discontinuation were amyotrophic lateral sclerosis, angiosarcoma, cardiac failure, cerebral hemorrhage, gastric hemorrhage, glioblastoma multiforme, non-cardiac chest pain, prostate cancer, sepsis, small cell lung cancer, and urinary tract infection (in 1 patient each). All-grade and grade ≥3 events of clinical interest included infection (87% and 19%, respectively), bleeding events (74%, 7%), major bleeding events (8%, 7%), and hypertension (29%, 13%). Atrial fibrillation/flutter occurred in 6% of patients (3% grade ≥3). Second primary malignancies excluding non-melanoma skin (all grades) occurred in 14% of patients Two deaths were reported (cardiac failure, n=1; multiple organ dysfunction syndrome, n=1); neither was considered treatment related. ORR was 97% (9% complete response; 88% partial response). Median TTR was 3.7 months (range 1.7-22.1). Median DOR was not reached; the estimated 66-month DOR rate was 89% (95% CI 80-94). ORR of 100% was seen across high-risk groups: del(17p) (9/9), del(11q) (15/15), unmutated IGHV (57/57), and complex karyotype (12/12). Median PFS was not reached; the estimated 72-month PFS rate was 87% (95% CI 77-93; Figure 1). The estimated 72-month EFS was 78% (95% CI 68-85). Reported EFS events overall included AEs (n=10/99, 10%), disease progression (n=9/99, 9%), and new anticancer therapy (n=3/99, 3%). Conclusions: The final data from ACE-CL-001 further support the long-term efficacy and safety of acalabrutinib monotherapy, with high response rates and rapid, durable responses seen in patients with TN CLL regardless of high-risk genomic features. With over 6 years of follow-up, this study firmly establishes the tolerability and safety profile of acalabrutinib seen consistently in subsequent studies, with a low incidence of atrial fibrillation/flutter seen and no new long-term safety issues identified. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Phase 1/2 Study of Acalabrutinib Monotherapy in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia: Final Results with >4 Years of Follow-up

Background: Treatment with Bruton tyrosine kinase (BTK) inhibitors has remarkably improved clinical outcomes for patients with chronic lymphocytic leukemia (CLL). Acalabrutinib is a highly selective, covalent BTK inhibitor approved for the treatment of CLL. Here we report the final analysis of the phase 1/2 study of acalabrutinib (multicenter, multicohort ACE-CL-001 study; NCT02029443) with median follow-up of 53 months in patients with relapsed/refractory (R/R) CLL/small lymphocytic lymphoma (SLL). Prior analyses were reported at median follow-up durations of 14 months (Byrd et al. N Engl J Med. 2016;374:323-32) and 41 months (Byrd et al. Blood. 2020;135:1204-13). Methods: Adult patients with CLL or SLL who had received ≥1 prior treatment and had an Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2 were included in the R/R cohort of the study. In the dose-escalation portion of the study, patients were enrolled into dose cohorts at acalabrutinib dosages of 100, 175, 250, and 400 mg once daily (QD) and 100 mg or 200 mg twice daily (BID). In the phase 2 portion of the study, patients received oral acalabrutinib 100 mg BID or 200 mg QD, later switching to 100 mg BID, until progressive disease or unacceptable toxicity occurred. The primary study endpoint was safety. Secondary endpoints included overall response rate (ORR), duration of response (DOR), and progression-free-survival (PFS), with post hoc analysis of event-free survival (EFS). Response rates were based on the iwCLL 2008 criteria with modification for lymphocytosis. Results: In total, 134 patients with R/R CLL/SLL received ≥1 dose of acalabrutinib (dosing information was previously reported; Byrd et al. Blood. 2020;135:1204-13). Median age was 66 years, and 97% of patients had ECOG PS ≤1, 73% unmutated IGHV, 27% del(17p), 20% del(11q), and 35% complex karyotype. The median number of prior therapies was 2 (range 1-13). At the final data cutoff date of July 15, 2021, at a median follow-up of 52.6 (range 0.56-88.8) months, 31% of patients remained on acalabrutinib. The most common reasons for discontinuing treatment were progressive disease (37%) and adverse events (AEs; 15%). The most commonly reported AEs were consistent with those reported in the previous update (Table 1); no new AEs emerged with longer term follow-up. AEs leading to discontinuation that occurred in >1 patient were pneumonia (5 patients), anemia, neutropenia, diarrhea, and thrombocytopenia (2 patients each). Events of clinical interest (all grades; grade ≥3, respectively) included atrial fibrillation/flutter (9%; 3%), hypertension (23%; 11%), infection (88%; 33%), bleeding events (71%; 6%), major bleeding events (8%; 6%), and ventricular tachyarrhythmias (2%, 1%). No cases of sudden death were reported. The ORR (partial response or better) was 90% (95% confidence interval [CI] 84-95); 4% of patients had complete response and 87% partial response (PR). The median DOR was 60.1 months (range 2.7-81.0). The 66-month estimated DOR rate was 45% (95% CI 36-55). Responses were similar regardless of high-risk features, including unmutated IGHV (n=73/81; 90%), del(17p) (n=27/31; 87%), del(11q) (n=20/23; 87%), and complex karyotype (n=17/20; 85%). The median PFS was 66.1 months (range 0.4-87.8; Figure 1), and the median EFS was 53.8 months (range 44.1-66.1). The 72-month estimated PFS was 45% (95% CI 36-54) and the 72-month estimated EFS was 37% (95% CI 29-46). Reported EFS events overall included AEs (n=18/134, 13%), death (n=5/134, 4%), disease progression (n=54/134, 40%), and new anticancer therapy (n=3/134, 2%). Conclusions: The results of this final analysis confirm the earlier reports of acalabrutinib efficacy and were later confirmed by similar outcomes of response durability and long-term tolerability in the pivotal ASCEND phase 3 trial in patients with R/R CLL/SLL (Jurczak et al. J Clin Oncol. 2022;40[suppl 16]:7538). Reported AEs indicate a tolerable and consistent safety profile, with low rates of atrial fibrillation and major bleeding events with median follow-up of 53 months (up to 7.4 years). No new safety signals were identified. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Comparison of Acupuncture vs Sham Acupuncture or Waiting List Control in the Treatment of Aromatase Inhibitor–Related Joint Pain

Aromatase inhibitors (AIs) have proven efficacy for the treatment of hormone-sensitive breast cancer; however, arthralgias (pain and stiffness) contribute to nonadherence with therapy for more than 50% of patients. To examine the effect of acupuncture in reducing AI-related joint pain through 52 weeks. A randomized clinical trial was conducted at 11 sites in the US from May 1, 2012, to February 29, 2016, with a scheduled final date of follow-up of September 5, 2017, to compare true acupuncture (TA) with sham acupuncture (SA) or waiting list control (WC). Women with early-stage breast cancer were eligible if they were taking an AI and scored 3 or higher on the Brief Pain Inventory Worst Pain (BPI-WP) item (score range, 0-10; higher scores indicate greater pain). Analysis was conducted for data received through May 3, 2021. Participants were randomized 2:1:1 to the TA (n = 110), SA (n = 59), or WC (n = 57) group. The TA and SA protocols were composed of 6 weeks of intervention at 2 sessions per week (12 sessions overall), followed by 6 additional weeks of intervention with 1 session per week. Participants randomized to WC received no intervention. All participants were offered 10 acupuncture sessions to be used between weeks 24 and 52. In this long-term evaluation, the primary end point was the 52-week BPI-WP score, compared by study group using linear regression, adjusted for baseline pain and stratification factors. Among 226 randomized women (mean [SD] age, 60.7 [8.6] years; 87.7% White; mean [SD] baseline BPI-WP score, 6.7 [1.5]), 191 (84.5%) completed the trial. In a linear regression, 52-week mean BPI-WP scores were 1.08 (95% CI, 0.24-1.91) points lower in the TA compared with the SA group (P = .01) and were 0.99 (95% CI, 0.12-1.86) points lower in the TA compared with the WC group (P = .03). In addition, 52-week BPI pain interference scores were statistically significantly lower in the TA compared with the SA group (difference, 0.58; 95% CI, 0.00-1.16; P = .05). Between 24 and 52 weeks, 12 (13.2%) of TA, 6 (11.3%) of SA, and 5 (10.6%) of WC patients reported receipt of acupuncture. In this randomized clinical trial, women with AI-related joint pain receiving 12 weeks of TA had reduced pain at 52 weeks compared with controls, suggesting long-term benefits of this therapy. ClinicalTrials.gov Identifier: NCT01535066.

Abstract 9724: Left Atrial Volume Index as a Predictor of Atrial Fibrillation Recurrence After Cardioversion

Introduction: The left atrial volume index (LAVI) is a standard measurement of the left atrium. To date, there is limited data on the risk of AF recurrence with different LAVI cut-point. We aim to determine the association of LAVI as a predictor of AF recurrence after external electrical cardioversion (ECV). Methods: We conducted a retrospective cohort study using data from a single tertiary care center from January 2013 to December 2019. Patients diagnosed with AF who underwent successful ECV were included with the final follow-up date of December 2020. The effect of LAVI on AF recurrence was determined by Cox regression analysis adjusted by age, sex, BMI, comorbidities, type of AF, ejection fraction, and medications. Results: A total of 296 patients, 61.8% male, with a mean age of 69.2 ± 11.2 years old were included with a mean follow-up time of 1 year. Antiarrhythmic drugs were used in 104 patients after the ECV. LAVI ≤ 34 ml/m2 is associated with a lower risk of AF recurrence with an adjusted hazard ratio (aHR) of 0.31 (95%CI: 0.20-0.40). LAVI &gt; 34 to &lt; 40 ml/m2, did not significantly increased the risk of AF recurrence (aHR 1.67, 95%CI: 0.97-2.87). LAVI of ≥ 40 ml/m2 and ≥ 50 ml/m2 significantly increased the risk of AF recurrence with aHR of 4.30 (95%CI: 2.61 - 7.10) and 4.97 (95%CI: 2.97 - 8.33), respectively. Conclusions: Normal LAVI is associated with a lower AF recurrence after ECV and LAVI ≥ 40 ml/m2 is associated with increased AF recurrence. LAVI is a predictor to consider before undergoing rhythm management in a patient with atrial fibrillation.

Clinical characteristics and short-term mortality of 102 hospitalized hemodialysis patients infected with SARS-CoV-2 omicron BA.2.2.1 variant in Shanghai, China

BackgroundThe aim of this study was to analyze clinical features and short-term mortality in hemodialysis (HD) patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) omicron BA.2.2.1 variant. MethodsIn a retrospective single-center case series, 102 consecutive hospitalized HD patients infected with the coronavirus omicron variant were assessed at Pudong Hospital in Shanghai, China, from April 6 to April 18, 2022; the final date of follow-up was May 16, 2022. Clinical, laboratory, chest CT, and treatment data were collected and analyzed. The association between these factors and all-cause mortality was studied using univariate and multivariate analyses. The relationship between lymphocyte count and short-term mortality was based on receiver operating characteristic (ROC) curve analysis. Kaplan–Meier analysis was used to assess overall survival. ResultsIn total, 102 patients were included in this study. The patients were divided into two groups: HD patients with pneumonia (N = 46) and without pneumonia (N = 56). Of the 102 patients, 12 (11.8%) died. Multivariate regression analysis revealed that all-cause mortality was correlated with lymphocyte counts and type B natriuretic peptide (BNP), C-reactive protein (CRP), and D-dimer levels (P < 0.05). The cut-off value of lymphocyte counts was 0.61 × 109/L for all-cause mortality. The overall survival rate was significantly different between HD patients with and without pneumonia (P < 0.05). ConclusionsLymphocyte counts are important for the prediction of short-term mortality in HD patients with SARS-CoV-2 infection. HD patients with lung involvement have poorer survival rates than those without lung involvement.

Effect of Lower vs Higher Oxygen Saturation Targets on Survival to Hospital Discharge Among Patients Resuscitated After Out-of-Hospital Cardiac Arrest

The administration of a high fraction of oxygen following return of spontaneous circulation in out-of-hospital cardiac arrest may increase reperfusion brain injury. To determine whether targeting a lower oxygen saturation in the early phase of postresuscitation care for out-of-hospital cardiac arrest improves survival at hospital discharge. This multicenter, parallel-group, randomized clinical trial included unconscious adults with return of spontaneous circulation and a peripheral oxygen saturation (Spo2) of at least 95% while receiving 100% oxygen. The trial was conducted in 2 emergency medical services and 15 hospitals in Victoria and South Australia, Australia, between December 11, 2017, and August 11, 2020, with data collection from ambulance and hospital medical records (final follow-up date, August 25, 2021). The trial enrolled 428 of a planned 1416 patients. Patients were randomized by paramedics to receive oxygen titration to achieve an oxygen saturation of either 90% to 94% (intervention; n = 216) or 98% to 100% (standard care; n = 212) until arrival in the intensive care unit. The primary outcome was survival to hospital discharge. There were 9 secondary outcomes collected, including hypoxic episodes (Spo2 &lt;90%) and prespecified serious adverse events, which included hypoxia with rearrest. The trial was stopped early due to the COVID-19 pandemic. Of the 428 patients who were randomized, 425 were included in the primary analysis (median age, 65.5 years; 100 [23.5%] women) and all completed the trial. Overall, 82 of 214 patients (38.3%) in the intervention group survived to hospital discharge compared with 101 of 211 (47.9%) in the standard care group (difference, -9.6% [95% CI, -18.9% to -0.2%]; unadjusted odds ratio, 0.68 [95% CI, 0.46-1.00]; P = .05). Of the 9 prespecified secondary outcomes collected during hospital stay, 8 showed no significant difference. A hypoxic episode prior to intensive care was observed in 31.3% (n = 67) of participants in the intervention group and 16.1% (n = 34) in the standard care group (difference, 15.2% [95% CI, 7.2%-23.1%]; OR, 2.37 [95% CI, 1.49-3.79]; P &lt; .001). Among patients achieving return of spontaneous circulation after out-of-hospital cardiac arrest, targeting an oxygen saturation of 90% to 94%, compared with 98% to 100%, until admission to the intensive care unit did not significantly improve survival to hospital discharge. Although the trial is limited by early termination due to the COVID-19 pandemic, the findings do not support use of an oxygen saturation target of 90% to 94% in the out-of-hospital setting after resuscitation from cardiac arrest. ClinicalTrials.gov Identifier: NCT03138005.

Performance Measurement for Opioid Use Disorder Medication Treatment and Care Retention.

Performance Measurement for Opioid Use Disorder Medication Treatment and Care Retention.

Impacts of COVID-19 pandemic on professional identity development of intern nursing students in China: A scoping review.

Clinical experience plays a vital role in the development of the professional identity (PI) of nursing students. China has applied a strict zero- COVID health policy in combating the COVID-19 pandemic since December 2019 and studies have been conducted in different places of China to explore PI development of nursing students during the pandemic time among the intern nursing students who are on clinical practices. This review study aims to synthesize the previous studies and provide a comprehensive picture of the impacts of the pandemic on the PI development of intern nursing students. Arksey and O'Malley's five-stage scoping review framework was used. Combinations of keywords were used to search relevant articles in both Chinese and English databases published from inception of the articles until the final search date (10 March 2022). The initially included articles were also appraised for their quality, and those that passed the appraisal were left for data analysis. The analytic results were cross-checked among the reviewers. Three themes emerged from the included studies: 1) the PI levels, 2) the impacts of personal and social factors of PL, and 3) the specific impact of the COVID-19 pandemic. The levels of students' PI ranged from 66%-80% of the total scores in PI instruments, almost the same levels as in pre-pandemic time, despite the elevated social image of nurses after the COVID-19 pandemic. There is no consensus about the impacts of most personal and social factors on students' PI across the studies. The impacts of COVID-19 on PI were both positive and negative. COVID-19 epidemic exerted complicated impacts on the PI of intern nursing students. While it is necessary to address the fear of the COVID-19 pandemic among intern nursing students, the pandemic may not be an opportunistic time to enhance the students' PI.

Effect of Helmet Noninvasive Ventilation vs Usual Respiratory Support on Mortality Among Patients With Acute Hypoxemic Respiratory Failure Due to COVID-19

Helmet noninvasive ventilation has been used in patients with COVID-19 with the premise that helmet interface is more effective than mask interface in delivering prolonged treatments with high positive airway pressure, but data about its effectiveness are limited. To evaluate whether helmet noninvasive ventilation compared with usual respiratory support reduces mortality in patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. This was a multicenter, pragmatic, randomized clinical trial that was conducted in 8 sites in Saudi Arabia and Kuwait between February 8, 2021, and November 16, 2021. Adult patients with acute hypoxemic respiratory failure (n = 320) due to suspected or confirmed COVID-19 were included. The final follow-up date for the primary outcome was December 14, 2021. Patients were randomized to receive helmet noninvasive ventilation (n = 159) or usual respiratory support (n = 161), which included mask noninvasive ventilation, high-flow nasal oxygen, and standard oxygen. The primary outcome was 28-day all-cause mortality. There were 12 prespecified secondary outcomes, including endotracheal intubation, barotrauma, skin pressure injury, and serious adverse events. Among 322 patients who were randomized, 320 were included in the primary analysis, all of whom completed the trial. Median age was 58 years, and 187 were men (58.4%). Within 28 days, 43 of 159 patients (27.0%) died in the helmet noninvasive ventilation group compared with 42 of 161 (26.1%) in the usual respiratory support group (risk difference, 1.0% [95% CI, -8.7% to 10.6%]; relative risk, 1.04 [95% CI, 0.72-1.49]; P = .85). Within 28 days, 75 of 159 patients (47.2%) required endotracheal intubation in the helmet noninvasive ventilation group compared with 81 of 161 (50.3%) in the usual respiratory support group (risk difference, -3.1% [95% CI, -14.1% to 7.8%]; relative risk, 0.94 [95% CI, 0.75-1.17]). There were no significant differences between the 2 groups in any of the prespecified secondary end points. Barotrauma occurred in 30 of 159 patients (18.9%) in the helmet noninvasive ventilation group and 25 of 161 (15.5%) in the usual respiratory support group. Skin pressure injury occurred in 5 of 159 patients (3.1%) in the helmet noninvasive ventilation group and 10 of 161 (6.2%) in the usual respiratory support group. There were 2 serious adverse events in the helmet noninvasive ventilation group and 1 in the usual respiratory support group. Results of this study suggest that helmet noninvasive ventilation did not significantly reduce 28-day mortality compared with usual respiratory support among patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. However, interpretation of the findings is limited by imprecision in the effect estimate, which does not exclude potentially clinically important benefit or harm. ClinicalTrials.gov Identifier: NCT04477668.

Long-Term Efficacy, Safety, and Subgroup Analysis of Savolitinib in Chinese Patients With NSCLCs Harboring MET Exon 14 Skipping Alterations

IntroductionSavolitinib has been found to have encouraging antitumor activity and a favorable safety profile in Chinese patients with pulmonary sarcomatoid carcinoma and other NSCLCs with MET exon 14 skipping alterations (MET ex14 positive) at the primary analysis of a phase 2 study. Here, we present the long-term efficacy and safety data of savolitinib, including subgroup analyses. MethodsThis multicenter, single-arm, open-label, phase 2 study in the People’s Republic of China enrolled MET inhibitor-naive adults with locally advanced or metastatic METex14-positive NSCLC (NCT02897479). Oral savolitinib at a dose of 400 or 600 mg was administered once daily (body weight dependent). The primary objectives of the final analysis were long-term overall survival (OS) and subgroup analyses by previous systemic treatment, NSCLC subtypes, and brain metastases. ResultsAt the final analysis cutoff date (June 28, 2021), a total of 70 patients were enrolled and receiving savolitinib, and median follow-up was 28.4 (interquartile range: 26.2–36.3) months. The median OS was 12.5 months (95% confidence interval [CI]: 10.5–21.4 [18- and 24-mo OS rates, 42.1% and 31.5%, respectively]). Median OS in pretreated or treatment-naive patients was 19.4 (95% CI: 10.5–31.3) and 10.9 (95% CI: 7.5–14.0) months, respectively; it was 10.6 months (95% CI: 4.6–14.0) in patients with pulmonary sarcomatoid carcinoma, 17.3 months (95% CI: 10.6–23.6) in other NSCLC subtypes, and 17.7 months (95% CI: 10.5–not evaluable) in patients with brain metastases. No new safety signals emerged with prolonged follow-up and exposure. ConclusionsThe updated results further confirm the favorable benefit and acceptable safety of savolitinib in Chinese patients with METex14-positive NSCLC.