Clinical Outcomes at 1 Year Following Transcatheter Left Atrial Appendage Occlusion in the United States

ObjectivesThe aim of this study was to report 1-year clinical outcomes following commercial transcatheter left atrial appendage occlusion (LAAO) in the United States.BackgroundThe National Cardiovascular Data Registry LAAO Registry was initiated to meet a condition of Medicare coverage and allow the assessment of clinical outcomes. The 1-year rates of thromboembolic events after transcatheter LAAO in such a large cohort of “real-world” patients have not been previously reported.MethodsPatients entered into the National Cardiovascular Data Registry LAAO Registry for a Watchman procedure between January 1, 2016, and December 31, 2018, were included. The primary endpoint was ischemic stroke. Key secondary endpoints included the rate of ischemic stroke or systemic embolism, mortality, and major bleeding. Major bleeding was defined as any bleeding requiring hospitalization, and/or causing a decrease in hemoglobin level > 2g/dL, and/or requiring blood transfusion that was not hemorrhagic stroke. The Kaplan-Meier method was used for 1-year estimates of cumulative event rates.ResultsThe study population consisted of 36,681 patients. The mean age was 76.0 ± 8.1 years, the mean CHA₂DS₂-VASc score was 4.8 ± 1.5, and the mean HAS-BLED score was 3.0 ± 1.1. Prior stroke was present in 25.5%, clinically relevant bleeding in 69.5%, and intracranial bleeding in 11.9%. Median follow-up was 374 days (IQR: 212-425 days). The Kaplan-Meier–estimated 1-year rate of ischemic stroke was 1.53% (95% CI: 1.39%-1.69%), the rate of ischemic stroke or systemic embolism was 2.19% (95% CI: 2.01%-2.38%), and the rate of mortality was 8.52% (95% CI: 8.19%-8.87%). The 1-year estimated rate of major bleeding was 6.93% (95% CI: 6.65%-7.21%). Most bleeding events occurred between discharge and 45 days following the procedure.ConclusionsThis study characterizes important outcomes in a national cohort of patients undergoing transcatheter LAAO in the United States. Clinicians and patients can integrate these data in shared decision making when considering this therapy.     

Left Ventricular Systolic Dysfunction and Cardiovascular Outcomes in Tetralogy of Fallot: Systematic Review and Meta-analysis

BackgroundAlthough there are robust data about the pathophysiology and prognostic implications of left ventricular (LV) systolic dysfunction in patients with acquired heart disease, similar prognostic data about LV systolic dysfunction are sparse in the tetralogy of Fallot (TOF) population. The purpose of this study was to perform a meta-analysis of all studies that assessed the relationship between LV ejection fraction (LVEF) and cardiovascular adverse events (CAEs) defined as death, aborted sudden death, or sustained ventricular tachycardia.MethodsWe used random-effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsOf the 1,809 citations, 7 studies with 2,854 patients (age 28 ± 4 years) were included. During 5.6 ± 3.4 years' follow-up, there were 82 deaths, 17 aborted sudden cardiac deaths, and 56 sustained ventricular tachycardia events. Overall, CAEs occurred in 5.1% (144 patients). As a continuous variable, LVEF was a predictor of CAE (HR 1.29, 95% CI, 1.09-1.53, P = 0.001) per 5% decrease in LVEF. Similarly, LVEF < 40% was also a predictor of CAE (HR 3.22, 95% CI, 2.16-4.80, P < 0.001).ConclusionsLV systolic dysfunction was an independent predictor of CAE, and we observed a 30% increase in the risk of CAE for every 5% decrease in LVEF, and a 3-fold increase in the risk of CAE in patients with LVEF <40% compared with other patients. These findings underscore the importance of incorporating LV systolic function in clinical risk stratification of patients with TOF and the need to explore new treatment options to address this problem.     

Implementation of Recommendations for Long-Acting Contraception Among Women Aged 13 to 18 Years in Primary Care

ObjectiveClinical specialty societies recommend long-acting reversible contraceptives (LARCs) as first-line contraception for adolescent women. We evaluated whether a combined educational and process improvement intervention enhanced LARC placement in primary care within an integrated health care system.MethodsThe intervention included journal clubs, live continuing education, point-of-care guidelines, and new patient materials. We conducted a retrospective cohort study across 3 time periods: baseline (January 2013?September 2015), early implementation (October 2015–March 2016), and full implementation (April 2016–June 2017). The primary outcome was the proportion of LARCs placed by primary care clinicians among women aged 13 to 18 years compared with gynecology clinicians.ResultsKaiser Foundation Health Plan of Colorado cared for approximately 20,000 women aged 13 to 18 years in each calendar quarter between 2013 and 2017. Overall, LARC placement increased from 7.0 per 1000 members per quarter at baseline to 13.0 per 1000 during the full intervention. Primary care clinicians placed 6.2% of all LARCs in 2013, increasing to 32.1% by 2017 (P < .001), including 45.5% of contraceptive implants. Clinicians who attended educational sessions were more likely to adopt LARCs than those who did not (17.9% vs 6.4% respectively, P = .009). Neither overall LARC placement rates (relative risk, 1.9; 95% confidence interval, 0.7?5.6) nor contraceptive implant rates (relative risk, 3.0; 95% confidence interval, 0.9?9.8) increased significantly in clinicians who attended educational activities.ConclusionsThis multimodal intervention was associated with increased LARC placement for adolescent women in primary care. The combination of education and process improvement is a promising strategy to promote clinician behavior change.     

The U.S.-FORTA (Fit fOR The Aged) List: Consensus Validation of a Clinical Tool to Improve Drug Therapy in Older Adults

Background/ObjectivesPolypharmacy and multimorbidity is a threat to older people; hence, listing approaches should support physicians to optimize medication. The FORTA (Fit fOR The Aged) classification of drug appropriateness for older people provides positive or negative labels: A (A-bsolutely), B (B-eneficial), C (C-areful), and D (D-on't). Based on these categories, FORTA-labeled drug lists were developed in 7 European countries or regions; the same approach was used to develop a U.S.-FORTA List reflecting the country-specific availability and usage of drugs.Design/SettingA 2-step Delphi-type approach was employed to add, remove, or relabel drugs from the listing proposal and to add or remove new indications. The proposal utilized the European (EURO)-FORTA list as template.ParticipantsEight US-based geriatricians/pharmacists served as raters. Measurements: Raters gave recommendations and comments on the list items.ResultsThe first U.S.-FORTA List contains 273 items aligned to 27 main indication groups; 30 drugs and drug groups were added, and 23 removed as being unavailable in the United States. The highest percentage of changes in FORTA labels as compared to the EURO-FORTA List occurred for sleep disorders associated with dementia (40%). In 8 indications, the labels for 11 items were different from the proposal. Thus, for the majority of the items (n = 232, 95.5%), the proposals were accepted by the US raters. Only 16 (6.6%) of the proposed items (n = 243) had to be re-evaluated in the second round as a result of inconsistent rating in the first round.Conclusions and ImplicationsThe U.S.-FORTA List addresses the appropriateness of drugs for older people in the United States reflecting country-specific availability, usage, and expert rating. As shown for the FORTA list in Europe, this listing approach is among the few that are clinically validated and improve well-being and geriatric outcomes. The U.S.-FORTA List now largely enhances the global availability of this approach.     

miR-200、 miR -155及血管新生因子与复发性流产的相关性分析

目的 研究miR-200、miR-155及血管新生因子与原因不明复发性流产(unexplained recurrent spontaneousabortion,URSA)的相关性分析。 方法 选择2015年3月—2018年1月在青岛市妇女儿童医院妇产科就诊的URSA患者作为URSA组、要求终止妊娠的正常早孕患者作为对照组,检测绒毛组织中微小RNA(microRNA, miR)miR-200、miR-155、血管内皮生长因子(vascular endothelial growth factor,VEGF)、可溶性FMS样酪氨酸激酶1(soluble FMS like tyrosine kinase-1,sFlt-1)的表达量及血清中VEGF、sFlt-1的含量,对miR-200、miR-155靶向结合VEGF、sFlt-1进行生物信息学分析。 结果 URSA组的绒毛组织中miR-200(1.78±0.32 vs. 0.91±0.15)、sFlt-1(1.87±0.35 vs. 1.06±0.21)的相对表达量及血清中sFlt-1的含量[(12.39±2.31)ng/ml vs. (6.51±0.95)ng/ml]均高于对照组,差异有统计学意义(均P<0.05)。绒毛组织中miR-155相对表达量(0.60±0.10 vs. 0.93±0.16)、VEGF mRNA相对表达量(0.59±0.09 vs. 1.02±0.16)及蛋白表达量(0.62±0.07 vs. 1.04±0.18)、血清中VEGF的含量[(601.25±94.39)ng/ml vs. (935.12±132.47)ng/ml]低于对照组,差异有统计学意义(均P<0.05);URSA组患者绒毛组织中miR-200的表达量与血清中VEGF的含量、绒毛组织中VEGF的表达量均呈负相关,绒毛组织中miR-155的表达量与血清中sFlt-1的含量和绒毛组织中sFlt-1的表达量均呈负相关;miR-200、miR-155分别靶向结合VEGF、sFlt-1基因的3’UTR。 结论 miR-200表达增多、miR-155表达减少与URSA发生有关,miR-200靶向VEGF、miR-155靶向sFlt-1是介导该过程的可能机制。     

Intimate partner violence as a mechanism of traumatic ocular injury in women

ObjectiveDetermine the prevalence of intimate partner violence (IPV) as a mechanism of traumatic ocular injury in women, typical injury patterns, and the clinical course of affected patients. Encourage IPV screening and safety assessment in patients presenting with characteristic ocular trauma.MethodsMedical records of 211 female patients with traumatic ocular injuries evaluated at the University of Iowa Hospitals and Clinics between January 1995 and January 2015 were reviewed to determine the rate of IPV as a mechanism of ocular trauma. Twenty-one patients were excluded due to no documented trauma.ResultsLeading causes of traumatic ocular injuries in the 190 female patients included were accidental trauma with an inanimate object (n = 70/190, 36.8%), falls (n = 52/190, 27.4%), motor vehicle collisions (n = 21/190, 11.1%), and assault (n = 16/190, 8.4%). In 2.1% of cases (n = 4/190), no mechanism of traumatic injury was documented. Assault was the fourth leading mechanism of injury accounting for 8.4% of cases (n = 16/190), with IPV accounting for more than one third of cases with a documented perpetrator (n = 5/13). No perpetrator was documented in 18.8% (n = 3/16). All 5 patients with IPV-related injuries sustained scleral laceration or rupture; 4 out of 5 patients had no light perception vision and ultimately required enucleation.ConclusionIPV is an important mechanism of traumatic ocular injury. IPV-associated injuries tend to be severe in nature, as demonstrated by the high rate of globe laceration or rupture and subsequent enucleation in the study population. By appropriate screening and referral, ophthalmologists have an opportunity to redirect a potentially devastating course.     

Antiproliferative, cytotoxic and apoptogenic activity of Indian toad (Bufo melanostictus, Schneider) skin extract on U937 and K562 cells.

The antiproliferative, cytotoxic and apoptogenic activities of Bufo melanostictus (Indian common toad) skin extract (TSE) on U937 and K562 leukemic cell line has been investigated. TSE significantly (P<0.001) reduced the time-dependent cell proliferation and decreased MTT values in U937 and K562 cells. TSE (IC50 doses) suppressed the proliferating cell nuclear antigen expression in both the cells. It was demonstrated that, TSE (IC50 doses) primarily arrested the U937 and K562 cells at G1 phase of the cell cycle. Confocal microscopy showed the altered fragmented nuclei and apoptotic bodies formation in TSE (IC50 doses) treated U937 and K562 cells. Membrane blebbing, cell surface shrinkage and perforation were observed through scanning electron microscope. TSE-induced DNA fragmentation in U937 and K562 cells was reflected in single-cell gel electrophoresis. TSE significantly (P<0.001) increase the length-width ratio of DNA mass as compared to control in comet assay. The flow cytometric analysis of annexin-V binding to the cancer cells further supported the apoptotogenic activity of TSE. The effect of TSE on normal human peripheral blood mononuclear cells viability and cytotoxicity was studied in culture and found to be less cytotoxic than on the U937 and K562 cells. The findings from the present study suggested that TSE might possess potent antineoplastic agent having antiproliferative, cytotoxic and apoptogenic activity against U937 and K562 myeloid leukemic cells.     

Occupational injury and illness in the semiconductor manufacturing industry

Two thousand nine hundred and ninety-four reports of OSHA-reportable occupational injury or illness cases in 1984 from member companies of a national trade association of semiconductor manufacturing firms were analyzed. The 37 participating manufacturing facilities represented 16 companies employing over 95,000 persons, or approximately one-third of the U.S. work force for this industry in 1984. The annual incidence rate for all reportable injuries and illnesses was 2.7 per 100 full-time employees (FTE) for men and 3.7 per 100 FTE for women. Strains, sprains, or dislocations were the most frequently reported incidents (N = 956 [31.9%]), followed by cuts, lacerations, punctures, scratches, and abrasions (N = 445 [14.9%]), and chemical burns (N = 401 [13.4%]). Increased work-loss days per case were associated with manufacturing sites that did not have an employee health clinic on the premises, with custodial occupations, and with female gender.