Advantage of whole-mount histopathology in prostate cancer: current applications and future prospects.

BACKGROUND: Whole-mount histopathology (WMH) has been a powerful tool to investigate the characteristics of prostate cancer. However, the latest advancement of WMH was yet under summarization. In this review, we offer a comprehensive exposition of current research utilizing WMH in diagnosing and treating prostate cancer (PCa), and summarize the clinical advantages of WMH and outlines potential on future prospects. METHODS: An extensive PubMed search was conducted until February 26, 2023, with the search term "prostate", "whole-mount", "large format histology", which was limited to the last 4 years. Publications included were restricted to those in English. Other papers were also cited to contribute a better understanding. RESULTS: WMH exhibits an enhanced legibility for pathologists, which improved the efficacy of pathologic examination and provide educational value. It simplifies the histopathological registration with medical images, which serves as a convincing reference standard for imaging indicator investigation and medical image-based artificial intelligence (AI). Additionally, WMH provides comprehensive histopathological information for tumor volume estimation, post-treatment evaluation, and provides direct pathological data for AI readers. It also offers complete spatial context for the location estimation of both intraprostatic and extraprostatic cancerous region. CONCLUSIONS: WMH provides unique benefits in several aspects of clinical diagnosis and treatment of PCa. The utilization of WMH technique facilitates the development and refinement of various clinical technologies. We believe that WMH will play an important role in future clinical applications.

Effectiveness and Safety of Dabigatran in Atrial Fibrillation Patients with Severe Obesity: a Real-World Retrospective Cohort Study.

BACKGROUND: Direct oral anticoagulants such as dabigatran are the preferred anticoagulant in treating atrial fibrillation (AF) patients due to their effectiveness and safety. Whether this applies to severely obese patients needs to be determined. OBJECTIVE: To compare the effectiveness and safety of dabigatran with warfarin among AF patients with severe obesity. DESIGN: Retrospective cohort study. PARTICIPANTS: AF patients with a BMI >40kg/m2 or a weight >120kg receiving dabigatran or warfarin between 10/01/2010 and 12/31/2019 in a large integrated health system and followed through 08/01/2020. INTERVENTIONS: Not applicable. MAIN MEASURES: Primary effectiveness outcome was composite thromboembolism including transient ischemic attack, ischemic stroke, or systemic embolism. Primary safety outcome was composite bleeding including gastrointestinal bleeding, intracranial bleeding, or other bleeding. Secondary outcomes included the individual outcomes and all-cause mortality. Propensity score matching (PSM) was performed to create a 1:1 matched cohort and Cox proportional hazards model was used to estimate the hazard ratio (HR) of each outcome for dabigatran users compared to warfarin users. KEY RESULTS: A total of 6848 patients receiving either dabigatran or warfarin were identified. In a 1:1 matched cohort, dabigatran users had a HR of 0.71 (95% confidence interval (CI): 0.56-0.91) for composite thromboembolism, a HR of 1.24 (95%CI: 1.07-1.42) for composite bleeding, and a HR of 0.57 (95% CI: 0.45-0.71) for all-cause mortality when compared to warfarin users. CONCLUSIONS: Among AF patients with a BMI >40kg/m2 or a weight >120kg in a real-world clinical setting, dabigatran was effective in reducing the risk of thromboembolism and mortality but was associated with an increased risk of bleeding when compared to warfarin. Dabigatran may be a reasonable option for AF patients with severe obesity.

Risk of Acute Myocardial Infarction, Heart Failure, and Death in Migraine Patients Treated with Triptans.

OBJECTIVE: The goal of this study is to determine the strength of association between treatment with triptans and acute myocardial infarction, heart failure, and death. BACKGROUND: Case reports in the literature have raised concerns over an association between treatment of migraine headaches with triptans and cardiovascular events. This study aims to systematically evaluate this association in a contemporary population-based cohort. We hypothesized that triptan exposure is not associated with increased cardiovascular events. METHODS: A retrospective cohort study was conducted within an integrated healthcare delivery system in Southern California. From January 2009 to December 2018, 189,684 patients age ≥18 years had a diagnosis of migraine. In this group, 130,656 were exposed to triptans. Patients treated with triptans were matched 1:1 to those not exposed to triptans by using a propensity score. The primary outcome was acute myocardial infarction; secondary outcomes were heart failure, all-cause death, and combined acute myocardial infarction, heart failure, and death. RESULTS: The incidence rate of acute myocardial infarction was 0.67 per 1000 person-year in triptan-exposed vs 1.44 per 1000 person-year in not exposed patients. In propensity-matched analyses, the adjusted hazard ratio for triptan exposure was 0.95 (95% confidence interval [CI] 0.84-1.08) for acute myocardial infarction; 1.00 (95% CI 0.93-1.08) for all-cause death; 0.93 (95% CI 0.81-1.08) for heart failure; and 0.99 (95% CI 0.93-1.06) for a composite of acute myocardial infarction, heart failure, or death. Sensitivity analyses focusing on stratified subgroups based on age, gender, ethnicity, and several cardiac risk factors also revealed no significant association between triptan exposure and cardiovascular events. CONCLUSIONS: No association was found between exposure to triptans and an increased risk of cardiovascular events. These data provide reassurance regarding the cardiovascular safety of utilizing triptans for the medical management of migraine headaches.

Influence of Ambulatory Triglyceride Levels on Risk of Recurrence in Patients with Hypertriglyceridemic Pancreatitis.

BACKGROUND AND AIMS: To evaluate impact of ambulatory triglyceride levels on risk of recurrent pancreatitis in patients with hypertriglyceridemic pancreatitis. METHODS: We conducted a longitudinal retrospective cohort study of patients with serum triglyceride level ≥ 500 mg/dL during index hospitalization for acute pancreatitis within a regional integrated healthcare system between 2006 and 2013 (follow-up through 2015). Cases were identified based on combination of diagnosis codes and serum amylase/lipase. We used multivariable robust Poisson regression to determine independent effect of baseline (first outpatient) triglyceride measurement on risk of recurrent pancreatitis. Ambulatory triglyceride levels were categorized as normal (0-200 mg/dL), moderately elevated (201-500 mg/dL), and highly elevated (> 500 mg/dL). We further assessed factors related to likelihood of normalization of serum triglycerides (< 200 mg/dL) in the outpatient setting. RESULTS: One hundred and fifty-one patients met study inclusion criteria with median follow-up of 3 years. Overall, 45 (29.8%) patients experienced at least 1 recurrent attack with 25 (16.6%) experiencing multiple episodes. In multivariable analysis, patients that continued to have moderately elevated ((adjusted rate ratio RR 5.47 (95% CL 1.80, 16.65)) as well as highly elevated (RR 8.45 (2.55, 27.96)) triglycerides were at increased risk of disease recurrence compared to patients that achieved normalization. Patients with triglyceride measurement performed within 30 days from discharge were more likely to achieve normalization, 40 versus 26%, p = 0.03. CONCLUSIONS: For patients with hypertriglyceridemic pancreatitis, even modest elevation in subsequent triglyceride levels was associated with increased risk of recurrence. Future efforts should focus on ensuring timely care in the outpatient setting with a goal of normalizing triglycerides.

Autocrine VEGF maintains endothelial survival through regulation of metabolism and autophagy.

Autocrine VEGF is necessary for endothelial survival, although the cellular mechanisms supporting this function are unknown. Here, we show that--even after full differentiation and maturation--continuous expression of VEGF by endothelial cells is needed to sustain vascular integrity and cellular viability. Depletion of VEGF from the endothelium results in mitochondria fragmentation and suppression of glucose metabolism, leading to increased autophagy that contributes to cell death. Gene-expression profiling showed that endothelial VEGF contributes to the regulation of cell cycle and mitochondrial gene clusters, as well as several--but not all--targets of the transcription factor FOXO1. Indeed, VEGF-deficient endothelium in vitro and in vivo showed increased levels of FOXO1 protein in the nucleus and cytoplasm. Silencing of FOXO1 in VEGF-depleted cells reversed expression profiles of several of the gene clusters that were de-regulated in VEGF knockdown, and rescued both cell death and autophagy phenotypes. Our data suggest that endothelial VEGF maintains vascular homeostasis through regulation of FOXO1 levels, thereby ensuring physiological metabolism and endothelial cell survival.

Racial and Ethnic Minorities at Increased Risk for Gastric Cancer in a Regional US Population Study.

BACKGROUND AND AIMS: Limited data are available on risk factors for gastric cancer in the United States. We aimed to characterize risk for gastric cancer based on race/ethnicity and additional established risk factors. METHODS: We conducted a retrospective cohort study from 2008 to 2014 from an integrated health care system in Southern California to assess incidence of gastric cancer by race/ethnicity. We then conducted an age- and sex-matched case-cohort study to evaluate additional risk factors: Helicobacter pylori infection, tobacco use, family history, obesity, language, and socioeconomic status. Subgroup analysis was performed for language and socioeconomic status by race/ethnicity. RESULTS: The incidence of gastric cancer in the reference (non-Hispanic white) population was 8.2 (95% confidence interval [CI], 7.7-8.7) cases per 100,000 person-years. Incidence values for Asians, Hispanics, and non-Hispanic black persons were higher: 12.7 (95% CI, 11.1-14.3), 12.7 (95% CI, 11.7-13.7), and 11.8 (95% CI, 10.3-13.2) cases per 100,000 person-years, respectively (all P < .0001). In logistic regression analysis, we found race/ethnicity to be an independent risk factor for gastric cancer; the odds ratio (OR) for non-Hispanic black persons was 1.5 (95% CI, 1.22-1.72; P < .0001), the OR for Hispanics was 1.4 (95% CI, 1.22-1.57; P < .0001), and the OR for Asians was 1.5 (95% CI, 1.28-1.81; P < .0001), compared with the non-Hispanic white population. Other independent risk factors included infection with H pylori (OR, 4.6; 95% CI, 3.8-5.7), smoking history (OR, 1.4; 95% CI, 1.3-1.6), and family history of gastric cancer (OR, 3.4; 95% CI, 2.6-4.4) (all P < .0001). Non-English language was a significant risk factor for gastric cancer in Asians (P = .05). Higher annual median income was associated with reduced risk (OR, 0.84; 95% CI, 0.75-0.95; P = .0004). CONCLUSIONS: In a population study in Southern California, we found racial/ethnic minorities to have a 40%-50% increase in risk of gastric cancer compared with the non-Hispanic white population. In addition to H pylori infection, smoking, family history, and low socioeconomic status were also associated with increased risk. Further characterization of high-risk groups may identify populations appropriate for targeted screening.

Competing Risks for Mortality in Patients With Asymptomatic Pancreatic Cystic Neoplasms: Implications for Clinical Management.

OBJECTIVES: Pancreatic cystic neoplasms (PCNs) are being detected with increased frequency. Current clinical practice guidelines emphasize management based on cyst-related features. We aimed to evaluate the impact of comorbidity on mortality in PCN patients via competing risk analysis. METHODS: We analyzed a retrospective cohort of patients diagnosed between 2005-2010, with follow-up through 2015, for overall and cause-specific mortality. Comorbidities were classified by the Charlson comorbidity index. We used Cox proportional hazards regression to evaluate the independent effect of cyst features, age, gender, and comorbidities on cause-specific mortality. Subgroup analysis was performed to determine the cause-specific mortality based on four a priori clinical profiles-healthy patients with low- or high-risk cysts, and high-comorbidity patients with low- or high-risk cysts. RESULTS: A total of 1,800 patients with PCNs comprised the study cohort (median follow-up 5.7 years). A total of 402 deaths (22.3%) occurred during the study period: 43 pancreatic cancer and 359 non-pancreatic cancer deaths. Compared to healthy patients without any high-risk cyst features (reference group), patients with high comorbidity as well as high-risk cyst features had an increased risk of overall mortality (Cox hazard ratio 6.30, 95% confidence interval (CI) 4.71, 8.42, P<0.01), pancreatic cancer mortality (subdistribution hazard ratio (SHR) 51.13, 95% CI 6.35, 411.29, P<0.01), as well as non-pancreatic cancer mortality (SHR 5.24, 95% CI 3.85, 7.12, P<0.01). Meanwhile, low-risk patients with a high-risk cyst were more likely to experience pancreatic cancer mortality (SHR 68.14, 95% CI 9.27, 501.01, P<0.01) rather than non-pancreatic cancer mortality (SHR 1.22, 95% CI 0.88, 1.71, P=0.23), compared to the reference group. Similarly, compared to the reference group, high-risk patients with a low-risk cyst were more likely to experience non-pancreatic cancer mortality (SHR 3.96, 95% CI 2.98, 5.26, P<0.01) rather than pancreatic cancer mortality (SHR 2.35, 95% CI 0.14, 38.82, P=0.55). CONCLUSIONS: Most of the deaths in the study were unrelated to pancreatic cancer. This has implications for clinical management. By applying patient-related factors in conjunction with cyst features, we defined commonly encountered patient profiles to help guide PCN clinical management.

Socioeconomic factors associated with uptake and satisfaction with a post-hospitalization meals benefit in Medicare Advantage.

BACKGROUND: Kaiser Permanente Southern California began offering a 4-week supplemental benefit of home-delivered meals to Medicare Advantage members after discharge from a hospitalization for heart failure and other medical conditions in 2021. The purpose of this study is to explore the associations between socioeconomic disadvantage and food insecurity with patient uptake of and satisfaction with the meals. METHODS: Data for this cross-sectional study were drawn from survey and electronic medical record data for members referred for the meals benefit (n = 6169) and linked to a hospitalization encounter (n = 2254) between January and December 2021. Uptake was assessed using vendor records; measures of socioeconomic status included the neighborhood deprivation index (NDI) and prior receipt of medical financial assistance (MFA) from the health system. Patients were invited to complete an email or phone survey about their satisfaction with the meals and food insecurity. Multivariable log-binomial regression models were used to examine the association between socioeconomic disadvantage and food insecurity with meals uptake and satisfaction. RESULTS: Sixty-two percent of patients referred for the benefit accepted the meals (mean age: 79 ± 9, 59% people of color). While there was no significant relationship between NDI and meals uptake (RR: 0.99, 95% CI: 0.92-1.07, p = 0.77), patients who received prior MFA were more likely to accept the meals (RR: 1.09, 95% CI: 1.02-1.16, p < 0.01). Sixty-nine percent of patients who completed the survey (23% response rate) reported that meals were very or extremely helpful. Patients with food insecurity (29% of survey respondents) were more likely to report that the meals were helpful for their recovery compared to food secure patients (RR: 1.21, 95% CI: 1.09-1.35, p < 0.01). CONCLUSIONS: The home-delivered meals appeared to be particularly utilized by and helpful to patients with greater financial strain and/or food insecurity, suggesting that supplemental benefits could be more targeted toward addressing unmet needs of vulnerable adults.

Reinvent Aliphatic Arsenicals as Reversible Covalent Warheads toward Targeted Kinase Inhibition and Non-acute Promyelocytic Leukemia Cancer Treatment.

The success of arsenic in acute promyelocytic leukemia (APL) treatment is hardly transferred to non-APL cancers, mainly due to the low selectivity and weak binding affinity of traditional arsenicals to oncoproteins critical for cancer survival. We present herein the reinvention of aliphatic trivalent arsenicals (As) as reversible covalent warheads of As-based targeting inhibitors toward Bruton's tyrosine kinase (BTK). The effects of As warheads' valency, thiol protection, methylation, spacer length, and size on inhibitors' activity were studied. We found that, in contrast to the bulky and rigid aromatic As warhead, the flexible aliphatic As warheads were well compatible with the well-optimized guiding group to achieve nanomolar inhibition against BTK. The optimized As inhibitors effectively blocked the BTK-mediated oncogenic signaling pathway, leading to elevated antiproliferative activities toward lymphoma cells and xenograft tumor. Our study provides a promising strategy enabling rational design of new aliphatic arsenic-based reversible covalent inhibitors toward non-APL cancer treatment.

Addressing unmeasured confounding bias with a prior knowledge guided approach: coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in patients with stable ischemic heart disease.

Unmeasured confounding undermines the validity of observational studies. Although randomized clinical trials (RCTs) are considered the "gold standard" of study types, we often observe divergent findings between RCTs and empirical settings. We present the "L-table", a simulation-based, prior knowledge (e.g., RCTs) guided approach that estimates the true effect adjusting for the potential influence of unmeasured confounders when using observational data. Using electronic health record data from Kaiser Permanente Southern California, we compare the effectiveness of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) on endpoints at 1, 3, 5, and 10 years for patients with stable ischemic heart disease. We applied the L-table approach to the propensity score adjusted cohort to derive the omitted-confounder-adjusted estimated effects. After the L-table adjustment, CABG patients are 57.6% less likely to encounter major adverse cardiac and cerebrovascular event (MACCE) at 1 year (OR [95% CI] 0.424 [0.396, 0.517]), 56.4% less likely at 3 years (OR [95% CI] 0.436 [0.369, 0.527]), and 48.9% less likely at 5 years (OR [95% CI] 0.511 [0.451, 0.538]). CABG patients are also 49.5% less likely to die by the end of 10 years than PCI patients (OR [95% CI] 0.505 [0.446, 0.582]). We found the estimated true effects all shifted towards CABG as a more effective procedure that led to better health outcomes compared to PCI. Unlike existing sensitivity tools, the L-table approach explicitly lays out probable values and can therefore better support clinical decision-making. We recommend using L-table as a supplement to available techniques of sensitivity analysis. Supplementary Information: The online version contains supplementary material available at 10.1007/s10742-022-00282-y.

Association of a Medicare Advantage Posthospitalization Home Meal Delivery Benefit With Rehospitalization and Death.

Importance: The 2018 Chronic Care Act allowed Medicare Advantage plans to have greater flexibility in offering supplemental benefits, such as meals and services, to address unmet needs of beneficiaries with certain chronic conditions. Based on earlier studies of community-based nutritional support, such programs may result in reduced use. Objective: To evaluate the association of a 4-week posthospitalization home-delivered meals benefit with 30-day all-cause rehospitalization and mortality in patients admitted for heart failure (HF) and other acute medical conditions (non-HF). Design, Setting, and Participants: In this cohort study, patients who received meals (the meals group) were compared with 2 controls: (1) no meals in the 2019 historical cohort who would have been eligible for the benefit (the no meals-2019 group) and (2) no meals in the 2021 and 2022 concurrent cohort who were referred but did not receive the meals due to unsuccessful contacts and active declines (the no meals-2021/2022 group). This study took place in a large integrated health care system in southern California among Medicare Advantage members with a hospitalization for HF or other acute medical conditions at 15 Kaiser Permanente hospitals discharged to home. Exposure: The exposure was receipt of at least 1 and up to 4 shipments of home-delivered meals (total of 56 to 84 meals) after hospital discharge. Main Outcomes and Measures: The main outcomes were 30-day all-cause composite rehospitalization and death. Results: A total of 4032 adults with admission to the hospital for HF (mean [SD] age, 79 [9] years; 1951 [48%] White; 2001 [50%] female) and 7944 with non-HF admissions (mean [SD] age, 78 [8] years; 3890 [49%] White; 4149 [52%] female) were included in the analyses. Unadjusted rates of 30-day death and rehospitalization for the meals, no meals-2019, and no meals-2021/2022 cohorts were as follows: HF: 23.3%, 30.1%, and 38.5%; non-HF: 16.5%, 22.4%, and 32.9%, respectively. For HF, exposure to meals was significantly associated with lower odds of 30-day death and rehospitalization compared with the no meals-2021/2022 cohort (OR, 0.55; 95% CI, 0.43-0.71; P < .001) but was not significant compared with the no meals-2019 cohort (OR, 0.86; 95% CI, 0.72-1.04; P = .12). For non-HF, exposure to meals was associated with significantly lower odds of 30-day death and rehospitalization when compared with the no meals-2019 (OR, 0.64; 95% CI, 0.52-0.79; P < .001) and the no meals-2021/2022 (OR, 0.48; 95% CI, 0.37-0.62; P < .001) cohorts. Conclusions and Relevance: In this cohort study, exposure to posthospitalization home-delivered meals was associated with lower 30-day rehospitalization and mortality; randomized clinical trials are needed to confirm these findings.

Toll-like receptor 4 mediates synergism between alcohol and HCV in hepatic oncogenesis involving stem cell marker Nanog.

Alcohol synergistically enhances the progression of liver disease and the risk for liver cancer caused by hepatitis C virus (HCV). However, the molecular mechanism of this synergy remains unclear. Here, we provide the first evidence that Toll-like receptor 4 (TLR4) is induced by hepatocyte-specific transgenic (Tg) expression of the HCV nonstructural protein NS5A, and this induction mediates synergistic liver damage and tumor formation by alcohol-induced endotoxemia. We also identify Nanog, the stem/progenitor cell marker, as a novel downstream gene up-regulated by TLR4 activation and the presence of CD133/Nanog-positive cells in liver tumors of alcohol-fed NS5A Tg mice. Transplantation of p53-deficient hepatic progenitor cells transduced with TLR4 results in liver tumor development in mice following repetitive LPS injection, but concomitant transduction of Nanog short-hairpin RNA abrogates this outcome. Taken together, our study demonstrates a TLR4-dependent mechanism of synergistic liver disease by HCV and alcohol and an obligatory role for Nanog, a TLR4 downstream gene, in HCV-induced liver oncogenesis enhanced by alcohol.

Risk of Obesity Among Children Prescribed Atypical Antipsychotics for Six Months or More.

Objectives: The study investigates the risk of obesity for young children prescribed an atypical antipsychotic (AAP) for 6 months or more. AAPs are associated with risk of obesity. They are used in children for a variety of psychiatric conditions and are often prescribed off-label. Long-term risk of obesity in this age group is unknown as most studies are short-term investigations and generally combine younger children with adolescents and adults. Methods: A retrospective cohort of children, 10 years old or younger, prescribed either an AAP or selective serotonin reuptake inhibitor (SSRI) for 6 months or more were followed for up to 9.5 years. The primary endpoint was the body-mass index (BMI) reaching the 95th percentile. Results: One thousand six hundred fifty-five patients met inclusion criteria. One thousand one hundred eighteen patients were prescribed an AAP and 537 were prescribed an SSRI: 1152 (74.5%) patients were male and mean (standard deviation) age was 7.9 [1.90] years at study entry. Median follow-up was 3.58 years for the AAP cohort and 3.28 years for the SSRI cohort (p = 0.02). After adjusting for baseline demographic variables, BMI, and other concomitantly prescribed medications, children prescribed AAPs for 6 months or longer were twice as likely to become obese compared with children prescribed SSRIs (adjusted hazard ratio [HR] 2.06 [95% confidence interval; CI 1.60-2.66], p < 0.0001). Further stratification by AAP revealed that the obesity risk for patients prescribed aripiprazole was 34% greater than for those prescribed risperidone (adjusted HR 1.34 [95% CI 1.01-1.78], p = 0.0033). Conclusions: The risk of obesity for young children prescribed an AAP for 6 months or more is approximately double that of children prescribed an SSRI. The risk of obesity is greater with aripiprazole than risperidone in the first year. Prescribers should consider the risk of obesity when prescribing AAPs and consider alternative treatment modalities in this vulnerable patient population.

Safety and Effectiveness of Direct Oral Anticoagulants Versus Warfarin for Treating Left Ventricular Thrombus.

BACKGROUND: Patients with left ventricular thrombus are at high risk for ischemic stroke and systemic embolization. The mainstay of treatment is anticoagulation, but it remains unclear if direct-acting oral anticoagulants (DOACs) are a safe and effective treatment strategy compared to warfarin. We conducted a population-based retrospective cohort study to evaluate the effectiveness and safety of DOACs compared to warfarin in an integrated health system in the United States. METHODS: Consecutive patients with left ventricular thrombus on transthoracic echocardiogram from May 2010 to April 2020 were identified. Comparative effectiveness and safety of DOACs and warfarin were evaluated using multivariable Cox proportional hazard models and inverse probability of treatment weighting. RESULTS: Among 433 patients with left ventricular thrombus, 134 (30.9%) were treated with DOACs and 299 (69.1%) were treated with warfarin. Patients were followed for a median of 3.4 years. For the primary effectiveness outcome of ischemic stroke, systemic embolism, and transient ischemic attack, no significant difference was observed between use of DOACs compared to warfarin (adjusted hazard ratio [HR] of 0.75, 95% confidence interval [CI] 0.48-1.18, p = 0.21). For the primary safety outcome of intracranial hemorrhage, gastrointestinal bleeding, and other bleed requiring hospitalization, DOAC usage was associated with a lower risk of bleeding (HR 0.58, 95% CI 0.39-0.87, p = 0.0008). CONCLUSIONS: In this diverse population-based cohort of patients, DOAC treatment for left ventricular thrombus appears to be as safe and effective as warfarin treatment. These findings support the use of DOACs for patients with left ventricular thrombus.

Opioid and Naloxone Prescribing Following Insertion of Prompts in the Electronic Health Record to Encourage Compliance With California State Opioid Law.

Importance: Opioid addiction or dependency is a serious crisis in the US that affects public health as well as social and economic welfare. The State of California passed Assembly Bill (AB) 2760 in 2018 that mandates the coprescription of naloxone and opioids for patients with a high overdose risk. Objective: To assess whether the AB 2760-based electronic prompts were associated with increased naloxone orders for opioid users and reduced opioid prescribing when integrated into the practitioner workflow. Design, Setting, and Participants: This cohort study used interrupted time series mixed models to evaluate data obtained from the regional integrated health care system Kaiser Permanente Southern California (KPSC) from January 1, 2018, to December 31, 2019. Clinician participants were continuously employed at KPSC during the study period and ordered an opioid analgesic for eligible patients in 2018. Patient participants were KPSC members aged 18 years or older who received an opioid analgesic prescription during the study period. A series of AB 2760-based electronic prompts were integrated into the KPSC electronic health record system on December 27, 2018. The prompts are triggered or activated when 1 or more opioid prescribing conditions, defined in the AB 2760, are met at outpatient visits. Data were analyzed from January 8, 2021, to September 15, 2021. Exposures: Assembly Bill 2760-based electronic prompts for outpatient opioid prescriptions in the electronic health record system. Main Outcomes and Measures: Primary outcomes were changes in outpatient naloxone order rates among patients who were prescribed opioids and changes in outpatient opioid prescribing rates. Secondary outcomes were total morphine milligram equivalents (MMEs) ordered per prescriber-month, prompts-targeted objectives, and unintended consequences. Risk for opioid abuse among 3 types of patients was also assessed. Results: The 6515 eligible clinicians (mean [SD] age, 45.9 [9.43] years; 3604 men [55.3%]) included in the study served 500 711 unique patients in 1 903 289 outpatient encounters (mean [SD] age, 60.4 [15.67] years; 1 121 004 women [58.9%]) in which an opioid analgesic was prescribed. Naloxone order rate increased from 2.0% in December 2018 to 13.2% in January 2019 and then continued to increase to 27.1% in December 2019. Outpatient opioid prescribing rates decreased by 15.1% (rate ratio [RR], 0.85; 95% CI, 0.83-0.87) per prescriber-month when the electronic prompts were implemented. The postimplementation trend increased by 0.7% per prescriber-month (RR, 1.01; 95% CI, 1.01-1.01); the overall trend was still decreasing. The total MMEs per prescriber-month decreased by 7.8% (RR, 0.92; 95% CI, 0.89-0.96) after implementation of the prompts. The postimplementation trend tapered off. Other safe opioid prescribing measures also improved after implementation (decreases in concomitant muscle relaxants orders [RR, 0.94; 95% CI, 0.89-1.00], initial [RR, 0.86; 0.83-0.89] and renewal [RR, 0.65; 95% CI, 0.62-0.69] opioid orders, and long-term high-dose orders [RR, 0.96; 95% CI, 0.94-0.98]). Conclusions and Relevance: This study found an association between implementation of AB 2760-based prompts and increased naloxone order rate; improved opioid prescribing measures (ie, decreased concomitant muscle relaxants orders, initial and renewal opioid orders, and long-term high-dose orders), except monthly median MMEs; and reduced opioid prescribing. The findings suggest that opioid overdose risks can be mitigated by encouraging safe prescribing habits.

Hospital utilisation in home palliative care: caregiver health, preparedness and burden associations.

BACKGROUND: Prior studies show that family caregiver factors influence patient outcomes. The purpose of this analysis was to determine the association between family caregiver self-rated health, perception of preparedness and burden at the time of patient admission to home palliative care (HomePal) with downstream patient hospital utilisation and time to hospice enrolment and death. METHODS: Data for this cohort study (n=441) were drawn from a trial testing two models of HomePal. Caregiver self-rated health, preparedness (Preparedness for Caregiving Scale, CPS) and burden (Zarit-12) were measured at admission to HomePal. Caregivers were categorised as having good/very good/excellent or fair/poor health, scoring above or below the CPS median score (23), or having no/mild (0-10), moderate (11-20) or high (>20) burden. Proportional hazard competing risk models assessed the association between caregiver factors with hospital utilisation (emergency department visits, observation and inpatient stays). RESULTS: Patients whose caregivers reported poor health and low preparedness received more visits by home health aides and social workers, respectively (both, p<0.05). Adjusted models showed that worse caregiver health (HR: 0.69 (95% CI 0.52 to 0.92), p=0.01), low preparedness (HR: 0.73 (95% CI 0.57 to 0.94), p=0.01) and high burden (HR: 0.77 (95% CI 0.56 to 1.06), p=0.10) were associated with lower risk for hospital utilisation. There were no significant associations between caregiver factors with time to patient enrolment in hospice or death in adjusted models (both, p>0.05). CONCLUSION: Prospective studies are needed to understand how greater in-home supports for family caregivers with poor health could help achieve quality palliative care that aligns with families' priorities. TRIAL REGISTRATION NUMBER: NCT03694431; ClinicalTrials.gov.

Clinical Characteristics and Outcomes of Patients With Takotsubo Syndrome.

BACKGROUND: Characteristics and outcomes of patients with takotsubo syndrome remain to be defined. The goal of this study was to report the characteristics and long-term outcomes of patients presenting with takotsubo syndrome compared with other patients presenting with acute myocardial infarction (AMI) in a community-based population. METHODS: This retrospective population-based study included patients hospitalised for AMI from 2006 to 2016. Those patients with takotsubo syndrome were compared with the patients with AMI. The primary outcome was all-cause mortality. Matching was performed to assemble a cohort of patients with similar baseline characteristics. RESULTS: Among 26,015 patients hospitalised with an initial diagnosis of AMI, 530 (2.0%) were diagnosed with takotsubo syndrome. Patients with takotsubo syndrome were older (68.3 ± 11.3 vs 65.6 ± 12.2 years) and more likely to be women (93.4% vs 30.7%). Concomitant hypothyroidism, rheumatologic disorders, and lung disease were more prevalent in the takotsubo syndrome group, whereas diabetes and hyperlipidemia were less prevalent. Mortality was lower in the takotsubo syndrome group (1-year mortality 4.0% vs 8.9%; P < 0.001). The 530 patients with takotsubo syndrome were matched with 1,315 AMI patients with similar baseline characteristics. At a follow-up of 5.4 ± 3.3 years, patients with takotsubo syndrome had a lower risk for all-cause death than other patients who presented with AMI (hazard ratio 0.59, 95% CI 0.47-0.76). CONCLUSIONS: Among patients presenting with AMI, patients with takotsubo syndrome were older and more likely to be women. Patients with takotsubo syndrome had better long-term outcomes compared with matched AMI patients.

Characteristics and outcomes of patients with spontaneous coronary artery dissection who suffered sudden cardiac arrest.

PURPOSE: Spontaneous coronary artery dissection (SCAD) can cause life-threatening ventricular arrhythmias, but the characteristics and outcomes of this population are not well characterized. We sought to determine the characteristics and outcomes of patients with SCAD who suffered sudden cardiac arrest, whether treated with or without an implantable cardioverter-defibrillator (ICD). METHODS: Retrospective cohort study of patients diagnosed with SCAD between 2006 and 2016. RESULTS: Eleven of 208 SCAD patients suffered sudden cardiac arrest (5.3%). Those who suffered cardiac arrest were more likely to have pregnancy-associated SCAD (27.3% vs 7.1%, p = 0.018). They were more likely to have left main (18.2% vs 1.0%, p = 0.01) or proximal coronary vessel involvement (36.4% vs 8.1%, p = 0.002), and with left ventricular ejection fraction of < 50% (45.5% vs 13.2%, p = 0.013). Percutaneous coronary intervention was more commonly performed in patients who suffered cardiac arrest (54.6% vs 8.6%, p < 0.001). Left main or proximal LAD involvement increased the odds of cardiac arrest by over 6-fold (OR 6.2, 95% CI 1.2-32.9, p = 0.03). Eight of the 11 patients suffered VT/VF arrest, of which one was treated with an ICD and one with a wearable cardioverter-defibrillator. Of these, no shocks were reported at follow-up and no ventricular arrhythmic events were reported in those not receiving defibrillator treatment. CONCLUSION: Sudden cardiac arrest in SCAD patients is associated with left main or proximal coronary lesions. Secondary prevention ICD did not show benefit in this cohort. Future larger studies are needed to determine the role of ICD therapy in SCAD patients who suffer cardiac arrest.