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An increasing prevalence in deaths occurring within nursing homes has led to a growing concern surrounding quality issues in end-of-life (EOL) nursing home care. In addition, prior research has failed to emphasize the importance of state tested nursing aides (STNAs) in providing this type of care. The purpose of this study was to examine quality issues in EOL nursing home care within the context of STNAs' comfort in providing this care. A convenience sample of 108 STNAs from four nursing homes in the Cleveland, Ohio area used PDAs to provide answers to an audio questionnaire. Questions included emergent themes from the literature pertaining to EOL care in nursing homes, as well as materials from a national education initiative to improve palliative care. Findings demonstrated lack of comfort in discussing death with nursing home residents and their families and insufficient knowledge surrounding EOL decisions and certain types of EOL care. Overall, the level of comfort providing EOL care was found to be associated with STNAs' perceived importance of EOL care, understanding of hospice, and spiritual well-being. [ABSTRACT FROM AUTHOR]

BACKGROUND: Most patients with dementia will, at some point, need a proxy health care decision maker. It is unknown whether persons with various degrees of cognitive impairment can reliably report their health-related preferences. METHODS: The authors performed health state valuations (HSVs) of current and hypothetical future health states on 47 pairs of patients with mild to moderate cognitive impairment and their caregivers using computer-based standard gamble, time tradeoff, and rating scale techniques. RESULTS: Patients' mean (SD) age was 74.6 (9.3) years. About half of the patients were women (48%), as were most caregivers (73%), who were on average younger (mean age= 66.2 years, SD= 12.2). Most participants were white (83%); 17% were African American. The mean (SD) Mini-Mental State Examination (MMSE) score of patients was 24.2 (4.6) of 30. All caregivers and 77% of patients (36/47) completed all 18 components of the HSV exercise. Patients who completed the HSV exercise were slightly younger (mean age [SD]= 74.1 [8.5] v. 75.9 [11.8]; P = 0.569) and had significantly higher MMSE scores (mean score [SD] = 25.0 [4.3] v. 21.4 [4.4]; P = 0.018). Although MMSE scores below 20 did not preclude the completion of all 18 HSV ratings, being classified as having moderate cognitive impairment was associated with a lower likelihood of completing all scenario ratings (44% v. 82%). Patient and caregiver responses showed good consistency across time and across techniques and were logically consistent. CONCLUSION: Obtaining HSVs for current and hypothetical health states was feasible for most patients with mild cognitive impairment and many with moderate cognitive impairment. HSV assessments were consistent and reasonable. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The purpose of this study was to compare strategies of corticosteroid administration for the prevention of neonatal morbidity and death. STUDY DESIGN: A Markov decision model compared 3 strategies of antepartum corticosteroid administration: (1) to all pregnant women (universal), (2) to all pregnant women with a previous preterm delivery (high risk), and (3) to women who had preterm labor symptoms that placed them at risk for delivery within 7 days (current). A second model with addition of a 'rescue' arm to capture women who remained undelivered was also created. RESULTS: Compared with the current strategy, the universal strategy would result in roughly 1000 fewer cases of respiratory distress syndrome and > 3 million more women would receive corticosteroids annually. The addition of a rescue arm further reduces morbidity and mortality rates. CONCLUSION: A universal strategy of corticosteroid administration confers potential benefit for the prevention neonatal morbidity or death over the current strategy but requires that a large number of women be treated. [ABSTRACT FROM AUTHOR]

Abstract Background A feature common to all DNA sequencing technologies is the presence of base-call errors in the sequenced reads. The implications of such errors are application specific, ranging from minor informatics nuisances to major problems affecting biological inferences. Recently developed "next-gen" sequencing technologies have greatly reduced the cost of sequencing, but have been shown to be more error prone than previous technologies. Both position specific (depending on the location in the read) and sequence specific (depending on the sequence in the read) errors have been identified in Illumina and Life Technology sequencing platforms. We describe a new type of systematic error that manifests as statistically unlikely accumulations of errors at specific genome (or transcriptome) locations. Results We characterize and describe systematic errors using overlapping paired reads from high-coverage data. We show that such errors occur in approximately 1 in 1000 base pairs, and that they are highly replicable across experiments. We identify motifs that are frequent at systematic error sites, and describe a classifier that distinguishes heterozygous sites from systematic error. Our classifier is designed to accommodate data from experiments in which the allele frequencies at heterozygous sites are not necessarily 0.5 (such as in the case of RNA-Seq), and can be used with single-end datasets. Conclusions Systematic errors can easily be mistaken for heterozygous sites in individuals, or for SNPs in population analyses. Systematic errors are particularly problematic in low coverage experiments, or in estimates of allele-specific expression from RNA-Seq data. Our characterization of systematic error has allowed us to develop a program, called SysCall, for identifying and correcting such errors. We conclude that correction of systematic errors is important to consider in the design and interpretation of high-throughput sequencing experiments.

Abstract Background Proper knowledge of HIV transmission is not enough for people to adopt protective behaviors, but deficits in this information may increase HIV/AIDS vulnerability. Objective To assess drug users' knowledge of HIV/AIDS and the possible association between knowledge and HIV testing. Methods A Cross-sectional study conducted in 2006/7 with a convenience sample of 295 illicit drug users in Rio de Janeiro, assessing knowledge on AIDS/HIV transmission and its relationship with HIV testing. Information from 108 randomly selected drug users who received an educational intervention using cards illustrating situations potentially associated with HIV transmission were assessed using Multidimensional Scaling (MDS). Results Almost 40% of drug users reported having never used condoms and more than 60% reported not using condoms under the influence of substances. Most drug users (80.6%) correctly answered that condoms make sex safer, but incorrect beliefs are still common (e.g. nearly 44% believed HIV can be transmitted through saliva and 55% reported that HIV infection can be transmitted by sharing toothbrushes), with significant differences between drug users who had and who had not been tested for HIV. MDS showed queries on vaginal/anal sex and sharing syringes/needles were classified in the same set as effective modes of HIV transmission. The event that was further away from this core of properly perceived risks referred to blood donation, perceived as risky. Other items were found to be dispersed, suggesting inchoate beliefs on transmission modes. Conclusions Drug users have an increased HIV infection vulnerability compared to the general population, this specific population expressed relevant doubts about HIV transmission, as well as high levels of risky behavior. Moreover, the findings suggest that possessing inaccurate HIV/AIDS knowledge may be a barrier to timely HIV testing. Interventions should be tailored to such specific characteristics.

Abstract To redress gaps in injection drug users' (IDUs) knowledge about hepatitis risk and prevention, we developed a brief intervention to be delivered to IDUs at syringe exchange programs (SEPs) in three US cities. Following a month-long campaign in which intervention packets containing novel injection hygiene supplies and written materials were distributed to every client at each visit, intervention effectiveness was evaluated by comparing exposed and unexposed participants' self-reported injection practices. Over one-quarter of the exposed group began using the novel hygiene supplies which included an absorbent pad ("Safety Square") to stanch blood flow post-injection. Compared to those unexposed to the intervention, a smaller but still substantial number of exposed participants continued to inappropriately use alcohol pads post-injection despite exposure to written messages to the contrary (22.8% vs. 30.0%). It should also be noted that for those exposed to the intervention, 8% may have misused Safety Squares as part of pre-injection preparation of their injection site; attention should be paid to providing explicit and accurate instruction on the use of any health promotion materials being distributed. While this study indicates that passive introduction of risk reduction materials in injection drug users through syringe exchange programs can be an economical and relatively simple method of changing behaviors, discussions with SEP clients regarding explicit instructions about injection hygiene and appropriate use of novel risk reduction materials is also needed in order to optimize the potential for adoption of health promotion behaviors. The study results suggest that SEP staff should provide their clients with brief, frequent verbal reminders about the appropriate use when distributing risk reduction materials. Issues related to format and language of written materials are discussed.

Abstract Background The widespread problem of antibiotic resistance in pathogens such as Staphylococcus aureus has prompted the search for new antimicrobial approaches. In this study we report for the first time the use of a light-activated antimicrobial agent, methylene blue, to kill an epidemic methicillin-resistant Staphylococcus aureus (EMRSA-16) strain in two mouse wound models. Results Following irradiation of wounds with 360 J/cm2 of laser light (670 nm) in the presence of 100 μg/ml of methylene blue, a 25-fold reduction in the number of viable EMRSA was seen. This was independent of the increase in temperature of the wounds associated with the treatment. Histological examination of the wounds revealed no difference between the photodynamic therapy (PDT)-treated wounds and the untreated wounds, all of which showed the same degree of inflammatory infiltration at 24 hours. Conclusion The results of this study demonstrate that PDT is effective at reducing the total number of viable EMRSA in a wound. This approach has promise as a means of treating wound infections caused by antibiotic-resistant microbes as well as for the elimination of such organisms from carriage sites.

Abstract Background Romantic partnerships between drug-using couples, when they are recognized at all, tend to be viewed as dysfunctional, unstable, utilitarian, and often violent. This study presents a more nuanced portrayal by describing the interpersonal dynamics of 10 heroin and cocaine-using couples from Hartford, Connecticut. Results These couples cared for each other similarly to the ways that non-drug-using couples care for their intimate partners. However, most also cared by helping each other avoid the symptoms of drug withdrawal. They did this by colluding with each other to procure and use drugs. Care and collusion in procuring and using drugs involved meanings and social practices that were constituted and reproduced by both partners in an interpersonal dynamic that was often overtly gendered. These gendered dynamics could be fluid and changed over time in response to altered circumstances and/or individual agency. They also were shaped by and interacted with long-standing historical, economic and socio-cultural forces including the persistent economic inequality, racism and other forms of structural violence endemic in the inner-city Hartford neighborhoods where these couples resided. As a result, these relationships offered both risk and protection from HIV, HCV and other health threats (e.g. arrest and violence). Conclusion A more complex and nuanced understanding of drug-using couples can be tapped for its potential in shaping prevention and intervention efforts. For example, drug treatment providers need to establish policies which recognize the existence and importance of interpersonal dynamics between drug users, and work with them to coordinate detoxification and treatment for both partners, whenever possible, as well as provide additional couples-oriented services in an integrated and comprehensive drug treatment system.

PURPOSE: The influence of extended- spectrum beta-lactams on gram-negative bacterial resistance was studied. METHODS: Hospital pharmacists were asked to provide data on antimicrobial use and bacterial susceptibilities. Defined daily doses per 1000 patient-days of cefepime, ceftazidime, ceftriaxone, and piperacillin-tazobactam were assessed for significant associations with gram-negative susceptibility. To account for midyear changes in usage patterns and the lag between changes in usage and resistance, susceptibility over two-year periods was evaluated. RESULTS: Susceptibility data of more than 300,000 gram-negative isolates, representing 10 species of interest, were provided by 82 U.S. hospitals. Two-year periods (n = 45) were evaluable for 25 hospitals, containing 159 hospital-years of data and 204,513 clinical isolates. Use of cefepime increased, while use of ceftazidime, ceftriaxone, and piperacillin-tazobactam decreased. Excluding Pseudomonas aeruginosa, bacteria were most susceptible to cefepime, followed by piperacillin-tazobactam, ceftriaxone, and ceftazidime. Significantly decreased susceptibilities of gram-negative bacteria to the antibiotics themselves were observed with ceftazidime (Enterobacter aerogenes) and ceftriaxone (Escherichia coli). Extended-spectrum beta-lactams associated with significantly decreased susceptibilities of gram-negative bacteria to other beta-lactams included cefepime (E. aerogenes and E. coli susceptibility to ceftazidime), ceftazidime (Enterobacter cloacae susceptibility to cefepime), ceftriaxone (E. cloacae susceptibility to cefepime), piperacillin-tazobactam (E. cloacae, Klebsiella pneumoniae, and P. aeruginosa susceptibility to cefepime). There were insufficient susceptibility data to allow for impact analysis for piperacillin-tazobactam. CONCLUSION: Use of cefepime, ceftazidime, ceftriaxone, and piperacillin-tazobactam was associated with variably changing susceptibilities of several key gram-negative bacteria, either to themselves or to each other. Despite the increased use of cefepime, gram-negative bacterial susceptibility to cefepime remained high. [ABSTRACT FROM AUTHOR]

Introduction: Patients with gastroesophageal reflux (GERD) symptoms undergoing screening upper endoscopy for Barrett's esophagus (BE) frequently demonstrate columnar-lined epithelium, with forceps biopsies (FBs) failing to yield intestinal metaplasia (IM). Repeat endoscopy is then often necessary to confirm a BE diagnosis. The aim of this study was to assess the yield of IM leading to a diagnosis of BE by the addition of wide-area transepithelial sampling (WATS-3D) to FB in the screening of patients with GERD., Methods: We performed a prospective registry study of patients with GERD undergoing screening upper endoscopy. Patients had both WATS-3D and FB. Patients were classified by their Z line appearance: regular, irregular (<1 cm columnar-lined epithelium), possible short-segment BE (1 to <3 cm), and possible long-segment BE (≥3 cm). Demographics, IM yield, and dysplasia yield were calculated. Adjunctive yield was defined as cases identified by WATS-3D not detected by FB, divided by cases detected by FB. Clinicians were asked if WATS-3D results affected patient management., Results: Of 23,933 patients, 6,829 (28.5%) met endoscopic criteria for BE. Of these, 2,878 (42.1%) had IM identified by either FB or WATS-3D. Among patients fulfilling endoscopic criteria for BE, the adjunctive yield of WATS-3D was 76.5% and absolute yield was 18.1%. One thousand three hundred seventeen patients (19.3%) who fulfilled endoscopic BE criteria had IM detected solely by WATS-3D. Of 240 patients with dysplasia, 107 (44.6%) were found solely by WATS-3D. Among patients with positive WATS-3D but negative FB, the care plan changed in 90.7%., Discussion: The addition of WATS-3D to FB in patients with GERD being screened for BE resulted in confirmation of BE in an additional one-fifth of patients. Furthermore, dysplasia diagnoses approximately doubled., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Multidrug resistant Pseudomonas aeruginosa (PA) represents a serious threat to hospitalized patients. Characterizing the incidence of PA infection and degree of resistance can inform empiric treatment and preventative measures., Objectives: We sought to describe trends in incidence and resistance characteristics of PA bloodstream infections (BSI) observed within the Veterans Health Administration (VHA) system and identify factors contributing to higher observed mortality within this population., Methods: We characterized demographic and clinical features of unique patients among the VHA population presenting with their first episode of PA-BSI between 2009 and 2022 and summarized trends related to mortality and resistance phenotype based on year and geographical location. We additionally used logistic regression analysis to identify predictors of 30-day mortality among this cohort., Results: We identified 8039 PA-BSIs during the study period, 32.7% of which were hospital onset. Annual PA-BSI cases decreased by 35.8%, and resistance among all antimicrobial classes decreased during the study period, while the proportion of patients receiving early active treatment based on susceptibility testing results increased. Average 30-day mortality rate was 23.3%. Higher Charlson Comorbidity Index, higher mAPACHE score, VHA facility complexity 1b and hospital-onset cases were associated with higher mortality, and early active treatment was associated with lower mortality., Conclusions: PA-BSI resistance decreased across the VHA system during the study period. Further investigation of antimicrobial stewardship measures possibly contributing to the observed decreased resistance in this cohort and identification of measures to improve on the high mortality associated with PA-BSI in the VHA population is warranted., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Objective: Pseudomonas aeruginosa bloodstream infection (PA-BSI) and COVID-19 are independently associated with high mortality. We sought to demonstrate the impact of COVID-19 coinfection on patients with PA-BSI., Design: Retrospective cohort study., Setting: Veterans Health Administration., Patients: Hospitalized patients with PA-BSI in pre-COVID-19 (January 2009 to December 2019) and COVID-19 (January 2020 to June 2022) periods. Patients in the COVID-19 period were further stratified by the presence or absence of concomitant COVID-19 infection., Methods: We characterized trends in resistance, treatment, and mortality over the study period. Multivariable logistic regression and modified Poisson analyses were used to determine the association between COVID-19 and mortality among patients with PA-BSI. Additional predictors included demographics, comorbidities, disease severity, antimicrobial susceptibility, and treatment., Results: A total of 6,714 patients with PA-BSI were identified. Throughout the study period, PA resistance rates decreased. Mortality decreased during the pre-COVID-19 period and increased during the COVID-19 period. Mortality was not significantly different between pre-COVID-19 (24.5%, 95% confidence interval [CI] 23.3-28.6) and COVID-19 period/COVID-negative (26.0%, 95% CI 23.5-28.6) patients, but it was significantly higher in COVID-19 period/COVID-positive patients (47.2%, 35.3-59.3). In the modified Poisson analysis, COVID-19 coinfection was associated with higher mortality (relative risk 1.44, 95% CI 1.01-2.06). Higher Charlson Comorbidity Index, higher modified Acute Physiology and Chronic Health Evaluation score, and no targeted PA-BSI treatment within 48 h were also predictors of higher mortality., Conclusions: Higher mortality was observed in patients with COVID-19 coinfection among patients with PA-BSI. Future studies should explore this relationship in other settings and investigate potential SARS-CoV-2 and PA synergy., Competing Interests: FP receives grant funding and research support from Accelerate, Merck, and Pfizer. RAB receives grant funding and research support from NIH, VA, VenatoRx, Merck, Wockhardt, Entasis, and the Cystic Fibrosis Foundation. The other authors report no conflicts of interest., (© The Author(s) 2023.)

The combination of opioids and cocaine has been increasingly implicated in overdose fatalities, but it is unknown how much is intentional vs. fentanyl-adulterated drug supply. 2017-2019 data from the nationally representative National Survey on Drug Use and Health (NSDUH) was used. Variables included sociodemographics, health, and 30-day drug use. Opioid use captured heroin, and prescription pain reliever use not according to own doctor. Modified Poisson regressions were used to estimate prevalence ratios (PRs) for variables associated with opioid and cocaine use. Among the 167,444 responders, 817(0.49%) reported use of opioids on a regular or daily basis. Of these, 28% used cocaine ≥1 of prior 30 days, 11% >1 day. Of 332(0.20%) who used cocaine on a regular/daily basis, 48% used opioids ≥1 of prior 30 days, 25% >1 day. People with serious psychological distress were >6 times as likely to use both opioids and cocaine regularly/daily (PR = 6.48; 95% CI = [2.82-14.90]) and people who have never been married were 4 times as likely (PR = 4.17; 95% CI = [1.18-14.75]). Compared to those living in a small metropolitan region, people living in a large metropolitan region were >3 times as likely (PR = 3.29; 95% CI = [1.43-7.58]) and the unemployed were twice as likely (PR = 1.96; 95% CI = [1.03-3.73]). People with post-high school education were 53% less likely to use opioids and cocaine at least occasionally (PR = 0.47; 95% CI = [0.26-0.86]). People who use opioids or cocaine commonly choose to use the other. Knowing the characteristics of those most likely to use both should guide interventions for prevention and harm reduction., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Purpose: The clinical relevance of IgE-deficiency is not established. Previous studies have postulated a relationship between absent serum IgE and the incidence of specific malignancies. We sought to examine the relationship between undetectable total serum IgE (< 3 IU/mL) and first malignancy, considering both general all-cause malignancy risk and risk of specific malignancy subtypes in adult subjects., Methods: Retrospective cohort study at a single center of 39,965 adults aged 18 or older (median age 51, 65.1% female) with at least one serum total IgE measurement from 1998 to 2020. Analytics included chi 2 table and logistic regression modeling of the main outcome measures, which include diagnosis of first malignancy and first diagnosis of specific malignancy subtype., Results: Of the entire cohort, 2584 subjects (6.5%) developed a first malignancy and 2516 (6.3%) had an undetectable IgE. Of those with undetectable IgE levels, 8.9% developed a first malignancy versus 6.3% with detectable IgE measurements. After adjusting for risk factors, there was a significant association between undetectable IgE and risk/hazard of first malignancy (relative risk 1.49, 95% confidence interval (CI) 1.27-1.75) (hazard ratio 1.28, 95% CI 1.08-1.52). Results were similar in multiple sensitivity analyses. For type of malignancy developed, undetectable IgE was associated with increased risk of hematologic malignancy (relative risk 2.07, 95% CI 1.29-3.30) and skin malignancy (relative risk 1.52, 95% CI 1.13-2.05)., Conclusion: Compared to individuals with detectable IgE levels, patients with undetectable total serum IgE had increased risk and hazard of first malignancy in general, and increased risk of hematologic malignancy in particular., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Therapy resistance is a major challenge in the treatment of cancer. Here, we performed CRISPR-Cas9 screens across a broad range of therapies used in acute myeloid leukemia to identify genomic determinants of drug response. Our screens uncover a selective dependency on RNA splicing factors whose loss preferentially enhances response to the BCL2 inhibitor venetoclax. Loss of the splicing factor RBM10 augments response to venetoclax in leukemia yet is completely dispensable for normal hematopoiesis. Combined RBM10 and BCL2 inhibition leads to mis-splicing and inactivation of the inhibitor of apoptosis XIAP and downregulation of BCL2A1, an anti-apoptotic protein implicated in venetoclax resistance. Inhibition of splicing kinase families CLKs (CDC-like kinases) and DYRKs (dual-specificity tyrosine-regulated kinases) leads to aberrant splicing of key splicing and apoptotic factors that synergize with venetoclax, and overcomes resistance to BCL2 inhibition. Our findings underscore the importance of splicing in modulating response to therapies and provide a strategy to improve venetoclax-based treatments., Competing Interests: Declaration of interests E.M., E.C., M.J., C.B., C.-C.M., and D.M.B. are employees of Biosplice Therapeutics. O.A.-W. has served as a consultant for H3B Biomedicine, Foundation Medicine Inc., Merck, Prelude Therapeutics, and Janssen and is on the Scientific Advisory Board of Envisagenics Inc., AIChemy, Harmonic Discovery Inc., and Pfizer Boulder. O.A.-W. has received prior research funding from H3B Biomedicine, Nurix Therapeutics, and LOXO Oncology unrelated to the current manuscript. The remaining authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Screening for Barrett's esophagus (BE) with endoscopy plus forceps biopsy (FB) has poor compliance with the recommended Seattle protocol and fails to sample large areas of mucosa. This statistical modeling study estimates, for the first time, the actual frequency of missed BE cases by FB., Methods: Published, calibrated models in the literature were combined to calculate the age-specific prevalence of BE in white males with gastroesophageal reflux disease (GERD). We started with estimates of the prevalence of BE and GERD, and applied the relative risk for BE in patients with GERD based on the literature. This created estimates of the true prevalence of BE in white males with GERD by decade of life. The proportion of BE missed was calculated as the difference between the prevalence and the proportion with a positive screen., Results: The prevalence of BE in white males with GERD was 8.9%, 12.1%, 15.3%, 18.7% and 22.0% for the third through eighth decades of life. Even after assuming no false positives, missed cases of BE were about 50% when estimated for patients of ages 50 or 60 years, and over 60% for ages of 30, 40 or 70 years. Sensitivity analysis was done for all variables in the model calculations. For ages 50 and 60 years, this resulted in values from 30.3 to 57.3% and 36.4 to 60.9%., Conclusion: Screening for BE with endoscopy and FB misses approximately 50% of BE cases. More sensitive methods of BE detection or better adherence to the Seattle protocol are needed., (© 2022. The Author(s).)

Background: Ohio's age-adjusted opioid overdose fatality rate is double the national average. In an ever-evolving epidemic, it is crucial to monitor trends to inform public health interventions., Methods: A retrospective study was conducted using the Medical Examiner's decedent case files for all accidental opioid-related adult overdose deaths in Cuyahoga County (Cleveland), Ohio in 2017. Characterization of trends was based on autopsy/toxicology and first responder reports, medical records and death scene investigations., Results: Of 543 accidental opioid-related adult overdose fatalities, 64.1% died from 3+ drugs. The most common cause of death (COD) drugs included fentanyl (63.4%), heroin (44.4%), cocaine (37.0%) and carfentanil (35.0%). There were four times as many African American decedents as two years prior. Three or more COD drugs was >50% more common in those with fentanyl (Prevalence Ratio (PR) = 1.56[1.34-1.70]; p <.001) or carfentanil (PR = 1.51[1.33-1.70]; p <.001) as a COD drug, more common with a history of prescription drug abuse (PR = 1.16[1.02-1.33]; p =.025), but less common in divorced/widowed decedents (PR = 0.83[0.71-0.97]; p =.022). Carfentanil was nearly 4 times as prevalent in those with previous illicit drug use (PR = 3.88[1.09-13.70]; p =.025), and less common in those with previous medical history (PR = 0.72[0.55-0.94]; p =.016) or age 50+ (PR = 0.72[0.53-0.97]; p =.031)., Conclusions: Accidental opioid-related overdose fatalities in Cuyahoga County adults were dominated by 3+ COD drugs, with cocaine/fentanyl mixtures driving sharp increases in African American fatalities. Carfentanil was more prevalent in people fitting the profile of recreational drug use. This data can inform harm reduction interventions., Competing Interests: There are no conflicts of interest or personal or financial interests to declare., (© 2022 Published by Elsevier B.V.)

Background: There have been recent reports of myocarditis (including myocarditis, pericarditis or myopericarditis) as a side-effect of mRNA-based COVID-19 vaccines, particularly in young males. Less information is available regarding the risk of myocarditis from COVID-19 infection itself. Such data would be helpful in developing a complete risk-benefit analysis for this population., Methods: A de-identified, limited data set was created from the TriNetX Research Network, aggregating electronic health records from 48 mostly large U.S. Healthcare Organizations (HCOs). Inclusion criteria were a first COVID-19 diagnosis during the April 1, 2020 - March 31, 2021 time period, with an outpatient visit 1 month to 2 years before, and another 6 months to 2 years before that. Analysis was stratified by sex and age (12-17, 12-15, 16-19). Patients were excluded for any prior cardiovascular condition. Primary outcome was an encounter diagnosis of myocarditis within 90 days following the index date. Rates of COVID-19 cases and myocarditis not identified in the system were estimated and the results adjusted accordingly. Wilson score intervals were used for 95% confidence intervals due to the very low probability outcome., Results: For the 12-17-year-old male cohort, 6/6,846 (0.09%) patients developed myocarditis overall, with an adjusted rate per million of 450 cases (Wilson score interval 206 - 982). For the 12-15 and 16-19 male age groups, the adjusted rates per million were 601 (257 - 1,406) and 561 (240 - 1,313).For 12-17-year-old females, there were 3 (0.04%) cases of myocarditis of 7,361 patients. The adjusted rate was 213 (73 - 627) per million cases. For the 12-15- and 16-19-year-old female cohorts the adjusted rates per million cases were 235 (64 - 857) and 708 (359 - 1,397).The outcomes occurred either within 5 days (40.0%) or from 19-82 days (60.0%)., Conclusions: Myocarditis (or pericarditis or myopericarditis) from primary COVID19 infection occurred at a rate as high as 450 per million in young males. Young males infected with the virus are up 6 times more likely to develop myocarditis as those who have received the vaccine.

Given the convergence of the long and challenging development path for medical devices with the need for diagnostic capabilities for mild traumatic brain injury (mTBI/concussion), the effective role of public-private partnership (PPP) can be demonstrated to yield Food and Drug Administration (FDA) clearances and innovative product introductions. An overview of the mTBI problem and landscape was performed. A detailed situation analysis of an example of a PPP yielding an innovative product was further demonstrated. The example of PPP has led to multiple FDA clearances and product introductions in the TBI diagnostic product category where there was an urgent military and public need. Important lessons included defining the primary public and military health objective for new product introduction, the importance of the government-academia-industry PPP triad with a "collaboration towards solutions" Quality-by-Design (QbD) mindset to assure clinical validity with regulatory compliance, the development of device comparators and integration of measurements into a robust, evidence-based statistical and FDA pathway, and the utility of top-down, flexible, practical action while operating within governmental guidelines and patient safety., (© The Author(s) 2022.)

To frame the substantial prevalence of type 2 diabetes (T2D) as a 'Modern Preventable Pandemic' (MPP) and present certain replicable policy lessons from the COVID-19 crisis to address it. A literature and policy review was performed to analyze data about the COVID-19 and T2D pandemics to establish their multi-factorial health, social, and economic impacts. With the global prevalence of T2D tripling in the last two decades, T2D has become an MPP largely due to modifiable human behaviors. Certain successful elements of the response to the COVID-19 pandemic provide important lessons that can be adapted for the growing T2D MPP. With proper education and access to resources, it is possible to mitigate the T2D MPP through focused government policies as illustrated by many of the lessons of the COVID-19 pandemic response. Without such government intervention, the T2D MPP will continue to grow at an unsustainable pace with enormous health, social and economic implications. Immediate action is necessary. The scale of the T2D pandemic warrants a robust response in health policy as outlined through eight coordinated efforts; the lessons of the COVID-19 crisis should be studied and applied to the T2D MPP., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Since late 2014, fentanyl has become the major driver of opioid mortality in the United States. However, a descriptive analysis of fentanyl victims is limited. We studied the 2016 fentanyl and heroin overdose deaths and compared them to previously studied heroin-associated fatalities from 2012 over a wide range of demographic and investigative variables, including overdose scene findings, toxicology results, and prescription drug history. We observed a significant increase in fentanyl-related deaths (n = 421, 2016) versus heroin deaths (n = 160, 2012) but the baseline demographics between both cohorts remained similar. Victims were predominantly of ages 35-64 years (60%-64%), White (83%-85%), and male (73%-76%). 2016 fentanyl decedents were more likely to have naloxone administered upon overdose, and the majority still had a positive prescription history for a controlled substance. Toxicology data showed a decrease in mean morphine and 6-monoacetylmorphine concentrations when cointoxication with fentanyl occurred. Our study emphasizes the medical examiner's role as a public health data source and bridge between different stakeholders combating the opioid epidemic., (© 2021 American Academy of Forensic Sciences.)

Background: Wide area transepithelial sampling with three-dimensional computer-assisted analysis (WATS 3D ) is an adjunct to the standard random 4-quadrant forceps biopsies (FB, "Seattle protocol") that significantly increases the detection of Barrett's esophagus (BE) and associated neoplasia in patients undergoing screening or surveillance., Aims: To examine the cost-effectiveness of adding WATS 3D to the Seattle protocol in screening patients for BE., Methods: A decision analytic model was used to compare the effectiveness and cost-effectiveness of two alternative BE screening strategies in chronic gastroesophageal reflux disease patients: FB with and without WATS 3D . The reference case was a 60-year-old white male with gastroesophageal reflux disease (GERD). Effectiveness was measured by the number needed to screen to avert one cancer and one cancer-related death, and quality-adjusted life years (QALYs). Cost was measured in 2019 US$, and the incremental cost-effectiveness ratio (ICER) was measured in $/QALY using thresholds for cost-effectiveness of $100,000/QALY and $150,000/QALY. Cost was measured in 2019 US$. Cost and QALYs were discounted at 3% per year., Results: Between 320 and 337 people would need to be screened with WATS 3D in addition to FB to avert one additional cancer, and 328-367 people to avert one cancer-related death. Screening with WATS 3D costs an additional $1219 and produced an additional 0.017 QALYs, for an ICER of $71,395/QALY. All one-way sensitivity analyses resulted in ICERs under $84,000/QALY., Conclusions: Screening for BE in 60-year-old white male GERD patients is more cost-effective when WATS 3D is used adjunctively to the Seattle protocol than with the Seattle protocol alone.

Objective: Surgery is an effective but costly treatment for many patients with drug-resistant temporal lobe epilepsy (DR-TLE). We aim to evaluate whether, in the United States, surgery is cost-effective compared to medical management for patients deemed surgical candidates and whether surgical evaluation is cost-effective for patients with DR-TLE in general., Methods: We use a semi-Markov model to assess the cost-effectiveness of surgery and surgical evaluation over a lifetime horizon. We use second-order Monte Carlo simulations to conduct probabilistic sensitivity analyses to estimate variation in model output. We adopt both health care and societal perspectives, including direct health care costs (e.g., surgery, antiepileptic drugs) and indirect costs (e.g., lost earnings by patients and care providers.) We compare the incremental cost-effectiveness ratio to societal willingness to pay (∼$100,000 per quality-adjusted life-year [QALY]) to determine whether surgery is cost-effective., Results: Epilepsy surgery is cost-effective compared to medical management in surgically eligible patients by virtue of being cost-saving ($328,000 vs $423,000) and more effective (16.6 vs 13.6 QALY) than medical management in the long run. Surgical evaluation is cost-effective in patients with DR-TLE even if the probability of being deemed a surgical candidate is only 5%. From a societal perspective, surgery becomes cost-effective within 3 years, and 89% of simulations favor surgery over the lifetime horizon., Conclusion: For surgically eligible patients with DR-TLE, surgery is cost-effective. For patients with DR-TLE in general, referral for surgical evaluation (and possible subsequent surgery) is cost-effective. Patients with DR-TLE should be referred for surgical evaluation without hesitation on cost-effectiveness grounds., (© 2020 American Academy of Neurology.)

Cytomegalovirus (CMV) remains an important pathogen in the transplant population. As such, the US Food and Drug Administration has published a guidance to encourage and inform the development of therapeutics for the treatment and prevention of CMV disease in this population. This review summarizes important phase 3 trial design considerations for industry and provides rationale for some of the recommendations included in the guidance., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)