Adjunctive Use of Wide-Area Transepithelial Sampling-3D in Patients With Symptomatic Gastroesophageal Reflux Increases Detection of Barrett's Esophagus and Dysplasia.

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.

Increased Hazard Risk of First Malignancy in Adults with Undetectable Serum IgE: a Retrospective Cohort Study.

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 chi2 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.

High rate of missed Barrett's esophagus when screening with forceps biopsies.

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.

Wide Area Transepithelial Sampling with Computer-Assisted Analysis (WATS3D) Is Cost-Effective in Barrett's Esophagus Screening.

BACKGROUND: Wide area transepithelial sampling with three-dimensional computer-assisted analysis (WATS3D) 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 WATS3D 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 WATS3D. 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 WATS3D in addition to FB to avert one additional cancer, and 328-367 people to avert one cancer-related death. Screening with WATS3D 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 WATS3D is used adjunctively to the Seattle protocol than with the Seattle protocol alone.

Long-term reduction of health care costs and utilization after epilepsy surgery.

OBJECTIVE: To assess long-term direct medical costs, health care utilization, and mortality following resective surgery in persons with uncontrolled epilepsy. METHODS: Retrospective longitudinal cohort study of Medicaid beneficiaries with epilepsy from 2000 to 2008. The study population included 7,835 persons with uncontrolled focal epilepsy ages 18-64 years, with an average follow-up time of 5 years. Of these, 135 received surgery during the study period. To account for selection bias, we used risk-set optimal pairwise matching on a time-varying propensity score, and inverse probability of treatment weighting. Repeated measures generalized linear models were used to model utilization and cost outcomes. Cox proportional hazard was used to model survival. RESULTS: The mean direct medical cost difference between the surgical group and control group was $6,806 after risk-set matching. The incidence rate ratio of inpatient, emergency room, and outpatient utilization was lower among the surgical group in both unadjusted and adjusted analyses. There was no significant difference in mortality after adjustment. Among surgical cases, mean annual costs per subject were on average $6,484 lower, and all utilization measures were lower after surgery compared to before. SIGNIFICANCE: Subjects that underwent epilepsy surgery had lower direct medical care costs and health care utilization. These findings support that epilepsy surgery yields substantial health care cost savings.

Cost effectiveness of bronchial thermoplasty in patients with severe uncontrolled asthma.

RATIONALE: Based on its clinical effectiveness, bronchial thermoplasty (BT) was approved by the Food and Drug Administration in 2010 for the treatment of severe persistent asthma in patients 18 years and older whose asthma is not well-controlled with inhaled corticosteroids and long-acting beta-agonist medicines. OBJECTIVE: Assess the 10 year cost-effectiveness of BT for individuals with severe uncontrolled asthma. METHODS: Using a Markov decision analytic model, the cost-effectiveness of BT was estimated. The patient population involved a hypothetical cohort of 41-year-old patients comparing BT to usual care over a 10-year time frame. The main outcome measure was cost in 2013 dollars per additional quality adjusted life year (QALY). RESULTS: Treatment with BT resulted in 6.40 QALYs and $7512 in cost compared to 6.21 QALYs and $2054 for usual care. The incremental cost-effectiveness ratio for BT at 10 years was $29,821/QALY. At a willingness to pay per QALY of $50,000, BT continues to be cost effective unless the probability of severe asthma exacerbation drops below 0.63 exacerbation per year or the cost of BT rises above $10,384 total for all three bronchoscopic procedures needed to perform thermoplasty and to cover the entire bronchial tree (baseline = $6690). CONCLUSIONS: BT is a cost-effective treatment for asthmatics at high risk of exacerbations. Continuing to follow asthmatics treated with BT beyond 5 years will help inform longer efficacy and support its cost-effectiveness.

Ethical, Legal, and Social Implications of Personalized Genomic Medicine Research: Current Literature and Suggestions for the Future.

PURPOSE: This review identifies the prominent topics in the literature pertaining to the ethical, legal, and social issues (ELSI) raised by research investigating personalized genomic medicine (PGM). METHODS: The abstracts of 953 articles extracted from scholarly databases and published during a 5-year period (2008-2012) were reviewed. A total of 299 articles met our research criteria and were organized thematically to assess the representation of ELSI issues for stakeholders, health specialties, journals, and empirical studies. RESULTS: ELSI analyses were published in both scientific and ethics journals. Investigational research comprised 45% of the literature reviewed (135 articles) and the remaining 55% (164 articles) comprised normative analyses. Traditional ELSI concerns dominated the discourse including discussions about disclosure of research results. In fact, there was a dramatic increase in the number of articles focused on the disclosure of research results and incidental findings to research participants. Few papers focused on particular disorders, the use of racial categories in research, international communities, or special populations (e.g., adolescents, elderly patients, or ethnic groups). CONCLUSION: Considering that strategies in personalized medicine increasingly target individuals' unique health conditions, environments, and ancestries, further analysis is needed on how ELSI scholarship can better serve the increasingly global, interdisciplinary, and diverse PGM research community.

Dietary intake of calcium and magnesium and the metabolic syndrome in the National Health and Nutrition Examination (NHANES) 2001-2010 data.

Higher dietary intakes of Mg and Ca, individually, have been associated with a decreased risk for the metabolic syndrome (MetSyn). Experimental studies suggest that a higher intra-cellular ratio of Ca:Mg, which may be induced by a diet high in Ca and low in Mg, may lead to hypertension and insulin resistance. However, no previous epidemiological studies have examined the effects of the combined intake of Mg and Ca on MetSyn. Thus, we evaluated the association between dietary intakes of Ca and Mg (using 24-h recalls), independently and in combination, and MetSyn in the National Health and Nutrition Examination Study 2001-2010 data, which included 9148 adults (4549 men and 4599 women), with complete information on relevant nutrient, demographic, anthropometric and biomarker variables. We found an inverse association between the highest (>355 mg/d) v. the lowest (<197 mg/d) quartile of Mg and MetSyn (OR 0.70; 95% CI 0.57, 0.86). Women who met the RDA for both Mg (310-320 mg/d) and Ca (1000-1200 mg/d) had the greatest reduced odds of MetSyn (OR 0.59; 95% CI 0.45, 0.76). In men, meeting the RDA for Mg (400-420 mg/d) and Ca (1000-1200 mg/d), individually or in combination, was not associated with MetSyn; however, men with intakes in the highest quartile for Mg (≥ 386 mg/d) and Ca (≥ 1224 mg/d) had a lower odds of MetSyn (OR 0.74; 95% CI 0.59, 0.93). Our results suggest that women who meet the RDA for Mg and Ca have a reduced odds of MetSyn but men may require Ca levels higher than the RDA to be protected against MetSyn.

Impact of interferon free regimens on clinical and cost outcomes for chronic hepatitis C genotype 1 patients.

BACKGROUND & AIMS: Hepatitis C (HCV) is a common cause of chronic liver disease worldwide. Current standard treatment for genotype-1 patients uses a triple combination of pegylated-interferon alpha (IFN), ribavirin (RBV) and a direct-acting antiviral agent (DAA) with 75-80% sustained virologic response (SVR) rates. The aim is to determine cost-effectiveness of staging-guided vs. treat all HCV genotype-1 patients with interferon-based vs. interferon-free regimens. METHODS: A decision analytic Markov model simulating patients until death compared four strategies for treating HCV genotype-1: Triple therapy (IFN, RBV, DAA) with staging-guidance or treat all, and oral IFN-free regimen with staging-guidance or treat all. Strategies with staging initiated treatment at fibrosis stages F2-F4, with staging repeated every 5 years until age 70. The reference case was a treatment-naïve 50-year-old. Analysis was repeated for 50% increase in cost of oral therapy. Effectiveness was measured in quality-adjusted life years (QALYs). RESULTS: Treatment of all patients with oral IFN-free regimen was the most cost-effective strategy, with an ICER of $15,709/QALY at baseline cost of oral therapy. The ICER remained below $50,000/QALY in sensitivity analyses for baseline and +50% cost of oral therapy scenarios. The treat all strategy was also the most effective strategy; associated with the lowest risk of developing advanced liver disease. CONCLUSIONS: Treating all HCV patients with oral IFN-free regimen reduced the number of patients developing advanced liver disease and increased life expectancy. Additionally, IFN-free regimen without staging may be the most cost-effective approach for treating HCV genotype-1 patients. The efficacy and safety of these regimens must be confirmed using randomized clinical trials.

Key actors' perspectives on cost-effectiveness analysis in Uganda: a cross-sectional survey.

BACKGROUND: Cost effectiveness analysis (CEA) is a useful tool for allocation of constrained resources, yet CEA methodologies are rarely taught or implemented in developing nations. We aimed to assess exposure to, and interest in CEA, and identify barriers to implementation in Uganda. METHODS: A cross-sectional survey was carried out in Uganda using a newly developed self-administered questionnaire (via online and paper based approaches), targeting the main health care actors as identified by a previous study. RESULTS: Overall, there was a 68% response rate, with a 92% (69/75) response rate among the paper-based respondents compared to a 40% (26/65) rate with the online respondents. Seventy eight percent (74/95) of the respondents had no exposure to CEA. None of those with a master of medicine degree had any CEA exposure, and 80% of technical officers, who are directly involved in policy formulation, had no CEA exposure. Barriers to CEA identified by more than 50% of the participants were: lack of information technology (IT) infrastructure (hardware and software); lack of local experts in the field of CEA; lack of or limited local data; limited CEA training in schools; equity or ethical issues; and lack of training grants incorporating CEA. 93% reported a lot of interest in learning to conduct CEA, and over 95% felt CEA was important for clinical decision making and policy formulation. CONCLUSIONS: Among health care actors in Uganda, there is very limited exposure to, but substantial interest in conducting CEA and including it in clinical decision making and health care policy formation. Capacity to undertake CEA needs to be built through incorporation into medical training and use of regional approaches.

14-Year Epidemiologic study of Pseudomonas aeruginosa bloodstream infection incidence and resistance in the Veterans Health Administration system, 2009-2022.

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.

Intentional use of both opioids and cocaine in the United States.

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.

Association of COVID-19 coinfection with increased mortality among patients with Pseudomonas aeruginosa bloodstream infection in the Veterans Health Administration system.

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.

Trends in opioid overdose fatalities in Cuyahoga County, Ohio: Multi-drug mixtures, the African-American community and carfentanil.

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.

Risk of Myocarditis from COVID-19 Infection in People Under Age 20: A Population-Based Analysis.

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.

Intergenerational volunteering and quality of life for persons with mild to moderate dementia: results from a 5-month intervention study in the United States.

OBJECTIVES: To evaluate whether a structured intergenerational volunteering intervention would enhance quality of life (QOL) for persons with mild to moderate dementia. METHODS: Fifteen participants were randomized into intervention and control groups. The intervention group participated in hour-long structured volunteer sessions with a kindergarten class and an older elementary class in alternating weeks during a 5-month interval. Data on cognitive functioning, stress, depression, sense of purpose, and sense of usefulness were collected at baseline and at the close of the intervention. Change scores were computed and analyzed for all variables. RESULTS: There was a significant decrease in stress for the intervention group. CONCLUSIONS: This study adds preliminary findings that intergenerational volunteering interventions might contribute to QOL for persons with dementia, in part through a reduction in stress.

The fentanyl phase of the opioid epidemic in Cuyahoga County, Ohio, United States.

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.

All-cause health care utilization and costs associated with newly diagnosed multiple sclerosis in the United States.

BACKGROUND: Multiple sclerosis (MS) is a costly and crippling neurologic disease. Approximately 250,000 to 400,000 persons in the United States are currently diagnosed with MS. Most individuals experience their first symptoms between the ages of 20 and 40 years; therefore, this disease may have substantial impact over many years of life on health, quality of life, productivity, and employment. Whereas a number of studies have utilized a cross-sectional design to evaluate the costs associated with MS, no study has used a large administrative claims database to analyze the direct costs associated with newly diagnosed MS. OBJECTIVE: To estimate the additional health care utilization and costs in otherwise healthy patients with newly diagnosed MS. METHODS: This was a retrospective cohort analysis of the Medstat MarketScan Commercial Claims and Encounters database, which is composed of medical and pharmacy claims for approximately 8 million beneficiaries from 45 U.S. commercial health plans. Cases extracted from the database included adults aged 18 to 64 years with either (a) at least 2 medical claims with a diagnosis of MS (ICD-9-CM code 340) in any diagnosis field on the claim or (b) 1 prescription (medical or pharmacy) claim for injectable MS drug therapy (interferon beta-1a, interferon beta- 1b, glatiramer acetate) for dates of service between January 1, 2004, and December 31, 2006. Natalizumab was not used to identify MS cases, but was used to exclude potential comparison group subjects. The index date for patients with MS was the first qualifying diagnosis or pharmacy claim. Each MS patient was matched to 5 "healthy comparison" cases without MS diagnoses or treatment using the following variables: region, insurance type, gender, relation to employee, age, and enrollment period. Cases with any condition listed in the Charlson Comorbidity Index were excluded from both the MS and "healthy comparison" cohorts. Each "healthy comparison" case was assigned the index date of the matching MS patient. Continuous enrollment 12 months pre- and post-index was required for both the MS and "healthy comparison" groups. Costs broken down by type of utilization were adjusted to 2010 dollars using the appropriate medical component of the Consumer Price Index. Use of services and costs were compared using chi-square, t-tests, parametric and nonparametric tests. RESULTS: 1,411 MS cases (65.6% female) were matched to 7,055 "healthy comparison" cases (65.6% female). In the analyses of all-cause health care services during the 12-month post-index period, MS patients were significantly more likely to use all categories of health services examined. Compared with the "healthy comparison" group, new MS patients were 3.5 times as likely to be hospitalized (15.2% vs. 4.3% for MS vs. comparison, respectively), twice as likely to have at least 1 emergency room (ER) visit (25.5% vs. 12.2%) and 2.4 times as likely to have at least 1 visit for physical, occupational, or speech therapy (23.7% vs. 9.9%; P < 0.001 for all comparisons). MS patients also had higher mean 12-month costs related to each category of service (inpatient services $4,110 vs. $836; radiology services $1,693 vs. $259; ER $432 vs. $189; office visits $849 vs. $310; therapies $295 vs. $81, respectively; all P values < 0.001). Total mean 12-month all-cause health care costs were significantly higher for MS patients than for the "healthy comparison" group ($18,829 vs. $4,038, respectively, P < 0.001). Claims attributed to MS by diagnosis code in any field on the claim or use of an MS injectable drug accounted for a mean cost of $8,839 (46.9%), and MS injectable drugs accounted for $4,573 (24.3%) of total all-cause health care costs. CONCLUSIONS: Newly diagnosed MS patients have significantly higher rates of hospitalizations, radiology services, and ER and outpatient visits compared with non-MS "healthy comparison" patients. MS presents a considerable burden to the U.S. health care system within the first year of diagnosis.