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.

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.

WATS 3D : An Interobserver Study of Barrett's Esophagus-Associated Dysplasia Among Gastrointestinal Pathologists.

INTRODUCTION: Wide-area transepithelial sampling with 3-dimensional computer-assisted analysis (WATS 3D ) has been shown to increase the detection rate of dysplasia (and intestinal metaplasia) in patients with Barrett's esophagus (BE). The purpose of this study was to evaluate the interobserver variability and accuracy of diagnosing BE-associated dysplasia in WATS 3D specimens among gastrointestinal (GI) pathologists without prior experience with this technology. METHODS: Five GI pathologists underwent a 4-hour in-person (at microscope) and virtual training session and then evaluated digital images of discrete cellular foci from 60 WATS 3D cases with BE (20 nondysplastic BE [NDBE], 20 low-grade dysplasia [LGD], and 20 high-grade dysplasia/esophageal adenocarcinoma [HGD/EAC]). Each case consisted of 1 hematoxylin and eosin-stained image (cell block), and 1 liquid cytology or papanicolaou-stained smear image (120 images in total). RESULTS: The overall kappa value among the 5 study pathologists was excellent (overall kappa = 0.93; kappa = 0.93 and 0.97 for cell block and smear specimens, respectively). There were no significant differences noted in kappa values in interpretation of the cell block vs smear specimens or in any of the individual diagnostic categories when the latter were evaluated separately. Furthermore, agreement was perfect (100%) regarding detection of neoplasia (either LGD, HGD, or EAC). Diagnoses were made with complete confidence in 91% of instances. DISCUSSION: We conclude that GI pathologists, without any prior experience in interpretation of WATS 3D specimens, can undergo a short training session and then diagnose these specimens with a very high level of accuracy and reproducibility.

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.

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.

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.

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.

The case for "investigate all": Assessing the cost-effectiveness of investigating no CODIS hit cases in a sexual assault kit initiative.

An increasing number of US jurisdictions have begun to submit their previously untested sexual assault kits (SAKs) for DNA testing. However, best practices for what should happen after testing are not well established. Should all cases be investigated regardless of the testing outcome or only those that returned a DNA hit? We examine an early-adopter jurisdiction that has completed testing and investigating all 5165 previously never tested kits. We explore and compare the criminal justice outcomes and cost-effectiveness of investigating: all cases, those with CODIS hits, and those without CODIS hits. Findings indicate the SAK initiative produced a cost savings to the community: $26.48 million ($5127 p/kit) after the inclusion of tangible and intangible costs of future sexual assaults averted through convictions, of which $9.99 million ($1934 p/kit) was from also investigating no CODIS hit cases. When considering only the costs to law enforcement, investigating all cases cost $12,000 p/additional conviction. Findings also illustrate the cost-effectiveness of investigating no CODIS hits cases and support an "investigate all" approach. This study enhances our understanding of the economic value of what comes after testing kits and investigating cases and provides a framework for jurisdictions for prioritizing resources and maximizing outcomes from testing.

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.

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.

Cost-effectiveness of surgery for drug-resistant temporal lobe epilepsy in the US.

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.

Cost and Cost-Effectiveness of Image Guided Partial Breast Irradiation in Comparison to Hypofractionated Whole Breast Irradiation.

PURPOSE: Hypofractionated whole breast irradiation (HWBI) and accelerated partial breast irradiation (APBI) represent two adjuvant radiation therapy options after breast-conserving surgery. We performed a cost and cost-effectiveness analysis of an external beam image guided APBI technique compared with HWBI. METHODS AND MATERIALS: HWBI was defined as 40 Gy in 15 fractions to the whole breast with or without a 10-Gy/5-fraction boost. APBI was 30 Gy in 5 fractions per Livi et al and was evaluated as both intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy. The decision analytical model measured effectiveness in quality-adjusted life years. Micro-costing was conducted to estimate the true cost of the different treatment regimens, and incremental cost-effectiveness analysis was performed. RESULTS: Based on micro-costing, the cost of HWBI was $4551 with boost and $3666 without boost, compared with $2966 for APBI. Including indirect costs, HWBI with boost cost $6160, HWBI without boost cost $4940, and APBI cost $3569. Cost savings for APBI compared with HWBI with and without boost was $1585 and $700 based on direct costs and $2591 and $1371 including indirect costs. APBI was also more effective, at 0.2300 quality-adjusted life years compared with 0.2289 for HWBI with or without boost. Thus, APBI was both less costly and more effective. Basing cost on Medicare reimbursement (IMRT) leads to APBI again dominating HWBI, but basing cost for APBI on reimbursement billed as stereotactic body radiation therapy leads to HWBI being far more cost-effective. CONCLUSIONS: Image guided partial breast irradiation is less costly to deliver and has slightly improved efficacy compared with HWBI, with or without a boost. IMRT APBI should be considered a standard-of-care option in appropriately selected patients based on efficacy and value.

Cost-effectiveness of nivolumab for recurrent or metastatic head and neck cancer☆.

OBJECTIVE: Nivolumab is the first drug to demonstrate a survival benefit for platinum-refractory recurrent or metastatic head and neck cancer. We performed a cost-utility analysis to assess the economic value of nivolumab as compared to alternative standard agents in this context. MATERIALS AND METHODS: Using data from the CheckMate 141 trial, we constructed a Markov simulation model from the US payer's perspective to evaluate the cost-effectiveness of nivolumab compared to physician choice of either cetuximab, methotrexate or docetaxel. Alternative strategies considered included: single-agent cetuximab, methotrexate or docetaxel, or first testing for PD-L1 to select for nivolumab. Costs were extracted from Medicare and utilities from the literature and CheckMate. Probabilistic sensitivity analysis (PSA) was used to evaluate parameter uncertainty. $100,000/QALY was the primary threshold for cost-effectiveness. RESULTS: When comparing nivolumab to the standard arm of CheckMate, nivolumab demonstrated an incremental cost-effectiveness ratio (ICER) of $140,672/QALY. When comparing standard therapies, methotrexate was the most cost-effective with similar results for docetaxel. Nivolumab was cost-effective compared to single-agent cetuximab (ICER $89,786/QALY). Treatment selection by PD-L1 immunohistochemistry did not markedly improve the cost-effectiveness of nivolumab. Factors likely to positively impact the cost-effectiveness of nivolumab include better baseline quality-of-life, poor tolerability of standard treatments and/or a lower cost of nivolumab. CONCLUSIONS: Nivolumab is preferred to single-agent cetuximab but requires a willingness-to-pay of at least $150,000/QALY to be considered cost-effective when compared to docetaxel or methotrexate. Selection by PD-L1 does not markedly improve the cost-effectiveness of nivolumab. This informs patient selection and clinical care-path development.

Health impact and cost-effectiveness of a domestically-produced rotavirus vaccine in India: A model based analysis.

BACKGROUND: Currently, Indian officials are incorporating a domestically manufactured rotavirus vaccine (based on the 116E rotavirus strain) into the country's universal immunization program; this vaccine will cost significantly less than western rotavirus vaccines. Here, we examine the public health impact, cost, and cost-effectiveness of universal vaccination in India using the 116E vaccine. This work will allow comparison of universal 116E vaccination with other approaches to child mortality reduction, shed light on the future burden of rotavirus disease in India, and help stakeholders understand future resource needs. METHODS: Using information from published literature, we developed a dynamic simulation model of rotavirus transmission, natural history, and related utilization among Indian infants followed until age five. Infection risk depended on the degree of viral shedding in the population. Infection risk and severity were influenced by age, number of previous infections, and vaccination history. Probabilities of inpatient and outpatient health services utilization depended on symptom severity. With the model, we compared a strategy of nationwide 116E vaccination to one of no vaccination. Costs were considered from the perspective of all payers (including families) and from the societal perspective. RESULTS: We estimated that an established 116E vaccination program would reduce symptomatic rotavirus infection by 13.0%, while reducing population-wide rotavirus mortality by 34.6% (over 34,000 lives annually). Rotavirus outpatient visits would decline by 21.3%, and hospitalization would decline by 28.1%. The cost per disability-adjusted life year (DALY) averted was estimated at 3,429 Rupees (approximately $56). Predicted mortality reduction in children born during the first five years of vaccination implementation was nearly identical to that in children born in later years (34.4% versus 34.6%). CONCLUSIONS: 116E vaccination of Indian infants would likely substantially reduce rotavirus-related morbidity, mortality, and utilization at a cost considered highly cost-effective by standard criteria. Nearly the entire mortality reduction benefit of vaccination was attributable to direct protection of those vaccinated, as opposed to indirect "herd immunity" effects.

Exploring maternal attitudes towards adolescent contraception: implications for use of LARC.

Introduction Maternal attitudes have been shown to impact adolescent girls' sexual decision making and attitudes towards contraception. Given the potential for maternal influence on adolescent contraceptive use, we undertook an exploratory study of mothers' perceptions of the maternal role in adolescent contraceptive decision making, and maternal perceptions of long acting reversible contraceptives (LARC) for adolescent girls. Materials and methods We utilized a mixed methods study design. Acceptability of contraceptive methods and attitudes towards adolescent contraceptive use were assessed using a paper survey of 162 mothers of girls aged 11-19 years in Cleveland, Ohio, USA. Seven survey participants completed subsequent semi-structured interviews, which were analyzed using grounded theory methodology. Results Pills, condoms and injections were most frequently selected as acceptable by 55.4%, 55.4%, and 51.6% of women, respectively. One or more LARC methods were selected by 16.6% of the women. Of those (94.4%) agreed or strongly agreed that, "It is expected of me to make sure that my daughter knows about birth control methods." Important themes that emerged during interviews were the responsibility mothers felt to help their daughters navigate contraception options, appreciation of the effectiveness of LARC methods and concerns about the use of those methods by teenagers due to the invasiveness. Conclusion Our data suggest that mothers want to be involved and support adolescent decision making about contraceptives. We also found that mothers viewed LARC as less acceptable than other forms of birth control for adolescents and have specific concerns about LARC. These results suggest directions for future work to better characterize the impact of maternal attitudes on adolescent LARC use.