Background Yearly influenza immunization is recommended for immunocompromised (IC) individuals, although immune responses are lower than that for the non-immunocompromised and the data on vaccine effectiveness (VE) in the IC is scarce. We evaluated VE against influenza-associated hospitalization among IC adults.Methods We analyzed data from adults ≥ 18 years hospitalized with acute respiratory illness (ARI) during the 2017-2018 influenza season at 10 hospitals in the United States. IC adults were identified using pre-specified case-definitions, utilizing electronic medical record data. VE was evaluated with a test-negative case-control design using multivariate logistic regression with PCR-confirmed influenza as the outcome and vaccination status as the exposure, adjusting for age, enrolling site, illness onset date, race, days from onset to specimen collection, self-reported health, and self-reported hospitalizations.Results Of 3,524 adults hospitalized with ARI, 1,210 (34.3%) had an immunocompromising condition. IC adults were more likely to be vaccinated than non-IC (69.5% vs 65.2%), and less likely to have influenza (22% vs 27.8%). The mean age did not differ among IC and non-IC (61.4 vs 60.8 years old). The overall VE against influenza hospitalization, including immunocompetent adults, was 33% (95% CI, 21% to 44%). VE among IC vs non-IC adults was lower at 5% (−29% to 31%) vs. 41% (27% to 52%) (p<0.05 for interaction term).Conclusions VE in one influenza season was very low among IC individuals. Future efforts should include evaluation of VE among the different immunocompromising conditions and whether enhanced vaccines improve the suboptimal effectiveness among the immunocompromised.Competing Interest StatementDBM has received personal fees from Sequris, Pfizer, and Sanofi Pasteur, and grants from Pfizer. JF reports non-financial support from the Institute for Influenza Epidemiology. RKZ has received grants from Sanofi Pasteur and Merck & Co. All other authors report no potential conflicts.Clinical TrialThis study was not registered in ClinicalTrials.gov because it doesn't meet NIH's definition of a clinical trial.Funding StatementThis study was funded by the CDC (cooperative agreement IP15-002). Vanderbilt also received support from CTSA award number UL1 TR002243 from the National Center for Advancing Translational Sciences.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The study protocol was reviewed by the Institutional Review Board at each participating institution and CDC, as detailed below: CDC's IRB: ethical approval given University of Pittsburgh IRB: ethical approval given University of Michigan IRB: ethical approval given Baylor Scott & White Health IRB: ethical approval given Vanderbilt University IRB: ethical approval given All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData may be made available after completion of the study.

BACKGROUND: Current understanding of severe RSV infections in adults is limited by clinical under-recognition. We compared the prevalence, clinical characteristics, and outcomes of RSV infections vs influenza in adults hospitalized with acute respiratory illnesses in a prospective national surveillance network. METHODS: Hospitalized adults who met a standardized ARI case definition were prospectively enrolled across three respiratory seasons from hospitals participating across all sites of the U.S. Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN, 2016-2019). All participants were tested for RSV and influenza by RT-PCR. Multivariable logistic regression was used to test associations between laboratory-confirmed infection and characteristics and clinical outcomes. RESULTS: Among 10,311 hospitalized adults, 6% tested positive for RSV (n=622), 18.8% positive for influenza (n=1,940), and 75.1% negative for RSV and influenza (n=7,749). Congestive Heart Failure (CHF) or Chronic Obstructive Pulmonary Disease (COPD) was more frequent among adults with RSV than influenza (CHF: 37.3% vs. 28.8%, p<0.0001; COPD: 47.6% vs. 35.8%, p<0.0001). Patients with RSV more frequently had longer admissions [OR=1.38 (95% CI: 1.06-1.80) for stays >one week] and mechanical ventilation [OR=1.45 (95% CI: 1.09-1.93)] compared with influenza, but not compared to the influenza negative group [OR=1.03 (95% CI: 0.82-1.28); OR=1.17 (0.91-1.49), respectively.]. CONCLUSIONS: The prevalence of RSV across three recent respiratory illness seasons was considerable. Our findings suggest those with RSV might incur worse outcomes than influenza in hospitalized adults and frequently have pre-existing cardiopulmonary conditions. This study informs future vaccination strategies and underscores a need for RSV surveillance among adults experiencing severe ARI.

A robust epidemic-prone disease surveillance system is a critical component of public health infrastructure and supports compliance with the International Health Regulations (IHR). One digital health platform that has been implemented in numerous low- and middle-income countries is the District Health Information System Version 2 (DHIS2). In 2015, in the wake of the Ebola epidemic, the Ministry of Health in Guinea established a strategic plan to strengthen its surveillance system, including adoption of DHIS2 as a health information system that could also capture surveillance data. In 2017, the DHIS2 platform for disease surveillance was piloted in two regions, with the aim of ensuring the timely availability of quality surveillance data for better prevention, detection, and response to epidemic-prone diseases. The success of the pilot prompted the national roll-out of DHIS2 for weekly aggregate disease surveillance starting in January 2018. In 2019, the country started to also use the DHIS2 Tracker to capture individual cases of epidemic-prone diseases. As of February 2020, for aggregate data, the national average timeliness of reporting was 72.2%, and average completeness 98.5%; however, the proportion of individual case reports filed was overall low and varied widely between diseases. While substantial progress has been made in implementation of DHIS2 in Guinea for use in surveillance of epidemic-prone diseases, much remains to be done to ensure long-term sustainability of the system. This paper describes the implementation and outcomes of DHIS2 as a digital health platform for disease surveillance in Guinea between 2015 and early 2020, highlighting lessons learned and recommendations related to the processes of planning and adoption, pilot testing in two regions, and scale up to national level.

At nine US hospitals that enrolled children hospitalized with acute respiratory illness (ARI) during 2015-2016 through 2017-2018 influenza seasons, 50% of children with ARI received clinician-initiated testing for influenza and 35% of cases went undiagnosed due to lack of clinician-initiated testing. Marked heterogeneity in testing practice was observed across sites.

BACKGROUND: Evidence for vaccine effectiveness (VE) against influenza-associated pneumonia has varied by season, location, and strain. We estimate VE against hospitalization for radiographically identified influenza-associated pneumonia during 2015-2016 to 2017-2018 seasons in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN). METHODS: Among adults aged ≥18 years admitted to 10 US hospitals for acute respiratory illness (ARI), clinician-investigators used keywords from reports of chest imaging performed during 3 days around hospital admission to assign a diagnosis of 'definite/probable pneumonia'. We used a test-negative design to estimate VE against hospitalization for radiographically identified laboratory-confirmed influenza-associated pneumonia, comparing RT-PCR confirmed influenza cases with test-negative subjects. Influenza vaccination status was documented in immunization records or self-reported, including date and location. Multivariable logistic regression models were used to adjust for age, site, season, calendar-time, and other factors. RESULTS: Of 4,843 adults hospitalized with ARI included in the primary analysis, 266 (5.5%) had 'definite/probable pneumonia' and confirmed influenza. Adjusted VE against hospitalization for any radiographically confirmed influenza-associated pneumonia was 38% (95% confidence interval [CI]): 17%-53%); by type/subtype, it was 74% (95% CI: 52%-87%), influenza A (H1N1)pdm09; 25% (-15% to 50%), A (H3N2); and 23% (95% CI: -32% to 54%), influenza B. Adjusted VE against intensive care for any influenza was 57% (95% CI, 19%-77%). CONCLUSIONS: Influenza vaccination was modestly effective among adults in preventing hospitalizations and the need for intensive care associated with influenza pneumonia. VE was significantly higher against A (H1N1)pdm09 and was low against A (H3N2) and B.

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) is frequently compared with influenza. The Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) conducts studies on the etiology and characteristics of U.S. hospitalized adults with influenza. It began enrolling patients with COVID-19 hospitalizations in March 2020. Patients with influenza were compared with those with COVID-19 in the first months of the U.S. epidemic. METHODS: Adults aged ≥ 18 years admitted to hospitals in 4 sites with acute respiratory illness were tested by real-time reverse transcription polymerase chain reaction for influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19. Demographic and illness characteristics were collected for influenza illnesses during 3 seasons 2016-2019. Similar data were collected on COVID-19 cases admitted before June 19, 2020. RESULTS: Age groups hospitalized with COVID-19 (n = 914) were similar to those admitted with influenza (n = 1937); 80% of patients with influenza and 75% of patients with COVID-19 were aged ≥50 years. Deaths from COVID-19 that occurred in younger patients were less often related to underlying conditions. White non-Hispanic persons were overrepresented in influenza (64%) compared with COVID-19 hospitalizations (37%). Greater severity and complications occurred with COVID-19 including more ICU admissions (AOR = 15.3 [95% CI: 11.6, 20.3]), ventilator use (AOR = 15.6 [95% CI: 10.7, 22.8]), 7 additional days of hospital stay in those discharged alive, and death during hospitalization (AOR = 19.8 [95% CI: 12.0, 32.7]). CONCLUSIONS: While COVID-19 can cause a respiratory illness like influenza, it is associated with significantly greater severity of illness, longer hospital stays, and higher in-hospital deaths.

Adults aged ≥65 years are at increased risk for severe outcomes from COVID-19 and were identified as a priority group to receive the first COVID-19 vaccines approved for use under an Emergency Use Authorization (EUA) in the United States (1-3). In an evaluation at 24 hospitals in 14 states,* the effectiveness of partial or full vaccination(†) with Pfizer-BioNTech or Moderna vaccines against COVID-19-associated hospitalization was assessed among adults aged ≥65 years. Among 417 hospitalized adults aged ≥65 years (including 187 case-patients and 230 controls), the median age was 73 years, 48% were female, 73% were non-Hispanic White, 17% were non-Hispanic Black, 6% were Hispanic, and 4% lived in a long-term care facility. Adjusted vaccine effectiveness (VE) against COVID-19-associated hospitalization among adults aged ≥65 years was estimated to be 94% (95% confidence interval [CI] = 49%-99%) for full vaccination and 64% (95% CI = 28%-82%) for partial vaccination. These findings are consistent with efficacy determined from clinical trials in the subgroup of adults aged ≥65 years (4,5). This multisite U.S. evaluation under real-world conditions suggests that vaccination provided protection against COVID-19-associated hospitalization among adults aged ≥65 years. Vaccination is a critical tool for reducing severe COVID-19 in groups at high risk.

We observed decreased effectiveness of influenza vaccine with increasing time since vaccination for prevention of influenza A(H3N2), influenza A(H1N1)pdm09, and influenza B(Yamagata)-associated hospitalizations among adults. Maximum VE was observed shortly after vaccination, followed by an absolute decline in VE of about 8 to 9% per month post-vaccination.

BACKGROUND: Chlamydia, gonorrhea, and syphilis are common, treatable sexually transmitted infections (STIs) that are highly prevalent in the general U.S. population. Costs associated with diagnosing and treating these conditions for individual states' Medicaid participants are unknown. The purpose of this study was to estimate the cost of screening and treatment for three common STIs for state Medicaid program budgets in Maryland and South Carolina. METHODS: A retrospective, cross-sectional study was conducted using Medicaid administrative claims data over a two-year period. Claims were included based on the presence of one of the three study conditions in either diagnosis or procedure codes. Descriptive analyses were used to characterize the participant population and expenditures for services provided. RESULTS: Total Medicaid expenditures for STI care in state fiscal years 2016 and 2017 averaged $43.5 million and $22.3 million for each year in Maryland and South Carolina, respectively. Maryland had a greater proportion of costs associated with outpatient hospital and laboratory settings. Costs for care provided in the emergency department were highest in South Carolina. CONCLUSIONS: Diagnosis and treatment of commonly reported STIs may have a considerable financial impact on individual state Medicaid programs. Public health activities directed at STI prevention are important tools for reducing these costs to states.

BACKGROUND: Yearly influenza immunization is recommended for immunocompromised (IC) individuals, although immune responses are lower than that for the non-immunocompromised and the data on vaccine effectiveness (VE) in the IC is scarce. We evaluated VE against influenza-associated hospitalization among IC adults. METHODS: We analyzed data from adults ≥ 18 years hospitalized with acute respiratory illness (ARI) during the 2017-2018 influenza season at 10 hospitals in the United States. IC adults were identified using pre-specified case-definitions, utilizing electronic medical record data. VE was evaluated with a test-negative case-control design using multivariable logistic regression with PCR-confirmed influenza as the outcome and vaccination status as the exposure, adjusting for age, enrolling site, illness onset date, race, days from onset to specimen collection, self-reported health, and self-reported hospitalizations. RESULTS: Of 3,524 adults hospitalized with ARI, 1,210 (34.3%) had an immunocompromising condition. IC adults were more likely to be vaccinated than non-IC (69.5% vs 65.2%), and less likely to have influenza (22% vs 27.8%). The mean age did not differ among IC and non-IC (61.4 vs 60.8 years old). The overall VE against influenza hospitalization, including immunocompetent adults, was 33% (95% CI, 21% to 44%). VE among IC vs non-IC adults was lower at 5% (-29% to 31%) vs. 41% (27% to 52%) (p<0.05 for interaction term). CONCLUSIONS: VE in one influenza season was very low among IC individuals. Future efforts should include evaluation of VE among the different immunocompromising conditions and whether enhanced vaccines improve the suboptimal effectiveness among the immunocompromised.

We estimated vaccine effectiveness for prevention of influenza-associated hospitalizations among adults during the 2018-2019 influenza season. Adults admitted with acute respiratory illness to 14 hospitals of the US Hospitalized Adult Influenza Vaccine Effectiveness Network and testing positive for influenza were cases; patients testing negative were controls. Vaccine effectiveness was estimated using logistic regression and inverse probability of treatment weighting. We analyzed data from 2863 patients with mean age of 63 years. Adjusted VE against influenza A(H1N1)pdm09-associated hospitalization was 51% (95%CI 25, 68). Adjusted VE against influenza A(H3N2) virus-associated hospitalization was -2% (95%CI -65, 37) and differed significantly by age, with VE of -130% (95% CI -374, -27) among adults 18 to ≤56 years of age. Although vaccination halved the risk of influenza-A(H1N1)pdm09-associated hospitalizations, it conferred no protection against influenza A(H3N2)-associated hospitalizations. We observed negative VE for young-and middle-aged adults but cannot exclude residual confounding as a potential explanation.

BACKGROUND: Influenza causes significant morbidity and mortality and stresses hospital resources during periods of increased circulation. We evaluated the effectiveness of the 2019-2020 influenza vaccine against influenza-associated hospitalizations in the United States. METHODS: We included adults hospitalized with acute respiratory illness at 14 hospitals and tested for influenza viruses by reserve transcription polymerase chain reaction. Vaccine effectiveness (VE) was estimated by comparing the odds of current-season influenza vaccination in test-positive influenza cases versus test-negative controls, adjusting for confounders. VE was stratified by age and major circulating influenza types along with A(H1N1)pdm09 genetic subgroups. RESULTS: 3116 participants were included, including 18% (553) influenza-positive cases. Median age was 63 years. Sixty-seven percent (2079) received vaccination. Overall adjusted VE against influenza viruses was 41% (95% confidence interval [CI]: 27-52). VE against A(H1N1)pdm09 viruses was 40% (95% CI: 24-53) and 33% against B viruses (95% CI: 0-56). Of the two major A(H1N1)pdm09 subgroups (representing 90% of sequenced H1N1 viruses), VE against one group (5A+187A,189E) was 59% (95% CI: 34-75) whereas no significant VE was observed against the other group (5A+156K) [-1%, 95% CI: -61-37]. CONCLUSIONS: In a primarily older population, influenza vaccination was associated with a 41% reduction in risk of hospitalized influenza illness.

INTRODUCTION: The 2016-2017 and 2017-2018 influenza seasons were notable for high number of hospitalizations for influenza A(H3N2) despite vaccine and circulating strain match. METHODS: We evaluated vaccine effectiveness (VE) against hospitalization in the test-negative HAIVEN study. Nasal-throat swabs were tested by RT-PCR for influenza and VE was determined based on odds of vaccination by generalized estimating equations. Vaccine-specific antibody was measured in a subset of enrollees. RESULTS: A total of 6,129 adults were enrolled from ten hospitals. Adjusted VE against A(H3N2) was 22.8% (95% C.I. 8.3%, 35.0%), pooled across both years and 49.4% (95% C.I. 34.3%, 61.1%) against B/Yamagata. In 2017-2018, the A(H3N2) VE point estimate for the cell-based vaccine was 43.0% (95% C.I. -36.3%, 76.1%; 56 vaccine recipients) compared to 24.0% (95% C.I. 3.9%, 39.9%) for egg based vaccines. Among 643 with serology data, hemagglutinin antibodies against the egg-based A(H3N2) vaccine strain were increased in influenza-negative individuals. CONCLUSIONS: Low VE for the A/Hong Kong/4801/2014 vaccine virus in both A(H3N2) seasons emphasizes concerns for continued changes in H3N2 antigenic epitopes, including changes that may impact glycosylation and ultimately reduce VE.

BACKGROUND: Seasonal influenza causes substantial morbidity and mortality in older adults. High-dose inactivated influenza vaccine (HD-IIV), with increased antigen content compared to standard-dose influenza vaccines (SD-IIV), is licensed for use in people aged >/=65 years. We sought to evaluate the effectiveness of HD-IIV and SD-IIV for prevention of influenza-associated hospitalizations. METHODS: Hospitalized patients with acute respiratory illness were enrolled in an observational vaccine effectiveness study at eight hospitals in the United States Hospitalized Adult Influenza Vaccine Effectiveness Network during the 2015-2016 and 2016-2017 influenza seasons. Enrolled patients were tested for influenza, and receipt of influenza vaccine by type was recorded. Effectiveness of SD-IIV and HD-IIV was estimated using a test-negative design (comparing odds of influenza among vaccinated and unvaccinated patients). Relative effectiveness of SD-IIV and HD-IIV was estimated using logistic regression. RESULTS: Among 1487 enrolled patients aged >/=65 years, 1107 (74%) were vaccinated; 622 (56%) received HD-IIV and 485 (44%) received SD-IIV. Overall, 277 (19%) tested positive for influenza, including 98 (16%) who received HD-IIV, 87 (18%) who received SD-IIV, and 92 (24%) who were unvaccinated. After adjusting for confounding variables, effectiveness of SD-IIV was 6% (95% confidence interval [CI] -42%, 38%) and that of HD-IIV was 32% (95%CI -3%, 54%), for a relative effectiveness of HD-IIV versus SD-IIV of 27% (95%CI -1%, 48%). CONCLUSIONS: During two U.S. influenza seasons, vaccine effectiveness was low to moderate for prevention of influenza hospitalization among adults aged >/=65 years. High-dose vaccine offered greater effectiveness. None of these findings were statistically significant.

In response to the 2014-2016 West Africa Ebola virus disease (EVD) outbreak, a US congressional appropriation provided funds to the US Centers for Disease Control and Prevention (CDC) to support global health security capacity building in 17 partner countries, including Guinea. The 2014 funding enabled CDC to provide more than 300 deployments of personnel to Guinea during the Ebola response, establish a country office, and fund 11 implementing partners through cooperative agreements to support global health security engagement efforts in 4 core technical areas: workforce development, surveillance systems, laboratory systems, and emergency management. This article reflects on almost 4 years of collaboration between CDC and its implementing partners in Guinea during the Ebola outbreak response and the recovery period. We highlight examples of collaborative synergies between cooperative agreement partners and local Guinean partners and discuss the impact of these collaborations in strengthening the above 4 core capacities. Finally, we identify the key elements of the successful collaborations, including communication and information sharing as a core cooperative agreement activity, a flexible funding mechanism, and willingness to adapt to local needs. We hope these observations can serve as guidance for future endeavors seeking to establish strong and effective partnerships between government and nongovernment organizations providing technical and operational assistance.

Quality adolescent sexual and reproductive health (ASRH) services play an important role in supporting the overall health and well-being of adolescents. Improving access to this care can help reduce unintended pregnancies, sexually transmitted diseases (STDs), and human immunodeficiency virus (HIV) infection and their associated consequences, as well as promote health equity. The Centers for Disease Control and Prevention funded three grantees to implement a clinic-based ASRH quality improvement initiative complimented by activities to strengthen systems to refer and link youth to ASRH services. The purpose of this study is to describe the initiative and baseline assessment results of ASRH best practice implementation in participating health centers. The assessment found common use of the following practices: STD/HIV screening, education on abstinence and the use of dual protection, and activities to increase accessibility (e.g., offering after-school hours and walk-in and same-day appointments). The following practices were used less frequently: provider training for Long-Acting Reversible Contraception (LARC) insertion and removal, LARC availability, same-day provision of all contraceptive methods, and consistent sharing of information about confidentiality and minors' rights with adolescent clients. This study describes the types of training and technical assistance being implemented at each health center and discusses implications for future programming.

Background: Evidence establishing effectiveness of influenza vaccination for prevention of severe illness is limited. The US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) is a multi-year test-negative case-control study initiated in 2015-16 to estimate effectiveness of vaccine in preventing influenza hospitalization among adults. Methods: Adults aged >/=18 years admitted to eight US hospitals with acute respiratory illness and testing positive for influenza by PCR were cases; those testing negative were controls. VE was estimated with logistic regression adjusting for age, comorbidities and other confounding factors and stratified by frailty, two-year vaccination history, and clinical presentation. Results: We analyzed data from 236 cases and 1231 controls; mean age was 58 years. Over 90% of patients had >/=1 comorbidity elevating risk of influenza complications. Fifty percent of cases and 70% of controls were vaccinated. Vaccination was 51% (95%CI 29, 65) and 53% (95%CI 11, 76) effective in preventing hospitalization due to influenza A(H1N1)pdm09 and influenza B virus infection, respectively. Vaccine was protective for all age groups. Conclusions: During the 2015-16 US influenza A(H1N1)pdm09-predominant season, we found that vaccination halved the risk of influenza-association hospitalization among adults, most of whom were at increased risk of serious influenza complications due to comorbidity or age.

PURPOSE: Hospitalized patients with an acute respiratory illness (ARI) were compared to determine if demographic characteristics, timing or influenza vaccination biased who received clinical respiratory viral panel (RVP) testing. METHODS: 171 enrollees in an influenza vaccine effectiveness study and a sample of non-enrollees (N = 1029) admitted to a community hospital with ARI during December 2015 through April 2016 comprised the study sample. Those who received clinical RVP testing (n = 292) were compared to those who did not by age, sex, influenza vaccination status, and period (pre-peak influenza season vs. peak/post peak influenza season), using Chi square- and t-tests, and logistic regression. RESULTS: Mean age of participants was 70 years, 58% was female and 45% had been vaccinated against influenza in the 2015-2016 season. Those with clinical RVP testing were significantly younger (67 years) than those without RVP (71 years; P < 0.001), but did not differ with respect to sex or vaccination status. The odds of clinical RVP testing were significantly (P = 0.004) related to younger age (< 65 years) (Odds ratio (OR) = 1.51; 95% CI = 1.14-2.00) and to later period (peak/post peak influenza season; OR = 2.64; 95% CI = 1.84-3.79) but were unrelated to influenza vaccination status or the interaction of time and vaccination status. CONCLUSION: RVP testing was significantly higher among younger hospitalized patients with an ARI and during the peak and post peak influenza periods than earlier in the season, but influenza vaccination status was not a significant factor. Studies that enroll based on clinical RVP testing should account for potential differences by age.

BACKGROUND AND AIMS: In response to the opioid overdose epidemic, USA state Medicaid programs have adopted restrictive policies for opioid analgesics, yet effects on prescribing patterns and health outcomes are uncertain. This study aimed to examine effects of a prior authorization policy for extended-release/long-acting (ER/LA) opioids on opioid use in the Oklahoma, USA state Medicaid program. DESIGN: Retrospective difference-in-differences design study comparing changes in opioid use in Oklahoma Medicaid to control (Oregon Medicaid). SETTING: Oklahoma and Oregon, USA. PARTICIPANTS: Medicaid beneficiaries in the Oklahoma and Oregon fee-for-service Medicaid programs between July 2007 and June 2009 (33,724 in Oklahoma and 13,520 in Oregon) MEASUREMENTS: The primary outcome was incident opioid-naive ER/LA opioid use. Secondary outcomes included other opioid and non-opioid pain medication use. We also examined indicators of high-risk prescribing (e.g. high dosage opioid use) and opioid-related hospitalizations or emergency department (ED) visits. FINDINGS: The prior authorization policy was associated with 0.7 percentage point reduction in likelihood of incident opioid-naive ER/LA opioid use (95% confidence interval [CI]: -1.16 to -0.33 percentage points; 70% pre-policy mean reduction), 1.4 percentage point decrease in likelihood of any new ER/LA opioid prescriptions (95% CI: -2.1 to -0.7 percentage points; 33% pre-policy mean reduction), and decline of 0.16 in total ER/LA opioid prescriptions per enrollee (PPE) (95% CI:-0.29 to -0.04 PPE). There was significant increase in number of short-acting opioids filled after the policy (0.36; 95% CI: 0.22 to 0.50 PPE), increases in likelihood of having overlapping opioids and benzodiazepines, but significant reductions in likelihood of having overlapping opioids. No significant changes in opioid-related hospitalizations or ED visits were observed. CONCLUSIONS: Oklahoma, USA's July 2008 prior authorization policy for extended-release/long-acting (ER/LA) opioids appears to have reduced the number of opioid-naive patients initiating ER/LA opioid use by more than half, but may also have increased short-acting opioid prescriptions by 7%.

Sudden unexpected death of an individual with epilepsy can pose a challenge to death investigators, as most deaths are unwitnessed, and the individual is commonly found dead in bed. Anatomic findings (eg, tongue/lip bite) are commonly absent and of varying specificity, thereby limiting the evidence to implicate epilepsy as a cause of or contributor to death. Thus it is likely that death certificates significantly underrepresent the true number of deaths in which epilepsy was a factor. To address this, members of the National Association of Medical Examiners, North American SUDEP Registry, Epilepsy Foundation SUDEP Institute, American Epilepsy Society, and the Centers for Disease Control and Prevention constituted an expert panel to generate evidence-based recommendations for the practice of death investigation and autopsy, toxicological analysis, interpretation of autopsy and toxicology findings, and death certification to improve the precision of death certificate data available for public health surveillance of epilepsy-related deaths. The recommendations provided in this paper are intended to assist medical examiners, coroners, and death investigators when a sudden unexpected death in a person with epilepsy is encountered.

BACKGROUND: High dosage opioid use is a risk factor for opioid-related overdose commonly cited in guidelines, recommendations, and policies. In 2012, the Oregon Medicaid program developed a prior authorization policy for opioid prescriptions above 120 mg per day morphine equivalent dose (MED). This study aimed to evaluate the effects of that policy on utilization, prescribing patterns, and health outcomes. Methods: Using administrative claims data from Oregon and a control state (Colorado) between 2011 and 2013, we used difference-in-differences analyses to examine changes in utilization, measures of high risk opioid use, and overdose after introduction of the policy. We also evaluated opioid utilization in a cohort of individuals who were high dosage opioid users before the policy. Results: Following implementation of Oregon's high dosage policy, the monthly probability of an opioid fill over 120 mg MED declined significantly by 1.7 percentage points (95% confidence interval [CI]; -2.0% to -1.4%), whereas it increased significantly by 1.0 percentage points (95% CI 0.4% to 1.7%) for opioid fills < 61 mg MED. Fills of medications used to treat neuropathic pain also increased by 1.2 percentage points (95% CI 0.7% to 1.8%). The monthly probability of multiple pharmacy use declined by 0.1 percentage points (-0.2% to -0.0) following the prior authorization, but there were no significant changes in ED encounters or hospitalizations for opioid overdose. Among individuals who were using a high dosage opioid before the policy, there was a 20.3 percentage point (95% CI -15.3% to -25.3%) decline in estimated probability of having a high dosage fill after the policy. Conclusions: Oregon's prior authorization policy was effective at reducing high dosage opioid prescriptions. While multiple pharmacy use also declined, we found no impact on opioid overdose.

BACKGROUND: Out-of-pocket payment for prescription opioids is believed to be an indicator of abuse or diversion, but few studies describe its epidemiology. Prescription drug monitoring programs (PDMPs) collect controlled substance prescription fill data regardless of payment source and thus can be used to study this phenomenon. OBJECTIVE: To estimate the frequency and characteristics of prescription fills for opioids that are likely paid out-of-pocket by individuals in the Oregon Medicaid program. RESEARCH DESIGN: Cross-sectional analysis using Oregon Medicaid administrative claims and PDMP data (2012 to 2013). SUBJECTS: Continuously enrolled nondually eligible Medicaid beneficiaries who could be linked to the PDMP with two opioid fills covered by Oregon Medicaid. MEASURES: Patient characteristics and fill characteristics for opioid fills that lacked a Medicaid pharmacy claim. Fill characteristics included opioid name, type, and association with indicators of high-risk opioid use. RESULTS: A total of 33 592 Medicaid beneficiaries filled a total of 555 103 opioid prescriptions. Of these opioid fills, 74 953 (13.5%) could not be matched to a Medicaid claim. Hydromorphone (30%), fentanyl (18%), and methadone (15%) were the most likely to lack a matching claim. The 3 largest predictors for missing claims were opioid fills that overlapped with other opioids (adjusted odds ratio [aOR] 1.37; 95% confidence interval [CI], 1.34-1.4), long-acting opioids (aOR 1.52; 95% CI, 1.47-1.57), and fills at multiple pharmacies (aOR 1.45; 95% CI, 1.39-1.52). CONCLUSIONS: Prescription opioid fills that were likely paid out-of-pocket were common and associated with several known indicators of high-risk opioid use.

PURPOSE: The purposes of this study were to describe changes in implementation of evidence-based clinical practices among health center partners as part of a multicomponent, community-wide teen pregnancy prevention initiative; to better understand the barriers to and facilitators of implementation of the evidence-based clinical practices; and to describe the technical assistance and training provided to the health center partners and key lessons learned. METHODS: Health center data from the second and third years (2012 and 2013) of the teen pregnancy prevention community-wide initiative were analyzed from 10 communities (the first year was a planning year; program implementation began in the second year). Data were analyzed from 48 health center partners that contributed data in both years to identify evidence-based clinical practices that were being implemented and opportunities for improvement. In addition, data were analyzed from a purposive sample of 30 health center partners who were asked to describe their experiences in implementing evidence-based clinical practices in adolescent reproductive health care and barriers and facilitators to implementation. RESULTS: Across 48 health centers in the 10 communities, 52% reported an increase in the implementation of evidence-based clinical practices from 2012 to 2013, mostly in providing contraceptive access (23%) and offering Quick Start (19%). Among health centers that reported no change (13%), the majority reported that practices were already being implemented before the initiative. Finally, among health centers that reported a decrease in implementation of evidence-based clinical practices (35%), most reported a decrease in having either hormonal contraception or intrauterine devices available at every visit (15%), having HIV rapid testing available (10%), or participating in the federal 340B Drug Discount Program (2%). In addition, health systems and community-level factors influence health center implementation of evidence-based clinical practices. In particular, support from health center leadership, communication between leadership and staff, and staff attitudes and beliefs were reported as factors that facilitated the implementation of new practices. CONCLUSIONS: To increase adolescent's use of quality, client-centered, affordable and confidential reproductive health services, improvement in the implementation of evidence-based clinical practices is needed. Efforts to identify barriers to and facilitators for implementation of evidence-based clinical practices can inform for health centers of opportunities to build their capacity to ensure that evidence-based clinical practices are being implemented.

BACKGROUND: An evidence-based, step-by-step guide, the 4 Pillars Practice Transformation Program, was the foundation of an intervention to increase adult immunizations in primary care and was tested in a randomized controlled cluster trial. The purpose of this study is to report changes in influenza immunization rates and on factors related to receipt of influenza vaccine. METHODS: Twenty five primary care practices were recruited in 2013, stratified by city (Houston, Pittsburgh), location (rural, urban, suburban) and type (family medicine, internal medicine), and randomized to the intervention (n = 13) or control (n = 12) in Year 1 (2013-14). A follow-up intervention occurred in Year 2 (2014-15). Demographic and vaccination data were derived from de-identified electronic medical record extractions. RESULTS: A cohort of 70,549 adults seen in their respective practices (n = 24 with 1 drop out) at least once each year was followed. Baseline mean age was 55.1 years, 35 % were men, 21 % were non-white and 35 % were Hispanic. After one year, both intervention and control arms significantly (P < 0.001) increased influenza vaccination, with average increases of 2.7 to 6.5 percentage points. In regression analyses, likelihood of influenza vaccination was significantly higher in sites with lower percentages of patients with missed opportunities (P < 0.001) and, after adjusting for missed opportunities, the intervention further improved vaccination rates in Houston (lower baseline rates) but not Pittsburgh (higher baseline rates). In the follow-up intervention, the likelihood of vaccination increased for both intervention sites and those that reduced missed opportunities (P < 0.005). CONCLUSIONS: Reducing missed opportunities across the practice increases likelihood of influenza vaccination of adults. The 4 Pillars Practice Transformation Program provides strategies for reducing missed opportunities to vaccinate adults. TRIAL REGISTRATION: This study was registered as a clinical trial on 03/20/2013 at ClinicalTrials.gov, Clinical Trial Registry Number: NCT01868334 , with a date of enrollment of the first participant to the trial of April 1, 2013.

INTRODUCTION: National adult Tdap vaccination rates are low, reinforcing the need to increase vaccination efforts in primary care offices. The 4 Pillars Practice Transformation Program is an evidence-based, step-by-step guide to improving primary care adult vaccination with an online implementation tracking dashboard. This study tested the effectiveness of an intervention to increase adult Tdap vaccination that included the 4 Pillars Program, provider education, and one-on-one coaching of practice-based immunization champions. METHODS: 25 primary care practices participated in a randomized controlled cluster trial (RCCT) in Year 1 (6/1/2013-5/31/2014) and a pre-post study in Year 2 (6/1/2014-1/31/2015). Baseline year was 6/1/2012-5/31/2013, with data analyzed in 2016. Demographic and vaccination data were derived from de-identified electronic medical record (EMR) extractions. The primary outcomes were vaccination rates and percentage point (PP) changes/year. RESULTS: The cohort consisted of 70,549 patients 18years who were seen in the practices 1 time each year, with a baseline mean age=55years; 35% were men; 56% were non-white; 35% were Hispanic and 20% were on Medicare. Baseline vaccination rate averaged 35%. In the Year 1 RCCT, cumulative Tdap vaccination increased significantly in both intervention and control groups; in both cities, the percentage point increases in the intervention groups (7.7 PP in Pittsburgh and 9.9 PP in Houston) were significantly higher (P<0.001) than in the control groups (6.4 PP in Pittsburgh and 7.6 PP in Houston). In the Year 2 pre-post study, in both cities, active intervention groups increased rates significantly more (6.2 PP for both) than maintenance groups (2.2 PP in Pittsburgh and 4.1 PP in Houston; P<0.001). CONCLUSIONS: An intervention that includes the 4 Pillars Practice Transformation Program, staff education and coaching is effective for increasing adult Tdap immunization rates within primary care practices. Clinical Trial Registry Name/Number: NCT01868334.

PURPOSE: Despite the substantial evidence supporting the guidelines for the provision of reproductive health services for adolescents, research points to a persistent gap in their translation into health care practice. This study examines barriers and facilitators that health centers experience when implementing evidence-based clinical practices for adolescent reproductive health services and discusses strategies to address identified barriers. METHODS: Semistructured interviews were conducted with 85 leaders and staff of 30 health centers in Alabama, Georgia, Massachusetts, North Carolina, South Carolina, Pennsylvania, and Texas. Interview data were analyzed for emergent themes following a grounded theory approach. RESULTS: Data analysis revealed that certain factors at health system and community levels influenced health centers' efforts to implement evidence-based clinical practices for adolescent reproductive health care. In particular, support from health center leadership, communication between leadership and staff, and staff attitudes and beliefs were reported as factors that facilitated the implementation of new practices. CONCLUSIONS: Health center efforts to implement new practice guidelines should include efforts to build the capacity of health center leadership to mobilize staff and resources to ensure that new practices are implemented consistently and with quality.

PURPOSE: The purposes of the study were to describe baseline data in the implementation of evidence-based clinical practices among health center partners as part of a community-wide teen pregnancy prevention initiative and to identify opportunities for health center improvement. METHODS: Health center partner baseline data were collected in the first year (2011) and before program implementation of a 5-year community-wide teen pregnancy prevention initiative. A needs assessment on health center capacity and implementation of evidence-based clinical practices was administered with 51 health centers partners in 10 communities in the United States with high rates of teen pregnancy. RESULTS: Health centers reported inconsistent implementation of evidence-based clinical practices in providing reproductive health services to adolescents. Approximately 94.1% offered same-day appointments, 91.1% had infrastructure to reduce cost barriers, 90.2% offered after-school appointments, and 80.4% prescribed hormonal contraception without prerequisite examinations or testing. Approximately three quarters provided visual and audio privacy in examination rooms (76.5%) and counseling areas (74.5%). Fewer offered a wide range of contraceptive methods (67.8%) and took a sexual health history at every visit (54.9%). Only 45.1% reported Quick Start initiation of hormonal contraception, emergency contraception (43.1%), or intrauterine devices (12.5%) were "always" available to adolescents. CONCLUSIONS: The assessment highlighted opportunities for health center improvement. Strategies to build capacity of health center partners to implement evidence-based clinical practices may lead to accessibility and quality of reproductive health services for adolescents in the funded communities.

IMPORTANCE: Multiple myeloma has been classified as exhibiting "limited or suggestive evidence" of an association with exposure to herbicides in Vietnam War veterans. Occupational studies have shown that other pesticides (ie, insecticides, herbicides, fungicides) are associated with excess risk of multiple myeloma and its precursor state, monoclonal gammopathy of undetermined significance (MGUS); however, to our knowledge, no studies have uncovered such an association in Vietnam War veterans. OBJECTIVE: To examine the relationship between MGUS and exposure to Agent Orange, including its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in Vietnam War veterans. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort study conducted in 2013 to 2014, testing for MGUS in serum specimens collected and stored in 2002 by the Air Force Health Study (AFHS). The relevant exposure data collected by the AFHS was also used. We tested all specimens in 2013 without knowledge of the exposure status. The AFHS included former US Air Force personnel who participated in Operation Ranch Hand (Ranch Hand veterans) and other US Air Force personnel who had similar duties in Southeast Asia during the same time period (1962 to 1971) but were not involved in herbicide spray missions (comparison veterans). Agent Orange was used by the US Air Force personnel who conducted aerial spray missions of herbicides (Operation Ranch Hand) in Vietnam from 1962 to 1971. We included 479 Ranch Hand veterans and 479 comparison veterans who participated in the 2002 follow-up examination of AFHS. EXPOSURES: Agent Orange and TCDD. Serum TCDD levels were measured in 1987, 1992, 1997, and 2002. MAIN OUTCOMES AND MEASURES: Risk of MGUS measured by prevalence, odds ratios (ORs), and 95% CIs. RESULTS: The 479 Ranch Hand veterans and 479 comparison veterans had similar demographic and lifestyle characteristics and medical histories. The crude prevalence of overall MGUS was 7.1% (34 of 479) in Ranch Hand veterans and 3.1% (15 of 479) in comparison veterans. This translated into a 2.4-fold increased risk for MGUS in Ranch Hand veterans than comparison veterans after adjusting for age, race, BMI in 2002, and the change in BMI between 2002 and the time of blood draw for TCDD measurement (adjusted OR, 2.37; 95% CI, 1.27-4.44; P = .007). CONCLUSIONS AND RELEVANCE: Operation Ranch Hand veterans have a significantly increased risk of MGUS, supporting an association between Agent Orange exposure and multiple myeloma.

In southern California, ocular infections caused by Onchocerca lupi were diagnosed in 3 dogs (1 in 2006, 2 in 2012). The infectious agent was confirmed through morphologic analysis of fixed parasites in tissues and by PCR and sequencing of amplicons derived from 2 mitochondrially encoded genes and 1 nuclear-encoded gene. A nested PCR based on the sequence of the cytochrome oxidase subunit 1 gene of the parasite was developed and used to screen Simulium black flies collected from southern California for O. lupi DNA. Six (2.8%; 95% CI 0.6%-5.0%) of 213 black flies contained O. lupi DNA. Partial mitochondrial16S rRNA gene sequences from the infected flies matched sequences derived from black fly larvae cytotaxonomically identified as Simulium tribulatum. These data implicate S. tribulatum flies as a putative vector for O. lupi in southern California.

BACKGROUND: A key issue in the treatment of obesity in older adults is whether the health benefits of weight loss outweigh the potential risks with respect to musculoskeletal injury. OBJECTIVE: To compare change in weight, improvements in metabolic risk factors, and reported musculoskeletal adverse events in middle-aged (50-59 years) and older (65-74 years), obese women. MATERIALS AND METHODS: Participants completed an initial 6-month lifestyle intervention for weight loss, comprised of weekly group sessions, followed by 12 months of extended care with biweekly contacts. Weight and fasting blood samples were assessed at baseline, month 6, and month 18; data regarding adverse events were collected throughout the duration of the study. RESULTS: Both middle-aged (n = 162) and older (n = 56) women achieved significant weight reductions from baseline to month 6 (10.1 +/- 0.68 kg and 9.3 +/- 0.76 kg, respectively) and maintained a large proportion of their losses at month 18 (7.6 +/- 0.87 kg and 7.6 +/- 1.3 kg, respectively); there were no significant differences between the two groups with respect to weight change. Older women further experienced significant reductions in systolic blood pressure, HbA(1c), and C-reactive protein from baseline to month 6 and maintained these improvements at month 18. Despite potential safety concerns, we found that older women were no more likely to experience musculoskeletal adverse events during the intervention as compared with their middle-aged counterparts. CONCLUSION: These results suggest that older, obese women can experience significant health benefits from lifestyle treatment for obesity, including weight loss and improvements in disease risk factors. Further investigation of the impact of weight loss on additional health-related parameters and risks (eg, body composition, muscular strength, physical functioning, and injuries) in older adults is needed.