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Abstract: The effect of neutron-irradiation damage has been mainly simulated using high-energy ion bombardment. A recent MIT report (PSFC/RR-10-4, An assessment of the current data affecting tritium retention and its use to project towards T retention in ITER, Lipschultz et al., 2010) summarizes the observations from high-energy ion bombardment studies and illustrates the saturation trend in deuterium concentration due to damage from ion irradiation in tungsten and molybdenum above 1 displacement per atom (dpa). While this prior database of results is quite valuable for understanding the behavior of hydrogen isotopes in plasma facing components (PFCs), it does not encompass the full range of effects that must be considered in a practical fusion environment due to short penetration depth, damage gradient, high damage rate, and high primary knock-on atom (PKA) energy spectrum of the ion bombardment. In addition, neutrons change the elemental composition via transmutations, and create a high radiation environment inside PFCs, which influences the behavior of hydrogen isotope in PFCs, suggesting the utilization of fission reactors is necessary for neutron-irradiation. Under the framework of the US–Japan TITAN program, tungsten samples (99.99at.% purity from A.L.M.T. Co.) were irradiated by fission neutrons in the High Flux Isotope Reactor (HFIR), Oak Ridge National Laboratory (ORNL), at 50 and 300°C to 0.025, 0.3, and 2.4dpa, and the investigation of deuterium retention in neutron-irradiated tungsten was performed in the Tritium Plasma Experiment (TPE), the unique high-flux linear plasma facility that can handle tritium, beryllium and activated materials. This paper reports the recent results from the comparison of ion-damaged tungsten via various ion species (2.8MeV Fe2+, 20MeV W2+, and 700keV H−) with that from neutron-irradiated tungsten to identify the similarities and differences among them. [Copyright &y& Elsevier]

Background: In 2022-2023, 15- and 20-valent pneumococcal conjugate vaccines (PCV15/PCV20) were recommended for infants. We aimed to estimate the incidence of outpatient visits and antibiotic prescriptions in US children (≤17 years) from 2016-2019 for acute otitis media, pneumonia, and sinusitis associated with PCV15- and PCV20-additional (non-PCV13) serotypes to quantify PCV15/20 potential impacts., Methods: We estimated the incidence of PCV15/20-additional serotype-attributable visits and antibiotic prescriptions as the product of all-cause incidence rates, derived from national health care surveys and MarketScan databases, and PCV15/20-additional serotype-attributable fractions. We estimated serotype-specific attributable fractions using modified vaccine-probe approaches incorporating incidence changes post-PCV13 and ratios of PCV13 versus PCV15/20 serotype frequencies, estimated through meta-analyses., Results: Per 1000 children annually, PCV15-additional serotypes accounted for an estimated 2.7 (95% confidence interval, 1.8-3.9) visits and 2.4 (95% CI, 1.6-3.4) antibiotic prescriptions. PCV20-additional serotypes resulted in 15.0 (95% CI, 11.2-20.4) visits and 13.2 (95% CI, 9.9-18.0) antibiotic prescriptions annually per 1000 children. PCV15/20-additional serotypes account for 0.4% (95% CI, 0.2%-0.6%) and 2.1% (95% CI, 1.5%-3.0%) of pediatric outpatient antibiotic use., Conclusions: Compared with PCV15-additional serotypes, PCV20-additional serotypes account for > 5 times the burden of visits and antibiotic prescriptions. Higher-valency PCVs, especially PCV20, may contribute to preventing pediatric pneumococcal respiratory infections and antibiotic use., Competing Interests: Potential conflicts of interest. L. M. K. reports consulting fees from Merck Sharpe & Dohme and Vaxcyte for unrelated work. J. A. L. reports research grants from Pfizer and Merck Sharpe & Dohme; and consulting fees from Pfizer, Merck, Sharpe & Dohme, and Vaxcyte for unrelated work. S. Y. T. reports research grants from Pfizer for unrelated work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

On June 17, 2024, the Food and Drug Administration approved 21-valent pneumococcal conjugate vaccine (PCV) (PCV21; CAPVAXIVE; Merck Sharp & Dohme, LLC) for adults aged ≥18 years. PCV21 does not contain certain serotypes that are included in other licensed pneumococcal vaccines but adds eight new serotypes. The Advisory Committee on Immunization Practices (ACIP) recommends use of a PCV for all adults aged ≥65 years, as well as adults aged 19-64 years with certain risk conditions for pneumococcal disease if they have not received a PCV or whose vaccination history is unknown. Previously, options included either 20-valent PCV (PCV20; Prevnar20; Wyeth Pharmaceuticals, Inc.) alone or a 15-valent PCV (PCV15; VAXNEUVANCE; Merck Sharp & Dohme, LLC) in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax23; Merck Sharp & Dohme, LLC). Additional recommendations for use of PCV20 exist for adults who started their pneumococcal vaccination series with 13-valent PCV (PCV13; Prevnar13; Wyeth Pharmaceuticals, Inc.). The ACIP Pneumococcal Vaccines Work Group employed the Evidence to Recommendations framework to guide its deliberations on PCV21 vaccination among U.S. adults. On June 27, 2024, ACIP recommended a single dose of PCV21 as an option for adults aged ≥19 years for whom PCV is currently recommended. Indications for PCV have not changed from previous recommendations. This report summarizes evidence considered for these recommendations and provides clinical guidance for use of PCV21., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Katherine A. Poehling reports grant support from the North Carolina Baptist Foundation for support of Safe Sleep supplies for all newborns and Early Child Education Fellow with Love Out Loud, a local nonprofit; Optum Social Responsibility, for support of Intimate Partner Violence Collaborative Pilot; Atrium Health Wake Forest Baptist Clinical and Translational Science Institute for Because You Matter: Conversations You Want About COVID-19 and Text Messaging Follow-up for Patients who missed Well-child visits; and the Kate B. Reynolds Foundation for Re-imagining Health and Well-being by Mothers for our Babies, Families, and Community; volunteer service as a board member of the Children’s Law Center of Central North Carolina, a local nonprofit (https://www.childlawnc.org); and a volunteer role as senior editor of Academic Pediatrics. No other potential conflicts of interest were disclosed.

Background: A U.S. case-control study (2010-2014) demonstrated vaccine effectiveness (VE) for ≥ 1 dose of the thirteen-valent pneumococcal conjugate vaccine (PCV13) against vaccine-type (VT) invasive pneumococcal disease (IPD) at 86 %; however, it lacked statistical power to examine VE by number of doses and against individual serotypes., Methods: We used the indirect cohort method to estimate PCV13 VE against VT-IPD among children aged < 5 years in the United States from May 1, 2010 through December 31, 2019 using cases from CDC's Active Bacterial Core surveillance, including cases enrolled in a matched case-control study (2010-2014). Cases and controls were defined as individuals with VT-IPD and non-PCV13-type-IPD (NVT-IPD), respectively. We estimated absolute VE using the adjusted odds ratio of prior PCV13 receipt (1-aOR x 100 %)., Results: Among 1,161 IPD cases, 223 (19.2 %) were VT cases and 938 (80.8 %) were NVT controls. Of those, 108 cases (48.4 %; 108/223) and 600 controls (64.0 %; 600/938) had received > 3 PCV13 doses; 23 cases (17.6 %) and 15 controls (2.4 %) had received no PCV doses. VE ≥ 3 PCV13 doses against VT-IPD was 90.2 % (95 % Confidence Interval75.4-96.1 %), respectively. Among the most commonly circulating VT-IPD serotypes, VE of ≥ 3 PCV13 doses was 86.8 % (73.7-93.3 %), 50.2 % (28.4-80.5 %), and 93.8 % (69.8-98.8 %) against serotypes 19A, 3, and 19F, respectively., Conclusions: At least three doses of PCV13 continue to be effective in preventing VT-IPD among children aged < 5 years in the US. PCV13 was protective against serotypes 19A and 19F IPD; protection against serotype 3 IPD did not reach statistical significance., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Lee Harrison provides service on advisory boards (Pfizer, Sanofi, GSK) and a DSMB (Merck); while LH does not receive any fees for this work he is reimbursed for occasional travel. Tamara Pilishvili reports a relationship with GSK that includes: employment. During data collection, analysis, and write-up, TP was employed by CDC. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.]., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Methotrexate (MTX) is partially metabolized by aldehyde oxidase (AOX) in the liver and its clinical impact remains unclear. In this study, we aimed to demonstrate how AOX contributes to MTX-induced hepatotoxicity in vitro and clarify the relationship between concomitant AOX inhibitor use and MTX-associated liver injury development using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS)., Methods: We assessed intracellular MTX accumulation and cytotoxicity using HepG2 cells. We used the FAERS database to detect reporting odds ratio (ROR)-based MTX-related hepatotoxicity event signals., Results: AOX inhibition by AOX inhibitor raloxifene and siRNA increased the MTX accumulation in HepG2 cells and enhanced the MTX-induced cell viability reduction. In the FAERS analysis, the ROR for MTX-related hepatotoxicity increased with non-overlap of 95% confidence interval when co-administered with drugs with higher I max, u (maximum unbound plasma concentration)/IC 50 (half-maximal inhibitory concentration for inhibition of AOX) calculated based on reported pharmacokinetic data., Conclusion: AOX inhibition contributed to MTX accumulation in the liver, resulting in increased hepatotoxicity. Our study raises concerns regarding MTX-related hepatotoxicity when co-administered with drugs that possibly inhibit AOX activity at clinical concentrations.

Adult Pneumococcal Vaccine Program in the United States Streptococcus pneumoniae (pneumococcus) is a common cause of bacterial respiratory infections leading to substantial morbidity and mortality. Here, Kobayashi et al. discuss the recently updated U.S. guidelines for adult pneumococcal vaccination.

Despite the availability of effective vaccines against pneumococcal disease, pneumococcus is a common bacterial cause of pneumonia, causing approximately 100,000 hospitalizations among U.S. adults per year. In addition, approximately 30,000 invasive pneumococcal disease (IPD) cases and 3,000 IPD deaths occur among U.S. adults each year. Previous health care provider surveys identified gaps in provider knowledge about and understanding of the adult pneumococcal vaccine recommendations, and pneumococcal vaccine coverage remains suboptimal. To assess the feasibility and acceptability domains of the Advisory Committee on Immunization Practices (ACIP) Evidence to Recommendations (EtR) framework, a health care provider knowledge and attitudes survey was conducted during September 28-October 10, 2022, by the Healthcare and Public Perceptions of Immunizations Survey Collaborative before the October 2022 ACIP meeting. Among 751 provider respondents, two thirds agreed or strongly agreed with the policy option under consideration to expand the recommendations for the new 20-valent pneumococcal conjugate vaccine (PCV20) to adults who had only received the previously recommended 13-valent pneumococcal conjugate vaccine (PCV13). Gaps in providers' knowledge and perceived challenges to implementing recommendations were identified and were included in ACIP's EtR framework discussions in late October 2022 when ACIP updated the recommendations for PCV20 use in adults. Currently, use of PCV20 is recommended for certain adults who have previously received PCV13, in addition to those who have never received a pneumococcal conjugate vaccine. The survey findings indicate a need to increase provider awareness and implementation of pneumococcal vaccination recommendations and to provide tools to assist with patient-specific vaccination guidance. Resources available to address the challenges to implementing pneumococcal vaccination recommendations include the PneumoRecs VaxAdvisor mobile app and other CDC-developed tools, including summary documents and overviews of vaccination schedules and CDC's strategic framework to increase confidence in vaccines and reduce vaccine-preventable diseases, Vaccinate with Confidence., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Andrew M. Parker reports grants outside the submitted work from the National Institutes of Health, National Science Foundation, Department of Homeland Security, and Agency for Healthcare Research and Quality. Aaron M. Scherer reports grant funding from the National Institutes of Health. No other potential conflicts of interest were disclosed.

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Katherine A. Poehling reports institutional support from Safe Sleep for All Newborns, Love Out Loud Early Childhood Fellow, Intimate Partner Violence Collaborative Project, Because You Matter: Conversations You Want about COVID-19, text messaging follow-up for patients who missed well-child visits, and Reimagining Health and Wellness by Mothers for Our Babies, Families, and Communities. No other potential conflicts of interest were disclosed.

Background: Although use of the 13-valent pneumococcal conjugate vaccine (PCV13) among children has reduced incidence of pneumococcal disease, a considerable burden of disease remains. PCV15 is a new vaccine that contains pneumococcal serotypes 22F and 33F in addition to serotypes contained in PCV13. To inform deliberations by the Advisory Committee on Immunization Practices on recommendations for PCV15 use among U.S. children, we estimated the health impact and cost-effectiveness of replacing PCV13 with PCV15 within the routine infant immunization program in the United States. We also assessed the impact and cost-effectiveness of a supplementary PCV15 dose among children aged 2-5 years who have already received a full PCV13 series., Methods: We estimated the incremental number of pneumococcal disease events and deaths averted, costs per quality adjusted life-year (QALY) gained, and costs per life-year gained under different vaccination strategies using a probabilistic model following a single birth cohort of 3.9 million individuals (based on 2020 U.S. birth cohort). We assumed that vaccine effectiveness (VE) of PCV15 against the two additional serotypes was the same as the VE of PCV13. The cost of PCV15 use among children was informed from costs of PCV15 use among adults and from discussions with the manufacturer., Results: Our base case results found that replacing PCV13 with PCV15 prevented 92,290 additional pneumococcal disease events and 22 associated deaths, while also saving $147 million in costs. A supplementary PCV15 dose among children aged 2-5 years who were fully vaccinated with PCV13 prevented further pneumococcal disease events and associated deaths but at a cost of more than $2.5 million per QALY gained., Conclusions: A further decrease in pneumococcal disease in conjunction with considerable societal cost savings could be expected from replacing PCV13 with PCV15 within the routine infant immunization program in the United States., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Background: Descriptions of changes in invasive bacterial disease (IBD) epidemiology during the coronavirus disease 2019 (COVID-19) pandemic in the United States are limited., Methods: We investigated changes in the incidence of IBD due to Streptococcus pneumoniae, Haemophilus influenzae, group A Streptococcus (GAS), and group B Streptococcus (GBS). We defined the COVID-19 pandemic period as 1 March to 31 December 2020. We compared observed IBD incidences during the pandemic to expected incidences, consistent with January 2014 to February 2020 trends. We conducted secondary analysis of a health care database to assess changes in testing by blood and cerebrospinal fluid (CSF) culture during the pandemic., Results: Compared with expected incidences, the observed incidences of IBD due to S. pneumoniae, H. influenzae, GAS, and GBS were 58%, 60%, 28%, and 12% lower during the pandemic period of 2020, respectively. Declines from expected incidences corresponded closely with implementation of COVID-19-associated nonpharmaceutical interventions (NPIs). Significant declines were observed across all age and race groups, and surveillance sites for S. pneumoniae and H. influenzae. Blood and CSF culture testing rates during the pandemic were comparable to previous years., Conclusions: NPIs likely contributed to the decline in IBD incidence in the United States in 2020; observed declines were unlikely to be driven by reductions in testing., Competing Interests: Presented in part: 12th International Symposium on Pneumococci and Pneumococcal Diseases, Toronto, Canada, 19-23 June., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2023.)

Importance: The association of 13-valent pneumococcal conjugate vaccine (PCV13) use with pneumonia hospitalization in older adults, especially those with underlying medical conditions, is not well described., Objective: To evaluate the association of PCV13 use with pneumonia, non-health care-associated (non-HA) pneumonia, and lobar pneumonia (LP) hospitalization among US Medicare beneficiaries 65 years or older., Design, Setting, and Participants: This cohort study with time-varying exposure assignment analyzed claims data from US Medicare beneficiaries 65 years or older enrolled in Parts A/B with a residence in the 50 US states or the District of Columbia by September 1, 2014. New Medicare Parts A/B beneficiaries within 6 months after their 65th birthday were continuously included in the cohort after September 1, 2014, and followed through December 31, 2017. Participants were censored if they died, changed enrollment status, or developed a study outcome. Most of the analyses were conducted from 2018 to 2019, and additional analyses were performed from 2021 to 2022., Exposures: Use of PCV13 vaccination 14 days or more before pneumonia hospitalization., Main Outcomes and Measures: Discrete-time survival models were used to estimate the incidence rate ratio (IRR) and number of pneumonia hospitalizations averted through PCV13 use. The adjusted IRR for the association of PCV13 vaccination with pneumonia hospitalization was used to estimate vaccine effectiveness (VE)., Results: At the end of follow-up (December 2017), 24 121 625 beneficiaries (13 593 975 women [56.4%]; 418 005 [1.7%] Asian, 1 750 807 [4.8%] Black, 338 044 [1.4%] Hispanic, 111 508 [0.5%] Native American, and 20 700 948 [85.8%] White individuals) were in the cohort; 4 936 185 (20.5%) had received PCV13 only, and 10 646 220 (79.5%) had not received any pneumococcal vaccines. More than half of the beneficiaries in the cohort were younger than 75 years, White, and had either immunocompromising or chronic medical conditions. Coverage with PCV13 increased from 0.8% (September 2014) to 41.5% (December 2017). The VE for PCV13 was estimated at 6.7% (95% CI, 5.9%-7.5%) for pneumonia, 4.7% (95% CI, 3.9%-5.6%) for non-HA pneumonia, and 5.8% (95% CI, 2.6%-8.9%) for LP. From September 2014 through December 2017, an estimated 35 127 pneumonia (95% CI, 33 011-37 270), 24 643 non-HA pneumonia (95% CI, 22 761-26 552), and 1294 LP (95% CI, 797-1819) hospitalizations were averted through PCV13 use., Conclusions and Relevance: The study results suggest that PCV13 use was associated with reduced pneumonia hospitalization among Medicare beneficiaries 65 years or older, many of whom had underlying medical conditions. Increased PCV13 coverage and use of recently approved higher-valent pneumococcal conjugate vaccines may avert additional pneumonia hospitalizations in adults.

The 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13, Wyeth Pharmaceuticals, Inc, a subsidiary of Pfizer, Inc]) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Merck Sharp & Dohme LLC]) have been recommended for U.S. children, and the recommendations vary by age group and risk group (1,2). In 2021, 15-valent pneumococcal conjugate vaccine (PCV15 [Vaxneuvance, Merck Sharp & Dohme LLC]) was licensed for use in adults aged ≥18 years (3). On June 17, 2022, the Food and Drug Administration (FDA) approved an expanded usage for PCV15 to include persons aged 6 weeks-17 years, based on studies that compared antibody responses to PCV15 with those to PCV13 (4). PCV15 contains serotypes 22F and 33F (in addition to the PCV13 serotypes) conjugated to CRM197 (genetically detoxified diphtheria toxin). On June 22, 2022, CDC's Advisory Committee on Immunization Practices (ACIP) recommended use of PCV15 as an option for pneumococcal conjugate vaccination of persons aged <19 years according to currently recommended PCV13 dosing and schedules (1,2). ACIP employed the Evidence to Recommendation (EtR) Framework,* using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) † approach to guide its deliberations regarding use of these vaccines. Risk-based recommendations on use of PPSV23 for persons aged 2-18 years with certain underlying medical conditions § that increase the risk for pneumococcal disease have not changed., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Katherine A. Poehling reports institutional support from Safe Sleep for All Newborns, Love Out Loud Early Childhood Fellow, Intimate Partner Violence Collaborative Project, Because You Matter: Conversations You Want about COVID-19, text messaging follow-up for patients who missed well-child visits, and Reimagining Health and Wellness by Mothers for Our Babies, Families, and Communities. No other potential conflicts of interest were disclosed.

Background: As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination coverage increases in the United States, there is a need to understand the real-world effectiveness against severe coronavirus disease 2019 (COVID-19) and among people at increased risk for poor outcomes., Methods: In a multicenter case-control analysis of US adults hospitalized March 11-May 5, 2021, we evaluated vaccine effectiveness to prevent COVID-19 hospitalizations by comparing odds of prior vaccination with a messenger RNA (mRNA) vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with COVID-19 and hospital-based controls who tested negative for SARS-CoV-2., Results: Among 1212 participants, including 593 cases and 619 controls, median age was 58 years, 22.8% were Black, 13.9% were Hispanic, and 21.0% had immunosuppression. SARS-CoV-2 lineage B0.1.1.7 (Alpha) was the most common variant (67.9% of viruses with lineage determined). Full vaccination (receipt of 2 vaccine doses ≥14 days before illness onset) had been received by 8.2% of cases and 36.4% of controls. Overall vaccine effectiveness was 87.1% (95% confidence interval [CI], 80.7-91.3). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.4%; 95% CI, 79.3-9.7). Among 45 patients with vaccine-breakthrough COVID hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (62.9%; 95% CI,20.8-82.6) than without immunosuppression (91.3%; 95% CI, 85.6-94.8)., Conclusion: During March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing COVID-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: People with HIV (PWH) are at increased risk for invasive pneumococcal disease (IPD). Thirteen-valent pneumococcal conjugate vaccine (PCV13) was recommended for use in US children in 2010 and for PWH aged 19 years or older in 2012. We evaluated the population-level impact of PCV13 on IPD among PWH and non-PWH aged 19 years or older., Methods: We identified IPD cases from 2008 to 2018 through the Active Bacterial Core surveillance platform. We estimated IPD incidence using the National HIV Surveillance System and US Census Bureau data. We measured percent changes in IPD incidence from 2008 to 2009 to 2017-2018 by HIV status, age group, and vaccine serotype group, including serotypes in recently licensed 15-valent (PCV15) and 20-valent (PCV20) PCVs., Results: In 2008-2009 and 2017-2018, 8.4% (552/6548) and 8.0% (416/5169) of adult IPD cases were among PWH, respectively. Compared with non-PWH, a larger proportion of IPD cases among PWH were in adults aged 19-64 years (94.7%-97.4% vs. 56.0%-60.1%) and non-Hispanic Black people (62.5%-73.0% vs. 16.7%-19.2%). Overall and PCV13-type IPD incidence in PWH declined by 40.3% (95% confidence interval: -47.7 to -32.3) and 72.5% (95% confidence interval: -78.8 to -65.6), respectively. In 2017-2018, IPD incidence was 16.8 (overall) and 12.6 (PCV13 type) times higher in PWH compared with non-PWH; PCV13, PCV15/non-PCV13, and PCV20/non-PCV15 serotypes comprised 21.5%, 11.2%, and 16.5% of IPD in PWH, respectively., Conclusions: Despite reductions post-PCV13 introduction, IPD incidence among PWH remained substantially higher than among non-PWH. Higher-valent PCVs provide opportunities to reduce remaining IPD burden in PWH., Competing Interests: W.S. served as a consultant for VBI Vaccines. L.H.H. served as a consultant for GSK, Merck, Pfizer, and Sanofi Pasteur. The remaining authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

In 2021, 20-valent pneumococcal conjugate vaccine (PCV) (PCV20) (Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.) and 15-valent PCV (PCV15) (Merck Sharp & Dohme Corp.) were licensed by the Food and Drug Administration for adults aged ≥18 years, based on studies that compared antibody responses to PCV20 and PCV15 with those to 13-valent PCV (PCV13) (Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.). Antibody responses to two additional serotypes included in PCV15 were compared to corresponding responses after PCV13 vaccination, and antibody responses to seven additional serotypes included in PCV20 were compared with those to the 23-valent pneumococcal polysaccharide vaccine (PPSV23) (Merck Sharp & Dohme Corp.). On October 20, 2021, the Advisory Committee on Immunization Practices (ACIP) recommended use of either PCV20 alone or PCV15 in series with PPSV23 for all adults aged ≥65 years, and for adults aged 19-64 years with certain underlying medical conditions or other risk factors* who have not previously received a PCV or whose previous vaccination history is unknown. ACIP employed the Evidence to Recommendation (EtR) framework, † using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) § approach to guide its deliberations regarding use of these vaccines. Before this, PCV13 and PPSV23 were recommended for use for U.S. adults and the recommendations varied by age and risk groups. This was simplified in the new recommendations., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Katherine A. Poehling reports institutional support from Safe Sleep for All Newborns, Love Out Loud Early Childhood Fellowship, Intimate Partner Violence Collaborative Project, Because You Matter: Conversations You Want about COVID-19, text messaging follow-up for patients who missed well child visits, and Reimagining Health and Wellness by Mothers for Our Babies, Families, and Communities. H. Keipp Talbott reports institutional grants from the National Institutes of Health. No other potential conflicts of interest were disclosed.

The mRNA COVID-19 vaccines (Moderna and Pfizer-BioNTech) provide strong protection against severe COVID-19, including hospitalization, for at least several months after receipt of the second dose (1,2). However, studies examining immune responses and differences in protection against COVID-19-associated hospitalization in real-world settings, including by vaccine product, are limited. To understand how vaccine effectiveness (VE) might change with time, CDC and collaborators assessed the comparative effectiveness of Moderna and Pfizer-BioNTech vaccines in preventing COVID-19-associated hospitalization at two periods (14-119 days and ≥120 days) after receipt of the second vaccine dose among 1,896 U.S. veterans at five Veterans Affairs medical centers (VAMCs) during February 1-September 30, 2021. Among 234 U.S. veterans fully vaccinated with an mRNA COVID-19 vaccine and without evidence of current or prior SARS-CoV-2 infection, serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2 were also compared. Adjusted VE 14-119 days following second Moderna vaccine dose was 89.6% (95% CI = 80.1%-94.5%) and after the second Pfizer-BioNTech dose was 86.0% (95% CI = 77.6%-91.3%); at ≥120 days VE was 86.1% (95% CI = 77.7%-91.3%) for Moderna and 75.1% (95% CI = 64.6%-82.4%) for Pfizer-BioNTech. Antibody levels were significantly higher among Moderna recipients than Pfizer-BioNTech recipients across all age groups and periods since vaccination; however, antibody levels among recipients of both products declined between 14-119 days and ≥120 days. These findings from a cohort of older, hospitalized veterans with high prevalences of underlying conditions suggest the importance of booster doses to help maintain long-term protection against severe COVID-19. † ., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Vincent C. Marconi reports institutional support to Emory University from the AIDS Clinical Trials Group and the National Institutes of Health (NIH); grants from Lilly, Gilead, ViiV, NIH, and the Veterans Health Administration; payment or honoraria from Medscape, WebMD, ViiV, Integritas, and Lilly; travel support from NIH; and participation on an NIH Data Safety Monitoring Board. Miwako Kobayashi reports support for attending a meeting from the American Veterinary Medical Association. No other potential conflicts of interest were disclosed.

Background: Blastomycosis, coccidioidomycosis, and histoplasmosis cause various symptoms and syndromes, which may present similarly to other infections such as bacterial or viral community-acquired pneumonia, influenza, and tuberculosis., Methods: We used the IBM MarketScan Research Databases to identify adult outpatients with International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), diagnosis codes during 2016-2017 for blastomycosis, coccidioidomycosis, histoplasmosis, pneumonia (viral, bacterial, Streptococcus pneumoniae, and unspecified pneumonia), influenza; tuberculosis, and other lower and upper respiratory infections. We compared symptoms on and in the 90 days before diagnosis between patients with these diagnosis codes., Results: Fever was less common in blastomycosis (2.6%), histoplasmosis (5.3%), and coccidioidomycosis (9.4%) than in patients with influenza (18.5%) or pneumonia (12.6-16.3%). Fungal diseases resembled bacterial, viral, and unspecified pneumonias for many pulmonary symptoms. However, cough was more common with coccidioidomycosis (31.4%) and less common with histoplasmosis (14.0%) and blastomycosis (13.1%) versus influenza (20.2%). Although less frequent, solitary pulmonary nodule (5.2-14.4%), enlarged lymph nodes (3.7-9.0%), hyperhidrosis (<2%), and erythema nodosum (<2%) were particularly suggestive of fungal diseases., Conclusions: Despite limitations inherent in administrative coding, this analysis of symptom codes across disease types suggests that fungal diseases may be difficult to clinically distinguish from other causes of pneumonia except when certain uncommon symptoms are present. Healthcare providers caring for patients with pneumonia, especially if nonresponsive to conventional treatment, should consider fungal diseases as possible etiologies., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Evaluations of vaccine effectiveness (VE) are important to monitor as coronavirus disease 2019 (COVID-19) vaccines are introduced in the general population. Research staff enrolled symptomatic participants seeking outpatient medical care for COVID-19-like illness or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing from a multisite network. VE was evaluated using the test-negative design. Among 236 SARS-CoV-2 nucleic acid amplification test-positive and 576 test-negative participants aged ≥16 years, the VE of messenger RNA vaccines against COVID-19 was 91% (95% confidence interval, 83%-95%) for full vaccination and 75% (55%-87%) for partial vaccination. Vaccination was associated with prevention of most COVID-19 cases among people seeking outpatient medical care., (Published by Oxford University Press for the Infectious Diseases Society of America 2021.)

Three COVID-19 vaccines are authorized or approved for use among adults in the United States (1,2). Two 2-dose mRNA vaccines, mRNA-1273 from Moderna and BNT162b2 from Pfizer-BioNTech, received Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) in December 2020 for persons aged ≥18 years and aged ≥16 years, respectively. A 1-dose viral vector vaccine (Ad26.COV2 from Janssen [Johnson & Johnson]) received EUA in February 2021 for persons aged ≥18 years (3). The Pfizer-BioNTech vaccine received FDA approval for persons aged ≥16 years on August 23, 2021 (4). Current guidelines from FDA and CDC recommend vaccination of eligible persons with one of these three products, without preference for any specific vaccine (4,5). To assess vaccine effectiveness (VE) of these three products in preventing COVID-19 hospitalization, CDC and collaborators conducted a case-control analysis among 3,689 adults aged ≥18 years who were hospitalized at 21 U.S. hospitals across 18 states during March 11-August 15, 2021. An additional analysis compared serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2, the virus that causes COVID-19, among 100 healthy volunteers enrolled at three hospitals 2-6 weeks after full vaccination with the Moderna, Pfizer-BioNTech, or Janssen COVID-19 vaccine. Patients with immunocompromising conditions were excluded. VE against COVID-19 hospitalizations was higher for the Moderna vaccine (93%; 95% confidence interval [CI] = 91%-95%) than for the Pfizer-BioNTech vaccine (88%; 95% CI = 85%-91%) (p = 0.011); VE for both mRNA vaccines was higher than that for the Janssen vaccine (71%; 95% CI = 56%-81%) (all p<0.001). Protection for the Pfizer-BioNTech vaccine declined 4 months after vaccination. Postvaccination anti-spike IgG and anti-RBD IgG levels were significantly lower in persons vaccinated with the Janssen vaccine than the Moderna or Pfizer-BioNTech vaccines. Although these real-world data suggest some variation in levels of protection by vaccine, all FDA-approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Wesley H. Self reports grants and consultant fees from Merck and consultant fees from Aerpio Pharmaceuticals. Adit A. Ginde reports grant support from AbbVie and Faron Pharmaceuticals. Jonathan D. Casey reports a grant (N23HL153584) from the National Institutes of Health (NIH). D. Clark Files reports consultant fees from Cytovale and membership on a Medpace Data Safety Monitoring Board (DSMB). David N. Hager reports salary support from Incyte Corporation, EMPACT Precision Medicine, and the Marcus Foundation. Michelle N. Gong reports grant support from NIH and the Agency for Healthcare Research and Quality (AHRQ) and fees for participating on a DSMB for Regeneron and for participating on a scientific advisory panel for Philips Healthcare. Daniel J. Henning reports consulting fees from Cytovale and Opticyte. Ithan D. Peltan reports grants from NIH and Janssen Pharmaceuticals, institutional fees from Asahi Kasei Pharma and from Regeneron. Samuel M. Brown reports fees from Hamilton for chairing a DSMB, and institutional fees from Faron, Sedana, and Janssen; grants from Sedana, Janssen, NIH, and the Department of Defense (DoD); book royalties from Oxford University and Brigham Young University; and personal fees from New York University for service on a DSMB. Emily T. Martin reports personal fees from Pfizer for unrelated work and a grant from Merck for unrelated work. Akram Khan reports grants from United Therapeutics, Johnson & Johnson, 4D Medical, Lung LLC, and Reata Pharmaceuticals. Arnold S. Monto reports consulting fees from Sanofi-Pasteur and Seqirus. Steven Y. Chang was a speaker for La Jolla Pharmaceuticals and a Consultant for PureTech Health. Jennie H. Kwon reports grant support from NIH. Matthew C. Exline reports talks on nutrition in COVID pneumonia at APEN conference sponsored by Abbott Labs. Natasha Halasa reports grants from Sanofi and Quidel. James D. Chappell reports a grant from the National Center for Advancing Translational Sciences, NIH. Adam S. Lauring reports consultant fees from Sanofi and fees from Roche for membership on a trial steering committee. Carlos G. Grijalva reports consultant fees from Pfizer, Merck, and Sanofi-Pasteur and grants from Campbell Alliance/Syneos Health, NIH, the Food and Drug Administration, AHRQ, and Sanofi. Todd W. Rice reports personal fees from Cumberland Pharmaceuticals, Inc., as the Director of Medical Affairs, consultant fees from Avisa Pharma, LLC; and DSMB membership fees from Sanofi. Christopher J. Lindsell reports grants from NIH, DoD, and the Marcus Foundation; organizational contract fees from bioMerieux, Endpoint LLC, and Entegrion, Inc.; and a patent issued to Cincinnati Children’s Hospital Medical Center for risk stratification in sepsis and septic shock. No other potential conflicts of interest were disclosed.

COVID-19 mRNA vaccines (Pfizer-BioNTech and Moderna) have been shown to be highly protective against COVID-19-associated hospitalizations (1-3). Data are limited on the level of protection against hospitalization among disproportionately affected populations in the United States, particularly during periods in which the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, predominates (2). U.S. veterans are older, more racially diverse, and have higher prevalences of underlying medical conditions than persons in the general U.S. population (2,4). CDC assessed the effectiveness of mRNA vaccines against COVID-19-associated hospitalization among 1,175 U.S. veterans aged ≥18 years hospitalized at five Veterans Affairs Medical Centers (VAMCs) during February 1-August 6, 2021. Among these hospitalized persons, 1,093 (93.0%) were men, the median age was 68 years, 574 (48.9%) were non-Hispanic Black (Black), 475 were non-Hispanic White (White), and 522 (44.4%) had a Charlson comorbidity index score of ≥3 (5). Overall adjusted vaccine effectiveness against COVID-19-associated hospitalization was 86.8% (95% confidence interval [CI] = 80.4%-91.1%) and was similar before (February 1-June 30) and during (July 1-August 6) SARS-CoV-2 Delta variant predominance (84.1% versus 89.3%, respectively). Vaccine effectiveness was 79.8% (95% CI = 67.7%-87.4%) among adults aged ≥65 years and 95.1% (95% CI = 89.1%-97.8%) among those aged 18-64 years. COVID-19 mRNA vaccines are highly effective in preventing COVID-19-associated hospitalization in this older, racially diverse population of predominately male U.S. veterans. Additional evaluations of vaccine effectiveness among various age groups are warranted. To prevent COVID-19-related hospitalizations, all eligible persons should receive COVID-19 vaccination., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Vincent C. Marconi reports research grants from Eli Lilly and Co., Gilead Sciences, and ViiV Healthcare. No other potential conflicts of interest were disclosed.

Real-world evaluations have demonstrated high effectiveness of vaccines against COVID-19-associated hospitalizations (1-4) measured shortly after vaccination; longer follow-up is needed to assess durability of protection. In an evaluation at 21 hospitals in 18 states, the duration of mRNA vaccine (Pfizer-BioNTech or Moderna) effectiveness (VE) against COVID-19-associated hospitalizations was assessed among adults aged ≥18 years. Among 3,089 hospitalized adults (including 1,194 COVID-19 case-patients and 1,895 non-COVID-19 control-patients), the median age was 59 years, 48.7% were female, and 21.1% had an immunocompromising condition. Overall, 141 (11.8%) case-patients and 988 (52.1%) controls were fully vaccinated (defined as receipt of the second dose of Pfizer-BioNTech or Moderna mRNA COVID-19 vaccines ≥14 days before illness onset), with a median interval of 65 days (range = 14-166 days) after receipt of second dose. VE against COVID-19-associated hospitalization during the full surveillance period was 86% (95% confidence interval [CI] = 82%-88%) overall and 90% (95% CI = 87%-92%) among adults without immunocompromising conditions. VE against COVID-19- associated hospitalization was 86% (95% CI = 82%-90%) 2-12 weeks and 84% (95% CI = 77%-90%) 13-24 weeks from receipt of the second vaccine dose, with no significant change between these periods (p = 0.854). Whole genome sequencing of 454 case-patient specimens found that 242 (53.3%) belonged to the B.1.1.7 (Alpha) lineage and 74 (16.3%) to the B.1.617.2 (Delta) lineage. Effectiveness of mRNA vaccines against COVID-19-associated hospitalization was sustained over a 24-week period, including among groups at higher risk for severe COVID-19; ongoing monitoring is needed as new SARS-CoV-2 variants emerge. To reduce their risk for hospitalization, all eligible persons should be offered COVID-19 vaccination., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Samuel M. Brown reports personal fees from Hamilton, institutional fees from Faron Pharmaceuticals and Sedana, grants from Janssen, the National Institutes of Health (NIH), and the Department of Defense (DoD), book royalties from Oxford University and Brigham Young University, outside the submitted work. Jonathan D. Casey reports grants from NIH, outside the submitted work. Steven Y. Chang was a speaker for La Jolla Pharmaceuticals in 2018 and consulted for PureTech Health in 2020. James D. Chappell reports grants from NIH during the conduct of the study. Matthew C. Exline reports support from Abbott Labs for sponsored talks, outside the submitted work. D. Clark Files reports personal consultant fees from Cytovale and is a data and safety monitoring board (DSMB) member from Medpace, outside the submitted work. Adit A. Ginde reports grants from NIH, DoD, AbbVie, and Faron Pharmaceuticals, outside the submitted work. Michelle N. Gong reports grants from NIH and the Agency for Healthcare Research and Quality (AHRQ), DSMB membership fees from Regeneron, and personal fees from Philips Healthcare, outside the submitted work. Carlos G. Grijalva reports consultancy fees from Pfizer, Merck, and Sanofi-Pasteur; grants from Campbell Alliance/Syneos Health, NIH, the Food and Drug Administration, AHQR, and Sanofi, outside the submitted work. David N. Hager reports salary support from Incyte Corporation, the Marcus Foundation, and EMPACT Precision Medicine via Vanderbilt University Medical Center, outside the submitted work. Natasha Halasa reports grants and nonfinancial support from Sanofi, and Quidel outside the submitted work. Daniel J. Henning reports personal consultant fees from Cytovale and Opticyte. Akram Khan reports grants from United Therapeutics, Johnson & Johnson, 4D Medical, Lung LLC, and Reata Pharmaceuticals, outside the submitted work. Adam S. Lauring reports personal fees from Sanofi and Roche, outside the submitted work. Christopher J. Lindsell reports grants from NIH, DoD, and the Marcus Foundation; contract fees from bioMerieux, Endpoint LLC, and Entegrion Inc, outside the submitted work and has a patent for risk stratification in sepsis and septic shock issued. Emily T. Martin reports personal fees from Pfizer and grants from Merck, outside the submitted work. Arnold S. Monto reports consulting fees from Sanofi-Pasteur and Seqirus outside the submitted work. Ithan D. Peltan reports grants from NIH and Janssen Pharmaceuticals and institutional support from Asahi Kasei Pharma and Regeneron, outside the submitted work. Todd W. Rice reports personal fees from Cumberland Pharmaceuticals, Inc. and personal fees from Avisa Pharma, LLC and Sanofi, outside the submitted work. Wesley H. Self reports consulting fees from Aeprio Pharmaceuticals and Merck outside the submitted work. No other potential conflicts of interest were disclosed.

Background: The Diamond Princess cruise ship was the site of a large outbreak of coronavirus disease 2019 (COVID-19). Of 437 Americans and their travel companions on the ship, 114 (26%) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Methods: We interviewed 229 American passengers and crew after disembarkation following a ship-based quarantine to identify risk factors for infection and characterize transmission onboard the ship., Results: The attack rate for passengers in single-person cabins or without infected cabinmates was 18% (58/329), compared with 63% (27/43) for those sharing a cabin with an asymptomatic infected cabinmate, and 81% (25/31) for those with a symptomatic infected cabinmate. Whole genome sequences from specimens from passengers who shared cabins clustered together. Of 66 SARS-CoV-2-positive American travelers with complete symptom information, 14 (21%) were asymptomatic while on the ship. Among SARS-CoV-2-positive Americans, 10 (9%) required intensive care, of whom 7 were ≥70 years., Conclusions: Our findings highlight the high risk of SARS-CoV-2 transmission on cruise ships. High rates of SARS-CoV-2 positivity in cabinmates of individuals with asymptomatic infections suggest that triage by symptom status in shared quarters is insufficient to halt transmission. A high rate of intensive care unit admission among older individuals complicates the prospect of future cruise travel during the pandemic, given typical cruise passenger demographics. The magnitude and severe outcomes of this outbreak were major factors contributing to the Centers for Disease Control and Prevention's decision to halt cruise ship travel in US waters in March 2020., (Published by Oxford University Press for the Infectious Diseases Society of America 2020.)

Problem/condition: Adults are at risk for illness, hospitalization, disability and, in some cases, death from vaccine-preventable diseases, particularly influenza and pneumococcal disease. CDC recommends vaccinations for adults on the basis of age, health conditions, prior vaccinations, and other considerations. Updated vaccination recommendations from CDC are published annually in the U.S. Adult Immunization Schedule. Despite longstanding recommendations for use of many vaccines, vaccination coverage among U.S. adults remains low., Reporting Period: August 2017-June 2018 (for influenza vaccination) and January-December 2018 (for pneumococcal, herpes zoster, tetanus and diphtheria [Td]/tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis [Tdap], hepatitis A, hepatitis B, and human papillomavirus [HPV] vaccination)., Description of System: The National Health Interview Survey (NHIS) is a continuous, cross-sectional national household survey of the noninstitutionalized U.S. civilian population. In-person interviews are conducted throughout the year in a probability sample of households, and NHIS data are compiled and released annually. NHIS's objective is to monitor the health of the U.S. population and provide estimates of health indicators, health care use and access, and health-related behaviors. Adult receipt of influenza, pneumococcal, herpes zoster, Td/Tdap, hepatitis A, hepatitis B, and at least 1 dose of HPV vaccines was assessed. Estimates were derived for a new composite adult vaccination quality measure and by selected demographic and access-to-care characteristics (e.g., age, race/ethnicity, indication for vaccination, travel history [travel to countries where hepatitis infections are endemic], health insurance status, contacts with physicians, nativity, and citizenship). Trends in adult vaccination were assessed during 2010-2018., Results: Coverage for the adult age-appropriate composite measure was low in all age groups. Racial and ethnic differences in coverage persisted for all vaccinations, with lower coverage for most vaccinations among non-White compared with non-Hispanic White adults. Linear trend tests indicated coverage increased from 2010 to 2018 for most vaccines in this report. Few adults aged ≥19 years had received all age-appropriate vaccines, including influenza vaccination, regardless of whether inclusion of Tdap (13.5%) or inclusion of any tetanus toxoid-containing vaccine (20.2%) receipt was measured. Coverage among adults for influenza vaccination during the 2017-18 season (46.1%) was similar to the estimate for the 2016-17 season (45.4%), and coverage for pneumococcal (adults aged ≥65 years [69.0%]), herpes zoster (adults aged ≥50 years and aged ≥60 years [24.1% and 34.5%, respectively]), tetanus (adults aged ≥19 years [62.9%]), Tdap (adults aged ≥19 years [31.2%]), hepatitis A (adults aged ≥19 years [11.9%]), and HPV (females aged 19-26 years [52.8%]) vaccination in 2018 were similar to the estimates for 2017. Hepatitis B vaccination coverage among adults aged ≥19 years and health care personnel (HCP) aged ≥19 years increased 4.2 and 6.7 percentage points to 30.0% and 67.2%, respectively, from 2017. HPV vaccination coverage among males aged 19-26 years increased 5.2 percentage points to 26.3% from the 2017 estimate. Overall, HPV vaccination coverage among females aged 19-26 years did not increase, but coverage among Hispanic females aged 19-26 years increased 10.8 percentage points to 49.6% from the 2017 estimate. Coverage for the following vaccines was lower among adults without health insurance compared with those with health insurance: influenza vaccine (among adults aged ≥19 years, 19-49 years, and 50-64 years), pneumococcal vaccine (among adults aged 19-64 years at increased risk), Td vaccine (among all age groups), Tdap vaccine (among adults aged ≥19 years and 19-64 years), hepatitis A vaccine (among adults aged ≥19 years overall and among travelers aged ≥19 years), hepatitis B vaccine (among adults aged ≥19 years and 19-49 years and among travelers aged ≥19 years), herpes zoster vaccine (among adults aged ≥60 years), and HPV vaccine (among males and females aged 19-26 years). Adults who reported having a usual place for health care generally reported receipt of recommended vaccinations more often than those who did not have such a place, regardless of whether they had health insurance. Vaccination coverage was higher among adults reporting ≥1 physician contact during the preceding year compared with those who had not visited a physician during the preceding year, regardless of whether they had health insurance. Even among adults who had health insurance and ≥10 physician contacts during the preceding year, depending on the vaccine, 20.1%-87.5% reported not having received vaccinations that were recommended either for all persons or for those with specific indications. Overall, vaccination coverage among U.S.-born adults was significantly higher than that of foreign-born adults, including influenza vaccination (aged ≥19 years), pneumococcal vaccination (all ages), tetanus vaccination (all ages), Tdap vaccination (all ages), hepatitis B vaccination (aged ≥19 years and 19-49 years and travelers aged ≥19 years), herpes zoster vaccination (all ages), and HPV vaccination among females aged 19-26 years. Vaccination coverage also varied by citizenship status and years living in the United States., Interpretation: NHIS data indicate that many adults remain unprotected against vaccine-preventable diseases. Coverage for the adult age-appropriate composite measures was low in all age groups. Individual adult vaccination coverage remained low as well, but modest gains occurred in vaccination coverage for hepatitis B (among adults aged ≥19 years and HCP aged ≥19 years), and HPV (among males aged 19-26 years and Hispanic females aged 19-26 years). Coverage for other vaccines and groups with Advisory Committee on Immunization Practices vaccination indications did not improve from 2017. Although HPV vaccination coverage among males aged 19-26 years and Hispanic females aged 19-26 years increased, approximately 50% of females aged 19-26 years and 70% of males aged 19-26 years remained unvaccinated. Racial/ethnic vaccination differences persisted for routinely recommended adult vaccines. Having health insurance coverage, having a usual place for health care, and having ≥1 physician contacts during the preceding 12 months were associated with higher vaccination coverage; however, these factors alone were not associated with optimal adult vaccination coverage, and findings indicate missed opportunities to vaccinate remained., Public Health Actions: Substantial improvement in adult vaccination uptake is needed to reduce the burden of vaccine-preventable diseases. Following the Standards for Adult Immunization Practice (https://www.cdc.gov/vaccines/hcp/adults/for-practice/standards/index.html), all providers should routinely assess adults' vaccination status at every clinical encounter, strongly recommend appropriate vaccines, either offer needed vaccines or refer their patients to another provider who can administer the needed vaccines, and document vaccinations received by their patients in an immunization information system., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were reported.

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., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Christopher J. Lindsell reports grants from National Institutes of Health, U.S. Department of Defense, Marcus Foundation, Endpoint Health, Entegrion, bioMerieux, and Bioscape Digital, outside the submitted work. Jay S. Steingrub reports grants from National Institutes of Health, outside the submitted work. Akram Khan reports grants from United Therapeutics, Actelion Pharmaceuticals, Regeneron, and Reata Pharmaceuticals, outside the submitted work. Samuel M. Brown reports grants from National Institutes of Health, U.S. Department of Defense, Intermountain Research and Medical Foundation, and Janssen, and consulting fees paid to his employer from Faron and Sedana, all outside the submitted work. Ithan D. Peltan reports grants from National Institutes of Health and, outside the submitted work, grants from Asahi Kasei Pharma, Janssen Pharmaceuticals, and Regeneron. Adit A. Ginde reports grants from National Institutes of Health, U.S. Department of Defense and AbbVie, outside the submitted work. Carlos G. Grijalva reports consulting fees from Pfizer, Merck, and Sanofi-Pasteur, grants from Campbell Alliance/Syneos Health, National Institutes of Health, Food and Drug Administration, and Agency for Health Care Research and Quality, outside the submitted work. Michelle N. Gong reports grants from National Institutes of Health, Agency for Healthcare Research and Quality, and consulting fees from Regeneron, Philips Healthcare, all outside the submitted work. Steven Y. Chang reports consulting fees from PureTech Health and speaker fees from La Jolla Pharmaceuticals, both outside the submitted work. Jonathan D. Casey reports grants from National Institutes of Health, outside the submitted work. Todd W. Rice reports grants from National Institutes of Health and Endpoint Health, consulting work for Cumberland Pharmaceuticals, Inc, and Sanofi, Inc., outside the submitted work. Manjusha Gaglani reports grants from CDC-Abt Associates, outside the submitted work. Emily T. Martin reports personal fees from Pfizer and grants from Merck, outside the submitted work. Anurag Malani reports shareholder of Pfizer pharmaceuticals. Arnold S. Monto reports personal fees from Sanofi Pasteur and Seqirus, outside the submitted work. Fernanda P. Silveira reports grants from Shire, Qiagen, Ansun, and Novartis, outside the submitted work. Richard K. Zimmerman reports grants from Sanofi Pasteur, outside the submitted work. Donald B. Middleton reports grants and personal fees from Pfizer and personal fees from Seqirus, Sanofi Pasteur, and GlaxoSmithKline, outside the submitted work. No other potential conflicts of interest were disclosed.

Public health travel restrictions (PHTR) are crucial measures during communicable disease outbreaks to prevent transmission during commercial airline travel and mitigate cross-border importation and spread. We evaluated PHTR implementation for US citizens on the Diamond Princess during its coronavirus disease (COVID-19) outbreak in Japan in February 2020 to explore how PHTR reduced importation of COVID-19 to the United States during the early phase of disease containment. Using PHTR required substantial collaboration among the US Centers for Disease Control and Prevention, other US government agencies, the cruise line, and public health authorities in Japan. Original US PHTR removal criteria were modified to reflect international testing protocols and enable removal of PHTR for persons who recovered from illness. The impact of PHTR on epidemic trajectory depends on the risk for transmission during travel and geographic spread of disease. Lessons learned from the Diamond Princess outbreak provide critical information for future PHTR use.

On March 13, 2020, the United States declared a national emergency concerning the novel coronavirus disease 2019 (COVID-19) outbreak (1). In response, many state and local governments issued shelter-in-place or stay-at-home orders, restricting nonessential activities outside residents' homes (2). CDC initially issued guidance recommending postponing routine adult vaccinations, which was later revised to recommend continuing to administer routine adult vaccines (3). In addition, factors such as disrupted operations of health care facilities and safety concerns regarding exposure to SARS-CoV-2, the virus that causes COVID-19, resulted in delay or avoidance of routine medical care (4), likely further affecting delivery of routine adult vaccinations. Medicare enrollment and claims data of Parts A (hospital insurance), B (medical insurance), and D (prescription drug insurance) were examined to assess the change in receipt of routine adult vaccines during the pandemic. Weekly receipt of four vaccines (13-valent pneumococcal conjugate vaccine [PCV13], 23-valent pneumococcal polysaccharide vaccine [PPSV23], tetanus-diphtheria or tetanus-diphtheria-acellular pertussis vaccine [Td/Tdap], and recombinant zoster vaccine [RZV]) by Medicare beneficiaries aged ≥65 years during January 5-July 18, 2020, was compared with that during January 6-July 20, 2019, for the total study sample and by race and ethnicity. Overall, weekly administration rates of the four examined vaccines declined by up to 89% after the national emergency declaration in mid-March (1) compared with those during the corresponding period in 2019. During the first week following the national emergency declaration, the weekly vaccination rates were 25%-62% lower than those during the corresponding week in 2019. After reaching their nadirs of 70%-89% below 2019 rates in the second to third week of April 2020, weekly vaccination rates gradually began to recover through mid-July, but by the last study week were still lower than were those during the corresponding period in 2019, with the exception of PPSV23. Vaccination declined sharply for all vaccines studied, overall and across all racial and ethnic groups. While the pandemic continues, vaccination providers should emphasize to patients the importance of continuing to receive routine vaccinations and provide reassurance by explaining the procedures in place to ensure patient safety (3)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Coronavirus disease 2019 (COVID-19), the respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. In response to the first cases identified in the United States, close contacts of confirmed COVID-19 cases were investigated to enable early identification and isolation of additional cases and to learn more about risk factors for transmission. Close contacts of nine early travel-related cases in the United States were identified and monitored daily for development of symptoms (active monitoring). Selected close contacts (including those with exposures categorized as higher risk) were targeted for collection of additional exposure information and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction at the Centers for Disease Control and Prevention. Four hundred four close contacts were actively monitored in the jurisdictions that managed the travel-related cases. Three hundred thirty-eight of the 404 close contacts provided at least basic exposure information, of whom 159 close contacts had ≥1 set of respiratory samples collected and tested. Across all actively monitored close contacts, two additional symptomatic COVID-19 cases (i.e., secondary cases) were identified; both secondary cases were in spouses of travel-associated case patients. When considering only household members, all of whom had ≥1 respiratory sample tested for SARS-CoV-2, the secondary attack rate (i.e., the number of secondary cases as a proportion of total close contacts) was 13% (95% CI: 4-38%). The results from these contact tracing investigations suggest that household members, especially significant others, of COVID-19 cases are at highest risk of becoming infected. The importance of personal protective equipment for healthcare workers is also underlined. Isolation of persons with COVID-19, in combination with quarantine of exposed close contacts and practice of everyday preventive behaviors, is important to mitigate spread of COVID-19., Competing Interests: The authors have declared that no competing interests exist.

An estimated 30 million passengers are transported on 272 cruise ships worldwide each year* (1). Cruise ships bring diverse populations into proximity for many days, facilitating transmission of respiratory illness (2). SARS-CoV-2, the virus that causes coronavirus disease (COVID-19) was first identified in Wuhan, China, in December 2019 and has since spread worldwide to at least 187 countries and territories. Widespread COVID-19 transmission on cruise ships has been reported as well (3). Passengers on certain cruise ship voyages might be aged ≥65 years, which places them at greater risk for severe consequences of SARS-CoV-2 infection (4). During February-March 2020, COVID-19 outbreaks associated with three cruise ship voyages have caused more than 800 laboratory-confirmed cases among passengers and crew, including 10 deaths. Transmission occurred across multiple voyages of several ships. This report describes public health responses to COVID-19 outbreaks on these ships. COVID-19 on cruise ships poses a risk for rapid spread of disease, causing outbreaks in a vulnerable population, and aggressive efforts are required to contain spread. All persons should defer all cruise travel worldwide during the COVID-19 pandemic., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

The findings and conclusions in this report are those of the authors and do not necessarily represent the official positon of the Centers for Disease Control and Prevention., Background: Continued indirect effects provided by the childhood pneumococcal conjugate vaccine (13-valent pneumococcal conjugate vaccine [PCV13]) program in the United States have decreased disease in the adult population, reducing the potential direct effects of vaccinating older adults., Objective: We examined the incremental cost-effectiveness of continuing to recommend PCV13 in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) at age 65 compared to a strategy that only included a recommendation for PPSV23 at age 65., Methods: We used a probabilistic model following a cohort of 65 year olds in 2019. We used vaccination coverage and disease incidence estimates for healthy adults and adults with chronic medical conditions. We incorporated continued indirect effects from the childhood PCV13 program on adult disease incidence., Results: In the base case scenario, continuing to recommend PCV13 at age 65 cost $561,682 per quality-adjusted life year (QALY) gained. In a scenario where PPSV23 provided modest protection against non-invasive pneumococcal pneumonia, costs increased to $2.3 million per QALY. These estimates are larger than our prior estimates for cost-effectiveness of this recommendation in the context of predicted indirect effects due to new data indicating PCV13 provided limited impact on serotype 3, the major cause of the remaining PCV13-type disease. Under our prior assumptions about PCV13 effectiveness against serotype 3 disease, the cost of continuing the recommendation is $207,607 per QALY., Conclusion: Indirect effects from the childhood PCV13 program have dramatically increased the cost per QALY of continuing to recommend PCV13 at age 65 after only a few years., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019. Published by Elsevier Ltd.)

Two pneumococcal vaccines are currently licensed for use in adults in the United States: a 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13, Pfizer, Inc.]) and a 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Pneumovax 23, Merck and Co., Inc.]). In 2014, the Advisory Committee on Immunization Practices (ACIP)* recommended routine use of PCV13 in series with PPSV23 for all adults aged ≥65 years based on demonstrated PCV13 safety and efficacy against PCV13-type pneumonia among adults aged ≥65 years (1). At that time, ACIP recognized that there would be a need to reevaluate this recommendation because it was anticipated that PCV13 use in children would continue to reduce disease burden among adults through reduced carriage and transmission of vaccine serotypes from vaccinated children (i.e., PCV13 indirect effects). On June 26, 2019, after having reviewed the evidence accrued during the preceding 3 years (https://www.cdc.gov/vaccines/acip/recs/grade/PCV13.html), ACIP voted to remove the recommendation for routine PCV13 use among adults aged ≥65 years and to recommend administration of PCV13 based on shared clinical decision-making for adults aged ≥65 years who do not have an immunocompromising condition, † cerebrospinal fluid (CSF) leak, or cochlear implant, and who have not previously received PCV13. ACIP recognized that some adults aged ≥65 years are potentially at increased risk for exposure to PCV13 serotypes, such as persons residing in nursing homes or other long-term care facilities and persons residing in settings with low pediatric PCV13 uptake or traveling to settings with no pediatric PCV13 program, and might attain higher than average benefit from PCV13 vaccination. When patients and vaccine providers § engage in shared clinical decision-making for PCV13 use to determine whether PCV13 is right for a particular person, considerations might include both the person's risk for exposure to PCV13 serotypes and their risk for developing pneumococcal disease as a result of underlying medical conditions. All adults aged ≥65 years should continue to receive 1 dose of PPSV23. If the decision is made to administer PCV13, it should be given at least 1 year before PPSV23. ACIP continues to recommend PCV13 in series with PPSV23 for adults aged ≥19 years with an immunocompromising condition, CSF leak, or cochlear implant (2)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Objective: The number of patients with HCV-related cirrhosis is increasing, leading to a rising risk of complications and death. Prognostic stratification in patients with early-stage cirrhosis is still challenging. We aimed to develop and validate a clinically useful prognostic index based on genomic and clinical variables to identify patients at high risk of disease progression., Design: We developed a prognostic index, comprised of a 186-gene signature validated in our previous genome-wide profiling study, bilirubin (>1 mg/dL) and platelet count (<100,000/mm(3)), in an Italian HCV cirrhosis cohort (training cohort, n=216, median follow-up 10 years). The gene signature test was implemented using a digital transcript counting (nCounter) assay specifically developed for clinical use and the prognostic index was evaluated using archived specimens from an independent cohort of HCV-related cirrhosis in the USA (validation cohort, n=145, median follow-up 8 years)., Results: In the training cohort, the prognostic index was associated with hepatic decompensation (HR=2.71, p=0.003), overall death (HR=6.00, p<0.001), hepatocellular carcinoma (HR=3.31, p=0.001) and progression of Child-Turcotte-Pugh class (HR=6.70, p<0.001). The patients in the validation cohort were stratified into high-risk (16%), intermediate-risk (42%) or low-risk (42%) groups by the prognostic index. The high-risk group had a significantly increased risk of hepatic decompensation (HR=7.36, p<0.001), overall death (HR=3.57, p=0.002), liver-related death (HR=6.49, p<0.001) and all liver-related adverse events (HR=4.98, p<0.001)., Conclusions: A genomic and clinical prognostic index readily available for clinical use was successfully validated, warranting further clinical evaluation for prognostic prediction and clinical trial stratification and enrichment for preventive interventions., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Use of nucleic acid amplification tests (NAAT) for the diagnosis of Mycobacterium tuberculosis (TB) has been recommended on respiratory specimens submitted for acid-fast bacilli (AFB) testing. It also helps distinguish between TB and non-tuberculous mycobacteria (NTM) species in a setting where NTM rates are relatively high. The purposes of this study are to describe the trend and characteristics of all AFB smear-positive respiratory samples that underwent amplified Mycobacterium tuberculosis direct (MTD) testing, a type of NAAT, and to evaluate the clinical utility and necessity of the test for diagnosis of TB in a population with high-HIV prevalence., Methods: Prospective diagnostic testing and retrospective data analyses were conducted on all AFB smear-positive respiratory samples that underwent MTD testing from 2001 to 2011 at Grady Memorial Hospital (GMH), Atlanta, USA. The test performance was compared to culture., Results: A total of 2,240 AFB smear-positive specimens from 1,412 patients were tested and analyzed in the study. The proportion of specimens that were culture-positive for TB was 28.5%. Sensitivity, specificity, positive predictive value, and negative predictive value of the MTD were 99.0%, 98.0%, 95.3% and 99.6%, respectively. A downward trend was observed in the yearly numbers as well as the proportions of MTD-positive specimens during the study period (p<0.01). There were 2,027 (90.5%) specimens from patients with known HIV status, of which 70.6% was HIV positive and the majority of them (81.8%) had CD4 counts of less than 200 cells/µL. HIV-positives were more likely to have NTM compared to HIV negatives (67.7% vs. 35.4%, p<0.01)., Conclusion: Despite the decrease in the incidence of TB, NAAT continues to be an accurate and important diagnostic test in a population with high HIV prevalence, and it differentiates TB and NTM organisms.

Background: The University of Pennsylvania Smell Identification Test (UPSIT) is a popular olfactory function test used throughout the world. In Japan, however, it is not widely used because it is written in English and some of the test odorants are unfamiliar to the Japanese population. Recently, a cross-culturally modified UPSIT was developed. This study was designed to determine if the Japanese version of the UPSIT (UPSIT-J) is effective in Japanese populations., Methods: We administered the UPSIT-J to 50 normosmic Japanese subjects and 54 Japanese patients with known olfactory dysfunction. Subjects were also administered the Japanese standard olfactory threshold test (T&T olfactometry), the Odor Stick Identification Test for Japanese (OSIT-J) and i.v. olfactometry (the Alinamin test). Test results from the UPSIT-J and subjects' opinions were compared with the standard Japanese tests of olfactory function., Results: Most subjects reported that the UPSIT-J was easy and interesting compared with OSIT-J and easier and more interesting than the T&T olfactometry and Alinamin test. Identification rates for nine of the UPSIT-J odorants were found to be <80% for normal subjects. UPSIT-J scores correlated with subjects' self-reported levels of olfactory function (r(s) = 0.85), OSIT-J score (r(s) = 0.86), recognition threshold of the T&T olfactometry (r(s) = 0.80), and Alinamin test results (r(s) = 0.38 for latency; r(s) = 0.52 for duration time)., Conclusion: Although a cultural bias was detected for some test odorants, this study indicates that the UPSIT-J is effective for use in the clinic to assess olfactory function in the Japanese population.

Background & Aims: In approximately 70% of patients with hepatocellular carcinoma (HCC) treated by resection or ablation, disease recurs within 5 years. Although gene expression signatures have been associated with outcome, there is no method to predict recurrence based on combined clinical, pathology, and genomic data (from tumor and cirrhotic tissue). We evaluated gene expression signatures associated with outcome in a large cohort of patients with early stage (Barcelona-Clinic Liver Cancer 0/A), single-nodule HCC and heterogeneity of signatures within tumor tissues., Methods: We assessed 287 HCC patients undergoing resection and tested genome-wide expression platforms using tumor (n = 287) and adjacent nontumor, cirrhotic tissue (n = 226). We evaluated gene expression signatures with reported prognostic ability generated from tumor or cirrhotic tissue in 18 and 4 reports, respectively. In 15 additional patients, we profiled samples from the center and periphery of the tumor, to determine stability of signatures. Data analysis included Cox modeling and random survival forests to identify independent predictors of tumor recurrence., Results: Gene expression signatures that were associated with aggressive HCC were clustered, as well as those associated with tumors of progenitor cell origin and those from nontumor, adjacent, cirrhotic tissues. On multivariate analysis, the tumor-associated signature G3-proliferation (hazard ratio [HR], 1.75; P = .003) and an adjacent poor-survival signature (HR, 1.74; P = .004) were independent predictors of HCC recurrence, along with satellites (HR, 1.66; P = .04). Samples from different sites in the same tumor nodule were reproducibly classified., Conclusions: We developed a composite prognostic model for HCC recurrence, based on gene expression patterns in tumor and adjacent tissues. These signatures predict early and overall recurrence in patients with HCC, and complement findings from clinical and pathology analyses., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the association between fruit and vegetable access in the community and change in fruit and vegetable consumption among participants in community-based health promotion programmes., Design: Fruit and vegetable consumption and perceived access to fresh fruit and vegetables were measured by self-administered questionnaires at programme start, end and 1-year follow-up. Community produce availability was determined by grocery store assessments measuring the display space devoted to fruit and vegetable offerings, as well as price, variety and freshness. A total of nine communities were studied; 130 participants completed the fruit and vegetable portions of the questionnaires and could be linked to grocery store assessments., Results: Participants made modest but significant increases in fruit and vegetable consumption from programme start to end: the average increase was 2.88 (95% CI 1.52, 4.25) servings weekly; the average increase from start to follow-up was 2.52 (95% CI 1.09, 3.95) servings weekly. Greater perceived access to fruits and vegetables was significantly associated with higher increases in fruit and vegetable consumption from programme start to programme end. Greater availability of produce was associated with greater increases in fruit and vegetable servings from programme start to programme end as measured by store assessments., Conclusions: Environmental factors, such as access to fruits and vegetables, can modify the effects of community interventions. Interventions with the goal of increasing fruit and vegetable consumption should consider focusing on increasing access to fresh fruits and vegetables in target communities. Similarly, researchers may want to study access as an intervention, not just a contextual variable.

Contributions of hop-derived thiols were examined. Extremely strong fruity, black currant-like aromas were detected in beers hopped with some U.S. cultivars. 4-Mercapto-4-methylpentan-2-one (4MMP) was supposed to be the main contributor to the fruity aroma, and the contents between cultivars were investigated. In hop pellets, a negative correlation between 4MMP concentration and copper ion content in hops was observed. 4MMP was detected only in U.S., Australian, and New Zealand cultivars, but no European ones, which are treated with copper-containing fungicides (Bordeaux mixture) and therefore have a high content of copper ions. The 4MMP content was highest in Simcoe cultivars, followed by Summit, Apollo, Topaz, Cascade pellets, and also differed between crop years. It was indicated that most 4MMP exists freely in wort or in hop pellets with only small amounts formed from precursors and that the amounts increased during the fermentation process.

In 2003, the John A. Hartford Foundation Institute for Geriatric Nursing (Hartford Institute), in collaboration with the American Association of Colleges of Nursing, conducted a survey of baccalaureate schools of nursing in the United States to compare gerontological content to baseline data collected by the Hartford Institute in 1997. Since last surveyed in 1997, baccalaureate nursing programs have been the recipients of substantial new resources and initiatives focused on gerontological curriculum enhancement. While these initiatives are ongoing, and some are in an early stage of development, resurveying baccalaureate programs was seen as a means of taking a midcourse "pulse" as to the effectiveness of these efforts. Data suggest that there has been a fundamental shift in baccalaureate curriculum toward incorporation of a greater amount of gerontological content, integration of gerontological content in a greater number of nursing courses, and more diversity of clinical sites used for gerontological clinical experiences. As baccalaureate programs increasingly address the need to enhance gerontological nursing curricula, there continues to be an obligation to address the growing shortage of faculty with qualifications in gerontological nursing.

Nurses Improving Care to Health System Elders (NICHE) is a comprehensive program that hospitals use to foster system-wide improvements in the care of older patients. The authors report on a survey of 103 NICHE hospitals to determine perceptions of the NICHE program, the adoption of NICHE models and protocols, and the educational outcomes, policy changes, and benchmarks related to care of older patients established by the participating NICHE hospitals.

Background: Although several treatment and screening methods have been tried, the incidence of patients with end-stage renal disease (ESRD) on renal replacement therapy (RRT) continues to increase worldwide. By making a detailed analysis of the major primary renal diseases, we found there have been some favorable effects in the incidence rate of ESRD recently in Japan., Methods: A total of 339,478 patients in Japan and 909,591 patients in the United States started RRT between 1983 and 1999. We compared trends of average age and incidence rate in each age group with major primary renal diseases and in racial groups after adjusting for general population aging by using a linear regression analysis., Results: All trends in ESRD incidence rates among Japanese, US total, US white, and US black patients showed significant increases (P < 0.001). A significant positive linear relationship between year and mean age at start of RRT also was observed (P < 0.001). After adjustment for general population aging, the mean age increment in Japanese patients with glomerulonephritis was increased significantly, and the proportion of Japanese patients who had glomerulonephritis and were younger than 45 years was decreased, but this decrement was not observed in US patients with glomerulonephritis., Conclusion: The reduced number of new patients with ESRD with glomerulonephritis might be caused by early detection and early referral to nephrologists as a result of the Japanese urinalysis-screening program. To reduce the ESRD population, it will be necessary to establish more effective treatment methods to delay exacerbation of progressive renal diseases.

Objectives: The objective of this study was to determine the national practice patterns of nurse practitioners (NPs) providing care in long-term care (LTC) facilities, including the number and characteristics of LTC facilities that use NPs for any portion of care to residents, NP activities, and employment arrangements between NPs, physicians, and facilities., Design: Mailed survey., Participants: Participants included all physicians who are members of the American Medical Directors Association (AMDA)., Measurement: The survey instrument was constructed to obtain information in the following six domains: (1) the number of LTC facilities that have NPs involved in providing care; (2) the number of NPs engaged in care at these facilities; (3) the types of employment/financial arrangements between NPs and LTC facilities; (4) the types of services provided by the NPs; (5) the effectiveness of the NPs as perceived by the medical directors; and (6) the perceived future demand for NPs in LTC., Results: Of a total of 870 respondents (response rate 19%), 546 respondents (63%) reported the involvement of NPs in the care of residents in their facilities. In total, respondents identified 1160 NPs involved in care, with a median of two NPs per responding facility (range, 1-10). Respondents reported that NPs make sick/urgent resident visits (96%), provide preventive care to long-stay residents (88%), and perform alternating required regulatory 30/60 (88%), hospice care (80%), and wound care (78%). Significant variations in practice patterns were found between NPs employed by a LTC facility (19% of respondents) as compared with those NPs employed in other arrangements. Large majorities of medical directors stated that NPs are particularly effective in maintaining physician satisfaction (90%), resident satisfaction (87%), and family satisfaction (85%). An additional 34% of the respondents projected an increased need for NPs in nursing homes in the future., Conclusion: NPs involved in LTC are more likely to be involved in the care of residents in the nation's larger (>100-bed) LTC facilities. The substantial number and types of services provided by these NPs, coupled with the high resident, family, and physician satisfaction with their services, suggests the need for educational, policy, and reimbursement strategies to encourage the further involvement of NPs in the care of residents in nursing homes.

Percutaneous coronary intervention (PCI) devices are much more expensive in Japan than in the United States, but their prices were reduced in April 2002. This study evaluated the impact of that change in the price of PCI devices on medical expenses. In-hospital costs of 22 consecutive patients who underwent elective single-vessel PCI without a debulking procedure before April 2002 were collected and the in-hospital cost of each patient was recalculated by applying the current prices of the PCI devices and those in the USA. For patients treated with PCI before April 2002, the in-hospital cost was 1,456,375+/-358,781 yen, but when the current price is used, the in-hospital cost is estimated to be 1,355,812 +/-313,237 yen (7% reduction). If the prices of the devices were reduced to those in USA, there would be a 53% reduction (689,417 +/-99,139 yen). Although the change in the price of PCI devices in April 2002 has reduced in-hospital costs, the devices are still much more expensive in Japan than in the USA. Further reduction of the price is required to make PCI more cost-effective.

In 1995, the Japan Diabetes Society (JDS) appointed the Committee for the Classification and Diagnosis of Diabetes Mellitus. The Committee presented a final report in May 1999 in Japanese. This is the English version with minor modifications for readers outside Japan., Concept of Diabetes Mellitus: Diabetes mellitus represents a group of diseases of heterogeneous etiology, characterized by chronic hyperglycemia and other metabolic abnormalities, which are due to deficiency of insulin effect. After a long duration of metabolic derangement, specific complications of diabetes (retinopathy, nephropathy, and neuropathy) may occur. Arteriosclerosis is also accelerated. Depending on the severity of the metabolic abnormality, diabetes may be asymptomatic, or may be associated with symptoms (thirst, polyuria, and weight loss), or may progress to ketoacidosis and coma., Classification: Both etiological classification and staging of pathophysiology by the degree of deficiency of insulin effect need to be considered. The etiological classification of diabetes and related disorders of glycemia includes, (1) type 1; (2) type 2; (3) those due to specific mechanisms and diseases; and (4) gestational diabetes mellitus. Type 1 is characterized by destructive lesions of pancreatic beta cells either by an autoimmune mechanism or of unknown cause. Type 2 diabetes is characterized by combinations of decreased insulin secretion and decreased insulin sensitivity (insulin resistance). Category (3) includes two subgroups; subgroup A is diabetes in which specific mutations have been identified as a cause of genetic susceptibility, while subgroup B is diabetes associated with other pathologic conditions or diseases. The staging of glucose metabolism includes normal, borderline and diabetic stages. The diabetic stage is further classified into three substages; non-insulin requiring, insulin-requiring for glycemic control, and insulin-dependent (ID) for survival. In each individual, these stages may vary according to the deterioration or the improvement of the metabolic state, either spontaneously or by treatment., Diagnosis: The confirmation of chronic hyperglycemia is a prerequisite for the diagnosis of diabetes mellitus. The state of glycemia may be classified within three categories, diabetic type; borderline type; and normal type. Diabetic type is defined when fasting plasma glucose (FPG) is 7.0 mmol/l (126 mg/dl) or higher, and/or plasma glucose 2 h after 75 g glucose load (2hPG) is 11.1 mmol/l (200 mg/dl) or higher. A casual plasma glucose (PG) > or =11.1 mmol/l (200 mg/dl) also indicates diabetic type. Normal type is defined when FPG is below 6.1 mmol/l (110 mg/dl) and 2hPG below 7.8 mmol/l (140 mg/dl). Borderline type includes those who are neither diabetic nor normal types. These cutoff values are for venous PG measurements. The persistence of 'diabetic type' in a subject indicates that he or she has diabetes. For children, a dose of 1.75 g/kg (maximum, 75 g) is used for oral glucose tolerance test (OGTT). The procedure for clinical diagnosis is as follows. Diabetes mellitus is diagnosed when hyperglycemia meeting the criteria for 'diabetic type' is shown on two or more occasions examined on separate days. Diabetes can be diagnosed by a single PG test of 'diabetic type' if one of the following three conditions co-exists, (1) typical symptoms of diabetes mellitus; (2) HbA1c > or =6.5% by a standardized method; or (3) unequivocal diabetic retinopathy. If the above conditions ((1) or (2)) have been present in the past and well documented, the subject is diagnosed either to have diabetes or to be suspected of diabetes, even if the present level of glycemia does not reach that of 'diabetic type'. If the diagnosis of diabetes cannot be established by these procedures, re-testing of PG is recommended after an appropriate interval. The physician should assess not only the presence or absence of diabetes, but also its etiology and glycemic stage, and the presence and absence of diabetic complications or associated conditions., Epidemiological Aspects and Screening: In order to determine the prevalence of diabetes in a population, 'diabetic type' may be regarded as 'diabetes'. The use of 2hPG cutoff level of > or =11.1 mmol/l (200 mg/dl) is recommended. If this is difficult, the FPG cutoff level of > or =7.0 mmol/l (126 mg/dl) can be used, but is likely to lead to under-ascertainment. For screening, the most important point is not to overlook 'diabetes'. In addition to parameters of hyperglycemia, clinical information such as family history, obesity etc., should be regarded as indications for further testing., Normal Type and Borderline: Only FPG and 2hPG are adopted as cutoff values, but in clinical situations, it is recommended to measure PG also at 30 and 60 min during 75 g OGTT. Among people with normal type, those with 1hPG higher than 10.0 mmol/l (180 mg/dl) are at higher risk to develop diabetes than those with lower 1hPG. When OGTT is performed, the borderline type corresponds to the sum of impaired fasting glycemia (IFG) plus impaired glucose tolerance (IGT) according to the new WHO report. Subjects in this category are at higher risk of developing diabetes than those with 'normal type'. Those with low insulinogenic index (the ratio of increment of plasma insulin to that of PG at 30 min during OGTT) are at particularly high risk to develop diabetes. Microvascular complications are rare but arteriosclerotic complications are fairly frequent in this category., Gestational Diabetes Mellitus (gdm): The current definition of GDM is ' any glucose intolerance developed or detected during pregnancy'. We adopt the proposal of the Japan Society of Gynecology and Obstetrics for the diagnosis of GDM (1984). GDM is defined when two or more values during a 75 g OGTT are higher than the following cutoff levels; FPG > or =5.5 mmol/l (100 mg/dl), 1hPG > or =10.0 mmol/l (180 mg/dl) and 2hPG > or =8.3 mmol/l (150 mg/dl). As a screening test, subjects with casual PG > or =5.5 mmol/l (100 mg/dl) are recommended for further testing. Patients who have had documented glucose intolerance before pregnancy, and who present as 'diabetic type' should be under closer supervision than those who develop GDM during pregnancy for the first time. HbA1c: There is a large overlap in the distribution of HbA1c between groups with 'normal type' and 'borderline type' and mild 'diabetic type'. Therefore, HbA1c is not a suitable parameter to detect mild glucose intolerance. HbA1c higher than 6.5% suggests diabetes, but HbA1c below 6.5% alone should not be taken as evidence against the diagnosis of diabetes. COMPARISON WITH REPORTS OF AMERICAN DIABETES ASSOCIATION (ADA) IN 1997 AND WHO IN 1999: The present report is unique in the following points when compared with those of the ADA 'Diabetes Care 20 (1997) 1183' and WHO 'Report of a WHO Consultation (1999)'. (1) Diabetes due to specific mechanisms and diseases is divided into two subgroups; diabetes in which genetic susceptibility is clarified at the DNA level and diabetes associated with other diseases or conditions. (2) Cutoff PG levels are the same as those of ADA and WHO, but a term 'type' is added to each glycemic category, because a single coding of 'diabetic type' hyperglycemia does not define diabetes. Diabetes is diagnosed when 'diabetic type' hyperglycemia is shown on two or more occasions. (3) A single 'diabetic type' hyperglycemia is considered sufficient for the diagnosis of diabetes, if the patient has typical symptoms, HbA1c > or =6.5%, or diabetic retinopathy. (4) OGTT is recommended for those with mild hyperglycemia, because FPG criteria alone would overlook many subjects with 'diabetic type' in Japan. High 1hPG without elevation of FPG and 2hPG is also considered to be a risk factor for future diabetes. (5) Borderline type in the present report corresponds to the sum of IFG and IGT by WHO when OGTT is performed. (6) New criteria for GDM by OGTT are proposed.

We have studied the restriction fragment-length polymorphism in the 5'-flanking region of the human insulin gene in 47 nondiabetic Japanese subjects and in 52 subjects with non-insulin-dependent diabetes (NIDDM) to elucidate the ethnic variation of the genetic polymorphism and its relationship with NIDDM. Allelic frequencies in the nondiabetic subjects were 0.957 in class 1 (Bgl l fragments of 2800 +/- 300 bp), 0 in class 2 (fragments of 3500 +/- 300 bp), and 0.043 in class 3 (fragments of greater than 3900 bp with a mean of 4500 bp). Corresponding frequencies in the NIDDM subjects were 0.962, 0, and 0.038, respectively. Four subjects with NIDDM who had the class 3 allele did not exhibit any particular clinical characteristics compared with the rest of the patients. Thus, the class 3 allele or the large insertion of the human insulin gene is much less frequent in Japanese than reported in other races, including Caucasians, and this class of allele is not associated with NIDDM in Japanese. Ethnic homogeneity is, thus, important in the analysis and interpretation of the genetic polymorphism.