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Revisión This review article incorporates information from the 4th Global Meningococcal Initiative summit meeting. Since the introduction of stringent COVID-19 infection control and lockdown measures globally in 2020, there has been an impact on IMD prevalence, surveillance, and vaccination compliance. Incidence rates and associated mortality fell across various regions during 2020. A reduction in vaccine uptake during 2020 remains a concern globally. In addition, several Neisseria meningitidis clonal complexes, particularly CC4821 and CC11, continue to exhibit resistance to antibiotics, with resistance to ciprofloxacin or beta-lactams mainly linked to modifications of gyrA or penA alleles, respectively. Beta-lactamase acquisition was also reported through horizontal gene transfer (blaROB-1) involving other bacterial species. Despite the challenges over the past year, progress has also been made on meningococcal vaccine development, with several pentavalent (serogroups ABCWY and ACWYX) vaccines currently being studied in late-stage clinical trial programmes. Medical writing support was funded by Sanofi Pasteur. Sí

Introduction Use of the 13-valent pneumococcal conjugate vaccine in nonimmunocompromised adults aged ≥65 years is controversial. Higher-valency conjugate vaccines (15-valent and 20-valent ) are under development; their potential cost effectiveness in older adults is unknown, particularly when potential indirect (herd immunity) effects from childhood vaccination are considered. Methods A Markov model estimated the cost effectiveness of current U.S. recommendations and alternative strategies using currently available and in-development pneumococcal conjugate vaccines in seniors. Separately, strategies using a hypothetical 20-valent vaccine adding the 7 most common disease-causing non–13-valent vaccine serotypes were considered. Sensitivity analyses were performed and alternative scenarios were examined. Data were gathered and the analyses were performed in 2020. Results In analyses considering only existing and in-development vaccines, sole 20-valent vaccine use cost $172,491/quality-adjusted life year gained compared with current U.S. recommendations under baseline assumptions (equal serotype effectiveness and no childhood vaccination indirect effects). Strategies using 15-valent vaccine were more costly and less effective. When 13-valent/20-valent vaccines were assumed ineffective against pneumococcal serotype 3 and 15-valent vaccine was fully effective, 15-valent vaccine cost $237,431/quality-adjusted life year gained. With indirect effects considered, 15-valent or 20-valent vaccine cost >$449,000/quality-adjusted life year gained. When adding hypothetical 20-valent vaccine under baseline assumptions, hypothetical 20-valent vaccine cost $139,348/quality-adjusted life year gained. Conclusions In-development pneumococcal conjugate vaccines may be economically unreasonable in older adults, regardless of serotype effectiveness assumptions, particularly when considering potential indirect effects from use of those vaccines in children. Adult vaccines containing high-risk serotypes not contained in childhood vaccines may be more promising.

Background Treatment of severe group A Streptococcus (GAS) infections requires timely and appropriate antibiotic therapy. We describe the epidemiology of antimicrobial-resistant invasive GAS (iGAS) infections in the United States (US). Methods We analyzed population-based iGAS surveillance data at 10 US sites from 2006 through 2017. Cases were defined as infection with GAS isolated from normally sterile sites or wounds in patients with necrotizing fasciitis or streptococcal toxic shock syndrome. GAS isolates were emm typed. Antimicrobial susceptibility was determined using broth microdilution or whole genome sequencing. We compared characteristics among patients infected with erythromycin-nonsusceptible (EryNS) and clindamycin-nonsusceptible (CliNS) strains to those with susceptible infections. We analyzed proportions of EryNS and CliNS among isolates by site, year, risk factors, and emm type. Results Overall, 17 179 iGAS cases were reported; 14.5% were EryNS. Among isolates tested for both inducible and constitutive CliNS (2011–2017), 14.6% were CliNS. Most (99.8%) CliNS isolates were EryNS. Resistance was highest in 2017 (EryNS: 22.8%; CliNS: 22.0%). All isolates were susceptible to β-lactams. EryNS and CliNS infections were most frequent among persons aged 18–34 years and in persons residing in long-term care facilities, experiencing homelessness, incarcerated, or who injected drugs. Patterns varied by site. Patients with nonsusceptible infections were significantly less likely to die. The emm types with >30% EryNS or CliNS included types 77, 58, 11, 83, and 92. Conclusions Increasing prevalence of EryNS and CliNS iGAS infections in the US is predominantly due to expansion of several emm types. Clinicians should consider local resistance patterns when treating iGAS infections.

Background The COVID-19 pandemic has resulted in unprecedented healthcare challenges, and COVID-19 has been linked to secondary infections. Candidemia, a fungal healthcare-associated infection, has been described in patients hospitalized with severe COVID-19. However, studies of candidemia and COVID-19 coinfection have been limited in sample size and geographic scope. We assessed differences in patients with candidemia with and without a COVID-19 diagnosis. Methods We conducted a case-level analysis using population-based candidemia surveillance data collected through the Centers for Disease Control and Prevention’s Emerging Infections Program during April–August 2020 to compare characteristics of candidemia patients with and without a positive test for COVID-19 in the 30 days before their Candida culture using chi-square or Fisher’s exact tests. Results Of the 251 candidemia patients included, 64 (25.5%) were positive for SARS-CoV-2. Liver disease, solid-organ malignancies, and prior surgeries were each >3 times more common in patients without COVID-19 coinfection, whereas intensive care unit–level care, mechanical ventilation, having a central venous catheter, and receipt of corticosteroids and immunosuppressants were each >1.3 times more common in patients with COVID-19. All-cause in-hospital fatality was 2 times higher among those with COVID-19 (62.5%) than without (32.1%). Conclusions One-quarter of candidemia patients had COVID-19. These patients were less likely to have certain underlying conditions and recent surgery commonly associated with candidemia and more likely to have acute risk factors linked to COVID-19 care, including immunosuppressive medications. Given the high mortality, it is important for clinicians to remain vigilant and take proactive measures to prevent candidemia in patients with COVID-19.

Objectives Routine surveillance for streptococcal toxic shock syndrome (STSS), a severe manifestation of invasive group A Streptococcus (GAS) infections, likely underestimates its true incidence. The objective of our study was to evaluate routine identification of STSS in a national surveillance system for invasive GAS infections. Methods Active Bacterial Core surveillance (ABCs) conducts active population-based surveillance for invasive GAS disease in selected US counties in 10 states. We categorized invasive GAS cases with a diagnosis of STSS made by a physician as STSS–physician and cases that met the Council of State and Territorial Epidemiologists (CSTE) clinical criteria for STSS based on data in the medical record as STSS–CSTE. We evaluated agreement between the 2 methods for identifying STSS and compared the estimated national incidence of STSS when applying proportions of STSS–CSTE and STSS–physician among invasive GAS cases from this study with national invasive GAS estimates for 2017. Results During 2014-2017, of 7572 invasive GAS cases in ABCs, we identified 1094 (14.4%) as STSS–CSTE and 203 (2.7%) as STSS–physician, a 5.3-fold difference. Of 1094 STSS–CSTE cases, we identified only 132 (12.1%) as STSS–physician cases. Agreement between the 2 methods for identifying STSS was low (κ = 0.17; 95% CI, 0.14-0.19). Using ABCs data, we estimated 591 cases of STSS–physician and 3618 cases of STSS–CSTE occurred nationally in 2017. Conclusions We found a large difference in estimates of incidence of STSS when applying different surveillance methods and definitions. These results should help with better use of currently available surveillance data to estimate the incidence of STSS and to evaluate disease prevention efforts, in addition to guiding future surveillance efforts for STSS.

Background Incidence of invasive disease due to Haemophilus influenzae serotype a (Hia) increased an average of 13% annually from 2002 through 2015. We describe clinical characteristics and adverse clinical outcomes of US invasive Hia cases detected through multistate surveillance during 2011–2015. Methods Medical record data were abstracted for cases reported in 8 jurisdictions conducting active population- and laboratory-based surveillance for invasive Hia disease across the United States. Isolates from sterile sites were serotyped using real-time polymerase chain reaction. Adverse clinical outcomes were defined as any possible complication of meningitis, bacteremic pneumonia, or bacteremia (including hearing loss and developmental delay, but excluding death) and were assessed at hospital discharge and one-year post-disease onset. Results During 2011–2015, 190 Hia cases were reported to the 8 participating sites; 169 (88.9%) had data abstracted. Many patients were aged Conclusions Hia infection can cause severe disease that requires hospitalization and may also cause short- and long-term adverse clinical outcomes, especially among children. Novel vaccines could prevent morbidity and mortality.

BackgroundWhole genome sequencing (WGS) surveillance and electronic health record data mining have the potential to greatly enhance the identification and control of hospital outbreaks. The objective was to develop methods for examining economic value of a WGS surveillance-based infection prevention (IP) program compared to standard of care (SoC).MethodsThe economic value of a WGS surveillance-based IP program was assessed from a hospital’s perspective using historical outbreaks from 2011–2016. We used transmission network of outbreaks to estimate incremental cost per transmission averted. The number of transmissions averted depended on the effectiveness of intervening against transmission routes, time from transmission to positive culture results and time taken to obtain WGS results and intervene on the transmission route identified. The total cost of an IP program included cost of staffing, WGS, and treating infections.ResultsApproximately 41 out of 89 (46%) transmissions could have been averted under the WGS surveillance-based IP program, and it was found to be a less costly and more effective strategy than SoC. The results were most sensitive to the cost of performing WGS and the number of isolates sequenced per year under WGS surveillance. The probability of the WGS surveillance-based IP program being cost-effective was 80% if willingness to pay exceeded $2400 per transmission averted.ConclusionsThe proposed economic analysis is a useful tool to examine economic value of a WGS surveillance-based IP program. These methods will be applied to a prospective evaluation of WGS surveillance compared to SoC.

Background/objectives Recently revised vaccination recommendations for US adults, aged 65 years and older, include both 23-valent pneumococcal polysaccharide vaccine (PPSV23) and 13-valent pneumococcal conjugate vaccine (PCV13), with PCV13 now recommended for immunocompetent older people based on shared decision making. The public health impact and cost-effectiveness of this recommendation or of pneumococcal vaccine uptake improvement interventions are unclear. Design Markov decision analysis. Setting and participants Hypothetical 65-year-old general and black population cohorts. Intervention Current pneumococcal vaccination recommendations for US older people, an alternative policy omitting PCV13 in immunocompetent older people, and vaccine uptake improvement programs. Results The current pneumococcal vaccination recommendation was the most effective strategy, but afforded slight public health benefits compared to an alternative (PPSV23 for all older people plus PCV13 for the immunocompromised) and cost greater than $750 000 per quality-adjusted life-year (QALY) gained in either population group with a vaccine uptake improvement program (absolute uptake increase = 12.3%; cost = $1.78/eligible patient) in place. The alternative strategy was more economically favorable, but cost greater than $100 000/QALY in either population, with or without an uptake intervention. Results were robust in sensitivity analyses; however, in black older people, the alternative strategy with an uptake program was most likely to be favored in probabilistic sensitivity analyses at a $150 000/QALY gained threshold. Conclusion Current pneumococcal vaccination recommendations for US older people are economically unfavorable compared to an alternative strategy omitting PCV13 in the immunocompetent. The alternative recommendation with an uptake improvement program may be economically reasonable in black population analyses and could be worth considering as a population-wide recommendation if mitigating racial disparities is a priority. J Am Geriatr Soc 68:1271-1278, 2020.

Background Neurosurgery is a notoriously difficult career to enter and requires medical students to engage in extracurricular activities to demonstrate their commitment to the specialty. The National Undergraduate Neuroanatomy Competition (NUNC) was established in 2013 as a means for students to display this commitment as well as academic ability. Methods A bespoke 22-item questionnaire was designed to determine career outcomes and the role of competition attendance in job applications. It was distributed using the SurveyMonkey website to the 87 attendees at the 2013 and 2014 competitions. Results Responses were received by 40 competitors (response rate, 46.0%). Twenty-four responders (60.0%) intended to pursue a career in either neurosurgery (n = 18) or neurology (n = 6). This included 10 responders (25.0%) who had successfully entered either neurosurgery (n = 9) or neurology (n = 1). The performance of these 10 was significantly better than the other responders (57.0 ± 13.6% vs. 46.5 ± 13.5% [n = 30]; P = 0.036). Seventeen responders (42.5%) either included their attendance at NUNC in a post-Foundation job application or intend to. Conclusions The NUNC provides the opportunity for medical students to demonstrate their interest in neurosurgery. It has the potential to be used as a tool for recognizing medical students suitable for neurosurgery training.

Introduction Aspirin and a potent platelet P2Y12 inhibitor, such as prasugrel or ticagrelor, are not always sufficient to prevent thrombus formation in patients with ST-elevation MI (STEMI), leading to “slow flow” or “no reflow” effects after stenting. GPIIb/IIIa inhibitors, such as eptifibatide, may help in this setting, but are not used routinely due to their bleeding risk. GPVI has critical roles in thrombosis and a minimal role in haemostasis. Here we tested whether depletion of GPVI has effects on thrombus formation after MI in an animal model and investigated the effects of a novel platelet GPVI inhibitor, glenzocimab (a Fab fragment of a monoclonal antibody), on platelet activation and thrombus formation when combined with aspirin and ticagrelor. Methods We used intravital microscopy in a murine model of ST-elevation myocardial infarction and ischaemia-reperfusion injury to investigate microvascular thrombosis. We investigated the antithrombotic effects of adding glenzocimab (previously known as ACT017) to blood from healthy donors and 20 patients with ACS treated with aspirin and ticagrelor. We compared the effect of glenzocimab with the GPIIb/IIIa inhibitor eptifibatide ex-vivo. We stimulated platelets with collagen and atherosclerotic plaque material that was sourced from patients undergoing carotid endarterectomy. We investigated effects on platelet aggregation, spreading, signalling, adhesion, thrombin generation, thrombus formation and clot stability ex vivo. Results Genetic depletion of GPVI in an animal model of myocardial infarction reduced microvascular thrombosis. Ex vivo, aspirin and ticagrelor partially inhibited atherosclerotic plaque-induced platelet aggregation (assessed by multiple electrode aggregometry) by 48% compared to control (34±3 vs. 65±4 U; P Conclusions The addition of glenzocimab to aspirin and ticagrelor provides synergistic inhibition of multiple critical mechanisms of atherothrombosis. Glenzocimab and the GPIIb/IIIa inhibitor, eptifibatide, share many similar antithrombotic effects, although glenzocimab has less impact on mechanisms involved in haemostasis compared to eptifibatide. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Academy of Medical Sciences UK Clinical Lecturer Starter GrantRoyal Embassy of Saudi Arabia

Aims The open abdomen following emergency laparotomy for peritoneal contamination is becoming an increasingly popular method of managing severe intra-abdominal sepsis. However, this approach has been associated with increased morbidity and mortality. The aim of this study is to compare patient populations and post-operative outcomes from patients undergoing primary closure or those managed with an open abdomen after emergency laparotomy. Methods A retrospective case note review was undertaken of all patients recorded on the NELA database over a five-year period at a district general hospital. Patients with no intra-abdominal contamination or who were palliated peri-operatively were excluded. Data collected included P-possum morbidity and mortality, post-operative complications (Clavien-Dindo), length of stay and in-hospital mortality. Results 811 NELA entries were reviewed; 313 were included with 79% (n = 248) undergoing primary closure. Cohorts were similar in age and sex. P-possum morbidity and mortality scores were significantly higher in the open abdomen group (89% vs 79%, p = 0.0003; 38% vs 24%, p = 0.0003, respectively). Of the outcome variables, significant complications (34% vs 11%, p = 0.001), length of stay (31 vs 18 days, p = 0.0001) and mortality (11% vs 4%, p = 0.001) were significantly higher in the open compared to closed abdomen group. Only 10% of patients undergoing primary closure required further surgery. Conclusions This study highlights that the open abdomen is used in higher risk patients, with significantly poorer outcomes. This approach, which confers a significant physiological burden requiring further intervention should be used with caution in selected cases.

BackgroundThe COVID-19 pandemic continues to affect the United States and the world. Media reports have suggested that the wave of the alpha variant in the Spring of 2021 in the US caused more cases among younger patients and racial and ethnic subgroups.ApproachWe analyzed electronic health record data from a multihospital health system to test whether younger patients accounted for more cases and more severe disease, and whether racial disparities are widening. We compared demographics, patient characteristics, and hospitalization variables for patients admitted from November 2020 through January 2021 to those admitted in March and April 2021.ResultsWe analyzed data for 37, 502 unique inpatients and outpatients at 21 hospitals from November 1, 2020 to April 30, 2021. Compared to patients from November through January, those with positive tests in March and April were younger and less likely to die. Among patients under age 50, those with positive tests in March and April were three times as likely to be hospitalized and twice as likely to require ICU admission or mechanical ventilation. Individuals identified as Black represented a greater proportion of cases and hospitalizations in March and April as compared to November through January.ConclusionsWe found that relative COVID-19 hospitalization rates for younger individuals and individuals identified as Black were rising over time. These findings have important implications for ongoing public health measures to mitigate the impact of the pandemic.

Neisseria meningitidis remains a major cause of meningitis, sepsis, and other serious infections globally. Almost all meningococcal infections are caused by one of six capsular groups (A, B, C, W, ...

Background Injection drug use (IDU) is a known, but infrequent risk factor on candidemia; however, the opioid epidemic and increases in IDU may be changing the epidemiology of candidemia. Methods Active population-based surveillance for candidemia was conducted in selected US counties. Cases of candidemia were categorized as IDU cases if IDU was indicated in the medical records in the 12 months prior to the date of initial culture. Results During 2017, 1191 candidemia cases were identified in patients aged >12 years (incidence: 6.9 per 100 000 population); 128 (10.7%) had IDU history, and this proportion was especially high (34.6%) in patients with candidemia aged 19–44. Patients with candidemia and IDU history were younger than those without (median age, 35 vs 63 years; P < .001). Candidemia cases involving recent IDU were less likely to have typical risk factors including malignancy (7.0% vs 29.4%; relative risk [RR], 0.2 [95% confidence interval {CI}, .1–.5]), abdominal surgery (3.9% vs 17.5%; RR, 0.2 [95% CI, .09–.5]), and total parenteral nutrition (3.9% vs 22.5%; RR, 0.2 [95% CI, .07–.4]). Candidemia cases with IDU occurred more commonly in smokers (68.8% vs 18.5%; RR, 3.7 [95% CI, 3.1–4.4]), those with hepatitis C (54.7% vs 6.4%; RR, 8.5 [95% CI, 6.5–11.3]), and in people who were homeless (13.3% vs 0.8%; RR, 15.7 [95% CI, 7.1–34.5]). Conclusions Clinicians should consider injection drug use as a risk factor in patients with candidemia who lack typical candidemia risk factors, especially in those with who are 19–44 years of age and have community-associated candidemia.

Problem/Condition Candidemia is a bloodstream infection (BSI) caused by yeasts in the genus Candida. Candidemia is one of the most common health care–associated BSIs in the United States, with all-cause in-hospital mortality of up to 30%. Period Covered 2012–2016. Description of System CDC’s Emerging Infections Program (EIP), a collaboration among CDC, state health departments, and academic partners that was established in 1995, was used to conduct active, population-based laboratory surveillance for candidemia in 22 counties in four states (Georgia, Maryland, Oregon, and Tennessee) with a combined population of approximately 8 million persons. Laboratories serving the catchment areas were recruited to report candidemia cases to the local EIP program staff. A case was defined as a blood culture that was positive for a Candida species collected from a surveillance area resident during 2012–2016. Isolates were sent to CDC for species confirmation and antifungal susceptibility testing. Any subsequent blood cultures with Candida within 30 days of the initial positive culture in the same patient were considered part of the same case. Trained surveillance officers collected clinical information from the medical chart for all cases, and isolates were sent to CDC for species confirmation and antifungal susceptibility testing. Results Across all sites and surveillance years (2012–2016), 3,492 cases of candidemia were identified. The crude candidemia incidence averaged across sites and years during 2012–2016 was 8.7 per 100,000 population; important differences in incidence were found by site, age group, sex, and race. The crude annual incidence was the highest in Maryland (14.1 per 100,000 population) and lowest in Oregon (4.0 per 100,000 population). The crude annual incidence of candidemia was highest among adults aged ≥65 years (25.5 per 100,000 population) followed by infants aged 18 years, 34% were treated with fluconazole alone, 30% with echinocandins alone, and 34% with both. The all-cause, in-hospital case-fatality ratio was 25% for any time after admission; the all-cause in-hospital case-fatality ratio was 8% for

Background The 13-valent pneumococcal vaccine (PCV13) was introduced for US children in 2010 and for immunocompromised adults ≥19 years old in series with the 23-valent polysaccharide vaccine (PPSV23) in 2012. We evaluated PCV13 indirect effects on invasive pneumococcal disease (IPD) among adults with and without PCV13 indications. Methods Using Active Bacterial Core surveillance and the National Health Survey, using Active Bacterial Core surveillance and the National Health Interview Survey, we estimated and compared IPD incidence in 2013–2014 and 2007–2008, by age and serotype group (PCV13, PPSV23-unique, or nonvaccine types [NVTs]), among adults with and without PCV13 indications. Results IPD incidence declined among all adults. Among adults 19–64 years, PCV13-type IPD declined 57% (95% confidence interval [CI], −68% to −43%) in adults with immunocompromising conditions (indication for PCV13 use), 57% (95% CI, −62% to –52%) in immunocompetent adults with chronic medical conditions (CMCs, indications for PPSV23 use alone), and 74% (95% CI, −78% to −70%) in adults with neither vaccine indication. Among adults aged ≥65 years, PCV13-type IPD decreased 68% (95% CI, −76% to −60%) in those with immunocompromising conditions, 68% (95% CI, −72% to −63%) in those with CMCs, and 71% (95% CI, −77% to −64%) in healthy adults. PPSV23-unique types increased in adults 19‒64 years with CMCs, and NVTs did not change among adults with or without PCV13 indications. From 2013 to 2014, non-PCV13 serotypes accounted for 80% of IPD. Conclusions IPD incidence among US adults declined after PCV13 introduction in children. Similar reductions in PCV13-type IPD in those with and without PCV13 indications suggest that observed benefits are largely due to indirect effects from pediatric PCV13 use rather than direct use among adults.

INTRODUCTION: In US adults aged

In the U.S., pneumococcal polysaccharide vaccine (PPSV23) uptake among high-risk adults aged

Background Vaccination of children with 13-valent pneumococcal conjugate vaccine (PCV13) led to declines in vaccine-type pneumococcal nasopharyngeal carriage among adults through indirect effects. In August 2014, PCV13 immunization of all U.S. adults ≥65 years of age was recommended. This study sought to define prevalence and serotype distribution of pneumococcal carriage among adults ≥65 years of age and to describe risk factors for colonization soon after introduction of PCV13 in adults. Methods A cross-sectional survey of non-institutionalized U.S. adults ≥65 years of age was conducted in four states in 2015–2016. Demographic information, risk factors for disease, PCV13 vaccination history, and nasopharyngeal (NP) and oropharyngeal (OP) swabs were collected. NP and OP swabs were processed separately and pneumococcal isolates were serotyped by Quellung reaction. Antimicrobial susceptibility of pneumococcal isolates was performed. NP swabs also underwent real-time PCR for pneumococcal detection and serotyping. Results Of 2989 participants, 45.3% (1354/2989) had been vaccinated with PCV13. Fifty-five (1.8%) carried pneumococcus (45 identified by culture and 10 by real-time PCR only) and PCV13 serotypes were found in eight (0.3%) participants. Almost half (22/45) of pneumococcal isolates were not susceptible to at least one of the antibiotics tested. Vaccine-type carriage among vaccinated and unvaccinated individuals was similar (0.2% vs. 0.1%, respectively). Respiratory symptoms were associated with higher odds of pneumococcal colonization (adjusted OR: 2.1; 95% CI = 1.1–3.8). Conclusions Pneumococcal carriage among non-institutionalized adults ≥65 years of age was very low. Less than 0.5% of both vaccinated and unvaccinated individuals in our study carried vaccine-type serotypes. Over a decade of PCV vaccination of children likely led to indirect effects in adults. However, given the low vaccine-type carriage rates we observed in an already high PCV13 adult coverage setting, it is difficult to attribute our findings to the direct versus indirect effects of PCV13 on adult carriage.

Background The COVID-19 pandemic is causing declines in childhood immunization rates. We examined potential COVID-19-related changes in pediatric 13-valent pneumococcal conjugate vaccine (PCV13) use, subsequent impact on childhood and adult pneumococcal disease rates, and how those changes might affect the favorability of PCV13 use in non-immunocompromised adults aged ≥65 years. Methods A Markov model estimated pediatric disease resulting from decreased PCV13 use in children aged 53% increase in pneumococcal disease was required to favor PCV13 use in non-immunocompromised seniors at a $200,000 per quality-adjusted life-year gained threshold, which corresponded to absolute decreases in pediatric PCV13 vaccination of >50% over a 2-year period. In sensitivity analyses, senior PCV13 vaccination was unfavorable if absolute decreases in pediatric PCV13 receipt were within plausible ranges, despite model assumptions favoring PCV13 use in seniors. Conclusion COVID-19-related decreases in pediatric PCV13 use would need to be both substantial and prolonged to make heightened PCV13 use in non-immunocompromised seniors economically favorable.

Background Pneumococcal vaccination policy for US adults is evolving, but previous research has shown that programs to increase vaccine uptake are economically favorable, despite parameter uncertainty. Using value of information (VOI) analysis and prior analyses, we examine the value of further research on vaccine uptake program parameters. Methods In US 50–64-year-olds, current vaccine recommendations with and without an uptake program were analyzed. In older adults, current recommendations and an alternative strategy (polysaccharide vaccine for all, adding conjugate vaccine only for the immunocompromised) with and without uptake programs were examined. Uptake program parameters were derived from a clinical trial (absolute uptake increase 12.3% [range 0–25%], per-person cost $1.78 [range $0.70–$2.26]), with other parameters obtained from US databases. VOI analyses incorporated probabilistic sensitivity analysis outputs into R-based regression techniques. Results In 50–64-year-olds, an uptake program cost $54,900/QALY gained compared to no uptake program. For ages ≥65, the program cost $287,000/QALY gained with the alternative strategy and $765,000/QALY with current recommendations. In younger adults, population-level expected value of perfect information (EVPI) was $59.7 million at $50,000/QALY gained and $2.8 million at $100,000/QALY gained. In older adults, EVPI values ranged from ~$1 million to $34.5 million at $100,000 and $200,000/QALY thresholds. The population expected value of partial perfect information (EVPPI) for combined uptake program cost and uptake improvement parameters in the younger population was $368,700 at $50,000/QALY and $43,900 at $100,000/QALY gained thresholds. In older adults, population EVPPI for vaccine uptake program parameters was $0 at both thresholds, reaching a maximum value of $445,000 at a $225,000/QALY threshold. Other model parameters comprised larger components of the global EVPI. Conclusion VOI results do not support further research on pneumococcal vaccine uptake programs in adults at commonly cited US cost-effectiveness benchmarks. Further research to reduce uncertainty in other aspects of adult pneumococcal vaccination is justifiable.

Introduction Return-to-duty (RTD) readiness assessment for service members (SM) following concussion requires complex clinical considerations. The Portable Warrior Test of Tactical Agility (POWAR-TOTAL) is a functional assessment which improves on previous laboratory-based RTD assessments. Methods Sixty-four SM diagnosed with concussion and 60 healthy control (HC) SM participated in this study. Group differences were analyzed to validate the POWAR-TOTAL. The High-level Mobility Assessment Test (HiMAT) was used to examine concurrent construct validity. An exploratory logistic regression analysis examined predictive validity. Results The groups were demographically well-matched except for educational level. POWAR-TOTAL measures were statistically significantly different between the groups with moderate to large effect sizes. Concussed participants were less likely to be able to complete all trials of the POWAR-TOTAL. Motor scores correlated highly with HiMAT scores. POWAR-TOTAL motor task performance and membership in the control group was significantly associated with self-reported physical readiness to deploy. Conclusion The POWAR-TOTAL is a clinically feasible, military relevant assessment that is sensitive to differences between concussed and HC SM. This analysis supports the discriminant and construct validity of the POWAR-TOTAL, and may be useful for medical providers evaluating RTD readiness for SM who have sustained a concussion.

Covid-19 had caused more than 1,4 million deaths worldwide by November 26th, 2020. Age is a strong predictor of Covid-19 mortality. Crude death rates have been used to compare the response of countries, however, this measure does not account for age structure. We report age-adjusted mortality and rates at similar timeframes, ~100 days from the 50th confirmed case, for 51 countries, as well as 50 states in the US and the District of Columbia. We found age-adjusted mortality rate at ~ 100 days is 18 times greater in New Jersey (largest mortality in the U.S.), compared to Maine (lowest mortality in the U.S). Similar patterns were present in world countries. In Japan, the age-adjusted mortality rate was 0.1; while in Peru was 47.6 at ~ 100 days of Covid-19 transmission (476 times higher). Europe, Latin America, and the US, resulted in highest age-adjusted mortality rates worldwide during the first 100 days of transmission. The data suggest that measures taken by different territories might be a factor for the different mortality rates across regions and countries worldwide. Age-adjustments are needed to compare mortality between populations with different age-structures. This article is protected by copyright. All rights reserved.

Background Candidemia is a common opportunistic infection causing substantial morbidity and mortality. Because of an increasing proportion of non-albicans Candida species and rising antifungal drug resistance, the Infectious Diseases Society of America (IDSA) changed treatment guidelines in 2016 to recommend echinocandins over fluconazole as first-line treatment for adults with candidemia. We describe candidemia treatment practices and adherence to the updated guidelines. Methods During 2017–2018, the Emerging Infections Program conducted active population-based candidemia surveillance at 9 US sites using a standardized case definition. We assessed factors associated with initial antifungal treatment for the first candidemia case among adults using multivariable logistic regression models. To identify instances of potentially inappropriate treatment, we compared the first antifungal drug received with species and antifungal susceptibility testing (AFST) results from initial blood cultures. Results Among 1835 patients who received antifungal treatment, 1258 (68.6%) received an echinocandin and 543 (29.6%) received fluconazole as initial treatment. Cirrhosis (adjusted odds ratio = 2.06; 95% confidence interval, 1.29–3.29) was the only underlying medical condition significantly associated with initial receipt of an echinocandin (versus fluconazole). More than one-half (n = 304, 56.0%) of patients initially treated with fluconazole grew a non-albicans species. Among 265 patients initially treated with fluconazole and with fluconazole AFST results, 28 (10.6%) had a fluconazole-resistant isolate. Conclusions A substantial proportion of patients with candidemia were initially treated with fluconazole, resulting in potentially inappropriate treatment for those involving non-albicans or fluconazole-resistant species. Reasons for nonadherence to IDSA guidelines should be evaluated, and clinician education is needed.

BackgroundSince the introduction of Haemophilus influenzae serotype b (Hib) conjugate vaccines in the United States, invasive H. influenzae disease epidemiology has changed, and racial disparities have not been recently described.MethodsActive population- and laboratory-based surveillance for H. influenzae was conducted through Active Bacterial Core surveillance at 10 US sites. Data from 2008–2017 were used to estimate projected nationwide annual incidence, as cases per 100 000.ResultsDuring 2008–2017, Active Bacterial Core surveillance identified 7379 H. influenzae cases. Of 6705 patients (90.9%) with reported race, 76.2% were White, 18.6% were Black, 2.8% were Asian/Pacific Islander, and 2.4% were American Indian or Alaska Native (AI/AN). The nationwide annual incidence was 1.8 cases/100 000. By race, incidence was highest among AI/AN populations (3.1) and lowest among Asian/Pacific Islander populations (0.8). Nontypeable H. influenzae caused the largest incidence within all races (1.3), with no striking disparities identified. Among AI/AN children aged ConclusionsWhile nontypeable H. influenzae causes the largest H. influenzae burden overall, AI/AN populations experience disproportionately high rates of Hia and Hib, with the greatest disparity among AI/AN children aged

Accurate knowledge of the charged particle bunch longitudinal (time) profile is important in the context of wakefield accelerators, Compton Light sources, x-ray SASE FELs and THz radiation sources. However, it is still a challenge to obtain this information for subpicosecond long bunches and microbunched beams with the required femtosecond (fs) resolution and nondestructively. Apart from determining the profile in a nondestructive manner, the ideal bunch diagnostic would enable extraction of all required information in a single shot, have a sufficiently high repetition rate to monitor each bunch, small footprint, good cost efficiency and reliability. In this paper we present the design of a longitudinal bunch profile monitor that can determine the charged particle bunch profile with femtosecond resolution, nondestructively and in a single shot via the spectral analysis of coherent Smith-Purcell radiation (cSPr). It is based on the simultaneous deployment of three gratings with different periodicities, each with its own set of detectors. The number of the frequency sampling points is equal to the number of the optical channels and the discrimination against background radiation is based on the different polarization properties of cSPr and background radiation. The rationales for the choices made to optimize the monitor operation will be presented and the criteria for determining the number of frequency sampling points will be discussed. The possible future developments of the monitor are also presented and discussed.

The purpose of this study was to compare the independent and combined effects of high‐intensity interval training (HIIT) and essential amino acids (EAA) on lean mass, muscle characteristics of the quadriceps, and 24‐hr whole‐body protein turnover (WBPT) in overweight and obese adults. An exploratory aim was to evaluate potential modulatory effects of sex. Sixty‐six adults (50% female; Age: 36.7 ± 6.0 yrs; %BF: 36.0 ± 7.8%) were assigned to 8 wks of: (a) HIIT, 2 days/wk; (b) EAA supplementation, 3.6 g twice daily; (c) HIIT + EAA; or (d) control. At baseline, 4 wks, and 8 wks, total body, thigh LM and muscle characteristics were measured via dual‐energy x‐ray absorptiometry and B‐mode ultrasound, respectively. In a subsample, changes in WBPT was measured using [N15]alanine. Differences between groups were assessed using linear mixed models adjusted for baseline values, followed by 95% confidence intervals on adjusted mean change scores (Δ). HIIT and HIIT + EAA improved thigh LM (Δ: +0.17 ± 0.05 kg [0.08, 0.27]; +0.22 ± 0.05 kg [0.12,0.31]) and vastus lateralis cross‐sectional area (Δ: +2.73 ± 0.52 cm2 [1.69,3.77]; +2.64 ± 0.53 cm2 [1.58,3.70]), volume (Δ: +54.50 ± 11.69 cm3 [31.07, 77.92]; +62.39 ± 12.05 cm3 [38.26, 86.52]), and quality (Δ: −5.46 ± 2.68a.u. [−10.84, −0.09]; −7.97 ± 2.76a.u.[−13.49, −2.45]). Protein synthesis, breakdown, and flux were greater with HIIT + EAA and EAA compared to HIIT (p, In overweight and obese adults, eight weeks of high‐intensity interval training, with or without essential amino acid supplementation (EAA), improved thigh lean mass size and quality; EAA may enhance muscular adaptation via increases in protein turnover, supporting greater improvements in muscular size and quality.

Brazil introduced 10-valent pneumococcal conjugate vaccine (PCV10) into its immunization program in 2010. We assessed antimicrobial susceptibility of Streptococcus pneumoniae (Spn) obtained from a national surveillance system for invasive pneumococcal diseases (IPD) before/after PCV10 introduction.Antimicrobial non-susceptible isolates were defined as intermediate or resistant. Minimum inhibitory concentrations (MICs) to penicillin and ceftriaxone were analyzed by year. Antimicrobial susceptibility rates were assessed for each three-year-period using the pre-PCV10-period as reference. Susceptibility of vaccine-types was evaluated for 2017-2019.11,380 isolates were studied. Spn with penicillin ≥ 0.125 mg/L and ceftriaxone ≥ 1.0 mg/L decreased in the three-years after PCV10 introduction (2011-2013: penicillin, 28.1-22.5%; ceftriaxone, 11.3%-7.6%) versus pre-PCV10-years (2007-2009: penicillin, 33.8-38.1%; ceftriaxone, 17.2%-15.6%). After 2013, the proportion of Spn with those MICs to penicillin and ceftriaxone increased to 39.4% and 19.7% in 2019, respectively. Non-susceptibility to penicillin and ceftriaxone increased in 2014-2016, and again in 2017-2019 especially among children 5 years with meningitis (penicillin, 53.9%; ceftriaxone, 28.0%); multidrug-resistance reached 25% in 2017-2019. Serotypes 19A, 6C and 23A were most associated with antimicrobial non-susceptibility.Antimicrobial non-susceptible Spn decreased in the three-years after vaccination but subsequently increased and was associated with non-PCV10-types. Antimicrobial susceptibility surveillance is fundamental for guiding antibiotic therapy policies.

IntroductionThe novel coronavirus SARS-CoV2 and the associated disease, Covid-19, continue to pose a global health threat. The CovidCalculatorUK is an open-source online tool (covidcalculatoruk.org) that estimates the probability that an individual patient, who presents to a UK hospital, will later test positive for SARS-CoV2. The objective is to aid cohorting decisions and minimise nosocomial transmission of SARS-CoV2.MethodsThis n = 500 prospective, observational, multicentre, validation study compared the CovidCalculatorUK’s estimated probability of Covid-19 with the first SARS-CoV2 oropharyngeal/nasopharyngeal swab result for individual patients admitted to hospital during the study period (01.04.20 − 18.05.20). A comparison with senior clinicians’ estimates of the probability of Covid-19 was also made.ResultsPatients who were prospectively grouped, by the CovidCalculatorUK, into 0-30% estimated probability, 30-60% and 60-100% estimated probability went on to have first swab SARS-CoV2 positive results in: 15.7%, 30.5% and 61.9% of cases, respectively. CovidCalculatorUK performance demonstrated an area under the curve of 0.76 (95% CI 0.71 – 0.81) (p < 0.001). Senior clinician stratification of the estimated probability of Covid-19 performed similarly to the CovidCalculatorUK.ConclusionThe CovidCalculatorUK provides a reasonably accurate estimate of the probability of an individual testing positive on their first SARS-CoV2 nasopharyngeal/oropharyngeal swab. The CovidCalculatorUK output performs similarly to a senior clinician’s estimate. Further evolution of the calculator may improve performance.

Context.—Recent developments in machine learning have stimulated intense interest in software that may augment or replace human experts. Machine learning may impact pathology practice by offering new capabilities in analysis, interpretation, and outcomes prediction using images and other data. The principles of operation and management of machine learning systems are unfamiliar to pathologists, who anticipate a need for additional education to be effective as expert users and managers of the new tools.Objective.—To provide a background on machine learning for practicing pathologists, including an overview of algorithms, model development, and performance evaluation; to examine the current status of machine learning in pathology and consider possible roles and requirements for pathologists in local deployment and management of machine learning systems; and to highlight existing challenges and gaps in deployment methodology and regulation.Data Sources.—Sources include the biomedical and engineering literature, white papers from professional organizations, government reports, electronic resources, and authors' experience in machine learning. References were chosen when possible for accessibility to practicing pathologists without specialized training in mathematics, statistics, or software development.Conclusions.—Machine learning offers an array of techniques that in recent published results show substantial promise. Data suggest that human experts working with machine learning tools outperform humans or machines separately, but the optimal form for this combination in pathology has not been established. Significant questions related to the generalizability of machine learning systems, local site verification, and performance monitoring remain to be resolved before a consensus on best practices and a regulatory environment can be established.

Background Traditional methods of outbreak investigations utilize reactive whole genome sequencing (WGS) to confirm or refute the outbreak. We have implemented WGS surveillance and a machine learning (ML) algorithm for the electronic health record (EHR) to retrospectively detect previously unidentified outbreaks and to determine the responsible transmission routes. Methods We performed WGS surveillance to identify and characterize clusters of genetically-related Pseudomonas aeruginosa infections during a 24-month period. ML of the EHR was used to identify potential transmission routes. A manual review of the EHR was performed by an infection preventionist to determine the most likely route and results were compared to the ML algorithm. Results We identified a cluster of 6 genetically related P. aeruginosa cases that occurred during a 7-month period. The ML algorithm identified gastroscopy as a potential transmission route for 4 of the 6 patients. Manual EHR review confirmed gastroscopy as the most likely route for 5 patients. This transmission route was confirmed by identification of a genetically-related P. aeruginosa incidentally cultured from a gastroscope used on 4of the 5 patients. Three infections, 2 of which were blood stream infections, could have been prevented if the ML algorithm had been running in real-time. Conclusions WGS surveillance combined with a ML algorithm of the EHR identified a previously undetected outbreak of gastroscope-associated P. aeruginosa infections. These results underscore the value of WGS surveillance and ML of the EHR for enhancing outbreak detection in hospitals and preventing serious infections.

Victorian poetry constitutes a particular field of cultural production that displays the increasing acceptance, power, and, dominance of medievalist discourses, and of values attributed to the medieval world, over the course of nineteenth century in Britain. Analysis of a range of medievalist poems by Matthew Arnold, Elizabeth Barrett Browning, Dante Rossetti, William Morris, Thomas Hardy, and A. C. Swinburne demonstrates how this particular topical genre of Victorian poetry served to disseminate specific ideological values held by its authors and do so at a level of power and authority unique to the poetry of the period. This analysis compels us to understand Victorian medievalism not as a decorative veneer atop bedrock Victorian culture but rather as a dynamic ‘system’ of interrelated components—linguistic, visual, conceptual, material—deployed by various thinkers, writers, artists, and artisans to transform that culture in potentially profound ways

Neisseria meningitidis is a major cause of bacterial meningitis and septicaemia worldwide and is associated with high case fatality rates and serious life-long complications among survivors. Twelve serogroups are recognised, of which six (A, B, C, W, X and Y) are responsible for nearly all cases of invasive meningococcal disease (IMD). The incidence of IMD and responsible serogroups vary widely both geographically and over time. For the first time, effective vaccines against all these serogroups are available or nearing licensure. Over the past two decades, IMD incidence has been declining across most parts of the world through a combination of successful meningococcal immunisation programmes and secular trends. The introduction of meningococcal C conjugate vaccines in the early 2000s was associated with rapid declines in meningococcal C disease, whilst implementation of a meningococcal A conjugate vaccine across the African meningitis belt led to near-elimination of meningococcal A disease. Consequently, other serogroups have become more important causes of IMD. In particular, the emergence of a hypervirulent meningococcal group W clone has led many countries to shift from monovalent meningococcal C to quadrivalent ACWY conjugate vaccines in their national immunisation programmes. Additionally, the recent licensure of two protein-based, broad-spectrum meningococcal B vaccines finally provides protection against the most common group responsible for childhood IMD across Europe and Australia. This review describes global IMD epidemiology across each continent and trends over time, the serogroups responsible for IMD, the impact of meningococcal immunisation programmes and future needs to eliminate this devastating disease.

Carbapenem-nonsusceptible Citrobacter spp. (CNSC) are increasingly recognized as health care-associated pathogens. Information regarding their clinical epidemiology, genetic diversity, and mechanisms of carbapenem resistance is lacking. We examined microbiology records of adult patients at the University of Pittsburgh Medical Center (UMPC) Presbyterian Hospital (PUH) from 2000 to 2018 for CNSC, as defined by ertapenem nonsusceptibility. Over this time frame, the proportion of CNSC increased from 4% to 10% (P = 0., Carbapenem-nonsusceptible Citrobacter spp. (CNSC) are increasingly recognized as health care-associated pathogens. Information regarding their clinical epidemiology, genetic diversity, and mechanisms of carbapenem resistance is lacking. We examined microbiology records of adult patients at the University of Pittsburgh Medical Center (UMPC) Presbyterian Hospital (PUH) from 2000 to 2018 for CNSC, as defined by ertapenem nonsusceptibility. Over this time frame, the proportion of CNSC increased from 4% to 10% (P = 0.03), as did daily defined carbapenem doses/1,000 patient days (6.52 to 34.5; R2 = 0.831; P

Evidence to inform the management of systemic fungal infections in the setting of a cardiac implantable electronic devices (CIED), such as a permanent pacemaker or implantable cardioverter-defibrillator, is scant and limited to case reports and series. The available literature suggests high morbidity and mortality. To better characterize the shared experience of these cases and their outcomes, we performed a systematic review. We investigated all published reports of systemic fungal infections-fungemia and fungal vegetative disease-in the context of CIED, drawing from PubMed, EMBASE, and the Cochrane database of systematic reviews, inclusive of patients who received treatment between January 2000 and May 2020. Exclusion criteria included presence of ventricular assist device and concurrent bacteremia, bacterial endocarditis, bacterial vegetative infection, or viremia. Among 6261 screened articles, 48 cases from 41 individual studies were identified. Candida and Aspergillus species were the most commonly isolated fungi. There was significant heterogeneity in antifungal medication selection and duration. CIED extraction-either transvenous or surgical-was associated with increased survival to hospital discharge (92%) and clinical recovery at latest follow-up (81%), compared to cases where CIED extraction was deferred (56% and 40%, respectively). Importantly, there were no prospective data, and the data were limited to individual case reports and one small case series. In summary, CIED extraction is associated with improved fungal clearance and patient survival. Reported antifungal regimens are heterogeneous and nonuniform. Prospective studies are needed to verify these results and define optimal antifungal regimens.

Background Haemophilus influenzae serotype a (Hia) can cause invasive disease similar to serotype b; no Hia vaccine is available. We describe the epidemiology of invasive Hia disease in the United States overall and specifically in Alaska during 2008–2017. Methods Active population- and laboratory-based surveillance for invasive Hia disease was conducted through Active Bacterial Core surveillance sites and from Alaska statewide invasive bacterial disease surveillance. Sterile-site isolates were serotyped via slide agglutination or real-time polymerase chain reaction. Incidences in cases per 100 000 were calculated. Results From 2008 to 2017, an estimated average of 306 invasive Hia disease cases occurred annually in the United States (estimated annual incidence: 0.10); incidence increased by an average of 11.1% annually. Overall, 42.7% of cases were in children aged Conclusions Incidence of invasive Hia disease has increased since 2008, with the highest burden among AI/AN children. These data can inform prevention strategies, including Hia vaccine development.

BACKGROUND: Most countries use 3-dose pneumococcal conjugate vaccine (PCV) schedules; a 4-dose (3 primary and 1 booster) schedule is licensed for US infants. We evaluated the invasive pneumococcal disease (IPD) breakthrough infection incidence in children receiving 2 vs 3 primary PCV doses with and without booster doses (2 + 1 vs 3 + 1; 2 + 0 vs 3 + 0). METHODS: We used 2001–2016 Active Bacterial Core surveillance data to identify breakthrough infections (vaccine-type IPD in children receiving ≥1 7-valent pneumococcal conjugate vaccine [PCV7] or 13-valent pneumococcal conjugate vaccine [PCV13] dose) among children aged RESULTS: We identified 71 PCV7 and 49 PCV13 breakthrough infections among children receiving a schedule of interest. PCV13 breakthrough infection rates were higher in children aged CONCLUSIONS: Fewer PCV breakthrough infections occurred in the first year of life with 3 primary doses. Differences in breakthrough infection rates by schedule decreased as vaccine serotypes decreased in circulation.

BackgroundCandidemia is a common healthcare-associated bloodstream infection with high morbidity and mortality. There are no current estimates of candidemia burden in the United States (US).MethodsIn 2017, the Centers for Disease Control and Prevention conducted active population-based surveillance for candidemia through the Emerging Infections Program in 45 counties in 9 states encompassing approximately 17 million persons (5% of the national population). Laboratories serving the catchment area population reported all blood cultures with Candida, and a standard case definition was applied to identify cases that occurred in surveillance area residents. Burden of cases and mortality were estimated by extrapolating surveillance area cases to national numbers using 2017 national census data.ResultsWe identified 1226 candidemia cases across 9 surveillance sites in 2017. Based on this, we estimated that 22 660 (95% confidence interval [CI], 20 210–25 110) cases of candidemia occurred in the US in 2017. Overall estimated incidence was 7.0 cases per 100 000 persons, with highest rates in adults aged ≥ 65 years (20.1/100 000), males (7.9/100 000), and those of black race (12.3/100 000). An estimated 3380 (95% CI, 1318–5442) deaths occurred within 7 days of a positive Candida blood culture, and 5628 (95% CI, 2465–8791) deaths occurred during the hospitalization with candidemia.ConclusionsOur analysis highlights the substantial burden of candidemia in the US. Because candidemia is only one form of invasive candidiasis, the true burden of invasive infections due to Candida is higher. Ongoing surveillance can support future burden estimates and help assess the impact of prevention interventions.

Background Reported outbreaks of invasive group A Streptococcus (iGAS) infections among people who inject drugs (PWID) and people experiencing homelessness (PEH) have increased, concurrent with rising US iGAS rates. We describe epidemiology among iGAS patients with these risk factors. Methods We analyzed iGAS infections from population-based Active Bacterial Core surveillance (ABCs) at 10 US sites from 2010 to 2017. Cases were defined as GAS isolated from a normally sterile site or from a wound in patients with necrotizing fasciitis or streptococcal toxic shock syndrome. GAS isolates were emm typed. We categorized iGAS patients into four categories: injection drug use (IDU) only, homelessness only, both, and neither. We calculated annual change in prevalence of these risk factors using log binomial regression models. We estimated national iGAS infection rates among PWID and PEH. Results We identified 12 386 iGAS cases; IDU, homelessness, or both were documented in ~13%. Skin infections and acute skin breakdown were common among iGAS patients with documented IDU or homelessness. Endocarditis was 10-fold more frequent among iGAS patients with documented IDU only versus those with neither risk factor. Average percentage yearly increase in prevalence of IDU and homelessness among iGAS patients was 17.5% and 20.0%, respectively. iGAS infection rates among people with documented IDU or homelessness were ~14-fold and 17- to 80-fold higher, respectively, than among people without those risks. Conclusions IDU and homelessness likely contribute to increases in US incidence of iGAS infections. Improving management of skin breakdown and early recognition of skin infection could prevent iGAS infections in these patients.

ObjectiveRecovery of multidrug-resistant (MDR) Pseudomonas aeruginosa and Klebsiella pneumoniae from a cluster of patients in the medical intensive care unit (MICU) prompted an epidemiologic investigation for a common exposure.MethodsClinical and microbiologic data from MICU patients were retrospectively reviewed, MICU bronchoscopes underwent culturing and borescopy, and bronchoscope reprocessing procedures were reviewed. Bronchoscope and clinical MDR isolates epidemiologically linked to the cluster underwent molecular typing using pulsed-field gel electrophoresis (PFGE) followed by whole-genome sequencing.ResultsOf the 33 case patients, 23 (70%) were exposed to a common bronchoscope (B1). Both MDR P. aeruginosa and K. pneumonia were recovered from the bronchoscope’s lumen, and borescopy revealed a luminal defect. Molecular testing demonstrated genetic relatedness among case patient and B1 isolates, providing strong evidence for horizontal bacterial transmission. MDR organism (MDRO) recovery in 19 patients was ultimately linked to B1 exposure, and 10 of 19 patients were classified as belonging to an MDRO pseudo-outbreak.ConclusionsSurveillance of bronchoscope-derived clinical culture data was important for early detection of this outbreak, and whole-genome sequencing was important for the confirmation of findings. Visualization of bronchoscope lumens to confirm integrity should be a critical component of device reprocessing.

Objectives To describe the epidemiology and incidence of invasive methicillin‐resistant Staphylococcus aureus (MRSA) infections in nursing home (NH) residents, which has previously not been well characterized. Design Retrospective analysis of public health surveillance data. Setting Healthcare facilities in 33 U.S. counties. Participants Residents of the surveillance area. Measurements Counts of NH‐onset and hospital‐onset (HO) invasive MRSA infections (cultured from sterile body sites) identified from the Centers for Disease Control and Prevention Emerging Infections Program (EIP) population‐based surveillance from 2009 to 2013 were compared. Demographic characteristics and risk factors of NH‐onset cases were analyzed. Using NH resident‐day denominators from the Centers for Medicare and Medicaid Services Skilled Nursing Facility Cost Reports, incidence of NH‐onset invasive MRSA infections from facilities in the EIP area was determined. Results A total of 4,607 NH‐onset and 4,344 HO invasive MRSA cases were reported. Of NH‐onset cases, median age was 74, most infections were bloodstream infections, and known risk factors for infection were common: 1,455 (32%) had previous MRSA infection or colonization, 1,014 (22%) had decubitus ulcers, 1,098 (24%) had recent central venous catheters, and 1,103 (24%) were undergoing chronic dialysis; 2,499 (54%) had been discharged from a hospital in the previous 100 days. The in‐hospital case‐fatality rate was 19%. The 2013 pooled mean incidence of NH‐onset invasive MRSA infections in the surveillance area was 2.4 per 100,000 patient‐days. Conclusion More NH‐onset than HO cases occurred, primarily in individuals with known MRSA risk factors. These data reinforce the importance of infection prevention practices during wound and device care in NH residents, especially those with a history of MRSA infection or colonization.

BACKGROUND: The aim of this study is to describe the molecular epidemiology of Neisseria meningitidis invasive disease before the introduction of serogroup C conjugate vaccine in Amazonas State in 2010. METHODS: Meningococcal disease reported cases were investigated in Amazonas State during the period 2000 to 2010. N. meningitidis isolates (n = 196) recovered from patients were genotyped by multilocus sequence typing (MLST) and sequencing of porB, porA, fetA, fHbp, and penA. Antimicrobial susceptibility was determined using E-test. RESULTS: In the study period, 948 cases were reported; the incidence was 2.8 for the entire state and 4.8 per 100,000 in the capital of Manaus. Most meningococcal disease was caused by N. meningitidis belonging to ST-32 (72%; 141/196) or ST-103 (21%; 41/196) clonal complexes. Capsular switching (B→C) was suggested within clonal complex (cc) 32. There were 6 (3%; 6/196) strains with intermediate susceptibility to penicillin and a single strain was resistant to rifampicin. Since 2007, serogroup C strains belonging to the cc103 have predominated and case-fatality has increased. CONCLUSIONS: We demonstrate a high rate of meningococcal disease in Amazonas State, where, like other parts of Brazil, serogroup C replaced serogroup B during 2000s. These data serve as a baseline to measure impact of serogroup C conjugate vaccine introduction in 2010. This study emphasizes the need for enhanced surveillance to monitor changes in meningococcal disease trends following the introduction of meningococcal vaccines.

Background Despite substantial attention to the individual topics, little is known about the relationship between racial disparities and antimicrobial-resistant and/or healthcare-associated infection trends, such as for methicillin-resistant Staphylococcus aureus (MRSA). Methods We analyzed Emerging Infections Program 2005-2014 surveillance data (9 US states) to determine whether reductions in invasive MRSA incidence (isolated from normally sterile body sites) affected racial disparities in rates. Case classification included hospital-onset (HO, culture >3 days after admission), healthcare-associated community onset (HACO, culture ≤3 days after admission and dialysis, hospitalization, surgery, or long-term care residence within 1 year prior), or community-associated (CA, all others). Negative binomial regression models were used to evaluate the adjusted rate ratio (aRR) of MRSA in black patients (vs in white patients) controlling for age, sex, and temporal trends. Results During 2005-2014, invasive HO and HACO (but not CA) MRSA rates decreased. Despite this, blacks had higher rates for HO (aRR, 3.20; 95% confidence interval [CI], 2.35-4.35), HACO (aRR, 3.84; 95% CI, 2.94-5.01), and CA (aRR, 2.78; 95% CI, 2.30-3.37) MRSA. Limiting the analysis to chronic dialysis patients reduced, but did not eliminate, the higher HACO MRSA rates among blacks (aRR, 1.83; 95% CI, 1.72-1.96), even though invasive MRSA rates among dialysis patients decreased during 2005-2014. These racial differences did not change over time. Conclusions Previous reductions in healthcare-associated MRSA infections have not affected racial disparities in MRSA rates. Improved understanding of the underlying causes of these differences is needed to develop effective prevention interventions that reduce racial disparities in MRSA infections.

BACKGROUND. Following Haemophilus influenzae serotype b (Hib) conjugate vaccine introduction in the 1980s, Hib disease in young children dramatically decreased, and epidemiology of invasive H. influenzae changed. METHODS. Active surveillance for invasive H. influenzae disease was conducted through Active Bacterial Core surveillance sites. Incidence rates were directly standardized to the age and race distribution of the US population. RESULTS. During 2009–2015, the estimated mean annual incidence of invasive H. influenzae disease was 1.70 cases per 100 000 population. Incidence was highest among adults aged ≥65 years (6.30) and children aged

Background Bacille Calmette-Guerin (BCG) vaccination is known to cause false-positive tuberculin skin test (TST) results from cross-reactions with mycobacterial antigens. However, the duration of BCG vaccination influence on the TST is poorly characterized. The objective of this study was to assess the long-term effect of BCG vaccination on TST reactivity. Methods Data on TST reactivity were prospectively collected during 1935 to 1947 as part of a clinical trial among Native Americans/Alaskan Natives and were retrospectively collected thereafter between 1948 and 1998. TST induration of ≥ 10 mm was defined as a positive reaction. Kaplan-Meier analysis and multivariate Cox regression were used to compare the time to TST conversion and reversion between the BCG and placebo groups. Results BCG vaccination after infancy was associated with an increased risk of TST reactivity in the first 15 years after vaccination (adjusted hazard ratio [HR], 2.33). This association remained during the interval 16 to 55 years after vaccination, although the effect was attenuated (adjusted HR, 1.26). Age at vaccination modestly impacted the effect of BCG on TST results in the first 15 years. Positive TST results among the BCG-vaccinated group were more likely to revert to negative results during the first 15 years but not in the latter period. Conclusions This study provides evidence that BCG vaccination after infancy may influence TST results beyond the 10-year period conventionally accepted by the Centers for Disease Control and Prevention (CDC), extending up to 55 years after vaccination. This suggests that BCG vaccination should be taken into account when interpreting TST results regardless of the time elapsed since vaccination.

Causes of morbidity and mortality for various species of tenrecs have not been widely published, aside from several reports of neoplasia, and these data are crucial for advancing objectives for preventive medicine, diagnosis, and treatment. A survey on husbandry, morbidity, and mortality of lesser hedgehog tenrecs ( Echinops telfairi ) in Association of Zoos and Aquariums (AZA) institutions was conducted. Out of 32 institutions, 20 responded with data for 98 living and 93 dead animals. The most common causes of mortality among the dead animals were neoplasia (24%), hepatic lipidosis (11%), septicemia (8.6%), pneumonia (8.6%), cardiomyopathy (7.5%), renal disease (6.5%), osteomyelitis (3.2%), and trauma (3.2%). There was no statistically significant correlation between sex and neoplasia. Data about educational usage were specifically provided by survey respondents for 50 of the tenrecs, with only 42% being excluded from educational programming. Tenrecs are common to many AZA institutions as both educational and exhibit animals, and this study provides a helpful reference for expected health problems and highlights the need for future investments into medical diagnosis and treatment for these animals.

Background Early palliative care for advanced cancer patients improves quality of life and survival, but less is known about its effect on intensive care unit (ICU) use at the end of life. This analysis assessed the effect of a comprehensive early palliative care program on ICU use and other outcomes among patients with advanced cancer. Patients and methods A retrospective cohort of patients with advanced cancer enrolled in an early palliative care program (n = 275) was compared with a concurrent control group of patients receiving standard care (n = 195) during the same time period by using multivariable logistic regression analysis. The multidisciplinary outpatient palliative care program used early end-of-life care planning, weekly interdisciplinary meetings to discuss patient status, and patient-reported outcomes assessment integrated within the electronic health record. Results Patients in the control group had statistically significantly higher likelihood of ICU admission at the end of life (odds ratios [ORs]: last 6 months, 3.07; last month, 3.59; terminal admission, 4.69), higher likelihood of death in the hospital (OR, 4.14) or ICU (OR, 5.57), and lower likelihood of hospice enrollment (OR, 0.13). Use of chemotherapy or radiation did not significantly differ between groups, nor did length of ICU stay, code status, ICU procedures (other than cardiopulmonary resuscitation), disposition location, and outcomes after ICU admission. Conclusion Early palliative care significantly reduced ICU use at the end of life but did not change ICU events. This study supports early initiation of palliative care for advanced cancer patients before hospitalizations and intensive care. The Oncologist 2017;22:318-323 IMPLICATIONS FOR PRACTICE: Palliative care has shown clear benefit in quality of life and survival in advanced cancer patients, but less is known about its effect on intensive care. This retrospective cohort study at a university hospital showed that in the last 6 months of life, palliative care significantly reduced intensive care unit (ICU) and hospital admissions, reduced deaths in the hospital, and increased hospice enrollment. It did not, however, change patients' experiences within the ICU, such as number of procedures, code status, length of stay, or disposition. The findings further support that palliative care exerts its benefit before, rather than during, the ICU setting.

Background Invasive community-associated methicillin-resistant Staphylococcus aureus (MRSA) incidence in the United States is higher among black persons than white persons. We explored the extent to which socioeconomic factors might explain this racial disparity. Methods A retrospective cohort was based on the Centers for Disease Control and Prevention's Emerging Infections Program surveillance data for invasive community-associated MRSA cases (isolated from a normally sterile site of an outpatient or on hospital admission day ≤3 in a patient without specified major healthcare exposures) from 2009 to 2011 in 33 counties of 9 states. We used generalized estimating equations to determine census tract-level factors associated with differences in MRSA incidence and inverse odds ratio-weighted mediation analysis to determine the proportion of racial disparity mediated by socioeconomic factors. Results Annual invasive community-associated MRSA incidence was 4.59 per 100000 among whites and 7.60 per 100000 among blacks (rate ratio [RR], 1.66; 95% confidence interval [CI], 1.52-1.80). In the mediation analysis, after accounting for census tract-level measures of federally designated medically underserved areas, education, income, housing value, and rural status, 91% of the original racial disparity was explained; no significant association of black race with community-associated MRSA remained (RR, 1.05; 95% CI, .92-1.20). Conclusions The racial disparity in invasive community-associated MRSA rates was largely explained by socioeconomic factors. The specific factors that underlie the association between census tract-level socioeconomic measures and MRSA incidence, which may include modifiable social (eg, poverty, crowding) and biological factors (not explored in this analysis), should be elucidated to define strategies for reducing racial disparities in community-associated MRSA rates.