The burden of all-cause mortality following influenza-associated hospitalizations, FluSurv-NET, 2010-2019.

BACKGROUND: While the estimated number of U.S. influenza-associated deaths is reported annually, detailed data on the epidemiology of influenza-associated deaths, including the burden of in-hospital versus post-hospital discharge deaths are limited. METHODS: Using data from the 2010-11 through 2018-19 seasons from the Influenza Hospitalization Surveillance Network, we linked cases to death certificates to identify patients who died from any cause during their influenza hospital stay or within 30 days post discharge. We described demographic and clinical characteristics of patients who died in hospital versus post discharge and characterized locations and causes of death (COD). RESULTS: Among 121,390 cases hospitalized with laboratory-confirmed influenza over 9 seasons, 5.5% died; 76% of deaths were in patients ≥65 years, 71% were non-Hispanic White, and 34% had ≥4 underlying medical conditions. Among all patients with an influenza-associated hospitalization who died, 48% of deaths occurred after hospital discharge; the median days from discharge to death was 9 days (IQR 3-19 days). Post-discharge deaths more often occurred in older patients and among those with underlying medical conditions. Only 37% of patients who died had "influenza" as a COD on their death certificate. Influenza was more frequently listed as a COD among persons who died in-hospital compared with cardiovascular disease among those who died after discharge. CONCLUSIONS: All-cause mortality burden is substantial among patients hospitalized with influenza, with almost 50% of deaths occurring within 30 days after hospital discharge. Surveillance systems should consider capture of post-discharge outcomes to better characterize the impact of influenza on all-cause mortality.

Timing of influenza antiviral therapy and risk of death in adults hospitalized with influenza-associated pneumonia, FluSurv-NET, 2012-2019.

BACKGROUND: Pneumonia is common in adults hospitalized with laboratory-confirmed influenza, but the association between timeliness of influenza antiviral treatment and severe clinical outcomes in patients with influenza-associated pneumonia is not well characterized. METHODS: We included adults aged ≥18 years hospitalized with laboratory-confirmed influenza and a discharge diagnosis of pneumonia over 7 influenza seasons (2012-2019) sampled from a multi-state population-based surveillance network. We evaluated 3 treatment groups based on timing of influenza antiviral initiation relative to admission date (day 0, day 1, days 2-5). Baseline characteristics and clinical outcomes were compared across groups using unweighted counts and weighted percentages accounting for the complex survey design. Logistic regression models were generated to evaluate the association between delayed treatment and 30-day all-cause mortality. RESULTS: 26,233 adults were sampled in the analysis. Median age was 71 years and most (92.2%) had ≥1 non-immunocompromising condition. Overall, 60.9% started antiviral treatment on day 0, 29.5% on day 1, and 9.7% on days 2-5 (median 2 days). Baseline characteristics were similar across groups. Thirty-day mortality occurred in 7.5%, 8.5%, and 10.2% of patients who started treatment on day 0, day 1, and days 2-5, respectively. Compared to those treated on day 0, adjusted OR for death was 1.14 (95%CI: 1.01-1.27) in those starting treatment on day 1 and 1.40 (95%CI: 1.17-1.66) in those starting on days 2-5. DISCUSSION: Delayed initiation of antiviral treatment in patients hospitalized with influenza-associated pneumonia was associated with higher risk of death, highlighting the importance of timely initiation of antiviral treatment at admission.

Retropharyngeal Abscess Complicated by Mediastinitis in Infants.

INTRODUCTION: Most paediatric upper respiratory infections are virally mediated and result in self-limiting reactive lymphadenopathy. In children younger than 5 years, retropharyngeal lymph nodes may give rise to deep neck space infections in this potential space. Retropharyngeal infections are rare after 5 years because lymph nodes undergo atrophy. METHODS: We present a series of 6 cases of paediatric retropharyngeal abscesses (RPA) complicated by mediastinitis, managed at a tertiary hospital over a 4-year period. RESULTS: All our cases presented with fever, difficulty feeding, and neck swelling. The age range was 11 weeks-11 months, and all tested negative for human immunodeficiency virus. The diagnosis and complications were confirmed on computed tomography (CT) scan. The CT scans consistently revealed RPA with varying degrees of deep neck space and mediastinal extension. All children were promptly taken to theatre for source control. Two were extubated successfully immediately after surgery, and the other 4 were extubated in the paediatric intensive care unit, with the longest duration of intubation being 3 days. Methicillin-sensitive Staphylococcus aureus (MSSA) was cultured in all 6 cases. CONCLUSION: Management of these cases may be challenging, and young children with RPA require close care and airway monitoring. CT or magnetic resonance imaging is essential to delineate the extent of infection. Surgical drainage should be performed when there is a large abscess, a complication occurs, or an inadequate response in 24-48 h to medical management.

The impact of a regionally based translational cancer research collaborative in Australia using the FAIT methodology.

BACKGROUND: Translating research, achieving impact, and assessing impact are important aspirations for all research collaboratives but can prove challenging. The Hunter Cancer Research Alliance (HCRA) was funded from 2014 to 2021 to enhance capacity and productivity in cancer research in a regional centre in Australia. This study aimed to assess the impact and benefit of the HCRA to help inform future research investments of this type. METHOD: The Framework to Assess the Impact from Translational health research (FAIT) was selected as the preferred methodology. FAIT incorporates three validated methodologies for assessing impact: 1) Modified Payback; 2) Economic Analysis; and 3) Narrative overview and case studies. All three FAIT methods are underpinned by a Program Logic Model. Data were collected from HCRA and the University of Newcastle administrative records, directly from HCRA members, and website searches. RESULTS: In addition to advancing knowledge and providing capacity building support to members via grants, fellowships, scholarships, training, events and targeted translation support, key impacts of HCRA-member research teams included: (i) the establishment of a regional biobank that has distributed over 13,600 samples and became largely self-sustaining; (ii) conservatively leveraging $43.8 M (s.a.$20.5 M - $160.5 M) in funding and support from the initial $9.7 M investment; (iii) contributing to clinical practice guidelines and securing a patent for identification of stem cells for endometrial cell regeneration; (iv) shifting the treatment paradigm for all tumour types that rely on nerve cell innervation, (v) development and implementation of the world's first real-time patient treatment verification system (Watchdog); (vi) inventing the effective 'EAT' psychological intervention to improve nutrition and outcomes in people experiencing radiotherapy for head and neck cancer; (vi) developing effective interventions to reduce smoking rates among priority groups, currently being rolled out to disadvantaged populations in NSW; and (vii) establishing a Consumer Advisory Panel and Consumer Engagement Committee to increase consumer involvement in research. CONCLUSION: Using FAIT methodology, we have demonstrated the significant impact and downstream benefits that can be achieved by the provision of infrastructure-type funding to regional and rural research collaboratives to help address inequities in research activity and health outcomes and demonstrates a positive return on investment.

Changes in the Incidence of Invasive Bacterial Disease During the COVID-19 Pandemic in the United States, 2014-2020.

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.

Epidemiology of Invasive Nontypeable Haemophilus influenzae Disease-United States, 2008-2019.

BACKGROUND: Nontypeable Haemophilus influenzae (NTHi) is the most common cause of invasive H. influenzae disease in the United States (US). We evaluated the epidemiology of invasive NTHi disease in the US, including among pregnant women, infants, and people with human immunodeficiency virus (PWH). METHODS: We used data from population- and laboratory-based surveillance for invasive H. influenzae disease conducted in 10 sites to estimate national incidence of NTHi, and to describe epidemiology in women of childbearing age, infants aged ≤30 days (neonates), and PWH living in the surveillance catchment areas. H. influenzae isolates were sent to the Centers for Disease Control and Prevention for species confirmation, serotyping, and whole genome sequencing of select isolates. RESULTS: During 2008-⁠2019, average annual NTHi incidence in the US was 1.3/100 000 population overall, 5.8/100 000 among children aged <1 year, and 10.2/100 000 among adults aged ≥80 years. Among 225 reported neonates with NTHi, 92% had a positive culture within the first week of life and 72% were preterm. NTHi risk was 23 times higher among preterm compared to term neonates, and 5.6 times higher in pregnant/postpartum compared to nonpregnant women. More than half of pregnant women with invasive NTHi had loss of pregnancy postinfection. Incidence among PWH aged ≥13 years was 9.5 cases per 100 000, compared to 1.1 cases per 100 000 for non-PWH (rate ratio, 8.3 [95% confidence interval, 7.1-9.7]; P < .0001). CONCLUSIONS: NTHi causes substantial invasive disease, especially among older adults, pregnant/postpartum women, and neonates. Enhanced surveillance and evaluation of targeted interventions to prevent perinatal NTHi infections may be warranted.

Comparison of Influenza and Coronavirus Disease 2019-Associated Hospitalizations Among Children Younger Than 18 Years Old in the United States: FluSurv-NET (October-April 2017-2021) and COVID-NET (October 2020-September 2021).

BACKGROUND: Influenza virus and SARS-CoV-2 are significant causes of respiratory illness in children. METHODS: Influenza- and COVID-19-associated hospitalizations among children <18 years old were analyzed from FluSurv-NET and COVID-NET, 2 population-based surveillance systems with similar catchment areas and methodology. The annual COVID-19-associated hospitalization rate per 100 000 during the ongoing COVID-19 pandemic (1 October 2020-30 September 2021) was compared with influenza-associated hospitalization rates during the 2017-2018 through 2019-2020 influenza seasons. In-hospital outcomes, including intensive care unit (ICU) admission and death, were compared. RESULTS: Among children <18 years, the COVID-19-associated hospitalization rate (48.2) was higher than influenza-associated hospitalization rates: 2017-2018 (33.5), 2018-2019 (33.8), and 2019-2020 (41.7). The COVID-19-associated hospitalization rate was higher among adolescents 12-17 years old (COVID-19: 59.9; influenza range: 12.2-14.1), but similar or lower among children 5-11 (COVID-19: 25.0; influenza range: 24.3-31.7) and 0-4 (COVID-19: 66.8; influenza range: 70.9-91.5) years old. Among children <18 years, a higher proportion with COVID-19 required ICU admission compared with influenza (26.4% vs 21.6%; P < .01). Pediatric deaths were uncommon during both COVID-19- and influenza-associated hospitalizations (0.7% vs 0.5%; P = .28). CONCLUSIONS: In the setting of extensive mitigation measures during the COVID-19 pandemic, the annual COVID-19-associated hospitalization rate during 2020-2021 was higher among adolescents and similar or lower among children <12 years compared with influenza during the 3 seasons before the COVID-19 pandemic. COVID-19 adds substantially to the existing burden of pediatric hospitalizations and severe outcomes caused by influenza and other respiratory viruses.

Secondary Cases of Invasive Disease Caused by Encapsulated and Nontypeable Haemophilus influenzae - 10 U.S. Jurisdictions, 2011-2018.

Haemophilus influenzae (Hi) can cause meningitis and other serious invasive disease. Encapsulated Hi is classified into six serotypes (a-f) based on chemical composition of the polysaccharide capsule; unencapsulated strains are termed nontypeable Hi (NTHi). Hi serotype b (Hib) was the most common cause of bacterial meningitis in children in the pre-Hib vaccine era, and secondary transmission of Hi among children (e.g., to household contacts and in child care facilities) (1,2) led to the Advisory Committee on Immunization Practices (ACIP) recommendation for antibiotic chemoprophylaxis to prevent Hib disease in certain circumstances.* High Hib vaccination coverage since the 1990s has substantially reduced Hib disease, and other serotypes now account for most Hi-associated invasive disease in the United States (3). Nevertheless, CDC does not currently recommend chemoprophylaxis for contacts of persons with invasive disease caused by serotypes other than Hib and by NTHi (non-b Hi). Given this changing epidemiology, U.S. surveillance data were reviewed to investigate secondary cases of invasive disease caused by Hi. The estimated prevalence of secondary transmission was 0.32% among persons with encapsulated Hi disease (≤60 days of one another) and 0.12% among persons with NTHi disease (≤14 days of one another). Isolates from all Hi case pairs were genetically closely related, and all patients with potential secondary infection had underlying medical conditions. These results strongly suggest that secondary transmission of non-b Hi occurs. Expansion of Hi chemoprophylaxis recommendations might be warranted to control invasive Hi disease in certain populations in the United States, but further analysis is needed to evaluate the potential benefits against the risks, such as increased antibiotic use.

Characteristics and Outcomes of Hospitalized Pregnant Women With Influenza, 2010 to 2019 : A Repeated Cross-Sectional Study.

BACKGROUND: Pregnant women may be at increased risk for severe influenza-associated outcomes. OBJECTIVE: To describe characteristics and outcomes of hospitalized pregnant women with influenza. DESIGN: Repeated cross-sectional study. SETTING: The population-based U.S. Influenza Hospitalization Surveillance Network during the 2010-2011 through 2018-2019 influenza seasons. PATIENTS: Pregnant women (aged 15 to 44 years) hospitalized with laboratory-confirmed influenza identified through provider-initiated or facility-based testing practices. MEASUREMENTS: Clinical characteristics, interventions, and in-hospital maternal and fetal outcomes were obtained through medical chart abstraction. Multivariable logistic regression was used to evaluate the association between influenza A subtype and severe maternal influenza-associated outcomes, including intensive care unit (ICU) admission, mechanical ventilation, extracorporeal membrane oxygenation, or in-hospital death. RESULTS: Of 9652 women aged 15 to 44 years and hospitalized with influenza, 2690 (27.9%) were pregnant. Among the 2690 pregnant women, the median age was 28 years, 62% were in their third trimester, and 42% had at least 1 underlying condition. Overall, 32% were vaccinated against influenza and 88% received antiviral treatment. Five percent required ICU admission, 2% required mechanical ventilation, and 0.3% (n = 8) died. Pregnant women with influenza A H1N1 were more likely to have severe outcomes than those with influenza A H3N2 (adjusted risk ratio, 1.9 [95% CI, 1.3 to 2.8]). Most women (71%) were still pregnant at hospital discharge. Among 754 women who were no longer pregnant at discharge, 96% had a pregnancy resulting in live birth, and 3% experienced fetal loss. LIMITATION: Maternal and fetal outcomes that occurred after hospital discharge were not captured. CONCLUSION: Over 9 influenza seasons, one third of reproductive-aged women hospitalized with influenza were pregnant. Influenza A H1N1 was associated with more severe maternal outcomes. Pregnant women remain a high-priority target group for vaccination. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Impact of Pneumococcal Conjugate Vaccines on Antibiotic-Nonsusceptible Invasive Pneumococcal Disease in the United States.

BACKGROUND: Antibiotic-nonsusceptible invasive pneumococcal disease (NS-IPD) incidence declined dramatically in the United States after introduction of pneumococcal conjugate vaccines (PCVs) into the infant immunization schedule (7-valent PCV7 in 2000, replaced by the 13-valent PCV13 in 2010). We evaluated the long-term impact of PCVs on NS-IPD. METHODS: We identified IPD cases through the Centers for Disease Control Active Bacterial Core surveillance during 1998-2018. Isolates intermediate or resistant to ≥1 antibiotic class were classified as nonsusceptible. We calculated annual rates of IPD (cases per 100 000 persons). RESULTS: From 1998 through 2018, NS-IPD incidence decreased from 43.9 to 3.2 among children <5 years and from 19.8 to 9.4 among adults ≥65 years. Incidence of vaccine-type NS-IPD decreased in all age groups, whereas incidence of nonvaccine type (NVT) NS-IPD increased in all age groups; the greatest absolute increase in NVT NS-IPD occurred among adults ≥65 years (2.3 to 7.2). During 2014-2018, NVTs 35B, 33F, 22F, and 15A were the most common NS-IPD serotypes. CONCLUSIONS: Nonsusceptible IPD incidence decreased after PCV7 and PCV13 introduction in the United States. However, recent increases in NVT NS-IPD, most pronounced among older adults, have been observed. New higher valency PCVs containing the most common nonsusceptible serotypes, including 22F and 33F, could help further reduce NS-IPD.

Epidemiology, Clinical Characteristics, and Outcomes of Influenza-Associated Hospitalizations in US Children Over 9 Seasons Following the 2009 H1N1 Pandemic.

BACKGROUND: Recent population-based data are limited regarding influenza-associated hospitalizations in US children. METHODS: We identified children <18 years hospitalized with laboratory-confirmed influenza during 2010-2019 seasons, through the Centers for Disease Control and Prevention's Influenza Hospitalization Surveillance Network. Adjusted hospitalization and in-hospital mortality rates were calculated, and multivariable logistic regression was conducted to evaluate risk factors for pneumonia, intensive care unit (ICU) admission, mechanical ventilation, and death. RESULTS: Over 9 seasons, adjusted influenza-associated hospitalization incidence rates ranged from 10 to 375 per 100 000 persons each season and were highest among infants <6 months old. Rates decreased with increasing age. The highest in-hospital mortality rates were observed in children <6 months old (0.73 per 100 000 persons). Over time, antiviral treatment significantly increased, from 56% to 85% (P < .001), and influenza vaccination rates increased from 33% to 44% (P = .003). Among the 13 235 hospitalized children, 2676 (20%) were admitted to the ICU, 2262 (17%) had pneumonia, 690 (5%) required mechanical ventilation, and 72 (0.5%) died during hospitalization. Compared with those <6 months of age, hospitalized children ≥13 years old had higher odds of pneumonia (adjusted odds ratio, 2.7 [95% confidence interval, 2.1-3.4], ICU admission (1.6 [1.3-1.9]), mechanical ventilation (1.6 [1.1-2.2]), and death (3.3 [1.2-9.3]). CONCLUSIONS: Hospitalization and death rates were greatest in younger children at the population level. Among hospitalized children, however, older children had a higher risk of severe outcomes. Continued efforts to prevent and attenuate influenza in children are needed.

Day of trophectoderm biopsy and embryo quality are associated with outcomes following euploid embryo transfer.

PURPOSE: To compare clinical outcomes following transfer of euploid blastocysts of varying quality biopsied on day 5 versus day 6. METHODS: Retrospective cohort study to evaluate embryo transfer outcomes for women undergoing autologous cryopreserved next generation sequencing euploid single embryo transfer from 10/2015 to 2/2022 at an academic IVF program. The primary outcome was live birth rate (LBR). Secondary outcomes included ongoing pregnancy rate (OPR), implantation rate (IR), and miscarriage rate (SAB rate). RESULTS: Five hundred and fifty-five transfers from 418 patients were analyzed. Euploid embryos biopsied on day 5 resulted in higher LBR compared to those biopsied on day 6 (62.3% vs. 49.6%; aRR 0.81 95% CI 0.65-0.996). When stratified by biopsy day and blastocyst quality, there was no difference in IR, OPR, and SAB rate for good, fair, and poor quality blastocysts biopsied on day 5 versus day 6. However, day 5 good quality embryos were associated with a higher LBR compared to day 6 good quality embryos (74.3% vs. 51.3%; aRR 0.69; 95% CI 0.48-0.999). There were no significant differences in LBR for fair and poor quality embryos biopsied on day 5 versus day 6. CONCLUSION: Overall LBR are higher for euploid embryos biopsied on day 5 versus day 6. When stratified by embryo quality and day of biopsy, LBR are significantly higher for good quality day 5 versus day 6 embryos. When choosing between multiple euploid embryos, day 5 biopsied good quality embryos should be preferentially selected for transfer over day 6 embryos of the same quality.

Association between serum estradiol level on day of progesterone start and outcomes from frozen blastocyst transfer cycles utilizing oral estradiol.

PURPOSE: Supraphysiologic serum estradiol levels may negatively impact the likelihood of conception and live birth following IVF. The purpose of this study is to determine if there is an association between serum estradiol level on the day of progesterone start and clinical outcomes following programmed frozen blastocyst transfer cycles utilizing oral estradiol. METHODS: This is a retrospective cohort study at an academic fertility center analyzing 363 patients who underwent their first autologous single (SET) or double frozen embryo transfer (DET) utilizing oral estradiol and resulting in blastocyst transfer from June 1, 2012, to June 30, 2018. Main outcome measures included implantation, clinical pregnancy, live birth, and miscarriage rates. Cycles were stratified by quartile of serum estradiol on the day of progesterone start and separately analyzed for SET cycles only. Poisson and Log binomial regression were used to calculate relative risks (RR) with 95% confidence intervals (CI) for implantation, clinical pregnancy, live birth, and miscarriage with adjustments made for age and BMI. RESULTS: Cycles with the highest quartile of estradiol (mean 528 pg/mL) were associated with lower risks of implantation (RR 0.66, CI 0.50-0.86), ongoing pregnancy (RR 0.66, CI 0.49-0.88), and live birth (RR 0.70, CI 0.52-0.94) compared with those with the lowest estradiol quartile (mean 212 pg/mL). Similar findings were seen for analyses limited to SETs. There was no significant difference in miscarriage rate or endometrial thickness between groups. CONCLUSION: High levels of serum estradiol on the day of progesterone start may be detrimental to implantation, pregnancy, and live birth following frozen blastocyst transfer.

Racial Disparities in Invasive Haemophilus influenzae Disease-United States, 2008-2017.

BACKGROUND: Since 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. METHODS: Active 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. RESULTS: During 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 <5 years, incidence of H. influenzae serotype a (Hia) was 16.7 times higher and Hib incidence was 22.4 times higher than among White children. Although Hia incidence was lower among White and Black populations than among AI/AN populations, Hia incidence increased 13.6% annually among White children and 40.4% annually among Black children aged <5 years. CONCLUSIONS: While 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 <5 years. Prevention tools are needed to reduce disparities affecting AI/AN children and address increasing Hia incidence in other communities.

Multistate, Population-Based Distributions of Candidate Vaccine Targets, Clonal Complexes, and Resistance Features of Invasive Group B Streptococci Within the United States, 2015-2017.

BACKGROUND: Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and meningitis and an important cause of invasive infections in pregnant and nonpregnant adults. Vaccines targeting capsule polysaccharides and common proteins are under development. METHODS: Using whole genome sequencing, a validated bioinformatics pipeline, and targeted antimicrobial susceptibility testing, we characterized 6340 invasive GBS isolates recovered during 2015-2017 through population-based Active Bacterial Core surveillance (ABCs) in 8 states. RESULTS: Six serotypes accounted for 98.4% of isolates (21.8% Ia, 17.6% V, 17.1% II, 15.6% III, 14.5% Ib, 11.8% IV). Most (94.2%) isolates were in 11 clonal complexes (CCs) comprised of multilocus sequence types identical or closely related to sequence types 1, 8, 12, 17, 19, 22, 23, 28, 88, 452, and 459. Fifty-four isolates (0.87%) had point mutations within pbp2x associated with nonsusceptibility to 1 or more ß-lactam antibiotics. Genes conferring resistance to macrolides and/or lincosamides were found in 56% of isolates; 85.2% of isolates had tetracycline resistance genes. Two isolates carrying vanG were vancomycin nonsusceptible (minimum inhibitory concentration = 2 µg/mL). Nearly all isolates possessed capsule genes, 1-2 of the 3 main pilus gene clusters, and 1 of 4 homologous alpha/Rib family determinants. Presence of the hvgA virulence gene was primarily restricted to serotype III/CC17 isolates (465 isolates), but 8 exceptions (7 IV/CC452 and 1 IV/CC17) were observed. CONCLUSIONS: This first comprehensive, population-based quantitation of strain features in the United States suggests that current vaccine candidates should have good coverage. The ß-lactams remain appropriate for first-line treatment and prophylaxis, but emergence of nonsusceptibility warrants ongoing monitoring.

Invasive Group A Streptococcal Infections Among People Who Inject Drugs and People Experiencing Homelessness in the United States, 2010-2017.

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.

Epidemiology of Invasive Haemophilus influenzae Serotype a Disease-United States, 2008-2017.

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 <5 years (incidence: 0.64), with highest incidence among children aged <1 year (1.60). Case fatality was 7.8% overall and was highest among adults aged ≥65 years (15.1%). Among children aged <5 years, the incidence was 17 times higher among American Indian and Alaska Native (AI/AN) children (8.29) than among children of all other races combined (0.49). In Alaska, incidences among all ages (0.68) and among children aged <1 year (24.73) were nearly 6 and 14 times higher, respectively, than corresponding US incidences. Case fatality in Alaska was 10.2%, and the vast majority (93.9%) of cases occurred among AI/AN. 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.

The impact of fertility preservation on the timing of breast cancer treatment, recurrence, and survival.

BACKGROUND: Many young women with breast cancer undergo fertility preservation (FP) before cancer treatment. This study examined the impact of FP on breast cancer outcomes. METHODS: The authors performed a retrospective cohort study of 272 women aged 20 to 45 years with newly diagnosed stage 0 to III breast cancer who underwent an FP consultation between 2005 and 2017. Among these women, 123 (45.2%) underwent FP (fertility preservation-positive [FP+]). The remaining 149 women did not undergo FP (fertility preservation-negative [FP-]). RESULTS: The characteristics at enrollment were similar with the exception of ethnicity (FP+, 87.8% White; FP-, 67.8% White; P = .002) and BRCA status (FP+, 27.7% BRCA+; FP-, 15.5% BRCA+; P = .021). The median follow-up was approximately 4 years. Women who underwent FP had longer times to first treatment (FP+, 37 days; FP-, 31 days; adjusted hazard ratio [aHR], 0.74; confidence interval [CI], 0.56-0.99) and neoadjuvant chemotherapy (FP+, 36 days; FP-, 26 days; aHR, 0.41; CI, 0.24-0.68) and from surgery to adjuvant chemotherapy (FP+, 41 days; FP-, 33 days; aHR, 0.58; CI, 0.38-0.90). Adjusted 3- and 5-year invasive disease-free survival (IDFS) rates were comparable between the 2 groups (3-year IDFS: FP+, 85.4%; FP-, 79.4%; P = .411; 5-year IDFS: FP+, 73.7%; FP-, 67.1%; P = .288). Similarly, no difference in overall survival (OS) was observed between the 2 groups (3-year OS: FP+, 95.5%; FP-, 93.5%; P = .854; 5-year OS: FP+, 84.2%; FP-, 81.4%; P = .700). CONCLUSIONS: FP after a breast cancer diagnosis delays the time to treatment by a small amount, but this delay does not lead to inferior IDFS or OS.

The cost-effectiveness of preimplantation genetic testing for aneuploidy in the United States: an analysis of cost and birth outcomes from 158,665 in vitro fertilization cycles.

BACKGROUND: A controversial and unresolved question in reproductive medicine is the utility of preimplantation genetic testing for aneuploidy as an adjunct to in vitro fertilization. Infertility is prevalent, but its treatment is notoriously expensive and typically not covered by insurance. Therefore, cost-effectiveness is critical to consider in this context. OBJECTIVE: This study aimed to analyze the cost-effectiveness of preimplantation genetic testing for aneuploidy for the treatment of infertility in the United States. STUDY DESIGN: As reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System, a national data registry, in vitro fertilization cycles occurring between 2014 and 2016 in the United States were analyzed. A probabilistic decision tree was developed using empirical outputs to simulate the events and outcomes associated with in vitro fertilization with and without preimplantation genetic testing for aneuploidy. The treatment strategies were (1) in vitro fertilization with intended preimplantation genetic testing for aneuploidy and (2) in vitro fertilization with transfers of untested embryos. Patients progressed through the treatment model until they achieved a live birth or 12 months after ovarian stimulation. Clinical costs related to both treatment strategies were extracted from the literature and considered from both the patient and payer perspectives. Outcome metrics included incremental cost (measured in 2018 US dollars), live birth outcomes, incremental cost-effectiveness ratio, and incremental cost per live birth between treatment strategies. RESULTS: The study population included 114,157 first fresh in vitro fertilization stimulations and 44,508 linked frozen embryo transfer cycles. Of the fresh stimulations, 16.2% intended preimplantation genetic testing for aneuploidy and 83.8% did not. In patients younger than 35 years old, preimplantation genetic testing for aneuploidy was associated with worse clinical outcomes and higher costs. At age 35 years and older, preimplantation genetic testing for aneuploidy led to more cumulative births but was associated with higher costs from both perspectives. From a patient perspective, the incremental cost per live birth favored the no preimplantation genetic testing for aneuploidy strategy from the <35 years age group to the 38 years age group and beginning at age 39 years favored preimplantation genetic testing for aneuploidy. From a payer perspective, the incremental cost per live birth favored preimplantation genetic testing for aneuploidy regardless of patient age. CONCLUSION: The cost-effectiveness of preimplantation genetic testing for aneuploidy is dependent on patient age and perspective. From an economic perspective, routine preimplantation genetic testing for aneuploidy should not be universally adopted; however, it may be cost-effective in certain scenarios.

Hospitalizations Associated with COVID-19 Among Children and Adolescents - COVID-NET, 14 States, March 1, 2020-August 14, 2021.

Although COVID-19-associated hospitalizations and deaths have occurred more frequently in adults,† COVID-19 can also lead to severe outcomes in children and adolescents (1,2). Schools are opening for in-person learning, and many prekindergarten children are returning to early care and education programs during a time when the number of COVID-19 cases caused by the highly transmissible B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, is increasing.§ Therefore, it is important to monitor indicators of severe COVID-19 among children and adolescents. This analysis uses Coronavirus Disease 2019-Associated Hospitalization Surveillance Network (COVID-NET)¶ data to describe COVID-19-associated hospitalizations among U.S. children and adolescents aged 0-17 years. During March 1, 2020-August 14, 2021, the cumulative incidence of COVID-19-associated hospitalizations was 49.7 per 100,000 children and adolescents. The weekly COVID-19-associated hospitalization rate per 100,000 children and adolescents during the week ending August 14, 2021 (1.4) was nearly five times the rate during the week ending June 26, 2021 (0.3); among children aged 0-4 years, the weekly hospitalization rate during the week ending August 14, 2021, was nearly 10 times that during the week ending June 26, 2021.** During June 20-July 31, 2021, the hospitalization rate among unvaccinated adolescents (aged 12-17 years) was 10.1 times higher than that among fully vaccinated adolescents. Among all hospitalized children and adolescents with COVID-19, the proportions with indicators of severe disease (such as intensive care unit [ICU] admission) after the Delta variant became predominant (June 20-July 31, 2021) were similar to those earlier in the pandemic (March 1, 2020-June 19, 2021). Implementation of preventive measures to reduce transmission and severe outcomes in children is critical, including vaccination of eligible persons, universal mask wearing in schools, recommended mask wearing by persons aged ≥2 years in other indoor public spaces and child care centers,†† and quarantining as recommended after exposure to persons with COVID-19.§§.