Incidence and Transmission of SARS-CoV-2 in US Child Care Centers After COVID-19 Vaccines.

Importance: SARS-CoV-2 surveillance studies in US child care centers (CCCs) in the post-COVID-19 vaccine era are needed to provide information on incidence and transmission in this setting. Objective: To characterize SARS-CoV-2 incidence and transmission in children attending CCCs (students) and their child care providers (CCPs) and household contacts. Design, Setting, and Participants: This prospective surveillance cohort study was conducted from April 22, 2021, through March 31, 2022, and included 11 CCCs in 2 cities. A subset (surveillance group) of CCPs and students participated in active surveillance (weekly reverse transcription-polymerase chain reaction [RT-PCR] swabs, symptom diaries, and optional baseline and end-of-study SARS-CoV-2 serologic testing), as well as all household contacts of surveillance students. Child care center directors reported weekly deidentified self-reported COVID-19 cases from all CCPs and students (self-report group). Exposure: SARS-CoV-2 infection in CCC students. Main Outcomes and Measures: SARS-CoV-2 incidence, secondary attack rates, and transmission patterns were determined from diary entries, self-reports to CCC directors, and case logs. Incidence rate ratios were measured using Poisson regression clustering on centers with a random intercept and unstructured matrix. Results: From a total population of 1154 students and 402 CCPs who self-reported cases to center directors, 83 students (7.2%; mean [SD] age, 3.86 [1.64] years; 55 male [66%]), their 134 household contacts (118 adults [mean (SD) age, 38.39 (5.07) years; 62 female (53%)], 16 children [mean (SD) age, 4.73 (3.37) years; 8 female (50%)]), and 21 CCPs (5.2%; mean [SD] age, 38.5 [12.9] years; 18 female [86%]) participated in weekly active surveillance. There were 154 student cases (13%) and 87 CCP cases (22%), as defined by positive SARS-CoV-2 RT-PCR or home antigen results. Surveillance students had a higher incidence rate than self-report students (incidence rate ratio, 1.9; 95% CI, 1.1-3.3; P = .01). Students were more likely than CCPs to have asymptomatic infection (34% vs 8%, P < .001). The CCC secondary attack rate was 2.7% to 3.0%, with the upper range representing possible but not definite secondary cases. Whether the index case was a student or CCP, transmission within the CCC was not significantly different. Household cumulative incidence was 20.5%, with no significant difference in incidence rate ratio between adults and children. Household secondary attack rates were 50% for children and 67% for adults. Of 30 household cases, only 5 (17%) represented secondary infections caused by 3 students who acquired SARS-CoV-2 from their CCC. Pre- and poststudy seroprevalence rates were 3% and 22%, respectively, with 90% concordance with antigen or RT-PCR results. Conclusions and Relevance: In this study of SARS-CoV-2 incidence and transmission in CCCs and students' households, transmission within CCCs and from children infected at CCCs into households was low. These findings suggest that current testing and exclusion recommendations for SARS-CoV-2 in CCCs should be aligned with those for other respiratory viruses with similar morbidity and greater transmission to households.

Using the MCRISP Network for Surveillance of Pediatric Exanthema in Child Care Centers.

BACKGROUND: Systematic monitoring of exanthema is largely absent from public health surveillance despite emerging diseases and threats of bioterrorism. Michigan Child Care Related Infections Surveillance Program (MCRISP) is the first online program in child care centers to report pediatric exanthema. METHODS: MCRISP aggregated daily counts of children sick, absent, or reported ill by parents. We extracted all MCRISP exanthema cases from October 1, 2014 through June 30, 2019. Cases were assessed with descriptive statistics and counts were used to construct epidemic curves. RESULTS: 360 exanthema cases were reported from 12,233 illnesses over 4.5 seasons. Children ages 13-35 months had the highest rash occurrence (45%, n = 162), followed by 36-59 months (41.7%, n = 150), 0-12 months (12.5%, n = 45), and kindergarten (0.8%, n = 3). Centers reported rashes of hand-foot-mouth disease (50%, n = 180), nonspecific rash without fever (15.3%, n = 55), hives (8.1%, n = 29), fever with nonspecific rash (6.9%, n = 25), roseola (3.3%, n = 12), scabies (2.5%, n = 9), scarlet fever (2.5%, n = 9), impetigo (2.2%, n = 8), abscess (1.95, n = 7), viral exanthema without fever (1.7%, n = 6), varicella (1.7%, n = 6), pinworms (0.8%, n = 3), molluscum (0.6%, n = 2), cellulitis (0.6%, n = 2), ringworm (0.6%, n = 2), and shingles (0.2%, n = 1). CONCLUSION: Child care surveillance networks have the potential to act as sentinel public health tools for surveillance of pediatric exanthema outbreaks.

Expanding Surveillance Toward Sharing Data with the Community: Qualitative Insights from a Childcare Center Illness Surveillance Program.

Childcare attendance is a recognized independent risk factor for pediatric infectious diseases due to the pathogen-sharing behaviors of young children and the crowded environments of childcare programs. The Michigan Child Care Related Infections Surveillance Program (MCRISP) is a novel online illness surveillance network used by community childcare centers to track disease incidence. It has been used to warn local public health departments about emerging outbreaks. The flow of data from MCRISP, however, remains largely unidirectional-from data reporter to public health researchers. With the intent to ultimately improve the system for users, we wanted to better understand how community illness data collected by MCRISP might best benefit childcare stakeholders themselves. Using a ground-up design approach, we conducted a series of focus groups among childcare directors participating in MCRISP. All primary data reporters from each of the 30 MCRISP-affiliated childcare centers were eligible to participate in the focus groups. A thematic assessment from the focus groups revealed that participants wanted surveillance system improvements that would (1) support subjective experiences with objective data, (2) assist with program decision making, (3) provide educational resources, and (4) prioritize the user's experience. Our findings support a framework by which community disease surveillance networks can move toward greater transparency and 2-way data flow. Ultimately, a more mutually beneficial surveillance system improves stakeholder engagement, provides opportunities for rapid mitigation strategies, and can help allocate timely resources in responding to emerging outbreaks and pandemics.

A "resistance calculator": Simple stewardship intervention for refining empiric practices of antimicrobials in acute-care hospitals.

OBJECTIVE: In the era of widespread resistance, there are 2 time points at which most empiric prescription errors occur among hospitalized adults: (1) upon admission (UA) when treating patients at risk of multidrug-resistant organisms (MDROs) and (2) during hospitalization, when treating patients at risk of extensively drug-resistant organisms (XDROs). These errors adversely influence patient outcomes and the hospital's ecology. DESIGN AND SETTING: Retrospective cohort study, Shamir Medical Center, Israel, 2016. PATIENTS: Adult patients (aged >18 years) hospitalized with sepsis. METHODS: Logistic regressions were used to develop predictive models for (1) MDRO UA and (2) nosocomial XDRO. Their performances on the derivation data sets, and on 7 other validation data sets, were assessed using the area under the receiver operating characteristic curve (ROC AUC). RESULTS: In total, 4,114 patients were included: 2,472 patients with sepsis UA and 1,642 with nosocomial sepsis. The MDRO UA score included 10 parameters, and with a cutoff of ≥22 points, it had an ROC AUC of 0.85. The nosocomial XDRO score included 7 parameters, and with a cutoff of ≥36 points, it had an ROC AUC of 0.87. The range of ROC AUCs for the validation data sets was 0.7-0.88 for the MDRO UA score and was 0.66-0.75 for nosocomial XDRO score. We created a free web calculator (https://assafharofe.azurewebsites.net). CONCLUSIONS: A simple electronic calculator could aid with empiric prescription during an encounter with a septic patient. Future implementation studies are needed to evaluate its utility in improving patient outcomes and in reducing overall resistances.

Targeting the Type II Secretion System: Development, Optimization, and Validation of a High-Throughput Screen for the Identification of Small Molecule Inhibitors.

Nosocomial pathogens that develop multidrug resistance present an increasing problem for healthcare facilities. Due to its rapid rise in antibiotic resistance, Acinetobacter baumannii is one of the most concerning gram-negative species. A. baumannii typically infects immune compromised individuals resulting in a variety of outcomes, including pneumonia and bacteremia. Using a murine model for bacteremia, we have previously shown that the type II secretion system (T2SS) contributes to in vivo fitness of A. baumannii. Here, we provide support for a role of the T2SS in protecting A. baumannii from human complement as deletion of the T2SS gene gspD resulted in a 100-fold reduction in surviving cells when incubated with human serum. This effect was abrogated in the absence of Factor B, a component of the alternative pathway of complement activation, indicating that the T2SS protects A. baumannii against the alternative complement pathway. Because inactivation of the T2SS results in loss of secretion of multiple enzymes, reduced in vivo fitness, and increased sensitivity to human complement, the T2SS may be a suitable target for therapeutic intervention. Accordingly, we developed and optimized a whole-cell high-throughput screening (HTS) assay based on secreted lipase activity to identify small molecule inhibitors of the T2SS. We tested the reproducibility of our assay using a 6,400-compound library. With small variation within controls and a dynamic range between positive and negative controls, the assay had a z-factor of 0.65, establishing its suitability for HTS. Our screen identified the lipase inhibitors Orlistat and Ebelactone B demonstrating the specificity of the assay. To eliminate inhibitors of lipase activity and lipase expression, two counter assays were developed and optimized. By implementing these assays, all seven tricyclic antidepressants present in the library were found to be inhibitors of the lipase, highlighting the potential of identifying alternative targets for approved pharmaceuticals. Although no T2SS inhibitor was identified among the compounds that reduced lipase activity by ≥30%, our small proof-of-concept pilot study indicates that the HTS regimen is simple, reproducible, and specific and that it can be used to screen larger libraries for the identification of T2SS inhibitors that may be developed into novel A. baumannii therapeutics.

Glioblastoma cell line-derived spheres in serum­containing medium versus serum-free medium: a comparison of cancer stem cell properties.

In addition to the primary culturing of cancer stem cells (CSCs) from tumor tissues, CSCs are found in established tumor cell lines. However, it is unclear how culture conditions affect CSC enrichment. Additionally, the differentiation potential of cell line-derived CSCs has not been well studied. In our study, the glioblastoma cell lines LN229, T98G, U251n and U87, were cultured as spheres in serum-containing medium (serum spheres) or serum-free medium (serum-free spheres). We found that LN229 and U251n cells expressed multiple stem cell markers such as Nestin, Sox2, Musashi-1 and CD44, and their serum spheres expressed even higher levels of Nestin, Sox2 and Musashi-1 compared to monolayer cells and serum­free spheres. LN229 and U251n cells showed higher migration and colony formation potential compared to T98G and U87 cells, which did not express Nestin, Sox2 and Musashi-1. Serum spheres of LN229 and U251n cells also exhibited higher resistance to temozolomide compared to serum-free spheres. All tumor cell lines showed neuronal differentiation (Tuj-1 positive). Only U251n serum spheres exhibited both astrocytic (GFAP­positive) and neuronal differentiation. We conclude that sphere culture in serum-containing medium provides the most efficient enrichment of cancer stem cells. U251n cells are distinguished from other tumor cells due to their potential for multilineage differentiation.

Randomized equivalence study evaluating the possibility of switching hemodialysis patients receiving subcutaneous human erythropoietin directly to intravenous darbepoetin alfa.

BACKGROUND: Darbepoetin alfa is an erythropoiesis-stimulating agent (ESA) used either intravenously or subcutaneously with no dose penalty; however, the direct switch from subcutaneous recombinant human erythropoietin (rHuEPO) to intravenous darbepoetin has barely been studied. OBJECTIVE: To establish the equivalence of a direct switch from subcutaneous rHuEPO to intravenous darbepoetin versus an indirect switch from subcutaneous rHuEPO to intravenous darbepoetin after 2 months of subcutaneous darbepoetin in patients undergoing hemodialysis. METHODS: In this open, randomized, 6-month, prospective study, patients with end-stage kidney disease who were on hemodialysis were randomized into 2 groups: direct switch from subcutaneous rHuEPO to intravenous darbepoetin (group 1) and indirect switch from subcutaneous rHuEPO to intravenous darbepoetin after 2 months of subcutaneous darbepoetin (group 2). A third, nonrandomized group (control), consisting of patients treated with intravenous rHuEPO who were switched to intravenous darbepoetin, was also studied to reflect possible variations of hemoglobin (Hb) levels due to change from one type of ESA to the other. The primary outcome was the proportion of patients with stable Hb levels at month 6. Secondary endpoints included Hb stability at month 3, dosage requirements for darbepoetin, and safety of the administration route. RESULTS: Among 154 randomized patients, the percentages with stable Hb levels were equivalent in groups 1 and 2, respectively, at month 3 (86.0% vs 91.3%) and month 6 (82.1% vs 81.6%; difference -0.5 [90% CI -12.8 to 11.8]). Mean Hb levels between baseline and month 6 remained stable in both groups, with no variation in mean darbepoetin dose. Mean ferritin levels remained above 100 microg/L in the 3 groups during the whole study, and darbepoetin was well tolerated. CONCLUSIONS: This study has shown equivalent efficacy on Hb stability without the need for dosage increase in patients switched directly from subcutaneous rHuEPO to intravenous darbepoetin.

The "tract" of history in the treatment of lumbar degenerative disc disease.

In this paper past, present, and future treatments of degenerative disc disease (DDD) of the lumbar spine are outlined in a straight forward manner. This is done to review previous knowledge of the disease, define current treatment procedures, and discuss future perspectives. An analysis of a subject of this magnitude dictates that one describes as accurate a history as possible: an anatomical/historical "tract" with emphasis on all possible deviations. Although spinal disorders have been recognized for a long time, the view of DDD as a particular disease entity is a more recent development. In this paper, the authors attempt to outline the history of DDD of the lumbar spine in an unbiased and scientific fashion. Physiological, diagnostic, and therapeutic implications will all be addressed in this study.