Methodological Issues in Clinical Drug Development for Essential Tremor

Essential tremor (ET) is one of the most common tremor disorders in the world. Despite this, only two medications have received Level A recommendations from the American Academy of Neurology to treat it (primidone and propranolol). Even though these medications provide relief to a large group of ET patients, up to 50% of patients are non-responders. Additional medications to treat ET are needed. This review discusses some of the methodological issues that should be addressed for quality clinical drug development in ET

Defining Variability in Evaluation and Management of Children with Chronic Osteomyelitis

Pediatric chronic osteomyelitis is a rare, debilitating condition lacking management guidelines. In a national survey of 162 pediatric infectious disease physicians through the Emerging Infections Network, tremendous variability in diagnostic approaches and management were noted, highlighting a need for prospective study to better define the spectrum of pathogens and disease

Building a National Framework to Pair Scientists and Schools During a Global Pandemic

The coronavirus disease 2019 (COVID-19) pandemic forced the suspension of in-person education in schools serving students in kindergarten through 12th grade (K-12) across the United States. As time passed, teachers, students, and parents struggled with remote education. With limited guidance at the federal level, physicians and school leaders across the country collaborated to develop local solutions for schools. This article describes the lessons learned from the development of 4 academic-community partnerships and collaboration among these partnerships to provide national leadership on managing COVID-19 mitigation in the K-12 environment. In addition, we describe a pathway forward for using academic-community partnerships to improve child health

Community SARS-CoV-2 Surge and Within-School Transmission

OBJECTIVES: When the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic began, experts raised concerns about in-person instruction in the setting of high levels of community transmission. We describe secondary transmission of SARS-CoV-2 within North Carolina (NC) K-12 school districts during a winter surge to determine if mitigation strategies can hinder within-school transmission. METHODS: From 10/26/2020–02/28/2021, 13 NC school districts participating in the ABC Science Collaborative were open for in-person instruction, adhered to basic mitigation strategies, and tracked community- and school-acquired SARS-CoV-2 cases. Public health officials adjudicated each case. We combined these data with that from August 2020 to evaluate the effect of the SARS-CoV-2 winter surge on infection rates, as well as weekly community- and school-acquired cases. We evaluated the number of secondary cases generated by each primary case, as well as the role of athletic activities in school-acquired cases. RESULTS: More than 100,000 students and staff from 13 school districts attended school in-person; of these, 4,969 community-acquired SARS-CoV-2 infections were documented by molecular testing. Through contact tracing, NC local health department staff identified an additional 209 infections among >26,000 school close contacts (secondary attack rate <1%). Most within-school transmissions in high schools (75%) were linked to school-sponsored sports. School-acquired cases slightly increased during the surge; however, within-school transmission rates remained constant, from pre-surge to surge, with approximately 1 school-acquired case for every 20 primary cases. CONCLUSIONS: With adherence to basic mitigation strategies, within-school transmission of SARS-CoV-2 can be interrupted, even during a surge of community infections

international Epidemiology of Carbapenemase-Producing Escherichia Coli

BACKGROUND: Carbapenemase-producing (CP) Escherichia coli (CP-Ec) are a global public health threat. We aimed to describe the clinical and molecular epidemiology and outcomes of patients from several countries with CP-Ec isolates obtained from a prospective cohort. METHODS: Patients with CP-Ec were enrolled from 26 hospitals in 6 countries. Clinical data were collected, and isolates underwent whole-genome sequencing. Clinical and molecular features and outcomes associated with isolates with or without metallo-β-lactamases (MBLs) were compared. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after the index culture. RESULTS: Of the 114 CP-Ec isolates in Consortium on resistance against carbapenems in Klebsiella and other Enterobacterales-2 (CRACKLE-2), 49 harbored an MBL, most commonly blaNDM-5 (38/49, 78%). Strong regional variations were noted with MBL-Ec predominantly found among patients in China (23/49). Clinically, MBL-Ec were more often from urine sources (49% vs 29%), less often met criteria for infection (39% vs 58%, P = .04), and had lower acuity of illness when compared with non-MBL-Ec. Among patients with infection, the probability of a better DOOR outcome for a randomly selected patient with MBL-Ec as compared with non-MBL-Ec was 62% (95% CI: 48.2-74.3%). Among infected patients, non-MBL-Ec had increased 30-day (26% vs 0%; P = .02) and 90-day (39% vs 0%; P = .001) mortality compared with MBL-Ec. CONCLUSIONS: Emergence of CP-Ec was observed with important geographic variations. Bacterial characteristics, clinical presentations, and outcomes differed between MBL-Ec and non-MBL-Ec. Mortality was higher among non-MBL isolates, which were more frequently isolated from blood, but these findings may be confounded by regional variations

School Masking Policies and Secondary SARS-CoV-2 Transmission.

OBJECTIVES: Throughout the COVID-19 pandemic, masking has been a widely used mitigation practice in kindergarten through 12th grade (K-12) school districts to limit within-school transmission. Prior studies attempting to quantify the impact of masking have assessed total cases within schools; however, the metric that more optimally defines effectiveness of mitigation practices is within-school transmission, or secondary cases. We estimated the impact of various masking practices on secondary transmission in a cohort of K-12 schools. METHODS: We performed a multistate, prospective, observational, open cohort study from July 26, 2021 to December 13, 2021. Districts reported mitigation practices and weekly infection data. Districts that were able to perform contact tracing and adjudicate primary and secondary infections were eligible for inclusion. To estimate the impact of masking on secondary transmission, we used a quasi-Poisson regression model. RESULTS: A total of 1 112 899 students and 157 069 staff attended 61 K-12 districts across 9 states that met inclusion criteria. The districts reported 40 601 primary and 3085 secondary infections. Six districts had optional masking policies, 9 had partial masking policies, and 46 had universal masking. In unadjusted analysis, districts that optionally masked throughout the study period had 3.6 times the rate of secondary transmission as universally masked districts; and for every 100 community-acquired cases, universally masked districts had 7.3 predicted secondary infections, whereas optionally masked districts had 26.4. CONCLUSIONS: Secondary transmission across the cohort was modest (&lt;10% of total infections) and universal masking was associated with reduced secondary transmission compared with optional masking

Test-to-Stay After SARS-CoV-2 Exposure: A Mitigation Strategy for Optionally Masked K-12 Schools.

OBJECTIVES: We evaluated the impact of a test-to-stay (TTS) program on within-school transmission and missed school days in optionally masked kindergarten through 12th grade schools during a period of high community severe acute respiratory syndrome coronavirus 2 transmission. METHODS: Close contacts of those with confirmed severe acute respiratory syndrome coronavirus 2 infection were eligible for enrollment in the TTS program if exposure to a nonhousehold contact occurred between November 11, 2021 and January 28, 2022. Consented participants avoided school exclusion if they remained asymptomatic and rapid antigen testing at prespecified intervals remained negative. Primary outcomes included within-school tertiary attack rate (test positivity among close contacts of positive TTS participants) and school days saved among TTS participants. We estimated the number of additional school-acquired cases resulting from TTS and eliminating school exclusion. RESULTS: A total of 1675 participants tested positive or received at least 1 negative test between days 5 and 7 and completed follow-up; 92% were students and 91% were exposed to an unmasked primary case. We identified 201 positive cases. We observed a tertiary attack rate of 10% (95% confidence interval: 6%-19%), and 7272 (89%) of potentially missed days were saved through TTS implementation. We estimated 1 additional school-acquired case for every 21 TTS participants remaining in school buildings during the entire study period. CONCLUSIONS: Even in the setting of high community transmission, a TTS strategy resulted in substantial reduction in missed school days in optionally masked schools

Incidence and Secondary Transmission of SARS-CoV-2 Infections in Schools

BACKGROUND: In an effort to mitigate the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), North Carolina (NC) closed its K–12 public schools to in-person instruction on 03/14/2020. On 07/15/2020, NC’s governor announced schools could open via remote learning or a “hybrid” model that combined in-person and remote instruction. In August 2020, 56 of 115 NC school districts joined the ABC Science Collaborative (ABCs) to implement public health measures to prevent SARS-CoV-2 transmission and share lessons learned. We describe secondary transmission of SARS-CoV-2 within participating NC school districts during the first 9 weeks of in-person instruction in the 2020–2021 academic school year. METHODS: From 08/15/2020–10/23/2020, 11 of 56 school districts participating in ABCs were open for in-person instruction for all 9 weeks of the first quarter and agreed to track incidence and secondary transmission of SARS-CoV-2. Local health department staff adjudicated secondary transmission. Superintendents met weekly with ABCs faculty to share lessons learned and develop prevention methods. RESULTS: Over 9 weeks, 11 participating school districts had more than 90,000 students and staff attend school in-person; of these, there were 773 community-acquired SARS-CoV-2 infections documented by molecular testing. Through contact tracing, NC health department staff determined an additional 32 infections were acquired within schools. No instances of child-to-adult transmission of SARS-CoV-2 were reported within schools. CONCLUSIONS: In the first 9 weeks of in-person instruction in NC schools, we found extremely limited within-school secondary transmission of SARS-CoV-2, as determined by contact tracing

Masking Adherence in K–12 Schools and SARS-CoV-2 Secondary Transmission

OBJECTIVES: Masking is an essential coronavirus 2019 mitigation tool assisting in the safe return of kindergarten through 12th grade children and staff to in-person instruction; however, masking adherence, compliance evaluation methods, and potential consequences of surveillance are currently unknown. We describe two school districts' approaches to promote in-school masking and the consequent impact on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) secondary transmission.METHODS: Two North Carolina school districts developed surveillance programs with daily vs. weekly interventions to monitor in-school masking adherence. Safety teams recorded the proportion of students and staff appropriately wearing masks and provided real-time education after observation of improper masking. Primary infections, within-school transmission, and county-level SARS-CoV-2 infection rates were assessed.RESULTS: Proper mask use was high in both intervention groups and districts. There were variations by grade level, with lower rates in elementary schools, and proper adherence being higher in the weekly surveillance group. Rates of secondary transmission were low in both districts with surveillance programs, regardless of intervention frequency.CONCLUSIONS: Masking surveillance interventions are effective at ensuring appropriate masking at all school levels. Creating a culture of safety within schools led by local leadership is important and a feasible opportunity for school districts with return to in-person school. In our study of schools with high masking adherence, secondary transmission was low