Abstract
Background
Data on risk factors for coronavirus disease 2019 (COVID-19)–associated hospitalization are needed to guide prevention efforts and clinical care. We sought to identify factors ...independently associated with COVID-19–associated hospitalizations.
Methods
Community-dwelling adults (aged ≥18 years) in the United States hospitalized with laboratory-confirmed COVID-19 during 1 March–23 June 2020 were identified from the COVID-19–Associated Hospitalization Surveillance Network (COVID-NET), a multistate surveillance system. To calculate hospitalization rates by age, sex, and race/ethnicity strata, COVID-NET data served as the numerator and Behavioral Risk Factor Surveillance System estimates served as the population denominator for characteristics of interest. Underlying medical conditions examined included hypertension, coronary artery disease, history of stroke, diabetes, obesity, severe obesity, chronic kidney disease, asthma, and chronic obstructive pulmonary disease. Generalized Poisson regression models were used to calculate adjusted rate ratios (aRRs) for hospitalization.
Results
Among 5416 adults, hospitalization rates (all reported as aRR 95% confidence interval) were higher among those with ≥3 underlying conditions (vs without) (5.0 3.9–6.3), severe obesity (4.4 3.4–5.7), chronic kidney disease (4.0 3.0–5.2), diabetes (3.2 2.5–4.1), obesity (2.9 2.3–3.5), hypertension (2.8 2.3–3.4), and asthma (1.4 1.1–1.7), after adjusting for age, sex, and race/ethnicity. Adjusting for the presence of an individual underlying medical condition, higher hospitalization rates were observed for adults aged ≥65 or 45–64 years (vs 18–44 years), males (vs females), and non-Hispanic black and other race/ethnicities (vs non-Hispanic whites).
Conclusions
Our findings elucidate groups with higher hospitalization risk that may benefit from targeted preventive and therapeutic interventions.
Severe obesity, chronic kidney disease, diabetes, obesity, hypertension, asthma, age ≥45 years, male sex, and non-Hispanic black and other race/ethnicity are associated with increased risk of coronavirus disease 2019–associated hospitalizations.
Abstract
Many refugee children experience trauma in early childhood. Effective, tailored interventions are needed to improve refugee children’s access to preventive mental health. We interviewed ...refugee-serving stakeholders and parents participating in an evidence-based preventive mental health and wellness intervention adapted for Afghan refugee children and families who may have experienced trauma. Interview guide development was informed by two implementation science frameworks: the Consolidated Framework for Implementation Research and the Model for Adaptation Design and Impact. A three-person team coded transcripts via rapid qualitative analysis, and the study team reached consensus on themes. Six refugee-serving facilitators and five refugee parents discussed key determinants of successful implementation. Themes included: (i) modeling cultural humility to promote communication about emotions; (ii) needed linguistic support and referral networks to avoid miscommunications and missed communications; (iii) bridging connections between children, families and schools; (iv) different takeaways, or differing goals and expectations between facilitators and participants; and (v) timely, specific cultural considerations to overcome participation barriers. Overall, we found key determinants of successful implementation of a preventive mental health and wellness intervention for refugee children and families included adaptations to enhance cultural humility and sensitivity to cultural context while strengthening communication among facilitators, children and families.
Prospective cohort study to characterize the clinical features and course of spinal muscular atrophy type I (SMA-I).
Patients were enrolled at 3 study sites and followed for up to 36 months with ...serial clinical, motor function, laboratory, and electrophysiologic outcome assessments. Intervention was determined by published standard of care guidelines. Palliative care options were offered.
Thirty-four of 54 eligible subjects with SMA-I (63%) enrolled and 50% of these completed at least 12 months of follow-up. The median age at reaching the combined endpoint of death or requiring at least 16 hours/day of ventilation support was 13.5 months (interquartile range 8.1-22.0 months). Requirement for nutritional support preceded that for ventilation support. The distribution of age at reaching the combined endpoint was similar for subjects with SMA-I who had symptom onset before 3 months and after 3 months of age (p=0.58). Having 2 SMN2 copies was associated with greater morbidity and mortality than having 3 copies. Baseline electrophysiologic measures indicated substantial motor neuron loss. By comparison, subjects with SMA-II who lost sitting ability (n=10) had higher motor function, motor unit number estimate and compound motor action potential, longer survival, and later age when feeding or ventilation support was required. The mean rate of decline in The Children's Hospital of Philadelphia Infant Test for Neuromuscular Disorders motor function scale was 1.27 points/year (95% confidence interval 0.21-2.33, p=0.02).
Infants with SMA-I can be effectively enrolled and retained in a 12-month natural history study until a majority reach the combined endpoint. These outcome data can be used for clinical trial design.
Prevention of respiratory syncytial virus (RSV) illness in all infants is a major public health priority. However, no vaccine is currently available to protect this vulnerable population. ...Palivizumab, the only approved agent for RSV prophylaxis, is limited to high-risk infants, and the cost associated with the requirement for dosing throughout the RSV season makes its use impractical for all infants. We describe the development of a monoclonal antibody as potential RSV prophylaxis for all infants with a single intramuscular dose. MEDI8897*, a highly potent human antibody, was optimized from antibody D25, which targets the prefusion conformation of the RSV fusion (F) protein. Crystallographic analysis of Fab in complex with RSV F from subtypes A and B reveals that MEDI8897* binds a highly conserved epitope. MEDI8897* neutralizes a diverse panel of RSV A and B strains with >50-fold higher activity than palivizumab. At similar serum concentrations, prophylactic administration of MEDI8897* was ninefold more potent than palivizumab at reducing pulmonary viral loads by >3 logs in cotton rats infected with either RSV A or B subtypes. MEDI8897 was generated by the introduction of triple amino acid substitutions (YTE) into the Fc domain of MEDI8897*, which led to more than threefold increased half-life in cynomolgus monkeys compared to non-YTE antibody. Considering the pharmacokinetics of palivizumab in infants, which necessitates five monthly doses for protection during an RSV season, the high potency and extended half-life of MEDI8897 support its development as a cost-effective option to protect all infants from RSV disease with once-per-RSV-season dosing in the clinic.
Objective
This 24‐week, phase IIb, double‐blind study was undertaken to evaluate the efficacy and safety of mavrilimumab (a monoclonal antibody to granulocyte–macrophage colony‐stimulating factor ...receptor α) and golimumab (a monoclonal antibody to tumor necrosis factor anti‐TNF) in patients with rheumatoid arthritis (RA) who have had an inadequate response to disease‐modifying antirheumatic drugs (DMARDs) (referred to as DMARD‐IR) and/or inadequate response to other anti‐TNF agents (referred to as anti‐TNF–IR).
Methods
Patients with active RA and a history of DMARD‐IR (≥1 failed regimen) or DMARD‐IR (≥1 failed regimen) and anti‐TNF–IR (1–2 failed regimens) were randomized 1:1 to receive either mavrilimumab 100 mg subcutaneously every other week or golimumab 50 mg subcutaneously every 4 weeks alternating with placebo every 4 weeks, administered concomitantly with methotrexate. The primary end points were the American College of Rheumatology 20% improvement (ACR20), 50% improvement, and 70% improvement response rates at week 24, percentage of patients achieving a Disease Activity Score in 28 joints using C‐reactive protein level (DAS28‐CRP) of <2.6 at week 24, percentage of patients with a score improvement of >0.22 on the Health Assessment Questionnaire (HAQ) disability index (DI) at week 24, and safety/tolerability measures. This study was not powered to formally compare the 2 treatments.
Results
At week 24, differences in the ACR20, ACR50, and ACR70 response rates between the mavrilimumab treatment group (n = 70) and golimumab treatment group (n = 68) were as follows: in all patients, −3.5% (90% confidence interval 90% CI −16.8, 9.8), −8.6% (90% CI −22.0, 4.8), and −9.8% (90% CI −21.1, 1.4), respectively; in the anti‐TNF–IR group, 11.1% (90% CI −7.8, 29.9), −8.7% (90% CI −28.1, 10.7), and −0.7% (90% CI −18.0, 16.7), respectively. Differences in the percentage of patients achieving a DAS28‐CRP of <2.6 at week 24 between the mavrilimumab and golimumab groups were −11.6% (90% CI −23.2, 0.0) in all patients, and −4.0% (90% CI −20.9, 12.9) in the anti‐TNF–IR group. The percentage of patients achieving a >0.22 improvement in the HAQ DI score at week 24 was similar between the treatment groups. Treatment‐emergent adverse events were reported in 51.4% of mavrilimumab‐treated patients and 42.6% of golimumab‐treated patients. No deaths were reported, and no specific safety signals were identified.
Conclusion
The findings of this study demonstrate the clinical efficacy of both treatments, mavrilimumab at a dosage of 100 mg every other week and golimumab at a dosage of 50 mg every 4 weeks, in patients with RA. Both regimens were well‐tolerated in patients who had shown an inadequate response to DMARDs and/or other anti‐TNF agents.
Refugee children are less likely than their non-refugee peers to receive timely diagnoses and treatment for mental and/or behavioral health problems, despite facing multiple risk factors including ...potential exposure to trauma during premigration, migration, and postmigration experiences. Social–Emotional Learning offers preventive mental health education for children through well-established, evidenced-based curricula. Although there are clear benefits of Social–Emotional Learning curricula, which can help children achieve long-term success emotionally and academically, Social–Emotional Learning curricula are not easily accessible for refugee children, often because of language and socioeconomic barriers. In this pilot study, we evaluated the feasibility and acceptability of an adapted Social–Emotional Learning program that included culturally specific, multilingual, trauma-informed wellness, and physical education during the COVID-19 pandemic: EMPOWER (Emotions Program Outside the Clinic With Wellness Education for Refugees). We used the Intervention Mapping framework which guided the (1) planning, (2) program development, and (3) mixed-method evaluation of the feasibility and acceptability of the EMPOWER pilot. We found that this adaptation was well-received by Afghan refugee families and that COVID-19 safety measures were well-understood after participation. Challenges emerged around videoconferencing connectivity and around finding a common language for discussing emotions. Future iterations of the program and evaluations will require continued partnerships with community members and organizations. As we continue and expand EMPOWER, we aim to evaluate short-term improvement in Social–Emotional Learning competence as well as long-term mental and behavioral health outcomes for children and their families.
Streptococcus pyogenes is a human commensal and a bacterial pathogen responsible for a wide variety of human diseases differing in symptoms, severity, and tissue tropism. The completed genome ...sequences of >37 strains of S. pyogenes, representing diverse disease-causing serotypes, have been published. The greatest genetic variation among these strains is attributed to numerous integrated prophage and prophage-like elements, encoding several virulence factors. A comparison of isogenic strains, differing in prophage content, would reveal the effects of these elements on streptococcal pathogenesis. However, curing strains of prophage is often difficult and sometimes unattainable. We have applied a novel counter-selection approach to identify rare S. pyogenes mutants spontaneously cured of select prophage. To accomplish this, we first inserted a two-gene cassette containing a gene for kanamycin resistance (KanR) and the rpsL wild-type gene, responsible for dominant streptomycin sensitivity (SmS), into a targeted prophage on the chromosome of a streptomycin resistant (SmR) mutant of S. pyogenes strain SF370. We then applied antibiotic counter-selection for the re-establishment of the KanS/SmR phenotype to select for isolates cured of targeted prophage. This methodology allowed for the precise selection of spontaneous phage loss and restoration of the natural phage attB attachment sites for all four prophage-like elements in this S. pyogenes chromosome. Overall, 15 mutants were constructed that encompassed every permutation of phage knockout as well as a mutant strain, named CEM1ΔΦ, completely cured of all bacteriophage elements (a ~10% loss of the genome); the only reported S. pyogenes strain free of prophage-like elements. We compared CEM1ΔΦ to the WT strain by analyzing differences in secreted DNase activity, as well as lytic and lysogenic potential. These mutant strains should allow for the direct examination of bacteriophage relationships within S. pyogenes and further elucidate how the presence of prophage may affect overall streptococcal survival, pathogenicity, and evolution.
Despite the therapeutic value of current rheumatoid arthritis (RA) treatments, agents with alternative modes of action are required. Mavrilimumab, a fully human monoclonal antibody targeting the ...granulocyte-macrophage colony-stimulating factor receptor-α, was evaluated in patients with moderate-to-severe RA.
In a phase IIb study (NCT01706926), patients with inadequate response to ≥1 synthetic disease-modifying antirheumatic drug(s), Disease Activity Score 28 (DAS28)-C reactive protein (CRP)/erythrocyte sedimentation rate ≥3.2, ≥4 swollen joints despite methotrexate (MTX) were randomised 1:1:1:1 to subcutaneous mavrilimumab (150, 100, 30 mg), or placebo every other week (eow), plus MTX for 24 weeks. Coprimary outcomes were DAS28-CRP change from baseline to week 12 and American College of Rheumatology (ACR) 20 response rate (week 24).
326 patients were randomised (150 mg, n=79; 100 mg, n=85; 30 mg, n=81; placebo, n=81); 305 completed the study (September 2012-June 2013). Mavrilimumab treatment significantly reduced DAS28-CRP scores from baseline compared with placebo (change from baseline (SE); 150 mg: -1.90 (0.14), 100 mg: -1.64 (0.13), 30 mg: -1.37 (0.14), placebo: -0.68 (0.14); p<0.001; all dosages compared with placebo).Significantly more mavrilimumab-treated patients achieved ACR20 compared with placebo (week 24: 73.4%, 61.2%, 50.6% vs 24.7%, respectively (p<0.001)). Adverse events were reported in 43 (54.4%), 36 (42.4%), 41 (50.6%) and 38 (46.9%) patients in the mavrilimumab 150, 100, 30 mg eow and placebo groups, respectively. No treatment-related safety signals were identified.
Mavrilimumab significantly decreased RA disease activity, with clinically meaningful responses observed 1 week after treatment initiation, representing a novel mechanism of action with persuasive therapeutic potential.
NCT01706926; results.
Detection of clusters of Legionnaires' disease, a leading waterborne cause of pneumonia, is challenging. Clusters vary in size and scope, are associated with a diverse range of aerosol-producing ...devices, including exposures such as whirlpool spas and hotel water systems typically associated with travel, and can occur without an easily identified exposure source. Recently, jurisdictions have begun to use SaTScan spatio-temporal analysis software prospectively as part of routine cluster surveillance. We used data collected by the Active Bacterial Core surveillance platform to assess the ability of SaTScan to detect Legionnaires' disease clusters. We found that SaTScan analysis using traditional surveillance data and geocoded residential addresses was unable to detect many common Legionnaires' disease cluster types, such as those associated with travel or a prolonged time between cases. Additionally, signals from an analysis designed to simulate a real-time search for clusters did not align with clusters identified by traditional surveillance methods or a retrospective SaTScan analysis. A geospatial analysis platform better tailored to the unique characteristics of Legionnaires' disease epidemiology would improve cluster detection and decrease time to public health action.
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