Effect of Bamlanivimab vs Placebo on Incidence of COVID-19 Among Residents and Staff of Skilled Nursing and Assisted Living Facilities: A Randomized Clinical Trial.

Importance: Preventive interventions are needed to protect residents and staff of skilled nursing and assisted living facilities from COVID-19 during outbreaks in their facilities. Bamlanivimab, a neutralizing monoclonal antibody against SARS-CoV-2, may confer rapid protection from SARS-CoV-2 infection and COVID-19. Objective: To determine the effect of bamlanivimab on the incidence of COVID-19 among residents and staff of skilled nursing and assisted living facilities. Design, Setting, and Participants: Randomized, double-blind, single-dose, phase 3 trial that enrolled residents and staff of 74 skilled nursing and assisted living facilities in the United States with at least 1 confirmed SARS-CoV-2 index case. A total of 1175 participants enrolled in the study from August 2 to November 20, 2020. Database lock was triggered on January 13, 2021, when all participants reached study day 57. Interventions: Participants were randomized to receive a single intravenous infusion of bamlanivimab, 4200 mg (n = 588), or placebo (n = 587). Main Outcomes and Measures: The primary outcome was incidence of COVID-19, defined as the detection of SARS-CoV-2 by reverse transcriptase-polymerase chain reaction and mild or worse disease severity within 21 days of detection, within 8 weeks of randomization. Key secondary outcomes included incidence of moderate or worse COVID-19 severity and incidence of SARS-CoV-2 infection. Results: The prevention population comprised a total of 966 participants (666 staff and 300 residents) who were negative at baseline for SARS-CoV-2 infection and serology (mean age, 53.0 [range, 18-104] years; 722 [74.7%] women). Bamlanivimab significantly reduced the incidence of COVID-19 in the prevention population compared with placebo (8.5% vs 15.2%; odds ratio, 0.43 [95% CI, 0.28-0.68]; P < .001; absolute risk difference, -6.6 [95% CI, -10.7 to -2.6] percentage points). Five deaths attributed to COVID-19 were reported by day 57; all occurred in the placebo group. Among 1175 participants who received study product (safety population), the rate of participants with adverse events was 20.1% in the bamlanivimab group and 18.9% in the placebo group. The most common adverse events were urinary tract infection (reported by 12 participants [2%] who received bamlanivimab and 14 [2.4%] who received placebo) and hypertension (reported by 7 participants [1.2%] who received bamlanivimab and 10 [1.7%] who received placebo). Conclusions and Relevance: Among residents and staff in skilled nursing and assisted living facilities, treatment during August-November 2020 with bamlanivimab monotherapy reduced the incidence of COVID-19 infection. Further research is needed to assess preventive efficacy with current patterns of viral strains with combination monoclonal antibody therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT04497987.

Pharmacokinetics of ceftaroline in normal body weight and obese (classes I, II, and III) healthy adult subjects.

The pharmacokinetic profile of ceftaroline has not been well characterized in obese adults. The purpose of this study was to evaluate the pharmacokinetics of ceftaroline in 32 healthy adult volunteers aged 18 to 50 years in the normal, overweight, and obese body size ranges. Subjects were evenly assigned to 1 of 4 groups based on their body mass index (BMI) and total body weight (TBW) (ranges, 22.1 to 63.5 kg/m(2) and 50.1 to 179.5 kg, respectively). Subjects in the lower-TBW groups were matched by age, sex, race/ethnicity, and serum creatinine to the upper-BMI groups. Serial plasma and urine samples were collected over 12 h after the start of the infusion, and the concentrations of ceftaroline fosamil (prodrug), ceftaroline, and ceftaroline M-1 (inactive metabolite) were assayed. Noncompartmental and population pharmacokinetic analyses were used to evaluate the data. The mean plasma ceftaroline maximum concentration and area under the curve were ca. 30% lower in subjects with a BMI of ≥40 kg/m(2) compared to those <30 kg/m(2). A five-compartment pharmacokinetic model with zero-order infusion and first-order elimination optimally described the plasma concentration-time profiles of the prodrug and ceftaroline. Estimated creatinine clearance (eCLCR) and TBW best explained ceftaroline clearance and volume of distribution, respectively. Although lower ceftaroline plasma concentrations were observed in obese subjects, Monte Carlo simulations suggest the probability of target attainment is ≥90% when the MIC is ≤1 µg/ml irrespective of TBW or eCLCR. No dosage adjustment for ceftaroline appears to be necessary based on TBW alone in adults with comparable eCLCR. Confirmation of these findings in infected obese patients is necessary to validate these findings in healthy volunteers. (This study has been registered at ClinicalTrials.gov under registration no. NCT01648127.).

Staphylococcus aureus infection of the optic nerve.

A 71-year-old woman presented with painful vision loss in the right eye followed by ophthalmoplegia. Magnetic resonance imaging demonstrated optic nerve sheath enlargement and enhancement. Biopsy of the optic nerve sheath revealed purulent and necrotic material that was positive for methicillin-sensitive Staphylococcus aureus. The patient underwent enucleation of the right eye and was treated with systemic antibiotics with clinical stabilization. Imaging, pathological and treatment aspects of optic nerve sheath abscess are discussed.

Bioeconomic factors of beef heifer maturity to consider when establishing criteria to optimally select and/or retain herd replacements.

Understanding the biology of heifer maturity and its relationship to calving difficulty and subsequent breeding success is a vital step in building a bioeconomic model to identify optimal production and profitability. A limited dependent variable probit model is used to quantify the responses among heifer maturities, measured by a maturity index (MI), on dystocia and second pregnancy. The MI account for heifer age, birth BW, prebreeding BW, nutrition level, and dam size and age and is found to be inversely related to dystocia occurrence. On average there is a 2.2% increase in the probability of dystocia with every 1 point drop in the MI between the MI scores of 50 and 70. Statistically, MI does not directly alter second pregnancy rate; however, dystocia does. The presence of dystocia reduced second pregnancy rates by 10.67%. Using the probability of dystocia predicted from the MI in the sample, it is found that on average, every 1 point increase in MI added 0.62% to the probability of the occurrence of second pregnancy over the range represented by the data. Relationships among MI, dystocia, and second pregnancy are nonlinear and exhibit diminishing marginal effects. These relationships indicate optimal production and profitability occur at varying maturities, which are altered by animal type, economic environment, production system, and management regime. With these captured relationships, any single group of heifers may be ranked by profitability given their physical characteristics and the applicable production, management, and economic conditions.

Using measurable physical characteristics to forecast beef heifer maturity: the identification of a maturity index.

A target BW is often used to estimate sexual maturity in beef heifers. The target BW, a percentage of mature BW, is generally an average for the breed, herd, or both. Heifer development is done in groups or herds, and not all heifers respond similarly to the same development regimen. Generally, heifers fed at a higher plane of nutrition gain more BW and tend to have increased pregnancy rates, but this usually increases feed costs. Therefore, determining when increased feed costs exceed the economic gains resulting from greater conception rates is critical and requires the inclusion of economic information and relationships. This research focused on the individual heifer as the decision point, and identification of the individual heifer target BW was based on clearly defined biological relationships observed before breeding. These relationships were captured in a maturity index (MI) identified through a series of steps and guided by current, accepted knowledge of heifer growth and development. Using an in-sample mean absolute percent error comparison, it was determined the MI was more accurate than the current group or herd methods in forecasting actual maturity and target BW. Maturity index demonstrated the flexibility in achieving similar maturities with beef heifers of varying characteristics using alternative nutritional programs. The MI was also the only significant predictor of first pregnancy. These results allow for more precision in determining sexual maturity and probability of first pregnancy in beef heifers and serve as the basis for future studies in determining profit differences among heifers.

Acute pancreatitis associated with liraglutide.

OBJECTIVE: To report what is, to our knowledge, the first postmarketing case of acute pancreatitis associated with liraglutide. CASE SUMMARY: A 60-year-old female with type 2 diabetes presented with a 16-hour history of mid-epigastric pain 3 weeks after treatment was changed from exenatide 10 µg twice daily, which she had taken for 4 years, to liraglutide 1.8 mg daily. Her serum lipase level was elevated (478 units/L) at admission, and other laboratory values were within normal limits. Liraglutide was discontinued at admission. Standard therapy for pancreatitis resulted in symptom resolution and a significant decrease in serum lipase (131 units/L) by hospital day 4; she was discharged on hospital day 5. DISCUSSION: Based on the Naranjo scale, this case represents a probable adverse drug reaction. Eight cases of pancreatitis were observed in liraglutide-treated patients in premarketing clinical trials. Extensive literature describing exenatide-related pancreatitis and premarketing reports of liraglutide-related pancreatitis, along with the temporal relationship between the initiation of liraglutide and the onset of this patient's symptoms, suggest that the episode of pancreatitis was induced by liraglutide. CONCLUSIONS: Liraglutide should be used cautiously in patients with a history of pancreatitis, and clinicians should have a high index of suspicion for this rare, but potentially serious, adverse effect.

Measurement characteristics of dietary psychosocial scales in a Weight Gain Prevention Study with 8- to 10-year-old African-American girls.

Few measurement instruments for children's eating behaviors and beliefs have been specifically validated for African-American children. Validation within this population is important because of potential cultural and ethnic influences. Objectives were to evaluate established and newly developed or adapted dietary psychosocial measures in a sample of 303 preadolescent African-American girls and their caregivers. Acceptable internal consistency (Cronbach's alpha > or = 0.70) was found for measures of girls' self-efficacy for healthy eating, outcome expectancies for healthy eating, positive family support for healthy eating and household availability of low-fat food and fruit, juice and vegetables (FJV). Evidence for concurrent validity was found with significant associations between self-efficacy for healthy eating and lower intake of energy (r = -0.17) and fat grams (r = -0.16). Greater FJV availability was associated with greater FJV intake (r = 0.14) and lower body mass index (BMI) in girls (r = -0.12). Positive family support for healthy eating was associated with higher BMI in girls (r = 0.41). These results contribute to the development of scales to evaluate prevention interventions related to dietary intake in African-American children.

Childhood obesity: are we missing the big picture?

Childhood obesity is increasing worldwide, raising alarm about future trends of cardiovascular disease, diabetes and cancer. This article discusses what may underlie our failure to respond effectively to the obesity epidemic, and presents a wider perspective for future research and public health agendas. So far targeting individual-level determinants and clinical aspects of childhood obesity has produced limited success. There is growing interest in understanding the wider determinants of obesity such as the built environment (e.g. walkability), social interactions, food marketing and prices, but much needs to be learned. Particularly, we need to identify distal modifiable factors with multiple potential that would make them attractive for people and policymakers alike. For example, walking-biking-friendly cities can reduce obesity as well as energy consumption, air pollution and traffic delays. Such agenda needs to be driven by strong evidence from research involving multi-level influences on behaviour, as well as the study of wider politico-economic trends affecting people's choices. This article highlights available evidence and arguments for research and policy needed to curb the obesity epidemic. The upstream approach underlying these arguments aims to make healthy choices not only the most rational, but also the most feasible and affordable.

A novel promoter polymorphism in the gene encoding complement component 5 receptor 1 on chromosome 19q13.3 is not associated with asthma and atopy in three independent populations.

BACKGROUND: The inflammatory functions of complement component 5 (C5) are mediated by its receptor, C5R1, which is expressed on bronchial, epithelial, vascular endothelial and smooth muscle cells. A susceptibility locus for murine allergen-induced airway hyper-responsiveness was identified in a region syntenic to human chromosome 19q13, where linkage to asthma has been demonstrated and where the gene encoding C5R1 is localized. OBJECTIVE: The aim of this study was to screen for novel polymorphisms in the C5R1 gene and to determine whether any identified polymorphisms are associated with asthma and/or atopy and whether they are functional. METHODS: Single-nucleotide polymorphism (SNP) detection in the gene encoding C5R1 was performed by direct sequencing. Genotyping was performed in three populations characterized for asthma and/or atopy: (1) 823 German children from The Multicenter Allergy Study; (2) 146 individuals from Tangier Island, Virginia, a Caucasian isolate; and (3) asthma case-parent trios selected from 134 families (N=783) in Barbados. Functional studies were performed to evaluate differences between the wild-type and the variant alleles. RESULTS: We identified a novel SNP in the promoter region of C5R1 at position -245 (T/C). Frequency of the -245C allele was similar in the German (31.5%) and Tangier Island (36.3%) populations, but higher in the Afro-Caribbean population (53.0%; P=0.0039 to <0.0001). We observed no significant associations between the -245 polymorphism and asthma or atopy phenotypes. Upon examination of the functional consequences of the -245T/C polymorphism, we did not observe any change in promoter activity. CONCLUSION: This new marker may provide a valuable tool to assess the risk for C5a-associated disorders, but it does not appear to be associated with asthma and/or atopy.

Nutrition in chronic disease management in the elderly.

Older Americans experience chronic disease at rates well above other segments of our society. Rates of health services use are also 2 to 3 times that of younger age groups. The most rapidly growing segments of America's aging population are also its most nutritionally vulnerable-women, minorities, and those 85 years of age and older. The routine incorporation of nutrition screening and intervention into chronic disease management protocols will lower healthcare services usage, decrease healthcare costs, help relieve the burden of human suffering experienced by older Americans with chronic disease, and improve quality of life for our nation's elders.

Testing for gene-gene interaction controlling total IgE in families from Barbados: evidence of sensitivity regarding linkage heterogeneity among families.

Genetic heterogeneity has been proposed as a hallmark feature of allergic disease. To test the hypothesis that total IgE levels are jointly influenced by a locus on chromosome 12q21.1-q21.31 and a locus on 17q11.2-q21.2, we conducted multipoint allele-sharing analyses using nonparametric linkage (NPL) methods on Afro-Caribbean families from Barbados to test for evidence of gene-gene interactions. Significant correlations were observed between NPL scores at D12S1052 and both D17S1293 and D17S1299 for a dichotomized phenotype of total IgE. An analysis of family-specific NPL scores revealed that evidence for interaction was being driven largely by one multiplex pedigree (NPL = 12.01, 12.23, and 12.16 at D12S1052, D17S1293, and D17S1299, respectively). Using the programs SIMWALK (v2.0) and GOLD, a different set of haplotypes in this influential family was observed around D12S1052 and the 17q loci compared to the other Barbados pedigrees. Our findings are a classic example of founder effect, provide evidence for sensitivity of this type of linkage analysis to unusual pedigrees, and highlight an element of genetic heterogeneity that has been given little attention in the study of complex traits.

Gender and smoking behavior in a worksite smoking cessation program.

Gender-specific patterns in smoking behavior among 844 men and women who participated in a worksite smoking cessation program were explored. Although gender did not predict outcome, men and women did differ on a number of smoking behaviors and smoking history variables. Male participants smoked cigarettes with a higher nicotine content and smoked a greater number of cigarettes per day. Females reported having made more previous attempts to quit, less confidence about quitting, greater effort to quit, greater worry about smoking-related illness, and that they would be less likely to quit on their own if this program were not offered. Females did tend to report receiving higher levels of general social support, as well as partner support for quitting smoking; however, greater support did not lead to higher quit rates. At the 2-year assessment, 14.3% of female participants (n = 532) reported abstinence, while 13.5% of male participants (n = 312) reported abstinence, when missing data were recoded as smoking.

Office procedures. No-scalpel vasectomy.

Vasectomy is a safe, permanent, and inexpensive method of surgical sterilization for men. No-scalpel vasectomy is an innovative approach for exposing the vas deferens that is associated with fewer complications than the standard technique of vasectomy (incisional). It has been used in this country since 1986. The no-scalpel vasectomy, preoperative counseling, management of complications, and evaluation of the postvasectomy semen specimen are described.

A worksite smoking intervention: a 2 year assessment of groups, incentives and self-help.

Sixty-three companies in the Chicago area were recruited to participate in a worksite smoking cessation program. Participants in each worksite received a television program and newspaper supplement (part of a community-wide media campaign), and one of three conditions: (1) self-help manuals alone (M), (2) self-help manuals and incentives for 6 months (IM) or (3) maintenance manuals, incentives and cognitive-behavioral support groups for 6 months (GIM). Results at the 2 year assessment are examined using a random-effects regression model. In addition, various definitions of quit-rate commonly used in smoking cessation research are explored and the advantages of using a public health approach in the worksite are examined.

Olanzapine, a novel atypical antipsychotic, reverses d-amphetamine-induced inhibition of midbrain dopamine cells.

This study compared the ability of the novel atypical antipsychotic olanzapine with that of clozapine to reverse the d-amphetamine-induced inhibition of substantia nigra (A9) and ventral tegmental area (A10) dopamine (DA) cells. Extracellular single-unit recordings were made from A9 and A10 DA cells in anesthetized rats. When administered alone, neither olanzapine nor clozapine altered the firing rate of A9 or A10 DA cells. Administration of d-amphetamine (0.5, 1.0 and 2.0 mg/kg, IV, decreased the firing rate of A9 and A10 DA cells. Olanzapine completely reversed the inhibitory effects of d-amphetamine on A10 DA cells (ED100 = 0.18 mg/kg, IV) and on A9 DA cells (ED100 = 1.0 mg/mg, IV). Clozapine completely reversed the inhibitory effects of d-amphetamine on A10 DA cells (ED100 = 3.8 mg/kg, IV), but only partially reversed the effects of d-amphetamine on A9 DA cells at the highest dose tested (8.0 mg/kg, IV). Thus, olanzapine, like clozapine, was more potent in reversing the effects of d-amphetamine on A10 than A9 DA cells. In addition, olanzapine was more potent than clozapine in the reversal of d-amphetamine effects on A9 and A10 DA cells. These results indicate that olanzapine and clozapine have similar effects on DA unit activity and predict that olanzapine should have an atypical antipsychotic profile in man.

Electrophysiological effects of olanzapine, a novel atypical antipsychotic, on A9 and A10 dopamine neurons.

This study examined the effects of the novel atypical antipsychotic olanzapine (LY170053) on the activity of substantia nigra pars compacta (A9) and ventral tegmental area (A10) dopamine cells in anesthetized rats. Acute administration of olanzapine (10, 20 mg/kg sc) increased the number of spontaneously active A10, but not A9, dopamine cells. Chronic administration of olanzapine (10, 20 mg/kg/day x 21 days) decreased the number of spontaneously active A10, but not A9, dopamine cells. Administration of the dopamine agonist apomorphine reversed the effects of chronic olanzapine on A10 cells, indicating a possible depolarization-inactivation mechanism. In conclusion, olanzapine has selective effects on A10 versus A9 dopamine cells following acute and chronic administration. These effects of olanzapine on dopamine cells are similar to the effects observed with clozapine and may play an important role in the atypical antipsychotic profile of olanzapine.

The role of total IgE as a predictor of asthma in Barbadian subjects - abstract

Assessment of the epidemiology of asthma requires that the asthma phenotype be characterized. A study was conducted in Barbados among 24 families (n = 175 persons). The geometric mean serum total IgE (tIgE) was 559.8 ng/ml, and was significantly higher in asthmatic subjects (n = 88; means = 1352.1) than in non-asthmatic subjects (n = 87; means = 229.6; t-test, p < 0.001). Asthma subjects reported shortness of breath (80.7 percent), cough (77.3 percent), wheezing (72.7 percent). An index of asthma severity was created based on questionnaire data. Shortness of breath, cough and wheeze were similarly correlated with the index of severity; however, none of the symptoms were significantly correlated with tIgE. Similarly, tIgE was not correlated with the severity score of any of the individual variables that comprised the severity score. The findings in this study of Afro-Caribbean subjects living in a tropical setting concur with those of Caucasian subjects living in developed, temperate locales, whereby tIgE is a good means of classifying the presence or absence of asthma. The poor association between tIgE and severity of asthma and asthma symptoms warrants further investigation into the validation of the severity scale, but raises the question regarding the absence of a relationship between tIgE and asthma severity (AU)