IMPORTANCEHospitalized patients with COVID-19 are at risk for venous and arterial thromboembolism and death. Optimal thromboprophylaxis dosing in high-risk patients is unknown.OBJECTIVE To evaluate the effects of therapeutic-dose low-molecular-weight heparin (LMWH) vs institutional standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTSThe HEP-COVID multicenter randomized clinical trial recruited hospitalized adult patients with COVID-19 with D-dimer levels more than 4 times the upper limit of normal or sepsis-induced coagulopathy score of 4 or greater from May 8, 2020, through May 14, 2021, at 12 academic centers in the US.INTERVENTIONS Patients were randomized to institutional standard prophylactic or intermediate-dose LMWH or unfractionated heparin vs therapeutic-dose enoxaparin, 1 mg/kg subcutaneous, twice daily if creatinine clearance was 30 mL/min/1.73 m 2 or greater (0.5 mg/kg twice daily if creatinine clearance was 15-29 mL/min/1.73 m 2 ) throughout hospitalization. Patients were stratified at the time of randomization based on intensive care unit (ICU) or non-ICU status. MAIN OUTCOMES AND MEASURESThe primary efficacy outcome was venous thromboembolism (VTE), arterial thromboembolism (ATE), or death from any cause, and the principal safety outcome was major bleeding at 30 ± 2 days. Data were collected and adjudicated locally by blinded investigators via imaging, laboratory, and health record data. RESULTSOf 257 patients randomized, 253 were included in the analysis (mean [SD] age, 66.7 [14.0] years; men, 136 [53.8%]; women, 117 [46.2%]); 249 patients (98.4%) met inclusion criteria based on D-dimer elevation and 83 patients (32.8%) were stratified as ICU-level care. There were 124 patients (49%) in the standard-dose vs 129 patients (51%) in the therapeutic-dose group. The primary efficacy outcome was met in 52 of 124 patients (41.9%) (28.2% VTE, 3.2% ATE, 25.0% death) with standard-dose heparins vs 37 of 129 patients (28.7%) (11.7% VTE, 3.2% ATE, 19.4% death) with therapeutic-dose LMWH (relative risk [RR], 0.68; 95% CI, 0.49-0.96; P = .03), including a reduction in thromboembolism (29.0% vs 10.9%; RR, 0.37; 95% CI, 0.21-0.66; P < .001). The incidence of major bleeding was 1.6% with standard-dose vs 4.7% with therapeutic-dose heparins (RR, 2.88; 95% CI, 0.59-14.02; P = .17). The primary efficacy outcome was reduced in non-ICU patients (36.1% vs 16.7%; RR, 0.46; 95% CI, 0.27-0.81; P = .004) but not ICU patients (55.3% vs 51.1%; RR, 0.92; 95% CI, 0.62-1.39; P = .71). CONCLUSIONS AND RELEVANCEIn this randomized clinical trial, therapeutic-dose LMWH reduced major thromboembolism and death compared with institutional standard heparin thromboprophylaxis among inpatients with COVID-19 with very elevated D-dimer levels. The treatment effect was not seen in ICU patients.

Nine mathematical models were compared for their ability to predict daily milk yields (n = 294,986) in standard 305-d and extended lactations of dairy cows of Costa Rica. Lactations were classified by parity (first and later), lactation length (9 to 10, 11 to 12, 13 to 14, 15 to 16, and 16 to 17 mo), and calving to conception interval (1 to 2, 3 to 4, 5 to 6, 7 to 8, and 9 to 10 mo). Of the nine models, the diphasic model and lactation persistency model resulted in the best goodness of fit as measured by adjusted coefficient of determination, residual standard deviation, and Durbin-Watson coefficient. All other models showed less accuracy and positively correlated residuals. In extended lactations, models were also fitted using only test-day records before 305 d, which resulted in a different ranking. The diphasic model showed the best prediction of milk yield in standard and extended lactations. We concluded that the diphasic model provided accurate estimates of milk yield for standard and extended lactations. Interpretation of parameters deserves further attention because of the large variation observed. As expected, the calving to conception interval was found to have a negative effect on milk yield for cows with a standard lactation length. In extended lactations, these negative effects of pregnancy on milk yield were not observed.

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Among patients with diabetes and stable ischemic heart disease, higher SYNTAX scores predict higher rates of major cardiovascular events and were associated with more favorable outcomes of revascularization compared with medical therapy among patients suitable for CABG. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes; NCT00006305).

The aim of this study was to determine risk factors associated with milk fever (MF) occurrence in Costa Rican grazing dairy cattle. A total of 69,870 cows from 126 dairy herds were included in the study. Data were collected in the Veterinary Automated Management and Production Control Program software by the Population Medicine Research Program of the Veterinary Medicine School, National University of Costa Rica, from 1985 to 2014. To determine the risk factors for MF, 2 logistic regression mixed models were evaluated. The first model used breed, month of calving, ecological life zone, herd nested within ecological life zone, and parity as fixed effects. The second model excluded first-lactation animals and cows without production information, had the same fixed effects of the first model, and added previous MF case, previous lactation length, previous dry period length, previous corrected 305-d milk yield, and calving interval length as fixed effects. Both models used animal and year as random effects. Of the 235,971 recorded lactations, 4,312 (1.83%) reported MF event. The significantly associated risk factors for MF occurrence, ranked by their highest odds ratio (OR), were parity (OR = 52.59), previous dry period length (OR = 4.21), ecological life zone (OR = 3.20), breed (OR = 3.04), previous corrected 305-d milk yield (OR = 2.39), previous MF case (OR = 2.35), and month of calving (OR = 1.36). The findings of this study are the first data reported using an epidemiological approach to study risk factors for MF in Costa Rican dairy cattle. Some of these results might be used to improve preventive management practices at the farms to reduce the incidence of this metabolic disease in grazing dairy herds.

Local breeding schemes for Holstein cattle of Costa Rica were compared with the current practice based on continuous semen importation (SI) by deterministic simulation. Comparison was made on the basis of genetic response and correlation between breeding goals. A local breeding goal was defined on the basis of prevailing production circumstances and compared against a typical breeding goal for an exporting country. Differences in genetic response were <3%, and the correlation between breeding goals was 0.99. Therefore, difference between breeding objectives proved negligible. For the evaluation of genetic response, the current scheme based on SI was evaluated against a progeny testing (PT) scheme and a closed nucleus (CN) breeding scheme, both local. Selection intensities and accuracy of selection were defined according to current population size and reproduction efficiency parameters. When genotype x environment interaction (G x E) was ignored, SI was the strategy with the highest genetic response: 5.0% above the CN breeding scheme and 33.2% above PT. A correlation between breeding values in both countries lower than one was assumed to assess the effect of G x E. This resulted in permanent effects on the relative efficiencies of breeding strategies because of the reduction in the rate of genetic response when SI was used. When the genetic correlation was assumed equal to 0.75, the genetic response achieved with SI was reduced at the same level as local PT. When an initial difference in average genetic merit of the populations was assumed, this only had a temporal effect on the relative ranking of strategies, which is reverted after some years of selection because the rate of change in genetic responses remains unchanged. Given that the actual levels of genetic correlation between countries may be around 0.60, it was concluded that a local breeding scheme based on a nucleus herd could provide better results than the current strategy based on SI.

Nonunion of anterior tibial spine of tibia in children is quite rare, but it could be associated with significant instability of the knee as it involves the fixation of anterior cruciate ligament. We report one case in which open reduction and internal fixation was carried out with good functional results. A literature review was performed to identify the cases reported of tibial eminence nonunion in children.

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