Lamivudine and Entecavir for Acute Hepatitis B: A Systematic Review and Meta-Analysis.

BACKGROUND: Acute hepatitis B infection is associated with severe liver disease and chronic sequelae in some cases. The purpose of this review was to determine the efficacy of nucleoside analogues (NA) (lamivudine versus entecavir) compared to placebo or no intervention for treating acute primary HBV infection. METHODS: A meta-analysis for drug intervention was performed, following a fixed-effect model. Randomized controlled trials (RCTs) and quasi-randomized studies that evaluated the outcomes of NA in acute hepatitis B infection were included. The following outcomes were considered: virological cure (PCR negative), elimination of acute infection (seroconversion of HBsAg), mortality, and serious adverse events. RESULTS: Five trials with 627 adult participants with severe acute hepatitis B defined by biochemical and serologic parameters were included. Virological cure did not favor any intervention: OR 0.96, 95% CI 0.54 to 1.7 (p = 0.90), I2 = 58%. Seroconversion of HBsAg to negative favored placebo/standard-of-care compared to lamivudine: OR 0.54, 95% CI 0.33 to 0.9 (p = 0.02), I2 = 31%. The only trial that compared entecavir and lamivudine favored entecavir over lamivudine (OR: 3.64, 95% CI 1.31-10.13; 90 participants). Adverse events were mild. CONCLUSION: There is insufficient evidence that NA obtain superior efficacy compared with placebo/standard-of-care in patients with acute viral hepatitis, based on low quality evidence.

Influence of epidemiological and clinical factors in the reactogenicity to Comirnaty® vaccine in health care workers of a Spanish university teaching hospital (COVIVAC study) / Influencia de factores epidemiológicos y clínicos en la reactogenicidad a la vacuna Comirnaty® en trabajadores sanitarios de un hospital universitario español (estudio COVIVAC)

Introduction. Comirnaty® is an mRNA vaccine against COVID-19 which has been administered to millions of people since the end of 2020. Our aim was to study epidemiological and clinical factors influencing reactogenicity and functional limitation after the first two doses of the vaccine in health care workers (HCWs). Material and methods. Prospective post-authorization cohort study to monitor safety and effectiveness of the vaccine. Results. Local side effects were mild and presented both with first and second dose of Comirnaty. Systemic side effects were more frequent after 2nd dose. Nevertheless, previous SARS-CoV-2 infection was associated with systemic effects after the first dose of the vaccine (OR ranging from 2 to 6). No severe adverse effects were reported. According to multivariate analysis, the degree of self-reported functional limitation after the first dose increased with age, female sex, previous COVID-19 contact, previous SARS-CoV-2 infection, and Charlson Comorbidity Index (CCI). After the second dose, the degree of functional limitation observed was lower in those with previous SARS-CoV-2 infection, and it was positively associated to the degree of functional limitation after the first dose. Conclusion. Systemic adverse effects were more frequent after the second dose of Comirnaty. Previous SARS-CoV-2 infection was associated with systemic effects after the first dose. Age, female sex, previous COVID-19, previous isolation due to COVID-19 contact, and CCI showed to be independent predictors of the degree of functional limitation after the 1st dose of Comirnaty®. After the 2nd dose, the degree of functional limitation was lower in those who previously had SARS-CoV-2 infection (AU)

Introducción. Comirnaty® es una vacuna de ARNm contra el COVID-19 que se ha administrado a millones de personas desde finales de 2020. Nuestro objetivo fue estudiar los factores epidemiológicos y clínicos que influyen en la reactogenicidad y la limitación funcional asociadas tras las dos primeras dosis de la vacuna en trabajadores de la salud. Metodología. Estudio de cohorte prospectivo post-autorización para evaluar la seguridad y eficacia de la vacuna. Resultados. Los efectos secundarios locales fueron leves y se presentaron tanto con la primera como con la segunda dosis de Comirnaty. Los efectos secundarios sistémicos fueron más frecuentes después de la segunda dosis. No obstante, la infección previa por SARS-CoV-2 se asoció con efectos sistémicos tras la primera dosis de la vacuna (OR de 2 a 6). No se informaron efectos adversos graves. El análisis multivariante demostró que el grado de limitación funcional tras la primera dosis aumentó con la edad, el sexo femenino, contacto previo con COVID-19, la infección previa por SARS CoV-2 y el índice de comorbilidad de Charlson (ICC). Tras la segunda dosis, el grado de limitación funcional observado fue menor en aquellos con infección previa por SARS-CoV-2, y se asoció positivamente al grado de limitación funcional tras la primera dosis.Conclusión. Los efectos adversos sistémicos fueron más frecuentes después de la segunda dosis de Comirnaty. La infección previa por SARS-CoV-2 se asoció con efectos sistémicos después de la primera dosis. La edad, el sexo femenino, infección por COVID-19 previa, el aislamiento previo por contacto de COVID-19 y el ICC se mostraron como predictores independientes del grado de limitación funcional tras la 1ª dosis de Comirnaty®. Después de la 2.ª dosis, el grado de limitación funcional fue menor en los que previamente tenían infección por SARS-CoV-2 (AU)

Trends in COVID-19-related in-hospital mortality in women and men.

INTRODUCTION: Whether political, scientific and medical development in a country is associated with better clinical results according to gender in patients with COVID-19 has not yet been clearly elucidated. OBJECTIVE: To determine the trends of COVID-19-related in-hospital mortality in women and men from March 2020 to February 2022. METHODS: Clinical data of all patients with COVID-19 cared for at 21 Spanish hospitals were used, both of those who were discharged and of those who died during hospitalization. The association between hospital length of stay and mortality was analyzed with logistic regression models. RESULTS: Out of 7,974 patients that were included, 3,234 were women; 928 patients died. A significant decreasing trend in mortality was identified. When the analysis was carried out by gender, no significant mortality trend was found in women (OR = 0.96 [0.90-1.03], p = 0.239), while in men there was a significant decreasing trend identified (OR = 0.87 [0.82-0.92], p < 0.001). CONCLUSION: Health policies, together with clinical and preventive interventions, may explain these results. Response to treatment and behavioral differences may explain why mortality does not decrease for women.

INTRODUCCIÓN: Todavía no se comprende si el desarrollo político, científico y médico en un país se asocia a mejores resultados clínicos de los pacientes con COVID-19 según el sexo. OBJETIVO: Determinar las tendencias de mortalidad hospitalaria asociada a COVID-19 en mujeres y hombres entre marzo de 2020 y febrero de 2022. MÉTODOS: Se utilizaron los datos clínicos de todos los pacientes con COVID-19 atendidos en 21 hospitales españoles, tanto de quienes fueron dados de alta como de quienes fallecieron durante el ingreso. La asociación entre la fecha del ingreso y la mortalidad se analizó con modelos de regresión logística. RESULTADOS: Fueron incluidos 7974 pacientes, de los cuales 3234 fueron mujeres y 928 fallecieron. Se encontró una tendencia significativa y decreciente en la mortalidad según avanzaba la fecha del ingreso. Cuando el análisis se realizó por sexos, no se halló una tendencia significativa en las mujeres (RM = 0.96 [0.90-1.03], p = 0.239), pero sí en los hombres (RM = 0.87 [0.82-0.92], p < 0.001). CONCLUSIÓN: Las políticas de salud, junto con las intervenciones clínicas y preventivas, pueden dar cuenta de los resultados. Diferencias en la respuesta al tratamiento o en los comportamientos pueden explicar por qué la mortalidad no disminuye en las mujeres.

Epidemiology of Herpes Zoster in the pre-vaccination era: establishing the baseline for vaccination programme's impact in Spain.

BackgroundHerpes zoster (HZ) affects 1 in 3 persons in their lifetime, and the risk of HZ increases with increasing age and the presence of immunocompromising conditions. In Spain, vaccination guidelines were recently updated to include the recommendation of the new recombinant zoster vaccine (RZV) for certain risk groups.AimTo describe the epidemiology of HZ-related hospitalisations in Spain in order to prioritise vaccination recommendations and define a baseline to monitor the effectiveness of vaccination policies.MethodsRetrospective study using the National Health System's Hospital Discharge Records Database, including all HZ-related hospitalisations from 1998 to 2018.ResultsThe 65,401 HZ-related hospitalisations, corresponded to an annual mean hospitalisation rate of 6.75 per 100,000 population. There was an increasing trend of HZ hospitalisations over the study period. This rate was higher in males and older age groups, particularly over 65 years. Comorbidities with higher risk of readmission were leukaemia/lymphoma (RR 2.4; 95% CI: 2.3-2.6) and solid malignant neoplasm (RR 2.2; 95% CI: 2.1-2.4). Comorbidities associated with higher risk of mortality were leukaemia/lymphoma (RR 2.9; 95% CI: 2.7-3.2), solid malignant neoplasm (RR 2.9; 95% CI: 2.7-3.1) and HIV infection (RR 2.2; 95% CI: 1.8-2.7).ConclusionOf all patients hospitalised with HZ, those with greater risk of mortality or readmission belonged to the groups prioritised by the current vaccination recommendations of the Spanish Ministry of Health. Our study provided relevant information on clinical aspects of HZ and established the base for future assessments of vaccination policies.

Tendencia de mortalidad hospitalaria por COVID-19 en mujeres y hombres / Trends in COVID-19-related in-hospital mortality in women and men

Resumen Introducción: Todavía no se comprende si el desarrollo político, científico y médico en un país se asocia a mejores resultados clínicos de los pacientes con COVID-19 según el sexo. Objetivo: Determinar las tendencias de mortalidad hospitalaria asociada a COVID-19 en mujeres y hombres entre marzo de 2020 y febrero de 2022. Métodos: Se utilizaron los datos clínicos de todos los pacientes con COVID-19 atendidos en 21 hospitales españoles, tanto de quienes fueron dados de alta como de quienes fallecieron durante el ingreso. La asociación entre la fecha del ingreso y la mortalidad se analizó con modelos de regresión logística. Resultados: Fueron incluidos 7974 pacientes, de los cuales 3234 fueron mujeres y 928 fallecieron. Se encontró una tendencia significativa y decreciente en la mortalidad según avanzaba la fecha del ingreso. Cuando el análisis se realizó por sexos, no se halló una tendencia significativa en las mujeres (RM = 0.96 [0.90-1.03], p = 0.239), pero sí en los hombres (RM = 0.87 [0.82-0.92], p < 0.001). Conclusión: Las políticas de salud, junto con las intervenciones clínicas y preventivas, pueden dar cuenta de los resultados. Diferencias en la respuesta al tratamiento o en los comportamientos pueden explicar por qué la mortalidad no disminuye en las mujeres.

Abstract Introduction: Whether political, scientific and medical development in a country is associated with better clinical results according to gender in patients with COVID-19 has not yet been clearly elucidated. Objective: To determine the trends of COVID-19-related in-hospital mortality in women and men from March 2020 to February 2022. Methods: Clinical data of all patients with COVID-19 cared for at 21 Spanish hospitals were used, both of those who were discharged and of those who died during hospitalization. The association between hospital length of stay and mortality was analyzed with logistic regression models. Results: Out of 7,974 patients that were included, 3,234 were women; 928 patients died. A significant decreasing trend in mortality was identified. When the analysis was carried out by gender, no significant mortality trend was found in women (OR = 0.96 [0.90-1.03], p = 0.239), while in men there was a significant decreasing trend identified (OR = 0.87 [0.82-0.92], p < 0.001). Conclusion: Health policies, together with clinical and preventive interventions, may explain these results. Response to treatment and behavioral differences may explain why mortality does not decrease for women.

Equine insulin dysregulation causes tissue specific alterations of proinflammatory cytokines and acute phase proteins in a NF-kB independent manner.

Similar to human diabetes, equine metabolic syndrome (EMS) causes insulin dysregulation leading to debilitating sequela including laminitis. The pathophysiological mechanisms underlying EMS and laminitis are not well known. Therefore, using an insulin-resistant equine model, we hypothesized that insulin dysregulation induces an increased expression of inflammatory proteins in a tissue specific manner. Two groups of horses (n = -5/group) were categorized as insulin-resistant (IR) or insulin-sensitive (IS), using a frequently sampled intra-venous glucose tolerance test. Biopsies from skeletal muscle, and visceral and subcutaneous adipose tissues were collected in both groups. Protein expression was quantified via Western blotting in order to investigate HSP90, α 2 macroglobulin (A2M), Fibrinogen α, ß, γ isoforms as well as cytokines, including interleukin-1ß (IL-1ß) and interleukin-6 (IL-6), in muscle and adipose tissues. Protein expression of HSP90, A2M and IL1-ß was significantly greater in visceral adipose tissue of IR horses compared to IS horses. Fibrinogen (α and γ) expression was only significantly increased in subcutaneous adipose tissue of IR group compared to IS group. In contrast, no statistically significant difference in protein expression of proinflammatory cytokines and acute phase proteins was reported in skeletal muscle of IR vs. IS horses. Relative protein expression of total and phospho-NFκB protein expression was not statistically significantly changed in adipose tissues of IR horses compared to IS horses. In conclusion, proinflammatory cytokines and acute phase proteins were upregulated in adipose tissue, but not in skeletal muscle, through an NF-kB independent pathway. Insights from this study could reveal novel biomarkers and potential therapeutic targets for EMS.

Azithromycin in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Azithromycin has been widely used in the management of COVID-19. However, the evidence on its actual effects remains disperse and difficult to apply in clinical settings. This systematic review and meta-analysis summarizes the available evidence to date on the beneficial and adverse effects of azithromycin in patients with COVID-19. METHODS: The PRISMA 2020 statement criteria were followed. Randomized controlled trials (RCTs) and observational studies comparing clinical outcomes of patients treated with and without azithromycin, indexed until 5 July 2021, were searched in PubMed, Embase, The Web of Science, Scopus, The Cochrane Central Register of Controlled Trials and MedRXivs. We used random-effects models to estimate pooled effect size from aggregate data. RESULTS: The initial search produced 4950 results. Finally, 16 studies, 5 RCTs and 11 with an observational design, with a total of 22 984 patients, were included. The meta-analysis showed no difference in mortality for those treated with or without azithromycin, in observational studies [OR: 0.90 (0.66-1.24)], RCTs [OR: 0.97 (0.87-1.08)] and also when both types of studies were pooled together [with an overall OR: 0.95 (0.79-1.13)]. Different individual studies also reported no significant difference for those treated with or without azithromycin in need for hospital admission or time to admission from ambulatory settings, clinical severity, need for intensive care, or adverse effects. CONCLUSIONS: The results presented in this systematic review do not support the use of azithromycin in the management of COVID-19. Future research on treatment for patients with COVID-19 may need to focus on other drugs.

Investigating the Use of Dry Matter Intake and Energy Balance Prepartum as Predictors of Digestive Disorders Postpartum.

One objective was to evaluate the association of dry matter intake as a percentage of body weight (DMI%BW) and energy balance (EB) prepartum and postpartum, and energy-corrected milk (ECM) postpatum with digestive disorders postpartum. For this, ANOVA was used, and DMI%BW, EB, and ECM were the outcome variables, and left displaced abomasum (LDA), indigestion, and other digestive disorders (ODDZ) were the explanatory variables. The main objective was to evaluate prepartum DMI%BW and EB as predictors of digestive disorders. For this, logistic regression was used, and LDA, indigestion, and ODDZ were the outcome variables and DMI%BW and EB were the explanatory variables. Data from 689 cows from 11 experiments were compiled. Left displaced abomasum was not associated with prepartum DMI%BW or EB. Postpartum data were normalized to the day of the event (day 0). Cows that developed LDA had lesser postpartum DMI%BW on days -24, -23, -12, -7 to 0 and from days 1 to 8, 10 to 12, and 14 and 16, lesser postpartum EB from days -7 to -5, -3 to 0, and 12, and lesser postpartum energy-corrected milk on days -19, -2, -1, 0, 7, 9, 10, 15, and 17 relative to diagnosis than cows without LDA. Cows that developed indigestion had lesser prepartum DMI%BW and EB than cows without indigestion, and lesser postpartum DMI%BW on days -24, -1, 0, 1, and 2, and greater DMI%BW on day 26, lesser ECM on days -24, -2, -1, 0, 1, and 2 relative to diagnosis. Postpartum EB was not associated with indigestion postpartum. Cows that developed ODDZ had lesser prepartum DMI%BW on day -8 and from days -5 to -2, lesser prepartum EB on day -8 and from days -5 to -2, and lesser postpartum DMI%BW than cows without ODDZ. Each 0.1 percentage point decrease in the average DMI%BW and each Mcal decrease in the average EB in the last 3 days prepartum increased the odds of having indigestion by 9% each. Cutoffs for DMI%BW and EB during the last 3 days prepartum to predict indigestion were established and were ≤1.3%/day and ≤0.68 Mcal/day, respectively. In summary, measures of prepartum DMI%BW and EB were associated with indigestion and ODDZ postpartum and were predictors of indigestion postpartum, although the effect sizes were small.

Effect of oral calcium administration on metabolic status and uterine health of dairy cows with reduced postpartum rumination and eating time.

BACKGROUND: Hypocalcemia has detrimental effects on health and performance of dairy cows. As hypocalcemic cows show reduced feed intake, we hypothesized that cows with reduced combined rumination and eating time (CRET) may benefit from Ca supplementation. The objective was to evaluate the effect of postpartum oral Ca administration on metabolic status (Calcium [Ca], fatty acids [FA], and ß-Hydroxybutyrate [BHB] serum concentrations) and incidence of puerperal metritis (PM) in dairy cows with reduced postpartum CRET. Cows in an organic-certified dairy, diagnosed with reduced CRET (< 489 min/d; n = 88) during the first day postpartum were assigned into 1 of 2 treatments: i) Calcium administration (CA; n = 45) that received 1 Ca oral capsule (Bovikalc bolus, Boehringer Ingelheim, St. Joseph, MO) containing CaCl2 and CaSO4 (43 g of Ca) once per day, for 3 consecutive days, starting at d 1 postpartum; and ii) Control (CON; n = 43) that did not receive oral Ca. A convenience group consisting of cows with CRET ≥489 min/d was used for comparison and did not receive oral Ca (NOR; n = 96). RESULTS: At day 1 postpartum cows with reduced CRET had lower Ca serum concentrations (CA = 2.08 mmol/L; CON = 2.06 mmol/L) compared with NOR cows (2.17 mmol/L). Calcium concentrations at d 3, 5, and 12 postpartum were not different among the three groups. Serum FA concentrations at d 1, 3 and 5 postpartum were higher in both CA and CON cows compared with NOR. At d 12, only CA cows had higher FA concentrations than NOR cows. Serum BHB concentrations at d 3 were highest in CA, with no difference between CON and NOR. At d 5, BHB concentrations were higher in CA, followed by CON, and NOR. No effect was observed for Ca administration on incidence of PM and reproductive performance. CON cows had lower survival at 30 DIM (86.5%) than NOR cows (97.9%). CONCLUSIONS: The use of remote sensor technology identified cows with reduced rumination and eating time that had lower postpartum serum concentrations of calcium and altered metabolic status. However, oral calcium administration to cows with reduced CRET did not affect incidence of metabolic disorders nor reproductive health and subsequent pregnancy. Although survival at 30 days postpartum was lower for non-Ca supplemented cows, the identification of effective interventions in cows with reduced CRET requires further consideration.

Observed and expected combined effects of metritis and other postpartum diseases on time to conception and rate of conception failure in first lactation cows in Iran.

Previous observational studies have produced strong evidence that metritis alone has an impact on reproductive performance in dairy cows; but few studies have examined the combined effect of metritis and other postpartum diseases on reproduction performance in dairy cows. Information on the combined effects of postpartum diseases on fertility in dairy cows can have practical herd-health management implications. The objective of the study reported here was to examine the observed and expected combined effects of metritis and other postpartum diseases (retained fetal membranes (RFM), clinical hypocalcemia, left displaced abomasum, clinical mastitis, lameness) on time to conception and rate of conception failure in first-lactation cows up to 150 days postpartum. The study was conducted on two commercial dairy herds in Iran. Median number of days to conception was higher in 30 cows affected with metritis and RFM (90 days), compared to 287 healthy cows (57 days), 16 cows affected with RFM alone (60 days) or 44 cows affected with metritis alone (60 days), after controlling for herd and calving month (p < 0.05). In cows affected with metritis and RFM, the rate of conception failure was 3.8 times greater than that of healthy cows, after controlling for study herd and calving month (hazard ratio = 3.8; 95% CI = 2.3, 6.6; p < 0.01); this observed combined effect on conception failure was two times higher than the expected combined effect based on adding or multiplying absolute independent excesses due to metritis or RFM. In addition, we observed an interaction effect between metritis and lameness on conception failure, after controlling for herd, calving month, and RFM; but study results were inconclusive. In this study, the observed combined effect of metritis and RFM on time to conception and rate of conception failure was far in excess, compared to that in cows exposed to metritis or RFM alone. Attending veterinarians or farm managers can consider this information when making breeding and culling decisions on dairy farms.

Cross-sectional evaluation of the interaction between activity relative-time expenditure and comorbidity concerning physical quality of life.

Quality of life (QoL) is a matter of concern in both healthy and diseased individuals. Lifestyle factors such as physical activity and sleep have a direct impact on QoL. In this context, interactions between activity time expenditure and QoL might be different in comorbid and non comorbid patients. Besides, the quantification and evaluation of time expenditure is ordinarily measured as the absolute time devoted to each activity. The objective of this study is the evaluation of the influence and interactions of activity-relative time expenditure and co-morbidity in Physical QoL.The study involved 302 consecutive patients, from an Internal Medicine ambulatory evaluation. Validated questionnaires were used to collect demographic variables and time expenditure variables. QoL was gathered with de survey short form-36questionnaire. Comorbidity was compiled with de Charlson Comorbidity Index. SPSS v20.0 was used for statistical analysis.As hypothesized, healthy subjects had higher Physical QoL score than comorbid subjects (P < .05). Physical activity and sleep relative time expenditure were statistically significant and associated to a better QoL in comorbid patients (P < .05). Interestingly, sleep was found to have statistically significant interaction with a score of ≥2 in the Charlson Comorbidity Index. Age, gender, comorbidity, physical activity relative time expenditure, and the interaction between relative time dedicated to sleep and comorbidity were found statistically significant in a multivariate model on Physical QoL prediction.Activity-relative time expenditure could be an adequate measure of daily activity pattern in the evaluation of QoL. Relative time spent in physical activity and sleep might be positively associated to Physical QoL. Sleep and comorbidity could have a statistically significant interaction in the prediction of Physical QoL.

The association of treatment with hydroxychloroquine and hospital mortality in COVID-19 patients.

This study investigates the association between the treatment with hydroxychloroquine and mortality in patients admitted with COVID-19. Routinely recorded, clinical data, up to the 24th of April 2020, from the 2075 patients with COVID-19, admitted in 17 hospitals in Spain between the 1st of March and the 20th of April 2020 were used. The following variables were extracted for this study: age, gender, temperature, and saturation of oxygen on admission, treatment with hydroxychloroquine, azithromycin, heparin, steroids, tocilizumab, a combination of lopinavir with ritonavir, and oseltamivir, together with data on mortality. Multivariable logistic regression models were used to investigate the associations. At the time of collecting the data, 301 patients had died, 1449 had been discharged home from the hospitals, 240 were still admitted, and 85 had been transferred to hospitals not included in the study. Median follow-up time was 8 (IQR 5-12) days. Hydroxychloroquine had been used in 1857 patients. Hydroxychloroquine was associated with lower mortality when the model was adjusted for age and gender, with OR (95% CI): 0.44 (0.29-0.67). This association remained significant when saturation of oxygen < 90% and temperature > 37 °C were added to de model with OR 0.45 (0.30-0.68) p < 0.001, and also when all the other drugs, and time of admission, were included as covariates. The association between hydroxychloroquine and lower mortality observed in this study can be acknowledged by clinicians in hospitals and in the community. Randomized-controlled trials to assess the causal effects of hydroxychloroquine in different therapeutic regimes are required.

The association between treatment with heparin and survival in patients with Covid-19.

This study investigates the association between the treatment with heparin and mortality in patients admitted with Covid-19. Routinely recorded, clinical data, up to the 24th of April 2020, from the 2075 patients with Covid-19, admitted in 17 hospitals in Spain between the 1st of March and the 20th of April 2020 were used. The following variables were extracted for this study: age, gender, temperature, and saturation of oxygen on admission, treatment with heparin, hydroxychloroquine, azithromycin, steroids, tocilizumab, a combination of lopinavir with ritonavir, and oseltamivir, together with data on mortality. Multivariable logistic regression models were used to investigate the associations. At the time of collecting the data, 301 patients had died, 1447 had been discharged home from the hospitals, 201 were still admitted, and 126 had been transferred to hospitals not included in the study. Median follow up time was 8 (IQR 5-12) days. Heparin had been used in 1734 patients. Heparin was associated with lower mortality when the model was adjusted for age and gender, with OR (95% CI) 0.55 (0.37-0.82) p = 0.003. This association remained significant when saturation of oxygen < 90%, and temperature > 37 °C were added to de model with OR 0.54 (0.36-0.82) p = 0.003, and also when all the other drugs were included as covariates OR 0.42 (0.26-0.66) p < 0.001. The association between heparin and lower mortality observed in this study can be acknowledged by clinicians in hospitals and in the community. Randomized controlled trials to assess the causal effects of heparin in different therapeutic regimes are required.

Combined effect of mastitis and parity on pregnancy loss in lactating Holstein cows.

The main objective of this study was to examine the combined effect of mastitis and parity on pregnancy loss (PL) in lactating Holstein cows. A secondary objective was to estimate the cost of mastitis including that of PL attributable to mastitis. A total of 1,774 lactation periods from 1,047 Holstein cows with different parities from one dairy farm were included in a matched case-control study. All study cows were diagnosed pregnant by transrectal ultrasonography on day 33 after timed artificial insemination (TAI). Case cows (n = 222 lactations) were those later diagnosed non-pregnant by transrectal palpation on day 47 or 75 after TAI. Control cows (n = 1,552 lactations) were those confirmed pregnant by transrectal palpation on day 75 after TAI. Case cows were matched with eligible controls according to year of calving and calving-to-conception interval (CCI) ± 3 days. Cows with different parities were classified as exposed to subclinical mastitis (somatic cell score (SCS) > 4.5 in at least one Dairy Herd Improvement Association (DHIA) test day) or clinical mastitis (with or without evidence of subclinical mastitis) during two exposure periods: 1-42 days before breeding or 1-75 days during gestation (1 to PL diagnosis day in case cows, or 1-75 day in control cows). Conditional logistic regression was used to model the odds of PL as a function of previous exposure to mastitis in different parities. Cost of PL attributable to mastitis ($/case) among cows with mastitis was estimated based on attributable risk calculated in the epidemiologic analysis. We observed a higher than expected combined effect between exposure to mastitis (subclinical or clinical) before breeding and parity 3 or ≥ 4, and during gestation and parity ≥ 4 on PL. The cost of PL attributable to mastitis was highest ($196/case) in cows in parity ≥ 4 affected with clinical mastitis during gestation. Overall, study results indicate the impact of mastitis on PL is higher in older cows (parity ≥ 3). Dairy farmers and attending veterinarians can consider the combined effect of mastitis and parity when evaluating causes for PL and strategies for optimizing reproductive performance in dairy cows.

Epidemiologic and economic analyses of pregnancy loss attributable to mastitis in primiparous Holstein cows.

The main objective of the study reported here was to examine the association between pregnancy loss (PL) and previous exposure to clinical or subclinical mastitis before breeding or during gestation in primiparous Holstein cows. A secondary objective was to estimate the cost of clinical mastitis during gestation, including that of PL attributable to mastitis in study cows. A total of 687 primiparous Holstein cows from 1 dairy farm were included in a matched case-control study. Study cows were declared pregnant via ultrasound on d 33 after timed artificial insemination (TAI). Case cows (n = 78) were those diagnosed as nonpregnant by rectal palpation on d 47 or 75 after TAI. Control cows were those confirmed as pregnant by rectal palpation on d 47 and 75 after TAI. Case cows were matched with eligible controls according to year of calving and calving-to-conception interval ±3 d. Cows were assigned to 1 of 3 groups: (1) cows not affected with clinical or subclinical mastitis; (2) cows affected with subclinical mastitis (Dairy Herd Improvement Association somatic cell score >4.5); and (3) cows affected with clinical mastitis during 2 exposure periods, 1 to 42 d before breeding or during gestation (1 to PL diagnosis day for case cows, and 1 to 75 d for control cows). Conditional logistic regression was used to model the odds of PL as a function of previous exposure to mastitis in study cows. Mastitis before breeding was not associated with PL. The odds of PL were 2.21 times greater in cows affected with clinical mastitis during gestation (95% confidence interval = 1.01, 4.83), compared with cows without mastitis, after controlling for breeding type and lameness. The cost of clinical mastitis during gestation was $149, which includes the cost ($27) of PL attributable to mastitis. In conclusion, this study provides evidence that clinical mastitis during gestation can cause PL in primiparous dairy cows leading to economic losses.

Quantifying known and emerging uterine pathogens, and evaluating their association with metritis and fever in dairy cows.

Metritis is caused by polymicrobial infection; however, recent metagenomic work challenges the importance of known pathogens such as Escherichia coli and Trueperella pyogenes while identifying potential new pathogens such as Bacteroides pyogenes, Porphyromonas levii and Helcococcus ovis. This study aims to quantify known and emerging uterine pathogens, and to evaluate their association with metritis and fever in dairy cows. Metritis was diagnosed at 6 ±â€¯2 days postpartum, a uterine swab was collected and rectal temperature was measured. 39 cows were classified into three groups: Healthy (n = 14), Metritis without fever (MNoFever; n = 12), and Metritis with fever (MFever; n = 13). Absolute copy number was determined for total bacteria and for 8 potentially pathogenic bacteria using droplet digital PCR. Both MNoFever and MFever cows had higher copy number of total bacteria, Fusobacterium necrophorum, Prevotella melaninogenica, Bacteroides pyogenes, Porphyromonas levii, and Helcococcus ovis than Healthy cows. MNoFever and MFever groups were similar. There was no difference among groups in copy number of Escherichia coli, Trueperella pyogenes, and Bacteroides heparinolyticus, and they all had low copy numbers. Our work confirms the importance of some bacteria identified by culture-based studies in the pathogenesis of metritis such as Fusobacterium necrophorum and Prevotella melaninogenica; however, it challenges the importance of others such as Escherichia coli and Trueperella pyogenes at the time of metritis diagnosis. Additionally, Bacteroides pyogenes, Porphyromonas levii, and Helcococcus ovis were recognized as emerging pathogens involved in the etiology of metritis. Furthermore, fever was not associated with the total bacterial load or specific bacteria.