An evidence-based medicine approach to small animal anaesthetic mortality in a referral practice: the influence of initiating three recommendations on subsequent anaesthetic deaths.

OBJECTIVE: To evaluate anaesthetic death after implementation of recommendations and its risk factors in a small animal practice. STUDY DESIGN: Observational cohort study. ANIMALS: All cats and dogs anaesthetized at the Centre Hospitalier Vétérinaire des Cordeliers during two periods, from April 15th, 2008 to April 15th, 2010 (period 1) and from June 15th, 2010 to August 24th, 2011 (period 2). METHODS: Death occurring during or before full recovery from anaesthesia was recorded. At the end of period 1, a logistic regression model was generated to describe anaesthetic death and identify risk factors. Potential risk factors in our practice setting were identified, and three recommendations, relating to improving physical status and anaesthetic/analgesic regimen implemented for period 2. The relationship between anaesthetic death and recorded variables were analyzed, and where relevant, compared between periods. RESULTS: Six thousand two hundred and thirty-one animals underwent general anaesthesia. The overall death rate during period 1 was 1.35% (48 in 3546, 95% CI [1.0-1.7%]) and during period 2 was 0.8% (21 in 2685, 95% CI [0.6-1.2%]). For sick animals (ASA status 3 and over), the overall death rate was 4.8% (45 of 944 95% [CI 3.5-6.4%]) during period 1 and 2.2% (18 of 834 95% CI [1.3-3.5%]) during period 2; this represented a significant decrease in death rate in period 2 (p = 0.002). In period 2, the main factors associated with an increased odds ratio of anaesthetic death were poor health status (ASA physical status classification) and old age. Species, gender, anaesthetic regimen, the nature and urgency of the procedure were not associated with risk. CONCLUSION AND CLINICAL RELEVANCE: Following evidence based recommendations, the death rate related to anaesthesia was significantly decreased during period 2 compared to period 1. Application of evidence-based medicine may contribute to an effective approach to decrease death rates. Other factors, not monitored in this study, may also have had an impact.

Effectiveness of second booster compared to first booster and protection conferred by previous SARS-CoV-2 infection against symptomatic Omicron BA.2 and BA.4/5 in France.

In face of evidence of rapid waning of vaccine effectiveness against Omicron and its sub-lineages, a second booster with mRNA vaccines was recommended for the most vulnerable in France. We used a test negative design to estimate the effectiveness of the second booster relative to the first booster and the protection conferred by a previous SARS-CoV-2 infection, against symptomatic Omicron BA.2 or BA.4/5. We included symptomatic ≥60 years old individuals tested for SARS-CoV-2 in March 21-October 30, 2022. Compared to a 181-210 days old first booster, a second booster restored protection with a relative effectiveness of 41% [95%CI: 39-42%], 7-30 days post-vaccination. This gain in protection was lower than the one observed with the first booster, at equal time points since vaccination. High levels of protection were associated to previous SARS-CoV-2 infection, especially when the infection was recent and occurred when an antigenic-related variant was dominant.

Protection against symptomatic SARS-CoV-2 infection conferred by the Pfizer-BioNTech Original/BA.4-5 bivalent vaccine compared to the mRNA Original monovalent vaccines - A matched cohort study in France.

This cohort study evaluated the protection against symptomatic Omicron BA.5 infection conferred by the Pfizer-BioNTech Original/BA.4-5 bivalent vaccine compared to mRNA Original monovalent vaccines (Pfizer- BioNTech or Moderna). Individuals of ≥60 years old, who received a booster dose between 03/10/2022 and 06/11/2022, when both bivalent and monovalent vaccines were used in France, were included and matched according to the type of booster vaccine received. The outcome of interest was a positive SARS-CoV-2 RT-PCR or antigenic test associated to self-reported symptoms, ≥ seven days after receiving the booster dose. Data were analysed with a Cox Proportional-Hazards model adjusted for the presence of previous infection, age, sex, and the presence of medium risk comorbidities. A total of 136,852 individuals were included and followed for a median period of 77 days. The bivalent vaccine conferred an additional protection of 8 % [95 % CI: 0 %-16 %, p = 0.045] against symptomatic Omicron BA.5infection compared to the monovalent vaccines.

Vaccine effectiveness and duration of protection of COVID-19 mRNA vaccines against Delta and Omicron BA.1 symptomatic and severe COVID-19 outcomes in adults aged 50 years and over in France.

The emergence of SARS-CoV-2 variants calls for continuous monitoring of vaccine effectiveness (VE). We estimated the absolute effectiveness of complete 2-dose primary vaccination and booster vaccination with COVID-19 mRNA vaccines, and the duration of protection against Delta and Omicron BA.1 symptomatic infection and severe outcomes. French residents aged ≥50 years, who presented with SARS-CoV-2-like symptoms and tested for SARS-CoV-2 between June 6, 2021 and February 10, 2022 were included. A test-negative study was conducted to estimate VE against symptomatic infection, using conditional logistic regression models. Cox proportional hazard regressions were performed to assess additional protection against severe COVID-19 outcomes (any hospitalization, and intensive care units [ICU] admission or in-hospital death). In total, 273732 cases and 735 919 controls were included. VE against symptomatic infection after 2-doses vaccination was 86% (95% CI: 75-92%) for Delta and 70% (58-79%) for Omicron, 7-30 days post vaccination. Protection waned over time, reaching 60% (57-63%) against Delta and 20% (16.-24%) for Omicron BA.1 > 120 days after vaccination. The booster dose fully restored protection against symtpomatic Delta infection (95% [81-99%]) but only partially against symptomatic Omicron BA.1 infection (63% [59-67%]). VE against Delta-related severe outcomes was above 95% with 2 doses, and persisted for at least four months. Protection against any Omicron BA.1-hospitalization was 92% (65%-99%) at 8-30 days, and 82% (67%-91%) > 120 days from the second dose. Against BA.1 ICU admission or in-patient death, VE stood at 98% (0-100%) at 8-30 days, and was 90% (40-99%) > 120 days from the second dose. Protection confered by mRNA vaccines against severe disease caused by either Delta or Omicron BA.1 appeared high and sustained over time. Protection against symptomatic diseases after 2 doses decreased rapidly, especially against Omicron BA.1. A booster dose restored high protection against Delta but only a partial one against Omicron BA.1.

Risk of anaesthetic mortality in dogs and cats: an observational cohort study of 3546 cases.

OBJECTIVE: To evaluate the anaesthetic death risk for dogs and cats in a French private practice. STUDY DESIGN: Observational cohort study. ANIMAL POPULATION: All small animals anesthetized at the Centre Hospitalier Vétérinaire des Cordeliers between April 15th, 2008 and April 15th, 2010. METHODS: General anaesthesia was defined as a drug-induced unconsciousness characterised by a controlled and reversible depression of the central nervous system and analgesia, sufficient to allow endotracheal intubation. Patient outcome (alive or dead) was assessed at the end of anaesthesia defined as the meeting point of the return of consciousness, rectal temperature >36 °C and ability to maintain sternal recumbency. Death occurring during anaesthesia was recorded. Relationship between anaesthetic death and ASA status, species, age, nature of the procedure, anaesthetic protocol and occurrence of epidural administration of a combination of morphine and bupivacaine were analysed. RESULTS: During the study period 3546 animals underwent general anaesthesia. The overall death rate in the present study was 1.35% (48 in 3546, 95% CI 0.96-1.75). The death rate of healthy animals (ASA 1 and 2) was 0.12% (3 in 2602 95% CI 0.02-0.34). For sick animals (ASA status 3 and over), the overall death rate was 4.77% (45 in 944 95% CI 3.36-6.18). The death rates in the ASA 3, 4 and 5 categories were 2.90%, 7.58% and 17.33%, respectively. The main factor associated with increased odds of anaesthetic death in ASA categories 3 and over was poor health status (ASA physical status classification). The nature of the procedure the patient underwent and epidural administration of a combination of morphine and bupivacaine were not correlated with the occurrence of death during anaesthesia. Neither species nor age effects were detected. CONCLUSION AND CLINICAL RELEVANCE: Specific factors were associated with increased odds of anaesthetic death, especially poor health status. Efforts must be directed towards thorough preoperative patient evaluation and improvement of clinical conditions if possible. Identification of risk factors before anaesthesia should lead to increased surveillance by trained staff. This could result in better outcomes.

Severe hospital events following symptomatic infection with Sars-CoV-2 Omicron and Delta variants in France, December 2021-January 2022: A retrospective, population-based, matched cohort study.

Background: A rapid increase in incidence of the SARS-CoV-2 Omicron variant (sub-lineage BA.1) occurred in France in December 2021, while the Delta variant was prevailing since July 2021. We aimed to determine whether the risk of a severe hospital event following symptomatic SARS-CoV-2 infection differs for Omicron versus Delta. Methods: We conducted a retrospective cohort study to compare severe hospital events (admission to intensive care unit or death) between Omicron and Delta symptomatic cases matched according to week of virological diagnosis and age. The analysis was adjusted for age, sex, vaccination status, presence of comorbidities and region of residence, using Cox proportional hazards model. Findings: Between 06/12/2021-28/01/2022, 184 364 cases were included, of which 931 had a severe hospital event (822 Delta, 109 Omicron). The risk of severe event was lower among Omicron versus Delta cases; the difference in severity between the two variants decreased with age (adjusted Hazard Ratio (aHR)=0·13 95%CI: 0·08-0·20 among 40-64 years, aHR=0·50 95%CI: 0·26-0.98 among 80+ years). The risk of severe event increased with the presence of comorbidities (for very-high-risk comorbidity, aHR=4·15 95%CI: 2·86-6·01 among 40-64 years) and in males (aHR=2·28 95%CI: 1·82-2·85among 40-64 years) and was higher in unvaccinated compared to primo-vaccinated (aHR=7·29 95%CI: 5·58-9·54 among 40-64 years). A booster dose reduced the risk of severe hospital event in 80+ years infected with Omicron (aHR=0·29; 95%CI: 0·12-0·69). Interpretation: This study confirms the lower severity of Omicron compared to Delta. However, the difference in disease severity is less marked in the elderly. Further studies are needed to better understand the interactions between age and severity of variants. Funding: The study was performed as part of routine work at Public Health France.

Monitoring PRRSV-1 in suckling piglets in an endemic herd using reverse transcriptase quantitative real time polymerase chain reaction: comparison of the rate of detection in serum and oral fluid samples and evaluation of pooling.

BACKGROUND: Defining shedding and exposure status for PRRSV is essential in herd stabilisation protocols and weaning-age pigs is a key subpopulation. Oral fluid (OF) sampling is a welfare-friendly and cost saving promising alternative to blood sampling. The first objective of our study was to compare the rate of detection of PRRSV-1 in individual serum sample, individual OF sample, litter-based OF sample, collected the day before weaning. The second objective was to evaluate the interest of pooling samples. RESULTS: The study was performed on a 210-sows, PRRSV-1 exposed, with confirmed shedding, non-vaccinated against PRRSV, herd. 80 litters were sampled and 26 were viropositive and therefore included. The rate of detection of PRRSV-1 with RT-qrtPCR in blood samples, iOF and cOF was 67, 23 and 77%, respectively. The Ct values from RT-qrtPCR on collective OF were statistically lower if the serum of the piglet of the litter was positive. The lower the Cycle threshold (Ct) value of RT-qrtPCR on collective OF, the higher the probability that the serum sampled in the same litter was positive. Ability to detect PRRSV RNA after pooling was 67% for sera and 58% for cOF. CONCLUSIONS: The rate of detection of PRRSV-1 was about the same in cOF and blood samples. Virus sequencing, if required, should be performed on individual serum samples. The smaller the Ct of a cOF sample from a litter, the greater the likelihood that the serum sample from a piglet of that litter is positive.A cost-effective and representative sampling protocol to monitor sow herds stabilisation of a sow batch could be: to collect both cOF and one serum sample per litter; to perform firstly RT-qrtPCR on pooled cOF; in case of negative results to consider the batch negative; in case of positive results in a unvaccinated herd or a killed vaccine vaccinated one to consider the batch positive; in case of positive result in a herd vaccinated with a modified live vaccine serum samples of litters with positive cOF should be tested for sequencing (selecting the litters with the lowest Ct for cOF).

Seasonal infertility in sows: a five year field study to analyze the relative roles of heat stress and photoperiod.

The objective of this study was to analyze the relative roles of high temperature and photoperiod as environmental factors of seasonal infertility in swine. The results of five years (2003-2007) of ultrasound pregnancy diagnosis carried out in 266 indoor farms were analyzed. For all farms, the data covered the entire study period. The farms were situated in four French regions. The data of 22,773 batches and 610,117 sows were included. Seasonal infertility was defined as the relative difference between the fertility rate in 'summer' (inseminations in weeks 25-42) and 'winter' (inseminations in weeks 1-18 of the same year). In each region, two meteorological variables were defined, based on the data of a reference weather station: the number of hot days (maximum temperature >or= 25 degrees C) and tropical days (maximum temperature >or= 32 degrees C and minimum temperature >or= 18 degrees C). The mean fertility was 85%. The median seasonal infertility was 2.8% and more than 7.1% for a quarter of farms. Seasonal infertility did not vary with areas or baseline fertility (defined for each studied farm as the average winter fertility over five years). Seasonal infertility differed with the year (p<0.001). Seasonal infertility was significantly higher during 2003 than in the other four years, which did not differ among each other. In the four regions, 2003 was the year with the highest number of hot days and 2007 with the least. Our study strengthens the hypothesis of a prominent role of photoperiod in seasonal infertility and of an additional role of heat stress the hottest years.