Association of results of the glutaraldehyde coagulation test with plasma acute phase protein concentrations and hematologic findings in hospitalized cows.

Introduction: The glutaraldehyde test (GAT) allows for animal-side semi-quantitative estimation of fibrinogen and gamma-globulin concentrations in blood samples of adult cattle and therefore detection of inflammatory disease conditions. However, the test has potential limitations, especially due to the latency period until sufficiently high fibrinogen and/or gamma-globulin concentrations are reached. The aim of the present study was therefore to assess the association between results of GAT with other inflammatory markers including hematologic variables, fibrinogen, plasma haptoglobin and serum amyloid A (SAA) concentrations. Methods: For the purpose of this prospective observational study, a convenience sample of 202 cows with a broad range of inflammatory and non-inflammatory clinical conditions was included. The GAT was run on EDTA blood, fibrinogen was measured using the Clauss and the heat precipitation method, and commercially available ELISA tests were used for determination of plasma haptoglobin and SAA concentrations. Results: Shortened GAT coagulation times were more closely correlated to serum globulin (rs = -0.72) than to plasma fibrinogen concentrations measured with the heat precipitation (rs = -0.64) and the Clauss method (rs = -0.70). Cows with a markedly (≤3 min) or moderately (4-6 min) shortened coagulation time had higher (p < 0.001) plasma haptoglobin and SAA concentrations than cows with a negative test result. Total leukocyte, monocyte and neutrophil concentrations did not differ significantly between groups. An identified cut-off for the GAT coagulation time of ≤14 min had a sensitivity and specificity of 54.4 and 100%, respectively, for the prediction of an inflammatory state based on clinical findings and/or increased plasma haptoglobin or SAA concentrations. Discussion: In conclusion, this study demonstrates considerable diagnostic agreement between positive GAT results and increased plasma concentrations of haptoglobin and SAA. Despite high specificity, the test lacks sensitivity in case of acute inflammatory conditions indicating that plasma acute phase protein concentrations and hematologic findings can provide additional diagnostic information if the GAT is negative.

Effect of oxytocin use during colostrum harvest and association of cow characteristics with colostrum yield and IgG concentration in Holstein dairy cows.

Our objectives were to determine the effect of oxytocin use during colostrum harvest on colostrum yield (CY) and IgG concentration in Holstein dairy cows on a commercial dairy in New York and to describe associations of cow characteristics with these outcomes. Animals were enrolled between July and October 2023 using a randomized block design, with day of enrollment as the unit of randomization. A median (range) of 10 (3 to 19) cows were enrolled/d. Treatments were 1) 40 IU Oxytocin (OXY40), 2) 20 IU Oxytocin (OXY20), and 3) an untreated control group (CNTR). Oxytocin was administered intramuscularly (IM) approximately 45 s before unit attachment in a rotary parlor. Colostrum weight was measured using the colostrum bucket-embedded scale or a platform scale when the yield was less than the smallest bucket scale. The concentration of IgG ([IgG]) in colostrum was determined using radial immunodiffusion (RID) and used to calculate total IgG, and dry matter (%) was determined by oven drying. Individual cow characteristics such as parity, calf sex, weight, dystocia score, stillbirth, milk production in wk 4 of lactation, and for multiparous cows, dry period length, previous lactation dry off linear score (LS) were collected. Data were analyzed separately for primiparous and multiparous cows using backward stepwise elimination to produce final mixed effects ANOVA models Primiparous cows (n = 201) were randomized to 35.8% (n = 72) OXY40, 32.8% (n = 66) OXY20, and 31.3% (n = 63) CNTR. Multiparous groups (n = 435) were randomized to 34.7% (n = 151) OXY40, 29.7% (n = 129) OXY20, and 35.6% (n = 155) CNTR. The median (range) CY was 6.0 (0 to 20.6) kg and [IgG] was 98.5 (0.1 to 293.6) g/L in the study population. In primiparous cows, OXY40 had a higher colostrum yield (LSM [95% CI]) of 5.4 (4.9 to 5.9) kg compared with both OXY20 (4.1 [3.5 to 4.7] kg) and CNTR (3.8 [3.3 to 4.3] kg) (P < 0.001). In multiparous cows, OXY40, OXY20, and CTNR did not differ in CY (5.9 [5.3 to 6.5], 5.7 [6.3 to 5.1], and 5.4 [6.0 to 4.8] kg, respectively, P = 0.43), but colostrum yield was greater in parity 2 compared with all other parities, cows giving birth to male calves, cows with the highest milk production at wk 4 of lactation, and with a dry period of >65 d. Oxytocin use did not affect [IgG] in either primiparous or multiparous cows (P > 0.56), but [IgG] was highest in cows in parity ≥4 and lowest in cows dry >65 d. In summary, oxytocin use at 40 IU IM in primiparous was associated with a higher CY but not [IgG]. Oxytocin use likely addressed disturbed milk ejection and therefore increased CY in heifers milked for the first time in a rotary parlor. This study confirms cow characteristics associated with colostrum production within a single herd.

Quantitative Benefit-Risk Evaluation of Rivaroxaban in Patients After Peripheral Arterial Revascularization: The VOYAGER PAD Trial.

BACKGROUND: The VOYAGER PAD (Efficacy and Safety of Rivaroxaban in Reducing the Risk of Major Thrombotic Vascular Events in Subjects With Symptomatic Peripheral Artery Disease Undergoing Peripheral Revascularization Procedures of the Lower Extremities) trial compared rivaroxaban (2.5 mg twice a day) plus aspirin with aspirin alone in patients with symptomatic peripheral artery disease requiring endovascular or surgical limb revascularization, with 50% receiving clopidogrel background therapy. The New Drug Indication application includes benefit-risk assessments using clinical judgment to balance benefits against risks. During its review, the US Food and Drug Administration requested additional quantitative benefit-risk analyses with formal weighting approaches. METHODS AND RESULTS: Benefits and risks were assessed using rate differences between treatment groups (unweighted analysis). To account for clinical importance of the end points, a multi-criteria decision analysis was conducted using health state utility values as weights. Monte Carlo simulations incorporated statistical uncertainties of the event rates and utility weights. Intent-to-treat and on-treatment analyses were conducted. For unweighted intent-to-treat analyses, rivaroxaban plus aspirin would result in 120 (95% CI, -208 to -32) fewer events of the primary composite end point (per 10 000 patient-years) compared with aspirin alone. Rivaroxaban caused an excess of 40 (95% CI, 8-72) Thrombolysis in Myocardial Infarction major bleeding events, which was largely driven by nonfatal, nonintracranial hemorrhage Thrombolysis in Myocardial Infarction major bleeding events. For weighted analyses, rivaroxaban resulted in the utility equivalent of 13.7 (95% CI, -85.3 to 52.6) and 68.1 (95% CI, 7.9-135.7) fewer deaths per 10 000 patient-years (intent-to-treat and on-treatment, respectively), corresponding to probabilities of 64.4% and 98.7%, respectively, that benefits outweigh risks favoring rivaroxaban per Monte Carlo simulation. CONCLUSIONS: These analyses show a favorable benefit-risk profile of rivaroxaban therapy in the VOYAGER PAD trial, with findings generally consistent between the unweighted and weighted approaches.

Estimation of udder emptying based on milk constituents of strip samples after milking.

Milk ejection disorders were induced by oxytocin receptor blockade. We tested the hypothesis that the degree of udder emptying at incomplete milk ejection can be estimated based on the concentration of various milk constituents in different milk fraction samples. To induce different levels of spontaneous udder emptying (SUE) 10 Holstein dairy cows were milked either with or without i.v. injection of the oxytocin receptor blocking agent atosiban (ATO). In ATOearly, 12 µg/kg BW ATO was injected immediately before and in ATOlate directly after a 1 min manual udder preparation. The normal milking routine served as Control treatment. In all 3 treatments the udder was completely emptied by the i.v. injection of 10 IU oxytocin (OT) at the end of spontaneous milk flow. During all experimental milkings 4 milk samples were taken in all treatments: at the start of udder preparation (foremilk; FM), immediately after cessation of spontaneous milk flow and cluster detachment by hand stripping (strip milk; SM), from spontaneous removed milk in the bucket 1 (milk before OT; MBOT) and from the milk obtained after OT injection in the bucket 2 (milk after OT; MAOT). Fat, protein, lactose and electrolytes (Na, Cl and K) were measured in each milk sample. In addition, electrical conductivity (EC) was determined in parallel to continuous milk flow recording. The treatments induced individual degrees of SUE; therefore, the final evaluations of data were based on SUE classes instead of treatments. The most pronounced differences of milk constituents at different degrees of SUE were found for the milk fat content. The fat content of SM and MBOT remained almost unchanged up to 60% SUE, but was considerably higher if >80% of the milk was spontaneously removed. The concentrations of Na and Cl were highest and of K lowest if less than 20% on milk was received in the different samples. The EC was higher in SM and MBOT if <20% of milk was received. In conclusion, the blockade of the OT effect influences primarily the fat content, which confirmed an OT-induced fat secretion during milking. Similar effects are likely found in situations of disturbed milk ejections, caused by a lacking or reduced release of OT in response to different degrees of tactile udder stimulation. Our results show that the measurement of fat content and the EC in strip milk samples collected after cluster detachment can be used to estimate the completeness of udder emptying.

Methods, design, and initial results of an angiographic core lab from VOYAGER-PAD.

Background: Anatomy is critical in risk stratification and therapeutic decision making in coronary disease. The relationship between anatomy and outcomes is not well described in PAD. We sought to develop an angiographic core lab within the VOYAGER-PAD trial. The current report describes the methods of creating this core lab, its study population, and baseline anatomic variables. Methods: Patients undergoing lower-extremity revascularization for symptomatic PAD were randomized in VOYAGER-PAD. The median follow up was 2.25 years. Events were adjudicated by a blinded Clinical Endpoint Committee. Angiograms were collected from study participants; those with available angiograms formed this core lab cohort. Angiograms were scored for anatomic and flow characteristics by trained reviewers blinded to treatment. Ten percent of angiograms were evaluated independently by two reviewers; inter-rater agreement was assessed. Clinical characteristics and the treatment effect of rivaroxaban were compared between the core lab cohort and noncore lab participants. Anatomic data by segment were analyzed. Results: Of 6564 participants randomized in VOYAGER-PAD, catheter-based angiograms from 1666 patients were obtained for this core lab. Anatomic and flow characteristics were collected across 16 anatomic segments by 15 reviewers. Concordance between reviewers for anatomic and flow variables across segments was 90.5% (24,417/26,968). Clinical characteristics were similar between patients in the core lab and those not included. The effect of rivaroxaban on the primary efficacy and safety outcomes was also similar. Conclusions: The VOYAGER-PAD angiographic core lab provides an opportunity to correlate PAD anatomy with independently adjudicated outcomes and provide insights into therapy for PAD. (ClinicalTrials.gov Identifier: NCT02504216).

Clinical context and communication in shared decision-making about major surgery: Findings from a qualitative study with colorectal, orthopaedic and cardiac patients.

Increasing numbers of older people undergo major surgery in the United Kingdom (UK), with many at high risk of complications due to age, co-morbidities or frailty. This article reports on a study of such patients and their clinicians engaged in shared decision-making. Shared decision-making is a collaborative approach that seeks to value and centre patients' preferences, potentially addressing asymmetries of knowledge and power between clinicians and patients by countering medical authority with greater patient empowerment. We studied shared decision-making practices in the context of major surgery by recruiting 16 patients contemplating either colorectal, cardiac or joint replacement surgery in the UK National Health Service (NHS). Over 18 months 2019-2020, we observed and video-recorded decision-making consultations, studied the organisational and clinical context for consultations, and interviewed patients and clinicians about their experiences of making decisions. Linguistic ethnography, the study of communication and interaction in context, guided us to analyse the interplay between interactions (during consultations between clinicians, patients and family members) and clinical and organisational features of the contexts for those interactions. We found that the framing of consultations as being about life-saving or life-enhancing procedures was important in producing three different genres of consultations focused variously on: resolving problems, deliberation of options and evaluation of benefits of surgery. We conclude that medical authority persists, but can be used to create more deliberative opportunities for decision-making through amending the context for consultations in addition to adopting appropriate communication practices during surgical consultations.

Creatine supplementation for optimization of physical function in the patient at risk of functional disability: A systematic review and meta-analysis.

BACKGROUND: The efficacy of creatine replacement through supplementation for the optimization of physical function in the population at risk of functional disability is unclear. METHODS: We conducted a systematic literature search of MEDLINE, EMBASE, the Cochrane Library, and CINAHL from inception to November 2022. Studies included were randomized controlled trials (RCTs) comparing creatine supplementation with placebos in older adults and adults with chronic disease. The primary outcome was physical function measured by the sit-to-stand test after pooling data using random-effects modeling. We also performed a Bayesian meta-analysis to describe the treatment effect in probability terms. Secondary outcomes included other measures of physical function, muscle function, and body composition. The risk of bias was assessed using the Cochrane risk-of-bias tool. RESULTS: We identified 33 RCTs, comprising 1076 participants. From six trials reporting the primary outcome, the pooled standardized mean difference (SMD) was 0.51 (95% confidence interval [CI]: 0.01-1.00; I2 = 62%; P = 0.04); using weakly informative priors, the posterior probability that creatine supplementation improves physical function was 66.7%. Upper-body muscle strength (SMD: 0.25; 95% CI: 0.06-0.44; I2 = 0%; P = 0.01), handgrip strength (SMD 0.23; 95% CI: 0.01-0.45; I2 = 0%; P = 0.04), and lean tissue mass (MD 1.08 kg; 95% CI: 0.77-1.38; I2 = 26%; P < 0.01) improved with creatine supplementation. The quality of evidence for all outcomes was low or very low because of a high risk of bias. CONCLUSION: Creatine supplementation improves sit-to-stand performance, muscle function, and lean tissue mass. It is crucial to conduct high-quality prospective RCTs to confirm these hypotheses (PROSPERO number, CRD42023354929).

Preoperative N-terminal pro-B-type natriuretic peptide and myocardial injury after stopping or continuing renin-angiotensin system inhibitors in noncardiac surgery: a prespecified analysis of a phase 2 randomised controlled multicentre trial.

BACKGROUND: Patients with elevated preoperative plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP >100 pg ml-1) experience more complications after noncardiac surgery. Individuals prescribed renin-angiotensin system (RAS) inhibitors for cardiometabolic disease are at particular risk of perioperative myocardial injury and complications. We hypothesised that stopping RAS inhibitors before surgery increases the risk of perioperative myocardial injury, depending on preoperative risk stratified by plasma NT-proBNP concentrations. METHODS: In a preplanned analysis of a phase 2a trial in six UK centres, patients ≥60 yr old undergoing elective noncardiac surgery were randomly assigned either to stop or continue RAS inhibitors before surgery. The pharmacokinetic profile of individual RAS inhibitors determined for how long they were stopped before surgery. The primary outcome, masked to investigators, clinicians, and patients, was myocardial injury (plasma high-sensitivity troponin-T ≥15 ng L-1 or a ≥5 ng L-1 increase, when preoperative high-sensitivity troponin-T ≥15 ng L-1) within 48 h after surgery. The co-exposures of interest were preoperative plasma NT-proBNP (< or >100 pg ml -1) and stopping or continuing RAS inhibitors. RESULTS: Of 241 participants, 101 (41.9%; mean age 71 [7] yr; 48% females) had preoperative NT-proBNP >100 pg ml -1 (median 339 [160-833] pg ml-1), of whom 9/101 (8.9%) had a formal diagnosis of cardiac failure. Myocardial injury occurred in 63/101 (62.4%) subjects with NT-proBNP >100 pg ml-1, compared with 45/140 (32.1%) subjects with NT-proBNP <100 pg ml -1 {odds ratio (OR) 3.50 (95% confidence interval [CI] 2.05-5.99); P<0.0001}. For subjects with preoperative NT-proBNP <100 pg ml-1, 30/75 (40%) who stopped RAS inhibitors had myocardial injury, compared with 15/65 (23.1%) who continued RAS inhibitors (OR for stopping 2.22 [95% CI 1.06-4.65]; P=0.03). For preoperative NT-proBNP >100 pg ml-1, myocardial injury rates were similar regardless of stopping (62.2%) or continuing (62.5%) RAS inhibitors (OR for stopping 0.98 [95% CI 0.44-2.22]). CONCLUSIONS: Stopping renin-angiotensin system inhibitors in lower-risk patients (preoperative NT-proBNP <100 pg ml -1) increased the likelihood of myocardial injury before noncardiac surgery.

Stress indicators in dairy cows adapting to virtual fencing.

Virtual fencing (VF) enables livestock grazing without physical fences by conditioning animals to a virtual boundary delimited with an audio tone (AT) and an electric pulse (EP). The present study followed the adaptation process of lactating dairy cows to a VF system with changing virtual boundaries and investigated its impact on animal welfare. Twenty cows were divided into stratified groups (2× VF; 2× electric fencing, EF) of five individuals. Each group grazed half-days in a separate EF paddock of comparable size during 3 d of acclimation (P0), followed by 21, 14, 14, and 7 d of experimental treatment (P1 to P4). At the start of the trial, all cows were equipped with an IceQube pedometer (Peacock Technology Ltd, Stirling, UK) and a VF collar (Nofence AS, Batnfjordsøra, Norway). During P0, cows were accustomed to their first paddock with a deactivated virtual boundary and wearing the sensors. In P1 to P4, an active virtual boundary for the VF groups, and a second EF for the EF groups was set up parallel to an outer EF within their paddock. Throughout the trial, the sensors continuously tracked cow positions and activity behavior at 15-min intervals. From P1 onwards, the VF collars additionally recorded each AT and EP per cow with a georeferenced time stamp. During P0 to P4, daily feed intake, body weight, and milk yield were recorded in the barn. A total of 26 milk samples were collected per cow to determine milk cortisol levels. Behavioral observations were conducted for 2 h on day 23 to record agonistic behaviors, vocalizations, and excretions. The total number of stimuli per cow ranged from 37 to 225 ATs (mean ±â€…SD: 1.9 ±â€…3.3 per day) and 3 to 11 EPs (mean ±â€…SD: 0.1 ±â€…0.7 per day) throughout the trial. The maximum number of EPs per day was 8 for an individual cow and occurred once on D1. Mean EP/AT decreased by 55% during the first three half-days of grazing and with each paddock change from 0.2 EP/AT in week 1 to 0.03, 0.02, and 0 EP/AT in weeks 4, 6, and 8, respectively. Linear and generalized mixed effects models revealed that milk yield and cortisol, feed intake, body weight, and activity and lying behavior did not significantly differ between VF and EF groups. A higher number of agonistic behaviors were observed in the VF groups when the VF system was activated. However, due to the short observation periods only few contacts were observed in total. Overall, all cows adapted to the VF system without evidence of lasting adverse effects on animal welfare.

Virtual fences are commercially available but face restrictions in some countries due to animal welfare concerns. For virtual fencing (VF), animals are equipped with collars that emit audio tones (ATs) followed by electric pulses (EPs) when they cross a virtual boundary tracked by global navigation. Existing studies have so far not covered the aspect of longer-term learning, impacting possibly VF suitability. The present study followed therefore the learning process of dairy cows with changing virtual boundaries and examined behavior and stress indicators in dairy cows during an 8-wk adaptation to VF across four experimental periods. Four control and treatment groups of five cows each were investigated. EPs occurred most frequently on days 1 to 3 and remained low for the remaining experiment. In the latter two experimental periods, almost no EPs were recorded while ATs were still triggered, indicating that it took the animals two introductions to a new fence line to respond to the ATs only. Animal welfare was assessed by monitoring cow activity and lying behavior, milk yield, milk cortisol, feed intake, body weight, and frequencies of agonistic interactions, vocalizations, and excretions. All cows adapted to the VF system without compromising animal welfare during the study period.

Method of Anesthesia and Perioperative Risk Factors, Maternal Anesthesia Complications, and Neonatal Mortality Following Cesarean Delivery in Africa: A Substudy of a 7-Day Prospective Observational Cohort Study.

BACKGROUND: The African Surgical Outcomes Study (ASOS) found that maternal mortality following cesarean delivery in Africa is 50 times higher than in high-income countries, and associated with obstetric hemorrhage and anesthesia complications. Mothers who died were more likely to receive general anesthesia (GA). The associations between GA versus spinal anesthesia (SA) and preoperative risk factors, maternal anesthesia complications, and neonatal outcomes following cesarean delivery in Africa are unknown. METHODS: This is a secondary explanatory analysis of 3792 patients undergoing cesarean delivery in ASOS, a prospective observational cohort study, across 22 African countries. The primary aim was to estimate the association between preoperative risk factors and the outcome of the method of anesthesia delivered. Secondary aims were to estimate the association between the method of anesthesia and the outcomes (1) maternal intraoperative hypotension, (2) severe maternal anesthesia complications, and (3) neonatal mortality. Generalized linear mixed models adjusting for obstetric gravidity and gestation, American Society of Anesthesiologists (ASA) category, urgency of surgery, maternal comorbidities, fetal distress, and level of anesthesia provider were used. RESULTS: Of 3709 patients, SA was performed in 2968 (80%) and GA in 741 (20%). Preoperative factors independently associated with GA for cesarean delivery were gestational age (adjusted odds ratio [aOR], 1.093; 95% confidence interval [CI], 1.052-1.135), ASA categories III (aOR, 11.84; 95% CI, 2.93-46.31) and IV (aOR, 11.48; 95% CI, 2.93-44.93), eclampsia (aOR, 3.92; 95% CI, 2.18-7.06), placental abruption (aOR, 6.23; 95% CI, 3.36-11.54), and ruptured uterus (aOR, 3.61; 95% CI, 1.36-9.63). SA was administered to 48 of 94 (51.1%) patients with eclampsia, 12 of 28 (42.9%) with cardiac disease, 14 of 19 (73.7%) with preoperative sepsis, 48 of 76 (63.2%) with antepartum hemorrhage, 30 of 55 (54.5%) with placenta previa, 33 of 78 (42.3%) with placental abruption, and 12 of 29 (41.4%) with a ruptured uterus. The composite maternal outcome "all anesthesia complications" was more frequent in GA than SA (9/741 [1.2%] vs 3/2968 [0.1%], P < .001). The unadjusted neonatal mortality was higher with GA than SA (65/662 [9.8%] vs 73/2669 [2.7%], P < .001). The adjusted analyses demonstrated no association between method of anesthesia and (1) intraoperative maternal hypotension and (2) neonatal mortality. CONCLUSIONS: Analysis of patients undergoing anesthesia for cesarean delivery in Africa indicated patients more likely to receive GA. Anesthesia complications and neonatal mortality were more frequent following GA. SA was often administered to high-risk patients, including those with eclampsia or obstetric hemorrhage. Training in the principles of selection of method of anesthesia, and the skills of safe GA and neonatal resuscitation, is recommended.

A Transcriptomic Approach to Understand Patient Susceptibility to Pneumonia After Abdominal Surgery.

OBJECTIVE: To describe immune pathways and gene networks altered following major abdominal surgery and to identify transcriptomic patterns associated with postoperative pneumonia. BACKGROUND: Nosocomial infections are a major healthcare challenge, developing in over 20% of patients aged 45 or over undergoing major abdominal surgery, with postoperative pneumonia associated with an almost 5-fold increase in 30-day mortality. METHODS: From a prospective consecutive cohort (n=150) undergoing major abdominal surgery, whole-blood RNA was collected preoperatively and at 3 time-points postoperatively (2-6, 24, and 48 h). Twelve patients diagnosed with postoperative pneumonia and 27 matched patients remaining infection-free were identified for analysis with RNA-sequencing. RESULTS: Compared to preoperative sampling, 3639 genes were upregulated and 5043 downregulated at 2 to 6 hours. Pathway analysis demonstrated innate-immune activation with neutrophil degranulation and Toll-like-receptor signaling upregulation alongside adaptive-immune suppression. Cell-type deconvolution of preoperative RNA-sequencing revealed elevated S100A8/9-high neutrophils alongside reduced naïve CD4 T-cells in those later developing pneumonia. Preoperatively, a gene-signature characteristic of neutrophil degranulation was associated with postoperative pneumonia acquisition ( P =0.00092). A previously reported Sepsis Response Signature (SRSq) score, reflecting neutrophil dysfunction and a more dysregulated host response, at 48 hours postoperatively, differed between patients subsequently developing pneumonia and those remaining infection-free ( P =0.045). Analysis of the novel neutrophil gene-signature and SRSq scores in independent major abdominal surgery and polytrauma cohorts indicated good predictive performance in identifying patients suffering later infection. CONCLUSIONS: Major abdominal surgery acutely upregulates innate-immune pathways while simultaneously suppressing adaptive-immune pathways. This is more prominent in patients developing postoperative pneumonia. Preoperative transcriptomic signatures characteristic of neutrophil degranulation and postoperative SRSq scores may be useful predictors of subsequent pneumonia risk.

Prediction, prognosis, and professionalism in perioperative medicine.

Guidelines provide a framework to take better care of our patients. They are published by different professional groups and are based on all the research done for us by hardworking colleagues. Compiling a guideline is an enormous amount of work and is generally done with the utmost care. However, recommendations often require a subjective interpretation of published research, where personal and academic interests can influence the outcome. We discuss two recently published guidelines on perioperative cardiovascular assessment that led to different conclusions on some important areas of patient care.

Discontinuation vs. continuation of renin-angiotensin system inhibition before non-cardiac surgery: the SPACE trial.

BACKGROUND AND AIMS: Haemodynamic instability is associated with peri-operative myocardial injury, particularly in patients receiving renin-angiotensin system (RAS) inhibitors (angiotensin-converting-enzyme inhibitors/angiotensin II receptor blockers). Whether stopping RAS inhibitors to minimise hypotension, or continuing RAS inhibitors to avoid hypertension, reduces peri-operative myocardial injury remains unclear. METHODS: From 31 July 2017 to 1 October 2021, patients aged ≥60 years undergoing elective non-cardiac surgery were randomly assigned to either discontinue or continue RAS inhibitors prescribed for existing medical conditions in six UK centres. Renin-angiotensin system inhibitors were withheld for different durations (2-3 days) before surgery, according to their pharmacokinetic profile. The primary outcome, masked to investigators, clinicians, and patients, was myocardial injury [plasma high-sensitivity troponin-T (hs-TnT) ≥ 15 ng/L within 48 h after surgery, or ≥5 ng/L increase when pre-operative hs-TnT ≥15 ng/L]. Pre-specified adverse haemodynamic events occurring within 48 h of surgery included acute hypertension (>180 mmHg) and hypotension requiring vasoactive therapy. RESULTS: Two hundred and sixty-two participants were randomized to continue (n = 132) or stop (n = 130) RAS inhibitors. Myocardial injury occurred in 58 (48.3%) patients randomized to discontinue, compared with 50 (41.3%) patients who continued, RAS inhibitors [odds ratio (for continuing): 0.77; 95% confidence interval (CI) 0.45-1.31]. Hypertensive adverse events were more frequent when RAS inhibitors were stopped [16 (12.4%)], compared with 7 (5.3%) who continued RAS inhibitors [odds ratio (for continuing): 0.4; 95% CI 0.16-1.00]. Hypotension rates were similar when RAS inhibitors were stopped [12 (9.3%)] or continued [11 (8.4%)]. CONCLUSIONS: Discontinuing RAS inhibitors before non-cardiac surgery did not reduce myocardial injury, and could increase the risk of clinically significant acute hypertension. These findings require confirmation in future studies.

The mouthpiece chamber vacuum pattern indicates the cessation of milk flow and suits as an indicator to reduce teat end vacuum at a quarter level.

We investigated the suitability of the quarter mouthpiece chamber vacuum (MPCV) as an indicator for cessation of quarter milk flow to potentially adjust the teat end vacuum at a quarter level. We tested the hypothesis that a MPCV increase is a clear indicator of quarter milk flow cessation. In addition, we tested if a quarter-individual vacuum reduction at MPCV increase reduces the mechanical effect on the teat. Ten dairy cows were milked twice daily with a quarter-specific vacuum supply with continuously high (51 kPa; TRT51) or low vacuum setting (41 kPa; TRT41), or high vacuum setting combined with a quarter-specific vacuum reduction by 10 kPa immediately after the quarter-specific MPCV increase (TRT51/41). Whole udder milk flow was continuously recorded. Each treatment was repeated at 4 subsequent milkings. The high vacuum settings (TRT51; TRT51/41) reached higher values in peak flow rate and average milk flow and consequently shorter machine-on time. The time from start of milking until the steep increase of the MPCV was shorter in front than rear quarters, and hence the time from start of MPCV increase until end of milking was longer in front than rear teats. Teat condition of the right front teats was measured for teat wall diameter by ultrasound and teat tissue thickness by cutimeter at 5 and 20 min after each experimental milking. The teat measurements were taken at the teat tip (distal barrel) and 2 cm above the teat tip (proximal barrel). The proximal teat wall diameter tended to be higher in TRT51 than in TRT41, both 5 and 20 min after milking. The distal teat wall diameter at 5 min was greater in TRT51 than in TRT41. In TRT51/41 the teat wall diameter at both locations was intermediate, not significantly different from either TRT51 or TRT41. The distal teat tissue thickness was greater in TRT51 than in TRT41, and tended to be greater in TRT51/41 than in TRT41 at 5 min. The proximal teat tissue thickness at 5 min was higher in TRT51 and TRT51/41 than in TRT41. The teat tissue thickness decreased from 5 to 20 min only in the proximal barrel. The quarter-individual MPCV increase appears to be a suitable indicator of the cessation of milk flow. The lack of a significant reduction of mechanical effect on the teat by a reduced vacuum of 41 kPa indicates that the vacuum level chosen may be still too high under conditions of a separate vacuum supply for each quarter, which prevents a vacuum drop caused by the whole udder milk flow.

One-year Outcomes after Discharge from Noncardiac Surgery and Association between Predischarge Complications and Death after Discharge: Analysis of the VISION Prospective Cohort Study.

BACKGROUND: In previous analyses, myocardial injury after noncardiac surgery, major bleeding, and sepsis were independently associated with most deaths in the 30 days after noncardiac surgery, but most of these deaths occurred during the index hospitalization for surgery. The authors set out to describe outcomes after discharge from hospital up to 1 yr after inpatient noncardiac surgery and associations between predischarge complications and postdischarge death up to 1 yr after surgery. METHODS: This study was an analysis of patients discharged after inpatient noncardiac surgery in a large international prospective cohort study across 28 centers from 2007 to 2013 of patients aged 45 yr or older followed to 1 yr after surgery. The study estimated (1) the cumulative postdischarge incidence of death and other outcomes up to a year after surgery and (2) the adjusted time-varying associations between postdischarge death and predischarge complications including myocardial injury after noncardiac surgery, major bleeding, sepsis, infection without sepsis, stroke, congestive heart failure, clinically important atrial fibrillation or flutter, amputation, venous thromboembolism, and acute kidney injury managed with dialysis. RESULTS: Among 38,898 patients discharged after surgery, the cumulative 1-yr incidence was 5.8% (95% CI, 5.5 to 6.0%) for all-cause death and 24.7% (95% CI, 24.2 to 25.1%) for all-cause hospital readmission. Predischarge complications were associated with 33.7% (95% CI, 27.2 to 40.2%) of deaths up to 30 days after discharge and 15.0% (95% CI, 12.0 to 17.9%) up to 1 yr. Most of the association with death was due to myocardial injury after noncardiac surgery (15.6% [95% CI, 9.3 to 21.9%] of deaths within 30 days, 6.4% [95% CI, 4.1 to 8.7%] within 1 yr), major bleeding (15.0% [95% CI, 8.3 to 21.7%] within 30 days, 4.7% [95% CI, 2.2 to 7.2%] within 1 yr), and sepsis (5.4% [95% CI, 2.2 to 8.6%] within 30 days, 2.1% [95% CI, 1.0 to 3.1%] within 1 yr). CONCLUSIONS: One in 18 patients 45 yr old or older discharged after inpatient noncardiac surgery died within 1 yr, and one quarter were readmitted to the hospital. The risk of death associated with predischarge perioperative complications persists for weeks to months after discharge.

Efficacy of oral administration of specific immunoglobulins in preventing neonatal calf diarrhoea in dairy herds.

BACKGROUND: The aim of this study was to evaluate the efficacy of bovine concentrated lactoserum (BCL) containing specific immunoglobulin G against Escherichia coli, rotavirus and coronavirus in preventing neonatal calf diarrhoea (NCD). METHODS: A total of 489 newborn calves from 35 herds were orally given either BCL or a placebo before the first feeding of colostrum and clinically supervised by the farmers for the first 14 days of life. The diarrhoea score was defined according to the following criteria: 0 = no diarrhoea; 1 = light diarrhoea without medical treatment; 2 = diarrhoea requiring oral treatment (rehydration and/or antibiotic therapy); and 3 = severe diarrhoea requiring parenteral rehydration or resulting in death. RESULTS: A total of 138 calves suffered from diarrhoea (28%), and 65 (13%) showed signs of diarrhoea requiring treatment. The odds of getting NCD were reduced (odds ratio = 0.326; p < 0.001) in the BCL group. There was a tendency towards a reduction in the duration of NCD in the BCL group (2.25 (±1.7) days vs. 2.88 (±2.7) days in the placebo group) (p = 0.052). Furthermore, no calves died in the BCL group, whereas four calves died in the placebo group. LIMITATIONS: Because of the design of the study using animals in practice, the mechanisms explaining the clinical findings remain as hypotheses. Diarrhoea scoring performed by farmers has to be analysed and interpreted with caution. CONCLUSIONS: This study demonstrates that BCL as a single preventive treatment is effective in reducing the incidence of NCD even in a region with good general management of dairy calves and overall good colostrum quality.

Rivaroxaban Plus Aspirin Versus Aspirin Alone After Endovascular Revascularization for Symptomatic PAD: Insights From VOYAGER PAD.

BACKGROUND: Rivaroxaban plus aspirin compared with aspirin alone reduced major cardiac and ischemic limb events after lower extremity revascularization (LER) in the VOYAGER PAD (Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease) trial. The effect has not been described in patients undergoing endovascular LER. METHODS: The VOYAGER PAD trial randomized 6564 patients with symptomatic peripheral artery disease to a double-blinded treatment with 2.5 mg of rivaroxaban BID or matching placebo and 100 mg of aspirin daily. The primary efficacy outcome was a composite of acute limb ischemia, major amputation of a vascular pathogenesis, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety end point was Thrombolysis in Myocardial Infarction major bleeding. A prespecified subgroup of patients who underwent endovascular revascularization was included. RESULTS: Endovascular LER occurred in 4379 (66.7%) patients and surgical LER in 2185 (33.3%). Over a 3-year follow-up, rivaroxaban reduced the risk of the primary outcome by 15% (hazard ratio [HR], 0.85 [95% CI, 0.76-0.96]) with an absolute risk reduction of 0.92% at 6 months and 1.04% at 3 years and a consistent benefit in those receiving endovascular (HR, 0.89 [95% CI, 0.76-1.03]) or surgical LER (HR, 0.81 [95% CI, 0.67-0.98]; P interaction=0.43). For endovascular-treated patients, rivaroxaban reduced the risk of acute limb ischemia or major amputation of a vascular pathogenesis by 30% (HR, 0.70 [95% CI, 0.54-0.90]; P=0.005) with an absolute risk reduction of 1.0% at 6 months and 2.0% at 3 years compared with aspirin alone. Among endovascular-treated patients, the median duration of concomitant dual antiplatelet therapy with clopidogrel treatment was 31 days (interquartile range, 30-58). There was a consistent benefit for rivaroxaban regardless of background clopidogrel. Thrombolysis in Myocardial Infarction major bleeding was significantly higher for the rivaroxaban and aspirin group for the endovascular cohort (HR, 1.66 [95% CI, 1.06-2.59]) with an absolute risk increase of 0.9% at 3 years with no increase in intracranial or fatal bleeding observed (HR, 0.86 [95% CI, 0.40-1.87]; P=0.71). Mortality with rivaroxaban was higher in the endovascular-treated patients (HR, 1.24 [95% CI, 1.02-1.52]), although this finding was isolated to specific regions. CONCLUSIONS: Rivaroxaban added to aspirin or dual antiplatelet therapy after LER for peripheral artery disease reduces ischemic risk and increases major bleeding without an increased risk of intracranial or fatal bleeding. These benefits are consistent in those treated with endovascular and surgical approaches with significant benefits for major adverse limb events. These data support the use of rivaroxaban in addition to aspirin or dual antiplatelet therapy after endovascular intervention for symptomatic peripheral artery disease.