Early Administration Research Articles

P077 The Yorkshire Bone Network- why every region needs a Bone Network!

Abstract Background/Aims The Yorkshire Bone Network (YBN) was formalised in 2019, from a founding group of Yorkshire clinicians with a special interest in osteoporosis, meeting every four months since 1994 to discuss new drugs as they were licensed, the research underpinning them, complex clinical cases and educational topics in osteoporosis. This group was formalised into a Network in order to expand the membership and invite contributions from an increased range of specialists from different disciplines and Trusts across Yorkshire. Further aims were to reach consensus on the management of key osteoporosis issues across Yorkshire and deliver Regional guidelines. Methods The YBN now has 35 members from Rheumatology, Endocrinology, Metabolic Bone and Elderly Medicine departments from 12 different Trusts across Yorkshire. Meetings are four-monthly, continuing on Zoom during the pandemic, and now in-person again. Each meeting involves discussion of complex clinical osteoporosis cases for management decisions, alongside an educational or guidelines development session, delivered by a member of the Network or an invited guest speaker. Results We have: Agreed a consensus statement on the use of Romosozumab in Yorkshire, specifically covering cardiovascular screening for potential patients. This has given clinicians confidence in identifying appropriate patients and prescribing this new drug. This should also ensure equity of drug access to patients across the region, who are being assessed using the same framework. We have written guidelines on the role of bone densitometry in patients with coeliac disease. This has been provided to local Gastroenterologists, with the aim of reducing unnecessary bone densitometry referrals, reducing the burden on patients and radiology departments. We have provided regional recommendations for the early (before 14 days) administration of IV zoledronate for inpatients post fractured neck of femur, avoiding discharge prior to treatment. This has been adopted and is being audited to assess impact in one of our District General Hospitals. We have provided educational sessions on bone turnover markers, FRAXPlus, glucocorticoid-induced osteoporosis and renal bone disease. Conclusion The Yorkshire Bone Network is an excellent example of collaborative working. It is a valuable forum for clinical decision making for complex patients across the region. It has allowed the development of guidelines and consensus statements which are in clinical use, thus minimising variation in patient care across the region and improving clinician confidence. It continues to be an enjoyable way of forming new links between colleagues both within our own Trusts and across the region, with new members joining each year. Time is needed to co-ordinate the meetings, provide minutes and liaise with colleagues but the benefits far outweigh the effort! We would strongly recommend the formation of similar networks across the UK, given the benefits to both patients and clinicians. Disclosure C.Y.J. Vandevelde: None. S. Sultan: None. L. Hordon: None.

Skeletal consequences of preterm birth in pigs as a model for preterm infants.

Preterm birth affects about 10% of all live births with many resultant health challenges, including metabolic bone disease of prematurity (MBDP), which is characterized by elevated alkaline phosphatase, suppressed phosphate, and deficient skeletal development. Because of the lack of an animal model, very little is known about bone structure, strength, and quality after preterm birth. This study investigated the utility of a pig model to replicate clinical features of preterm birth, including MBDP, and sought to determine if early postnatal administration of IGF-1 was an effective treatment. Preterm pigs, born by caesarean section at 90% gestation, were reared in intensive care facilities (respiratory, thermoregulatory, and nutritional support) and compared with sow-reared term pigs born vaginally. Preterm pigs were systemically treated with vehicle or IGF-1 (recombinant human IGF-1/BP-3, 2.25mg/kg/d). Tissues were collected at postnatal days 1, 5, and 19 (the normal weaning period in pigs). Most bone-related outcomes were affected by preterm birth throughout the study period, whereas IGF-1 supplementation had almost no effect. By day 19, alkaline phosphatase was elevated, phosphate and calcium were reduced, and the bone resorption marker C-terminal crosslinks of type I collagen was elevated in preterm pigs compared to term pigs. Preterm pigs also had decrements in femoral cortical cross-sectional properties, consistent with reduced whole-bone strength. Thus, the preterm pig model replicates many features of preterm bone development in infants, including features of MBDP, and allows for direct interrogation of skeletal tissues, enhancing the field's ability to examine underlying mechanisms.

Time Savings and Safety of EMS Administration of Antibiotics for Open Fractures

ABSTRACT Introduction Early administration of antibiotics for open fractures reduces serious bone and soft tissue infections. The effectiveness of antibiotics in reducing these infections is time-dependent, with various surgical associations recommending administration within one hour of injury, or within one hour of patient arrival to the emergency department (ED). The extent to which prehospital antibiotic administration in these situations might reduce the time to treatment has not been previously reported. The purpose of this study was to describe current prehospital use of antibiotics for traumatic injury, to assess the safety of prehospital antibiotic administration, and to estimate the potential time-savings associated with antibiotic administration by EMS clinicians. Methods This was a retrospective analysis of the 2019 through 2022 ESO Data Collaborative research data set. Included subjects were patients that had a linked ICD-10 code indicating an open extremity fracture and who received prehospital antibiotics. Time to antibiotic administration was calculated as the elapsed time from EMS dispatch until antibiotic administration. The minimum potential time saved by EMS antibiotic administration was calculated as the elapsed time from administration until ED arrival. To assess safety, epinephrine and diphenhydramine administration were used as proxies for the adverse events of anaphylaxis and minor allergic reactions. Results There were 523 patients meeting the inclusion criteria. The median (and interquartile range [IQR]) elapsed time from EMS dispatch until antibiotic administration was 31 (IQR: 24-41) minutes. The median potential time savings associated with prehospital antibiotic administration was 15 (IQR: 8-22) minutes. Notably, 144 (27.5%) of the patients who received prehospital antibiotics had total prehospital times exceeding one hour. None of the patients who received antibiotics also received epinephrine for presumed anaphylaxis. Conclusions EMS clinicians were able to safely administer antibiotics to patients with open fractures a median of 15 minutes before arrival at the hospital, and 99 percent of the patients receiving antibiotics had them administered within one hour of EMS dispatch. EMS administration of antibiotics may be a safe way to increase compliance with recommendations for early antibiotic administration for open fractures.

DO ORTHOPAEDIC TRAUMA SOCIETY (OTS) SIMPLE FRACTURES RECEIVE A DIFFERENT STANDARD OF TREATMENT TO OTS COMPLEX FRACTURES?

IntroductionOpen fractures of the tibia are disabling injuries with a significant risk of deep infection. Treatment involves early antibiotic administration, early and aggressive surgical debridement, and may require complex soft tissue coverage techniques. The extent of disruption to the skin and soft-tissue envelope often varies, with ‘simple’ open fractures (defined by the Orthopaedic Trauma Society (OTS) open fracture severity classification) able to be closed primarily, whilst others may require shortening or soft-tissue reconstruction. This study aimed to determine whether OTS simple tibial open fractures received different rates of adequate debridement and plastic surgical presence at initial debridement, compared with OTS complex injuries, and whether rates of fracture-related infection, nonunion, or reoperation differed between the groups.Materials & MethodsA consecutive series of open tibia fractures managed at a tertiary UK Major Trauma Centre between January 2021 and November 2022 were included. Patient demographics, injury characteristics, timing of antibiotic delivery, timing and method of definitive fixation, and frequency of plastic surgical presence at initial debridement were retrospectively collected. The delivery of bone ends at initial debridement was used as a proxy for adequacy of surgical debridement. The primary outcome measure was rate of fracture-related infection, secondary outcomes included rates of reoperation, nonunion, and amputation. Chi2 Tests and independent samples T-tests were used to assess nominal and continuous outcomes respectively between simple and complex injuries. Ordinal data was assessed using nonparametric equivalent tests.Results79 patients with open fractures of the tibia were included. 70.8% of patients were male, with mean age 50.4 years (SD 19.2) and BMI 26.4 Kg/m2 (SD 6.0). Injuries were mostly sustained by low-energy falls (n = 28, 35.4%) and from road traffic accidents (n = 26, 32.9%). 27 (34.2%) were OTS simple open fractures. Simple open fractures were most commonly Gustillo-Anderson grade 1 (38.5%), or 2 (30.8%), whilst complex open fractures were mostly grade 3B (66.7%) (p < 0.001). Fracture-related infection rates in OTS simple and complex open fractures were 25.9% and 25.5% respectively (p = 0.967), and nonunion rates were 32% and 37.8% (p = 0.637). Primary amputation was less common in simple (0%) than in complex open fractures (20%, p = 0.012), there were no differences in delayed amputation rates (7.4% and 6% respectively, p = 0.811). Simple open fractures were less likely to have plastic surgeons present at initial debridement compared to complex open fractures (18.5% and 44%, p = 0.025), and less likely to have bone ends delivered through the skin at initial debridement (25.9% and 61.2%, p = 0.003). There were no differences in patient age, delays to antibiotic administration, or reoperation rates between OTS simple and OTS complex fractures (p > 0.05).ConclusionsDespite involving less significant soft tissue injury, OTS simple open tibia fractures had comparable deep infection and nonunion rates to complex fractures and received early plastic surgical input and adequate debridement less frequently. The severity of open fractures with less significant soft tissue injury may be underrecognized and therefore undertreated, although further prospective study is needed.

CINCA/NOMID is a rare autoinflammatory syndrome in rheumatological practice. Experience of diagnosis, management and therapy with interleukin-1 inhibitors

Objective: to present the experience of diagnosis, management and therapy with interleukin-1 inhibitors (iIL1) in patients with Chronic Infantile Onset Neurologic Cutaneous Articular/Neonatal Onset Multisystem Inflammatory Disease (CINCA/NOMID) according to the Russian Federal Rheumatological Center data.Material and methods. From 2007 to 2023, eight patients were included in the study (7 men) aged 10 months to 33 years, including 3 with a disease duration of more than 10 years (13, 17 and 33 years). Genetic testing was performed in all patients and mutations in the NLRP3 gene were identified in 6 cases.Results and discussion. The age of onset of the disease ranged from 0 to 6 months. The delay in diagnosis and prescription of therapy ranged from 10 months to 33 years. All patients had the classic manifestations of CINCA/NOMID, including fever, rash, central nervous system (CNS) involvement, elevated ESR and CRP levels, 6 patients had articular manifestations, 7 had ocular manifestations and 6 had sensorineural hearing loss. Amyloidosis was detected in 1 case. All patients were prescribed iIL1. Anakinra was used in 6 patients (in 5 as the first line, in 1 as the second line therapy) with a positive response; subsequently 2 of these patients were switched to canakinumab once every 4 weeks (1 patient deteriorated and was readministered anakinra). Five patients received canakinumab (3 as first-line therapy, 2 as second-line therapy), 1 patient was switched to anakinra due to insufficient CNS response. The response to iIL1 therapy was positive in all patients, but incomplete in some of them due to the severity of the manifestations and the presence of irreversible organ damage.Conclusion. Patients with CINCA/NOMID have a severe disease and a poor prognosis. In this context, early administration of iIL1 is necessary. In the case of CNS involvement, the use of anakinra is preferable, as it is characterized by better penetration of the blood-brain barrier and is therefore more effective. Later it is possible to switch the patient to canakinumab, however, to achieve a complete response, it is sometimes necessary to increase the dose of the drug and reduce the interval between doses.

A Systematic Review and Meta-Analysis of the Timing of Vasopressor Therapy in Patients with Septic Shock: Assessing Clinical Outcomes and Implication

Background Septic shock, is associated with a high mortality rate and increased expenses. Currently, the first-line therapy for septic shock entails administering resuscitation fluids followed by infusing vasopressors when the blood pressure goal is not achieved. The recommended first-line vasopressor is norepinephrine, followed by vasopressin, epinephrine, angiotensin II, and dopamine. There is still a controversy on when each vasopressor should be administered. Therefore, we conducted this review to determine the impact and implications of vasopressor timing in septic shock patients. Methods PubMed, Medline, Cochrane Library, Web of Science, and Google Scholar databases were comprehensively searched for potential studies until October 2023. The methodological quality and bias assessment of valid records was examined with the Newcastle Ottawa Scale and Cochrane’s risk of bias tool. Additionally, all the meta-analyses were performed with Review Manager software. Results Twelve articles were eligible for review and analysis. Pooled analyses of data from 7 of these studies demonstrated lower incidence of mortality and shorter duration to achieve target mean arterial pressure in the early vs. late epinephrine groups (OR:0.44; 95%CI: 0.35–0.55; p<0.00001 and MD:-1.17; 95%CI:-2.00– -0.34; p=0.0006). However, the length of ICU stay didn’t differ between the early and late norepinephrine group (MD:0.55; 95%CI: -0.52–1.62; p=0.31). The subgroup analyses show that early vasopressin is associated with a decreased mortality than late administration (OR:0.60; 95%CI:0.41–0.90; p=0.01). Similarly, the pooled analysis has shown that early concomitant administration of vasopressin and norepinephrine is associated with a shorter duration to achieve target MAP than norepinephrine alone (MD:-3.15; 95%CI:-4.40– -1.90;p<0.00001). Conclusion Early administration of norepinephrine has a mortality benefit and improves the duration taken to attain and sustain the goal MAP. Furthermore, early vasopressin possesses the potential to lower the fatality rate in individuals experiencing septic shock. However, further research is required to validate this finding.

Pilot Study on the Impact of Early Subcutaneous Basal Insulin Administration in Diabetic Ketoacidosis.

Purpose/Background: Recent studies have shown improved outcomes with the initiation of earlier subcutaneous (SQ) basal insulin. The purpose of this study was to examine the effects of early SQ basal insulin administration on hospital length of stay in patients with mild to moderate diabetic ketoacidosis (DKA). Methods: This was a retrospective, single-center study from a large community teaching hospital that included patients 18 years or older with mild to moderate DKA, identified using ICD-10 codes, who received intravenous (IV) insulin. Patients who received SQ basal insulin prior to a documented anion gap ≤12 mmol/L were considered to have received early SQ basal insulin and were compared to patients who received SQ basal insulin after closure of their anion gap (AG). The primary outcome was hospital length of stay. Secondary outcomes included intensive care unit length of stay, duration of IV insulin, time to anion gap closure, and incidences of rebound hyperglycemia. Safety outcomes included incidences of hypoglycemia, and hypokalemia. Results: Of 301 patients screened, 108 patients were included in the final analysis. Forty patients received early SQ basal insulin and 68 did not. Median hospital length of stay in the nonearly group was 71 h, compared to 62 h in the early group (P = .57). Secondary and safety outcomes were similar between groups. Conclusions: In this study, there was no statistically significant difference in length of stay in patients that received early SQ basal insulin. Larger trials are needed to determine the significance of earlier SQ basal insulin in DKA.

Attenuating mitochondrial dysfunction and morphological disruption with PT320 delays dopamine degeneration in MitoPark mice

BackgroundMitochondria are essential organelles involved in cellular energy production. Changes in mitochondrial function can lead to dysfunction and cell death in aging and age-related disorders. Recent research suggests that mitochondrial dysfunction is closely linked to neurodegenerative diseases. Glucagon-like peptide-1 receptor (GLP-1R) agonist has gained interest as a potential treatment for Parkinson's disease (PD). However, the exact mechanisms responsible for the therapeutic effects of GLP-1R-related agonists are not yet fully understood.MethodsIn this study, we explores the effects of early treatment with PT320, a sustained release formulation of the GLP-1R agonist Exenatide, on mitochondrial functions and morphology in a progressive PD mouse model, the MitoPark (MP) mouse.ResultsOur findings demonstrate that administration of a clinically translatable dose of PT320 ameliorates the reduction in tyrosine hydroxylase expression, lowers reactive oxygen species (ROS) levels, and inhibits mitochondrial cytochrome c release during nigrostriatal dopaminergic denervation in MP mice. PT320 treatment significantly preserved mitochondrial function and morphology but did not influence the reduction in mitochondria numbers during PD progression in MP mice. Genetic analysis indicated that the cytoprotective effect of PT320 is attributed to a reduction in the expression of mitochondrial fission protein 1 (Fis1) and an increase in the expression of optic atrophy type 1 (Opa1), which is known to play a role in maintaining mitochondrial homeostasis and decreasing cytochrome c release through remodeling of the cristae.ConclusionOur findings suggest that the early administration of PT320 shows potential as a neuroprotective treatment for PD, as it can preserve mitochondrial function. Through enhancing mitochondrial health by regulating Opa1 and Fis1, PT320 presents a new neuroprotective therapy in PD.Graphical

Early intravenous hydrocortisone in sepsis: A randomized control trial (Protocol)

Background: The evidence of the appropriate timing of hydrocortisone is still weak and controversial. Observational studies showed a trend towards greater benefits when hydrocortisone was given earlier in the course of septic shock resuscitation. This study evaluates the effects of early intravenous low-dose hydrocortisone administered at the beginning of the onset of sepsis-induced hypotension compared with standard care. Methods: This study is a single-center, parallel-group, double-blinded, randomized control trial, conducted in a non-trauma emergency department. Adult patients with sepsis-induced hypotension will be included. Patients will be randomly assigned in a 1:1 ratio to receive early intravenous low-dose hydrocortisone or standard care. Blood inflammatory biomarkers at baseline will be collected. The primary outcome is 28-day mortality. Resuscitation-related secondary outcomes and safety outcomes will also be observed. Outcomes will be compared between groups. Subgroup analyses considering inflammatory biomarker levels will also be performed to evaluate the effect of early intravenous hydrocortisone, especially in patients with hyperinflammation. Hypothesis: We hypothesize that early intravenous low-dose hydrocortisone administration in patients with sepsis-induced hypotension would result in less mortality and improve resuscitation outcomes, especially in subgroup of patients with hyperinflammation. Ethics and dissemination: The study protocol was approved by the Siriraj Institutional Review Board with the certificate of approval number Si 917/2023. Trial registration: Clinicaltrial.gov NCT06217939

An observational study on the impact of overcrowding towards door-to-antibiotic time among sepsis patients presented to emergency department of a tertiary academic hospital

BackgroundThe latest Surviving Sepsis Campaign 2021 recommends early antibiotics administration. However, Emergency Department (ED) overcrowding can delay sepsis management. This study aimed to determine the effect of ED overcrowding towards the management and outcome of sepsis patients presented to ED.MethodsThis was an observational study conducted among sepsis patients presented to ED of a tertiary university hospital from 18th January 2021 until 28th February 2021. ED overcrowding status was determined using the National Emergency Department Overcrowding Score (NEDOCS) scoring system. Sepsis patients were identified using Sequential Organ Failure Assessment (SOFA) scores and their door-to-antibiotic time (DTA) were recorded. Patient outcomes were hospital length of stay (LOS) and in-hospital mortality. Statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 26. P-value of less than 0.05 for a two-sided test was considered statistically significant.ResultsTotal of 170 patients were recruited. Among them, 33 patients presented with septic shock and only 15% (n = 5) received antibiotics within one hour. Of 137 sepsis patients without shock, 58.4% (n = 80) received antibiotics within three hours. We found no significant association between ED overcrowding with DTA time (p = 0.989) and LOS (p = 0.403). However, in-hospital mortality increased two times during overcrowded ED (95% CI 1–4; p = 0.041).ConclusionED overcrowding has no significant impact on DTA and LOS which are crucial indicators of sepsis care quality but it increases overall mortality outcome. Further research is needed to explore other factors such as lack of resources, delay in initiating fluid resuscitation or vasopressor so as to improve sepsis patient care during ED overcrowding.

Door-to-Diuretic Time and Short-Term Outcomes in Acute Heart Failure. A Systematic Review and Meta-Analysis.

Acute heart failure (AHF) is a leading cause of unplanned hospitalization often associated with poor outcomes. Decongestion with intravenous loop diuretics is the mainstay of treatment. Metrics such as door-to-diuretic time, the time between presentation of AHF to the hospital and administration of intravenous diuretics, may play an important role in faster decongestion and thereby reduce mortality. We sought to investigate whether early diuretic administration (door-to-diuretic [D2D] time 60≤mins) was associated with improved outcomes among hospitalized HF patients. A systematic search of PubMed and Scopus databases was performed from inception until June, 2023. The primary endpoints were all cause in hospital and 30-day mortality. Secondary endpoints were length of hospital stay and heart failure readmission. We used a random-effects model to calculate odds ratios (OR) for binary outcomes and mean differences (MD) for continuous data. Our meta-analysis included 6 observational studies involving 19,916 patients. No significant differences (p>0.05) were observed between shorter D2D and delayed D2D time with respect to in-hospital mortality (OR: 0.62; 95% CI: 0.35-1.09), 30-day mortality (OR: 0.83; 95% CI: 0.51-1.33; P=0.44), length of hospital stay (MD: -0.02; 95% CI: -0.26 to 0.22) and HF readmission (OR: 1.00; 95% CI: 0.86-1.20). Evidence from existing literature, which is largely limited to observational comparisons, highlights comparable outcomes between the two treatment strategies. Early diuretic administration, particularly within 60 minutes of hospital presentation, does not demonstrate any prognostic benefits.

Efficacy of delayed pegfilgrastim administration following consolidation therapy with high-dose cytarabine (HiDAC) in acute myeloid leukemia (AML) patients.

To study the effects of delaying pegfilgrastim administration following high-dose cytarabine (HiDAC) consolidation in AML patients on time to neutrophil count recovery, infectious complications, and survival. Single-center retrospective chart review of 55 patients receiving pegfilgrastim as early administration (within 72h) or delayed administration (after 72h) of HiDAC. The difference in neutrophil recovery time was similar between the early and delayed groups (18days versus 19days, p < 0.28). Infections were seen in four patients in the early administration group following chemotherapy compared to none in the delayed group (p = 0.04). Febrile neutropenia rates were also decreased in the delayed administration group (23.1% versus 10.3%, p = 0.28) as well as a trend towards longer median survival (16months versus 19months, p = 0.69) and overall survival (21months versus 31months, p = 0.47). A difference in time to neutrophil recovery was not observed between the early and delayed administration groups yet decreased infectious complications may support the delayed administration of pegfilgrastim in these patients.

Effect of Early Cyclosporine Treatment on Survival in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

Early cyclosporine administration is a potentially useful treatment in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). However, previous studies have reported conflicting results regarding the survival benefits. Therefore, in this study, we evaluated the survival of patients with SJS/TEN according to whether they received early cyclosporine administration. This retrospective cohort study was conducted using a Japanese national administrative claims database. Data on patients admitted to the hospital with SJS/TEN between April 1, 2016, and March 31, 2021, were extracted. Patients with missing data, those discharged within two days of admission, pregnant women, and children aged <16 years were excluded. Patients who received cyclosporine on the day of admission (early cyclosporine group) were compared with those who did not (comparison group). The primary endpoint was in-hospital mortality. Secondary endpoints were 30- and 50-day mortality and length of hospital stay. The effect of early cyclosporine treatment was evaluated after baseline adjustment using doubly robust estimation. Among 3807 enrolled patients (mean age, 65.5 years; 53.8% women), the early cyclosporine and comparison groups included 115 and 3692 patients, respectively. After adjustment, cyclosporine treatment decreased in-hospital mortality by 6.03% (95% confidence interval (CI), 5.27-6.82%), 30-day mortality by 2.94% (95% CI, 2.43-3.50%), and 50-day mortality by 4.38% (95% CI, 3.70-5.04%), but increased the length of hospital stay by 9.45 days (95% CI, 1.00-20.23 days). Early cyclosporine administration can improve the survival of patients with SJS/TEN but is associated with a longer hospital stay.

Gastrointestinal response to the early administration of antimicrobial agents in growing turkeys infected with Escherichia coli

This study investigated the effects of the early administration of enrofloxacin (E) or doxycycline (D) for the first 5 consecutive days of life, or the continuous administration of the coccidiostat monensin (M) throughout the rearing period on gastrointestinal function in turkeys infected with avian pathogenic Escherichia coli (APEC) in an early or later stage of rearing. Experiment 1 lasted 21 d, and turkeys in groups E, D, and M were infected with APEC on d 15. Experiment 2 lasted 56 d, and it had a factorial arrangement of treatments where birds in groups E, D, and M were infected with APEC on d 15 or d 50. In both experiments, control groups (C) consisted of infected and uninfected birds without antibiotic or coccidiostat administration. On d 21 (Experiment 1) and d 56 (Experiment 2), 8 birds from each subgroup were killed, and the ileal and cecal digesta were sampled to analyze the activity of bacterial enzymes and the concentrations of short-chain fatty acids (SCFA). The experimental treatments did not affect the final body weight or body weight gain of birds. Both experiments demonstrated that APEC contributed to an increase in ammonia levels of the cecal digesta (means from 2 experiments: 0.311 vs. 0.225 mg/g in uninfected birds) and ileal pH (6.79 vs. 6.00) and viscosity (2.43 vs. 1.83 mPa⋅s). Moreover, the E. coli challenge enhanced the extracellular activity of several cecal bacterial enzymes, especially in older turkeys infected with APEC in a later stage of life. The continuous administration of monensin throughout the rearing period resulted in a weaker gastrointestinal response in older birds, compared with the other 2 antibiotics administered for the first 5 d of life. The results of the study are inconclusive as both desirable and undesirable effects of preventive early short-term antibiotic therapy were observed in turkeys, including normalization of ileal viscosity and cecal ammonia concentration (positive effect), and disruption in cecal SCFA production (negative effect).

IJCM_19A: Aspirin delays the onset of hypertensive disorders of pregnancy among nulliparous pregnant women: a secondary analysis of the ASPIRIN Trial

Background: Hypertensive disorders of pregnancy (HDP) remain a primary contributor for maternal and perinatal death and results in long-term health risks for both the mother and child. Heterogeneous studies have evaluated the possible benefit of low dose aspirin (50 to 150 mg per day) in pregnancy to minimize the risk of HDP. Objective: To assess the impact of low-dose Aspirin (LDA) starting in early pregnancy on delaying preterm hypertensive disorders of pregnancy. Methodology: This was a non-prespecified secondary analysis of a randomized masked trial of Low-dose Aspirin (LDA). Nulliparous singleton pregnancies between 6 weeks and 0 days and 13 weeks 6 days in 6 low- middle income countries (Democratic Republic of Congo, Guatemala, India, Kenya, Pakistan, Zambia) enrolled in the ASPIRIN Trial were included. The incidence of HDP at delivery at three gestational age periods (&lt; 37 weeks) between women who were randomized to Aspirin or Placebo. Women were included if they were randomized and had an outcome at or beyond 20 weeks (Modified Intent to Treat). Results: Amongst the 11,976 pregnancies, LDA did not significantly lower HDP at delivery. Conclusion: In low-risk nulliparous singleton pregnancies, early administration of LDA resulted in lower rates of preterm HDP and delivery before 34 and 37 weeks. LDA works in part by delaying HDP.

Early administration of canine parvovirus monoclonal antibody prevented mortality after experimental challenge.

To evaluate the effectiveness of canine parvovirus monoclonal antibody (CPMA) as a treatment against canine parvovirus (CPV-2)-induced mortality and to support USDA product licensure. 28 purpose-bred Beagle dogs aged 8 weeks were randomized to the treated (n = 21) or control (7) group. Dogs were challenged intranasally with 104.2 TCID50 virulent CPV-2b on Day 0 and monitored for 14 days for fecal viral shed and clinical disease. All dogs began shedding CPV-2 on Day 4 and were treated intravenously with a single dose of either CPMA (0.2 mL/kg) or saline (equal volume). No additional treatments were given to either group. Feces and sera were collected for quantitative analysis of fecal viral shed (hemagglutination) and antibody responses (hemagglutination inhibition and dot-blot ELISA), respectively. Dogs were monitored twice daily for parameters including lymphopenia, fever, vomiting, abnormal feces, inappetence, and lethargy. Humane endpoints triggered euthanasia by a veterinarian masked to treatment groups. The primary outcome variable was prevention of mortality as compared to controls. Mortality was prevented in all CPMA-treated dogs compared to 57% mortality in the control group (P = .0017, Fisher exact test). Canine parvovirus monoclonal antibody-treated dogs also experienced less severe and/or shorter durations of diarrhea, fever, vomiting, CPV-2 shedding in feces, and lymphopenia. Both groups showed similar immunoglobulin M responses as measured by semiquantitative analysis. Intravenous administration of CPMA can effectively improve clinical outcome when administered early in CPV-2 disease. Canine parvovirus monoclonal antibody treatment after proven infection does not interfere with adaptive immunity.

Inpatient treatment modalities of coronavirus disease 2019 in the Egyptian population: A bi-center retrospective observational study.

Many protocols for the treatment of coronavirus disease 2019 (COVID-19) have been published. In addition to an abundance of studies and meta-analyses on the treatment of COVID-19, different medications used in the intensive care unit will have a significant impact on mortality. The study attempted to highlight, compare, and quantify the impact on outcomes. Data were collected from subjects' files, encompassing all physiological parameters, hematological profiles, and available laboratory results. In addition, all treatment modalities administered to the subjects were documented in medical files. Survival analysis was conducted using Kaplan-Meier curves and Cox proportional hazards. The study included 120 subjects with confirmed COVID-19. Subjects treated with systemic corticosteroids (hazard Ratio [HR 0.45, 95% Confidence Interval [CI] 0.01-1.32; P = 0.01) and tocilizumab (HR 0.98, 95% CI 0.49-1.98; P = 0.05) exhibited lower mortality, while those treated with remdesivir (HR 1.13, 95% CI 0.53-2.43; P = 0.05) showed increased mortality. In patients with COVID-19, improved mortality was observed with early rather than late treatment with noninvasive mechanical ventilation (NIV) (HR 0.01 vs. 1.72, P = 0.05) and tocilizumab (HR 0.45 vs. 1.50, P = 0.05). The early use of NIV is associated with decreased mortality compared to late use. Corticosteroids demonstrate a mortality-reducing effect. In addition, early administration of tocilizumab is associated with decreased mortality compared to late use.

Impact of early levosimendan administration in patients with decompensated chronic heart failure on oxidative stress parameters — the rationale and study design

Impact of early levosimendan administration in patients with decompensated chronic heart failure on oxidative stress parameters — the rationale and study design

Cat bite injuries to the hand and forearm: the impact of antibiotic treatment on microbiological findings and clinical outcome

IntroductionPatients and physicians often underestimate cat bite injuries. The deep and narrow wound seals quickly and provides an environment for the inoculated saliva and bacteria. Interestingly, the literature reports no bacterial growth in the microbiological workup of wound swaps in up to 43%. The time between bite injury and the first clinical presentation, the start of antibiotic treatment and surgical debridement might affect these findings. Therefore, the current project examines if (1) these factors impact the outcome of microbiological results following cat bite injuries and (2) the detection of bacterial growth leads to higher complication rates, longer hospital stays, longer total treatment time, or higher total treatment costs.Materials and methodsThis single-center retrospective study analyzed data from 102 adult patients. All patients received antibiotic and surgical treatment following a cat bite injury. Microbiological samples were collected during surgery in all cases. The time from the bite incident to the first presentation, beginning of antibiotic administration, and surgical debridement was calculated. Demographic data, complication rate, length of hospital stay, total treatment time, and total treatment costs were recorded. (1) A generalized linear model was fitted using the microbiological outcome as the dependent variable. (2) Two groups (negative or positive microbiological results) were formed and statistically compared.ResultsThe median age was 50 (SD 16), and 72% were female. (1) The time from the bite incident to the first clinical presentation, antibiotic administration, or surgical treatment was not associated with the outcome of the microbiological result. (2) No significant differences were observed between the two groups.ConclusionsOur data do not suggest that early antibiotic administration or delayed surgical treatment affects the outcome of the microbiological workup following cat bite injuries to the hand and forearm. The microbiological outcome did not affect the complication rate, treatment time, and total treatment costs.

Efficacy of different doses of corticosteroids in treating severe COVID-19 pneumonia

BackgroundTo investigate the efficacy of different doses of corticosteroids in treating severe coronavirus disease 2019 (COVID-19) pneumonia.MethodsBetween May 01, 2023, and June 20, 2023, 48 patients with severe COVID-19 pneumonia were treated at the Department of Respiratory and Critical Care Medicine of Jinan Fourth People's Hospital. The observation group (21 patients) received standard care and high-dose corticosteroids, (high-dose group). The control group (27 patients) received standard care and low-dose corticosteroids (low-dose group). We collected baseline data and recorded inflammatory marker levels after 3 days of treatment, body temperature recovery time, length of stay, and 28-day all-cause mortality. The results of outpatient follow-up were recorded after 1 month.ResultsThere were no significant differences in 28-day mortality and length of stay. The number of days it took for body temperature to return to normal in the high-dose group was less than in the low-dose group. The high-dose group had significantly more reduced inflammatory factors (C-reactive protein (CRP), interleukin-6 (IL-6). A total of 20 discharged patients were given 8–16 mg of methylprednisolone, depending on chest computed tomography (CT) and clinical symptoms after 1 month; in all discharged patients using oral corticosteroids, CT features improved.ConclusionHigh-dose corticosteroids had a significantly positive effect on the reduction of inflammatory factors and shortening body temperature recovery time. In the treatment of severe COVID-19 pneumonia, early administration of high-dose, short-course corticosteroids should be implemented.