Lactatemia during treatment of status asthmaticus in children

Background: Transient increase of lactate levels with or without metabolic acidosis has been seldom reported as a complication of β2-adrenergic therapy administered during asthma attacks in children. Objective: The study is aimed to investigate the frequency of lactatemia in children with acute asthma treated with nebulized β2-agonists, and to delineate its causes and effects on prognosis. Methods: We studied 32 asthmatic children; 68.8% had intermittent asthma, and 31.2% had mild persistent asthma. Their ages ranged from 6 to 8 years with a mean of 6.48±0.68 years. Patients were enrolled during acute asthma exacerbation (62.5% had severe and 37.5% had moderate attacks)from the Cairo University Children's Hospital. Patients underwent clinical evaluation, and routine investigations (CBC, PEFR, and total serum IgE) then received nebulized salbutamol at 0.1 mg/kg/dose (minimum 2.5 mg) every 20 min for three doses together with O2. Plasma lactate was determined before, 1 h after, and 24 h following the inhalation therapy. Blood gases were also evaluated before and after the β2-agonist treatment. Results: At 1 h post-treatment, all patients had appreciable lactatemia (4.44±0.78 mmol/L, p < 0.001) compared to the pre-treatment level with a rise of 257±121.5%. Patients with severe attacks demonstrated a higher mean value compared to those with moderate attacks (4.69±0.8 mmol/L versus 4.02±0.6 mmol/L, p < 0.05). At 24 h post-treatment, lactate levels returned to the normal values in most patients (1.91±0.59 mmol/L, p < 0.001) as compared to the 1 h post-treatment level. None of our patients developed metabolic acidosis and all of them showed significant clinical improvement. Our results strongly accuse nebulized salbutamol as the possible pathogenetic factor for lactatemia during therapy of acute asthma attacks, while overworked respiratory muscles and hypoxemia have been excluded as contributing factors. Conclusion: Transient lactatemia is not uncommon during β2-agonist therapy in asthmatic children with acute exacerbation, and is harmless in most cases. Prediction of lactic acidosis prevents inappropriate intensification of therapy especially in patients with more severe attacks or impending respiratory failure.Keywords: Asthma, exacerbation, lactate, lactatemia, β2-agonist, salbutamolEgypt J Pediatr Allergy Immunol 2004; 2(2): 83-8

Association of macrophage migration inhibitory factor promoter polymorphism -173G/C with susceptibility to childhood asthma

Abstract Introduction: macrophage migration inhibitory factor (miF) is a proinflammatory cytokine that plays an important role in the pathogenesis of asthma. Polymorphisms associated with inflammatory diseases exist in the promoter region of miF, which alter its expression. We aimed to study the association of MIF promoter polymorphism -173G/C with childhood asthma. (p = 0.019, OR = 3.12,. Material and methods: in this case-control study, we recruited 60 pediatric patients with bronchial asthma and 90 age-and sex-matched healthy controls. MIF-173G/C was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCr-rFlP). Results: Genotype distribution between cases and healthy controls was statistically evaluated. Our results revealed that the frequency of the MIF-173C allele was significantly higher in children with asthma than in the control group (p = 0.002, odds ratio [OR] = 3.61, 95% confidence interval [CI] = 1.63-7.97). The frequency of the MIF-173CC genotype was higher in the asthmatic children than in the controls (p = 0.028, OR = 6.24, 95% CI = 1.24-31.29). Comparing carriage of the MIF-173C allele in pediatric patients with asthma with that observed in healthy controls (GC + CC vs. GG) revealed a positive association with the disease Conclusions: These results suggest that MIF-173G/C polymorphism confers an increased risk of susceptibility to the development of childhood asthma in an Egyptian population

Demographics of dogs, cats, and rabbits attending veterinary practices in Great Britain as recorded in their electronic health records

Abstract Background Understanding the distribution and determinants of disease in animal populations must be underpinned by knowledge of animal demographics. For companion animals, these data have been difficult to collect because of the distributed nature of the companion animal veterinary industry. Here we describe key demographic features of a large veterinary-visiting pet population in Great Britain as recorded in electronic health records, and explore the association between a range of animal’s characteristics and socioeconomic factors. Results Electronic health records were captured by the Small Animal Veterinary Surveillance Network (SAVSNET), from 143 practices (329 sites) in Great Britain. Mixed logistic regression models were used to assess the association between socioeconomic factors and species and breed ownership, and preventative health care interventions. Dogs made up 64.8% of the veterinary-visiting population, with cats, rabbits and other species making up 30.3, 2.0 and 1.6% respectively. Compared to cats, dogs and rabbits were more likely to be purebred and younger. Neutering was more common in cats (77.0%) compared to dogs (57.1%) and rabbits (45.8%). The insurance and microchipping relative frequency was highest in dogs (27.9 and 53.1%, respectively). Dogs in the veterinary-visiting population belonging to owners living in least-deprived areas of Great Britain were more likely to be purebred, neutered, insured and microchipped. The same association was found for cats in England and for certain parameters in Wales and Scotland. Conclusions The differences we observed within these populations are likely to impact on the clinical diseases observed within individual veterinary practices that care for them. Based on this descriptive study, there is an indication that the population structures of companion animals co-vary with human and environmental factors such as the predicted socioeconomic level linked to the owner’s address. This ‘co-demographic’ information suggests that further studies of the relationship between human demographics and pet ownership are warranted

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men