Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 8.328
Filter
1.
Stroke Vasc Neurol ; 7(2): 158-165, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1832554

ABSTRACT

RATIONALE: Haematoma growth is common early after intracerebral haemorrhage (ICH), and is a key determinant of outcome. Tranexamic acid, a widely available antifibrinolytic agent with an excellent safety profile, may reduce haematoma growth. METHODS AND DESIGN: Stopping intracerebral haemorrhage with tranexamic acid for hyperacute onset presentation including mobile stroke units (STOP-MSU) is a phase II double-blind, randomised, placebo-controlled, multicentre, international investigator-led clinical trial, conducted within the estimand statistical framework. HYPOTHESIS: In patients with spontaneous ICH, treatment with tranexamic acid within 2 hours of onset will reduce haematoma expansion compared with placebo. SAMPLE SIZE ESTIMATES: A sample size of 180 patients (90 in each arm) would be required to detect an absolute difference in the primary outcome of 20% (placebo 39% vs treatment 19%) under a two-tailed significance level of 0.05. An adaptive sample size re-estimation based on the outcomes of 144 patients will allow a possible increase to a prespecified maximum of 326 patients. INTERVENTION: Participants will receive 1 g intravenous tranexamic acid over 10 min, followed by 1 g intravenous tranexamic acid over 8 hours; or matching placebo. PRIMARY EFFICACY MEASURE: The primary efficacy measure is the proportion of patients with haematoma growth by 24±6 hours, defined as either ≥33% relative increase or ≥6 mL absolute increase in haematoma volume between baseline and follow-up CT scan. DISCUSSION: We describe the rationale and protocol of STOP-MSU, a phase II trial of tranexamic acid in patients with ICH within 2 hours from onset, based in participating mobile stroke units and emergency departments.


Subject(s)
Antifibrinolytic Agents , Stroke , Tranexamic Acid , Antifibrinolytic Agents/adverse effects , Cerebral Hemorrhage/chemically induced , Cerebral Hemorrhage/diagnostic imaging , Cerebral Hemorrhage/drug therapy , Clinical Trials, Phase II as Topic , Hematoma/chemically induced , Hematoma/drug therapy , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Stroke/therapy , Tranexamic Acid/adverse effects
2.
BJOG ; 129(2): 248-255, 2022 01.
Article in English | MEDLINE | ID: covidwho-1831883

ABSTRACT

OBJECTIVE: To evaluate the impact of Covid-19 vaccination (Pfizer-BioNTech BNT162b2) during the third trimester of pregnancy on maternal and neonatal outcomes. DESIGN: A multicentre, retrospective computerised database. POPULATION: Women who gave birth at >24 weeks of gestation in Israel, between January and April 2021, with full records of Covid-19 disease and vaccination status. METHODS: Women who received two doses of the vaccine were compared with unvaccinated women. Women who were recorded as having disease or a positive Covid-19 polymerase chain reaction (PCR) swab during pregnancy or delivery were excluded from both study groups. Univariate analysis was followed by multivariate logistic regression. MAIN OUTCOME MEASURES: Composite adverse maternal outcomes. Secondary outcomes were vaccination rate and composite adverse neonatal outcomes. RESULTS: The overall uptake of one or both vaccines was 40.2%; 712 women who received two doses of the Covid-19 vaccine were compared with 1063 unvaccinated women. Maternal composite outcomes were comparable between the groups; however, women who received the vaccine had higher rates of elective caesarean deliveries (CDs) and lower rates of vacuum deliveries. An adjusted multivariable logistic regression analysis demonstrated that Covid-19 vaccination was not associated with maternal composite adverse outcome (aOR 0.8, 95% CI 0.61-1.03); a significant reduction in the risk for neonatal composite adverse outcomes was observed (aOR 0.5, 95% CI 0.36-0.74). CONCLUSIONS: In a motivated population covered by a National Health Insurance Plan, we found a 40.2% rate of vaccination for the Covid-19 vaccine during the third trimester of pregnancy, which was not associated with adverse maternal outcomes and, moreover, decreased the risk for neonatal adverse outcomes. TWEETABLE ABSTRACT: Covid-19 vaccine during pregnancy is safe for both mother and fetus.


Subject(s)
COVID-19 , Vaccination , /administration & dosage , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Cohort Studies , Female , Humans , Infant, Newborn , Israel/epidemiology , Patient Safety , Pregnancy , Pregnancy Outcome/epidemiology , Pregnancy Trimester, Third , Retrospective Studies , SARS-CoV-2 , Treatment Outcome , Vaccination/methods , Vaccination/statistics & numerical data
4.
Heart Lung Circ ; 31(2): 292-298, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1828537

ABSTRACT

BACKGROUND: Patients with Coronavirus disease 2019 (COVID-19)-related acute respiratory disease (ARDS) increasingly receive extracorporeal membrane oxygenation (ECMO) support. While ECMO has been shown to increase risk of stroke, few studies have examined this association in COVID-19 patients. OBJECTIVE: We conducted a systematic review to characterise neurological events during ECMO support in COVID-19 patients. DESIGN: Systematic review of cohort and large case series of COVID-19 patients who received ECMO support. DATA SOURCES: Studies retrieved from PubMed, EMBASE, Cochrane, Cochrane COVID-19 Study Register, Web of Science, Scopus, Clinicaltrials.gov, and medRχiv from inception to November 11, 2020. ELIGIBILITY CRITERIA: Inclusion criteria were a) Adult population (>18 year old); b) Positive PCR test for SARS-CoV-2 with active COVID-19 disease; c) ECMO therapy due to COVID-19 ARDS; and d) Neurological events and outcome described while on ECMO support. We excluded articles when no details of neurologic events were available. RESULTS: 1,322 patients from 12 case series and retrospective cohort studies were included in our study. The median age was 49.2, and 75% (n=985) of the patients were male. Diabetes mellitus and dyslipidaemia were the most common comorbidities (24% and 20%, respectively). Most (95%, n=1,241) patients were on venovenous ECMO with a median P:F ratio at the time of ECMO cannulation of 69.1. The prevalence of intracranial haemorrhage (ICH), ischaemic stroke, and hypoxic ischaemic brain injury (HIBI) was 5.9% (n=78), 1.1% (n=15), and 0.3% (n=4), respectively. The overall mortality of the 1,296 ECMO patients in the 10 studies that reported death was 36% (n=477), and the mortality of the subset of patients who had a neurological event was 92%. CONCLUSIONS: Neurological injury is a concern for COVID-19 patients who receive ECMO. Further research is required to explore how neuromonitoring protocols can inform tailored anticoagulation management and improve survival in COVID-19 patients with ECMO support.


Subject(s)
Brain Ischemia , COVID-19 , Extracorporeal Membrane Oxygenation , Stroke , Adolescent , Adult , Extracorporeal Membrane Oxygenation/adverse effects , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Stroke/epidemiology , Stroke/etiology
6.
Expert Opin Biol Ther ; 22(2): 235-243, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1821662

ABSTRACT

BACKGROUND: P044 is a proposed biosimilar candidate of Teriparatide for reference medicine, Forsteo®. This study was designed to evaluate the Pharmacokinetic/Pharmacodynamic (PK/PD) bioequivalence between P044 and Forsteo®. METHODS: In this randomized, open-label, single-dose, crossover study, 66 healthy female subjects were randomized to receive P044 and Forsteo®. The primary PK endpoints of the study were the area under the concentration versus time from zero to infinity (AUC0-inf) and maximum plasma concentration (Cmax). Secondary endpoints included area under the concentration versus time from zero to the last quantifiable concentration (AUC0-last) and Cmax for PD parameter, additional PK parameters and safety. RESULTS: Sixty-six subjects were enrolled in the study and baseline demographics were similar between the two treatments. The two treatments presented similar PK/PD parameters and the 90% confidence interval for primary and secondary endpoints were within the bioequivalence acceptance range (80.00-125.00%) for all parameters. None of the subjects experienced serious adverse event, and all of the reported adverse events were mild and similar between two treatments. CONCLUSIONS: This study demonstrated the PK/PD similarity of P044 to reference medicine, Forsteo® and safety profiles were comparable between treatments. TRIAL REGISTRATION: EudraCT Number: 2019-004477-82.


Subject(s)
Biosimilar Pharmaceuticals , Biosimilar Pharmaceuticals/adverse effects , Cross-Over Studies , Double-Blind Method , Female , Healthy Volunteers , Humans , Therapeutic Equivalency
8.
AJR Am J Roentgenol ; 218(4): 651-657, 2022 04.
Article in English | MEDLINE | ID: covidwho-1817848

ABSTRACT

BACKGROUND. A possible association has been reported between COVID-19 messenger RNA (mRNA) vaccination and myocarditis. OBJECTIVE. The purpose of our study was to describe cardiac MRI findings in patients with myocarditis after COVID-19 mRNA vaccination. METHODS. This retrospective study included patients without known prior SARS-CoV-2 infection who underwent cardiac MRI between May 14, 2021, and June 14, 2021, for suspected myocarditis within 2 weeks of COVID-19 mRNA vaccination. Information regarding clinical presentation, hospital course, and events after hospital discharge were recorded. A cardiothoracic imaging fellow and cardiothoracic radiologist reviewed cardiac MRI examinations in consensus. Data were summarized descriptively. RESULTS. Of 52 patients without known prior SARS-CoV-2 infection who underwent cardiac MRI during the study period, five underwent MRI for suspected myocarditis after recent COVID-19 mRNA vaccination. All five patients were male patients ranging in age from 16 to 19 years (mean, 17.2 ± 1.0 [SD] years) who presented within 4 days of receiving the second dose of a COVID-19 mRNA vaccine. Troponin levels were elevated in all patients (mean peak troponin I value, 6.82 ± 4.13 ng/mL). Alternate possible causes of myocarditis were deemed clinically unlikely on the basis of medical history, physical examination findings, myocarditis viral panel, and toxicology screening. Cardiac MRI findings were consistent with myocarditis in all five patients on the basis of the Lake Louise criteria, including early gadolinium enhancement and late gadolinium enhancement (LGE) in all patients and corresponding myocardial edema in four patients. All five patients had a favorable hospital course and were discharged from the hospital in stable condition with improved or resolved symptoms after hospitalization (mean length of hospital stay, 4.8 days). Two patients underwent repeat cardiac MRI that showed persistent, although decreased, LGE. Three patients reported mild intermittent self-resolving chest pain after hospital discharge, and two patients had no recurrent symptoms after discharge. CONCLUSION. In this small case series, all patients with myocarditis after COVID-19 vaccination were male adolescents and had a favorable initial clinical course. All patients showed cardiac MRI findings typical of myocarditis from other causes. LGE persisted in two patients who underwent repeat MRI. These observations do not establish causality. CLINICAL IMPACT. Radiologists should be aware of a possible association of COVID-19 mRNA vaccination and myocarditis and recognize the role of cardiac MRI in the assessment of suspected myocarditis after COVID-19 vaccination.


Subject(s)
COVID-19 , Myocarditis , Adolescent , Adult , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Contrast Media , Gadolinium , Humans , Magnetic Resonance Imaging/methods , Male , Myocarditis/diagnostic imaging , Myocarditis/etiology , RNA, Messenger , Retrospective Studies , SARS-CoV-2 , Vaccination/adverse effects , Vaccines, Synthetic , Young Adult
9.
Trials ; 22(1): 573, 2021 Aug 28.
Article in English | MEDLINE | ID: covidwho-1817236

ABSTRACT

BACKGROUND: SARS-CoV-2 binds to membrane-bound angiotensin-converting enzyme 2 (ACE2) which may result in downregulation of membrane-bound ACE2. ACE2 is a key regulator of the renin-angiotensin system (RAS) and is responsible for degrading angiotensin II and thereby counteracting its pro-inflammatory, pro-fibrotic effects mediated through the angiotensin II type 1 receptor (AT1R). As AT1R is directly blocked by angiotensin receptor blockers (ARBs), these agents may offer a safe, low-cost solution for reducing COVID-19 respiratory outcomes. METHODS AND DISCUSSION: CLARITY is a pragmatic, adaptive, two-arm, multi-centre, comparative effectiveness phase III randomised controlled trial that examines whether ARBs reduce COVID-19 severity among high-risk patients. Recruiting in India and Australia, the trial will compare treatment with a maximum tolerated daily dose of an ARB to standard of care. Treatment allocation is blinded in India but open-label in Australia due to interruptions to placebo supply in the latter. The primary endpoint is a 7-point ordinal scale of clinical states, ranging from no limitation of activities (category 1) to death (category 7), assessed on day 14. Secondary outcomes include the 7-point scale assessed at day 28 and 28- and 90-day mortality. The design adapts the sample size based on accumulating data via frequent interim analyses and the use of predictive probability to determine whether the current sample size is sufficient or continuing accrual would be futile. The trial commenced recruitment on 18 August 2020. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04394117 . Registered on 19 May 2020. Clinical Trial Registry of India: CTRI/2020/07/026831).


Subject(s)
Angiotensin Receptor Antagonists , COVID-19 , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Renin-Angiotensin System , SARS-CoV-2
11.
Lancet ; 398(10301): 685-697, 2021 08 21.
Article in English | MEDLINE | ID: covidwho-1815297

ABSTRACT

BACKGROUND: Associations between high and low temperatures and increases in mortality and morbidity have been previously reported, yet no comprehensive assessment of disease burden has been done. Therefore, we aimed to estimate the global and regional burden due to non-optimal temperature exposure. METHODS: In part 1 of this study, we linked deaths to daily temperature estimates from the ERA5 reanalysis dataset. We modelled the cause-specific relative risks for 176 individual causes of death along daily temperature and 23 mean temperature zones using a two-dimensional spline within a Bayesian meta-regression framework. We then calculated the cause-specific and total temperature-attributable burden for the countries for which daily mortality data were available. In part 2, we applied cause-specific relative risks from part 1 to all locations globally. We combined exposure-response curves with daily gridded temperature and calculated the cause-specific burden based on the underlying burden of disease from the Global Burden of Diseases, Injuries, and Risk Factors Study, for the years 1990-2019. Uncertainty from all components of the modelling chain, including risks, temperature exposure, and theoretical minimum risk exposure levels, defined as the temperature of minimum mortality across all included causes, was propagated using posterior simulation of 1000 draws. FINDINGS: We included 64·9 million individual International Classification of Diseases-coded deaths from nine different countries, occurring between Jan 1, 1980, and Dec 31, 2016. 17 causes of death met the inclusion criteria. Ischaemic heart disease, stroke, cardiomyopathy and myocarditis, hypertensive heart disease, diabetes, chronic kidney disease, lower respiratory infection, and chronic obstructive pulmonary disease showed J-shaped relationships with daily temperature, whereas the risk of external causes (eg, homicide, suicide, drowning, and related to disasters, mechanical, transport, and other unintentional injuries) increased monotonically with temperature. The theoretical minimum risk exposure levels varied by location and year as a function of the underlying cause of death composition. Estimates for non-optimal temperature ranged from 7·98 deaths (95% uncertainty interval 7·10-8·85) per 100 000 and a population attributable fraction (PAF) of 1·2% (1·1-1·4) in Brazil to 35·1 deaths (29·9-40·3) per 100 000 and a PAF of 4·7% (4·3-5·1) in China. In 2019, the average cold-attributable mortality exceeded heat-attributable mortality in all countries for which data were available. Cold effects were most pronounced in China with PAFs of 4·3% (3·9-4·7) and attributable rates of 32·0 deaths (27·2-36·8) per 100 000 and in New Zealand with 3·4% (2·9-3·9) and 26·4 deaths (22·1-30·2). Heat effects were most pronounced in China with PAFs of 0·4% (0·3-0·6) and attributable rates of 3·25 deaths (2·39-4·24) per 100 000 and in Brazil with 0·4% (0·3-0·5) and 2·71 deaths (2·15-3·37). When applying our framework to all countries globally, we estimated that 1·69 million (1·52-1·83) deaths were attributable to non-optimal temperature globally in 2019. The highest heat-attributable burdens were observed in south and southeast Asia, sub-Saharan Africa, and North Africa and the Middle East, and the highest cold-attributable burdens in eastern and central Europe, and central Asia. INTERPRETATION: Acute heat and cold exposure can increase or decrease the risk of mortality for a diverse set of causes of death. Although in most regions cold effects dominate, locations with high prevailing temperatures can exhibit substantial heat effects far exceeding cold-attributable burden. Particularly, a high burden of external causes of death contributed to strong heat impacts, but cardiorespiratory diseases and metabolic diseases could also be substantial contributors. Changes in both exposures and the composition of causes of death drove changes in risk over time. Steady increases in exposure to the risk of high temperature are of increasing concern for health. FUNDING: Bill & Melinda Gates Foundation.


Subject(s)
Cause of Death/trends , Cold Temperature/adverse effects , Global Burden of Disease/statistics & numerical data , Global Health/statistics & numerical data , Hot Temperature/adverse effects , Mortality/trends , Bayes Theorem , Heart Diseases/epidemiology , Humans , Metabolic Diseases/epidemiology
12.
Adv Ther ; 39(1): 178-192, 2022 01.
Article in English | MEDLINE | ID: covidwho-1813867

ABSTRACT

Since 1955, the only available H1 antihistamines for intravenous administration have been first-generation formulations and, of those, only intravenously administered (IV) diphenhydramine is still approved in the USA. Orally administered cetirizine hydrochloride, a second-generation H1 antihistamine, has been safely used over-the-counter for many years. In 2019, IV cetirizine was approved for the treatment of acute urticaria. In light of this approval, this narrative review discusses the changing landscape of IV antihistamines for the treatment of histamine-mediated conditions. Specifically, IV antihistamines will be discussed as a treatment option for acute urticaria and angioedema, as premedication to prevent infusion reactions related to anticancer agents and other biologics, and as an adjunct treatment for anaphylaxis and other allergic reactions. Before the development of IV cetirizine, randomized controlled trials of IV antihistamines for these indications were lacking. Three randomized controlled trials have been conducted with IV cetirizine versus IV diphenhydramine in the ambulatory care setting. A phase 3 trial of IV cetirizine 10 mg versus IV diphenhydramine 50 mg was conducted in 262 adults who presented to the urgent care/emergency department with acute urticaria requiring antihistamines. For the primary efficacy endpoint, defined as change from baseline in a 2-h patient-rated pruritus score, non-inferiority of IV cetirizine to IV diphenhydramine was demonstrated (score - 1.6 vs - 1.5, respectively; 95% CI - 0.1, 0.3). Compared with IV diphenhydramine, IV cetirizine demonstrated fewer adverse effects including less sedation, a significantly shorter length of stay in the treatment center, and fewer returns to the treatment center at 24 and 48 h. Similar findings were demonstrated in another phase 2 acute urticaria trial and in a phase 2 trial assessing IV cetirizine for pretreatment for infusion reactions in the oncology/immunology setting. IV cetirizine is associated with similar patient outcomes, fewer adverse effects, and increased treatment center efficiency than IV diphenhydramine.


Subject(s)
Cetirizine , Urticaria , Administration, Intravenous , Adult , Cetirizine/adverse effects , Diphenhydramine/adverse effects , Histamine H1 Antagonists/adverse effects , Humans , Urticaria/chemically induced , Urticaria/drug therapy
13.
Eur J Clin Pharmacol ; 77(10): 1513-1521, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1813653

ABSTRACT

PURPOSE: To analyze the cases of torsade de pointes (TdP) and related symptoms reported in association with chloroquine (CQ), hydroxychloroquine (HCQ), and azithromycin (AZT) to the World Health Organization (WHO) global database of individual case safety reports (ICSRs) for drug monitoring (VigiBase) using qualitative and quantitative pharmacovigilance approaches. METHODS: The main characteristics of the ICSRs reporting TdP with CQ, HCQ, and AZT have been summarized. Co-reported drugs with risk to cause QT prolongation have been described. Reporting odds ratios (RORs) as a measure of disproportionality for reported TdP and individual drugs have been calculated. RESULTS: One hundred seventy ICSRs reporting TdP in association with the drugs of interest were identified (CQ: 11, HCQ: 31, CQ + HCQ: 1, HCQ + AZT: 27, AZT: 100). From these, 41 (24.3%) were received during the pandemic period (December 2019 to February 2021). The median age of the patients was 63, 53, and 63 years old for CQ, HCQ, and AZT, respectively. Reports included concomitant use of other QT-prolonging drugs (CQ 25.0%, HCQ 71.2%, AZT 64.6%). A proportion of the cases were fatal (CQ 25.0%, HCQ 8.6%, AZT 16.1%). Increased disproportionality has been found for the individual drugs and TdP: CQ (ROR: 7.41, 95% confidence interval (CI): 3.82, 12.96), HCQ (ROR: 8.49, 95% CI: 6.57, 10.98), azithromycin (ROR: 8.06, 95% CI: 6.76, 9.61). Disproportionality was also found for other related symptoms, Standardized MedDRA Query for torsade de pointes/QT prolongation (narrow): CQ (ROR: 11.95, 95% CI: 10.04-14.22); HCQ (ROR: 20.43, 95% CI: 19.13, 21.83), AZT (ROR: 7.78, 95% CI: 7.26, 8.34). CONCLUSIONS: The prescription of CQ, HCQ, and AZT should be restricted to therapeutic indications with established positive benefit/risk profile. Doctors and patients should be aware of this potential adverse reaction especially when several risk factors are present.


Subject(s)
Azithromycin/adverse effects , Chloroquine/adverse effects , Hydroxychloroquine/adverse effects , Torsades de Pointes/chemically induced , Adult , Aged , Azithromycin/administration & dosage , Chloroquine/administration & dosage , Drug Therapy, Combination , Female , Humans , Hydroxychloroquine/administration & dosage , Male , Middle Aged , Pharmacovigilance , Retrospective Studies
14.
J Med Virol ; 94(6): 2860-2869, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1813544

ABSTRACT

Progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the brain, caused by the John Cunningham virus (JCV) is usually seen in patients who are immunocompromised. Here, we describe a case of an immunocompetent patient diagnosed with PML and a comprehensive literature review. A 64-year-old Caucasian male presented with acute worsening of progressive neurological decline with difficulty in vision and reading. Based on history, examination, cerebrospinal fluid markers, histopathology, and magnetic resonance imaging brain at the time of presentation diagnosed the patient with PML in a setting of no immunosuppression disorder. The patient was started on Pelfilgrastim with significant systematic improvement. In our literature review, it was seen that the average age of symptom presentation was 57.5 with predominance in males. Most of the patients presented with progressive neurological deficits with symptomology ranging from mild confusion, aphasia, anxiety to sensory disturbances with numbness, hemiparesis, and hemianopsia. Out of the 21 cases, patients responded to mirtazapine and intravenous pulse methylprednisolone (IVMP). The mortality rate was close to 50% with 11 fatal cases and 10 nonfatal cases. Our case and literature review demonstrate the possibility that PML may very rarely occur in patients that are immunocompetent. Furthermore, our review showed that patients responded well to mirtazapine and IVMP. We also want to highlight that the mortality rate was lower in this review and was only compared to mortality in PML associated with immunocompromised status.


Subject(s)
JC Virus , Leukoencephalopathy, Progressive Multifocal , Brain/diagnostic imaging , Brain/pathology , Humans , Leukoencephalopathy, Progressive Multifocal/diagnostic imaging , Leukoencephalopathy, Progressive Multifocal/drug therapy , Magnetic Resonance Imaging/adverse effects , Male , Middle Aged , Mirtazapine/therapeutic use
15.
Cochrane Database Syst Rev ; 8: CD010168, 2021 08 17.
Article in English | MEDLINE | ID: covidwho-1813437

ABSTRACT

BACKGROUND: This is the second update of a Cochrane Review first published in 2015 and last updated in 2018. Appendectomy, the surgical removal of the appendix, is performed primarily for acute appendicitis. Patients who undergo appendectomy for complicated appendicitis, defined as gangrenous or perforated appendicitis, are more likely to suffer postoperative complications. The routine use of abdominal drainage to reduce postoperative complications after appendectomy for complicated appendicitis is controversial. OBJECTIVES: To assess the safety and efficacy of abdominal drainage to prevent intraperitoneal abscess after appendectomy (irrespective of open or laparoscopic) for complicated appendicitis; to compare the effects of different types of surgical drains; and to evaluate the optimal time for drain removal. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid Embase, Web of Science, the World Health Organization International Trials Registry Platform, ClinicalTrials.gov, Chinese Biomedical Literature Database, and three trials registers on 24 February 2020, together with reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that compared abdominal drainage versus no drainage in people undergoing emergency open or laparoscopic appendectomy for complicated appendicitis. We also included RCTs that compared different types of drains and different schedules for drain removal in people undergoing appendectomy for complicated appendicitis. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently identified the trials for inclusion, collected the data, and assessed the risk of bias. We used the GRADE approach to assess evidence certainty. We included intraperitoneal abscess as the primary outcome. Secondary outcomes were wound infection, morbidity, mortality, hospital stay, hospital costs, pain, and quality of life. MAIN RESULTS: Use of drain versus no drain We included six RCTs (521 participants) comparing abdominal drainage and no drainage in participants undergoing emergency open appendectomy for complicated appendicitis. The studies were conducted in North America, Asia, and Africa. The majority of participants had perforated appendicitis with local or general peritonitis. All participants received antibiotic regimens after open appendectomy. None of the trials was assessed as at low risk of bias. The evidence is very uncertain regarding the effects of abdominal drainage versus no drainage on intraperitoneal abscess at 30 days (risk ratio (RR) 1.23, 95% confidence interval (CI) 0.47 to 3.21; 5 RCTs; 453 participants; very low-certainty evidence) or wound infection at 30 days (RR 2.01, 95% CI 0.88 to 4.56; 5 RCTs; 478 participants; very low-certainty evidence). There were seven deaths in the drainage group (N = 183) compared to one in the no-drainage group (N = 180), equating to an increase in the risk of 30-day mortality from 0.6% to 2.7% (Peto odds ratio 4.88, 95% CI 1.18 to 20.09; 4 RCTs; 363 participants; low-certainty evidence). Abdominal drainage may increase 30-day overall complication rate (morbidity; RR 6.67, 95% CI 2.13 to 20.87; 1 RCT; 90 participants; low-certainty evidence) and hospital stay by 2.17 days (95% CI 1.76 to 2.58; 3 RCTs; 298 participants; low-certainty evidence) compared to no drainage. The outcomes hospital costs, pain, and quality of life were not reported in any of the included studies. There were no RCTs comparing the use of drain versus no drain in participants undergoing emergency laparoscopic appendectomy for complicated appendicitis. Open drain versus closed drain There were no RCTs comparing open drain versus closed drain for complicated appendicitis. Early versus late drain removal There were no RCTs comparing early versus late drain removal for complicated appendicitis. AUTHORS' CONCLUSIONS: The certainty of the currently available evidence is low to very low. The effect of abdominal drainage on the prevention of intraperitoneal abscess or wound infection after open appendectomy is uncertain for patients with complicated appendicitis. The increased rates for overall complication rate and hospital stay for the drainage group compared to the no-drainage group are based on low-certainty evidence. Consequently, there is no evidence for any clinical improvement with the use of abdominal drainage in patients undergoing open appendectomy for complicated appendicitis. The increased risk of mortality with drainage comes from eight deaths observed in just under 400 recruited participants. Larger studies are needed to more reliably determine the effects of drainage on morbidity and mortality outcomes.


Subject(s)
Abscess/prevention & control , Appendectomy/adverse effects , Appendicitis/surgery , Drainage/methods , Peritonitis/prevention & control , Postoperative Complications/prevention & control , Humans
16.
Cochrane Database Syst Rev ; 8: CD004122, 2021 08 26.
Article in English | MEDLINE | ID: covidwho-1813433

ABSTRACT

BACKGROUND: Hair has traditionally been removed from the surgical site before surgery; however, some studies claim that this increases surgical site infections (SSIs) and should be avoided. This is the second update of a review published in 2006 and first updated in 2011. OBJECTIVES: To determine whether routine preoperative hair removal (compared with no removal) and the method, timing, or setting of hair removal effect SSI rates. SEARCH METHODS: In November 2019, for this second update we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase; and EBSCO CINAHL Plus. We also searched clinical trial registries for ongoing and unpublished studies, and scanned the reference lists of included studies plus reviews to identify additional studies. We applied no date or language restrictions. SELECTION CRITERIA: We included randomised controlled trials or quasi-randomised trials that compared: · hair removal with no hair removal; · different methods of hair removal; and · hair removal at different times before surgery. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the relevance of each study. Data were extracted independently by both review authors and cross-checked. We carried out 'Risk of bias' assessment using the Cochrane 'Risk of bias' tool and assessed the certainty of evidence according to GRADE. Sensitivity analyses excluding studies at high risk of bias were conducted. MAIN RESULTS: We included 11 new studies in this update resulting in a total of 19 randomised and 6 quasi-randomised trials (8919 participants). Clipping compared with no hair removal Low certainty evidence suggests there may be little difference in risk of SSI when no hair removal is compared with hair removal using clippers (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.65 to 1.39; three studies with 1733 participants). Shaving with a razor compared with no hair removal Moderate certainty evidence suggests the risk of SSI is probably increased in participants who have hair removal with a razor compared with no removal (RR 1.82, 95% CI 1.05 to 3.14; seven studies with 1706 participants). In terms of absolute risk this represents 17 more SSIs per 1000 in the razor group compared with the no hair removal group (95% CI 1 more to 45 more SSI in the razor group). Based on low-certainty evidence, it is unclear whether there is a difference in stitch abscesses between hair removal with a razor and no hair removal (1 trial with 80 participants; RR 1.00, 95% CI 0.21 to 4.66). Based on narrative data from one trial with 136 participants, there may be little difference in length of hospital stay between participants having hair removed with a razor compared with those having no hair removal (low-certainty evidence). Based on narrative data from one trial with 278 participants, it is uncertain whether there is a difference in cost between participants having hair removed by shaving with a razor compared with no hair removal (very low certainty evidence). Depilatory cream compared with no hair removal Low certainty evidence suggests there may be little difference in SSI risk between depilatory cream or no hair removal, although there are were wide confidence intervals around the point estimate that included benefit and harm (RR 1.02, 95% CI 0.45 to 2.31; low-certainty evidence; 1 trial with 267 participants). Based on narrative data from one trial with 267 participants, it is uncertain whether there is a difference in cost between participants having hair removed with depilatory cream compared with no hair removal (very low certainty evidence). Shaving with a razor compared with clipping Moderate-certainty evidence from 7 studies with 3723 participants suggests the risk of SSI is probably increased by shaving with a razor compared with clipping (RR 1.64, 95% CI 1.16 to 2.33). Moderate-certainty evidence suggests the risk of skin injury is probably increased in people who have hair removal with a razor rather than clipping (3 trials with 1333 participants; RR 1.74, CI 95% 1.12 to 2.71). Shaving with a razor compared with depilatory cream Moderate-certainty evidence from 9 studies with 1593 participants suggests there is probably more SSI risk when razors are used compared with depilatory cream (RR 2.28, 95% CI 1.12 to 4.65). Low-certainty evidence suggests the risk of skin injury may be increased when using a razor rather than depilatory cream for hair removal (RR 6.95, CI 95% 3.45 to 13.98; 5 trials with 937 participants). Based on narrative data from three trials with 402 participants, it is uncertain whether depilatory cream is more expensive than shaving (very low certainty evidence). Hair removal on the day of surgery compared with one-day preoperatively Low-certainty evidence suggests that there may be a small reduction in SSI risk when hair is removed on the day of surgery compared with the day before surgery although there are were wide confidence intervals around the point estimate that included benefit and harm (one trial, 977 participants; RR 0.83, 95% CI 0.54 to 1.30). AUTHORS' CONCLUSIONS: Compared with no hair removal, there may be little difference in risk of SSI when clippers or depilatory cream are used (low-certainty evidence). However, there are probably fewer SSIs when hair is not removed compared with shaving with a razor (moderate-certainty evidence). If hair has to be removed, moderate-certainty evidence suggests using clippers or depilatory cream probably results in fewer SSIs and other complications compared with shaving using a razor. There may be a small reduction in SSIs when hair is removed on the day of, rather than the day before, surgery.


Subject(s)
Hair Removal , Surgical Wound Infection , Hair Removal/adverse effects , Humans , Surgical Wound Infection/prevention & control
17.
Circulation ; 145(5): 345-356, 2022 02.
Article in English | MEDLINE | ID: covidwho-1807751

ABSTRACT

BACKGROUND: Understanding the clinical course and short-term outcomes of suspected myocarditis after the coronavirus disease 2019 (COVID-19) vaccination has important public health implications in the decision to vaccinate youth. METHODS: We retrospectively collected data on patients <21 years old presenting before July 4, 2021, with suspected myocarditis within 30 days of COVID-19 vaccination. Lake Louise criteria were used for cardiac MRI findings. Myocarditis cases were classified as confirmed or probable on the basis of the Centers for Disease Control and Prevention definitions. RESULTS: We report on 139 adolescents and young adults with 140 episodes of suspected myocarditis (49 confirmed, 91 probable) at 26 centers. Most patients were male (n=126, 90.6%) and White (n=92, 66.2%); 29 (20.9%) were Hispanic; and the median age was 15.8 years (range, 12.1-20.3; interquartile range [IQR], 14.5-17.0). Suspected myocarditis occurred in 136 patients (97.8%) after the mRNA vaccine, with 131 (94.2%) after the Pfizer-BioNTech vaccine; 128 (91.4%) occurred after the second dose. Symptoms started at a median of 2 days (range, 0-22; IQR, 1-3) after vaccination. The most common symptom was chest pain (99.3%). Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%), or no anti-inflammatory therapies (8.6%). Twenty-six patients (18.7%) were in the intensive care unit, 2 were treated with inotropic/vasoactive support, and none required extracorporeal membrane oxygenation or died. Median hospital stay was 2 days (range, 0-10; IQR, 2-3). All patients had elevated troponin I (n=111, 8.12 ng/mL; IQR, 3.50-15.90) or T (n=28, 0.61 ng/mL; IQR, 0.25-1.30); 69.8% had abnormal ECGs and arrhythmias (7 with nonsustained ventricular tachycardia); and 18.7% had left ventricular ejection fraction <55% on echocardiogram. Of 97 patients who underwent cardiac MRI at a median 5 days (range, 0-88; IQR, 3-17) from symptom onset, 75 (77.3%) had abnormal findings: 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria. Among 26 patients with left ventricular ejection fraction <55% on echocardiogram, all with follow-up had normalized function (n=25). CONCLUSIONS: Most cases of suspected COVID-19 vaccine myocarditis occurring in persons <21 years have a mild clinical course with rapid resolution of symptoms. Abnormal findings on cardiac MRI were frequent. Future studies should evaluate risk factors, mechanisms, and long-term outcomes.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Myocarditis/diagnostic imaging , Myocarditis/physiopathology , Adolescent , Child , Electrocardiography/methods , Female , Humans , Magnetic Resonance Imaging, Cine/methods , Male , Myocarditis/blood , Myocarditis/etiology , Retrospective Studies , Time Factors , Young Adult
19.
Eur J Anaesthesiol ; 39(5): 463-472, 2022 May 01.
Article in English | MEDLINE | ID: covidwho-1806662

ABSTRACT

Tracheal intubation is among the most commonly performed and high-risk procedures in critical care. Indeed, 45% of patients undergoing intubation experience at least one major peri-intubation adverse event, with cardiovascular instability being the most common event reported in 43%, followed by severe hypoxemia in 9% and cardiac arrest in 3% of cases. These peri-intubation adverse events may expose patients to a higher risk of 28-day mortality, and they are more frequently observed with an increasing number of attempts to secure the airway. The higher risk of peri-intubation complications in critically ill patients, compared with the anaesthesia setting, is the consequence of their deranged physiology (e.g. underlying respiratory failure, shock and/or acidosis) and, in this regard, airway management in critical care has been defined as "physiologically difficult". In recent years, several randomised studies have investigated the most effective preoxy-genation strategies, and evidence for the use of positive pressure ventilation in moderate-to-severe hypoxemic patients is established. On the other hand, evidence on interventions to mitigate haemodynamic collapse after intubation has been elusive. Airway management in COVID-19 patients is even more challenging because of the additional risk of infection for healthcare workers, which has influenced clinical choices in this patient group. The aim of this review is to provide an update of the evidence for intubation in critically ill patients with a focus on understanding peri-intubation risks and evaluating interventions to prevent or mitigate adverse events.


Subject(s)
COVID-19 , Respiratory Insufficiency , Airway Management/adverse effects , Critical Illness/therapy , Humans , Intubation, Intratracheal/adverse effects , Intubation, Intratracheal/methods
20.
Hum Vaccin Immunother ; 18(1): 2020573, 2022 Dec 31.
Article in English | MEDLINE | ID: covidwho-1799504

ABSTRACT

Limited information is available about post-marketing safety of Japanese encephalitis (JE) vaccines. Using data from SmartVax, an active surveillance system for monitoring vaccine safety, adverse events following immunizations (AEFIs) were compared between the two JE vaccines available in Australia (a chimeric live attenuated vaccine [Imojev] and a Vero cell-derived inactivated vaccine [JEspect]). Data from 2756 patients (1855 Imojev and 901 JEspect) were included. Overall (7.0%), systemic (2.8%), and local (1.9%) AEFIs were uncommon. There were no significant differences in the odds of overall (OR = 1.27; 95%CI: 0.91-1.77), systemic (OR = 1.23; 95%CI: 0.74-2.06), or local (OR = 1.20; 95%CI: 0.65-2.22) AEFIs with Imojev compared to JEspect. There was an increase in odds of overall AEFI in patients aged <5 years (OR = 2.39; 95%CI: 1.10-5.19) compared to those aged >50 years. Both JE vaccines available in Australia are safe and well tolerated. Odds of AEFIs were age-dependent, young children should be carefully observed for AEFIs after vaccination.


Subject(s)
Encephalitis, Japanese , Japanese Encephalitis Vaccines , Animals , Australia , Child , Child, Preschool , Chlorocebus aethiops , Encephalitis, Japanese/prevention & control , Humans , Middle Aged , Vaccines, Attenuated/adverse effects , Vaccines, Inactivated/adverse effects , Vero Cells , Watchful Waiting
SELECTION OF CITATIONS
SEARCH DETAIL