Ibuprofen use and clinical outcomes in COVID-19 patients.

OBJECTIVE: It was recently suggested that ibuprofen might increase the risk for severe and fatal coronavirus disease 2019 (COVID-19) and should therefore be avoided in this patient population. We aimed to evaluate whether ibuprofen use in individuals with COVID-19 was associated with more severe disease, compared with individuals using paracetamol or no antipyretics. METHODS: In a retrospective cohort study of patients with COVID-19 from Shamir Medical Centre, Israel, we monitored any use of ibuprofen from a week before diagnosis of COVID-19 throughout the disease. Primary outcomes were mortality and the need for respiratory support, including oxygen administration and mechanical ventilation. RESULTS: The study included 403 confirmed cases of COVID-19, with a median age of 45 years. Of the entire cohort, 44 patients (11%) needed respiratory support and 12 (3%) died. One hundred and seventy-nine (44%) patients had fever, with 32% using paracetamol and 22% using ibuprofen, for symptom-relief. In the ibuprofen group, 3 (3.4%) patients died, whereas in the non-ibuprofen group, 9 (2.8%) patients died (p 0.95). Nine (10.3%) patients from the ibuprofen group needed respiratory support, compared with 35 (11%) from the non-ibuprofen group (p 1). When compared with exclusive paracetamol users, no differences were observed in mortality rates or the need for respiratory support among patients using ibuprofen. CONCLUSIONS: In this cohort of COVID-19 patients, ibuprofen use was not associated with worse clinical outcomes, compared with paracetamol or no antipyretic.

Effect of hyperbaric oxygen therapy on amphotericin-B induced acute renal failure in rats.

AIM: Acute renal injury may occur after amphotericin B (AmB) administration. The hypothesized injury mechanism is renal vasoconstriction and direct toxic damage. Hyperbaric oxygen therapy (HBO) is indicated for treatment of many ischemic events but not for acute renal failure (ARF). The aim of this study was to investigate the role of HBO therapy in AmB induced ARF. METHODS: ARF was induced in 41 Sprague-Dawley rats by a single dose of 75 mg/kg AmB. The rats were randomly divided into two groups; one group was treated with daily HBO for 3 consecutive days. The control group received no HBO treatment. Parameters of renal function were taken on the 5th day after AmB administration. RESULTS: Forty-one rats were treated with AmB, 21 received HBO and 20 served as controls. Body weight loss following the administration of AmB was 13.5+14.7% in the HBO treated rats, as opposed to 24.6+5% in the control group (P=0.004). Serum creatinine and urea were 0.49+0.13 mg/dL and 200.63+87.82 mg/dL in the treatment group and 0.70+0.22 mg/dL and 368.01+169.35 mg/dL, respectively in the control (P=0.001). CONCLUSION: In this model of AmB-induced ARF, HBO treatment alleviated renal injury as reflected by changes in serum creatinine and urea levels.

Factors associated with empyema in children with community acquired pneumonia.

AIM: Empyema is a potential complication of community acquired pneumonia but factors predicting this complication are lacking. METHODS: A retrospective study of all previously healthy pediatric patients admitted between January 2007 and July 2009 with CAP. Patients with non-lobar pneumonia, RSV bronchiolitis, underlying chronic disease, or hospital-acquired pneumonia were excluded. Preadmission, clinical characteristics on admission, and outcome were compared between patients with and without empyema. Management strategies in patients with empyema were also compared. RESULTS: Overall 356 patients were included. Median age was 3.8 ± 3.54 years and 60.7% were males. A total of 43 patients (12%) were diagnosed with empyema. The development of empyema was independently associated, on multivariate analysis, with older age, female gender and antibiotic therapy prior to admission, and with dyspnea, thrombocytopenia and involvement of more than one lobe on chest radiograph on admission. Patients who developed empyema had a longer and more complicated course. Hypoxemia on admission was significantly less frequent in patients with empyema who were treated with antibiotic therapy alone, compared to those treated with chest tube or video-assisted thoracoscopic surgery. CONCLUSION: Early identification of dyspnea and thrombocytopenia in patients with community acquired pneumonia could alert physicians on the potential development of empyema. Antibiotic therapy alone may be sufficient in patients with empyema who are mildly hypoxemic on admission.

Serum glucose and electrolyte levels in alcohol-intoxicated adolescents on admission to the emergency department: an unmatched case-control study.

Aimed at examining serum glucose and electrolytes concentrations in adolescents with acute alcohol intoxication (AAI) on admission to the pediatric Emergency Department (ED), a retrospective unmatched, case-control study was conducted. Two cohorts of adolescents were compared, patients presenting with AAI and patients presenting with non-alcohol intoxication. The study group included ED patients aged 12-18 years with AAI. The control group included ED patients aged 12-18 years who had poisoning from a non-illicit drug. Demographic characteristics and glucose and electrolyte blood levels were extracted from the medical files. The records of patients who were admitted between January 2007 and December 2009 were analyzed. The study group and the control group included 106 subjects and 27 subjects, respectively. The study subjects had serum ethanol levels in the range of 55.6-297 mg/dL. No case of hypoglycemia was recorded. The study subjects had higher glucose levels and lower potassium levels compared to the controls (p < 0.005 and p < 0.0001, respectively). No such difference was found when the levels of sodium and bicarbonate were compared (p = 0.3 and p = 0.14, respectively). In conclusion, the findings of this study suggest that at presentation to the ED adolescents with AAI are at low risk for hypoglycemia.

Bulging fontanelle in febrile infants: is lumbar puncture mandatory?

OBJECTIVE: To determine the aetiologies and clinical characteristics of infants with fever and a bulging fontanelle. DESIGN: The medical records of all febrile infants with a bulging fontanelle who underwent a lumbar puncture from January 2000 to February 2008 in Assaf Harofeh Medical Center, a university affiliated hospital in central Israel, were identified. RESULTS: 153 patients met the inclusion criteria. The male to female ratio was 100:53; age range was 3-11 months with a mean age of 5.6 (SD 1.8) months and a median age of 5 months. Cerebrospinal fluid pleocytosis was found in 42 cases (27.3%), including one case of bacterial meningitis (0.6%). Other leading diagnoses were aseptic meningitis (26.7%), upper respiratory tract infection (18.3%), viral disease not otherwise specified (15.6%), roseola infantum (8.5%) and acute otitis media (6.5%). Appearance on admission was described as good to excellent in 113 (73.8%) infants, none of whom had bacterial meningitis. 32 had aseptic meningitis and 17 had other bacterial disease (pneumonia, acute otitis media, pyelonephritis, bacteraemia, shigella or salmonella gastroenteritis). All the latter had, upon admission, symptoms, signs, laboratory tests or imaging studies suggesting a bacterial aetiology. CONCLUSIONS: In this large cohort, all infants who appeared well on admission and had normal clinical, laboratory and imaging studies had benign (non-bacterial) disease. In an infant who appears well and has no evidence of bacterial disease, it is reasonable to observe the infant and withhold lumbar puncture. Prospective studies should be carried out to confirm this approach.

Strategy for increasing detection rates of drug and alcohol abuse in paediatric emergency departments.

AIM: To determine whether implementation of criteria for performing a toxicology screen and increasing staff awareness improve detection of substance abuse among adolescents presenting to the emergency department. METHODS: Patients 12 to 18 years of age presenting to one of three emergency departments in Israel were included in a prospective cohort study. In the 'study' hospital, a set of criteria for urine toxicology screen and measurements of ethanol serum level were implemented. No specific interventions were implemented in the two other hospitals. The main outcome measure was the rate of substance abuse detection. RESULTS: The number of adolescents seen in the participating centres was 3200 at the study hospital, and 3493 and 2792 at the two other hospitals. High blood ethanol concentrations were found in 49 patients at the study hospital compared with 30 and 19 patients at the two other hospitals (p < 0.001). Illicit drugs were detected in 13, 4 and 1 patients, respectively (p = 0.002). CONCLUSIONS: Introducing structured guidelines for ordering toxicological screening increases the detection of alcohol and drug of abuse among adolescents presenting to paediatric emergency departments.

Bicycle-related injuries in children: disturbing profile of a growing problem.

CONTEXT: We observed a changing pattern of bicycle-related injuries in children, with the focus changing from head trauma to thoracic and abdominal injuries, and a trend to increasingly severe injuries. OBJECTIVE: To assess the changing injury pattern, and investigate the development of preventive measures to improve safety. DESIGN, SETTING, AND PARTICIPANTS: Retrospective record review of 142 paediatric patients admitted to our Department of Paediatric Surgery between 1996 and 2005 following bicycle-related injuries. Clinical, laboratory, diagnostic, and therapeutic aspects were analysed. Additional information concerning children's bicycle-related injuries in Israel was obtained from the Gertner Institute (Israel National Center for Trauma and Emergency Medicine Research) and from Beterem (The National Center for Children's Safety & Health, the Safe Kids Israeli Chapter) National Report on Child Injuries in Israel 2006. MAIN OUTCOME MEASURES: The nature and severity of injuries were reviewed, and two 5-year periods compared-from 1996 to 2000 (53 children-Group 1), and from 2001 to 2005 (89 children-Group 2). RESULTS: Head trauma was more common in the Group 1 patients (52.6% vs. 45.2%), but skull fractures and intracranial haemorrhage occurred more frequently in Group 2 (28.5% vs. 16.7%; 21.3% vs. 8.3%, respectively). Injury to the stomach or duodenum, kidneys and liver were all more common in Group 2. Splenic injury occurred with equal frequency in both groups, but more severe injuries were seen in Group 2. More children in Group 2 required intensive care (31% vs. 19.3%). CONCLUSIONS: There is a changing pattern of bicycle-related injuries in children, with chest and abdominal injuries dominating, and an increasing incidence of more severe injury. These findings are important in decision-making regarding preventive measures.

Observational pain assessment versus self-report in paediatric triage.

OBJECTIVE: To examine if observational pain assessment can be used for purposes of triage in children aged >3 years. METHODS: A prospective, single blind, controlled trial was undertaken in children who presented to the emergency department (ED) with pain. Pain was assessed in the waiting room and again at triage before any treatment was administered using the Alder Hey Triage Pain Score (AHTPS), an observational tool designed for triage, and a self-report tool, either the Wong-Baker Faces Pain Rating Scale (WBS) for 3-7-year-old children or a visual analogue scale (VAS) for 8-15-year-old children. Scores were compared by instrument (observational and self-report) and ED location (waiting room and triage room). RESULTS: 75 children (29 aged 3-7 years and 46 aged 8-15 years) were enrolled in the study. The AHTPS scores were significantly lower than the scores measured by the WBS/VAS (p<0.001). The level of pain measured by both methods (self-report, observational) was lower in the triage room. Compared with the AHTPS, the WBS and VAS scored significantly lower in the triage room than in the waiting room (p<0.042 and p<0.006, respectively). CONCLUSIONS: Observational pain assessment underestimates children's perception of pain and should not be recommended in children aged >3 years. Triage has a calming effect on children.

How much acetaminophen do paediatricians prescribe? A survey among Israeli paediatricians.

OBJECTIVE: To describe the current practice of Israeli paediatricians regarding acetaminophen dosing. METHODS: A cross-sectional survey among 200 paediatricians. The paediatricians were questioned of the recommended dose of acetaminophen, and whether they give prescriptions for acetaminophen and instruct their patients how to use it. RESULTS: The response rate was 36%. When asked on the recommended dose of acetaminophen, 30 (42%) physicians gave doses different from the dose recommended by the Israeli formulary. Thirty (42%) of the paediatricians answered that they usually or always give prescriptions for antipyretics. CONCLUSIONS: A large percentage of Israeli paediatricians do not provide parents proper instructions regarding the correct dosing of acetaminophen.

Treatment strategies for early presenting acetaminophen overdose: a survey of medical directors of poison centers in North America and Europe.

BACKGROUND: Acetaminophen is frequently used in self-poisoning in Western countries. Although treatment with N-acetylcysteine (NAC) reduces liver injury, no consensus exists on the preferred management of acetaminophen toxicity. OBJECTIVES: To describe the approach taken by toxicologists in North America and Europe toward the management of acetaminophen toxicity. METHODS: Medical directors of poison centers in the US, Canada, and Europe were surveyed by means of a questionnaire presenting two clinical scenarios of acetaminophen overdose: a healthy adolescent with no risk factors who had an acute ingestion of acetaminophen, and an adult with both acute ingestion and possible risk factors. For each case, several questions about the management of these patients were asked. RESULTS: Questionnaires were sent to medical directors of 76 poison centers in North America and 48 in Europe, with response rates of 62% and 44%, respectively. Forty percent of responders suggested using charcoal 4 hours after ingestion of a potential toxic dose of acetaminophen, and 90% recommended treatment with NAC when levels were above 150 microg/mL but below 200 microg/mL 4 hours after ingestion. Duration of treatment with oral NAC ranged from 24 to 96 hours; 38 responders suggested a duration of 72 hours. Of 49 centers recommending oral NAC, 18 (36.7%) said they might consider treatment for less than 72 hours. Eleven of 29 (37.9%) responders suggested treatment with intravenous NAC for more than 20 hours as their usual protocol or a protocol for specific circumstances. CONCLUSIONS: Our study showed large variability in the management of acetaminophen overdose. Variations in treatment protocols should be addressed in clinical trials to optimize the treatment for this common problem.

Management of paracetamol overdose: current controversies.

Paracetamol (acetaminophen) is one of the most frequently used analgesics, and is the most commonly used substance in self-poisoning in the US and UK. Paracetamol toxicity is manifested primarily in the liver. Treatment with N-acetyl-cysteine (NAC), if started within 10 hours from ingestion, can prevent hepatic damage in most cases. Pharmacokinetic data relating plasma paracetamol concentration to time after ingestion have been used to generate a 'probable hepatoxicity line' to predict which cases of paracetamol overdose will result in hepatotoxicity and should be treated with NAC. However, later studies use a 25% lower line as their 'possible hepatotoxicity line'. Although adopting the original line may save considerable resources, further studies are needed to determine whether such an approach is safe. On the basis of the metabolism of paracetamol, several risk factors for paracetamol toxicity have been proposed. These risk factors include long term alcohol (ethanol) ingestion, fasting and treatment with drugs that induce the cytochrome P450 2E1 enzyme system. Although some studies have suggested that these risk factors may be associated with worse prognosis, the data are inconclusive. However, until further evidence is available, we suggest that the lower line should be used when risk factors are present. In Canada and the UK, the intravenous regimen for NAC is used almost exclusively; in the US, an oral regimen is used. Both regimens have been shown to be effective. There is no large scale study with direct comparison between these 2 therapeutic protocols and controversy still exists as to which regimen is superior. During the last few years there has been an increase in the number of reports of liver failure associated with prolonged paracetamol administration for therapeutic reasons. The true incidence of this phenomenon is not known. We suggest testing liver enzyme levels if a child has received more than 75 mg/kg/day of paracetamol for more than 24 hours during febrile illness, and to treat with NAC when transaminase levels are elevated. Paracetamol overdose during pregnancy should be treated with either oral or intravenous NAC according to the regular protocols in order to prevent maternal, and potentially fetal, toxicity. Unless severe maternal toxicity develops, paracetamol overdose does not appear to increase the risk for adverse pregnancy outcome.

Leflunomide: new antirheumatic drug. Effect on pregnancy outcomes.

QUESTION: I am treating a 34-year-old woman with rheumatoid arthritis. She began taking the new drug leflunomide (Arava) 6 months ago and had good clinical response. She is now planning her first pregnancy. What should she do? ANSWER: Leflunomide is a new and effective disease-modifying antirheumatic drug. Animal studies have shown an increased rate of malformations and fetal death in various species, but there are no data on pregnancy outcomes in humans treated with leflunomide. Since the drug has a prolonged and unpredictable elimination half-life, it should be stopped during pregnancy. The manufacturer recommends that patients who wish to become pregnant be treated with cholestyramine, which enhances elimination.

Effects of prenatal exposure to marijuana.

QUESTION: I am treating a 27-year-old woman who is now in her 10th week of pregnancy. She smokes marijuana two to three times a week, but does not use other drugs. She also smokes 20 cigarettes a day. I am concerned about the effects of marijuana exposure on her baby. ANSWER: It is not always possible to isolate the effect of marijuana exposure from other possible confounders on pregnancy outcome. Although marijuana is not an established human teratogen, recent well conducted studies suggest it might have subtle negative effects on neurobehavioural outcomes, including sleep disturbances, impaired visual problem solving, hyperactivity, impassivity, inattention, and increased delinquency.

Hypertension and abdominal pain: uncommon presentation after exposure to a pine caterpillar.

UNLABELLED: The pine caterpillar Thaumatopoea wilkinsoni is found in pine woods all over Israel. Contact with its hair usually results in local reactions. Systemic reactions after contact with caterpillar hairs are known in other caterpillar species, but have been described only once after contact with T. wilkinsoni. We describe a group of adolescents who were exposed to T. wilkinsoni while camping in a pine wood. Three of them were referred to an emergency department. They had severe pruritus, pain and edema at the contact sites, with papular and urticarial rashes. Two of the patients had abdominal pain and one patient had hypertension for several hours. The hypertension resolved spontaneously. CONCLUSION: Skin eruptions are the most common manifestations of T. wilkinsoni contact, however, although systemic manifestations are rare, abdominal pain and hypertension may occur.

Distinction between processing of normal and mutant complement C3 within human skin fibroblasts.

Inherited C3 deficiency may result from mutations in the C3 gene affecting transcription or translation (type I deficiency). We described a type II C3 deficiency caused by a mutation yielding an abnormal non-secreted C3. The post-translational processing of mutant and normal C3 was analyzed in fibroblasts grown from skin biopsies. Mutant C3 is located mainly in the endoplasmic reticulum (ER), whereas normal C3 is seen evenly distributed throughout the cytoplasm. Most of the mutant C3 is degraded within the cell, and only a small fraction (around 8%) is secreted after 20 h chase. Processing of C3 at 19 degrees C was reduced in normal fibroblasts but completely blocked in mutant fibroblasts. ATP depletion blocked processing of normal proC3 to C3. In contrast, the mutant proC3 was partly degraded in ATP-depleted cells, yet its complete degradation and secretion were blocked. Intracellular degradation of the mutant C3 was not inhibited by NH4Cl, thus excluding cleavage within lysosomes. These results demonstrate that the type II mutant C3 studied here is retained in the ER probably by a quality contol machinery that identifies abnormal protein folding. Consequently, it is destined to undergo a two-step intracellular degradation; an initial ATP-independent step followed by an ATP-dependent step.