Sunnybrook Health Sciences Centre

About: Sunnybrook Health Sciences Centre is a healthcare organization based out in Toronto, Ontario, Canada. It is known for research contribution in the topics: Population & Medicine. The organization has 7689 authors who have published 15236 publications receiving 523019 citations. The organization is also known as: Sunnybrook.

Serious Adverse Reactions Induced by Minocycline: Report of 13 Patients and Review of the Literature

Abstract: Background: Minocycline has been reported to cause serious, albeit rare, adverse events, including serum sickness—like reaction, hypersensitivity syndrome reaction, and drug-induced lupus. A retrospective review of patients seen in our Adverse Drug Reaction Clinic as well as information obtained from the Health Protection Branch was done to identify patients with minocycline-induced reactions. In addition, the literature concerning serious reactions to minocycline was reviewed. Observations: Six patients with a hypersensitivity syndrome reaction, 6 patients with a serum sickness—like reaction, and 1 patient who had symptoms consistent with drug-induced lupus were identified. A review of the literature identified 11 cases of hypersensitivity syndrome reaction, 1 case of serum sickness—like reaction, and 24 cases of drug-induced lupus. Serum sickness—like reactions occur sooner than hypersensitivity syndrome reactions (15.6 vs 23.7 days,P=.04). Drug-induced lupus occurs on average 2 years after the start of minocycline therapy. Conclusions: Dermatologists need to be aware of the serious adverse reactions that can develop after minocycline use. In patients who may require long-term therapy with minocycline (>1 year), we suggest that antinuclear antibody and hepatic transaminase levels be determined at baseline. Rechallenge with minocycline or other tetracyclines is currently not recommended for patients who develop these serious reactions. Arch Dermatol. 1996;132:934-939

Interleukin 6: a fibroblast-derived growth inhibitor of human melanoma cells from early but not advanced stages of tumor progression.

Abstract: Recently we reported that human dermal fibroblasts, or conditioned media obtained from such cells, affect the growth of human melanoma cells as a direct function of tumor progression: melanoma cells obtained from early-stage (metastatically incompetent) primary lesions were growth inhibited, whereas cells obtained from more advanced (metastatically competent) primary lesions, or metastases, were growth stimulated. Ion-exchange and gel-filtration chromatography of fibroblast conditioned medium revealed the inhibitor to be a protein of molecular mass between 20 and 30 kDa and distinct from the stimulator. This is the approximate molecular mass of interleukin 6 (IL-6), a ubiquitous multifunctional cytokine known to affect in particular many kinds of hemopoietic and lymphoid cells. Since this cytokine is known to be made by fibroblasts, we attempted to determine if the human fibroblast-derived growth inhibitor (hFDGI) was identical to IL-6. Neutralizing antibodies specific for IL-6 completely eliminated the inhibitory activity of hFDGI. Moreover, exposure to human recombinant IL-6 was found to inhibit the growth of early-stage melanoma cells obtained from radial growth phase (RGP) or early vertical growth phase (VGP) primary lesions in three of four cases. In contrast, melanoma cells from a number of more advanced VGP primary lesions, or from distant metastases, were completely resistant to this IL-6-mediated growth inhibition. Acquisition of an "IL-6-resistant" phenotype by metastatically competent melanoma cell variants may provide such cells with a proliferative advantage within the dermal mesenchyme (a hallmark of melanoma cells that are malignant), helping them eventually to dominate advanced primary lesions and to establish secondary growths elsewhere.

Fifty Years of Research in ARDS.The Epidemiology of Acute Respiratory Distress Syndrome. A 50th Birthday Review

Abstract: Since its first description 50 years ago, no other intensive care syndrome has been as extensively studied as acute respiratory distress syndrome (ARDS). Despite this extensive body of research, many basic epidemiologic questions remain unsolved. The lack of gold standard tests jeopardizes accurate diagnosis and translational research. Wide variation in the population incidence has been reported, making even simple estimates of the burden of disease problematic. Despite these limitations, there has been an increase in the understanding of pathophysiology and important risk factors both for the development of ARDS and for important patient-centered outcomes like mortality. In this Critical Care Perspective, we discuss the historical context of ARDS description and attempts at its definition. We highlight the epidemiologic challenges of studying ARDS, as well as other intensive care syndromes, and propose solutions to address them. We update the current knowledge of ARDS trends in incidence and mortality, r...

Recommendations for HLA-B*15:02 and HLA-A*31:01 genetic testing to reduce the risk of carbamazepine-induced hypersensitivity reactions.

Abstract: OBJECTIVE To systematically review evidence on genetic risk factors for carbamazepine (CBZ)-induced hypersensitivity reactions (HSRs) and provide practice recommendations addressing the key questions: (1) Should genetic testing for HLA-B*15:02 and HLA-A*31:01 be performed in patients with an indication for CBZ therapy to reduce the occurrence of CBZ-induced HSRs? (2) Are there subgroups of patients who may benefit more from genetic testing for HLA-B*15:02 or HLA-A*31:01 compared to others? (3) How should patients with an indication for CBZ therapy be managed based on their genetic test results? METHODS A systematic literature search was performed for HLA-B*15:02 and HLA-A*31:01 and their association with CBZ-induced HSRs. Evidence was critically appraised and clinical practice recommendations were developed based on expert group consensus. RESULTS Patients carrying HLA-B*15:02 are at strongly increased risk for CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in populations where HLA-B*15:02 is common, but not CBZ-induced hypersensitivity syndrome (HSS) or maculopapular exanthema (MPE). HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported from Asian countries only, including China, Thailand, Malaysia, and India. HLA-B*15:02 is rare among Caucasians or Japanese; no HLA-B*15:02-positive patients with CBZ-SJS/TEN have been reported so far in these groups. HLA-A*31:01-positive patients are at increased risk for CBZ-induced HSS and MPE, and possibly SJS/TEN and acute generalized exanthematous pustulosis (AGEP). This association has been shown in Caucasian, Japanese, Korean, Chinese, and patients of mixed origin; however, HLA-A*31:01 is common in most ethnic groups. Not all patients carrying either risk variant develop an HSR, resulting in a relatively low positive predictive value of the genetic tests. SIGNIFICANCE This review provides the latest update on genetic markers for CBZ HSRs, clinical practice recommendations as a basis for informed decision making regarding the use of HLA-B*15:02 and HLA-A*31:01 genetic testing in patients with an indication for CBZ therapy, and identifies knowledge gaps to guide future research. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit.

Abstract: Background Proper sedation for neonates undergoing uncomfortable procedures may reduce stress and avoid complications. Midazolam is a short-acting benzodiazepine that is used increasingly in neonatal intensive care units (NICUs). However, its effectiveness as a sedative in neonates has not been systematically evaluated. Objectives Primary objecive To assess the effectiveness of intravenous midazolam infusion for sedation, as evaluated by behavioural and/or physiological measurements of sedation levels, in critically ill neonates in the NICU. Secondary objectives To assess effects of intravenous midazolam infusion for sedation on complications including the following. 1. Incidence of intraventricular haemorrhage (IVH)/periventricular leukomalacia (PVL). 2. Mortality. 3. Occurrence of adverse effects associated with the use of midazolam (hypotension, neurological abnormalities). 4. Days of ventilation. 5. Days of supplemental oxygen. 6. Incidence of pneumothorax. 7. Length of NICU stay (days). 8. Long-term neurodevelopmental outcomes. Search methods We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 5), MEDLINE via PubMed (1966 to 16 June 2016), Embase (1980 to 16 June 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 16 June 2016). We searched clinical trials databases, conference proceedings and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Selection criteria We selected for review randomised and quasi-randomised controlled trials of intravenous midazolam infusion for sedation in infants aged 28 days or younger. Data collection and analysis We abstracted data regarding the primary outcome of level of sedation. We assessed secondary outcomes such as intraventricular haemorrhage, periventricular leukomalacia, death, length of NICU stay and adverse effects associated with midazolam. When appropriate, we performed meta-analyses using risk ratios (RRs) and risk differences (RDs), and if the RD was statistically significant, we calculated the number needed to treat for an additional beneficial outcome (NNTB) or an additional harmful outcome (NNTH), along with their 95% confidence intervals (95% CIs) for categorical variables, and weighted mean differences (WMDs) for continuous variables. We assessed heterogeneity by performing the I-squared (I2) test. Main results We included in the review three trials enrolling 148 neonates. We identified no new trials for this update. Using different sedation scales, each study showed a statistically significantly higher sedation level in the midazolam group compared with the placebo group. However, none of the sedation scales used have been validated in preterm infants; therefore, we could not ascertain the effectiveness of midazolam in this population. Duration of NICU stay was significantly longer in the midazolam group than in the placebo group (WMD 5.4 days, 95% CI 0.40 to 10.5; I2 = 0%; two studies, 89 infants). One study (43 infants) reported significantly lower Premature Infant Pain Profile (PIPP) scores during midazolam infusion than during dextrose (placebo) infusion (MD -3.80, 95% CI -5.93 to -1.67). Another study (46 infants) observed a higher incidence of adverse neurological events at 28 days' postnatal age (death, grade III or IV IVH or PVL) in the midazolam group compared with the morphine group (RR 7.64, 95% CI 1.02 to 57.21; RD 0.28, 95% CI 0.07 to 0.49; NNTH 4, 95% CI 2 to 14) (tests for heterogeneity not applicable). We considered these trials to be of moderate quality according to GRADE assessment based on the following outcomes: mortality during hospital stay, length of NICU stay, adequacy of analgesia according to PIPP scores and poor neurological outcomes by 28 days' postnatal age. Authors' conclusions Data are insufficient to promote the use of intravenous midazolam infusion as a sedative for neonates undergoing intensive care. This review raises concerns about the safety of midazolam in neonates. Further research on the effectiveness and safety of midazolam in neonates is needed.