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Piotrowski A.,University of Alabama at Birmingham | Piotrowski A.,Medical University of Gdańsk | Xie J.,University of Alabama at Birmingham | Liu Y.F.,University of Alabama at Birmingham | And 25 more authors.
Nature Genetics | Year: 2014

Constitutional SMARCB1 mutations at 22q11.23 have been found in ∼50% of familial and <10% of sporadic schwannomatosis cases. We sequenced highly conserved regions along 22q from eight individuals with schwannomatosis whose schwannomas involved somatic loss of one copy of 22q, encompassing SMARCB1 and NF2, with a different somatic mutation of the other NF2 allele in every schwannoma but no mutation of the remaining SMARCB1 allele in blood and tumor samples. LZTR1 germline mutations were identified in seven of the eight cases. LZTR1 sequencing in 12 further cases with the same molecular signature identified 9 additional germline mutations. Loss of heterozygosity with retention of an LZTR1 mutation was present in all 25 schwannomas studied. Mutations segregated with disease in all available affected first-degree relatives, although four asymptomatic parents also carried an LZTR1 mutation. Our findings identify LZTR1 as a gene predisposing to an autosomal dominant inherited disorder of multiple schwannomas in ∼80% of 22q-related schwannomatosis cases lacking mutation in SMARCB1. © 2014 Nature America, Inc.


Razik R.,University of Toronto | Chong C.A.,Lakeridge Health Corporation | Nguyen G.C.,University of Toronto | Nguyen G.C.,Institute of Health Policy Management and Evaluation
Canadian Journal of Gastroenterology | Year: 2013

BACKGROUND: Traditionally regarded as a disease of the elderly, the incidence of diverticulitis of the colon has been on the rise, especially in younger cohorts. These patients have been found to experience a more aggressive disease course with more frequent hospitalization and greater need for surgical intervention. objective: To characterize factors that portend a poor prognosis in patients diagnosed with diverticulitis; in particular, to evaluate the role of demographic variables on disease course. METHODS: Using the Canadian Institute for Health Information Discharge Abstract Databases, readmission rates, length of stay, colectomy rates and mortality rates in patients hospitalized for diverticulitis were examined. Data were stratified according to age, sex and comorbidity (as defined by the Charlson index). RESULTS: In the cohort =30 years of age, a clear male predominance was apparent. Colectomy rate in the index admission, stratified according to age, demonstrated a J-shaped curve, with the highest rate in patients =30 years of age (adjusted OR 2.3 [95% CI 1.62 to 3.27]) compared with the 31 to 40 years of age group. In-hospital mortality increased with age. Cumulative rates of readmission at six and 12 months were 6.8% and 8.8%, respectively. CONCLUSION: In the present nationwide cohort study, younger patients (specifically those =30 years of age) were at highest risk for colectomy during their index admission for diverticulitis. It is unclear whether this observation was due to more virulent disease among younger patients, or surgeon and patient preferences. © 2013 Pulsus Group Inc. All rights reserved.


Nguyen G.C.,University of Toronto | Nguyen G.C.,Institute of Health Policy Management and Evaluation | Bollegala N.,University of Toronto | Chong C.A.,Lakeridge Health Corporation
Clinical Gastroenterology and Hepatology | Year: 2014

Background & Aims: Patients with inflammatory bowel diseases (IBD) are hospitalized frequently. We sought toidentify factors associated with risk for IBD-related readmission to the hospital. Methods: We performed a retrospective analysis of 26,403 patients hospitalized for IBD from 2004 through 2010 using the Canadian Institute for Health Information Discharge Abstract databases. We examined whether demographic factors, comorbidity, and hospital IBD admission volume were associated with readmission rates, length of stay, bowel resection, and mortality. Results: Young, middle-age, and elderly adults were more than twice as likely to undergo surgery during hospitalization than pediatric patients. Elderly patients with IBD had a nearly 40-fold greater in-hospital mortality than pediatric patients (odds ratio, 37.4; 95% confidence interval [CI], 5.17-270.0). In-hospital mortality was lower at hospitals with the highest volume of IBD patients than at those with low volume (odds ratio, 0.20; 95% CI, 0.05-0.97). Rates of readmission were lower for patients with ulcerative colitis than Crohn's disease (hazard ratio, 0.79; 95% CI, 0.72-0.86). The hazard ratios for readmission among young, middle-age, and elderly adults, compared with those of pediatric patients, were 0.79 (95% CI, 0.69-0.90), 0.57 (95% CI, 0.49-0.65), and 0.44 (95% CI, 0.37-0.53), respectively. Rates of readmission were lower at the highest-volume, compared with the lowest-volume, hospitals (hazard ratio, 0.78; 95% CI, 0.64-0.96). Conclusions: Based on a retrospective database analysis, pediatric patients with IBD are at greater risk for readmission to the hospital than older patients. Efforts should be made to determine whether factors that contribute to this risk are preventable. The lower risk of readmission at the highest-volume hospitals may reflect optimal management during hospitalization or follow-up evaluation. © 2014 AGA Institute.


Ricketts M.L.,University of Western Ontario | Baerlocher M.O.,Royal Victoria Hospital | Asch M.R.,Lakeridge Health Corporation | Myers A.,Lakeridge Health Corporation
Canadian Association of Radiologists Journal | Year: 2013

Background: It is important for physicians to be aware of the radiation doses as well as the risks associated with diagnostic imaging procedures that they are ordering. Methods: A survey was administered to patients, medical students, and referring physicians from a number of specialties to determine background knowledge regarding radiation exposure and risk associated with commonly ordered medical imaging tests. Results: A total of 127 patients, 32 referring physicians, and 30 medical students completed the survey. The majority of patients (92%) were not informed of the radiation risks associated with tests that they were scheduled to receive and had false perceptions about the use of radiation and its associated risks. Physicians and medical students had misconceptions about the use of ionizing radiation in a number of radiologic examinations; for example, 25% and 43% of physicians and medical students, respectively, were unaware that interventional procedures used ionizing radiation, and 28% of physicians were unaware that mammography used ionizing radiation. Computed tomographies and barium studies were thought to be associated with the least ionizing radiation among physicians. Conclusion: There is a need for educating the public, medical students, and referring physicians about radiation exposure and associated risk so that (1) patients receiving multiple medical imaging tests are aware of the radiation that they are receiving and (2) physicians and future physicians will make informed decisions when ordering such tests to limit the amount of radiation that patients receive and to promote informed consent among patients. © 2013 Canadian Association of Radiologists. All rights reserved.


Saltzman A.J.,Columbia University | Mancini-Dinardo D.,HealthCare Partners | Li C.,McMaster Childrens Hospital | Chung W.K.,Columbia University | And 16 more authors.
Circulation Research | Year: 2010

RATIONALE: The myosin-binding protein C isoform 3 (MYBPC3) variant Arg502Trp has been identified in multiple hypertrophic cardiomyopathy (HCM) cases, but compelling evidence to support or refute the pathogenicity of this variant is lacking. OBJECTIVE: To determine the prevalence, origin and clinical significance of the MYBPC3 Arg502Trp variant. METHODS AND RESULTS: The prevalence of MYBPC3 Arg502Trp was ascertained in 1414 sequential HCM patients of primarily European descent. MYBPC3 Arg502Trp was identified in 34 of these 1414 unrelated HCM patients. Segregation of MYBPC3 Arg502Trp with clinical status was assessed in family members. Disease haplotypes were examined in 17 families using two loci flanking MYBPC3. Family studies identified an additional 43 variant carriers, many with manifest disease, yielding a calculated odds ratio of 11 000:1 for segregation of MYBPC3 Arg502Trp with HCM. Analyses in 17 families showed at least 4 independent haplotypes flanked MYBPC3 Arg502Trp. Eight individuals (4 probands and 4 family members) also had another sarcomere protein gene mutation. Major adverse clinical events occurred in approximately 30% of MYBPC3 Arg502Trp carriers by age 50; these were significantly more likely (P<0.0001) when another sarcomere mutation was present. CONCLUSIONS: MYBPC3 Arg502Trp is the most common and recurrent pathogenic mutation in a diverse primarily European descent HCM cohort, occurring in 2.4% of patients. MYBPC3 Arg502Trp conveys a 340-fold increased risk for HCM by 45 years of age, when more than 50% of carriers have overt disease. HCM prognosis worsens when MYBPC3 Arg502Trp occurs in the setting of another sarcomere protein gene mutation. © 2010 American Heart Association, Inc.


Silverman M.S.,University of Toronto | Silverman M.S.,Lakeridge Health Corporation | Davis I.,Dalhousie University | Pillai D.R.,University of Toronto | Pillai D.R.,Public Health England
Clinical Gastroenterology and Hepatology | Year: 2010

Background & Aims: Clostridium difficile infection (CDI) can relapse in patients with significant comorbidities. A subset of these patients becomes dependent on oral vancomycin therapy for prolonged periods with only temporary clinical improvement. These patients incur significant morbidity from recurrent diarrhea and financial costs from chronic antibiotic therapy. Methods: We sought to investigate whether self- or family-administered fecal transplantation by low volume enema could be used to definitively treat refractory CDI. Results: We report a case series (n = 7) where 100% clinical success was achieved in treating these individuals with up to 14 months of follow-up. Conclusions: Fecal transplantation by low volume enema is an effective and safe option for patients with chronic relapsing CDI, refractory to other therapies. Making this approach available in health care settings has the potential to dramatically increase the number of patients who could benefit from this therapy. © 2010 AGA Institute.


PubMed | University of Toronto, Lakeridge Health Corporation and Princess Margaret Cancer Center
Type: Journal Article | Journal: Current oncology (Toronto, Ont.) | Year: 2016

We evaluated the feasibility, reliability, and validity of the Brain Metastases Symptom Checklist (bmsc), a novel self-report measure of common symptoms experienced by patients with brain metastases.Patients with first-presentation symptomatic brain metastases (n = 137) referred for whole-brain radiotherapy (wbrt) completed the bmsc at time points before and after treatment. Their caregivers (n = 48) provided proxy ratings twice on the day of consultation to assess reliability, and at week 4 after wbrt to assess responsiveness to change. Correlations with 4 other validated assessment tools were evaluated.The symptoms reported on the bmsc were largely mild to moderate, with tiredness (71%) and difficulties with balance (61%) reported most commonly at baseline. Test-retest reliability for individual symptoms had a median intraclass correlation of 0.59 (range: 0.23-0.85). Caregiver proxy and patient responses had a median intraclass correlation of 0.52. Correlation of absolute scores on the bmsc and other symptom assessment tools was low, but consistency in the direction of symptom change was observed. At week 4, change in symptoms was variable, with improvements in weight gain and sleep of 42% and 41% respectively, and worsening of tiredness and drowsiness of 62% and 59% respectively.The bmsc captures a wide range of symptoms experienced by patients with brain metastases, and it is sensitive to change. It demonstrated adequate test-retest reliability and face validity in terms of its responsiveness to change. Future research is needed to determine whether modifications to the bmsc itself or correlation with more symptom-specific measures will enhance validity.


PubMed | Cancer Care Ontario, University of Toronto, Lakeridge Health Corporation, London Health Sciences Center and Samuel Lunenfeld Research Institute
Type: Journal Article | Journal: The Annals of thoracic surgery | Year: 2014

The aim of this project was to develop a set of quality indicators to assess surgical decision making in the care of patients with non-small cell lung cancer (NSCLC).A multidisciplinary Expert Panel of 16 physicians used a modified Delphi process to identify quality indicators that evaluated the processes of care in patients with NSCLC. A systematic review identified potential indicators, which were rated on actionability, validity, usefulness, discriminability, and feasibility in two rounds of questionnaires. The first questionnaire was completed by the Expert Panel and by the larger thoracic surgical community of practice; the second questionnaire was sent to only the Expert Panel. Expert Panel members attended an in-person meeting to review the results of the two questionnaires and to compile the final list of indicators by consensus.From the literature review, 41 potential indicators were identified. An additional 16 indicators were suggested by the Expert Panel: 13 indicators in thetwo rounds of questionnaires and three after the discussion at the in-person meeting. One further indicator was identified after the in-person meeting. In the end, 17 indicators were chosen from seven domains: preoperative assessment, staging, surgical procedures, pathology, adjuvant therapy, surgical outcomes, and miscellaneousBy use of a modified Delphi process, 17 indicators to assess the quality of processes of surgical care for patients with NSCLC were developed.


Skeete D.H.-A.,Queen Elizabeth Hospital | Cesar-Rittenberg P.,Dalhousie University | Jong R.,Lakeridge Health Corporation | Murray S.K.,Dalhousie University | Colgan T.J.,Mount Sinai Hospital
Journal of Lower Genital Tract Disease | Year: 2010

OBJECTIVE: To describe 2 cases of myeloid sarcoma of the vagina, in a patient without a history of acute myeloid leukemia (AML) and in another whose condition was previously diagnosed with AML. MATERIALS AND METHODS: The clinical histories of 2 patients whose conditions were diagnosed with myeloid sarcoma of the vagina were obtained from their medical records. RESULTS: Case 1: A 77-year-old woman with no systemic illnesses presented with a vaginal lump. Clinically, there was a 6-cm periurethral mass that was examined by biopsy. The histopathologic specimen was evaluated on routine and immunohistochemical stains, and myeloid sarcoma was diagnosed after extensive immunohistochemical analysis. The patient was treated with pelvic radiation. She developed extensive myeloid sarcoma of the skin and AML 4.5 months later; she died 2 weeks later, 5 months after the initial presentation. Case 2: A 36-year-old woman with a known history of AML who has had multiple leukemic and extramedullary recurrences presented with a pelvic mass. Physical findings revealed large masses in the vagina and rectovaginal septum, which were confirmed as myeloid sarcoma after biopsy and histologic examination. The patient was treated with pelvic/vaginal radiation. Five months later, she had another leukemic relapse and died within 1 day of palliative chemotherapy. CONCLUSIONS: Myeloid sarcoma of the vagina is extremely rare. Most patients have a poor prognosis and either have a history of or will subsequently develop AML. © 2010, American Society for Colposcopy and Cervical Pathology.


Yousefi V.,Lakeridge Health Corporation
Journal of Clinical Outcomes Management | Year: 2011

• Background: Despite significant growth of hospital medicine in Canada over the past decade, little is known about the characteristics of hospitalist programs and how they operate. • Objective: To understand the type of activities hospitalists perform and the amount of time they spend on performing various tasks. • Methods: Over a 2-week period, a trained observer followed 7 hospitalists for 2-hour blocks during 11 shifts. The shifts were chosen to represent various times of day, evening, weekend, and night call shifts. Activities were recorded using data sheets capturing 1-minute increments, allowing for recording of simultaneous tasks. Activity categories were defined a priori. • Results: A total of 2070 minutes of observations were recorded. Hospitalists were found to be multi-tasking during 30% of the time. Direct and indirect patient care was observed in 17% and 66% of the time, respectively. Gathering information, communication, and documentation represented 37%, 34%, and 28% of indirect care. Hospitalists spent 8% of their time on traveling within the hospital and 8% on personal tasks. • Conclusion: Canadian hospitalists spend the majority of their time on indirect patient care. Better integrated electronic medical record systems may result in increased efficiency for hospitalists. Additionally, provincial health ministries must consider the amount of time hospitalists spend on nonbillable activities when reviewing inpatient fee codes to ensure sustainable funding mechanisms for hospitalist programs. Copyright 2011 by Turner White Communications Inc. All rights reserved.

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