Showing papers by "Sunnybrook Health Sciences Centre published in 2015"

Transfusion of plasma, platelets, and red blood cells in a 1: 1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: The PROPPR randomized clinical trial

Abstract: Importance Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials. Objective To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. Design, Setting, and Participants Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013. Interventions Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled). Main Outcomes and Measures Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status. Results No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, −4.2% [95% CI, −9.6% to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, −3.7% [95% CI, −10.2% to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, −5.4% [95% CI, −10.4% to −0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P P Conclusions and Relevance Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups. Trial Registration clinicaltrials.gov Identifier:NCT01545232

Long-Term Follow-Up of a Large Active Surveillance Cohort of Patients With Prostate Cancer

Abstract: Purpose Active surveillance is increasingly accepted as a treatment option for favorable-risk prostate cancer. Long-term follow-up has been lacking. In this study, we report the long-term outcome of a large active surveillance protocol in men with favorable-risk prostate cancer. Patients and Methods In a prospective single-arm cohort study carried out at a single academic health sciences center, 993 men with favorable- or intermediate-risk prostate cancer were managed with an initial expectant approach. Intervention was offered for a prostate-specific antigen (PSA) doubling time of less than 3 years, Gleason score progression, or unequivocal clinical progression. Main outcome measures were overall and disease-specific survival, rate of treatment, and PSA failure rate in the treated patients. Results Among the 819 survivors, the median follow-up time from the first biopsy is 6.4 years (range, 0.2 to 19.8 years). One hundred forty-nine (15%) of 993 patients died, and 844 patients are alive (censored rate, 8...

Colorectal cancer screening: a global overview of existing programmes

Abstract: Colorectal cancer (CRC) ranks third among the most commonly diagnosed cancers worldwide, with wide geographical variation in incidence and mortality across the world. Despite proof that screening can decrease CRC incidence and mortality, CRC screening is only offered to a small proportion of the target population worldwide. Throughout the world there are widespread differences in CRC screening implementation status and strategy. Differences can be attributed to geographical variation in CRC incidence, economic resources, healthcare structure and infrastructure to support screening such as the ability to identify the target population at risk and cancer registry availability. This review highlights issues to consider when implementing a CRC screening programme and gives a worldwide overview of CRC burden and the current status of screening programmes, with focus on international differences.

Sepsis: a roadmap for future research

Abstract: Sepsis is a common and lethal syndrome: although outcomes have improved, mortality remains high. No specific anti-sepsis treatments exist; as such, management of patients relies mainly on early recognition allowing correct therapeutic measures to be started rapidly, including administration of appropriate antibiotics, source control measures when necessary, and resuscitation with intravenous fluids and vasoactive drugs when needed. Although substantial developments have been made in the understanding of the basic pathogenesis of sepsis and the complex interplay of host, pathogen, and environment that affect the incidence and course of the disease, sepsis has stubbornly resisted all efforts to successfully develop and then deploy new and improved treatments. Existing models of clinical research seem increasingly unlikely to produce new therapies that will result in a step change in clinical outcomes. In this Commission, we set out our understanding of the clinical epidemiology and management of sepsis and then ask how the present approaches might be challenged to develop a new roadmap for future research.

Exploring the rising incidence of neuroendocrine tumors: a population-based analysis of epidemiology, metastatic presentation, and outcomes.

Abstract: BACKGROUND An increased incidence of neuroendocrine tumors (NETs) has been reported worldwide, but the reasons underlying this rise have not been identified By assessing patterns of metastatic presentation, this study sought to examine the epidemiologic characteristics of NETs and the contribution of early-stage detection to the rising incidence METHODS A population-based retrospective cohort study was conducted with prospectively maintained databases linked at the Institute for Clinical Evaluative Sciences Adult patients with a NET diagnosis from 1994 to 2009 in Ontario, Canada were included The main outcomes included the overall and site-specific incidence, proportion of metastatic disease, overall survival (OS), and recurrence-free survival (RFS) RESULTS Five thousand six hundred nineteen NET cases were identified The incidence of NETs increased from 248 to 586 per 100,000 per year Metastases were found in 208% at presentation and in another 38% after the initial diagnosis The proportion of metastases at presentation decreased from 1994 to 2009 (from 29% to 13%) Therefore, although the incidence of all NETs increased, the overall incidence of metastases did not change (063-069 per 100,000 per year) The 10-year OS rate was 465%, and the RFS rate was 646% In addition to the primary tumor site, independent predictors of worse OS included an advanced age (P < 0001), male sex (P < 0001), a low socioeconomic status (P < 0001), and rural living (P = 0049) CONCLUSIONS The incidence of NETs has markedly increased over the course of 15 years This is the first study to provide evidence suggesting that the increase in the incidence of NETs may be due to increased detection In addition to tumor characteristics, low income and rural residency portend worse survival for patients with NETs Cancer 2015;121:589–597 © 2014 American Cancer Society

Sentinel node biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: the SN FNAC study.

Abstract: Purpose An increasing proportion of patients (> 30%) with node-positive breast cancer will obtain an axillary pathologic complete response after neoadjuvant chemotherapy (NAC) If sentinel node (SN) biopsy (SNB) is accurate in this setting, completion node dissection (CND) morbidity could be avoided Patients and Methods In the prospective multicentric SN FNAC study, patients with biopsy-proven node-positive breast cancer (T0-3, N1-2) underwent both SNB and CND Immunohistochemistry (IHC) use was mandatory, and SN metastases of any size, including isolated tumor cells (ypN0[i+], ≤ 02 mm), were considered positive The optimal SNB identification rate (IR) ≥ 90% and false-negative rate (FNR) ≤ 10% were predetermined Results From March 2009 to December 2012, 153 patients were accrued to the study The SNB IR was 876% (127 of 145; 95% CI, 822% to 930%), and the FNR was 84% (seven of 83; 95% CI, 24% to 144%) If SN ypN0(i+)s had been considered negative, the FNR would have increased to 133% (11 of 83;

State of the Art: Iterative CT Reconstruction Techniques

Abstract: The current evidence on the clinical implementation of iterative reconstruction into CT protocols shows substantial promise for major improvements in image quality, chiefly noise reduction—with subsequent radiation dose reduction—and artifact suppression.

Presymptomatic cognitive and neuroanatomical changes in genetic frontotemporal dementia in the Genetic Frontotemporal dementia Initiative (GENFI) study: a cross-sectional analysis

Abstract: Summary Background Frontotemporal dementia is a highly heritable neurodegenerative disorder. In about a third of patients, the disease is caused by autosomal dominant genetic mutations usually in one of three genes: progranulin ( GRN ), microtubule-associated protein tau ( MAPT ), or chromosome 9 open reading frame 72 ( C9orf72 ). Findings from studies of other genetic dementias have shown neuroimaging and cognitive changes before symptoms onset, and we aimed to identify whether such changes could be shown in frontotemporal dementia. Methods We recruited participants to this multicentre study who either were known carriers of a pathogenic mutation in GRN, MAPT , or C9orf72 , or were at risk of carrying a mutation because a first-degree relative was a known symptomatic carrier. We calculated time to expected onset as the difference between age at assessment and mean age at onset within the family. Participants underwent a standardised clinical assessment and neuropsychological battery. We did MRI and generated cortical and subcortical volumes using a parcellation of the volumetric T1-weighted scan. We used linear mixed-effects models to examine whether the association of neuropsychology and imaging measures with time to expected onset of symptoms differed between mutation carriers and non-carriers. Findings Between Jan 30, 2012, and Sept 15, 2013, we recruited participants from 11 research sites in the UK, Italy, the Netherlands, Sweden, and Canada. We analysed data from 220 participants: 118 mutation carriers (40 symptomatic and 78 asymptomatic) and 102 non-carriers. For neuropsychology measures, we noted the earliest significant differences between mutation carriers and non-carriers 5 years before expected onset, when differences were significant for all measures except for tests of immediate recall and verbal fluency. We noted the largest Z score differences between carriers and non-carriers 5 years before expected onset in tests of naming (Boston Naming Test −0·7; SE 0·3) and executive function (Trail Making Test Part B, Digit Span backwards, and Digit Symbol Task, all −0·5, SE 0·2). For imaging measures, we noted differences earliest for the insula (at 10 years before expected symptom onset, mean volume as a percentage of total intracranial volume was 0·80% in mutation carriers and 0·84% in non-carriers; difference −0·04, SE 0·02) followed by the temporal lobe (at 10 years before expected symptom onset, mean volume as a percentage of total intracranial volume 8·1% in mutation carriers and 8·3% in non-carriers; difference −0·2, SE 0·1). Interpretation Structural imaging and cognitive changes can be identified 5–10 years before expected onset of symptoms in asymptomatic adults at risk of genetic frontotemporal dementia. These findings could help to define biomarkers that can stage presymptomatic disease and track disease progression, which will be important for future therapeutic trials. Funding Centres of Excellence in Neurodegeneration.

Phase 3 trials of stereotactic radiosurgery with or without whole-brain radiation therapy for 1 to 4 brain metastases: individual patient data meta-analysis.

Abstract: Purpose To perform an individual patient data (IPD) meta-analysis of randomized controlled trials evaluating stereotactic radiosurgery (SRS) with or without whole-brain radiation therapy (WBRT) for patients presenting with 1 to 4 brain metastases. Method and Materials Three trials were identified through a literature search, and IPD were obtained. Outcomes of interest were survival, local failure, and distant brain failure. The treatment effect was estimated after adjustments for age, recursive partitioning analysis (RPA) score, number of brain metastases, and treatment arm. Results A total of 364 of the pooled 389 patients met eligibility criteria, of whom 51% were treated with SRS alone and 49% were treated with SRS plus WBRT. For survival, age was a significant effect modifier ( P =.04) favoring SRS alone in patients ≤50 years of age, and no significant differences were observed in older patients. Hazard ratios (HRs) for patients 35, 40, 45, and 50 years of age were 0.46 (95% confidence interval [CI] = 0.24-0.90), 0.52 (95% CI = 0.29-0.92), 0.58 (95% CI = 0.35-0.95), and 0.64 (95% CI = 0.42-0.99), respectively. Patients with a single metastasis had significantly better survival than those who had 2 to 4 metastases. For distant brain failure, age was a significant effect modifier ( P =.043), with similar rates in the 2 arms for patients ≤50 of age; otherwise, the risk was reduced with WBRT for patients >50 years of age. Patients with a single metastasis also had a significantly lower risk of distant brain failure than patients who had 2 to 4 metastases. Local control significantly favored additional WBRT in all age groups. Conclusions For patients ≤50 years of age, SRS alone favored survival, in addition, the initial omission of WBRT did not impact distant brain relapse rates. SRS alone may be the preferred treatment for this age group.

Barriers to Goals of Care Discussions With Seriously Ill Hospitalized Patients and Their Families: A Multicenter Survey of Clinicians

Abstract: Importance Seriously ill hospitalized patients have identified communication and decision making about goals of care as high priorities for quality improvement in end-of-life care. Interventions to improve care are more likely to succeed if tailored to existing barriers. Objective To determine, from the perspective of hospital-based clinicians, (1) barriers impeding communication and decision making about goals of care with seriously ill hospitalized patients and their families and (2) their own willingness and the acceptability for other clinicians to engage in this process. Design, Setting, and Participants Multicenter survey of medical teaching units of nurses, internal medicine residents, and staff physicians from participating units at 13 university-based hospitals from 5 Canadian provinces. Main Outcomes and Measures Importance of 21 barriers to goals of care discussions rated on a 7-point scale (1 = extremely unimportant; 7 = extremely important). Results Between September 2012 and March 2013, questionnaires were returned by 1256 of 1617 eligible clinicians, for an overall response rate of 77.7% (512 of 646 nurses [79.3%], 484 of 634 residents [76.3%], 260 of 337 staff physicians [77.2%]). The following family member–related and patient-related factors were consistently identified by all 3 clinician groups as the most important barriers to goals of care discussions: family members’ or patients’ difficulty accepting a poor prognosis (mean [SD] score, 5.8 [1.2] and 5.6 [1.3], respectively), family members’ or patients’ difficulty understanding the limitations and complications of life-sustaining treatments (5.8 [1.2] for both groups), disagreement among family members about goals of care (5.8 [1.2]), and patients’ incapacity to make goals of care decisions (5.6 [1.2]). Clinicians perceived their own skills and system factors as less important barriers. Participants viewed it as acceptable for all clinician groups to engage in goals of care discussions—including a role for advance practice nurses, nurses, and social workers to initiate goals of care discussions and be a decision coach. Conclusions and Relevance Hospital-based clinicians perceive family member–related and patient-related factors as the most important barriers to goals of care discussions. All health care professionals were viewed as playing important roles in addressing goals of care. These findings can inform the design of future interventions to improve communication and decision making about goals of care.

In situ conversion of porphyrin microbubbles to nanoparticles for multimodality imaging

Abstract: Converting nanoparticles or monomeric compounds into larger supramolecular structures by endogenous or external stimuli is increasingly popular because these materials are useful for imaging and treating diseases. However, conversion of microstructures to nanostructures is less common. Here, we show the conversion of microbubbles to nanoparticles using low-frequency ultrasound. The microbubble consists of a bacteriochlorophyll-lipid shell around a perfluoropropane gas. The encapsulated gas provides ultrasound imaging contrast and the porphyrins in the shell confer photoacoustic and fluorescent properties. On exposure to ultrasound, the microbubbles burst and form smaller nanoparticles that possess the same optical properties as the original microbubble. We show that this conversion is possible in tumour-bearing mice and could be validated using photoacoustic imaging. With this conversion, our microbubble can potentially be used to bypass the enhanced permeability and retention effect when delivering drugs to tumours.

International Society for Bipolar Disorders Task Force on Suicide: meta-analyses and meta-regression of correlates of suicide attempts and suicide deaths in bipolar disorder.

Abstract: OBJECTIVES: Bipolar disorder is associated with a high risk of suicide attempts and suicide death The main objective of the present study was to identify and quantify the demographic and clinical correlates of attempted and completed suicide in people with bipolar disorder METHODS: Within the framework of the International Society for Bipolar Disorders Task Force on Suicide, a systematic review of articles published since 1980, characterized by the key terms bipolar disorder and 'suicide attempts' or 'suicide', was conducted, and data extracted for analysis from all eligible articles Demographic and clinical variables for which ≥ 3 studies with usable data were available were meta-analyzed using fixed or random-effects models for association with suicide attempts and suicide deaths There was considerable heterogeneity in the methods employed by the included studies RESULTS: Variables significantly associated with suicide attempts were: female gender, younger age at illness onset, depressive polarity of first illness episode, depressive polarity of current or most recent episode, comorbid anxiety disorder, any comorbid substance use disorder, alcohol use disorder, any illicit substance use, comorbid cluster B/borderline personality disorder, and first-degree family history of suicide Suicide deaths were significantly associated with male gender and first-degree family history of suicide CONCLUSIONS: This paper reports on the presence and magnitude of the correlates of suicide attempts and suicide deaths in bipolar disorder These findings do not address causation, and the heterogeneity of data sources should limit the direct clinical ranking of correlates Our results nonetheless support the notion of incorporating diagnosis-specific data in the development of models of understanding suicide in bipolar disorder Language: en

Intensive Care Unit Capacity in Low-Income Countries: A Systematic Review

Abstract: Purpose Access to critical care is a crucial component of healthcare systems. In low-income countries, the burden of critical illness is substantial, but the capacity to provide care for critically ill patients in intensive care units (ICUs) is unknown. Our aim was to systematically review the published literature to estimate the current ICU capacity in low-income countries. Methods We searched 11 databases and included studies of any design, published 2004-August 2014, with data on ICU capacity for pediatric and adult patients in 36 low-income countries (as defined by World Bank criteria; population 850 million). Neonatal, temporary, and military ICUs were excluded. We extracted data on ICU bed numbers, capacity for mechanical ventilation, and information about the hospital, including referral population size, public accessibility, and the source of funding. Analyses were descriptive. Results Of 1,759 citations, 43 studies from 15 low-income countries met inclusion criteria. They described 36 individual ICUs in 31 cities, of which 16 had population greater than 500,000, and 14 were capital cities. The median annual ICU admission rate was 401 (IQR 234-711; 24 ICUs with data) and median ICU size was 8 beds (IQR 5-10; 32 ICUs with data). The mean ratio of adult and pediatric ICU beds to hospital beds was 1.5% (SD 0.9%; 15 hospitals with data). Nepal and Uganda, the only countries with national ICU bed data, had 16.7 and 1.0 ICU beds per million population, respectively. National data from other countries were not available. Conclusions Low-income countries lack ICU beds, and more than 50% of these countries lack any published data on ICU capacity. Most ICUs in low-income countries are located in large referral hospitals in cities. A central database of ICU resources is required to evaluate health system performance, both within and between countries, and may help to develop related health policy.

Measuring diaphragm thickness with ultrasound in mechanically ventilated patients: feasibility, reproducibility and validity

Abstract: Ultrasound measurements of diaphragm thickness (T di) and thickening (TFdi) may be useful to monitor diaphragm activity and detect diaphragm atrophy in mechanically ventilated patients We aimed to establish the reproducibility of measurements in ventilated patients and determine whether passive inflation by the ventilator might cause thickening apart from inspiratory effort Five observers measured T di and TFdi in 96 mechanically ventilated patients The probe site was marked in 66 of the 96 patients TFdi was measured at peak and end-inspiration (airway occluded and diaphragm relaxed) in nine healthy volunteers inhaling to varying lung volumes The association with diaphragm electrical activity was quantified Right hemidiaphragm thickness was obtained on 95 % of attempts; left hemidiaphragm measurements could not be obtained consistently Right hemidiaphragm thickness measurements were highly reproducible (mean ± SD 24 ± 08 mm, repeatability coefficient 02 mm, reproducibility coefficient 04 mm), particularly after marking the location of the probe TFdi measurements were only moderately reproducible (median 11 %, IQR 3–17 %, repeatability coefficient 17 %, reproducibility coefficient 16 %) TFdi and diaphragm electrical activity were positively correlated, r 2 = 032, p < 001) At inspiratory volumes below 50 % of inspiratory capacity, passive inflation did not cause diaphragm thickening TFdi was considerably lower in patients on either partially assisted or controlled ventilation compared to healthy subjects (median 11 vs 35 %, p < 0001) Ultrasound measurements of right hemidiaphragm thickness are feasible and highly reproducible in ventilated patients At clinically relevant inspiratory volumes, diaphragm thickening reflects muscular contraction and not passive inflation This technique can be reliably employed to monitor diaphragm thickness, activity, and function during mechanical ventilation

Diagnostic Precursors to Bipolar Disorder in Offspring of Parents With Bipolar Disorder: A Longitudinal Study.

Abstract: Objective:The authors sought to identify diagnostic risk factors of manic, mixed, or hypomanic episodes in the offspring of parents with bipolar disorder (“high-risk offspring”).Method:High-risk offspring 6–18 years old (N=391) and demographically matched offspring (N=248) of community parents without bipolar disorder were assessed longitudinally with standardized diagnostic instruments by staff blind to parental diagnoses. Follow-up assessments were completed in 91% of the offspring (mean follow-up interval, 2.5 years; mean follow-up duration, 6.8 years).Results:Compared with community offspring, high-risk offspring had significantly higher rates of subthreshold mania or hypomania (13.3% compared with 1.2%), manic, mixed, or hypomanic episodes (9.2% compared with 0.8%), and major depressive episodes (32.0% compared with 14.9%). They also had higher rates of attention deficit hyperactivity disorder (30.7% compared with 18.1%), disruptive behavior disorders (27.4% compared with 15.3%), anxiety disorders (3...

Treatment of progressive multiple sclerosis: what works, what does not, and what is needed

Abstract: Disease-modifying drugs have mostly failed as treatments for progressive multiple sclerosis. Management of the disease therefore solely aims to minimise symptoms and, if possible, improve function. The degree to which this approach is based on empirical data derived from studies of progressive disease or whether treatment decisions are based on what is known about relapsing-remitting disease remains unclear. Symptoms rated as important by patients with multiple sclerosis include balance and mobility impairments, weakness, reduced cardiovascular fitness, ataxia, fatigue, bladder dysfunction, spasticity, pain, cognitive deficits, depression, and pseudobulbar affect; a comprehensive literature search shows a notable paucity of studies devoted solely to these symptoms in progressive multiple sclerosis, which translates to few proven therapeutic options in the clinic. A new strategy that can be used in future rehabilitation trials is therefore needed, with the adoption of approaches that look beyond single interventions to concurrent, potentially synergistic, treatments that maximise what remains of neural plasticity in patients with progressive multiple sclerosis.

Will the Real Benefits of Single-Shot Interscalene Block Please Stand Up? A Systematic Review and Meta-Analysis

Abstract: BACKGROUND:Interscalene block (ISB) can provide pain relief after shoulder surgery, but a reliable quantification of its analgesic benefits is lacking. This meta-analysis examines the effect of single-shot ISB on analgesic outcomes during the first 48 hours after shoulder surgery.METHODS:We retrieve

A population-based validation study of the DCIS Score predicting recurrence risk in individuals treated by breast-conserving surgery alone

Abstract: Validated biomarkers are needed to improve risk assessment and treatment decision-making for women with ductal carcinoma in situ (DCIS) of the breast. The Oncotype DX® DCIS Score (DS) was shown to predict the risk of local recurrence (LR) in individuals with low-risk DCIS treated by breast-conserving surgery (BCS) alone. Our objective was to confirm these results in a larger population-based cohort of individuals. We used an established population-based cohort of individuals diagnosed with DCIS treated with BCS alone from 1994 to 2003 with validation of treatment and outcomes. Central pathology assessment excluded cases with invasive cancer, DCIS < 2 mm or positive margins. Cox model was used to determine the relationship between independent covariates, the DS (hazard ratio (HR)/50 Cp units (U)) and LR. Tumor blocks were collected for 828 patients. Final evaluable population includes 718 cases, of whom 571 had negative margins. Median follow-up was 9.6 years. 100 cases developed LR following BCS alone (DCIS, N = 44; invasive, N = 57). In the primary pre-specified analysis, the DS was associated with any LR (DCIS or invasive) in ER+ patients (HR 2.26; P < 0.001) and in all patients regardless of ER status (HR 2.15; P < 0.001). DCIS Score provided independent information on LR risk beyond clinical and pathologic variables including size, age, grade, necrosis, multifocality, and subtype (adjusted HR 1.68; P = 0.02). DCIS was associated with invasive LR (HR 1.78; P = 0.04) and DCIS LR (HR 2.43; P = 0.005). The DCIS Score independently predicts and quantifies individualized recurrence risk in a population of patients with pure DCIS treated by BCS alone.

Active surveillance for the management of localized prostate cancer: Guideline recommendations.

Abstract: Introduction: The objective is to provide guidance on the role of active surveillance (AS) as a management strategy for low-risk prostate cancer patients and to ensure that AS is offered to appropriate patients assessed by a standardized protocol. Prostate cancer is often a slowly progressive or sometimes non-progressive indolent disease diagnosed at an early stage with localized tumours that are unlikely to cause morbidity or death. Standard active treatments for prostate cancer include radiotherapy (RT) or radical prostatectomy (RP), but the harms from over diagnosis and overtreatment are of a significant concern. AS is increasingly being considered as a management strategy to avoid or delay the potential harms caused by unnecessary radical treatment. Methods: A literature search of MEDLINE, EMBASE, the Cochrane library, guideline databases and relevant meeting proceedings was performed and a systematic review of identified evidence was synthesized to make recommendations relating to the role of AS in the management of localized prostate cancer. Results: No exiting guidelines or reviews were suitable for use in the synthesis of evidence for the recommendations, but 59 reports of primary studies were identified. Due to studies being either non-comparative or heterogeneous, pooled meta-analyses were not conducted. Conclusion: The working group concluded that for patients with low-risk (Gleason score ≤6) localized prostate cancer, AS is the preferred disease management strategy. Active treatment (RP or RT) is appropriate for patients with intermediate-risk (Gleason score 7) localized prostate cancer. For select patients with low-volume Gleason 3+4=7 localized prostate cancer, AS can be considered.

Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol.

Abstract: As of September 30, 2015, a total of 1589 laboratory-confirmed cases of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to the World Health Organization (WHO). At present there is no effective specific therapy against MERS-CoV. The use of convalescent plasma (CP) has been suggested as a potential therapy based on existing evidence from other viral infections. We aim to study the feasibility of CP therapy as well as its safety and clinical and laboratory effects in critically ill patients with MERS-CoV infection. We will also examine the pharmacokinetics of the MERS-CoV antibody response and viral load over the course of MERS-CoV infection. This study will inform a future randomized controlled trial that will examine the efficacy of CP therapy for MERS-CoV infection. In the CP collection phase, potential donors will be tested by the enzyme linked immunosorbent assay (ELISA) and the indirect fluorescent antibody (IFA) techniques for the presence of anti-MERS-CoV antibodies. Subjects with anti-MERS-CoV IFA titer of ≥1:160 and no clinical or laboratory evidence of MERS-CoV infection will be screened for eligibility for plasma donation according to standard donation criteria. In the CP therapy phase, 20 consecutive critically ill patients admitted to intensive care unit with laboratory-confirmed MERS-CoV infection will be enrolled and each will receive 2 units of CP. Post enrollment, patients will be followed for clinical and laboratory outcomes that include anti-MERS-CoV antibodies and viral load. This protocol was developed collaboratively by King Abdullah International Medical Research Center (KAIMRC), Gulf Cooperation Council (GCC) Infection Control Center Group and the World Health Organization—International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC-WHO) MERS-CoV Working Group. It was approved in June 2014 by the Ministry of the National Guard Health Affairs Institutional Review Board (IRB). A data safety monitoring board (DSMB) was formulated. The study is registered at http://www.clinicaltrials.gov (NCT02190799).

A report on older-age bipolar disorder from the International Society for Bipolar Disorders Task Force

Abstract: Objectives: In the coming generation, older adults with bipolar disorder (BD) will increase in absolute numbers as well as proportion of the general population. This is the first report of the International Society for Bipolar Disorder (ISBD) Task Force on Older-Age Bipolar Disorder (OABD). Methods: This task force report addresses the unique aspects of OABD including epidemiology and clinical features, neuropathology and biomarkers, physical health, cognition, and care approaches. Results: The report describes an expert consensus summary on OABD that is intended to advance the care of patients, and shed light on issues of relevance to BD research across the lifespan. Although there is still a dearth of research and health efforts focused on older adults with BD, emerging data have brought some answers, innovative questions, and novel perspectives related to the notion of late onset, medical comorbidity, and the vexing issue of cognitive impairment and decline. Conclusions: Improving our understanding of the biological, clinical, and social underpinnings relevant to OABD is an indispensable step in building a complete map of BD across the lifespan. © 2015 John Wiley

Results from a phase 2 study of enzalutamide (ENZA), an androgen receptor (AR) inhibitor, in advanced AR+ triple-negative breast cancer (TNBC).

Abstract: 1003 Background: The AR may be a therapeutic target for pts with androgen-driven TNBC. ENZA, a potent AR inhibitor, is approved in men with metastatic castration-resistant prostate cancer (mCRPC) and improves median PFS compared to bicalutamide in men with mCRPC (15.7 vs 5.8 mos; HR 0.44; p 0% by IHC; NCT01889238). Pts could be prescreened for AR, and have non-measurable bone disease and unlimited prior regimens; CNS metastases or seizure history were exclusionary. The primary endpoint was clinical benefit (CR, PR or SD) at 16 wks (CBR16) in ‘Evaluable’ pts defined as having both AR IHC ≥10% and a response assessment. CBR24, PFS, response rate, and safety were assessed. An androgen-driven gene signature (Dx) was created from gene profiling and outcomes were assessed accordingly. Stage 2 enrolled if CBR16 was ≥3 of 26 Evaluable pts; H0 was rejected if CBR16 was ≥9 in 62 yielding 85% po...

Faecal immunochemical tests versus guaiac faecal occult blood tests: what clinicians and colorectal cancer screening programme organisers need to know

Abstract: Although colorectal cancer (CRC) is a common cause of cancer-related death, it is fortunately amenable to screening with faecal tests for occult blood and endoscopic tests. Despite the evidence for the efficacy of guaiac-based faecal occult blood tests (gFOBT), they have not been popular with primary care providers in many jurisdictions, in part because of poor sensitivity for advanced colorectal neoplasms (advanced adenomas and CRC). In order to address this issue, high sensitivity gFOBT have been recommended, however, these tests are limited by a reduction in specificity compared with the traditional gFOBT. Where colonoscopy is available, some providers have opted to recommend screening colonoscopy to their patients instead of faecal testing, as they believe it to be a better test. Newer methods for detecting occult human blood in faeces have been developed. These tests, called faecal immunochemical tests (FIT), are immunoassays specific for human haemoglobin. FIT hold considerable promise over the traditional guaiac methods including improved analytical and clinical sensitivity for CRC, better detection of advanced adenomas, and greater screenee participation. In addition, the quantitative FIT are more flexible than gFOBT as a numerical result is reported, allowing customisation of the positivity threshold. When compared with endoscopy, FIT are less sensitive for the detection of advanced colorectal neoplasms when only one time testing is applied to a screening population; however, this is offset by improved participation in a programme of annual or biennial screens and a better safety profile. This review will describe how gFOBT and FIT work and will present the evidence that supports the use of FIT over gFOBT, including the cost-effectiveness of FIT relative to gFOBT. Finally, specific issues related to FIT implementation will be discussed, particularly with respect to organised CRC screening programmes.

Atrial Premature Beats Predict Atrial Fibrillation in Cryptogenic Stroke: Results From the EMBRACE Trial

Abstract: Background and Purpose—Many ischemic strokes or transient ischemic attacks are labeled cryptogenic but may have undetected atrial fibrillation (AF). We sought to identify those most likely to have subclinical AF. Methods—We prospectively studied patients with cryptogenic stroke or transient ischemic attack aged ≥55 years in sinus rhythm, without known AF, enrolled in the intervention arm of the 30 Day Event Monitoring Belt for Recording Atrial Fibrillation After a Cerebral Ischemic Event (EMBRACE) trial. Participants underwent baseline 24-hour Holter ECG poststroke; if AF was not detected, they were randomly assigned to 30-day ECG monitoring with an AF auto-detect external loop recorder. Multivariable logistic regression assessed the association between baseline variables (Holter-detected atrial premature beats [APBs], runs of atrial tachycardia, age, and left atrial enlargement) and subsequent AF detection. Results—Among 237 participants, the median baseline Holter APB count/24 h was 629 (interquartile r...