Novel Gadolinium-Free Ultrasmall Nanostructured Positive Contrast for Magnetic Resonance Angiography and Imaging.

Nanostructured contrast agents are promising alternatives to Gd3+-based chelates in magnetic resonance (MR) imaging techniques. A novel ultrasmall paramagnetic nanoparticle (UPN) was strategically designed to maximize the number of exposed paramagnetic sites and r1 while minimizing r2, by decorating 3 nm titanium dioxide nanoparticles with suitable amounts of iron oxide. Its relaxometric parameters are comparable to those of gadoteric acid (GA) in agar phantoms, and the r2/r1 ratio of 1.38 at 3 T is close to the ideal unitary value. The strong and prolonged contrast enhancement of UPN before renal excretion was confirmed by T1-weighted MR images of Wistar rats after intravenous bolus injection. Those results associated with good biocompatibility indicate its high potential as an alternative blood-pool contrast agent to the GA gold standard for MR angiography, especially for patients with severe renal impairment.

Applying behaviour change models to policy-making: development and validation of the Policymakers' Information Use Questionnaire (POLIQ).

BACKGROUND: The purpose of this study was to develop and validate the Policymakers' Information Use Questionnaire (POLIQ) to capture the intention of individuals in decision-making positions, such as health policy-makers, to act on research-based evidence in order to inform theory and the application of behaviour change models to decision-making spheres. METHODS: The development and validation comprised three steps: item generation, qualitative face validation with cognitive debriefing and factorial construct validation. Confirmatory factor analysis was applied to estimate item-domain correlations for five predefined constructs relating to content, beliefs, behaviour, control and intent. Cronbach's alpha coefficient was calculated to assess the overall consistency of questionnaire items with the predefined constructs. Participants in the item generation and face validation were health and policy researchers and two former decision-makers (former assistant deputy ministers) from the Canadian provincial level. Participants in the construct validation were 39 Canadian decision-makers at various positions of municipal, provincial and federal jurisdiction who participated in a series of policy dialogues focused on childhood disability. RESULTS: Cognitive debriefing allowed for small adjustments in language for clarity, including simultaneous validation of the English and French questionnaires. Participants found that the questions were clear and addressed the domains being targeted. Internal consistency of items belonging to the respective questionnaire domains was moderate to high, with estimated Cronbach's alpha values ranging from 0.67 to 0.84. Estimated item-domain correlations indicated moderate to high measurement performance for the domains norm, control and beliefs, whereas weak to moderate correlations resulted for the constructs content and intent. Estimated imprecision of factor loadings (95% confidence interval widths) was considerable for the questionnaire domains content and intent. CONCLUSION: Measuring decision-makers' behaviour in relation to research evidence use is challenging. We provide initial evidence on face validity and appropriate measurement properties of the POLIQ based on a convenience sample of decision-makers in social and health policy. Larger validation studies and further psychometric property testing will support further utility of the POLIQ.

The Effect of Context-Based Interventions at the Systems-Level on Participation of Children with Disabilities: A Systematic Review.

AIMS: To synthesize evidence on the impact of context-based interventions on the participation of children with disabilities in the community. METHODS: A systematic review was conducted using the American Academy for Cerebral Palsy and Developmental Medicine Guidelines for systematic reviews. Seven databases were searched; articles included were on children with developmental disabilities under the age of 19 years, describing systems-level, context-based interventions aimed to improve participation and Participation-related outcomes of the Family of Participation-related Constructs framework. Intervention characteristics were coded using the Community Wellbeing Framework (CWF). RESULTS: Eleven articles were included for knowledge synthesis. Four studies were level I, II, and III based on the Center for Evidence-Based Medicine hierarchy. All four showed that context-based interventions had a positive effect on participation and participation-related outcomes. All 11 studies had intervention properties that were coded to at least one domain on the CWF. CONCLUSION: There is a scarcity of high-quality studies that focus on context-based interventions at the systems-level, as opposed to the individual-level. Albeit low-level quality, existing evidence emphasized the importance of using known facilitators to participation, such as staff training, peer mentorship, awareness-raising, and development of partnerships to change the system and promote participation.

Effectiveness of interventions for managing multiple high-burden chronic diseases in older adults: a systematic review and meta-analysis.

INTRODUCTION: More than half of older adults (age ≥ 65 yr) have 2 or more high-burden multimorbidity conditions (i.e., highly prevalent chronic diseases, which are associated with increased health care utilization; these include diabetes [DM], dementia, depression, chronic obstructive pulmonary disease [COPD], cardiovascular disease [CVD], arthritis, and heart failure [HF]), yet most existing interventions for managing chronic disease focus on a single disease or do not respond to the specialized needs of older adults. We conducted a systematic review and meta-analysis to identify effective multimorbidity interventions compared with a control or usual care strategy for older adults. METHODS: We searched bibliometric databases for randomized controlled trials (RCTs) evaluating interventions for managing multiple chronic diseases in any language from 1990 to December 2017. The primary outcome was any outcome specific to managing multiple chronic diseases as reported by studies. Reviewer pairs independently screened citations and full-text articles, extracted data and assessed risk of bias. We assessed statistical and methodological heterogeneity and performed a meta-analysis of RCTs with similar interventions and components. RESULTS: We included 25 studies (including 15 RCTs and 6 cluster RCTs) (12 579 older adults; mean age 67.3 yr). In patients with [depression + COPD] or [CVD + DM], care-coordination strategies significantly improved depressive symptoms (standardized mean difference -0.41; 95% confidence interval [CI] -0.59 to -0.22; I2 = 0%) and reduced glycosylated hemoglobin (HbA1c) levels (mean difference -0.51; 95% CI -0.90 to -0.11; I2 = 0%), but not mortality (relative risk [RR] 0.79; 95% CI 0.53 to 1.17; I2 = 0%). Among secondary outcomes, care-coordination strategies reduced functional impairment in patients with [arthritis + depression] (between-group difference -0.82; 95% CI -1.17 to -0.47) or [DM + depression] (between-group difference 3.21; 95% CI 1.78 to 4.63); improved cognitive functioning in patients with [DM + depression] (between-group difference 2.44; 95% CI 0.79 to 4.09) or [HF + COPD] (p = 0.006); and increased use of mental health services in those with [DM + (CVD or depression)] (RR 2.57; 95% CI 1.90 to 3.49; I2 = 0%). INTERPRETATION: Subgroup analyses showed that older adults with diabetes and either depression or cardiovascular disease, or with coexistence of chronic obstructive pulmonary disease and heart failure, can benefit from care-coordination strategies with or without education to lower HbA1c, reduce depressive symptoms, improve health-related functional status, and increase the use of mental health services. PROTOCOL REGISTRATION: PROSPERO-CRD42014014489.

A reliable protocol for colorimetric determination of iron oxide nanoparticle uptake by cells.

Size, shape, and surface properties of superparamagnetic iron oxide nanoparticles (SPIONs) can influence their interaction with biological systems, particularly the incorporation by tumor cells and consequently the biological activity and efficiency in biomedical applications. Several strategies have been used to evaluate cellular uptake of SPIONs. While qualitative methods are generally based on microscopy techniques, quantitative assays are carried out by techniques such as inductively coupled plasma-mass spectrometry and flow cytometry. However, inexpensive colorimetric methods based on equipments commonly found in chemistry and biochemistry laboratories are preferred for routine measurements. Nevertheless, colorimetric assays must be used judiciously, particularly when nanoparticles are involved, since their interaction with biological constituents tends to lead to quite underestimated results. Thus, herein described is a colorimetric protocol using 2,2'-bipyridine as chromogenic ligand, where each step was optimized and validated by total reflection X-ray fluorescence spectroscopy, realizing a highly reproducible and reliable method for determination of iron content in cells incubated with SPIONs. The limit of blank and limit of detection were determined to be as low as 0.076 and 0.143 µg Fe/mL, using sample volumes as small as 190 µL and a number of cells as low as 2.0 × 105. Furthermore, three different types of surface-functionalized nanoparticles were incorporated in cells and evaluated through this protocol, enabling to monitor the additive effect of o-phosphorylethanolamine (PEA) and folic acid (FA) conjugation on iron oxide nanoparticles (SPION-PEA and SPION-PEA/FA), that enhanced the uptake by HeLa cells, respectively, by four and ten times when compared to SPIONs conjugated with nonbioactive molecules. Graphical abstract Colorimetric determination of superparamagnetic iron oxide nanoparticles (SPIONs) incorporated by cells.

Comparative safety and effectiveness of serotonin receptor antagonists in patients undergoing chemotherapy: a systematic review and network meta-analysis.

BACKGROUND: Although serotonin (5-HT3) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT3 receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy. METHODS: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT3 receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted. RESULTS: After screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13-4.17). For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a rank-heat plot with the surface under the cumulative ranking curve results, palonosetron + steroid was ranked the safest and most effective agent overall. CONCLUSIONS: Most 5-HT3 receptor antagonists were relatively safe when compared with each other, yet none of the studies compared active treatment with placebo for harms. However, dolasetron + dexamethasone may prolong the QTc compared to ondansetron + dexamethasone. All agents were effective for reducing risk of nausea, vomiting, and chemotherapy-induced nausea or vomiting. TRIAL REGISTRATION: This study was registered at PROSPERO: ( CRD42013003564 ).

Personalized Surgery for Gastric Adenocarcinoma: A Meta-analysis of D1 versus D2 Lymphadenectomy.

BACKGROUND: The recent publication of 5-year survival data for the Italian Gastric Cancer Study Group (IGCSG) D1 versus D2 lymphadenectomy for gastric cancer trial adds important data for analysis of whether a D2 lymphadenectomy improves survival. METHODS: Systematic searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1985 to February 1, 2014. Meta-analyses were performed using RevMan version 5 software. Long-term outcomes were analyzed. Subgroup analyses of T and N stage were performed. RESULTS: Outcomes of four randomized, controlled trials involving 1,599 patients (823 D1: 776 D2) enrolled from 1982 to 2005 were included for qualitative analysis and quantitative meta-analysis. Despite the addition of long-term survival data from the IGCSG, 5-year overall and nodal status survival was similar between D1 and D2 trials. However, subgroup analysis revealed a survival benefit for T3 patients (odds ratio 1.64, 95 % confidence interval 1.01-2.67) and a trend for survival benefit for advanced nodal stage (odds ratio 1.36, 95 % confidence interval 0.98-1.87) with D2 compared with D1 lymphadenectomy. CONCLUSIONS: As recent studies have demonstrated comparable short-term surgical outcomes for both D1 and D2 lymphadenectomies, consideration should be made for more extensive lymph node dissection among patients with advanced stage.

What studies are appropriate and necessary for staging gastric adenocarcinoma? Results of an international RAND/UCLA expert panel.

BACKGROUND: The approach for staging gastric adenocarcinoma (GC) has not been well defined, with heterogeneity in the application of staging modalities. METHODS: Utilizing a RAND/UCLA appropriateness methodology (RAM), a multidisciplinary expert panel of 16 physicians scored 84 GC staging scenarios. Appropriateness was scored from 1 to 9. Median appropriateness scores from 1 to 3 were considered inappropriate, 4-6 uncertain, and 7-9 appropriate. Agreement was reached when 12 or more of 16 panelists scored the scenario similarly. Appropriate scenarios were subsequently scored for necessity. RESULTS: Pretreatment TNM stage determination is necessary. Necessary staging maneuvers include esophagogastroduodenoscopy (EGD); biopsy of the tumor; documentation of tumor size, description, location, distance from gastroesophageal junction (GEJ), and any GEJ, esophageal, or duodenal involvement; if an EGD report is unclear, surgeons should repeat it to confirm tumor location. Pretreatment radiologic assessment should include computed tomography (CT)-abdomen and CT-pelvis, performed with multidetector CT scanners with 5-mm slices. Laparoscopy should be performed before resection of cT3-cT4 lesions or multivisceral resections. Laparoscopy should include inspection of the stomach, diaphragm, liver, and ovaries. CONCLUSIONS: Using a RAM, we describe appropriate and necessary staging tests for the pretreatment staging evaluation of GC, as well as how some of these staging maneuvers should be conducted.

The perspectives of patients, family members and healthcare professionals on readmissions: preventable or inevitable?

An understanding of what complex medical patients with chronic conditions, family members and healthcare professionals perceive to be the key reasons for the readmission is important to preventing their occurrence. In this context, we undertook a study to understand the perceptions of patients, family members and healthcare professionals regarding the reasons for, and preventability of, readmissions. An exploratory case design with semi-structured interviews was conducted with 49 participants, including patients, family members, nurses, case managers, physicians, discharge planners from a general internal medicine unit at a large and academic hospital. Data were analyzed using a directed content analysis approach that involved three investigators. Two contrasting themes emerged from the analysis of interview data set. The first theme was readmissions as preventable occurrences. Our analyses elucidated contributing factors to readmissions during the patients' hospital stay and after the patients were discharged. The second theme was readmissions as inevitable, occurring due to the progression of disease. Our study findings indicate that some readmissions are perceived to be inevitable due to the burden of disease while others are perceived to be preventable and associated with factors both in hospital and post-discharge. Continued interprofessional efforts are required to identify patients at risk for readmission and to organize and deliver care to improve health outcomes after hospitalization.

Patients' views on bedside nursing handover: creating a space to connect.

A study was undertaken to explore patients' experiences and perceptions associated with implementation of bedside nursing handover. Interviews were conducted with patients and analyzed using a directed content analysis. Three themes emerged through which patients described their experience with bedside nursing handover as follows: (1) creating a space for personal connection; (2) "bumping up to speed"; and (3) varying preferences. Health care leaders and nurses can use study findings to tailor strategies to engage patients, taking into account their preferences, in bedside nursing handover.

Gamification in Mobile Apps for Children With Disabilities: Scoping Review.

BACKGROUND: Children with disabilities face numerous challenges in accessing health services. Mobile health is an emerging field that could significantly reduce health inequities by providing more accessible services. Many mobile apps incorporate gamification elements such as feedback, points, and stories to increase engagement and motivation; however, little is known about how gamification has been incorporated in mobile apps for children with disabilities. OBJECTIVE: This scoping review aims to identify and synthesize the existing research evidence on the use of gamification in mobile apps for children with disabilities. Specifically, the objectives were to (1) identify the categories of these mobile apps (eg, treatment and educational) (2), describe the health-related outcomes they target, (3) assess the types and levels of gamification elements used within these apps, and (4) determine the reasons for incorporating gamification elements into mobile apps. METHODS: We searched MEDLINE, PsycINFO, CINAHL, Embase, the ACM Digital Library, and IEEE Xplore databases to identify papers published between 2008 and 2023. Original empirical research studies reporting on gamified mobile apps for children with disabilities that implemented at least 1 gamification strategy or tactic were included. Studies investigating serious games or full-fledged games were excluded. RESULTS: A total of 38 studies reporting on 32 unique gamified mobile apps were included. Findings showed that gamified apps focus on communication skills and oral health in children with autism spectrum disorder while also addressing self-management and academic skills for other disability groups. Gamified mobile apps have demonstrated potential benefits across different populations and conditions; however, there were mixed results regarding their impact. The gamification strategies included fun and playfulness (23/32, 72%), feedback on performance (17/32, 53%), and reinforcement (17/32, 53%) in more than half of apps, whereas social connectivity was used as a gamification strategy in only 4 (12%) mobile apps. There were 2 main reasons for integrating gamification elements into mobile apps described in 16 (42%) studies: increasing user engagement and motivation and enhancing intervention effects. CONCLUSIONS: This scoping review offers researchers a comprehensive review of the gamification elements currently used in mobile apps for the purposes of treatment, education, symptom management, and assessment for children with disabilities. In addition, it indicates that studies on certain disability groups and examinations of health-related outcomes have been neglected, highlighting the need for further investigations in these areas. Furthermore, research is needed to investigate the effectiveness of mobile-based gamification elements on health and health behavior outcomes, as well as the healthy development of children with disabilities.

Realist process evaluation of the knowledge translation programme of a patient-oriented research network.

RATIONALE: The Knowledge Translation (KT) Programme of a pan-Canadian strategic patient-oriented research network focused on brain-based developmental disabilities aimed to mobilize knowledge relevant to the network members. The programme also promotes and studies integrated Knowledge Translation (iKT) approaches involving different interested parties, such as researchers, patient-partners and decision-makers, in all parts of the knowledge creation process. AIMS AND OBJECTIVES: The objective of this study is to advance research programme evaluation methods through a realist evaluation of the process of implementing iKT activities. METHODS: Realist process evaluation included: (1) development of initial programme theories (using the partnership synergy theory); (2) data collection and analysis; (3) synthesis and refinement of theories through engagement with literature; and (4) presentation of findings in context-mechanism-outcome (C-M-O) configurations. A range of project documentation records were reviewed for analysis, and three co-leads, a programme coordinator, and a senior research associate were consulted to contextualize the implementation process of relevant KT activities. RESULTS: Based on the developed C-M-O configurations, we identified five key mechanisms of generating synergy in the iKT processes: (1) Visible shared leadership that embodies what iKT looks like; (2) Researchers' readiness for iKT; (3) Adaptation and flexible allocation of resources to emerging needs; (4) Power sharing to create practical and creative knowledge; and (5) Collective voice for potential transformative impacts at the policy level. CONCLUSIONS: The current realist evaluation demonstrated how partnerships between researchers, patient-partners and other interested parties can synergistically generate new ways of thinking among all interested parties, actionable strategies to integrate users in research, and solutions to disseminate knowledge. In particular, we identified a pivotal role for patient-partners to act as equal decision-maker helps building and maintaining partnerships and consolidating KT strategies.

Long-Term Environmental Methylmercury Exposure Is Associated with Peripheral Neuropathy and Cognitive Impairment among an Amazon Indigenous Population.

Widespread contamination of the Amazon basin with mercury has been reported to occur since at least the mid-80s due to heavy gold mining activity. Although initial studies have indicated that this may lead to deleterious neurological consequences to the indigenous populations living in the region, further research is needed to better characterize the neurological burden of such long-term exposure. With this aim, a cross-sectional exploratory study has been conducted with the Yanomami indigenous population residing in a northern Amazon region. All participants underwent a structured interview; detailed neurological examination, including assessment for cognitive, motor, coordination, and sensory functions; and laboratorial testing for serum hemoglobin, blood glucose, and methylmercury levels in hair samples. This study enrolled 154 individuals of 30.9 ± 16.8 years of age, of which 56.1% were female. Mean methylmercury levels in hair were 3.9 ± 1.7 µg/g. Methylmercury levels in hair > 6.0 µg/g were found in 10.3%. Among participants with hair methylmercury levels ≥ 6.0 µg/g, the prevalences of peripheral neuropathy and reduced cognitive performance were, respectively, 78.8% (95%CI 15-177%, p = 0.010) and 95.9% (95%CI 16-230.8%, p = 0.012) higher than those of individuals with lower levels. These results suggest that chronic mercury exposure may lead to significant and potentially irreversible neurotoxicity to Yanomami population living in the northern Amazon basin.

A RAND/UCLA appropriateness study of the management of familial gastric cancer.

BACKGROUND: Hereditary diffuse gastric cancer (HDGC) represents a minority of gastric cancer (GC) cases. The goal of this study is to use a RAND/University of California Los Angeles (UCLA) appropriateness methodology to examine indications for genetic referral, CDH1 testing, and consideration of prophylactic total gastrectomy (PTG). METHODS: A multidisciplinary expert panel of 16 physicians from six countries scored 47 scenarios. Appropriateness of scenarios was scored from 1 (highly inappropriate) to 9 (highly appropriate). Median appropriateness scores (AS) of 1-3 were considered inappropriate, 4-6 uncertain, and 7-9 appropriate. Agreement was reached when 12 of 16 panelists scored the statement similarly. Appropriate scenarios agreed upon were subsequently scored for necessity. RESULTS: The panel felt that patients with family history of diffuse gastric cancer (DGC), lobular breast cancer, or multiple family members with GC should be referred for genetic assessment and multidisciplinary decision-making. The panel felt that it is appropriate for patients with DGC to have CDH1 mutation testing in a family with (1) ≥2 cases of GC, with at least one case of DGC diagnosed before age of 50 years; (2) ≥3 cases of GC diagnosed at any age, one or more of which is DGC; (3) a patient diagnosed with DGC and lobular breast carcinoma; or (4) patients diagnosed with DGC under age of 35 years. The panel felt that PTG should be offered to CDH1 mutation carriers 20 years or older. CONCLUSIONS: Identification of genetic mutations in patients at risk for hereditary GC is important, and criteria for testing are suggested.

The value of bedside shift reporting enhancing nurse surveillance, accountability, and patient safety.

A study was undertaken to explore nurses' experiences and perceptions associated with implementation of bedside nurse-to-nurse shift handoff reporting. Interviews were conducted with nurses and analyzed using directed content analysis. Two themes emerged that illustrated the value of bedside shift reporting. These themes included clarifying information and intercepting errors and visualizing patients and prioritizing care. Nurse leaders can leverage study findings in their efforts to embed nurse-to-nurse bedside shift reporting in their respective organizations.

Children with Disabilities in Canada during the COVID-19 Pandemic: An Analysis of COVID-19 Policies through a Disability Rights Lens.

Children with disabilities were especially vulnerable during the COVID-19 pandemic, and policies designed to mitigate its effects were limited in addressing their needs. We analyzed Canadian policies related to children with disabilities and their families during the COVID-19 pandemic to identify the extent to which these policies aligned with the United Nations Convention on the Rights of Persons with Disabilities (UN CRPD) and responded to their mental health needs by conducting a systematic collection of Canadian provincial/territorial policies produced during the pandemic, building a categorization dictionary based on the UN CRPD, using text mining, and thematic analysis to identify policies' alignment with the UN CRPD and mental health supports. Mental health was addressed as a factor of importance in many policy documents, but specific interventions to promote or treat mental health were scarce. Most public health policies and recommendations are related to educational settings, demonstrating how public health for children with disabilities relies on education and community that may be out of the healthcare system and unavailable during extended periods of the pandemic. Policies often acknowledged the challenges faced by children with disabilities and their families but offered few mitigation strategies with limited considerations for human rights protection.

A commentary on the healthcare transition policy landscape for youth with disabilities or chronic health conditions, the need for an inclusive and equitable approach, and recommendations for change in Canada.

There is a growing number of youth with healthcare needs such as disabilities or chronic health conditions who require lifelong care. In Canada, transfer to the adult healthcare system typically occurs at age 18 and is set by policy regardless of whether youth and their families are ready. When the transition to adult services is suboptimal, youth may experience detrimental gaps in healthcare resulting in increased visits to the emergency department and poor healthcare outcomes. Despite the critical need to support youth with disabilities and their families to transition to the adult healthcare system, there is limited legislation to ensure a successful transfer or to mandate transition preparation in Canada. This advocacy and policy planning work was conducted in partnership with the Patient and Family Advisory Council (PFAC) within the CHILD-BRIGHT READYorNot™ Brain-Based Disabilities (BBD) Project and the CHILD-BRIGHT Policy Hub. Together, we identified the need to synthesize and better understand existing policies about transition from pediatric to adult healthcare, and to recommend solutions to improve healthcare access and equity as Canadian youth with disabilities become adults. In this perspective paper, we will report on a dialogue with key informants and make recommendations for change in healthcare transition policies at the healthcare/community, provincial and/or territorial, and/or national levels.

A meta-analysis of D1 versus D2 lymph node dissection.

BACKGROUND: Surgery is the only curative treatment for patients with gastric cancer. However, the extent of lymph node dissection is still debated. Therefore, with the publication of newer trial results, we conducted an updated meta-analysis of D1 versus D2 randomized controlled trials comparing outcomes. METHODS: Systematic searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from January 1, 1985, to December 31, 2010. Meta-analyses were performed using RevMan v5 software. Both short- and long-term outcomes were analyzed. Subgroup analyses of T stage and spleen/pancreas resection versus preservation were performed. RESULTS: Outcomes of 5 randomized trials involving 1642 patients (845 D1, 797 D2) enrolled from 1982 to 2005 were included. Despite the addition of the more recent trials, overall hospital mortality and reoperation rates were still higher in D2 cases. Subgroup analysis of recent trials and spleen/pancreas preservation revealed no significant difference in hospital mortality between groups. Five-year overall survival was similar between D1 versus D2 trials. Sub-analysis by tumor depth and spleen/pancreas preservation detected trends for improved survival with D2 lymphadenectomy in T3/T4 patients and those with spleen/pancreas preservation. CONCLUSION: Earlier trials show that D2 dissections have higher operative mortality, while recent trials have similar rates. A trend of improved survival exists among D2 patients who did not undergo resection of the spleen or pancreas, as well as for patients with T3/T4 cancers.

Systematic review of the predictors of positive margins in gastric cancer surgery and the effect on survival.

BACKGROUND: Complete resection is the only definitive treatment available for gastric cancer. Factors associated with positive margins and their survival effects have been the subject of many studies, but the appropriate management for these patients is still debated. The objective of this review is to examine positive margins after gastric cancer resections by exploring predictive factors, impact on survival, and optimal strategies for re-resection. METHODS: A systematic electronic literature search was conducted using Medline and EMBASE from January 1, 1998, to December 31, 2009. Studies on gastric or gastroesophageal junction adenocarcinoma that either investigated the predictors for positive margin or employed multivariate methods to analyze the survival effects of positive margins were selected. RESULTS: Twenty-two studies incorporating 19355 patients were included in this review. Positive margins were associated with larger tumor size, deeper wall penetration, more extensive gastric involvement, greater nodal involvement, higher stage, diffuse histology, higher Borrmann type, lymphatic vessel involvement, and total gastrectomy. Patient survival was independently associated with margin status, and this survival effect was more prominent in early cancers in most studies that performed subgroup analyses. CONCLUSIONS: The probability of acquiring positive margins is highly dependent on the biology and the extent of the tumor. There is a significant negative effect on survival, which is more prominent in cancers at early stages, making re-resection or a second operation important. Patients with more advanced disease can be offered more extensive surgery to remove disease, but this should be balanced against the risks of more extensive resections.

A systematic review of the indications for genetic testing and prophylactic gastrectomy among patients with hereditary diffuse gastric cancer.

BACKGROUND: Hereditary diffuse gastric cancer (HDGC) is a familial cancer syndrome specifically associated with germline mutations to the E-cadherin (CDH1) gene. HDGC is characterized by autosomal dominance and high penetrance and a high cumulative risk for advanced gastric cancer. Our purpose in this study was to identify and synthesize findings from all articles on: (1) current recommendations for CDH1 screening and prophylactic gastrectomy; (2) CDH1 testing results in HDGC patients; and (3) prophylactic gastrectomy results in HDGC patients. METHODS: Systematic electronic literature searches were conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1985 to 2009. RESULTS: Seventy articles were included in this review. Among patients with a positive family history of gastric cancer, 1085 were screened from 454 families, and 38.4% tested positive. Mutation-positive families also had a considerable family history of breast and colon cancer. Of the 322 patients screened for CDH1 mutations by current HDGC screening criteria, 29.2% tested positive. Among the 76.8% of patients who underwent prophylactic gastrectomy following positive CDH1 test results, 87.0% had positive final histopathology results and 64.6% had signet ring cells identified. Some of the patients with negative final histopathology results had opted to undergo prophylactic gastrectomy prior to CDH1 testing, and were ultimately found to be negative for CDH1 mutations. CONCLUSION: CDH1 mutation testing in families with a history of gastric cancer and prophylactic gastrectomy in mutation-positive patients are recommended for the management of HDGC.