How do the characteristics of breast cancer diagnostic assessment programmes influence service delivery: A mixed methods study.

Diagnostic assessment programmes (DAPs) coordinate multidisciplinary teamwork (MDT), and improve wait times and patient satisfaction. No research has established optimal DAP design. This study explored how DAP characteristics influence service delivery. A mixed methods case study of four breast cancer DAPs was conducted including qualitative interviews with health-care providers and retrospective chart review. Data were integrated using multiple approaches. Twenty-three providers were interviewed; 411 medical records were reviewed. The number of visits and wait times from referral to diagnosis and consultation were lowest at a one-stop model. DAP characteristics (rural-remote region, human resources, referral volume, organisation of services, adherence to service delivery targets and one-stop model) may influence service delivery (number of visits, wait times). MDT, influenced by other DAP characteristics (co-location of staff, patient navigators, team functioning), may also influence service delivery. While the one-stop model may be ideal, all sites experienced similar and unique challenges. Further research is needed to understand how to optimise the organisation and delivery of DAP services. Measures reflecting individual, team and patient-reported outcomes should be used to assess the effectiveness and impact of DAPs in addition to more traditional measures such as wait times.

Rural placement experiences in dental education and the impact on professional intentions and employment outcomes-A systematic review.

CONTEXT/INTRODUCTION: The availability of clinical dental services in rural locations is a major concern for many countries as dental care professionals gravitate to work in metropolitan areas. This systematic review examines the literature on Rural Placement Programs within dentistry and their impact on workforce intentions and employment outcomes. The review provides a detailed analysis of the methodological characteristics of the literature, considers the quality of the evidence and compares the outcomes within an international context. MATERIALS AND METHODS: The systematic review identified published literature between 2005 and 2016 from databases including EMBASE, MEDLINE, PubMed, NursingOVID and Cochrane. The PRISMA protocol was adopted for the development of the study, and the Health Gains Notation Framework was implemented to assess the quality of the selected research papers. RESULTS: Eleven studies considering Rural Clinical Placement Programs met the inclusion criteria. The studies were from Australia, South Africa, United States, Thailand and India. The evidence in this review indicates that well-designed, financially supported programmes that provide a perceived valuable clinical experience, good supervision and professional support in a rural environment can lead to dental students stating increased intentions to working in a rural location. However, there was a lack of evidence and research into whether these rural intentions result in positive action to take up employment in a rural location. CONCLUSION: The evidence suggests that well-prepared rural clinical placements, which have experienced clinical supervisors, good professional student support from the dental school, provide a valuable clinical experience and are sufficiently funded, can increase intentions to work in a rural location upon graduation. However, there is a lack of evidence in dentistry into whether intentions translate into practitioners taking clinical positions in a rural location. Future research should be planned, which will undertake longitudinal cohort studies to identify factors that have an important influence on rural job choice.

An Ontario Health (Cancer Care Ontario) Clinical Practice Guideline: Surveillance Strategies in Patients with Stage I, II, III or Resectable IV Melanoma Who Were Treated with Curative Intent.

AIMS: To make recommendations on managing the surveillance of patients with stage I, II, III or resectable IV melanoma who are clinically free of disease following treatment with curative intent. MATERIALS AND METHODS: This guideline was developed by Ontario Health's (Cancer Care Ontario's) Program in Evidence-Based Care and the Melanoma Disease Site Group (including seven medical oncologists, four surgical oncologists, three dermatologists, one radiation oncologist and one patient representative). The MEDLINE, EMBASE, Cochrane Library, PROSPERO databases and the main relevant guideline websites were searched. Internal and external reviews were conducted, with final approval by the Program in Evidence-Based Care and the Melanoma Disease Site Group. The Grading of Recommendations, Assessment, Development and Evaluation approach was followed, and the Modified Delphi method was used. RESULTS: Based on the current evidence (eight eligible original study papers and four relevant guidelines) and the clinical opinions of the authors of this guideline, the initial recommendations were made. To reach 75% agreement for each recommendation, the Melanoma Disease Site Group (16 members) voted twice and one recommendation was voted on three times. After a comprehensive internal and external review process (including national and international reviewers), 12 recommendations, three weak recommendations and six qualified statements were ultimately made. CONCLUSIONS: After a systematic review, a comprehensive internal and external review process and a consensus process, the current guideline has been created. The guideline authors believe that this guideline will help clinicians, patients and policymakers make well-informed healthcare decisions that will guide them in clinical melanoma surveillance and ultimately assist in improving patient outcomes.

What is the burden of axillary disease after neoadjuvant therapy in women with locally advanced breast cancer?

BACKGROUND: The burden of axillary disease in patients with locally advanced breast cancer (labc) after neoadjuvant therapy (nat) has not been extensively described in a large modern cohort. Here, we describe the extent of nodal metastases after nat in patients with labc. METHODS: All patients with labc treated at a single institution during 2002-2007 were identified. Demographic, radiologic, and pathologic variables were extracted. To assess the extent of lymph node metastases after nat, patients were separated into two groups: those with and without clinical or radiologic evidence of lymph node metastases before nat. Axillary lymph nodes retrieved at surgery that had no evidence of metastases after hematoxylin and eosin (h&e) staining underwent further pathology evaluation. RESULTS: Of the 116 patients identified, 115 were female (median age: 48.5). Before nat, 26 patients were clinically and radiologically node-negative; of those 26, 14 were histologically negative on final pathology. After serial sectioning and immunohistochemistry, 9 of 26 (35%) were node-negative. Of the 90 patients who had clinical or radiologic evidence of lymph node metastases before nat, 23 (26%) had no evidence of lymph node metastases on h&e staining. After serial sectioning and immunohistochemistry, 19 (21%) had no further axillary lymph node metastases. Overall, 76% of patients had pathology evidence of lymph node metastases after nat. CONCLUSIONS: Most patients with labc have axillary metastases after nat. Our findings support axillary lymph node dissection and locoregional radiation in most patients with labc after nat.

Long-term results of screening with magnetic resonance imaging in women with BRCA mutations.

BACKGROUND: The addition of breast magnetic resonance imaging (MRI) to screening mammography for women with BRCA mutations significantly increases sensitivity, but there is little data on clinical outcomes. We report screening performance, cancer stage, distant recurrence rate, and breast cancer-specific mortality in our screening study. METHODS: From 1997 to 2009, 496 women aged 25 to 65 years with a known BRCA1/2 mutation, of whom 380 had no previous cancer history, were enrolled in a prospective screening trial that included annual MRI and mammography. RESULTS: In 1847 screening rounds, 57 cancers were identified (53 screen-detected, 1 interval, and 3 incidental at prophylactic mastectomy), of which 37 (65%) were invasive. Sensitivity of MRI vs mammography was 86% vs 19% over the entire study period (P<0.0001), but was 74% vs 35% from 1997 to 2002 (P=0.02) and 94% vs 9% from 2003 to 2009 (P<0.0001), respectively. The relative sensitivities of MRI and mammography did not differ by mutation, age, or invasive vs non-invasive disease. Of the incident cancers, 97% were Stage 0 or 1. Of 28 previously unaffected women diagnosed with invasive cancer, 1 BRCA1 mutation carrier died following relapse of a 3 cm, node-positive breast cancer diagnosed on her first screen at age 48 (annual breast cancer mortality rate=0.5%). Three patients died of other causes. None of the 24 survivors has had a distant recurrence at a median follow-up of 8.4 years since diagnosis. CONCLUSION: Magnetic resonance imaging surveillance of women with BRCA1/2 mutations will detect the majority of breast cancers at a very early stage. The absence of distant recurrences of incident cancers to date is encouraging. However, longer follow-up is needed to confirm the safety of breast surveillance.

Predictors of survival in patients with non-curative stage IV cancer and malignant bowel obstruction.

PURPOSE: Malignant bowel obstruction (MBO) occurs in up to 15% of patients admitted to palliative care wards and management can be clinically challenging. Survival is generally poor with a reported median survival of 1-3 months; however, there are no studies describing predictors of survival for patients with MBO. PATIENTS AND METHODS: All patients admitted to a tertiary care hospital with a MBO were approached between March 1, 2006 and March 31, 2008 to enter the study. Demographic, clinical, laboratory, and radiographic information were prospectively collected from patient charts and the patient's functional status (Eastern Cooperative Oncology Group score, ECOG) at admission was recorded. Follow-up was until death or the end of the study (August 2008). Survival was estimated using Kaplan-Meier plots and Cox regression models were used to evaluate prognostic factors for survival. RESULTS: Thirty-five patients were recruited. Median patient age was 61% and 46% were female. Median survival of the cohort was 80 days (range 7-873). Median survival for patients with an ECOG performance status of 0-1 (n = 15) was 222 days, for ECOG 2 patients (n = 9), 63 days and for patients with an ECOG 3/4 score (n = 11) it was 27 days. ECOG status was the strongest predictor of survival on the multivariate analysis. In addition, a low blood urea nitrogen level or a high albumin on admission was also associated with prolonged survival. CONCLUSION: An ECOG score of 0/1 for patients with MBO in the setting of Stage IV non-curative cancer is the strongest predictor of overall survival.

Optimal assessment of residual disease after neo-adjuvant therapy for locally advanced and inflammatory breast cancer--clinical examination, mammography, or magnetic resonance imaging?

PURPOSE: Accurate assessment of residual disease after neo-adjuvant chemotherapy (NEC) for women with locally advanced and inflammatory breast cancer (LABC) is critical for planning surgery. The study's purpose was to prospectively determine the optimal method (clinical examination (CE), mammogram (MG), and magnetic resonance imaging (MRI)) for assessing residual disease after NEC for women with LABC. METHODS: Women with LABC who received NEC and surgery were enrolled. Patient demographics, tumor size as measured by CE, MG, and MRI both before and after NEC, and final pathologic size of tumor were collected. Response to NEC was calculated using RECIST criteria. Paired t-tests and the Pearson correlation were used to compare tumor size on CE, MG, MRI, and final pathology. RESULTS: Forty-eight women with 50 LABC were recruited. Mean pre-NEC tumor size was 8.2, 5.1, and 6.2 cm on CE, MG, and MRI. Mean post-NEC tumor size was 2.4, 4.3, 3.9, and 3.6 cm on CE, MG, MRI, and final pathology. The Pearson correlation co-efficient between post-NEC measurements and pathology was 0.63 (CE), 0.15 (MG), and 0.49 (MRI). CONCLUSION: We found that there was limited correlation between the extent of residual disease after NEC for patients with LABC as assessed by CE, MG, and MRI as compared to final pathology.

Qualitative assessment of patient experiences following sacrectomy.

BACKGROUND AND OBJECTIVES: The primary objective was to investigate patient experiences following sacral resection as a component of curative surgery for advanced rectal cancers, soft tissue and bone sarcomas. METHODS: Qualitative methods were used to examine the experiences, decision-making, quality of life, and supportive care needs of patients undergoing sacrectomy. Patients were identified from two prospective databases between 1999 and 2007. A semi-structured interview guide was generated and piloted. Patient interviews were transcribed verbatim and analyzed using standard qualitative research methodology. Grounded theory guided the generation of the interview guide and analysis. RESULTS: Twelve patients were interviewed (6 female, 32-82 years of age). The mean interview time was 34 min. Five themes were identified, including: (1) the life-changing impact of surgery on both patients' and their family's lives, (2) patient satisfaction with immediate care in hospital, (3) significant chronic pain related to sacrectomy, (4) patients' need for additional information regarding long-term recovery, and (5) patients' gratitude to be alive. CONCLUSIONS: Sacrectomy is a life-changing event for patients and their families. Patients undergoing sacrectomy need further information regarding the long-term consequences of this procedure. This need should be addressed in both preoperative multi-disciplinary consultations and at follow-up visits.

Locoregional management of in-transit metastasis in melanoma: an Ontario Health (Cancer Care Ontario) clinical practice guideline.

Objective: The purpose of this guideline is to provide guidance on appropriate management of satellite and in-transit metastasis (itm) from melanoma. Methods: The guideline was developed by the Program in Evidence-Based Care (pebc) of Ontario Health (Cancer Care Ontario) and the Melanoma Disease Site Group. Recommendations were drafted by a Working Group based on a systematic review of publications in the medline and embase databases. The document underwent patient- and caregiver-specific consultation and was circulated to the Melanoma Disease Site Group and the pebc Report Approval Panel for internal review; the revised document underwent external review. Recommendations: "Minimal itm" is defined as lesions in a location with limited spread (generally 1-4 lesions); the lesions are generally superficial, often clustered together, and surgically resectable. "Moderate itm" is defined as more than 5 lesions covering a wider area, or the rapid development (within weeks) of new in-transit lesions. "Maximal itm" is defined as large-volume disease with multiple (>15-20) 2-3 cm nodules or subcutaneous or deeper lesions over a wide area.■ In patients presenting with minimal itm, complete surgical excision with negative pathologic margins is recommended. In addition to complete surgical resection, adjuvant treatment may be considered.■ In patients presenting with moderate unresectable itm, consider using this approach for localized treatment: intralesional interleukin 2 or talimogene laherparepvec as 1st choice, topical diphenylcyclopropenone as 2nd choice, or radiation therapy as 3rd choice. Evidence is insufficient to recommend intralesional bacille Calmette- Guérin or CO2 laser ablation outside of a research setting.■ In patients presenting with maximal itm confined to an extremity, isolated limb perfusion, isolated limb infusion, or systemic therapy may be considered. In extremely select cases, amputation could be considered as a final option in patients without systemic disease after discussion at a multidisciplinary case conference.■ In cases in which local, regional, or surgical treatments for itm might be ineffective or unable to be performed, or if a patient has systemic metastases at the same time, systemic therapy may be considered.

Multidisciplinary cancer conferences: identifying opportunities to promote implementation.

BACKGROUND: Cancer care is complex and multimodal therapy is now considered the standard of care. Multidisciplinary cancer conferences (MCCs) offer a venue to prospectively discuss cancer patients and plan treatment. MCCs are believed to improve patient outcomes and consequently have been internationally adopted. The purpose of this study was to describe the prevalence of MCCs in Ontario and identify individual and organizational barriers to their adoption. METHODS: A cross-sectional, mailed questionnaire of general surgeons in Ontario, Canada who care for patients with cancer was used to assess prevalence, and organizational and individual barriers to MCC implementation. Responses were summarized overall, by hospital, and by academic status. RESULTS: The response rate was 44.2% (170/385). Respondents worked at 57 unique hospitals, of which 29 (52%) were reported to have MCCs, including all academic hospitals (7/7) and 22 of 50 (44%) community hospitals. Forty-nine MCCs were reported at 29 hospitals. MCCs occurred weekly at academic centers and biweekly or monthly at community hospitals. Few MCCs (28%) had a designated coordinator. Surgeons perceived that MCCs helped them to incorporate multidisciplinary opinions into their patient care plans, improved collegiality, and provided opportunity for continuing professional development. CONCLUSIONS: Despite the perceived benefits expressed by respondents, administrative support for MCCs may be minimal. In particular, surgeons at community hospitals may have limited access to multidisciplinary patient care planning. This information will be utilized to shape a provincial strategy for implementing MCCs. However, further research is required to understand barriers and enablers to establish and maintain MCCs, especially in community practice.

Taking the pulse of multidisciplinary cancer conferences for breast cancer care in Canada: A stocktake of current practice.

AIM: International guidelines highlight the importance of implementation supports and quality monitoring of multidisciplinary care for breast cancer. In Canada, Ontario has standards for formal multidisciplinary cancer conferences (MCCs), but other provinces/territories do not. This study aimed to stocktake MCCs for breast cancer in Canadian sites participating in the RUBY cohort study (Reducing the Burden of Breast Cancer in Young Women) to better understand variations in multidisciplinary care across Canada and to add to the international literature. METHODS: A cross-sectional survey was conducted with surgeons and surgical oncologists representing 34 clinical centres participating in RUBY. Questions were grouped according to: type of multidisciplinary care, implementation, function, practice, participation and presentation, operation, and demographics, and included a mix of Likert-based, tick box and open-ended questions. RESULTS: Twenty-two responses (65%) were received. 91% of respondents reported that formal MCCs are part of regular practice. However, variation exists in the supports in place for ongoing implementation of MCCs, the understanding of the functions of MCCs, and the patients presented for discussion. Results also suggest less formalized processes for MCC in provinces without practice standards. CONCLUSIONS: Response differences between Ontario and elsewhere suggest that standards for MCC and supports for their implementation make a positive difference in their operation. However, ongoing operational challenges and issues with attendance exist for all sites and suggest that along with development of practice standards, incentives for participation and further education on benefits and function of MCC may support uptake of MCCs in clinical practice.

Primary excision margins, sentinel lymph node biopsy, and completion lymph node dissection in cutaneous melanoma: a clinical practice guideline.

Background: For patients who are diagnosed with early-stage cutaneous melanoma, the principal therapy is wide surgical excision of the primary tumour and assessment of lymph nodes. The purpose of the present guideline was to update the 2010 Cancer Care Ontario guideline on wide local excision margins and sentinel lymph node biopsy (slnb), including treatment of the positive sentinel node, for melanomas of the trunk, extremities, and head and neck. Methods: Using Ovid, the medline and embase electronic databases were systematically searched for systematic reviews and primary literature evaluating narrow compared with wide excision margins and the use of slnb for melanoma of the truck and extremities and of the head and neck. Search timelines ran from 2010 through week 25 of 2017. Results: Four systematic reviews were chosen for inclusion in the evidence base. Where systematic reviews were available, the search of the primary literature was conducted starting from the end date of the search in the reviews. Where systematic reviews were absent, the search for primary literature ran from 2010 forward. Of 1213 primary studies identified, 8 met the inclusion criteria. Two randomized controlled trials were used to inform the recommendation on completion lymph node dissection.Key updated recommendations include:■ Wide local excision margins should be 2 cm for melanomas of the trunk, extremities, and head and neck that exceed 2 mm in depth.■ slnb should be offered to patients with melanomas of the trunk, extremities, and head and neck that exceed 0.8 mm in depth.■ Patients with sentinel node metastasis should be considered for nodal observation with ultrasonography rather than for completion lymph node dissection. Conclusions: Recommendations for primary excision margins, sentinel lymph node biopsy, and completion lymph node dissection in patients with cutaneous melanoma have been updated based on the current literature.

Multidisciplinary cancer conferences: a systematic review and development of practice standards.

BACKGROUND: Multidisciplinary cancer conferences (MCCs) are a forum for health care providers to discuss diagnostic and treatment aspects of a cancer patient's care. In Ontario, we have found that very few hospitals have developed cancer conferences or forums for the prospective discussion of patient cancer care. In this paper, we describe the process of creating a province-wide standards document for MCCs. METHODS: A systematic review and environmental scan were conducted to evaluate the literature regarding the impact of MCCs on physician practice patterns and patient outcomes, using the methodology of the Practice Guidelines Development Cycle. An Expert Panel was created to develop draft MCC standards. Ontario administrators and practitioners were surveyed to elicit feedback regarding the standards document. The findings were collated, and practice standards were developed. RESULTS: Multidisciplinary care, predominantly in the form of multidisciplinary clinics, has been shown to improve patient outcomes. While only limited evidence suggested a benefit for MCCs, they have been documented as influential in changing patient management plans. MCCs were also found to be part of standard cancer care on an international level. Ontario practitioners surveyed generally supported MCC implementation. DISCUSSION: We have described the process of creating an Ontario MCC standards document, including a literature review and an examination of the attitudes of Ontario practitioners and hospital administrators regarding the development and implementation of a MCC Standards document.

4-Piperazinyl-10H-thieno[2,3-b][1,5]benzodiazepines as potential neuroleptics.

A series of 4-substituted 10H-theino[2,3-b][1,5]benzodiazepines has been synthesized. These compounds have been assessed for their ability to block a conditioned avoidance response (CAR) and to produce catalepsy in rats and have been compared with several typical and atypical neuroleptics. The compounds which inhibit CAR at doses which produce no catalepsy are believed to cause less extrapyramidal side effects in the clinic. A number of compounds (9, 12, 17, 29, and 34) show potent neuroleptic activity, yet maintain a favorable separation of activity on these two parametrs. Three 5-piperazinyl-10H-thieno[2,3-b][1,4]benzodiazepine derivatives (46-48) analogous to compounds in the [1,5] series have been prepared for comparison and were found to be inactive.

10-Piperazinyl-4H-theino[3,2-b][1,5]- and -[3,4-b][1,5]benzodiazepines as potential neuroleptics.

The synthesis of 10-piperazinyl-4H-thieno[3,2-b][1,5]benzodiazepines is described. The activity of these compounds has been assessed on the basis of their ability to produce hypothermia in mice and block a conditioned avoidance response (CAR) and produce catalepsy in rats, and the results are compared with various classical and nonclassical neuroleptic drugs. A number of compounds (6, 17, 21, and 22) demonstrate potency greater than clozapine and also show low degree of catalepsy. It is believed that this profile of activity, unlike standard neuroleptics, is associated with the relative lack of extrapyramidal side effects in the clinic. The corresponding 9-piperazinyl-4H-thieno[1,4]benzodiazepines (12 and 35, limited analogues prepared in the respective series, were inactive.

Differential enhancement of locomotor activity by dopamine agonists following chronic morphine treatment.

Aniamls were administered increasing doses of morphine for 16 days. During withdrawal they were challenged with an apomorphine ester or lergotrile. These dopamine agonists produced quantitatively different effects on behaviour. The results suggest that chronic morphine administration leads to dopamine supersensitivity which may be anatomically distinct in origin.

Differential enhancement of locomotor activity by dopamine agonists following chronic neuroleptic treatment: an animal model of tardive dyskinesia.

Animals were administered clozapine or haloperidol for 22 days. Following treatment they were challenged with an apomorphine ester or lergotrile. Only haloperidol-treated animals exhibited significantly enhanced responses to apomorphine ester whereas administration of lergotrile potentiated locomotor activity in both treated groups. The results suggest that the use of different dopaminergic agonists may help to dissociate receptor supersensitivity arising from the antipsychotic actions of neuroleptics from that leading to the development of undesirable side effects.

Two dopamine receptors: supportive evidence with the rat rotational model.

Di-isobutyryl apomorphine (5 mg/kg i.p.) and lergotrile (5 mg/kg i.p.) produce long lasting turning behaviour in rats with 6-hydroxydopamine lesions at the level of the substantia nigra. Haloperidol (1.5 and 3.0 mg/kg p.o.) blocks the rotational behaviour due to the apomorphine ester but has no effect on lergotrile turning. Clozapine (10 and 20 mg/kg p.o.) blocks the lergotrile turning but stimulates the rotational behaviour produced by the apomorphine ester. The results support the concept of two anatomically separate dopamine receptors and their relevance to the study of antipsychotic activity is discussed.

Control of psoroptic scabies of cattle with fenvalerate.

Fenvalerate [Cyano(3-phenoxyphenyl)methyl-4-chloro-alpha-(1-methylethyl) benzene acetate] was evaluated as a one- or two-dip treatment at two different concentrations against cattle infested with Psoroptes ovis (Hering). One or two dips at 0.025% or one dip at 0.05% failed to eliminate P. ovis; two dips in fenvalerate at 0.05% provided complete elimination of all mites. Fenvalerate was equally effective against male, female, and immature mites, but did not exhibit ovicidal properties.

Preliminary trials using a macrocyclic lactone against psoroptic scabies of cattle.

A macrocyclic lactone, LL-F28249 alpha, C36H52O8, was evaluated as a one- or two-injection treatment in different formulations and concentrations against cattle infested with Psoroptes ovis (Hering). One injection of 2 mg kg-1 or two injections of 1 mg kg-1 of 3% active material in either an aqueous or oil formulation failed to eliminate all of the mites. A single injection of 3 mg kg-1 as a 5% aqueous formulation eliminated all mites for 35 days post-injection. At lower dosages of the aqueous formulation (3%), the male mites appeared to be less susceptible to the acaricide than either the female or immature mites.