Microbial water quality at contrasting recreational areas in a mixed-use watershed in eastern Canada.

Recreational water use is an important source of human enteric illness. Enhanced (episodic) surveillance of natural recreational waters as a supplement to beach monitoring can enrich our understanding of human health risks. From 2011 to 2013, water sampling was undertaken at recreational sites on a watershed in eastern Canada. This study compared the prevalence and associations of human enteric pathogens and fecal indicator organisms. Beach water samples had lower pathogen presence than those along the main river, due to different pollution sources and the hydrological disposition. Pathogen profiles identified from the beach sites suggested a more narrow range of sources, including birds, indicating that wild bird management could help reduce public health risks at these sites. The presence and concentration of indicator organisms did not differ significantly between beaches and the river. However, higher concentrations of generic Escherichia coli were observed when Salmonella and Cryptosporidium were present at beach sites, when Salmonella was present at the river recreational site, and when verotoxigenic E. coli were present among all sites sampled. In this watershed, generic E. coli concentrations were good indicators of potential contamination, pathogen load, and elevated human health risk, supporting their use for routine monitoring where enhanced pathogen testing is not possible.

Inguinal and Ilio-inguinal Lymphadenectomy in Management of Palpable Melanoma Lymph Node Metastasis: A Long-Term Prospective Evaluation of Morbidity and Quality of Life.

PURPOSE: Prospective data are lacking on long-term morbidity of inguinal lymphadenectomy including the influence of extent of surgery, use of radiotherapy, and patient factors. The aim of this study is to evaluate the effects of these factors on patient outcome, quality of life (QOL), regional symptoms, and limb volumes after inguinal or ilio-inguinal lymphadenectomy for melanoma. METHODS: Analysis of the subgroup of patients with inguinal lymph node field relapse of melanoma, treated by inguinal or ilio-inguinal lymphadenectomy in the ANZMTG/TROG randomized trial of adjuvant radiotherapy versus observation. RESULTS: Sixty-nine patients, 46 having undergone inguinal and 23 ilio-inguinal lymphadenectomy, with median follow-up of 73 months were analyzed. Mean limb volume increased rapidly after surgery (7% by 3 months) and continued to increase for at least another 18 months. Patients with body mass index (BMI) ≥ 25 kg/m2 had greater limb volume increase than normal-weight patients (13.3% versus 6.9%, P = 0.030). QOL improved over the first 18 months, but despite initial improvement, regional symptoms persisted long term. Type of surgery (inguinal or ilio-inguinal lymphadenectomy) had no demonstrably significant effect on limb volume (9.9% versus 13.4%, P = 0.35), QOL (P = 0.68), or regional symptoms (P = 0.65). There was no difference in overall survival between inguinal and ilio-inguinal lymphadenectomy [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.40-1.40, P = 0.43]. CONCLUSIONS: Inguinal lymphadenectomy for melanoma is a potentially morbid procedure with significant increases in limb volume. Patients report reasonable QOL but may have ongoing regional symptoms. Overweight/obesity is associated with poorer QOL, increased limb volume, and regional symptoms.

Estimating the Relative Role of Various Subcategories of Food, Water, and Animal Contact Transmission of 28 Enteric Diseases in Canada.

OBJECTIVE: Enteric illness represents a significant burden of illness in Canada and internationally. Building on previous research, an expert elicitation was undertaken to explore the routes of transmission for 28 pathogens involved in enteric illness in Canada. This article considers the subcategories of foodborne, waterborne, and animal contact transmission. METHODS: As part of an expert elicitation, 31 experts were asked to provide estimates of source attribution for subcategories of foodborne (n = 15), waterborne (n = 10), and animal contact (n = 3) transmission. The results from an online survey were combined using triangular probability distributions, and median and 90% credible intervals were produced. The total proportion and estimated number of cases of enteric illness attributable to each type of food commodity, water source, and animal exposure route were calculated using results from the larger elicitation survey and from a recent Canadian foodborne burden of illness study (Thomas et al., 2013). RESULTS: Thirty experts provided foodborne subcategory estimates for 15/28 pathogens, waterborne subcategory estimates for 14/28 pathogens and animal contact subcategory estimates for 5/28. The elicitation identified raw produce, recreational water, and farm animal contact as important risk factors for enteric illness. These results also highlighted the complexity of transmission, with greater uncertainty for certain pathogens and routes of transmission. CONCLUSIONS: This study is the first of its kind to explore subcategories of foodborne, waterborne, and animal contact transmission across such a range of enteric pathogens. Despite inherent uncertainty, these estimates present an important quantitative synthesis of the roles of foodborne commodities, water sources, and pathways of animal contact in the transmission of enteric illness in Canada.

Systematic review of expert elicitation methods as a tool for source attribution of enteric illness.

Expert elicitation is a useful tool to explore sources of uncertainty and to answer questions where data are expensive or difficult to collect. It has been used across a variety of disciplines and represents an important method for estimating source attribution for enteric illness. A systematic review was undertaken to explore published expert elicitation studies, identify key considerations, and to make recommendations for designing an expert elicitation in the context of enteric illness source attribution. Fifty-nine studies were reviewed. Five key themes were identified: the expert panel including composition and recruitment; the pre-elicitation material, which clarifies the research question and provides training in uncertainty and probability; the choice of elicitation tool and method (e.g., questionnaires, surveys, and interviews); research design; and analysis of elicited data. Careful consideration of these themes is critical in designing and implementing an expert elicitation in order to reduce bias and produce the best possible results. While there are various epidemiological and microbiological methods available to explore source attribution of enteric illness, expert elicitation provides an opportunity to identify gaps in our understanding and where such studies are not feasible or available, represents the only possible method for synthesizing knowledge about transmission.

Expert elicitation as a means to attribute 28 enteric pathogens to foodborne, waterborne, animal contact, and person-to-person transmission routes in Canada.

Enteric illness contributes to a significant burden of illness in Canada and globally. Understanding its sources is a critical step in identifying and preventing health risks. Expert elicitation is a powerful tool, used previously, to obtain information about enteric illness source attribution where information is difficult or expensive to obtain. Thirty-one experts estimated transmission of 28 pathogens via major transmission routes (foodborne, waterborne, animal contact, person-to-person, and other) at the point of consumption. The elicitation consisted of a (snowball) recruitment phase; administration of a pre-survey to collect background information, an introductory webinar, an elicitation survey, a 1-day discussion, survey readministration, and a feedback exercise, and surveys were administered online. Experts were prompted to quantify changes in contamination at the point of entry into the kitchen versus point of consumption. Estimates were combined via triangular probability distributions, and medians and 90% credible-interval estimates were produced. Transmission was attributed primarily to food for Bacillus cereus, Clostridium perfringens, Cyclospora cayetanensis, Trichinella spp., all three Vibrio spp. categories explored, and Yersinia enterocolitica. Multisource pathogens (e.g., transmitted commonly through both water and food) such as Campylobacter spp., four Escherichia coli categories, Listeria monocytogenes, Salmonella spp., and Staphylococcus aureus were also estimated as mostly foodborne. Water was the primary pathway for Giardia spp. and Cryptosporidium spp., and person-to-person transmission dominated for six enteric viruses and Shigella spp. Consideration of the point of attribution highlighted the importance of food handling and cross-contamination in the transmission pathway. This study provides source attribution estimates of enteric illness for Canada, considering all possible transmission routes. Further research is necessary to improve our understanding of poorly characterized pathogens such as sapovirus and E. coli subgroups in Canada.

Development of a Climate Change Vulnerability Assessment Using a Public Health Lens to Determine Local Health Vulnerabilities: An Ontario Health Unit Experience.

Climate change is negatively impacting the health of Canadians and is accordingly expected to have a significant impact on public health agencies and their response to these health impacts throughout the twenty-first century. While national and international research and assessments have explored the potential human health impacts of climate change, few assessments have explored the implications of climate change from a local public health perspective. An applied research approach to expand local knowledge and action of health vulnerabilities through a climate change action plan and vulnerability assessment was utilized by a local public health agency. Adoption and adaptation of the approach used may be valuable for public health organizations to assist their communities. Through completing a vulnerability assessment, an evidentiary base was generated for public health to inform adaptation actions to reduce negative health impacts and increase resiliency. Challenges in completing vulnerability assessments at the local level include the framing and scoping of health impacts and associated indicators, as well as access to internal expertise surrounding the analysis of data. While access to quantitative data may be limiting at the local level, qualitative data can enhance knowledge of local impacts, while also supporting the creation of key partnerships with community stakeholders which can ensure climate action continues beyond the scope of the vulnerability assessment.

Health outcomes associated with crack-cocaine use: Systematic review and meta-analyses.

BACKGROUND: Crack-cocaine use is prevalent largely in socio-economically marginalized populations in the Americas. Its use has been associated with diverse health outcomes, yet no recent or systematic reviews of these exist. METHODS: A systematic review of health outcomes associated with crack-cocaine use was performed, using MEDLINE, Scopus, Web of Science, CINAHL, PsycINFO, and LILACS up to October 2016. Search terms included crack-cocaine and health outcome-related keywords, targeting peer-reviewed studies on quantified health outcomes associated with crack-cocaine use. Random effects meta-analyses produced pooled odds ratios. Levels of evidence for major results were assessed using the GRADE approach. A review protocol was registered with PROSPERO (CRD42016035486). RESULTS: Of 4700 articles returned, 302 met eligibility criteria, reporting on health outcomes for 14 of 22 ICD-10 chapters. Conclusive evidence and meta-analyses showed positive associations between crack-cocaine use and blood/sexually transmitted diseases (HIV and hepatitis C virus, others); moderate evidence and meta-analyses supported associations with neonatal health, and violence. There were mixed associations for mental and other health outcomes, yet insufficient evidence to perform meta-analyses for many categories (e.g., mortality). Most underlying research was of limited or poor quality, with crack-cocaine commonly assessed as a secondary covariate. CONCLUSIONS: Crack-cocaine use was associated with a range of health outcomes, although it was unclear if there was direct causal impact, interactions between risk factors, or external drivers of both crack-cocaine use and outcomes. Rigorous epidemiological studies are needed to systematically assess health outcomes of crack-cocaine use and underlying pathways, also to inform evidence-based interventions.

The role of radiotherapy in the management of primary cutaneous neuroendocrine tumors (Merkel cell or trabecular carcinoma): experience at the Peter MacCallum Cancer Institute (Melbourne, Australia).

Clinical presentation, treatment, and radiation response data are presented for 20 patients with primary cutaneous neuroendocrine tumors (Merkel cell or trabecular carcinoma). Thirty-six sites were irradiated, 26 sites were local recurrences after surgery or metastases, only 3 primary tumors were irradiated de novo. In 22 out of 23 sites (96%) a complete response of measurable tumor was observed and 1 partial response (4%), an overall response rate of 100%. Thirteen sites were irradiated prophylactically with no measurable disease present and no recurrences have been seen in these areas. There was only 1 recurrence in an irradiated site (after a low radiation dose). Forty percent (8/20) either had distant metastases at presentation (5 patients) or developed them after radiotherapy (3 patients) and five of these patients have died of metastatic disease. Follow-up time ranged from 1-77 months, and actuarial 5-year survival was 63%. In view of these findings we would advocate the wider study of primary radiotherapy after biopsy or excision biopsy for the primary lesion, and prophylactic nodal irradiation with the object of avoiding extensive surgery in these often elderly patients.

Nodal radiation therapy for metastatic melanoma.

PURPOSE: The aim of this retrospective study was to review our experience of radiation therapy to regional nodes in patients with proven nodal metastases, with respect to regional control, late toxicity, and overall survival. METHODS AND MATERIALS: All patients with a histological diagnosis of malignant melanoma, with involvement of the regional nodes but without distant metastases, who commenced nodal irradiation between January 1985 and July 1995 at Peter MacCallum Cancer Institute were studied. The study population of 113 patients was divided into two categories: those with no residual macroscopic disease following nodal surgery (adjuvant group, 42 patients) and those who had no surgery (8) or had macroscopic residual disease following nodal surgery (63) (palliative group, 71 patients). RESULTS: In the adjuvant group at 5 years following commencement of nodal irradiation 26% were estimated to be failure-free. Of the 74% who had experienced treatment failure by 5 years, an estimated 20% failed first with nodal relapse, 52% with distant metastases, and 2% with both nodal relapse and distant metastases. The estimated 5-year overall survival for this group was 33%. In the palliative group 16 patients (23%) had an objective complete response. Altogether 48 patients (68%) had a symptomatic response. At 5 years the overall survival in this group was 8% and an estimated 4% were failure-free. Of the 96% who had failed by 5 years, 68% failed first in the regional nodes, 25% had distant metastases as the first failure, and 3% had both nodal relapse and distant metastases. CONCLUSION: We recommend adjuvant postoperative radiation therapy for patients with proven nodal metastases and high risk of regional recurrence (multiple nodes, extracapsular extension, or recurrent nodal disease) in addition to adjuvant interferon.

Analysis of toxicity of Merkel cell carcinoma of the skin treated with synchronous carboplatin/etoposide and radiation: a Trans-Tasman Radiation Oncology Group study.

PURPOSE: The acute and late toxicities of synchronous carboplatin, etoposide, and radiation therapy were prospectively assessed in a group of patients with high-risk Merkel cell carcinoma of the skin. PATIENTS AND METHODS: Forty patients from six different centers throughout Australia were entered into a Phase II study under the auspices of the Trans-Tasman Radiation Oncology Group. The trial was activated in 1996 and continues to accrue. Patients are eligible if they have disease localized to the primary site and nodes and are required to have at least one of the following high-risk features: recurrence after initial therapy, involved nodes, primary size greater than 1 cm, gross residual disease after surgery, or occult primary with nodes. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks, and synchronous carboplatin (area under curve [AUC] 4.5) and etoposide (80 mg/M(2) i.v.) were given on days 1-3 during weeks 1, 4, 7, and 10. The median age of the group was 67 years (43-78). RESULTS: The median duration of follow-up was 22 months (2-45). There were no treatment-related deaths. Grade 3 or 4 skin toxicity occurred in 63% of patients (95% CI 48, 78). The most serious acute effect was on neutrophils with Grade 3 or 4 (neutrophils < 1 x 10(9)/L), occurring in 60% (95% CI 45, 75) of cases. Complications from neutropenia (fever and sepsis) occurred in 16 patients (40% of cases). The median time for neutropenic complications was 27 days (9-35), and 10/16 (62%) cases of neutropenic fever occurred after the second cycle of chemotherapy. The probability of Grade 3 or 4 late effects on platelets (<50 x 10(9)/L) and hemoglobin (<8 g/dl) was 10% (95% CI 1, 20) and 6% (95% CI 2, 15), respectively. Of the 40 patients, 35 were able to complete 4 cycles of chemotherapy. There were no factors predictive for neutropenic toxicity at a p value < 0.05. CONCLUSIONS: The protocol has acceptable toxicity, and the treatment has been deliverable in a multi-institutional trial setting. Neutropenia is likely to occur with synchronous carboplatin/etoposide and radiation in this population of patients. The risk of a febrile neutropenia was greatest at the time of the second cycle of chemotherapy, when there was moist desquamation of skin or mucosal membranes that provided a portal for infection. This should be considered in the design of subsequent protocols with chemoradiotherapy.

Use of a radon mould technique for skin cancer: results from the Peter MacCallum Cancer Institute (1975-1984).

During the period from 1975 to 1984, 642 patients had non-melanoma skin cancers (NMSC) treated by a radon mould technique following the principles of the Manchester system. The results of 77 out of 642 (12%) with histologically verified lesions are presented. The sites of the lesions were as follows: head and neck 25 (32%), upper limbs 38 (49%), lower limbs 13 (17%) and trunk one case only. The histological diagnosis was squamous cell carcinoma 48 (62%), basal cell carcinoma in 22 (29%) and other in seven (9%). There were nine out of 77 (12%) failures, four with persistent disease, which did not clear after initial treatment (and for whom the radon mould was an inappropriate choice of technique), and five (6%) recurrences after clearance of the initial lesion. There was a sharp rise in failures after 1979 when there was a change of radon supplier, but no calibration error was substantiated. It is clearly beneficial for institutions to cross-check the manufacturer's brachytherapy source data. There have been no further recurrences or any symptomatic late morbidity. This is a safe, effective and practical radiotherapeutic technique for superficial lesions (not exceeding a depth of 4 mm) in areas of poor radiation tolerance, and may obviate the need for a prolonged fractionated course of external-beam radiation in selected patients. Alternatives to radon are discussed.

Public health impact of global heating due to climate change: potential effects on chronic non-communicable diseases.

OBJECTIVES: Several categories of ill health important at the global level are likely to be affected by climate change. To date the focus of this association has been on communicable diseases and injuries. This paper briefly analyzes potential impacts of global climate change on chronic non-communicable diseases (NCDs). METHOD: We reviewed the limited available evidence of the relationships between climate exposure and chronic and NCDs. We further reviewed likely mechanisms and pathways for climatic influences on chronic disease occurrence and impacts on pre-existing chronic diseases. RESULTS: There are negative impacts of climatic factors and climate change on some physiological functions and on cardio-vascular and kidney diseases. Chronic disease risks are likely to increase with climate change and related increase in air pollution, malnutrition, and extreme weather events. CONCLUSIONS: There are substantial research gaps in this arena. The health sector has a major role in facilitating further research and monitoring the health impacts of global climate change. Such work will also contribute to global efforts for the prevention and control of chronic NCDs in our ageing and urbanizing global population.

Kinetochore-generated pushing forces separate centrosomes during bipolar spindle assembly.

In animal somatic cells, bipolar spindle formation requires separation of the centrosome-based spindle poles. Centrosome separation relies on multiple pathways, including cortical forces and antiparallel microtubule (MT) sliding, which are two activities controlled by the protein kinase aurora A. We previously found that depletion of the human kinetochore protein Mcm21R(CENP-O) results in monopolar spindles, raising the question as to whether kinetochores contribute to centrosome separation. In this study, we demonstrate that kinetochores promote centrosome separation after nuclear envelope breakdown by exerting a pushing force on the kinetochore fibers (k-fibers), which are bundles of MTs that connect kinetochores to centrosomes. This force is based on poleward MT flux, which incorporates new tubulin subunits at the plus ends of k-fibers and requires stable k-fibers to drive centrosomes apart. This kinetochore-dependent force becomes essential for centrosome separation if aurora A is inhibited. We conclude that two mechanisms control centrosome separation during prometaphase: an aurora A-dependent pathway and a kinetochore-dependent pathway that relies on k-fiber-generated pushing forces.

Technique for axillary radiotherapy using computer-assisted planning for high-risk skin cancer.

High-risk skin cancer arising on the upper limb or trunk can cause axillary nodal metastases. Previous studies have shown that axillary radiotherapy improves regional control. There is little published work on technique. Technique standardization is important in quality assurance and comparison of results especially for trials. Our technique, planned with CT assistance, is presented. To assess efficacy, an audit of patients treated in our institution over a 15-month period was conducted. Of 24 patients treated, 13 were treated with radical intent, 11 with this technique. With a follow up of over 2 years, the technique had more than a 90% (10/11) regional control in this radical group. Both of the radical patients who were not treated according to the technique had regional failure. One case of late toxicity was found, of asymptomatic lymphoedema in a radically treated patient. This technique for axillary radiotherapy for regional control of skin cancer is acceptable in terms of disease control and toxicity as validated by audit at 2 years.