Increasing systemic treatment and shortages of oncology professionals in Canada require innovative approaches to the safe and effective delivery of intravenous (IV) cancer treatment. We conducted a systematic review of the clinical and scientific literature, and an environmental scan of models in Canada, the United Kingdom, Australia, and New Zealand. We then developed a framework for the organization and delivery of IV systemic treatment.medline, embase, cinahl, and HealthStar databases. The environmental scan retrieved published and unpublished sources, coupled with a free key word search using the Google search engine. The Systemic Treatment Working Group reviewed the evidence and developed a draft framework using evidence-based analysis, existing recommendations from various jurisdictions, and expert opinion based on experience and consensus. The draft was assessed by Ontario stakeholders and reviewed and approved by Cancer Care Ontario.The systematic review covered the The poor quantity and quality of the evidence necessitated a consensus-derived model. That model comprises four levels of care determined by a regional systemic treatment program and three integrated structures , each with a defined scope of practice and a specific organizational framework.New models of care are urgently required beyond large centres, particularly in geographically remote or rural areas. Despite limited applicable evidence, the development and successful implementation of this framework is intended to create sustainable, accessible, quality care and to measurably improve patient outcomes. In Canada, cancer is a major cause of morbidity and mortality, and the leading cause of potential years of life lost. Increasing demands for cancer services relate directly to annual cancer incidence increases of 3%, resulting mainly from population growth and aging md Education Registry revealed that only 34 medical oncology residents and 8 fellows are in oncology training for the entire country Several provincial and national bodies have convincingly demonstrated that ongoing clinical human resource shortages limit funding and filling of new oncology positions Given such changes, Canadian provinces need to devise innovative ways to deliver safe and effective systemic treatment in an ambulatory care setting for people with cancer. The risks of not pursuing a revised and sustainable model of systemic treatment delivery include adoption of ad hoc and inconsistent local solutions; cessation of service in some jurisdictions; and inequalities in access to, and standards of, care.The purpose of the present work was to provide a practical framework to guide standardized delivery of evidence-based systemic treatment in hospitals outside regional cancer centres, with special consideration for geographically dispersed regions. The primary goal of the framework is to provide safe, evidence-based systemic cancer treatment while maximizing the efficient use of resources and implementing the principle of patient-centred care provided as close to home as possible. Service provision; complexity of care; safety, accessibility, and quality across all care levels defined from the patient, organization, and system perspective; and appropriateness, transparency, and accountability were all taken into consideration. Quality, research, and education are interlinked and integral parts in the regional delivery of safe systemic treatment, ensuring the dissemination of new or improved evidence-based standards in this rapidly changing field.We used two core methodologies to develop this framework:a systematic review of scientific and clinical research evidence andan environmental scan of systemic treatment models developed in other jurisdictions.medline , embase , cinahl , and HealthStar . The terms used were “anti-neoplastic agents,” “chemotherapy,” “infusions intravenous,” and “neoplasms,” combined with “health facilities,” “organizational policy,” “continuity of patient care,” “outpatient clinics,” “ambulatory care facilities,” “hospitals rural,” “hospitals community,” “hospitals general,” “health care facilities,” and “health care policy”. Article bibliographies and personal files were also searched for relevant evidence.The scientific and clinical literature was systematically searched for published and unpublished reports pertaining to the organization and delivery of systemic treatment. Published sources included the medical databases The environmental scan retrieved published and unpublished sources  documenting systemic treatment delivery at hospitals outside a larger cancer centre. Documents from countries with health care systems similar to Canada’s  were considered. In addition, a free keyword search was conducted through the Internet Google search engine, and a search was made for documents mentioned in the text or references of identified reports.www.cancercare.on.ca/pdf/pebc12-10s.pdf The inclusion criteria were kept purposefully broad. Any study design was considered if it provided evidence on ways to deliver systemic treatment within ambulatory care institutions. Outcomes of interest included health care provider roles and education, service type and complexity, service volumes, quality assurance, facility requirements, and administrative and organizational responsibilities. Specific details of the development of the evidence base can be found online at The Regional Models of Care Systemic Treatment Working Group, comprising medical oncologists, a Cancer Care Ontario regional vice president, a regional cancer program administrator, a systemic treatment satellite nursing administrator, oncology nurses, administrators, pharmacists, and other professionals, reviewed the evidence and used a combination of evidence-based analysis, existing recommendations from various jurisdictions, and expert opinion based on experience and consensus to develop the framework. Given that the quantity and quality of evidence was generally poor, the panel agreed upon the framework elements through consensus of expert opinion.www.cancercare.on.ca/pdf/pebc12-10s.pdf A draft framework document was circulated to 191 stakeholders in Ontario for feedback, with 89% of respondents endorsing the framework and document recommendations. More details regarding the feedback obtained can be found at www.cancercare.on.ca/pdf/pebc12-10s.pdfEvidence on the current organization and delivery of systemic treatment across Canada, the United Kingdom, Australia, and New Zealand was gathered through a systematic search of the literature and a scan of documents from organizations concerned with systemic treatment quality practice. In Canada, the provinces of British Columbia, Saskatchewan, and Nova Scotia have instituted important initiativesrstp). The main goal of the model is to facilitate the provision of appropriate care in the appropriate setting within the appropriate time frame for all patients, regardless of the geographic location in which a patient receives systemic treatment. The model is composed of three integrated structures—integrated cancer programs (icps), affiliate institutions, and satellite institutions—each with a defined scope of practice.The Regional Model for Quality Systemic Treatment  consistsicps are multidisciplinary organizations that provide complex cancer care and that conduct cancer site–specific multidisciplinary care conferences (mccs). The mccs discuss unusual cases, oversee quality assurance, and provide assistance on cases seen at the rstp level 1–4 facilities in their own icp region. The mccs include surgical, radiation, and systemic therapy oncologists, nurses, pharmacists, social workers, pathologists, and radiologists. The icps provide leadership in the development of local guidelines for their region; they collect and assist in the analysis of outcome measures and quality indicators for funding, patient safety, and program organization and efficiency; and they may provide academic leadership, including educational support and access to research.The rstp. Satellite institutions have fewer oncology-related resources and have a formal linkage to the rstp for support in delivering systemic treatment.Affiliate institutions have their own systemic treatment programs, although they are linked through formal agreements with the rstps and will collaboratively determine the appropriate configuration for their model, including the formal linkages that will be required among institutions. The complexity of care delivered in each type of institution may vary; standards encompassing four institutional levels of care (levels 1–4) are recommended for the delivery of systemic treatment, with the level of complexity and the availability of services differentiating one level from another. The rstp determines the appropriate level of care for each institution. Levels are hierarchical, with the satellite responsibilities being encompassed within the affiliate and icp levels. The designation of a level requires that an institution meet all the standards for that level. As individual institutions expand or focus their services, the configuration of the model and the designation of institutional levels may change, after consultation between the rstp and the institution.All regional partner institutions will participate in the development of their The successful implementation of the framework is intended to create sustainable, accessible quality care and to measurably improve patient outcomes. The four levels and their standards are these:Level 4 (Satellite)icp or an affiliate level 3 institutionAmbulatory facilities, nursing, pharmacy, and physician support provided for the administration of low-risk to high-risk intravenous systemic treatment under the direction of an oncologist from an Systemic treatments given under the supervision of a physician with appropriate oncology trainingrstp are ensuredAccess to specialized services and to providers with a formalized linkage to the Level 3 (Affiliate)Systemic treatments given under direct supervision of an on-site staff medical oncologist, hematologist, or gynecologic oncologistLimited teaching and research responsibilitiesicp)Level 2 Limited teaching and research responsibilitiesicp)Level 1 (Academic institutions with teaching and research responsibilitiesind) program  with highly developed clinical trials infrastructure—for example, participation in the National Cancer Institute of Canada Clinical Trials Group ind program and Princess Margaret Hospital/U.S. National Institutes of Health phase II new drug consortiumExperimental investigational new drug rstp is to ensure safe, standardized, evidence-based care across the regions and equitable access to systemic treatment. a.The goal of the The Regional Models of Care Systemic Treatment Project Team used the modest evidence that was available from the published literature and the environmental scan and the expert opinion of the membership to reach consensus on the defining features for the organization and for delivery of systemic cancer treatment.For several years, Cancer Care Ontario regional networks delivered systemic treatment, particularly in rural areas, under a hub-and-spoke model; however, this delivery was accomplished without regional governance or management authorityAlthough developed in the Ontario context, this model may, we believe, be useful in other provinces. The goal of the model is to ensure that, regardless of where in a province a patient receives systemic treatment, the same standard of care is guaranteed: the patient receives appropriate care in the appropriate setting within the appropriate time frame by clinicians with the expertise to offer the services. A regional program model replaces a traditional hub-and-spoke model and better reflects the relationships between all partners delivering systemic treatment.rstp assumes regional leadership for the delivery of systemic treatment, with support from the provincial cancer organization. Although most regional authorities in Canada  have icps, it is important to acknowledge that, to best meet patient needs, cross-regional collaboration must also be considered in the planning of rstps. In addition, regional authorities without icps also exist, and therefore regional cancer services must be planned through a neighbouring icp. Under the rstp, systemic treatment icps, affiliates, and satellites would work collaboratively to ensure safe, evidence-based care that maximizes the capacity of care given across the region, while ensuring appropriate high-quality care.In the new model, the rstp agrees to the move. The present work provides a framework for all hospitals to meet the same standards and, at the same time, to achieve quality care and service when administering systemic treatment. Although the present article has been created to sustain the Ontario Cancer Care network in providing safe and accessible care, we believe that it is applicable to, and useful for, other jurisdictions.The structure for systemic treatment delivery in ambulatory centres provides a comprehensive regional and provincial framework. This framework has been formed through a combination of evidence and expert consensus. Consensus was achieved through a small working group and the larger Regional Models of Care Systemic Treatment Project Team. The framework outlines the four levels (institution types) of care that are recommended for the delivery of systemic treatment. A hospital is not prevented from moving up to the next level, provided that all the model requirements are met and that the All authors declared no conflicts of interest.


In the past decade, there is an increased focus on quality and safety in health care. Decreasing variation, increasing adherence to evidence based guidelines, monitoring processes, and measuring outcomes are critical for improving quality of care. Intensivists have broad knowledge of hospital organization, and need to be leaders in quality improvement efforts. In addition, the increase in travel tourism for health care to India is increasing, and there is a need to demonstrate outcomes comparable to other countries to compete effectively for this market. Public trust in health care providers could also be adversely affected if the public perceives that the care provided is not of high quality. The Medical Council of India (MCI) and the ministry of health are creating standards of care for physicians.[In the past two decades improvements in life-sustaining technologies (LST) resulted in an increase in the number of intensive care units (ICUs), and patient receiving LST in the ICUs. Care of the critically ill patients is resource-intensive, and 15-20% of hospital budgets are spent in the ICUs. The focus on quality and safety of medical care is increasing because of the high cost of health care and potential for harm.7 Clemmerysicians. For thesHistory of Quality ImprovementQuality Improvement Methods and implementationQuality Improvement Initiatives in ICUThe following review includesth century, reported his outcomes in surgical patients and advocated pubic reporting of outcomes by both physicians and hospitals.[Although there is an increase in focus on safety and quality in the past few decades, the concern about quality of health care is very old as indicated by the admonition “first do no harm”. Florence Nightingale kept records of her patients and outcomes to assess the impact of care, and suggested that knowledge of outcomes is crucial to improving care. Codman, one of the pioneers in QI in the early 20ospitals. The modeospitals. Donabediospitals. initiateThe report “To Err is Human” by the Institute of Medicine (IOM) in the United States in 1999, led to an increased focus on safety and quality of care. IOM suggested that care should be safe, effective, patient centered, timely, efficient, and equitable. IOM reported that that one of the primary quality problems is inappropriate use of resources, and suggested efforts to improve the use of resources by focusing on overuse, under use and misuse.16 As a ret al reported a 43% variation in resource use and costs  between intensivists without a significant difference in mortality or length of stay.[Quality is defined by the IOM as “the degree to which health services for individuals and populations increase the likelihood of desired health outcomes and are consistent with current professional knowledge.” Although there has been more emphasis on performances of healthcare providers and quality of care recently, the focus on quality of care is not new. Codman suggested, about 100 years ago, that hospitals must collect data on their outcomes, identify strong and weak points and compare the results with other hospitals. Unexplained variation in patient care is based more on physician biases rather than patient-related factors. In the study of intensive care physicians at a university hospital, Garland  of stay. VariatioAlthough physicians accept improving quality of care as a goal, they are sometimes skeptical of quality improvement efforts and consider participation in QI efforts as a non productive use of their time and view efforts to decrease variation as an interference with their autonomy. Physicians' behavior is influenced by suggestions from a respected colleague or role model, appropriate support for professional skill development, reinforcement by colleagues, feedback from patients, and visible results. Physicians need to agree that processes that influence clinical activity lead to measurable outcomes. Feedback and refining the process based on clinician input would get buy-in from frontline staff. Physician leaders need to be recognized as good clinicians and develop skills in communication, team building/coaching, negotiation and conflict resolution, quality improvement principles, so that they can implement QI initiatives effectively.–21 PhysiDonabedian proposed reviewing structure, process and outcome to improve quality of care. The modeThe success of QI projects depends on identifying projects which all stakeholders find useful and building a team culture. Performance measures and outcomes should be clearly defined, valid, and reliable. Documentation and data collection should be incorporated into daily work routines. Team development and process/outcome definition, followed by an iterative process of implementation, evaluation and process adjustment based on the evaluation are important steps in achieving the goals. Leadership buy-in and support is essential for implementation and success. A comprehensive plan with a description of the goals, plan for implementation, cost and benefits with business plan and timeline will be helpful in obtaining administrative support.Successful implementation of changes in practice are facilitated by check lists, disease specific pre-printed order sets, daily order sets that include goals for care. Standardized order sets facilitate implementation of best practices in addition to improving compliance with best practices. Establishing standards of care, monitoring processes and outcomes, creation of multidisciplinary teams, data recording as part of routine care, automated retrieval of information by using information technology facilitate QI efforts. A bedside electronic record facilitates data collection and retrieval. The experience of institutions with successful implementation strategies include: leadership support, incentives for senior leaders, physician and nursing leadership in implementing the initiatives, and involvement of bedside caregivers in the design and implementation of a QI projects.Identification of a clinical process that need be changed–based on benefits/risk/costs; patient care needs, informal discussions and payor prioritiesDesired outcomes.Multi-disciplinary teamProcess measures, protocol, dataTime needed for design, Implementation and reporting outcomesThe improvement is usually incremental and requires repeated evaluations and refinement of processes. A brief summary of the initiatives, categorized according to the principles of quality listed by IOM is provided in The process should involve multidisciplinary teams consisting of intensivists, ICU nursing staff and staff of respiratory therapy department with participation from other departments such as Infection Control and Blood Bank. Consensus guidelines which include inclusion and exclusion criteria, algorithms for implementing each of the process elements, definition of outcomes and data collection need to be created, As an example of one of the projects, the algorithm for implementation of daily Spontaneous Breathing Trials (SBT) was shown in Ventilator Associated Pneumonia (VAP) bundle: VAP increase length of stay and morbidity. Implementation of all the individual; components of the bundle has been shown to be effective in decreasing VAP.[sing VAP.–26 The cHead of the Bed elevation (HOB) to > 30 degreesDaily Sedation Interruption (SI)Daily spontaneous Breathing Trials (SBT)Oral careDeep venous Thrombosis (DVT) prophylaxisStress Ulcer ProphylaxisCompliance with process measures Ventilator days, length of stay (LOS)Incidence of VAP - Pneumonias/1000 ventilator daysReintubationsOutcomes:Sepsis Bundle: Standardized management of sepsis decreases costs and improves mortality.[ortality. Shorr reortality.Early Goal Directed Therapy  within six hours of identification of sepsisBlood cultures and other appropriate cultures prior to broad spectrum antibiotic therapyImaging studies to diagnose/confirm source of infectionAntibiotics within one hour of diagnosing sepsisSource control with appropriate balance of risks and benefits of chosen interventionConsider stress dose steroids in patients with vasopressor dependenceRecombinant Activated Protein C in appropriate patients with in 24h of recognition of severe sepsis/shockMaintain hemoglobin 7-9 gm/dl if there is no active bleeding, cardiac ischemia, or hypoperfusionManagement of adult respiratory syndrome with conservative fluid management, low tidal volumes, adequate Positive End Expiratory Pressure (PEEP) and limitation plateau pressuresGlycemic control to maintain blood glucose < 150 mg/dlReassessment and narrowing antibiotic therapy based on cultures results and limiting antibiotic use for 7-10 days.Compliance with individual measuresLOS in ICU and hospital28 day mortalityOutcomes:Central Line Associated Bacteremia (CLAB) Bundles: Shannon et al reported that CLAB not only increases morbidity and but also resulted in a loss to the hospital because the reimbursement is lower than the costs. Implementation of the CLAB bundle resulted in a decrease of 825 (7.7 to 1.4 infections/1000 catheter days).[et al reported that implementation of all elements of the bundle decrease CLAB rate from 7.7 to 1.4 infections/1000 catheter days.[er days). Pronovoster days.Hand WashingBarrier precautions Chlorhexidine skin preparationDaily assessment of need for central line and early discontinuationThe components of the bundle areCompliances with individual processesIncidence of CLAB (# of infections/1000 days)Outcomes:Communication: Pronovost et al reported that use of check list of daily goals during rounds improved communication and outcomes.[outcomes. DiscussiReview labs, cultures, X-raysSchedule tests/proceduresClinical; goals for volume status, mechanical ventilation and dailySpontaneous breathing trials, glycemic control: location, durationand review for catheters/tubesReview of medications including antibiotic coveragePain/sedation management and daily sedation interruptionNutrition, stress ulcer and DVT prophylaxisActivityCommunication – with consultants, familyDaily communication goals:Another tool to improve communication is to standardize format of communication between staff and physicians by following the SBAR toolS- Situation: description of clinical situationB- Background: clinical history/contextA- Assessment: a description of possible problemsR- Recommendations: a description of possible solutionsRapid Response Team (RRT): Foraida et al and others reported that implementation of RRT response resulted in a decrease in cardio respiratory events leading to cardiac arrest and improved survival. RRT helps to identify patients at risk and provide early resuscitation.[citation. The compRate <8 or 36/ minuteNew onset difficulty breathingNew pulse oximetry reading <85% for > 5 minutes in a patient with no prior history of chronic hypoxia2 >0.5 to obtain SaO2 >85%New requirement for FiO<40 or > 140/minute with new symptoms or any rate >160/minuteSystolic BP<80 or > 200 mm/hg or diastolic BP .110 mm/hg with symptoms Acute loss of consciousnessNew onset lethargy or difficulty walkingSeizureSudden loss of movement or weakness of face, arm or legChest pain unrelieved by nitroglycerinUnexplained agitation for > 10 minutesUncontrolled bleeding, large blood loss, bleeding to airwayNaloxone use without responseEnd-of-life care and family supportManagement of acute lung injuryEnteral nutritional supportGlycemic control in critically ill patients.Other QI measures that could be evaluated in the ICU include:The Institute of Medicine in the U.S. reported that there is a quality chasm in healthcare and suggested that the delivery of healthcare should be improved, so that it is safe, effective, patient-centered, timely, efficient and equitable. Both medical leadership and staff need to work together to achieve such a healthcare system. Effective implementation of existing treatments that were shown to be beneficial is more cost effective than implementing newer treatments that are marginally more effective. Intensivists, because of their broad knowledge of the hospital and interactions with multiple specialties are well suited for leading efforts to improve quality of care.


Aedes aegypti mosquito and can cause severe disease especially in children. Dengue fever is a major problem in tropical and sub-tropical regions of the world.Dengue fever is a virus infection that is spread by the We invited dengue experts from around the world to attend meetings to discuss dengue surveillance. We reviewed literature, heard detailed reports on surveillance programs, and shared expert opinions.Presentations by 22 countries were heard during the 2.5 day meetings. We describe the best methods of surveillance in general, the stakeholders in dengue surveillance, and the steps from mosquito bite to reporting of a dengue case to explore how best to carry out dengue surveillance. We also provide details and a comparison of the dengue surveillance programs by the presenting countries.The experts provided recommendations for achieving the best possible data from dengue surveillance accepting the realities of the real world . Their recommendations included: (1) Every dengue endemic country should make reporting of dengue cases to the government mandatory; (2) electronic reporting systems should be developed and used; (3) at minimum dengue surveillance data should include incidence, hospitalization rates, deaths by age group; (4) additional studies should be completed to check the sensitivity of the system; (5) laboratories should share expertise and data; (6) tests that identify dengue virus should be used in patients with fever for four days or less and antibody tests should be used after day 4 to diagnose dengue; and (7) early detection and prediction of dengue outbreaks should be goals for national surveillance systems. The Pediatric Dengue Vaccine Initiative organized Dengue Prevention Boards in the Asia-Pacific and the Americas regions consisting of dengue experts from endemic countries. Both Boards convened meetings to review issues in surveillance. Through presentations, facilitated discussions, and surveys, the Boards identified best practices in dengue surveillance including: (1) Dengue should be a notifiable disease in endemic countries; (2) World Health Organization regional case definitions should be consistently applied; (3) electronic reporting systems should be developed and used broadly to speed delivery of data to stakeholders; (4) minimum reporting should include incidence rates of dengue fever, dengue hemorrhagic fever, dengue shock syndrome, and dengue deaths, and hospitalization and mortality rates should be reported by age group; (5) periodic additional studies  should be conducted to assess under-detection, under-reporting, and the quality of surveillance; (6) laboratory methods and protocols should be standardized; (7) national authorities should encourage laboratories to develop networks to share expertise and data; and (8) RT-PCR and virus isolation (and possibly detection of the NS1 protein) are the recommended methods for confirmation of an acute dengue infection, but are recommended only for the four days after onset of fever—after day 4, IgM-capture enzyme-linked immunosorbent assay is recommended. Aedes aegypti mosquito, is the most important mosquito-borne viral disease affecting humans Dengue virus, which is most commonly transmitted by the Dengue prevention is limited vector control and treatment is limited to supportive care to avoid shock. To address the need for dengue prevention, several dengue vaccines are in development. One candidate entered expanded phase 2 clinical trials in 2009 Decision making prior to vaccine introduction and monitoring for effectiveness and safety after introduction require adequate country specific disease surveillance data As part of its program to facilitate the development and introduction of a dengue vaccine in endemic countries, Pediatric Dengue Vaccine Initiative (PDVI) Accurate burden of disease data will be needed for informed decision making regarding vaccine introduction In total, there were presentations on the surveillance programs from twenty two countries given by representatives of Ministry of Health or other agency participating in dengue surveillance in-country (e.g. Institute Pasteur) , and Venezuela) . BecauseThe core functions of a comprehensive surveillance system are detection, reporting, investigation, confirmation, analysis, interpretation, and response. Cooperation is essential between the healthcare system and the public health authority because for rapid response to emerging public health threats the public health authority is dependent on healthcare system to generate timely and accurate case reports.At the time of the meeting, WHO had published guidelines on the diagnosis of dengue including case definitions; but these guidelines were published more than 10 years ago One major difficulty with all previous guidelines is case classification Although meeting attendees reported using similar dengue case definition systems, surveillance methods varied between countries. Laboratory methods also vary as well as the testing algorithms and the interpretation of positives. For example, in Brazil and Colombia, healthcare providers complete case reports on both ambulatory and hospitalized patients, however, in Thailand and Vietnam the majority of reported cases are hospitalized. In only 12/22 (55%) of countries represented at the meeting confirmed all officially reported cases with laboratory testing. Nearly every country includes suspected dengue cases regardless of age, but in Cambodia surveillance is conducted only among children less than 15 years of age. In Singapore and Brazil, monitoring vector indices is an integral part of the dengue surveillance system, while in Puerto Rico it is not. The attendees reported that these differences were not currently a problem for country level analyses but make inter-country, regional, and global analyses and comparisons difficult. Moreover, some difference (e.g. lack of dengue surveillance among adults in Cambodia) could be an impediment to strategic planning and implementation of a dengue vaccine since the disease also affects adults as well as children. Moreover, the vaccination of children is likely to also have an impact on adult disease burden Since surveillance data are needed for health ministries to target control responses when outbreaks are detected, data must be collected in a timely fashion. In order to better understand the overall process, attendees reviewed the steps from infection to reporting . The incAe. aegypti breeding sites in the field. The data are then immediately available to plan interventions and follow-up. All countries are dependent on paper forms for case reporting before any additional investigation or action. Time is required for that report to reach the surveillance office, to be entered and analyzed, and finally be reported. However, many countries are developing improved methods for data collection for targeted interventions.The medium for reporting ranged from paper case report forms, to hand-held computers, to internet-based systems. A case study from Nicaragua showed that hand-held computers, although initially requiring significant investment in infrastructure and training, do reduce reporting time. In Kolkata, India, special mapping of cases has been used to target control activities. In Singapore and Brazil, ministries are also using intranet-based data entry software allowing staff to directly enter data on cases and Another key issue is the needs of stakeholders with interests in dengue diagnosis and surveillance. These stakeholders include the general public, senior policy-makers, academics, and legislators. A diverse group, their interests range from the parents of sick children who want immediate and accurate test results—knowing the diagnosis allows them to cope better—to healthcare workers, staff in laboratories, public health and vector control authorities. All want a point-of-care test to speed accurate diagnosis and treatment and allow rapid public health intervention. Others  are more likely interested in more accurate tests to allow improved burden of disease estimates which could effect budget allocations for control.In most countries diagnostic testing and surveillance relies on healthcare practitioners and laboratory staff to report cases but they receive little benefit. Confirmatory diagnostic tests such as virus isolation or reverse transcriptase-polymerase chain reaction testing (RT-PCR) require expertise and equipment usually found only in reference laboratories. However, several attendees explained that the time required for a sample to reach and to be processed at centralized facilities often results in delays that render the results useless to the treating physician. Further delays occur if the information provide on a sample is incomplete or if batch-testing of samples is conducted. After testing, the report generated requires verification, approval and delivery (e.g. mailing). As a consequence, health care providers in most countries must treat patients empirically The attendees concluded that simplified case reporting Attendees were asked to identify the strengths and weaknesses of their systems. Most indicated that their countries had adequate infrastructure and surveillance systems, and the adjectives “dedicated”, “committed”, “skilled”, and “motivated” were widely used to describe the quality of the personnel engaged in surveillance. They reported some country-specific but effective links between the various stakeholders; especially healthcare providers, laboratory staff, and the public health and vector control authorities. However, many of these relationships are dependent on personal contacts which are affected by staff turnover.A common perception among meeting attendees was that disease control is politically more important than prevention. That is, highly visible outbreak response through spraying is considered more important than outbreak prevention. Specifically, during outbreaks, public demand for action often leads to pesticide spraying Lack of preventive services in the provinces is seen as a further impediment to conducting adequate surveillance. Further, even when adequate infrastructure exists, data are rarely used locally; rather they are forwarded to the central ministry offices for official evaluation, missing the opportunity for an immediate local response. Diagnostic tests further complicate the situation because the results are often difficult to interpret by the healthcare providers and public health practitioners unfamiliar with the limitations of the tests As an outcome of the meeting, attendees agreed on best practices on laboratory practices, data gathering, analyses, reporting, and feedback for dengue surveillance.Every dengue endemic country should systematically gather data in an established dengue surveillance system Reporting should be encouraged from all levels of healthcare facilities in both the public and the private sectors Laboratory confirmation improves the specificity of surveillance A critical element for the successful laboratory diagnosis of an acute dengue infection is the timely collection of high quality samples. Monitoring the time from case identification to receipt of blood samples in the testing facility may assist in maintaining high quality specimens.RT-PCR and virus isolation are the two recommended methods for virus identification. Monitoring serotypes and sequencing isolates can provide useful markers for outbreak prediction In the first four days after onset of fever, either RT-PCR or virus isolation are the recommended assays for confirmation of dengue infection Support should be provided for quality control, proficiency testing and good laboratory practice at the WHO reference laboratory level, the national level and the local level At least weekly reporting of aggregate results was considered by the attendees as the minimum standard during peak transmission. To conserve resources, reporting could be reduced to biweekly during periods of low transmission. During an outbreak, more frequent reporting, perhaps on a daily basis, would be useful. However, it is important to note that reporting would be affected by the operating hours of the reporting facilities . Reports should reach the surveillance units within 48 hours of form completion.Especially since dengue occurs frequently in young adults in Southeast Asia, it is recommended that the usual categories for reporting in health information systems should be used, namely less than 1 year, 1–4 years, 5–14 years and older than 15 years. However, reporting the median age of cases across all ages is also a useful statistic to track, and may be more useful for comparison if countries are using different age categories. Moreover, if the median age is reported by countries not including cases of all ages because the peak incidence is in children, the overall age distribution could be modeled with the available data. Electronic reporting systems should be developed and used broadly and such applications would facilitate formal reporting among countries.Meeting attendees emphasized the need to determine the incidence of severe cases through measurement of incidence rates of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome, with hospitalization rates and mortality rates broken down by age group consistently applying the WHO regional case definitions. Weekly incidence of dengue, with data stratified by age, gender, and location should also be rapidly reported to allow effective use of vector control resources and to monitor intervention programs. In addition analyses should be conducted to detect and forecast dengue outbreaks through determination of the national threshold for outbreak alert and response In conclusion, the two Dengue Prevention Boards met to discuss the practice and logistics of dengue surveillance. The attendees applied their practical experience and discussed the strengths and weakness for the countries represented at the meeting. They then suggested best practices in dengue surveillance in endemic countries. For PDVI, improved surveillance serves many purposes including generating more accurate estimates of disease burden, further demonstrating the need for a dengue vaccine, supporting clinical evaluations of candidate dengue vaccines and providing more robust surveillance for monitoring the impact of the eventual introduction of dengue vaccines in national immunization programs.


Objectives. To assess previously determined geographic clusters of breast and lung cancer incidences among residents living near the Tittabawassee and Saginaw Rivers, Michigan, using a new set of environmental factors. Materials and Methods. Breast and lung cancer data were acquired from the Michigan Department of Community Health, along with point source pollution data from the U.S. Environmental Protection Agency. The datasets were used to determine whether there is a spatial association between disease risk and environmental contamination. GIS and spatial techniques were combined with statistical analysis to investigate local risk of breast and lung cancer. Results and Conclusion. The study suggests that neighborhoods in close proximity to the river were associated with a high risk of breast cancer, while increased risk of lung cancer was detected among neighborhoods in close proximity to point source pollution and major highways. Statistically significant (P ≤ .001) clusters of cancer incidences were observed among residents living near the rivers. These findings are useful to researchers and governmental agencies for risk assessment, regulation, and control of environmental contamination in the floodplains. Lung cancer is the leading cause of cancer-related death in Michigan and in the United States (U.S.), while breast cancer is the most frequently diagnosed cancer among Michigan women and the leading cause of death in the U.S. women between their late thirties and early fifties , 2. Studies on breast cancer suggest that breast cancer involves a complex interaction of internally (endogenous) and externally (exogenous) introduced factors . The mosFurthermore, some studies have noted differences in breast cancer incidences based on ethnicity, education level, and years of residence at the same location , 11, 12.The spatial variations of breast cancer occurrence suggest a potential hypothesis partially due to local and regional environmental risk factors , 11, 15.Lung cancer on the other hand involves several factors some of them include cigarette smoking, personal and family health history, and environmental pollution. Cigarette smoking, which accounts for 87 percent of all lung cancers, is recognized as the leading risk factor for lung cancer . Other fDue to emerging evidence of effects of air pollution on lung cancer there is an urgent need to conduct additional studies to establish a casual relationship between environmental pollution and lung cancer. Recent studies on lung cancer and environmental pollution suggest that urban/rural differences in lung cancer incidence is due to presence of a variety of known and potential human carcinogens in polluted air of urbanized areas , 19–21.Studies on socioeconomic risk factors suggest that race and education may also contribute to a higher risk of lung cancer. In several studies, for example, a higher risk of lung cancer was found among African Americans with lower education level and Whites as compared to recent immigrants from India and Africa, which may be attributed to smoking , 22–25.Although air pollution appears to be a minor contributor to lung cancer compared to smoking, it involuntarily affects a significant population and therefore requires greater attention. Growing evidence of an association between a lung cancer and environmental exposure reflects the importance of the need to assess its relative contribution , 23–26. The availability of large surveillance datasets and spatial techniques makes it easy to analyze breast and lung cancer data relative to environmental factors. In particular, Geographic Information Systems (GISs) are an emerging tool in environmental epidemiology studies, especially for cancer studies , 28. GISSince few studies have addressed the analysis of risk factors of breast and lung cancer incidences in the floodplains of the Tittabawassee and Saginaw Rivers, the overarching goal of this study is to determine whether there is a connection between environmental exposure and cancer disease by critically examining a priori clusters of cancer disease in Michigan State. The study hypothesizes that there is a potential link between increased risks of cancer disease and sources of pollution suspected to be environmentally contaminated. Three research questions were formulated to help with investigating the hypothesis. (1) Are there any environmental contaminants in the floodplains of the Tittabawassee and Saginaw Rivers that have a potential to contribute to breast and lung cancer within the at-risk population? (2) Is there a relationship between identified environmental contaminants and breast and lung cancer incidences in the study area? (3) Is there a relationship between spatial proximity to point source pollution and cancer incidence? To answer these questions we use geographically based exposure assessment strategies. The study employed GIS and spatial techniques combined with statistical analysis to examine occurrence of cancer incidences in relation to proximity from point source pollution, major highways, and the floodplains of the Tittabawassee and Saginaw Rivers.This retrospective study covers a period extending 14 years between 1989 and 2002 to investigate the occurrence of breast and lung cancer in relation to environmental contamination. The study suspects a major health risk due to the exposure of pollution sources. Therefore, the study design was focused on critically assessing previously determined geographic clusters of breast and lung cancer incidences among residents living near the Tittabawassee and Saginaw Rivers, Michigan, using a new set of environmental factors , 31. BreThe study area consists of 38 ZIP codes, located within the Bay, Midland, and Saginaw counties, central Michigan . AccordiPotential risk factors of cancer in this area comprise a variety of components of physical and built environments including industry , major highways, and hydrological infrastructure  . About hFour data categories were used to analyze the spatial risk of disease: disease data , sources of environmental pollution , the 2000 U.S. Census data, and baseline data .Data pertaining to cancer were acquired from the Michigan Department of Community Health (MDCH), Vital Records and Health Statistics Unit, Development Section . The poiThe disease data represent a list of annually diagnosed cancer cases (incidences) from the MDCH cancer registry database, which complies with quality standards of the National Cancer Institute's Surveillance, Epidemiology, and Results (SEER) Program. Each data record contains invasive cancer case, patient's ZIP code of residence at diagnosis, patient's gender, type of diagnosed cancer, and patient's age group. Since protecting the patient's privacy is required by law, the MDCH only provides ZIP code referenced cancer data where there are more than 5 000 people. Although this spatial unit is coarse, it was the best data available to support this level of analysis. Additionally, cancer data can easily be linked to census data to provide additional insights regarding potential trends and spatial patterns.n = 3 768) and lung cancer cases (n = 4 014). Additionally, the original classification of cancer was recorded for six age groups: less than 15; 15 to 29; 30 to 44; 45 to 64; 65 to 74; and over 75 years of age. In total, we had cancer data for twenty two ZIP codes containing numerous breast cancer cases  . A totalThe physical addresses of industrial facilities, representing point source pollution, were geocoded  and mapped using ESRI's ArcGIS 9.2 . Address matching was based on ESRI's USA street map data using U.S. Alphanumeric Ranges with Zone address locator style. To achieve a high success rate in assigning geographic coordinates and for quality control purposes, we performed a combination of automatic and interactive matching and crosschecking of addresses with a full user control over the entire process. As a result, 92% of addresses were matched with a score of 80 and higher, and 3% of addresses were matched with candidates tied. Based on the results of exploratory analysis, several point pollution sources were selected to analyze the decay distance-exposure relationship between location of selected sources and cancer incidence rates. Specifically, selection of pollution sources  was based on numerous criteria, including history of carcinogenic releases during the study period; and location of facility in the ZIP code characterized by low or high cancer incidence, and within a spatial cluster detected using spatial techniques. As a result of these criteria and exploratory analysis, 16 out of 128 industrial facilities were selected for thorough investigation. Also six of these facilities have been identified in recent studies as potential sources responsible for increased risk of breast cancer , and tenData analysis consisted of three major aspects: preliminary data analysis  and GIS mapping , statistical techniques , and spatial analysis . The analysis was conducted using numerous software applications, including ArcGIS 9.2, ArcView 3.3, GeoDa 0.95i ; ClusterSeer 2.0 and TerraSeer's STIS 1.6 ; Microsoft Excel ; and SPSS 17.0 . Preliminary analysis was done to explore, describe, and summarize the data, detect outliers and anomalies, or to detect relationships and generate hypotheses regarding the data. Basic statistics was generated to summarize the data using the mean, standard deviation, coefficient of variation, and 95% confidence level. The data were mapped to show spatial patterns and distributions of industrial facilities with regards to the cancer data.P ≤ .05 were employed to test whether there is a significant association between exposure to environmental pollution and outcome between exposed and unexposed groups: the cases and controls, correspondingly. The population in ZIP code 48883 , race , nativity (percent of native born), education level (percent of high school graduates), and residency (percent of population residing at the same address in 1995). To complete this analysis, ZIP codes with synthesized spatial clusters of breast and lung cancer were classified as areas of high disease risk and ZIP codes without clusters of cancer as areas of low or no disease risk.The ordinary kriging of cancer incidence data was performed to account for spatial variations within the data, to reduce impact of small population size or uncertainty, and because the rates were strongly positively skewed –39. The Four spatial techniques were used to identify clusters of increased cancer incidence rates, where a cluster represents any area within the study region of significant elevated risk of disease occurrence . EmployeIn the MDCH database there were 3 769 female breast cancer cases and 4 014 lung cancer cases registered over 14 years of the study period. The majority of both breast and lung cancer incidences  were adults over 45 years of age. Less than one percent of cancer patients were younger than the age of 30 . There were no female breast cancer patients younger than the age of 15, and only one breast cancer patient was of unknown age, whose record was excluded from the analysis.The highest average rate of breast cancer was recorded in 2000 during the study period, while the year 1998 was characterized by the lowest average rate of breast cancer. There was a notable difference between the mean incidence rate and standard deviation suggesting wide dispersion in the observations. The CI was relatively narrow, confirming overall accuracy of the breast cancer data. The temporal trend portrayed a stable progression of average annual rates; yet it was characterized by presence of a distinguishable peak of high incidence rate in 2000. Using the total number of cases as the denominator, the highest incidences were from ZIP codes 48603 (13.7%), 48601 (11.6%), 48640 (11.2%), and 48706 (10.8%), mainly located within Midland and Saginaw communities . The femThe highest average rate of lung cancer was recorded in 2000 during the study period, while the year 1990 had the lowest average rate of lung cancer. There was a notable difference between the mean incidence rate and standard deviation suggesting wide dispersion in the observations. The CI was relatively narrow, confirming overall accuracy of lung cancer data. The temporal trend was characterized by a slight increase. Moreover, there was a considerable increase incidence rates between 1990 and 1994 with an obvious peak in 2000. Using the total number of cases as the denominator, the highest incidences were from ZIP codes 48601 (15.8%), 48706 (14.3%), and 48603 (11%), located within Saginaw and Bay City communities . PopulatThe incidence rates were derived for the female population who were 15 years and older as the denominator; the overall rates ranged from 141 to 337 for every 10 000 females. The rates were highest among female residents living in ZIP codes 48734, 48880, 48640; and higher in 48603, 48618, 48732, 48706, and 48604 . These ZThe incidence rates were calculated using population who are 15 years and older as the denominator; the overall rates ranged from 61 to 184 per every 10 000 people. The incidence rates were highest among neighborhoods located in ZIP codes 48601, 48706, 48708; and higher in 48602, 48732, 48657, 48655, 48603, and 48650 . These aA closer examination of both the breast and lung cancer incidence rates suggests the presence of consistent nonhomogenous spatial patterns in the study region. Specifically, the female adult populations with increased risk of breast cancer reside in close proximity to the floodplains of the Tittabawassee and Saginaw Rives, while those with increased risk of lung cancer seem to reside near industrial facilities and major highways.P ≤ .05) was found in 40% of ZIP codes .A map of these odds ratio shows a significant association between exposure and outcome and is in agreement with spatial patterns of breast cancer incidence rates that were observed earlier confirming increased breast cancer risk around the floodplains of major rivers .For lung cancer, a positive association between possible exposure to environmental pollution and the lung cancer was observed in 32% of ZIP codes . However, populations residing in ZIP codes 48642 and 48623 had a negative association.A map of these odd ratios shows a significant association between exposure and outcome thus confirming increased risk near industrial facilities and major highways, which are located in southeastern portion of the study region . A negatWhen Empirical Bayesian Smoothing was applied, high incidence rates of breast cancer incidences were observed in ZIP codes 48640, 48603, and 48734. For lung cancer, the high incidence rates were observed in ZIP codes 48732, 48706, 48708, and 48601. None of the breast cancer incidence rates were statistically significant after a Local Moran's test was done, while only two ZIP codes 48732 and 48708 were statistically significant for lung cancer. These observations are pretty consistent with what we have observed with other techniques. Overall, these techniques provide preliminary evidence of high incidence rates in some geographic locations in the study region, which seem to be persistent.The assessment of cancer rates using Turnbull's method revealed additional insights regarding the nonhomogenous nature of the spatial distribution of both breast and lung cancer. P-value = .0006) and 48603 , located within Midland and Saginaw communities situated at the beginning of the Tittabawassee and Saginaw Rivers, respectively. For breast cancer, we investigated clusters within a population of 7 105 females at 95% confidence level. The method detected two statistically significant clusters of increased breast cancer incidence rates among residents living in ZIP codes 48640  and 48706 , located within Saginaw community (upstream of Saginaw River) and Bay City township , respectively.While for lung cancer we investigated clusters within a population of 13 504 people at 99% CI. We detected two statistically significant clusters of increased lung cancer incidence rates in ZIP codes 48602 . According to this analysis, the main risk socioeconomic factors for both breast and lung cancer in this study region was Hispanic race (for both breast and lung cancer) and residency at the same location (for breast cancer only).The areas identified with increased risk of breast and lung cancer were delineated to investigate the relative importance of socioeconomic characteristics. The discriminant analysis of risk areas of both breast and lung cancer successfully differentiated between high- and low-risk areas of cancer  and residency at the same location (for breast cancer) are more likely to be susceptible to the risk of cancer. These findings are consistent with results of previous studies suggesting differences in incidence of breast cancer based on ethnicity, and years of residence at the same location, and differences in the risk for lung cancer between ethnic groups , 22, 24.Findings from this study support the hypothesis that there is a spatial association between the risk of cancer and environmental exposure. The study period of 14 years, although it could be longer than 20 years in some cases, generally captures the latency of cancer, further provided evidence on the effects of long-term exposure to air pollution on lung cancer. Geographic locations near major rivers were associated with high risk of breast cancer, while spatial clusters of lung cancer were found near point source pollution and major highways. The study identified the presence of environmental contaminants with a potential to explain increased risks of breast and lung cancer. Although this study did not provide specific evidence of contribution of identified industrial facilities to elevated levels of breast cancer, it confirmed the role of point source pollution in explaining the spatial variability of lung cancer. Previously found clusters of breast cancer in the study area were determined based on proximity to soil dioxin contamination, without taking into account risk of cancer in relation to exposure from point source pollution . The newThe results of this study are useful to researchers and governmental agencies involved in regulation, control, and monitoring of environmental contamination within the floodplains of the Tittabawassee and Saginaw Rivers. Specifically, governmental agencies may consider control and monitoring of pollutants reported in releases of industrial facilities found to be associated with increased risk of lung cancer. Monitoring results could serve as the basis for the development of regulatory sanctions of pinpointed pollutants. These findings are also valuable for manufacturers to consider when conducting reassessment of production processes, in order to avoid or minimize releases of identified carcinogenic chemicals into the environment.


Dental caries (decay) during childhood is largely preventable however it remains a significant and costly public health concern, identified as the most prevalent chronic disease of childhood. Caries in children aged less than five years (early childhood caries) is a rapid and progressive disease that can be painful and debilitating, and significantly increases the likelihood of poor child growth, development and social outcomes. Early childhood caries may also result in a substantial social burden on families and significant costs to the public health system. A disproportionate burden of disease is also experienced by disadvantaged populations.This study involves the establishment of a birth cohort in disadvantaged communities in Victoria, Australia. Children will be followed for at least 18 months and the data gathered will explore longitudinal relationships and generate new evidence on the natural history of early childhood caries, the prevalence of the disease and relative contributions of risk and protective biological, environmental and behavioural factors. Specifically, the study aims to:1. Describe the natural history of early childhood caries , tracking pathways from early bacterial colonisation, through non-cavitated enamel white spot lesions to cavitated lesions extending into dentine.2. Enumerate oral bacterial species in the saliva of infants and their primary care giver.3. Identify the strength of concurrent associations between early childhood caries and putative risk and protective factors, including biological , environmental (fluoride exposure) and socio-behavioural factors .4. Quantify the longitudinal relationships between these factors and the development and progression of early childhood caries from age 1-18 months.There is currently a lack of research describing the natural history of early childhood caries in very young children, or exploring the interactions between risk and protective factors that extend to include contemporary measures of socio-behavioural factors. This study will generate knowledge about pathways, prevalence and preventive opportunities for early childhood caries, the most prevalent child health inequality. Dental caries (decay) during childhood is largely preventable however it remains a significant and costly public health concern, identified as the most prevalent chronic disease of childhood . Caries Knowledge regarding the prevalence of dental caries and its treatment in early childhood is currently limited in Australia, as in many countries , due comConsistent with the universal social gradient that exists across areas of general health and wellbeing, caries rates are higher among the more socially disadvantaged -12, partWhile much is known about the causes of dental caries in general, the development of caries in very early life is less well understood. Caries is a diet related, infectious and transmissible disease  of multiTo date, investigations of the development of ECC have almost exclusively focussed on either biological factors or socio-environmental factors, and studies that combine measurement of both areas are rare. While family and broader socio-environmental influences on oral health have become an increasing focus of attention ,22,23, lSpecifically this study aims to:1. Describe the natural history of ECC , tracking pathways from early bacterial colonisation, through non-cavitated enamel white spot lesions to cavitated lesions extending into dentine.2. Determine the oral bacterial species and their relative abundance in the saliva of infants and their primary care giver.3. Identify the strength of concurrent associations between ECC and putative risk and protective factors, including biological , environmental (fluoride exposure) and socio-behavioural factors .4. Quantify the longitudinal relationships between these factors and the development and progression of ECC from age 1-18 months.The specific hypotheses to be tested are:1. Higher levels of Mutans Streptococci (MS) in saliva, lower salivary buffering capacity and lower levels of salivary fluoride, calcium and phosphate are associated concurrently with higher rates of white spot lesions, cavitation (decayed), missing and filled teeth at ages 6, 12 and 18 months.2. After accounting for levels of child MS and salivary characteristics: Higher levels of maternal MS and lower infant exposure to fluoride (water or toothpaste) are associated concurrently with higher rates of white spot lesions, cavitation (decayed), missing and filled teeth at ages 6, 12 and 18 months.3. After accounting for levels of child MS and salivary characteristics: adverse parental health behaviours , lack of support for infant oral health  and adverse feeding practices  will be associated concurrently with higher rates of white spot lesions, cavitation (decayed), missing and filled teeth at ages 6, 12 and 18 months.4. Higher levels of child MS, lower salivary buffering capacity and lower levels of salivary fluoride, calcium and phosphate  will be associated prospectively with higher rates of white spot lesions, cavitation (decayed), missing and filled teeth at ages 6, 12 and 18 months.5. After accounting for concurrent biological and exposure factors: adverse parental health behaviours, lack of support for infant oral health and adverse feeding practices  will be associated prospectively with higher rates of white spot lesions, cavitation (decayed), missing and filled teeth at ages 6, 12 and 18 months.6. Finally, because socio-ecological risk factors typically operate in an interactive manner , after This research will employ a longitudinal, multi-disciplinary design to investigate the factors involved in the development of ECC within the socio-ecological model of health . Descriptive statistics will be produced for all cross sectional outcomes  and to examine distributional characteristics to inform scaling and choice of analytical techniques. Categorisation of the outcome will be considered based on clinical understanding of appropriate cut points. For exploratory analyses of relationships between ECC and biological, behavioural and environmental factors, we will employ a range of multivariable and multi-level models depending on the level of definition of ECC outcome. At the individual level, multiple linear regression and mixed models will be used for continuous outcomes; and multinomial logistic regression for categorised ECC outcomes. To examine the levels and rates of change in oral health status from ages 6 to18 months at surface level, multilevel random coefficient models and generalized estimating equations (GEEs) adjusting for clustering will be used. These techniques also permit inclusion of partial data from infants that are lost-to-follow-up.Ethics approval to conduct this study has been provided by the University of Melbourne Human Research Ethics Committee (HREC 0722543) and the Victorian Department of Education and Early Childhood Development. All participants will provide informed consent before baseline data is collected.To date, investigations of the development of early childhood caries have almost exclusively focussed on either biological factors or socio-environmental factors, and studies that combine measurement of both areas are rare. From a socio-ecological perspective, parent and child oral health behaviours occur within a cultural and economic context, the effects of which are mediated by individual capacities . Common The strengths of this study include the innovative application of a socio-ecological approach; collection of longitudinal data that will enable inferences to be made about causal pathways; and the focus on a high risk sample  for whom preventive intervention is a public health priority.CALD: Culturally and Linguistically Diverse; ECC: Early Childhood Caries; GEE: Generalised estimating equations; LSAC: Longitudinal Study of Australian Children; LGA: Local Government Area; MCH: Maternal and Child Health; MCHN: Maternal and Child Health Nurse; PCR: Polymerase chain reaction; SEIFA: Socioeconomic Index For Areas.The authors declare that they have no competing interests.EW conceived of the study, and all authors participated in its design and methodological development. AdS drafted the initial manuscript with assistance from all authors, who also read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/10/97/prepub


The emerging tick-borne zoonoses human monocytic ehrlichiosis (HME) and human granulocytic ehrlichiosis (HGE) are under reported in the United States. From 1986 through 1997, 1,223 cases  were reported by state health departments. HME was most commonly reported from southeastern and southcentral states, while HGE was most often reported from northeastern and upper midwestern states. The annual number of reported cases increased sharply, from 69 in 1994 to 364 in 1997, coincident with an increase in the number of states making these conditions notifiable. From 1986 through 1997, 827 probable and confirmed cases were diagnosed by serologic testing at the Centers for Disease Control and Prevention, although how many of these cases were also reported by states is not known. Improved national surveillance would provide a better assessment of the public health importance of ehrlichiosis.


An understanding of the health of potential volunteers in Africa is essential for the safe and efficient conduct of clinical trials, particularly for trials of preventive technologies such as vaccines that enroll healthy individuals. Clinical safety laboratory values used for screening, enrolment and follow-up of African clinical trial volunteers have largely been based on values derived from industrialized countries in Europe and North America. This report describes baseline morbidity during recruitment for a multi-center, African laboratory reference intervals study.Asymptomatic persons, aged 18–60 years, were invited to participate in a cross-sectional study at seven sites . Gender equivalency was by design. Individuals who were acutely ill, pregnant, menstruating, or had significant clinical findings were not enrolled. Each volunteer provided blood for hematology, immunology, and biochemistry parameters and urine for urinalysis. Enrolled volunteers were excluded if found to be positive for HIV, syphilis or Hepatitis B and C. Laboratory assays were conducted under Good Clinical Laboratory Practices (GCLP).Of the 2990 volunteers who were screened, 2387 (80%) were enrolled, and 2107 (71%) were included in the analysis . Major reasons for screening out volunteers included abnormal findings on physical examination , significant medical history  and inability to complete the informed consent process . Once enrolled, principle reasons for exclusion from analysis included detection of Hepatitis B surface antigen  and antibodies against Hepatitis C . This is the first large scale, multi-site study conducted to the standards of GCLP to describe African laboratory reference intervals applicable to potential volunteers in clinical trials. Approximately one-third of all potential volunteers screened were not eligible for analysis; the majority were excluded for medical reasons. Africa has the largest burden of HIV infection and AIDS worldwide In order to prepare a vaccine trial laboratory network following Good Clinical Laboratory Practices (GCLP) and to define a set of reference intervals suitable for future trial participants, the International AIDS Vaccine Initiative, the Medical Research Council in Uganda, the Rwanda-Zambia HIV Research Group, the Kenyan AIDS Vaccine Initiative and the Kenyan Medical Research Institute initiated a cross-sectional survey. The laboratory approach to this study was modeled on the Clinical and Laboratory Standards Institute (CLSI) guidelines for determining reference values and intervals for quantitative clinical laboratory tests This paper presents the recruitment, enrollment, and baseline morbidities of the 2,990 potential study volunteers.Clinically healthy adult (18–60 years) male and female volunteers were enrolled across seven sites in four countries in Eastern and Southern Africa . All potEligible volunteers were selected from a rural general population cohort enrolled into prospective HIV incidence studies in preparation for HIV vaccine trials.Volunteers for this study were drawn from community members who: 1) had expressed interest to participate in future clinical trials, or 2) were prescreened for a previous HIV vaccine phase 1 clinical trial and were not enrolled because the trial had completed enrollment.Half of this site's study volunteers were drawn from an HIV prevalence study in Kilifi Town, and half were selected from individuals who were enrolled in HIV incidence studies in preparation for HIV vaccine trials.Volunteers were drawn from an HIV prevalence study conducted in this peri-urban district of Nairobi in preparation for HIV incidence studies.The majority of volunteers from this site included medical students, staff and professionals from the KNH medical school and hospital facility. Community members not affiliated with the facility were also enrolled.Half of the volunteers from these two sites were drawn from large prospective studies of long-term, stable sexually active couples of HIV discordant status (the volunteer's partner was HIV positive), and half were drawn from couples identified during couples' VCT as concordant HIV-negative (both partners HIV uninfected).This study was approved by the Institutional Ethics Committees (EC) or Institutional Review Boards (IRB) at each participating institution, including Emory University; all institutions have an EC/IRB that is registered with the US Office of Human Research Protection.Interested potential volunteers were administered a brief screening questionnaire and symptom-directed examination prior to enrollment. Volunteers were screened out based on significant medical history including current clinical symptoms, immunosuppressive or corticosteroid medication, chemotherapy, hospitalizations, surgery or blood transfusions in the six months prior to screening. Volunteers with splenomegaly (Grade 2+ by Hackett's classification) were excluded. Menstruating women were asked to return in two weeks, and women who reported being pregnant were not enrolled. Breastfeeding was not an exclusion factor. No personal identifying information was collected from volunteers who were screened out prior to enrollment; only age, gender and reason for ineligibility.Following screening, written informed consent was obtained from all eligible volunteers. The consent process included an explanation and discussion of the study procedures, followed by an assessment of the potential volunteer's understanding of the study. Literacy was not a requirement to participate, and illiterate volunteers were consented with an independent third party present to confirm volunteer understanding of the consent process and study procedures. Only those volunteers who could demonstrate a satisfactory understanding following the consenting process were enrolled.After enrollment, a detailed medical history including reproductive history for women, data on contraception use, investigation of current medications and demographics  were collected from each enrolled volunteer. A physical examination was performed including evaluation of vital signs, weight and height. Blood was drawn for HIV, syphilis and Hepatitis C serology, Hepatitis B antigen, hematology (complete blood count), clinical chemistry , and CD4/CD8 T-cell count. The assays used are outlined in For comparative evaluation across centers, standardization of methods and equipment was deemed essential, and equipment was chosen that is easy to operate, suitable for lower-volume work and low-maintenance. For hematology measurements, all sites used the Beckman Coulter Act5 Diff analyzer . Biochemistry assays were performed on the VitaLab Selectra E . Both instruments had suppliers within the region to ensure regular service, maintenance and reagent supply. The two KAVI sites shared the same laboratory facilities at the KNH. Five laboratories used the FACSCount (BD Biosciences) due to its robust performance on the WHO/ NHLS CDREQAS program across African sites Staff received GCLP training as well as specific technical training on each analyzer depending on individual site requirements A central reference laboratory in Johannesburg, Republic of South Africa, assisted with the conduct of cross-validation studies which included the selection and shipment of proficiency panels of 60 samples from the reference centre to the sites for biochemistry, hematology and urinanalysis. Results were compared with the reference laboratory, across technicians, and across sites using the Bland-Altman Data were transcribed onto case report forms (CRF) scanned and emailed to a central server using DataFax . Quality assurance included on-site monitoring of source documents and CRFs, and automated checks of the electronic data. Data analyses were conducted using Stata  and SAS  software. Results are descriptive and include tabulations of screened and enrolled volunteers, and baseline study population characteristics. Appropriate statistical tests  are shown by their p-value.Screening and enrollment began in December 2004 and ended in October 2006. A total of 2990 individuals were screened across all sites, 1477 women (49.4%) and 1513 men (50.6%). Approximately 20% of screened volunteers were not enrolled with a further 10% excluded following enrollment . There wThe most common reasons for screen-outs prior to enrollment were splenomegaly , inability to demonstrate satisfactory comprehension during the informed consent process , hypertension , symptoms of upper respiratory infection  and menstruating women who did not return for re-screening . Some volunteers had more than one reason for exclusion. Most potential volunteers had been pre-screened for HIV; only 3 potential volunteers were found to be HIV infected at screening. Among enrolled volunteers, the prevalence of HBsAg was 4.4% (106/2387) and of Hepatitis C antibody was 4.0% (95/2387), with significant variations across sites . Dual HeAIDS vaccine trials in Africa have not typically employed local laboratory reference intervals for screening of potential volunteers and evaluation of adverse events during follow up . Several studies in the literature have suggested that individuals of African origin have different laboratory reference intervals for a few hematology parameters compared to Caucasians in industrialized countries. Africans have been described as having lower platelet counts Nearly one-third  of all persons screened for the current study were not eligible for analysis. Differences in the proportion of participants found ineligible both before and after screening were observed between gender, between countries, within country and between rural and urban areas . InfectiA goal of the study was to include equivalent numbers of men and women. More women were screened out, and more men were excluded from analysis, leaving a final cohort with a balanced gender makeup (48% women). The higher rate of female screen-outs was at least in part due to the 27 women who screened out due to reported pregnancy and the 44 who did not return when rescheduled due to menstruation at screening. Relatively few women (18) tested positive for pregnancy once enrolled, while the prevalence of Hepatitis B & C was significantly higher among enrolled men than women.The selection of study populations varied by site, and potential volunteers were frequently selected from participants of ongoing research, or individuals with a previous interest in participating in research studies. Therefore, the selection of volunteers for this study does not represent a random sample of the local residents. The exception to this is Masaka, where study volunteers were recruited from the general population after the entire adult population of three rural villages was informed of upcoming research activities. The MRC has been working in these communities for some time, and the many of the residents there have also participated in previous research activities Data were collected on rainy versus dry season, with some sites participated in a sub-study that included repeating laboratory tests in both the rainy and dry seasons. These data will be presented in a future report. It should be noted that the sites differ significantly in altitude above sea level, ranging from sea level to 1680 meters . This diSeveral laboratory implementation lessons were learned during the course of this study. To assure data were comparable across sites, significant training of staff in the principles of GCLP and laboratory management was conducted. Cross validation studies are essential prior to implementation of study testing to ensure that all sample processing and analytical procedures are conducted appropriately. Our work highlighted several problems of both a pre-analytical and analytical nature. We found that reagent supply and instrument maintenance were problematic at some sites and finding proper technical support and in country procurement sources could be difficult. To maximize cost-effectiveness and practicality in some cases, we allowed local product availability to dictate reagent use in some cases in lieu of universal standardization . EQA pro


Antiangiogenic Cancer Therapy have recognised the timeliness of such a book. This book provides a detailed and comprehensive overview of Antiangiogenic Cancer Therapy; past, present and future, making this book an important source for researchers and clinicians working in this area of cancer biology.One of the most widely pursued therapeutic strategies in cancer therapy has been to target the angiogenic process in tumour progression. Angiogenesis is the process by which a solid tumour develops its own blood supply by hijacking the surrounding vasculature to invade the growing tumour mass. Angiogenesis is essential for solid tumours to grow beyond the microscopic level and metastasise. Since the seminal discoveries made on angiogenesis by Judah Folkman over three decades ago, angiogenesis has been hotly pursued as a therapeutic target in cancer. Despite this, to date, there is no effective antiangiogenic agent that can be used as a single agent in the clinic. The editors of Antiangiogenic Cancer Therapy contains over 840 pages of text from 79 expert and authoritative international academic and industrial scientists and clinicians. The book is divided into four themed parts (I–IV), 1: angiogenesis and cancer, II: targeting angiogenesis for cancer therapy, III: translating angiogenesis inhibitors to the clinic and IV: treatment of specific cancers with angiogenesis inhibitors. Each part is subdivided into several chapters relevant to the theme and written by well-recognised experts on the topic of the chapter. The book spans 32 chapters. Each chapter is a comprehensive stand-alone review, including a detailed content section, an introductory discussion section, a conclusion/summary section and a comprehensive bibliography. This format allows the reader to access information in its entirety on a given topic and is aided by a very useful index at the back of the book. One minor drawback to this format is that there is some repetition, which is inevitable given the topics covered and the extensive nature of this book. The book benefits from a multitude of helpful summary tables, beautiful illustrations and drawings throughout and a section of colour figures in the centre of the book.Antiangiogenic Cancer Therapy contains five chapters and provides a detailed background to angiogenesis in cancer as a basis for the proceeding parts. Chapter 1 is an interesting first chapter that discusses strategies to prolong the non-angiogenic dormant state of human cancers. Dormant tumours are pre-angiogenic where cells exhibit balanced apoptosis and proliferation. Interestingly, this chapter looks at imaging of dormant tumours and discusses molecular mechanisms and biomarkers for the angiogenic switch, metastatic dormancy and induction of dormancy using antiangiogeneic therapies. Chapter 2 follows by reviewing vascular endothelial growth factor (VEGF): basic biology and clinical implications in extensive detail. This chapter provides a background to VEGF and VEGF receptor biology, and discusses the role of VEGF signalling in physiological angiogenesis and pathological conditions, such as cancer and intraocular neovascular syndromes. The third chapter discusses angiogenesis in solid tumours and contains several informative 3-dimensional illustrations and excellent images of tumour blood vessels. Chapter 4 covers the pathophysiological role of VEGF in haematological malignancies and follows on very nicely from the earlier chapter. The final chapter of part I, chapter 5, discusses the tumour microenvironment and angiogenesis and includes an informative section on cancer metastasis.Part I of Antiangiogenic Cancer Therapy introduces strategies involved in targeting angiogenesis for cancer therapy and spans 12 chapters. The second part starts with chapter 6, which provides a comprehensive review of tyrosine kinase inhibitors of angiogenesis and other multi-targeted agents, and is concluded by providing an informative perspective section. Chapter 7 deals with the development of antiangiogenic monoclonal antibodies for cancer therapy. This chapter provides a detailed background on antibody structure, discovery and engineering, describes the mechanism of action of antibody-based therapy and provides an informative section on the VEGF/VEGFR pathway and the effects of monoclonal VEGF antibody therapy (bevacizumab) in colorectal, lung, renal and breast cancer. Chapter 8 follows by focusing on FGF and the FGFR system in angiogenesis and includes both signal transduction inhibitors and dominant-negative signalling molecules. Chapter 9 covers the development of VEGF trap as a novel antiangiogenic therapy and discusses its promising preclinical evaluation in cancer models and potential use for vascular eye disease. There is some overlap in this chapter with some of the earlier chapters . Interestingly, this chapter concludes by discussing the next generation targets in angiogenesis including angiopoietins and DII4. Chapter 10 follows with a detailed look at proteinases and their inhibitors in angiogenesis. A comprehensive list of metalloproteinase (MMP) inhibitor agents in the clinic (phase I–III stages) and other small molecule inhibitors  is included. This chapter also provides a transparent overview of the disappointing performance of MMP inhibitors in clinical trials. Chapter 11 focuses on prostaglandins and COX-2 and their role in antiangiogenic therapy. A useful table is included with the outcomes for various combination treatments  with celecoxib (COX-2 inhibitor) in breast, lung, colon, pancreatic and oesophageal cancers. The role of COX-2 inhibitors in cancer treatment remains uncertain, and the chapter concludes with a helpful section on future directions for these agents. Chapter 12 discusses integrins, adhesion and coadhesion inhibitors in angiogenesis. This chapter includes a thorough background on the biology of the extracellular matrix (ECM) and the integrin family, and discusses the current status on targeting various types of integrins, for example, collagen-binding, laminin-binding, fibronectin-binding and the effects on angiogenesis. Chapter 13 provides an overview of conventional therapies with antiangiogenic activity. This chapter has some overlap with other chapters, but interestingly describes the PPAR family and inhibitors, effects of mTOR inhibitors, metronomic dosing in chemotherapy and discusses the need for combined treatment regimes when using antiangiogenic agents. Chapter 14 deals with vascular disrupting agents (VDAs) in preclinical and clinical (phase I/II) development either as single agents or in combination with radiotherapy and conventional drugs. This chapter also addresses gene therapy and ligand-based approaches to targeting the vasculature. An interesting chapter follows (chapter 15) on vascular and haematopoietic stem cells as targets for antiangiogenic therapy. Chapter 16 describes genetic strategies for targeting angiogenesis and discusses the utilisation of microarray techniques to identify downstream and upstream modulator/regulators of angiogenesis. There are several detailed sections on gene therapy-mediated delivery systems in this chapter and an excellent section on future considerations, recommendations and conclusions relating to this chapter's topic. Chapter 17 covers the identification of new targets using expression profiles with several sections including; a section on expression profiling methods, computational analysis of expression profiling data and validation of expression profiles. This chapter concludes very positively with a section on success stories in the field.Part II of Antiangiogenic Cancer Therapy provides an overview of translating angiogenesis inhibitors into the clinic, including translational and clinical trial design for effective treatment using angiogenesis inhibitors. Part III starts with chapter 18, which provides background to the Federal Drug Administration (FDA) oversight of clinical trials, and includes details on the requirement for demonstration of safety and efficacy, important oncology end points, and has an informative section on the use of targeted therapies versus conventional cytotoxics. Chapter 19 follows, and is an important chapter, which describes surrogate markers for antiangiogeneic cancer therapy and their rationale, including the use and identification of markers in serum, plasma, urine and tumour biopsies and ex vivo markers. This chapter compliments the next chapter, chapter 20, which provides a detailed overview of non-invasive surrogates, and includes sections on general imaging and types of measurements, indirect measurements of vascularity and blood flow, a discussion of blood flow measurements and indirect tests not measuring blood flow , and details on specific (direct) imaging and current developments. This chapter has an excellent conclusions and perspectives section at the end that includes key questions regarding the role of imaging in therapy. The theme of markers continues into chapter 21, which discusses pharmacodynamic (PD) markers in tissues, including direct and indirect PD analysis of angiogenesis inhibitors and multi-targeted agents. This chapter contains several informative tables that summarise PD markers in tumours and concludes with a section on challenges and perspectives. The final chapter of part III, chapter 22 discusses blood-based biomarkers for VEGF inhibitors, outlines the importance of identifying and analysing suitable biomarkers and describes various marker types, such as soluble markers, endothelial cell markers, cellular markers in peripheral blood and markers found within other cell populations. The chapter concludes with a helpful future directions section.Part III of Antiangiogenic Cancer Therapy provides several comprehensive chapters (23–32) on the treatment of specific cancers with angiogenic inhibitors. Each chapter reviews a different cancer type, including colorectal, rectal, breast, lung and prostate cancer, haematological malignancies, glioma, Kaposi's sarcoma and melanoma. The final chapter discusses the treatment of renal cell carcinoma (RCC) with sunitinib, which is regarded as the new reference standard for the first-line treatment for RCC. It is slightly disappointing that there is no overall conclusion section at the end of the book. Several key conclusions are reiterated in the final chapters of Antiangiogenic Cancer Therapy that are echoed throughout the book, (a) there are limitations to antiangiogenic therapy in many cancers, and currently, most antiangiogenic agents need to be used in combination with other agents and (b) there is an increasing need for valid markers of response, improved imaging and the development of non-invasive methods for detecting response.Part IV of Antiangiogenic Cancer Therapy is a comprehensive book that has detailed and expertly written chapters, useful tables and beautiful illustrations. The book is excellently edited. There is absolutely no doubt that Antiangiogenic Cancer Therapy is an important and timely contribution to the field that is applicable to scientists and clinicians alike.In summary,


Since the launch of Landsat-1 28 years ago, remotely sensed data have been used to map features on the earth's surface. An increasing number of health studies have used remotely sensed data for monitoring, surveillance, or risk mapping, particularly of vector-borne diseases. Nearly all studies used data from Landsat, the French Système Pour l'Observation de la Terre, and the National Oceanic and Atmospheric Administration's Advanced Very High Resolution Radiometer. New sensor systems are in orbit, or soon to be launched, whose data may prove useful for characterizing and monitoring the spatial and temporal patterns of infectious diseases. Increased computing power and spatial modeling capabilities of geographic information systems could extend the use of remote sensing beyond the research community into operational disease surveillance and control. This article illustrates how remotely sensed data have been used in health applications and assesses earth-observing satellites that could detect and map environmental variables related to the distribution of vector-borne and other diseases.


Tracheobronchopathia osteochondroplastica (TO) is a relativelyrare benign disease, around 300 and 130 cases have been reportedin English and Japanese literature, respectively. Most of thecases have been diagnosed incidentally at autopsy. Due to thewidespread use of fiberoptic bronchoscopy (FOB), the number ofcases diagnosed upon examination is increasing. Here, we report acase of a 72 year-old man with a history of crown aspiration, whowas diagnosed as TO upon removal of a foreign body using FOB. Thediagnosis of TO and the removal of an aspirated crown by FOB arediscussed.