Exhaled nitric oxide in pediatrics: what is new for practice purposes and clinical research in children?

Fractional exhaled NO (FeNO) is universally considered an indirect marker of eosinophilic airways inflammation, playing an important role in the physiopathology of childhood asthma. Advances in technology and standardization have allowed a wider use of FeNO in clinical practice in children from the age of four years. FeNO measurements add a new dimension to the traditional clinical tools (symptoms scores, lung function tests) in the assessment of asthma. To date a number of studies have suggested a possible use of FeNO in early identification of exacerbation risk and in inhaled corticosteroids titration. The aim of this paper is to address practical issues of interest to paediatric clinicians who are attempting to use FeNO measurements as an adjunctive tool in the diagnosis and management of childhood airway diseases.     

Links Between Exposure to Violence and HIV-Infection

Abstract

Among women, a history of exposure to violence is associated with both an increased likelihood of substance use and an increased risk of HIV-infection. Thus substance use and other behaviors which can affect the risk of HIV exposure are often influenced by the psychosocial sequelae of violent victimization. Because these issues are interrelated, mental health interventions focused on any one of these issues in isolation may be less effective than an integrated approach. The current paper reviews the extant literature on these topics and proposes that treatment of women substance users must address the relationships between psychological trauma and increased HIV-risk behaviors and that attention to substance abuse and psychological trauma are necessary foci of services to HIV-infected women.     

Impediments to safer heterosexual sex: a review of research with young people.

This article reviews the existing British literature on the micro-social details of young people's heterosexual encounters, emphasizing the cultural factors which impede the adoption of health education advice. Most of the findings cited come from qualitative projects that relied primarily on detailed interviews or group discussions. Six issues are highlighted: difficulties in talking about sex; the gender-role expectations brought to an encounter; the primary function of condoms as contraceptives; problems in buying, carrying and using condoms; how the stage of a particular relationship affects behaviour, and gendered power relations. Several important issues are not addressed in the existing literature. The survey data on sexual behaviour suggest that HIV has had little impact on sexual activity, apart from a reported increase in condom use. Qualitative studies reveal the moral categories, gender-role expectations, power inbalances and other cultural factors that prevent a high level of knowledge about HIV transmission from being translated into safer heterosexual behaviour. Their findings provide important insights into how realistic and practical safer sex messages are. They suggest that to promote health in respect to HIV it is necessary not only to advocate specific precautionary behaviour, such as using condoms, but also to address wider cultural issues relating to the taboos around the discussion of sex and the empowerment of women.     

Coronary computed tomography angiography and its increasing application in day to day cardiology practice

Coronary artery disease (CAD) is the leading single cause of death in Australia affecting around 1.4 million people. Coronary computed tomography angiography has an established role in the assessment of patients with low to intermediate pretest probability for CAD who have chest pain and is typically used with the aim to rule out significant coronary artery stenosis. Use was initially limited because of concerns over radiation exposure, a Medicare rebate restricted to specialist referrals and an absence of data supporting its use as an alternative to functional testing in patients with chest pain. Recent advances in scanner technology and image sequencing, along with data from randomised control trials, have addressed these issues and indicate that coronary computed tomography angiography will play a greater role in the assessment of CAD in the coming years.     

Intraoperative endoscopy: An important skill for general surgeons

Flexible endoscopy represents an important set of skills for general surgeons. The intraoperative use of endoscopy, during the course of surgical procedures performed on the gastrointestinal tract, is vital to surgical practice. Endoscopic confirmation of pathology prior to beginning surgery, intraoperative anastomotic evaluation and margin assessment, and combined laparoscopic–endoscopic approaches are just a few examples that emphasize the value added when surgeons perform gastrointestinal endoscopy as a routine adjunct to foregut, bariatric, and colorectal surgical procedures. Intraoperative endoscopy improves surgical outcomes by providing useful clinical information important to decision-making, allowing surgeons to address technical issues, preventing them from manifesting as post-operative complications.     

Immunology and immunotherapy of colorectal cancer

This review critically discusses data on immunology of colorectal cancer, starting from pathology and molecular biology, and then considering the molecular characterisation of colon cancer antigens and the clinical trials of immunotherapy. A careful evaluation of histopathological studies on intra-epithelial infiltration by T cells in primary tumours, together with the analysis of HLA expression by colorectal cancer cells, suggest that anti-tumour T cell immune responses may take place in vivo in those patients, influencing prognosis and shaping the tumour immunological profile. Moreover, the molecular characterisation of tumour antigens expressed by colorectal carcinomas, together with improved understanding of mechanisms of the immune response and more sensitive methods for the in vivo detection of T cell responses, are now allowing researchers to design new and more effective vaccination protocols, with encouraging preliminary results. By drawing together the experimental evidence from different research fields, this review provides support for the concept that colorectal carcinoma is immunogenic and may reasonably be considered as a target for immunotherapy, and attempts to address critical issues and envisage future developments in this challenging research field.     

CLIENT PARTICIPATION AND ADVOCACY IN GERIATRIC ASSESSMENT

This paper is an attempt to put into practical perspective the current general discussions on “user rights”, and to address some of the issues raised in relation to the provision of services for elderly people, with particular reference to the role of Regional Geriatric Assessment Teams (RGATs). Policies and practices relating to six areas identified by the Commonwealth Department of Community Services and Health as providing a framework for “user rights” initiatives are presented from the experiences of three Melbourne assessment teams, illustrating the ways in which assessment services have addressed these issues and resolved potential conflicts of interest.     

Use of quantitative microbial risk assessment for evaluation of the benefits of laundry sanitation

The goal of this study was to evaluate the risk assessment process for quantifying the contribution of contamination in the home to microbial infections. Whereas risks of enteric pathogens spread through food has been assessed, the spread of fecal-oral pathogens through surfaces likely at low rates would be difficult to address through epidemiologic studies. An alternative is quantitative risk assessment. The 4-step process of hazard identification, dose-response, exposure assessment, and risk characterization can be used; however, exposure assessment may follow a complicated pathway consisting of survival and transference. Microbial hazards in the home have focused primarily on enteric bacteria. Dose-response data are available; however, the transfer from the hands to the dose is uncertain. Through day care studies, Shigella has been shown to be transferred in this manner, and a dose-response model is available. By using these data and information on the transference of bacteria between clothing and hands, risk estimates were made for contaminated laundry. Risks were calculated as high as 10 per million population to much lower levels associated with lower excretion rates of the bacteria in the feces. Approximately a 90% and 99% reduction in the probability of disease through laundering and use of a sanitizing detergent, respectively, were suggested by the models. Better data are needed on incidence of disease in the population, excretion rates over the course of an infection, amount of feces spread in the home, distribution of bacteria, survival, and the transfer of the bacteria from surfaces to the hands and to the mouth.     

A patient satisfaction survey for haemophilia treatment centres

The importance of patient satisfaction has continued to grow such that patient satisfaction is now viewed as a vital component of health-care delivery. This is evidenced by the expanding body of research in the area and the use of measures of patient satisfaction as indicators of health-care quality. The value of patient satisfaction is particularly apparent in the setting of chronic disease where medical care utilization is high, compliance with therapy is critical and the patient-provider relationship is often long-term. Although several validated tools exist to quantify general measures of patient satisfaction, there is a recognized need for disease-specific instruments. Not only are there issues that are unique to haemophilia, but many patients receive care via a specialized comprehensive clinic model. The authors were unaware of an instrument that could adequately address patient satisfaction issues specific to haemophilia; thus, they undertook to develop one. The patient satisfaction survey presented here contains fixed-choice, Likert-scale and open-ended questions adapted from previously validated questionnaires. Assessment of face validity and internal consistency indicate that the survey is measuring one underlying construct - patient satisfaction. Information acquired through this survey will provide a quantitative assessment of patient satisfaction within a clinic population of persons with bleeding disorders and could be used to guide decisions regarding provision of health-care services.     

Carcinogenicity of ambient air pollution: use of biomarkers,lessons learnt and future directions

The association between ambient air pollution (AAP) exposure and lung cancer risk has been investigated in prospective studies and the results are generally consistent, indicating that long-term exposure to air pollution can cause lung cancer. Biomarkers can enhance research on the health effects of air pollution by improving exposure assessment, increasing the understanding of mechanisms, and enabling the investigation of individual susceptibility. In this review, we assess DNA adducts as biomarkers of exposure to AAP and early biological effect, and DNA methylation as biomarker of early biological change and discuss critical issues arising from their incorporation in AAP health impact evaluations, such as confounding, individual susceptibilities, timing, intensity and duration of exposure, and investigated tissue. DNA adducts and DNA methylation are treated as paradigms. However, the lessons, learned from their use in the examination of AAP carcinogenicity, can be applied to investigations of other biomarkers involved in AAP carcinogenicity.     

Washington State hospital survey 2000: Gloves, handwashing agents, and moisturizers

Hand dermatitis as a result of frequent exposure to water and cleansing agents is a significant problem in the health care industry. In developing prevention efforts to address this problem, it is necessary to make appropriate recommendations for moisturizers that are compatible with latex gloves and/or handwashing agents that contain chlorhexidine gluconate (CHG). Infection control personnel or employee health nurses in all 106 Washington hospitals were interviewed to determine what types of gloves, handwashing agents, and moisturizers are in current use in the hospital setting. The interview also addressed awareness of skin care issues involving the compatibility of moisturizers with latex gloves and handwashing agents that contain CHG. Latex gloves were available in 90% of the hospitals. Handwashing agents containing CHG were available in 33% of the hospitals. Moisturizers were supplied for the nursing personnel in 61% of the hospitals; most of these moisturizers were compatible with latex gloves and agents containing CHG. Seventy-four percent of the infection control personnel were aware of the compatibility issues of petroleum-based moisturizers with latex gloves, and 48% were aware of the need to avoid the use of anionic moisturizers in combination with CHG handwashing agents.     

Animal models for assessment of GMO allergenicity: advantages and limitations

Incidence of IgE-mediated allergic reactions to foods is increasing as well as the severity of associated symptoms and numerous foods are now incriminated, probably in relation with modifications of dietary habits and increased exposure to new or modified food ingredients. Therefore, the introduction on the market of food composed of or derived from genetically modified organisms (GMOs) raised the question of their potential allergenicity. Particularly with regards to the allergenicity of a newly expressed protein, it is necessary to obtain, from several steps in the risk assessment process, a cumulative body of evidence which minimises any uncertainty. This may include the use of animal model despite no fully reliable validated model is available yet. Such animal models should allow to address 3 major issues: Is the novel protein a sensitizer, i.e. does it possess intrinsic properties that allow to sensitize a predisposed individual? Is the protein an elicitor i.e. is it able to elicit an allergic reaction in a sensitised individual? And is the protein an adjuvant, i.e. can it facilitate or enhance the sensitisation to an other protein? Animal models under investigation currently include mice, rats and guinea pigs but models such as dogs and swine also appeared a few years ago. The aim is to mimic the mechanism and characteristics of the sensitisation phase and/or the elicitation phase of the allergic reaction as it occurs in atopic humans. They are necessary because sensitisation studies can obviously not be done in human and because in vitro tests cannot reproduce the complexity of the immune system. We propose a mouse model which mimics both phases of the allergic reaction. It has permitted to evidence that biochemical and clinical manifestations occuring during the active phases of the allergic reaction differ according to the structure of the allergen used for the challenge. This may allow to compare the allergenic potential of a genetically modified protein with that of the conventional one and to identify possible unintended effects. However, pathogenesis of food allergy in human is very complex and multifactorial, including individual differences in susceptibility, environmental factors, conditions of exposure, ... No animal model can take into account all these factors and allow a reliable prediction of the prevalence and severity of allergic reactions which would result from the exposure to a (novel) protein. Nevertheless, point by point analysis using the different models available may provide useful informations on the potential allergenicity of a novel protein.     

The Lab Without Walls: A Deployable Approach to Tropical Infectious Diseases

The Laboratory Without Walls is a modular field application of molecular biology that provides clinical laboratory support in resource-limited, remote locations. The current repertoire arose from early attempts to deliver clinical pathology and public health investigative services in remote parts of tropical Australia, to address the shortcomings of conventional methods when faced with emerging infectious diseases. Advances in equipment platforms and reagent chemistry have enabling rapid progress, but also ensure the Laboratory Without Walls is subject to continual improvement. Although new molecular biology methods may lead to more easily deployable clinical laboratory capability, logistic and technical governance issues continue to act as important constraints on wider implementation.     

A practical approach to familial and hereditary colorectal cancer.

Recent genetic research has isolated the primary genetic defect underlying many of the hereditary colorectal cancer syndromes. Obtaining a detailed family history is the first step in identifying individuals at increased risk of developing colorectal cancer. Once identified, individuals and their families may benefit from earlier, more intensified surveillance, prophylactic surgery, cancer risk assessment and education, and genetic testing. Clinicians, especially those with many patients with colorectal cancer in their practice, must be able to address the complex issues associated with the familial and hereditary colorectal cancer syndromes. A well-integrated partnership among colorectal surgeons, gastroenterologists, oncologists, and medical geneticists is necessary to address these complex issues and provide comprehensive medical care.     

“Is medical cannabis safe for my patients?” A practical review of cannabis safety considerations

Medical cannabis use is increasing worldwide. Clinicians are commonly asked by patients to provide guidance on its safety and efficacy. Although there has been an increase in research on the role of medical cannabis for a number of different conditions, we found that there was a paucity of clear safety guidance on its use. We aim to address this issue by answering two pertinent clinician safety questions:1 Can medical cannabis be safely used in this patient?2. What strategies can be used to ensure that any harms from medical cannabis are mitigated?To address these questions, we reviewed available evidence and provided expert clinical opinion to summarize the fundamental components for evaluating medical cannabis safety and strategies to reduce risk from its use. Our review resulted in a safety-focused framework for medical cannabis initiation and utilization. We provide clear recommendations for patients being considered for cannabis (e.g. precautions, contraindications and drug interactions). Risk mitigation strategies such as appropriate chemovar (strain) selection, routes of administration, and dosing are reviewed. As with any other pharmacotherapy, we review the key components of monitoring and address potential issues that may arise while using medical cannabis. We propose a structured assessment and monitoring strategy that can be used by clinicians recommending cannabis (CRC) to guide patients through each step of their cannabis journey. This framework can be used to ensure that medical cannabis utilization is associated with the lowest possible risk to the patient.     

Allocation of case management resources in long-term care: predicting high use of case management time

The expansion of publicly funded home care services and case management (CM) programs has fueled concerns about containing the costs of these programs. For CM practice, the issue is one of tailoring CM to those who really need it and are most likely to benefit from it. This concern calls for a better understanding of factors that increase the need for CM resources, defined as the use of CM time. This study of 242 clients in a Medicaid-waiver-funded home care program found clients' problem behaviors, higher functional ability, informal support problems, and problems with service provider agencies to be predictive of greater use of CM time. These findings suggest the need to develop appropriate assessment of problem areas, implement effective protocols to manage specific problems, and address such issues as appropriate levels of staffing and provider accountability.     

An Outcomes Evaluation of Computerized Treatment for Problem Drinking using Breaking Free Online

Online alcohol screening interventions have been developed to address the significant public health and economic costs of alcohol consumption. However, none of these allow access to an extended range of intervention techniques. Therefore, a new online intervention has been developed, Breaking Free Online (BFO), that allows access to a wider range of intervention techniques. This study was an outcomes evaluation examining effectiveness of BFO with 300 service users seeking support for alcohol misuse. Participants completed an online assessment of alcohol consumption and dependence, depression, anxiety and quality of life, and then completed the same assessment following a period of engagement with BFO. Significant reductions were seen in alcohol consumption and dependence, depression and anxiety, and a significant increase in quality of life. This initial outcomes data indicates that BFO delivered as an E-BI may be an effective and cost-effective intervention for treatment of alcohol misuse.     

Role of microRNAs in doxorubicin-induced cardiotoxicity: an overview of preclinical models and cancer patients

Cardiotoxicity is a well-known side effect of doxorubicin (DOX), but the mechanisms leading to this phenomenon are still not completely clear. Prediction of drug-induced dysfunction onset is difficult and is still largely based on detection of cardiac troponin (cTn), a circulating marker of heart damage. In the last years, several investigations focused on the possible involvement of microRNAs (miRNAs) in DOX-induced toxicity in vitro, with contrasting results. Recently, several groups employed animal models to mimic patient’s condition, investigate the biological pathways perturbed by DOX, and identify diagnostic markers of cardiotoxicity. We reviewed the results from several studies investigating cardiac miRNAs expression in rodent models of DOX-treatment. We also discussed the data from two publications indicating the possible use of circulating miRNA as biomarkers of DOX-induced cardiotoxicity. Unfortunately, limited information was derived from these studies, as selection methods of candidate-miRNAs and heterogeneity in cardiotoxicity assessment greatly hampered the novelty and robustness of the findings. Nevertheless, at least one circulating miRNA, miR-1, showed a good potential as early biomarker of drug-mediated cardiac dysfunction onset. The use of animal models to investigate DOX-induced cardiotoxicity surely helps narrowing the gap between basic research and clinical practice. Despite this, several issues, including selection of relevant miRNAs and less-than-optimal assessment of cardiotoxicity, greatly limited the results obtained so far. Nonetheless, the association of patients-based studies with the use of preclinical models may be the key to address the many unanswered questions regarding the pathophysiology and early detection of cardiotoxicity.