Testing Of Treatment Strategies Research Articles

Pre-infection of pigs with Mycoplasma hyopneumoniae modifies outcomes of infection with European swine influenza virus of H1N1, but not H1N2, subtype

Swine influenza virus (SIV) and Mycoplasma hyopneumoniae (Mhp) are widespread in farms and are major pathogens involved in the porcine respiratory disease complex (PRDC). The aim of this experiment was to compare the pathogenicity of European avian-like swine H1N1 and European human-like reassortant swine H1N2 viruses in naïve pigs and in pigs previously infected with Mhp. Six groups of SPF pigs were inoculated intra-tracheally with either Mhp, or H1N1, or H1N2 or Mhp+H1N1 or Mhp+H1N2, both pathogens being inoculated at 21 days intervals in these two last groups. A mock-infected group was included. Although both SIV strains induced clinical signs when singly inoculated, results indicated that the H1N2 SIV was more pathogenic than the H1N1 virus, with an earlier shedding and a greater spread in lungs. Initial infection with Mhp before SIV inoculation increased flu clinical signs and pathogenesis (hyperthermia, loss of appetite, pneumonia lesions) due to the H1N1 virus but did not modify significantly outcomes of H1N2 infection. Thus, Mhp and SIV H1N1 appeared to act synergistically, whereas Mhp and SIV H1N2 would compete, as H1N2 infection led to the elimination of Mhp in lung diaphragmatic lobes. In conclusion, SIV would be a risk factor for the severity of respiratory disorders when associated with Mhp, depending on the viral subtype involved. This experimental model of coinfection with Mhp and avian-like swine H1N1 is a relevant tool for studying the pathogenesis of SIV-associated PRDC and testing intervention strategies for the control of the disease.

Lessons to Learn from Crohn's Disease Clinical Trials: Implications for Ulcerative Colitis

The perception that Crohn's disease is a more severe process than ulcerative colitis, led to the initial development of a majority drugs, and testing of treatment strategies, in the former. In the absence of similar studies in ulcerative colitis, information of Crohn's disease studies may help the clinician in decision making in UC. Studies on aminosalicylates show that drugs with a topical effect which are not effective in Crohn's disease may still have efficacy in ulcerative colitis, and this should be considered in future drug development. The best efficacy of corticorteroids is achieved with high doses of 1 mg/kg/day, and reaching remission may be delayed by several weeks, although non-response in the initial days should lead to treatment escalation, in particular in severe patients. Thiopurines have a steroid-sparing effect, and the duration of treatment should be at least 4 years; caution should be exerted in using these drugs in EBV negative young patients and in the older population for the risk of lymphoma. Anti-TNF monoclonal antibody therapy is optimized by use of induction followed by scheduled maintenance as opposed to episodic treatment, resulting in higher sustained response rates and lower immunogenicity. Associations of non-biological immunosuppressants with anti-TNF antibodies can further increase therapeutic efficacy maintaining a safe profile. Patients under combined therapy with sustained clinical and biological remission and mucosal healing may be candidates to stop anti-TNF treatment. The majority of these recommendations need to be specifically studied in patients with ulcerative colitis before generalization in clinical practice.

A Five-Step Guide for Moving from Observational Studies to Interventional Research for Women Veterans

A Five-Step Guide for Moving from Observational Studies to Interventional Research for Women Veterans

A Scoping Review of Self-Management Interventions for Adults With Multiple Sclerosis

The purpose of this scoping review is to identify self-management tasks and skills that are being taught in existing interventions for persons with multiple sclerosis and to describe intervention strategies used to facilitate the learning of self-management tasks and skills. Multiple strategies were used to search for studies published or in press between 1980 and 2008 that evaluated self-management interventions. The main exclusion criteria were case studies, inadequate description of the intervention, and traditional clinical patient education interventions. Two independent coders categorized the interventions by using Lorig and Holman's self-management framework and Abraham and Michie's taxonomy of behavior change techniques. Twenty-seven interventions were identified from 34 articles. Common intervention topics included fatigue management (n = 12), coping, depression, and stress management (n = 10), and medication management (n = 6). Also, no 2 interventions used the same delivery format to implement the same combination of intervention strategies. Furthermore, markedly different intervention strategies were used to improve the same outcomes. These results highlight a need to systematically test intervention strategies one at a time, or in a clear specified combination, as well as compare existing interventions to determine which are most effective in supporting persons with multiple sclerosis to learn and incorporate self-management tasks and skills.

An economic evaluation of alternative test-intervention strategies to prevent fetal growth restriction in singleton pregnancies

AimTo investigate the potential cost-effectiveness of alternative ‘test and treat’ strategies in the prevention of fetal growth restriction compared to a strategy of no screening in the UK.MethodsEconomic evaluation using...

Simplifying mathematical modelling to test intervention strategies for Chlamydia

In recent years, there has been a rise in applications of mathematical modelling in sexually transmitted infections. This paper outlines a new approach to ma-thematical modelling that tests intervention efforts on Chlamydia. The aim was to produce a simple model that can be used when new data comes to hand without the need to re-run the simulation. A simple model was developed to study the effects of interventions in lowering rates of Chlamydia in a high-risk population of 16 to 24 year olds. Parameters are informed by the best available data. The model was verified by running it backwards in time to see if it correctly ‘retrodicts’ rates ofChlamydia in the past. The model predicted that Chlamydia would disappear long-term if there were 45% condom use, annual check-ups and 23.5% successful contact tracing among the high-risk 16 – 24 year old age group. The model’s expressions can be applied readily to different populations of interest and to address specific questions, indicating that the model is a quick and easy tool to apply in public health policy making. Key words: Mathematical modelling, Chlamydia, public health interventions, partner notification, annual check-up, condom use.

International survey of vestibular rehabilitation therapists by the Barany Society Ad Hoc Committee on Vestibular Rehabilitation Therapy

The goal of this study was to determine how occupational and physical therapists learn about vestibular rehabilitation therapy, their educational backgrounds, referral patterns, and their ideas about entry-level and advanced continuing education in vestibular rehabilitation therapy. The Barany Society Ad Hoc Committee for Vestibular Rehabilitation Therapy invited therapists around the world to complete an E-mail survey. Participants were either known to committee members or other Barany Society members, known to other participants, identified from their self-listings on the Internet, or volunteered after reading notices published in publications read by therapists. Responses were received from 133 therapists in 19 countries. They had a range of educational backgrounds, practice settings, and referral patterns. Few respondents had had any training about vestibular rehabilitation during their professional entry-level education. Most respondents learned about vestibular rehabilitation from continuing education courses, interactions with their colleagues, and reading. All of them endorsed the concept of developing standards and educating therapists about vestibular anatomy and physiology, vestibular diagnostic testing, vestibular disorders and current intervention strategies. Therefore, the Committee recommends the development of international standards for education and practice in vestibular rehabilitation therapy.

Are we there yet? The state of the evidence base for guidelines on breaking bad news to cancer patients

The way clinicians break bad news to cancer patients has been retrospectively associated with poor psychosocial outcomes for patients. Education and practice in breaking bad news may be ineffective for improving patients’ well-being unless it is informed by a sound evidence base. In the health field, research efforts are expected to advance evidence over time to inform evidence-based practice. Key characteristics of an advancing evidence base are a predominance of new data, and rigorous intervention studies which prospectively demonstrate improved outcomes. This review aimed to examine the progress of the evidence base in breaking bad news to cancer patients. Manual and computer-based searches (Medline and PsycINFO) were performed to identify publications on the topic of breaking bad news to cancer patients published between January 1995 and March 2009. Relevant publications were coded in terms of whether they provided new data, examined psychosocial outcomes for patients or tested intervention strategies and whether intervention studies met criteria for design rigour. Of the 245 relevant publications, 55.5% provided new data and 16.7% were intervention studies. Much of the intervention effort was directed towards improving provider skills rather than patient outcomes (9.8% of studies). Less than 2% of publications were rigorous intervention studies which addressed psychosocial outcomes for patients. Rigorous intervention studies which evaluate strategies for improving psychosocial outcomes in relation to breaking bad news to cancer patients are needed. Current practice and training regarding breaking bad news cannot be regarded as evidence-based until further research is completed.

Sources of Extracellular, Oxidatively-Modified DNA Lesions: Implications for Their Measurement in Urine

There is a robust mechanistic basis for the role of oxidation damage to DNA in the aetiology of various major diseases (cardiovascular, neurodegenerative, cancer). Robust, validated biomarkers are needed to measure oxidative damage in the context of molecular epidemiology, to clarify risks associated with oxidative stress, to improve our understanding of its role in health and disease and to test intervention strategies to ameliorate it. Of the urinary biomarkers for DNA oxidation, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is the most studied. However, there are a number of factors which hamper our complete understanding of what meausrement of this lesion in urine actually represents. DNA repair is thought to be a major contributor to urinary 8-oxodG levels, although the precise pathway(s) has not been proven, plus possible contribution from cell turnover and diet are possible confounders. Most recently, evidence has arisen which suggests that nucleotide salvage of 8-oxodG and 8-oxoGua can contribute substantially to 8-oxoG levels in DNA and RNA, at least in rapidly dividing cells. This new observation may add an further confounder to the conclusion that 8-oxoGua or 8-oxodG, and its nucleobase equivalent 8-oxoguanine, concentrations in urine are simply a consequence of DNA repair. Further studies are required to define the relative contributions of metabolism, disease and diet to oxidised nucleic acids and their metabolites in urine in order to develop urinalyis as a better tool for understanding human disease.

Cost, Effectiveness, and Cost-Effectiveness

Pluck the goose so as to obtain the most feathers with the least hissing . — —Jean-Baptiste Colbert, Minister of Finance to King Louis XIV of France Incremental or marginal cost-effectiveness ratios are founded on a number of assumptions that weaken their suitability as a way to balance competing economic and clinical priorities. We therefore propose a more relevant and responsible way to gauge the impact of clinical management strategies based on “consumer protection” principles—explicit disclosure of (1) the total magnitude of expected benefit in the target population (in life-years or quality-adjusted life-years), (2) the total monetary cost (in per capita inflation-adjusted dollars), and (3) a formal plan by which the added costs would be paid. Health policy decisions should therefore be based on the inherent trade-offs in the component measures of cost and effectiveness and not on a simple ratio of the two. Cost-effectiveness ratios are thereby rendered superfluous. Incremental or marginal cost-effectiveness ratios are widely viewed as rational ways to balance competing clinical and economic priorities that arise as a consequence of the inevitable disconnect between an individual’s wants and the society’s willingness to pay for those wants.1–5 The purpose of this essay is to question the practical relevance of these ratios with respect to strategic planning in health care, and offer a suitable alternative. In doing so, we will focus on the more pragmatic issues underlying cost-effectiveness analysis, and gloss over a variety of technical details such as the difference between a privately financed free market and the publicly financed healthcare market, between costs and charges, and between unadjusted and quality-adjusted outcomes. Our pragmatic perspective is not likely to be welcomed by orthodox experts in cost-effectiveness analysis. We believe, however, that any such criticisms can be blunted by recognizing the important distinctions between regulatory and clinical …

Evidence to Support Aggressive Management of High-Density Lipoprotein Cholesterol: Implications of Recent Imaging Trials

High-density lipoprotein (HDL) is a "regression particle" based on its unique lipid particle biology. This unique property predicts that, in theory, therapies that raise HDL cholesterol should be able to induce regression of atherosclerosis. Presently, the principle pharmacotherapy for increasing HDL cholesterol is niacin. Niacin has been shown to regress atherosclerosis when used as monotherapy, in combination with a statin, and in combination with nonstatin therapies (including cholesterol-binding resins) and fibrates. Insights into the atherosclerosis benefits of combination lipid-lowering therapy with niacin have come from imaging studies utilizing quantitative coronary angiography, carotid ultrasound, and intravascular ultrasound showing modest inverse correlations between the extent of HDL increase and atherosclerosis regression. Recent adverse atherosclerosis and clinical effects seen with cholesterol ester transfer protein inhibition indicate that HDL-raising effects alone are insufficient to predict clinical benefit of new HDL therapies. Thus, although clinical trial evidence is necessary to understand the full scope of the safety and efficacy profile of novel HDL therapeutics, atherosclerosis imaging will be an important component of preclinical testing of these agents as they emerge and in head-to-head testing of treatment strategies.

Gangliosides as targets for autoimmune injury to the nervous system

Immune responses directed towards gangliosides and their microbial mimics are important mediators of several subtypes of acute post-infectious autoimmune neuropathy, collectively referred to as the Guillain-Barré syndromes. In this diverse group of paralytic syndromes, the immunopathology is in a proportion of cases characterised by anti-ganglioside antibody deposits, accompanied by inflammatory destruction of both axonal and glial components within the PNS. By gaining an understanding of the immunological mechanisms underlying these pathological pathways, it should be possible to select the correct targets for therapeutic intervention. Recent years has seen particular progress in our understanding of the basis for, and immunological consequences of molecular mimicry between gangliosides and microbial glycans, the relationships between ganglioside antibody specificity and different clinical phenotypes of GBS, the pathological basis for antibody-mediated nerve injury and the testing of intervention strategies in pre-clinical models. The focus of this mini-review is to provide a brief background to this field, summarise a selection of recent highlights focused on our own research, identify areas of outstanding knowledge and present data that supports novel therapeutic approaches based on the latest experimental findings.

The Things to Come of SHAPE: Cost and Effectiveness of Cardiovascular Prevention

It has been proposed recently that asymptomatic adults undergo routine screening for subclinical atherosclerosis using electron-beam computed tomography or carotid ultrasound as the basis for the pharmacologic prevention of cardiovascular events. The expected cost and effectiveness of this conditional test-treatment strategy are herein analyzed in comparison with the conventional conditional strategy, based on Framingham risk factor assessment, and with an unconditional treatment strategy that does not rely on testing. These analyses show that the unconditional treatment strategy, albeit more costly, is more effective and more cost-effective than either conditional testing strategy. In conclusion, greater attention should be paid to improving the population-wide delivery of and long-term adherence to proven preventive therapy than to the identification of "high-risk" treatment targets.

ISBNPA 2007: Marketing, serious games and nanny states. Observations from the sixth annual meeting of the International Society of Behavioral Nutrition and Physical Activity, Oslo 2007

This commentary paper provides a selective overview of topics addressed at the sixth annual meeting of the International Society of Behavioral Nutrition and Physical Activity (ISBNPA). With 31 symposiums, 42 free paper sessions and 236 poster presentations ISBNPA 2007 provided a comprehensive overview of the state of the art and of new avenues for behavioral nutrition and physical activity research. Research presented at the conference helps to identify and specify important nutrition and physical activity behaviors for health promotion, as well as the correlates, predictors and determinants of these behaviors, and to build and test intervention strategies that go beyond traditional health education. ISBNPA 2007 also indicates that ISBNPA should strive to become more international by inclusion of more scientists from countries outside North America, Western Europe and Australia. ISBNPA should maintain its encouragement of research that is firmly rooted in behavioral theory and research that goes beyond applying cross-sectional research designs, and that addresses the most important public health issues associated with behavioral nutrition and physical activity.

Interventions for Residents with Dementia and Their Family and Staff Caregivers: Evaluating the Effectiveness of Measures of Outcomes in Long-Term Care

This article describes six instruments developed for programs of research testing nursing interventions for individuals with dementia in Special Care Units and their family and staff caregivers. The Functional Abilities Checklist measures the functional abilities of residents with dementia. The Family Perceptions of Care Tool assesses family member satisfaction with care of the institutionalized relative with dementia. The Family Perceptions of Caregiving Role instrument evaluates stress experienced by family members of individuals with dementia related to their caregiving roles in long-term care settings. The Caregiver Stress Inventory and Staff Perceptions of Caregiving Role tools measure staff stress related to caring for residents with dementia. Finally, the Attitudes About Families Checklist assesses general staff attitudes about families of residents with dementia. Each instrument and its psychometric properties are described. The advantages of these instruments for research and clinical use with individuals with dementia are discussed.

Experimental Reproduction of Postweaning Multisystemic Wasting Syndrome in Pigs by Dual Infection with Mycoplasma hyopneumoniae and Porcine Circovirus Type 2

The objectives of this study were to investigate the interactions between Mycoplasma hyopneumoniae and porcine circovirus type 2 (PCV2) and to establish a model for studying the pathogenesis of and testing intervention strategies for the control of PCV2-associated porcine respiratory disease complex (PRDC). Sixty-seven pigs were randomly assigned to four groups. Group 1 (n=17) pigs served as controls, group 2 (n=17) pigs were inoculated with M. hyopneumoniae, group 3 (n=17) pigs were dual infected with M. hyopneumoniae and PCV2, and group 4 (n=16) pigs were inoculated with PCV2. Pigs were inoculated intratracheally with M. hyopneumoniae at 4 weeks of age followed by intranasal inoculation with PCV2 at 6 weeks of age. Dual-infected pigs had moderate dyspnea, lethargy, and reduced weight gain. The overall severity of macroscopic lung lesions, PCV2-associated microscopic lesions in lung and lymphoid tissues, and the amount of PCV2-antigen associated with these lesions were significantly (P <0.05) higher in dual-infected pigs compared with all other groups. Four of 17 (23.5%) dual-infected pigs had decreased growth rate and severe lymphoid depletion and granulomatous lymphadenitis associated with high amounts of PCV2-antigen consistent with postweaning multisystemic wasting syndrome (PMWS). PCV2-antigen in lung tissue was most often associated with M. hyopneumoniae-induced peribronchial lymphoid hyperplasia, suggesting that this is an important site for PCV2 replication in the lung. This study indicates that M. hyopneumoniae potentiates the severity of PCV2-associated lung and lymphoid lesions, increases the amount and prolongs the presence of PCV2-antigen, and increases the incidence of PMWS in pigs.

Assessing the impact of cancer on work outcomes: what are the research needs?

Cancer may have a major impact on the capacity of survivors to work, with important economic, personal, and social implications. In this commentary, the authors identify six methodologic criteria for evaluating the return‐to‐work literature for cancer survivors, and they propose a conceptual model to guide future research.

The empirical status of empirically supported psychotherapies: assumptions, findings, and reporting in controlled clinical trials.

This article provides a critical review of the assumptions and findings of studies used to establish psychotherapies as empirically supported. The attempt to identify empirically supported therapies (ESTs) imposes particular assumptions on the use of randomized controlled trial (RCT) methodology that appear to be valid for some disorders and treatments (notably exposure-based treatments of specific anxiety symptoms) but substantially violated for others. Meta-analytic studies support a more nuanced view of treatment efficacy than implied by a dichotomous judgment of supported versus unsupported. The authors recommend changes in reporting practices to maximize the clinical utility of RCTs, describe alternative methodologies that may be useful when the assumptions underlying EST methodology are violated, and suggest a shift from validating treatment packages to testing intervention strategies and theories of change that clinicians can integrate into empirically informed therapies.

Cancer Fatalism

Cancer fatalism--the belief that death is inevitable when cancer is present--has been identified as a barrier to participation in cancer screening, detection, and treatment. Yet this literature has not been reviewed in a comprehensive and systematic manner. Therefore, this literature review addressed (1) philosophical and theoretical underpinnings of cancer fatalism; (2) relationships among demographic factors, cancer fatalism, and cancer screening; (3) the role of cancer fatalism for patients diagnosed with cancer; and (4) intervention strategies. Most of the reviewed studies were descriptive or correlational, did not have an explicit theoretical framework, had varied definitions of fatalism, and reported screening as "intent to screen" or as "past screening behaviors." Review of the studies suggests that cancer fatalism develops over time and is most frequently reported among medically underserved persons and those with limited knowledge of cancer. Cancer fatalism may be modified through culturally relevant interventions that incorporate spirituality. Emphasis must be placed on recognizing the role of cancer fatalism when planning health promotion activities. Future studies should focus on the consistent measurement of cancer fatalism and testing intervention strategies.

The lessons of noninterventional and interventional prospective studies on the development of atopic disease during childhood.

The lessons of noninterventional and interventional prospective studies on the development of atopic disease during childhood.