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Project: screen South Africa.

In South Africa, carcinoma of the cervix affects 1 in 29 women. A national screening programme to address the problem has been implemented. The programme faces serious challenges including shortage of funds, a lack of trained laboratory personnel and the HIV epidemic.

Female↗

Benchmarking and quality in residential and nursing homes: lessons from the US.

BACKGROUND: Performance measurement and benchmarking are common concerns in the delivery of long term care. It is common to measure the performance of providers and to publicly report these data. This paper examines selected technical challenges facing those who design, implement and disseminate health care quality performance measures. METHOD: Review of the application of measures of performance in the US nursing home sector. RESULTS: Using examples drawn from the skilled nursing home arena, problems ranging from data reliability and validity, the multi-dimensional nature of quality measures and selection bias as well as differential measurement abilities are discussed. CONCLUSIONS: Benchmarking of performance is an inherently complex issue. However, to ensure that such comparisons are both fair and valid requires measures to be more technically sophisticated and sensitive to real changes attributable to changes in care.

Benchmarking↗

Informatics for mutagenesis: the design of mutabase--a distributed data recording system for animal husbandry, mutagenesis, and phenotypic analysis.

The increasing use of high-throughput methods for the production of biologically important information and the increasing diversity of that information pose considerable bioinformatics challenges. These challenges will be met by implementing electronic data management systems not only to capture the data, but increasingly to provide a platform for data integration and mining as we enter the post-genomic era. We discuss the design and implementation of such a data capture system, 'Mutabase', as a model of how such electronic systems might be designed and implemented. Mutabase was created in support of a large-scale, phenotype-driven mouse mutagenesis program at MRC Mammalian Genetics Unit, Harwell, in collaboration with SmithKline Beecham Pharmaceuticals, Queen Mary and Westfield College, London, and Imperial College of Science, Technology and Medicine, London. The aim of this mutagenesis project is to make a significant contribution to the existing mouse mutant resource, closing the phenotype gap and providing many more models for fundamental research and disease modeling. Mutabase records experimental details at the 'point of generation' and provides a number of dissemination and analysis tools for the experimental data, as well as providing a means of assessing various aspects of progress of the program. Mutabase uses a hypertext-based interface to provide interaction between a number of intranet-based client workstations and a central industrial strength database. Mutabase utilizes a variety of techniques in order to implement the user interface system including Perl/CGI, Java Servlets, and an experimental CORBA server. We discuss the relative merits of these methods in the context of the need to provide sound informatics approaches for the support of systematic mutagenesis programs.

Animal Husbandry↗

Physiologic consequences of local heart irradiation in rats.

Noninvasive methods have been used to study the long-term cardiovascular and pulmonary functional changes at rest and after exercise in adult rats following local heart irradiation with single x-ray doses of 15, 17.5 or 20 Gy, and in non-irradiated control animals. Rats that had undergone a chronic exercise program were compared with untrained cohorts. The earliest dysfunction detected was an increased respiratory rate (f) at 10 weeks after irradiation in the highest dose group. In contrast, both telemetric heart-rate (HR) and rhythm and indirect systolic blood pressure measurements performed at rest only revealed changes starting at 43 weeks after irradiation with 20 Gy, up to which point the rats showed no clinical signs of heart failure. However, the number of minutes required for the recovery of the HR to pre-exercise levels following the implementation of a standardized exercise challenge was elevated in untrained rats compared with their trained cohorts at 18 weeks after irradiation with 20 Gy. Increases in recovery times were required in the two lowest dose groups, starting at 26 weeks after irradiation. It was concluded that the reserve capacity of the cardiopulmonary system masks functional decrements at rest for many months following local heart irradiation, necessitating the use of techniques which reveal reductions in reserve capacities. Further, the influence of local irradiation to the heart and lungs deserves closer scrutiny due to mutual interactions.

Animals↗

Moving Beyond Morphology to Multiplexed Molecular Imaging as the Next Frontier in Diagnostic Pathology.

Diagnostic pathology has long relied on the morphologic interpretation of hematoxylin and eosin-stained tissues to guide diagnosis and assess prognostic features. Although pathologists intuitively recognize spatial patterns and architectural organization, these assessments remain largely qualitative and difficult to quantify systematically. Immunohistochemistry and immunofluorescence have introduced molecular specificity but are limited in multiplexing capacity, whereas bulk genomic and transcriptomic assays provide high molecular depth but lose spatial context by averaging signals across heterogeneous cell populations. Recent advances in spatial proteomics-including mass spectrometry-based imaging and cyclic immunofluorescence-now enable multiplexed, single-cell protein analysis within intact tissue architecture. These technologies have revealed complex immune and stromal microenvironments, spatially organized biomarkers predictive of therapeutic response, and molecular gradients underlying disease progression. By integrating histologic and molecular information, spatial proteomics bridges traditional microscopy with high-dimensional omics, allowing quantitative, spatially resolved insights into tissue organization and disease mechanisms. This review summarizes recent developments in multiplexed spatial proteomics from both scientific and pathologic perspectives, highlighting how these technologies extend beyond morphology to quantify histologic patterns, refine biomarker discovery, and facilitate clinical translation. The review also examines translational challenges and barriers to clinical implementation, including costs, standardization requirements, and workflow integration.

Humans↗

Learning curve analysis of a patient lift-assist device.

One of the challenges facing ergonomists in the implementation of an ergonomic solution is addressing the concerns related to their impact on productivity. The focus of the current study was to (1) apply standard learning curve analysis to the learning that takes place as an individual works with a patient handling device and (2) compare the effects of two different training protocols on measures of learning. Eighteen subjects completed 11 replications of a patient transfer task after participating in either an "interactive" training protocol or "see-one-do-one" training protocol. The results show that the learning rate for this task was 83% with no difference as a function of training protocol. The results do indicate that the effect of Training Method was significant (p<0.05) for time to complete the first patient lift task (370s for the interactive training vs. 475s for see-one-do-one training). The results of the analysis of the survey data supported the objective results in that the only measure that was responsive to training type (p<0.05) was related to comfort level in performing the patient lift task for the first time. The results emphasize the importance in considering learning when introducing an intervention in the workplace, and showed that in this instance, training type had an immediate impact on productivity, but that this effect diminished over time.

Adult↗

Trial of management of borderline and other low-grade abnormal smears (TOMBOLA): Trial design.

Cervical screening reduces the risk of cervical cancer by detecting and treating cervical intraepithelial neoplasia (CIN). The management of women with low-grade cervical abnormalities is controversial. Two management policies exist: repeat smears in primary care and colposcopy examination. It is not clear which of these is the more effective and efficient. There is also uncertainty as to the most effective and efficient management of women at colposcopy when an area of abnormality is seen on the cervix - immediate treatment or biopsy and selective recall for treatment if the biopsy result suggests this is necessary. The result of a human papillomavirus (HPV) test might assist in deciding the appropriate management of women with low-grade abnormalities. TOMBOLA, a pragmatic randomised-controlled trial set within the cervical screening programmes in Scotland and England, addresses these three areas of uncertainty. Almost four and a half thousand women aged 20-59 with a low-grade cervical abnormality have been recruited and randomised to either repeat smears or colposcopy examination. Women in the colposcopy arm of the trial are further randomised to a policy of either immediate treatment or biopsy and selective recall for treatment if they have an abnormal transformation zone. Women are followed up to an exit examination at 3 years. HPV testing is undertaken at recruitment and at the exit examination. The primary endpoint is cumulative incidence of CIN2/3. A range of other clinical, psychosocial and economic outcomes is being considered. This paper describes the design of the trial, and discusses the rationale underlying aspects of the design and the challenges faced in designing and implementing the trial.

Alphapapillomavirus↗

Near-real-time feedback control system for liver thermal ablations based on self-referenced temperature imaging.

Our challenge was to design and implement a dedicated temperature imaging feedback control system to guide and assist in a thermal liver ablation procedure in a double-donut 0.5T open MR scanner. This system has near-real-time feedback capability based on a newly developed "self-referenced" temperature imaging method using "moving-slab" and complex-field-fitting techniques. Two phantom validation studies and one ex vivo experiment were performed to compare the newly developed self-referenced method with the conventional subtraction method and evaluate the ability of the feedback control system in the same MR scanner. The near-real-time feedback system was achieved by integrating the following primary functions: (1) imaging of the moving organ temperature; (2) on-line needle tip tracking; (3) automatic turn-on/off the heating devices; (4) a Windows operating system-based novel user-interfaces. In the first part of the validation studies, microwave heating was applied in an agar phantom using a fast spoiled gradient recalled echo in a steady state sequence. In the second part of the validation and ex vivo study, target visualization, treatment planning and monitoring, and temperature and thermal dose visualization with the graphical user interface of the thermal ablation software were demonstrated. Furthermore, MR imaging with the "self-referenced" temperature imaging method has the ability to localize the hot spot in the heated region and measure temperature elevation during the experiment. In conclusion, we have demonstrated an interactively controllable feedback control system that offers a new method for the guidance of liver thermal ablation procedures, as well as improving the ability to assist ablation procedures in an open MR scanner.

Algorithms↗

Acceptability of community and health facility-based directly observed treatment of tuberculosis in Tanzanian urban setting.

SETTING: An urban district in Dar es Salaam, Tanzania. OBJECTIVE: To assess the acceptability of community and health facility-based direct observation of treatment (DOT) of tuberculosis (TB) patients in Temeke district. DESIGN: Both quantitative and qualitative study methodologies were used. Eight focus group discussions were carried out with TB patients, treatment supporters, health workers and community members. Quantitative study was also carried out among TB patients and treatment supporters. RESULTS: A total of 268 patients and 103 treatment supporters were enrolled in the study. The majority of the patients (75%) were satisfied with the DOT options they received. Males were more satisfied with community-based DOT (84%) than females (67%) (OR 4.96, 95% CI 1.38-17.86). The majority (81%) were willing to supervise another TB patient. The results of the qualitative study demonstrated that community-based DOT was preferred because it was found to be convenient, reduced costs, saved time of the patients and reduced workload in health services. The main challenge of community-based DOT was to ensure effective supervision and monitoring of patients and treatment supporters in the community. CONCLUSION: The results from the quantitative and qualitative studies indicate that both DOT options were acceptable. The study has also identified key challenges and opportunities for effective implementation of community-based DOT interventions that are relevant, sensitive and acceptable to the population. Community-based DOT is a viable option and can complement and strengthen the existing health facility-based DOT, especially in countries like Tanzania where the health system is overwhelmed with increasing number of TB and HIV/AIDS patients.

Adult↗

Conducting ethical research in pediatrics: a brief historical overview and review of pediatric regulations.

Achieving proper balance between the social good that comes from performing research that involves children and offering the appropriate level of protection to children who participate in research is a significant challenge. As investigators design and implement research protocols, they should be aware of the ethical and legal requirements that govern research with human participants. This is especially true of research that involves children and other vulnerable groups. The welfare of children participating in research depends on knowledgeable, caring, and responsible investigators who place the well-being of the research participant above all other aspects of the research project. The purpose of this article is to provide a brief overview of the history of research involving children, to provide a basis for understanding the context within which the current federal regulations were written, and to provide an overview of the regulatory requirements that relate to research involving children. Good research is ethical research, and that requires investigators who take seriously the importance of participant welfare, meaningful informed consent, and respect for research participants.

Child↗

The California Health Interview Survey 2001: translation of a major survey for California's multiethnic population.

The cultural and linguistic diversity of the U.S. population presents challenges to the design and implementation of population-based surveys that serve to inform public policies. Information derived from such surveys may be less than representative if groups with limited or no English language skills are not included. The California Health Interview Survey (CHIS), first administered in 2001, is a population-based health survey of more than 55,000 California households. This article describes the process that the designers of CHIS 2001 underwent in culturally adapting the survey and translating it into an unprecedented number of languages: Spanish, Chinese, Vietnamese, Korean, and Khmer. The multiethnic and multilingual CHIS 2001 illustrates the importance of cultural and linguistic adaptation in raising the quality of population-based surveys, especially when the populations they intend to represent are as diverse as California's.

Adolescent↗

Global paediatric pulmonology: out of Africa.

Respiratory illness is the major cause of mortality and morbidity in African children. The spectrum of disease includes acute and chronic respiratory illness. As a result of the HIV epidemic currently occurring in sub-Saharan Africa, HIV-associated acute and chronic respiratory disease has emerged as a major factor in the epidemiology of childhood respiratory illness. Pneumonia is the leading causes of childhood mortality responsible for approximately 21% of deaths in African children under five years of age each year. The HIV pandemic has increased the incidence, severity and pneumonia mortality in African children. Pulmonary tuberculosis (TB) is an important cause of morbidity and death. Globally, the highest TB incidence rates occur in sub-Saharan African countries; many of these countries are also experiencing a dual HIV epidemic, resulting in an exponential increase in TB cases. The burden of childhood respiratory illness has necessitated novel and improved ways of diagnosis, treatment and prevention, particularly in the context of limited resources. Improved diagnosis, treatment and prevention of pneumonia have been a research focus, particularly in HIV-infected children. African studies have provided information on the epidemiology, aetiology and outcome from pneumonia in HIV-infected and uninfected children. The efficacy of trimethoprim-sulphamethoxazole prophylaxis in reducing mortality and morbidity in HIV-infected African children was shown in the only randomized controlled trial. Two large studies have shown the efficacy of the pneumococcal conjugate vaccine in an African context. Regarding TB, areas of research include diagnostic studies and improved preventative strategies. Promising diagnostic studies for childhood TB include the use of sputum induction, PCR techniques and blood interferon assays. The immune reconstitution inflammatory syndrome (IRIS) has emerged as a new clinical entity in HIV-infected children with TB associated with use of antiretroviral therapy. New preventative strategies for TB include novel vaccines and primary prophylaxis. Available, effective interventions for prevention and treatment of childhood respiratory disease exist; the challenge is to achieve widespread implementation and high coverage rates in African countries. Greater access to newer vaccines and, in HIV-infected children, to anti-retroviral therapy and prophylaxis is necessary to further reduce the burden of childhood respiratory illness in Africa.

Africa↗

Cardiovascular disease prevention in Russia: challenges and opportunities.

OBJECTIVES: This paper examines the challenges that have faced the implementation of cardiovascular disease (CVD) prevention programmes in Russia since the 1980s in two regions of Russia, and identifies opportunities for improving such efforts. STUDY DESIGN AND METHODS: This study used a mixed methods design consisting of archival data review of health-related policy documents and legislation, and key informant interviews. RESULTS: CVD is the leading cause of death in Russia, with rapid increases in prevalence following the collapse of the Soviet Union in 1991. The MONICA, Tacis and CINDI programmes have played major roles in the development of non-communicable and CVD prevention policies and programmes in Russia since the 1980s. These programmes have assisted in policy and guideline development, and programme implementation. However, significant barriers in realizing such policies and sustaining prevention programmes have been encountered. CONCLUSION: Numerous barriers exist in developing and implementing CVD prevention programmes in Russia. More government engagement backed by strong public support is necessary in order to sustain and build capacity for CVD prevention in Russia.

Cardiovascular Diseases↗

Is it time for brushless scrubbing with an alcohol-based agent?

The practice of surgical scrubbing in perioperative settings is changing rapidly. This article presents information about eliminating the traditional scrub brush technique and using an alcohol formulation for surgical hand scrubs. Also covered are antimicrobial agents, relevant US Food and Drug Administration classifications, skin and fingernail care, and implementation of changes. The article challenges surgical team members to evaluate a new and different approach to surgical hand scrubbing.

Alcohols↗

Stroke rehabilitation: are highly structured units more conducive to physical activity than less structured units?

OBJECTIVE: To determine if the physical design and organizational structure of rehabilitation units is related to the amount of patients' motor activity. DESIGN: An observational study was conducted; time samples of the motor activity of patients following stroke were taken between 7AM and 7PM both on weekdays and weekends. SETTING: Two rehabilitation units associated with general hospitals with different physical design and organizational structure. One unit was spread over a large area and had a highly organized daily structure; the other was small and informally organized. SUBJECTS: Inpatients with hemiplegia as a result of stroke who gave consent to participate. MAIN OUTCOME MEASURE: The nature and frequency of 14 motor activities were compared between units. RESULTS: No significant difference was found in any of the observed motor activities between the units when using independent groups t tests (p = 0.1-0.8). Subjects in both units spent more than 70% of their day in activities largely unrelated to physical outcome (eg, conversing with visitors or doing nothing observable) and less than 20% of the day in activities that could potentially contribute to their recovery (eg, in therapy or exercising independently). CONCLUSIONS: Rehabilitation units are not functioning as learning environments. The challenge is to identify and implement measures that will change this finding.

Aged↗

Present issues in the determination of troponins and other markers of cardiac damage.

OBJECTIVE: To review some of the recently proposed improvements and the corresponding apparent issues in the field of biochemical markers of cardiac damage. CONCLUSIONS: The continuous development of new analytical tools for the biochemical evaluation of patients with suspected myocardial injury brings without doubt new challenges of careful technological evaluation, implementation, and standardization but it may also provide a unique opportunity to markedly enhance our diagnostic performance in the clinical setting of acute coronary syndrome.

Biomarkers↗

Acute myocardial infarction.

Acute myocardial infarction is a common disease with serious consequences in mortality, morbidity, and cost to the society. Coronary atherosclerosis plays a pivotal part as the underlying substrate in many patients. In addition, a new definition of myocardial infarction has recently been introduced that has major implications from the epidemiological, societal, and patient points of view. The advent of coronary-care units and the results of randomised clinical trials on reperfusion therapy, lytic or percutaneous coronary intervention, and chronic medical treatment with various pharmacological agents have substantially changed the therapeutic approach, decreased in-hospital mortality, and improved the long-term outlook in survivors of the acute phase. New treatments will continue to emerge, but the greatest challenge will be to effectively implement preventive actions in all high-risk individuals and to expand delivery of acute treatment in a timely fashion for all eligible patients.

Angioplasty, Balloon, Coronary↗

The rationale and design of the CPCRA (Terry Beirn Community Programs for Clinical Research on AIDS) 058 FIRST (Flexible Initial Retrovirus Suppressive Therapies) trial.

The CPCRA (Terry Beirn Community Programs for Clinical Research on AIDS) 058 FIRST (Flexible Initial Retrovirus Suppressive Therapies) trial is a large, long-term, randomized, prospective comparison of three different antiretroviral strategies in highly active antiretroviral therapy-naïve, HIV-1-infected persons. The trial was designed as a flexible framework upon which other studies could be added to answer more limited, but still important, questions. This article presents the study design, discusses the challenges we have faced in implementing the trial, and describes our preliminary experiences. Control Clin Trials 2001;22:176-190

Acquired Immunodeficiency Syndrome↗