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Background: This study aims to assess the rate at which screening colonoscopy is performed on patients younger or older than the age range specified in national guidelines, or at shorter intervals than recommended. Such non-indicated use of the procedure is considered low-value care, or overuse. This study is the first systematic review of the rate of non-indicated completed screening colonoscopy in the USA.Methods: PubMed and Embase were queried for relevant studies on overuse of screening colonoscopy published from January 1, 2002, until January 23, 2019. English-language studies that were conducted for screening colonoscopy after 2001 for average-risk patients were included. Studies must have followed national guidelines for detecting rates of overuse. We followed methods outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the reporting recommendations of the Meta-analysis of Observational Studies in Epidemiology group (MOOSE).Results: A total of 772 papers were reviewed for inclusion; 42 were reviewed in full text. Of those reviewed, six studies met eligibility criteria, including a total of 459,503 colonoscopies of which 242,756 were screening colonoscopies. The rate of overuse ranged credibly from 17 to 25.7%.Discussion: This study demonstrates that screening colonoscopy is regularly performed in the USA more often, and in populations older or younger, than recommended by national guidelines. Such overuse wastes resources and places patients at unnecessary risk of harm. Efforts to reduce non-indicated screening colonoscopy are needed. [ABSTRACT FROM AUTHOR]

Background: This paper reviews recent literature employing Artificial Intelligence/Machine Learning (AI/ML) methods for diagnostic evaluation of head and neck cancers (HNC) using automated image analysis.Methods: Electronic database searches using MEDLINE via OVID, EMBASE and Google Scholar were conducted to retrieve articles using AI/ML for diagnostic evaluation of HNC (2009-2020). No restrictions were placed on the AI/ML method or imaging modality used.Results: In total, 32 articles were identified. HNC sites included oral cavity (n = 16), nasopharynx (n = 3), oropharynx (n = 3), larynx (n = 2), salivary glands (n = 2), sinonasal (n = 1) and in five studies multiple sites were studied. Imaging modalities included histological (n = 9), radiological (n = 8), hyperspectral (n = 6), endoscopic/clinical (n = 5), infrared thermal (n = 1) and optical (n = 1). Clinicopathologic/genomic data were used in two studies. Traditional ML methods were employed in 22 studies (69%), deep learning (DL) in eight studies (25%) and a combination of these methods in two studies (6%).Conclusions: There is an increasing volume of studies exploring the role of AI/ML to aid HNC detection using a range of imaging modalities. These methods can achieve high degrees of accuracy that can exceed the abilities of human judgement in making data predictions. Large-scale multi-centric prospective studies are required to aid deployment into clinical practice. [ABSTRACT FROM AUTHOR]

Background: This paper investigates the difference in survival of melanoma patients across stage and sex by utilising net survival measures. Metrics are presented at both the individual and population level.Methods: Flexible parametric models were fitted to estimate life-expectancy metrics to be applied to a group of 104,938 subjects with a melanoma skin cancer diagnosis from 2000 to 2017. Period analysis was used for better predictions for newly diagnosed patients, and missing-stage information was imputed for 9918 patients. Female relative survival was assigned to male subjects to demonstrate the survival discrepancies experienced between sexes.Results: At the age of 60, males diagnosed at the regional stage lose an average of 4.99 years of life compared to the general population, and females lose 4.79 years, demonstrating the sex variation in expected mortality. In 2017, males contributed 3545 more life years lost than females, and a potential 1931 life years could be preserved if sex differences in survival were eliminated.Conclusions: This study demonstrates the survival differences across population subgroups as a result of a melanoma cancer diagnosis. Females experience better prognosis across age and stage at diagnosis; however, further investigation is necessary to better understand the mechanisms behind this difference. [ABSTRACT FROM AUTHOR]

Global initiatives have raised awareness of the need for cross-departmental and cross-sectoral activities to support urban health, sustainability, and equity, with respective indicators routinely used as a way to catalyze and monitor action toward pre-defined goals. Despite the existence of at least 145 urban health indicator (UHI) tools globally, there has been very little research on the use of indicators by policy- and decision-makers; more attention has been devoted to their development and validation. This paper describes the second part of a two-part systematic review of the characteristics (part A) and use (part B, this part) of UHI tools by municipal built environment policy- and decision-makers. Part B is a narrative synthesis of studies on the use of UHI tools. This PRISMA-P compliant review follows a mixed methods sequential explanatory design. The search was conducted using seven bibliographic databases, grey literature searches, and key journal hand searches. Ten studies describing the use of ten UHI tools in seven countries were included in the narrative synthesis, resulting in development of a theory of change (ToC). We found that both expert-led and participatory indicator projects can be underpinned by research evidence and residents' knowledge. Our findings contradict the dominant view of indicator use in policy-making as a linear process, highlighting a number of technical, organizational, political, knowledge, and contextual factors that affect their use. Participatory UHI tools with community involvement were generally more effective at supporting "health in all policies" and "whole-of-society" approaches to governing healthy cities than expert-led processes. UHI tool producers proposed a range of techniques to address urban health complexity characteristics. Finally, in combining data from both parts of the review, we found that potentially important UHI tool features, such as neighbourhood-scale data, were influential in the use of indicators by built environment policy- and decision-makers. [ABSTRACT FROM AUTHOR]

Delivering well-coordinated care is essential for optimizing clinical outcomes, enhancing patient care experiences, minimizing costs, and increasing provider satisfaction. The Veterans Health Administration (VA) has built a strong foundation for internally coordinating care. However, VA faces mounting internal care coordination challenges due to growth in the number of Veterans using VA care, high complexity in Veterans' care needs, the breadth and depth of VA services, and increasing use of virtual care. VA's Health Services Research and Development service with the Office of Research and Development held a conference assessing the state-of-the-art (SOTA) on care coordination. One workgroup within the SOTA focused on coordination between VA providers for high-need Veterans, including (1) Veterans with multiple chronic conditions; (2) Veterans with high-intensity, focused, specialty care needs; (3) Veterans experiencing care transitions; (4) Veterans with severe mental illness; (5) and Veterans with homelessness and/or substance use disorders. We report on this workgroup's recommendations for policy and organizational initiatives and identify questions for further research. Recommendations from a separate workgroup on coordinating VA and non-VA care are contained in a companion paper. Leaders from research, clinical services, and VA policy will need to partner closely as they develop, implement, assess, and spread effective practices if VA is to fully realize its potential for delivering highly coordinated care to every Veteran. [ABSTRACT FROM AUTHOR]

Mobility is a key aspect of active ageing enabling participation and autonomy into later life. Remaining active brings multiple physical but also social benefits leading to higher levels of well-being. With globally increasing levels of urbanisation alongside demographic shifts meaning in many parts of the world this urban population will be older people, the challenge is how cities should evolve to enable so-called active ageing. This paper reports on a co-design study with 117 participants investigating the interaction of existing urban spaces and infrastructure on mobility and well-being for older residents (aged 55 + years) in three cities. A mixed method approach was trialled to identify locations beneficial to subjective well-being and participant-led solutions to urban mobility challenges. Spatial analysis was used to identify key underlying factors in locations and infrastructure that promoted or compromised mobility and well-being for participants. Co-designed solutions were assessed for acceptability or co-benefits amongst a wider cross-section of urban residents (n = 233) using online and face-to-face surveys in each conurbation. Our analysis identified three critical intersecting and interacting thematic problems for urban mobility amongst older people: The quality of physical infrastructure; issues around the delivery, governance and quality of urban systems and services; and the attitudes and behaviors of individuals that older people encounter. This identified complexity reinforces the need for policy responses that may not necessarily involve design or retrofit measures, but instead might challenge perceptions and behaviors of use and access to urban space. Our co-design results further highlight that solutions need to move beyond the generic and placeless, instead embedding specific locally relevant solutions in inherently geographical spaces, populations and processes to ensure they relate to the intricacies of place. [ABSTRACT FROM AUTHOR]

An established body of research has used secondary data sources (such as proprietary business databases) to demonstrate the importance of the neighborhood food environment for multiple health outcomes. However, documenting food availability using secondary sources in low-income urban neighborhoods can be particularly challenging since small businesses play a crucial role in food availability. These small businesses are typically underrepresented in national databases, which rely on secondary sources to develop data for marketing purposes. Using social media and other crowdsourced data to account for these smaller businesses holds promise, but the quality of these data remains unknown. This paper compares the quality of full-line grocery store information from Yelp, a crowdsourced content service, to a "ground truth" data set (Detroit Food Map) and a commercially-available dataset (Reference USA) for the greater Detroit area. Results suggest that Yelp is more accurate than Reference USA in identifying healthy food stores in urban areas. Researchers investigating the relationship between the nutrition environment and health may consider Yelp as a reliable and valid source for identifying sources of healthy food in urban environments. [ABSTRACT FROM AUTHOR]

Introduction: Pulmonary metastasectomy for colorectal cancer is a commonly performed and well-established practice of ∼50 years standing. However, there have been no controlled studies, randomised or otherwise. We sought to investigate the evidence base that has been used in establishing its status as a standard of care.Methods: Among 51 papers used in a recent systematic review and quantitative synthesis, a citation network analysis was performed. A total of 344 publications (the 51 index papers and a further 293 cited in them) constitute the citation network.Results: The pattern of citation is that of a citation cascade. Specific analyses show the frequent use of historical or landmark papers, which add authority. Papers expressing an opposing viewpoint are rarely cited.Conclusions: The citation network for this common and well-established practice provides an example of selective citation. This pattern of citation tends to escalate belief in a clinical practice even when it lacks a high-quality evidence base and may create an impression of more authority than is warranted. [ABSTRACT FROM AUTHOR]

Background: Although electronic prescribing (e-prescribing) holds promise for preventing prescription errors in the ambulatory setting, research on its effectiveness is inconclusive.Objective: To assess the impact of a stand-alone e-prescribing system on the rates and types of ambulatory prescribing errors.Design, Participants: Prospective, non-randomized study using pre-post design of 15 providers who adopted e-prescribing with concurrent controls of 15 paper-based providers from September 2005 through June 2007.Intervention: Use of a commercial, stand-alone e-prescribing system with clinical decision support including dosing recommendations and checks for drug-allergy interactions, drug-drug interactions, and duplicate therapies.Main Measures: Prescribing errors were identified by a standardized prescription and chart review.Key Results: We analyzed 3684 paper-based prescriptions at baseline and 3848 paper-based and electronic prescriptions at one year of follow-up. For e-prescribing adopters, error rates decreased nearly sevenfold, from 42.5 per 100 prescriptions (95% confidence interval (CI), 36.7-49.3) at baseline to 6.6 per 100 prescriptions (95% CI, 5.1-8.3) one year after adoption (p < 0.001). For non-adopters, error rates remained high at 37.3 per 100 prescriptions (95% CI, 27.6-50.2) at baseline and 38.4 per 100 prescriptions (95% CI, 27.4-53.9) at one year (p = 0.54). At one year, the error rate for e-prescribing adopters was significantly lower than for non-adopters (p < 0.001). Illegibility errors were very high at baseline and were completely eliminated by e-prescribing (87.6 per 100 prescriptions at baseline for e-prescribing adopters, 0 at one year).Conclusions: Prescribing errors may occur much more frequently in community-based practices than previously reported. Our preliminary findings suggest that stand-alone e-prescribing with clinical decision support may significantly improve ambulatory medication safety.Trial Registration: ClinicalTrials.gov, Taconic Health Information Network and Community (THINC), NCT00225563, http://clinicaltrials.gov/ct2/show/NCT00225563?term=Kaushal&rank=6 . [ABSTRACT FROM AUTHOR]

Objective: To determine whether the integration of an automated electronic clinical portfolio into clinical clerkships can improve the quality of feedback given to students on their patient write-ups and the quality of students' write-ups.Design: The authors conducted a single-blinded, randomized controlled study of an electronic clinical portfolio that automatically collects all students' clinical notes and notifies their teachers (attending and resident physicians) via e-mail. Third-year medical students were randomized to use the electronic portfolio or traditional paper means. Teachers in the portfolio group provided feedback directly on the student's write-up using a web-based application. Teachers in the control group provided feedback directly on the student's write-up by writing in the margins of the paper. Outcomes were teacher and student assessment of the frequency and quality of feedback on write-ups, expert assessment of the quality of student write-ups at the end of the clerkship, and participant assessment of the value of the electronic portfolio system.Results: Teachers reported giving more frequent and detailed feedback using the portfolio system (p = 0.01). Seventy percent of students who used the portfolio system, versus 39% of students in the control group (p = 0.001), reported receiving feedback on more than half of their write-ups. Write-ups of portfolio students were rated of similar quality to write-ups of control students. Teachers and students agreed that the system was a valuable teaching tool and easy to use.Conclusions: An electronic clinical portfolio that automatically collects students' clinical notes is associated with improved teacher feedback on write-ups and similar quality of write-ups. [ABSTRACT FROM AUTHOR]

There has been a substantially increased interest in biomedical research impact assessment over the past 5 years. This can be studied by a number of methods, but its influence on clinical guidelines must rank as one of the most important. In cancer, there are 43 UK guidelines (and associated Health Technology Assessments) published (up to October 2006) across three series, each of which has an evidence base in the form of references, many of which are papers in peer-reviewed journals. These have all been identified and analysed to determine their geographical provenance and type of research, in comparison with overall oncology research published in the peak years of guideline references (1999-2001). The UK papers were cited nearly three times as frequently as would have been expected from their presence in world oncology research (6.5%). Within the United Kingdom, Edinburgh and Glasgow stood out for their unexpectedly high contributions to the guidelines' scientific base. The cited papers from the United Kingdom acknowledged much more explicit funding from all sectors than did the UK cancer research papers at the same research level. [ABSTRACT FROM AUTHOR]

Racial-ethnic minorities receive lower quality and intensity of health care compared with whites across a wide range of preventive, diagnostic, and therapeutic services and disease entities. These disparities in health care contribute to continuing racial-ethnic disparities in the burden of illness and death. Several national medical organizations and the Institute of Medicine have issued position papers and recommendations for the elimination of health care disparities. However, physicians in practice are often at a loss for how to translate these principles and recommendations into specific interventions in their own clinical practices. This paper serves as a blueprint for translating principles for the elimination of racial-ethnic disparities in health care into specific actions that are relevant for individual clinical practices. We describe what is known about reducing racial-ethnic disparities in clinical practice and make recommendations for how clinician leaders can apply this evidence to transform their own practices. [ABSTRACT FROM AUTHOR]

Background: Medical symptoms independent of body location burden individuals to varying degrees and may require care by more than one expert. Various paper and computer-based tools exist that aim to comprehensively capture data for optimal clinical management and research. Methods: A web-based interdisciplinary symptom evaluation (WISE) was newly designed, constructed, and technically implemented. For worldwide applicability and to avoid copyright infringements, open source software tools and free validated questionnaires available in multiple languages were used. Highly secure data storage limits access strictly to those who use the tool for collecting, storing, and evaluating their data. Concept and implementation is illustrated by a WISE sample tailored for the requirements of a single center in Switzerland providing interdisciplinary care to orofacial pain and temporomandibular disorder patients. Results: By combining a symptom- burden checklist with in-depth questionnaires serving as case-finding instruments, an algorithm was developed that assists in clarifying case complexity and need for targeted expert evaluation. This novel modular approach provides a personalized, response-tailored instrument for the time- and cost-effective collection of symptom-burden focused quantitative data. The tool includes body drawing options and instructional videos. It is applicable for biopsychosocial evaluation in a variety of clinical settings and offers direct feedback by a case report summary. Conclusions: In clinical practice, the new instrument assists in clarifying case complexity and referral need, based on symptom burden and response -tailored case finding. It provides single-case summary reports from a biopsychosocial perspective and includes graphical symptom maps. Secure, centrally stored data collection of anonymous data is possible. The tool enables personalized medicine, facilitates interprofessional education and collaboration, and allows for multicenter patient-reported outcomes research. [ABSTRACT FROM AUTHOR]

Background: Patient complexity is often operationalized by counting multiple chronic conditions (MCC) without considering contextual factors that can affect patient risk for adverse outcomes.Objective: Our objective was to develop a conceptual model of complexity addressing gaps identified in a review of published conceptual models.Data Sources: We searched for English-language MEDLINE papers published between 1 January 2004 and 16 January 2014. Two reviewers independently evaluated abstracts and all authors contributed to the development of the conceptual model in an iterative process.Results: From 1606 identified abstracts, six conceptual models were selected. One additional model was identified through reference review. Each model had strengths, but several constructs were not fully considered: 1) contextual factors; 2) dynamics of complexity; 3) patients' preferences; 4) acute health shocks; and 5) resilience. Our Cycle of Complexity model illustrates relationships between acute shocks and medical events, healthcare access and utilization, workload and capacity, and patient preferences in the context of interpersonal, organizational, and community factors.Conclusions/implications: This model may inform studies on the etiology of and changes in complexity, the relationship between complexity and patient outcomes, and intervention development to improve modifiable elements of complex patients. [ABSTRACT FROM AUTHOR]

Study design:Literature review/semi-structured interviews.Objective:To develop a spinal cord injury (SCI) research strategy for Australia and New Zealand.Setting:Australia.Methods:The National Trauma Research Institute Forum approach of structured evidence review and stakeholder consultation was employed. This involved gathering from published literature and stakeholder consultation the information necessary to properly consider the challenge, and synthesising this into a briefing document.Results:A research strategy 'roadmap' was developed to define the major steps and key planning questions to consider; next, evidence from published SCI research strategy initiatives was synthesised with information from four one-on-one semi-structured interviews with key SCI research stakeholders to create a research strategy framework, articulating six key themes and associated activities for consideration. These resources, combined with a review of SCI prioritisation literature, were used to generate a list of draft principles for discussion in a structured stakeholder dialogue meeting.Conclusion:The research strategy roadmap and framework informed discussion at a structured stakeholder dialogue meeting of 23 participants representing key SCI research constituencies, results of which are published in a companion paper. These resources could also be of value in other research strategy or planning exercises.Sponsorship:This project was funded by the Victorian Transport Accident Commission and the Australian and New Zealand Spinal Cord Injury Network. [ABSTRACT FROM AUTHOR]

This paper summarizes survey and interview results from a cross-sectional study of New Zealand health care chaplaincy personnel concerning their involvement in multiple bioethical issues encountered by patients, families and clinical staff within the health care context. Some implications of this study concerning health care chaplaincy, ecclesiastical institutions, health care institutions and government responsibilities are discussed and recommendations presented. [ABSTRACT FROM AUTHOR]

In many Western science systems, funding structures increasingly stimulate academic research to contribute to practical applications, but at the same time the rise of bibliometric performance assessments have strengthened the pressure on academics to conduct excellent basic research that can be published in scholarly literature. We analyze the interplay between these two developments in a set of three case studies of fields of chemistry in the Netherlands. First, we describe how the conditions under which academic chemists work have changed since 1975. Second, we investigate whether practical applications have become a source of credibility for individual researchers. Indeed, this turns out to be the case in catalysis, where connecting with industrial applications helps in many steps of the credibility cycle. Practical applications yield much less credibility in environmental chemistry, where application-oriented research agendas help to acquire funding, but not to publish prestigious papers or to earn peer recognition. In biochemistry practical applications hardly help in gaining credibility, as this field is still strongly oriented at fundamental questions. The differences between the fields can be explained by the presence or absence of powerful upstream end-users, who can afford to invest in academic research with promising long term benefits. [ABSTRACT FROM AUTHOR]

Personal autonomy is widely valued. Recognition of its vulnerability in health care contexts led to the inclusion of respect for autonomy as a key concern in biomedical ethics. The principle of respect for autonomy is usually associated with allowing or enabling patients to make their own decisions about which health care interventions they will or will not receive. In this paper, we suggest that a strong focus on decision situations is problematic, especially when combined with a tendency to stress the importance of patients' independence in choosing. It distracts attention from other important aspects of and challenges to autonomy in health care. Relational understandings of autonomy attempt to explain both the positive and negative implications of social relationships for individuals' autonomy. They suggest that many health care practices can affect autonomy by virtue of their effects not only on patients' treatment preferences and choices, but also on their self-identities, self-evaluations and capabilities for autonomy. Relational understandings de-emphasise independence and facilitate well-nuanced distinctions between forms of clinical communication that support and that undermine patients' autonomy. These understandings support recognition of the value of good patient-professional relationships and can enrich the specification of the principle of respect for autonomy. [ABSTRACT FROM AUTHOR]

Background: Latino immigrants face a higher burden of colorectal cancer (CRC) and screening rates are low.Objective: To assess the effectiveness of a multilevel intervention in increasing the rate of CRC screening among Latino immigrants.Design: A randomized controlled trial, with randomization at the physician level.Participants: Pairs of 65 primary care physicians and 65 Latino immigrant patients participated, 31 in the intervention and 34 in the control group.Intervention: CRC educational video in Spanish on a portable personal digital video display device accompanied by a brochure with key information for the patient, and a patient-delivered paper-based reminder for their physician.Measurements: Completed CRC screening, physician recommendation for CRC screening, and patient adherence to physician recommended CRC screening.Results: The overall rate of completed screening for CRC was 55% for the intervention and 18% for the control group (p = 0.002). Physicians recommended CRC screening for 61% of patients in the intervention group versus 41% in the control group (p = 0.08). Of those that received a recommendation, 90% in the intervention group adhered to it versus 26% in the control group (p = 0.007).Conclusions: The intervention was successful in increasing rates of completed CRC screening primarily through increasing adherence after screening was recommended. Additional efforts should focus on developing new strategies to increase physician recommendation for CRC screening, while employing effective patient adherence interventions. [ABSTRACT FROM AUTHOR]

Patients' experience of stereotype threat in clinical settings and encounters may be one contributor to health care disparities. Stereotype threat occurs when cues in the environment make negative stereotypes associated with an individual's group status salient, triggering physiological and psychological processes that have detrimental consequences for behavior. By recognizing and understanding the factors that can trigger stereotype threat and understanding its consequences in medical settings, providers can prevent it from occurring or ameliorate its consequences for patient behavior and outcomes. In this paper, we discuss the implications of stereotype threat for medical education and trainee performance and offer practical suggestions for how future providers might reduce stereotype threat in their exam rooms and clinics. [ABSTRACT FROM AUTHOR]

Chronic lymphocytic leukemia (CLL) and the other low-grade non-Hodgkin lymphomas are among the most common lymphoid malignancies. Recent studies suggest that more than 4% of the general population over age 40 harbor a population of clonal B cells with the phenotype of either CLL or another B-cell malignancy, a condition now designated monoclonal B-cell lymphocytosis (MBL). Although all cases of CLL appear to be preceded by MBL, the majority of individuals with MBL will not develop a hematologic malignancy. The biologic characteristics and clinical implications of MBL appear to differ based on whether it is identified during the diagnostic evaluation of lymphocytosis or incidentally discovered through screening of individuals with normal lymphocyte counts as part of research studies using highly sensitive detection methods. In this paper, we provide a state of the art review on the prevalence, nomenclature, biology, natural history and clinical management of MBL. [ABSTRACT FROM AUTHOR]

Background: Failed referrals for specialty care are common and often represent medical errors. Technological structures and processes account for many failures. Scheduling appointments for subspecialty evaluation is a first step in outpatient referral and consultation.Objective: We determined whether moving from paper-based referrals to a Web-based system with automated tracking features was associated with greater scheduling of appointments among referred patients.Design: Staggered implementation of a quality-improvement project, with comparison of intervention and control groups.Participants: Patients 21 or more years of age referred from any of 11 primary-care clinics to any of 25 specialty clinics.Interventions: Faxed referrals were replaced by a Web-based application shared by generalists and specialists, with enhanced communications and automated notification to the specialty office.Measurements: We compared scheduling before and after implementation and time from referral to appointment. A logistic regression analysis adjusted for demographics.Main Results: Among 40,487 referrals, 54% led to scheduled specialty visits before intervention, compared to 83% with intervention. The median time to appointment was 168 days without intervention and 78 days with intervention. Scheduling increased more when duplicate referrals were not generated (54% for single orders, 24% for multiple orders). After adjustment, referrals with the intervention were more than twice as likely to have scheduled visits.Conclusions: With a new Web-based referrals system, referrals were more than twice as likely to lead to a scheduled visit. This system improves access to specialty medical services. [ABSTRACT FROM AUTHOR]

Fourier transform infrared (FTIR) spectroscopy is a vibrational spectroscopic technique that uses infrared radiation to vibrate molecular bonds within the sample that absorbs it. As different samples contain different molecular bonds or different configurations of molecular bonds, FTIR allows us to obtain chemical information on molecules within the sample. Fourier transform infrared microspectroscopy in conjunction with a principal component-discriminant function analysis (PC-DFA) algorithm was applied to the grading of prostate cancer (CaP) tissue specimens. The PC-DFA algorithm is used alongside the established diagnostic measures of Gleason grading and the tumour/node/metastasis system. Principal component-discriminant function analysis improved the sensitivity and specificity of a three-band Gleason score criterion diagnosis previously reported by attaining an overall sensitivity of 92.3% and specificity of 99.4%. For the first time, we present the use of a two-band criterion showing an association of FTIR-based spectral characteristics with clinically aggressive behaviour in CaP manifest as local and/or distal spread. This paper shows the potential for the use of spectroscopic analysis for the evaluation of the biopotential of CaP in an accurate and reproducible manner. [ABSTRACT FROM AUTHOR]

Background: Overuse of antibiotics in the treatment of acute respiratory tract infection (ARI) contributes to the growing problem of antibiotic-resistant infections.Objective: To identify factors that influence community practitioners to prescribe antibiotics and examine how they differ from the recommendations of the Centers for Disease Control and Prevention (CDC) guideline for treatment of ARI.Design: Paper case vignette study using a fractional factorial design.Participants: One hundred one community practitioners and eight faculty members.Main Measurements: We asked community practitioners to estimate how likely they would be to prescribe antibiotics in each of 20 cases of ARI and then used multiple regression to infer the importance weights of each of nine clinical findings. We then compared practitioners' weights with those of a panel of eight faculty physicians who evaluated the cases following the CDC guidelines rather than their own judgments.Main Results: Practitioners prescribed antibiotics in 44.5% of cases, over twice the percentage treated by the panel using the CDC guidelines (20%). In deciding to prescribe antibiotic treatment, practitioners gave little or no weight to patient factors such as whether the patients wanted antibiotics. Although weighting patterns differed among practitioners, the majority (72%) gave the greatest weight to duration of illness. When illness duration was short, the rate of prescribing (20.1%) was the same as the rate of the faculty panel (20%).Conclusions: Based on hypothetical cases of ARI, community practitioners prescribed antibiotics at twice the rate of faculty following CDC practice guidelines. Practitioners were most strongly influenced by duration of illness. The effect of duration was strongest when accompanied by fever or productive cough, suggesting that these situations would be important areas for practitioner education and further clinical studies. [ABSTRACT FROM AUTHOR]

Background: Treatment decisions about menopause are predicated on a transient duration of vasomotor symptoms. However, evidence supporting a specific duration is weak.Objective: To estimate the natural progression of vasomotor symptoms during the menopause transition by systematically compiling available evidence using meta-analytic techniques.Data Sources: We searched MEDLINE, hand searched secondary references in relevant studies, book chapters, and review papers, and contacted investigators about relevant published research.Review Methods: English language, population-based studies reporting vasomotor symptom prevalence among women in menopausal transition in time intervals based on years to or from final menstrual period were included. Two reviewers independently assessed eligibility and quality of studies and extracted data for vasomotor symptom prevalence.Results: The analyses included 10 studies (2 longitudinal, 8 cross sectional) with 35,445 participants. The percentage of women experiencing symptoms increased sharply in the 2 years before final menstrual period, peaked 1 year after final menstrual period, and did not return to premenopausal levels until about 8 years after final menstrual period. Nearly 50% of all women reported vasomotor symptoms 4 years after final menstrual period, and 10% of all women reported symptoms as far as 12 years after final menstrual period. When data were examined according to symptom severity ('any' vs. 'bothersome'), bothersome symptoms peaked about 1 year earlier and declined more rapidly than symptoms of any severity level.Conclusions: Our findings suggest a median symptom duration of about 4 years among symptomatic women. A longer symptom duration may affect treatment decisions and clinical guidelines. Further prospective, longitudinal studies of menopausal symptoms should be conducted to confirm these results. [ABSTRACT FROM AUTHOR]

This study explores the ways in which women's contraceptive behavior in a rural area of Thailand is shaped by both past and present context, based on the life course framework. Although the importance of contextual influences for contraceptive behavior is well established in the literature, relatively little research has been conducted that explores how behavior is influenced by historical and contemporaneous contextual factors and by individual life experiences. In addition, much of this research has neglected the role of the normative environment within which contraceptive use takes place. The focus of this paper centers on the effect of contraceptive environment at both early and late stages of the life course and on how this effect is shaped by individual experience with migration to urban areas. This study takes advantage of a unique, prospective longitudinal data set with detailed information on community context at multiple points in time, an important improvement upon prior research. The results show that contraceptive behavior is particularly responsive to current community context, with past context primarily exerting an indirect effect on behavior through shaping current contextual influences. [ABSTRACT FROM AUTHOR]

Indian society suffers from substantial inequalities in education, employment, and income based on caste and ethnicity. Compensatory or positive discrimination policies reserve 15% of the seats in institutions of higher education and state and central government jobs for people of the lowest caste, the Scheduled Caste; 7.5% of the seats are reserved for the Scheduled Tribe. These programs have been strengthened by improved enforcement and increased funding in the 1990s. This positive discrimination has also generated popular backlash and on-the-ground sabotage of the programs. This paper examines the changes in educational attainment between various social groups for a period of nearly 20 years to see whether educational inequalities have declined over time. We use data from a large national sample survey of over 100,000 households for each of the four survey years--1983, 1987-1988, 1993-1994, and 1999-2000--and focus on the educational attainment of children and young adults aged 6-29. Our results show a declining gap between dalits, adivasis, and others in the odds of completing primary school. Such improvement is not seen for Muslims, a minority group that does not benefit from affirmative action. We find little improvement in inequality at the college level. Further, we do not find evidence that upper-income groups, the so-called creamy layer of dalits and adivasis, disproportionately benefit from the affirmative action programs at the expense of their lower-income counterparts. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) 'pulsed' with an appropriate antigen may elicit an antitumour immune response in mouse models. However, while attempting to develop a DC immunotherapy protocol for the treatment of breast cancer based on the tumour-associated MUC1 glycoforms, we found that unpulsed DCs can affect tumour growth. Protection from RMA-MUC1 tumour challenge was achieved in C57Bl/6 MUC1 transgenic mice by immunising with syngeneic DCs pulsed with a MUC1 peptide. However, unpulsed DCs gave a similar level of protection, making it impossible to evaluate the effect of immunisation of mice with DCs pulsed with the specific peptide. Balb/C mice could also be protected from tumour challenge by immunisation with unpulsed DCs prior to challenge with murine mammary tumour cells (410.4) or these cells transfected with MUC1 (E3). Protection was achieved with as few as three injections of 50,000 naïve DCs per mouse per week, was not dependent on injection route, and was not specific to cell lines expressing human MUC1. However, the use of Rag2-knockout mice demonstrated that the adaptive immune response was required for tumour rejection. Injection of unpulsed DCs into mice bearing the E3 tumour slowed tumour growth. In vitro, production of IFN-gamma and IL-4 was increased in splenic cells isolated from mice immunised with DCs. Depleting CD4 T cells in vitro partially decreased cytokine production by splenocytes, but CD8 depletion had no effect. This paper shows that naïve syngeneic DCs may induce an antitumour immune response and has implications for DC immunotherapy preclinical and clinical trials. [ABSTRACT FROM AUTHOR]

Tamoxifen (Tam) is effective for the treatment and prevention of breast cancer. However, it has toxic drawbacks and has limited-duration utility because, over time, human tumours become refractory to Tam. Recently, a new nontoxic peptide, alpha-fetoprotein-derived peptide (AFPep) has been proposed for the treatment and prevention of breast cancer. The purpose of this paper is to determine whether combining AFPep with Tam would increase efficacy and reduce toxicity in experimental models of breast cancer. Low doses of AFPep and Tam were more effective in combination than either agent alone against breast cancer growth in cell culture, in tumour-xenografted mice, and in carcinogen-exposed rats. alpha-Fetoprotein-derived peptide interfered with Tam-induced uterine hyperplasia in immature mice, and showed no toxic effects. Unlike Tam, AFPep did not inhibit binding of oestradiol (E(2)) to oestrogen receptor (ER). Thus, these two agents utilise different mechanisms to interfere with ER functionality, yet work cooperatively to reduce breast cancer growth and alleviate Tam's troubling toxicity of uterine hyperplasia and appear to be a rational combination for the treatment of ER-positive breast cancer. [ABSTRACT FROM AUTHOR]

While great strides have been made recently in improving end-of-life care in the United States, people with dementia often die with inadequate pain control, with feeding tubes in place, and without the benefits of hospice care. In this paper, we discuss the most important and persistent challenges to providing excellent end-of-life care for patients with dementia, including dementia not being viewed as a terminal illness; the nature of the course and treatment decisions in advanced dementia; assessment and management of symptoms; the caregiver experience and bereavement; and health systems issues. We suggest approaches for overcoming these barriers in the domains of education, clinical practice, and public policy. As the population ages, general internists increasingly will be called upon to provide primary care for a growing number of patients dying with dementia. There are great opportunities to improve end-of-life care for this vulnerable and underserved population. [ABSTRACT FROM AUTHOR]

Purpose: This paper reports on the development and validation of two biologic response modifier (BRM) subscales for use with the Functional Assessment of Cancer Therapy-General (FACT-G) quality of life (QOL) questionnaire.Methods: Using the FACT-G as a base, 17 additional questions related to symptoms common to interferon and retinoid therapy were developed. Data collected at baseline (n = 191) and week 2 (n = 168) in a randomized trial of interferon +/- 13-cis-retinoic acid in advanced renal cell carcinoma patients were used to validate this measure.Results: Using a combined empirical and conceptual approach, the 17 questions were reduced to 13 questions consisting of two subscales: 'BRM-physical' (7 items; baseline coefficient alpha(alpha) = 0.70; week-2 alpha = 0.75) and 'BRM-mental' (6 items; baseline alpha = 0.79; week-2 alpha = 0.78). Internal consistency of the trial outcome index (TOI) combining physical well-being, functional well-being and the BRM subscales, was 0.91 for baseline assessments and 0.92 for week 2. Discriminant validity was demonstrated for the TOI by its ability to differentiate among prognostic risk groups, and for the total FACT-G, TOI and total FACT-BRM scores by their ability to distinguish between groups differing in performance, response and toxicity status.Conclusions: The 'BRM-physical' and 'BRM-mental' subscales can be combined with the FACT-G to form the 'FACT BRM' scale, useful for measuring QOL in cancer patients who are receiving treatment with biologic response modifiers. [ABSTRACT FROM AUTHOR]

We have previously reported that interleukin 10 (IL-10) signalling stimulated activation of a specific enhancer element, termed HTE-1, to promote tissue inhibitor of matrix metalloproteinase1 (TIMP-1) expression in human bone metastatic PC-3 subclone (PC-3 ML) cells. Recently, we have identified an IL-10 responsive signal molecule, termed IL-10E1, which binds the HTE-1 element and cloned the gene encoding for the 22 kDa protein. In this paper, we have examined the mechanism of IL-10/IL-10 receptor signalling in two distinct human prostate cell lines, a 'normal' prostate epithelial cell line, termed NPTX-1532 and highly metastatic PC-3 ML tumour cells. Signalling cascade studies revealed that IL-10 stimulated tyrosine phosphorylation of JAK1 and TYK2 receptor kinases and tyrosine phosphorylation of IL-10E1. Phosphorylation, triggered IL-10E1's rapid translocation to the nucleus by 10-30 min. Deletion analysis combined with transient transfection experiments revealed that the n-terminal domain (approximately 74 a.a.) of the IL-10E1 protein, the nt-nls peptide, was stimulated by IL-10 to translocate to the nucleus and induce TIMP-1 expression. Site-directed mutagenesis further showed that phosphorylation of two tyrosine moieties (Y57 and Y62) of the nt-nls peptide was required for IL-10 activation of signalling and TIMP-1 expression. The data demonstrate, for the first time, that IL-10 receptor signalling of TIMP-1 expression is regulated by tyrosine phosphorylation of a novel gene, IL-10E1, in human prostate cells. [ABSTRACT FROM AUTHOR]

Although women had been under recognized in the literature on HIV/AIDS, increasing numbers of studies have focused on the lives and experiences of women living with HIV/AIDS. Areas of research in which the study of women and HIV continues to be noticeably lacking include health related quality of life (HRQOL). This paper describes HRQOL in an inner city sample of 287 HIV positive non-pregnant women, interviewed as part of a larger multi-site CDC funded study of the reproductive health of women. The average age of the respondents was 33 years and women had known their HIV status an average of 41 months. HRQOL was assessed using a 17-item modified version of the Medical Outcomes Study-HIV Health Survey and demonstrated acceptable internal consistency (0.64-0.89) and variability. Women in our study were similar to other HIV-positive female samples and reported lower levels of well-being and functioning than some HIV-positive male samples. Women's responses to individual items and areas of potential need for health care are discussed. Examination of HRQOL in women with HIV can aid in the comparison of how women and men are affected by HIV and can help health care professionals identify needed services and include possible interventions to promote quality of life. [ABSTRACT FROM AUTHOR]

This paper reports on results of the EORTC protocol 30892, an open, prospective, randomized study of 310 patients with previously untreated metastatic prostate cancer with favourable prognostic factors who were treated by either flutamide (FLU) or cyproterone acetate (CPA) monotherapy. The final analysis with regard to the main end points, time to progression and survival are still pending. Final results related to the evaluation of sexual functioning prior to and under treatment are reported here. Of 310 randomized patients 294 were eligible for evaluation within this side study. The median age was 71 years (range 48-85). Potential risk factors related to age, general health and prostate cancer were evaluated. For evaluation of sexual functions a five-item questionnaire was used which was administered by the investigator. The protocol allowed time dependent observations at 3-monthly follow-up visits. Sexual functioning was dependent on age but not on prostate cancer-related parameters. Sexual functions at entry were similar within the two treatment groups, spontaneous (nightly) erections and sexual activity were seen in 43-51% and 29-35% of cases. Under treatment, sexual functions under FLU and CPA declined slowly with median times of 12.9 and 5.8 months versus 13.7 and 8.9 months respectively for spontaneous erections and sexual activity. Eventually, with an average observation time in excess of 2 years, loss of spontaneous erections and of sexual activity occurred in 80% versus 92% and in 78% versus 88% of men under FLU versus CPA treatment respectively. None of these differences reached statistical significance. Maintenance of potency under treatment with FLU as reported in the literature is not confirmed in this study. However, loss of sexual functions under monotherapy with both antiandrogens is slow and 10-20% of men retain sexual activity after 2-6 years of treatment. This observation can be exploited in new treatment schemes and is likely to lead to improved quality of life. The advantage of FLU in time and total preservation of sexual functions is statistically not significant and must be balanced against the side effects of FLU and other pure antiandrogens, which may exceed those of CPA especially with respect to gynaecomastia. Hepatic toxicity may limit the long-term use of both drugs. [ABSTRACT FROM AUTHOR]

The development of new pharmaceutical interventions for persons with human immunodeficiency virus (HIV) infection has resulted in extended survival and a need for valid, reliable and responsive instruments to assess health-related QoL (HRQoL). This paper reviews the reliability and validity of an HRQoL instrument, the AIDS Health Assessment Questionnaire (AIDS-HAQ), among persons participating in an observational database of HIV infection. The AIDS-HAQ includes nine subscales: disability, energy, general health, pain, cognitive functioning, mental health, social functioning, health distress and symptoms. Individuals complete the AIDS-HAQ quarterly. Data are reported for 440 individuals entering the study with early HIV infection. Fifty-nine progressed to symptomatic disease and 109 to AIDS after 1 year. The subscales of the instrument resulted in high internal consistency reliability (range = 0.79-0.88). Concurrent validity data reflected the ability to distinguish between patients with increasing disease severity. In all domains, except cognitive functioning, individuals who progressed to AIDS had significant decrements (p < 0.01) in HRQoL compared with symptomatic and asymptomatic patients. Significant decrements (p < 0.01) were observed for disability, general health, energy and symptoms for patients who progressed to symptomatic disease from an asymptomatic status. Individuals who had decreasing CD4+ counts also had significant declines (p < 0.001) in disability, general health, social functioning, pain and symptoms. The AIDS-HAQ is an instrument that can be used when comparing group differences and within group changes in observational databases, naturalistic studies and clinical trials. [ABSTRACT FROM AUTHOR]