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PubMed2001

Is informed choice in genetic testing a different breed of informed decision-making? A discussion paper.

Traditionally genetic counselling has promoted a non-directive approach to patients' decision-making but the feasibility of this has been questioned. Unlike most branches of medicine, which are shifting away from a paternalistic model, genetic counselling is approaching shared decision-making from a different perspective. There are certain features of genetic counselling and genetic testing which may complicate the drive towards shared decision-making and informed choice: 1. Genetic test results can have broader implications than non-genetic test results. 2. Genetic test results may be perceived by the patient differently to non-genetic test results. 3. Carrier status for autosomal recessive conditions may be difficult for patients to conceptualize. 4. Decisions in genetic counselling are often multiple and sequential. 5. Most information in genetic counselling is based on probabilities and uncertainties. Each of these features is discussed in relation to achieving shared decision-making in genetic testing and the implications for genetic counsellors are described. The points raised, however, have broader implications for medicine as several of the features, although central to genetic testing, are not entirely unique. Lessons learnt from genetic testing and genetic counselling in achieving shared decision-making could help develop methods of promoting informed choice in other medical arenas such as cancer screening.

Decision Making↗

PubMed2002

CT and MR in pulmonary embolism: A changing role for nuclear medicine in diagnostic strategy.

The goal of this article is to summarize current data on computed tomography (CT) and magnetic resonance (MR) in the diagnosis of acute pulmonary embolism (PE) in relation to the radionuclide ventilation perfusion scan. It is important for the nuclear medicine, CT, and MR communities to develop a shared approach to this disorder. Triage using chest radiographs appears to be a practical method for enhancing both nuclear medicine and CT/MR performance. The realization that there is no clinically available gold standard for the diagnosis of PE suggests that the imaging community should replace impractical and idealistic discussions with more realistic outcome-oriented approaches. A simplified one-step evaluation of the pulmonary arteries and the lower extremity veins for deep venous thrombus can provide a comprehensive examination for PE. CT is currently a more practical diagnostic tool, whereas MR offers a scientific probe for pulmonary physiology including the regional mapping of ventilation-perfusion relationships. Nuclear medicine, CT, and MR thus form an imaging triad for the diagnosis of acute PE.

Humans↗

PubMed1989

Glucose effects on cytoplasmic Ca2+ of individual pancreatic beta-cells recorded by two procedures for dual-wavelength fluorometry.

Two different dual-wavelength microfluorometric systems were used to measure the cytoplasmatic Ca2+ concentration (Cai2+) of individual pancreatic beta-cells loaded with the indicator fura-2. Fluorescence was excited continuously at 340 nm with frequent manual checks at 360 nm. Alternatively, the 340/380 nm fluorescence excitation ratio was recorded based on automated samples at the two wavelengths every 10 msec. Irrespective of the experimental technique a rise of the glucose concentration from 3 to 20 mM resulted in an initial lowering of Cai2+ followed by a rise with a peak and a subsequent sustained intermediary level. The increase of Cai2+ depended on the presence of extracellular Ca2+. In some cells the pattern differed and the increase of the glucose concentration induced large oscillations of Cai2+. Glucose-induced increase of Cai2+ was associated with small rapid fluctuations, which were detectable only with the fast time-sharing approach. The characteristic Cai2+ response to glucose was maintained by some beta-cells after culture for more than 3 weeks. The results indicate that the glucose sensitivity of individual beta-cells varies, and that many electrically coupled cells within an islet collectively determine the characteristic pattern of rhythmic depolarization.

Animals↗

PubMed1992

Australian reports into drug use and the possibility of heroin maintenance.

Official Australian reports into drug use reveal a high level of agreement over the nature of drug use and the problems associated with drug use. We examine the lines of argument which make up the shared approach of past reports into drugs, and assess to what degree the connections between these lines of argument are changing. This assessment reflects on the possibility of arguing that heroin should be made available for the treatment (including maintenance) of heroin-dependent users. This paper is derived from a report prepared for a feasibility study which examined whether or not heroin should be made available in the Australian Capital Territory in a controlled manner. After a close reading of a number of official reports, we conclude that it is possible to argue that heroin should become available.

Journal Article↗

PubMedDate not supplied

Integrating approaches to psychotherapy in psychosis*.

OBJECTIVE: The evidence base for specific psychological treatments for psychosis is now well established, but many practitioners see themselves as integrationist in approach. The basic tenets of integration are explored with an emphasis on understanding how different levels of need can be conceptualized and then used to 'adapt' a treatment to meet those needs in an individual. The needs are then incorporated into an integrated treatment formulation. METHOD: The evidence base is strongest for cognitive behavioural and family approaches, but the present paper summarizes concepts from two specific models of therapy that are intrinsically integrational in their approach: cognitive analytic therapy and psychodynamic interpersonal therapy. RESULTS: Both approaches show aspects of integration. However, following this approach to integration to its limit would ultimately lead to one undifferentiated therapy. CONCLUSIONS: Both approaches share a common set of values of developing specific ways of increasing collaboration and working together, and these values are shown to underpin adaptive ways of working with psychosis, but further critical analysis of the development of integrative models is needed.

Adult↗

PubMed2002

A new essential hypertension susceptibility locus on chromosome 2p24-p25, detected by genomewide search.

Essential hypertension (EH) is a complex disorder that results from the interaction of a number of susceptibility genes and environmental factors. We studied an isolated Sardinian village (Talana) in which the prevalence of hypertension is comparable to that in most Western populations. Talana exhibits features, such as slow demographic growth, high inbreeding, a low number of founders, stable lifestyle and culture, and accurate genealogical records, that make it suitable for the study of complex disorders. Clinical assessment of the entire adult population (N= approximately 1,000) identified approximately 100 hypertensive subjects. For our study, we selected the individuals with the most-severe EH (i.e., diastolic blood pressure >100 mm Hg), belonging to a single deep-rooted pedigree (12 generations), whose common ancestors lived in the 17th century. We performed a three-stage genomewide search using 36 affected individuals, by means of parametric linkage and allele-sharing approaches. LOD scores >1 were observed on chromosomes 1, 2, 13, 15, 17, and 19 (stage I). The most striking result was found in a 7.57-cM region on chromosome 2p24-p25. All five nonparametric linkage statistics estimated by the SimWalk2 program lie above the significance threshold of P<.008 for the whole region. Similar significance was obtained for 2p24-25 when parametric linkage (LOD score 1.99) and linkage disequilibrium mapping (P=.00006) were used, suggesting that a hypertension-susceptibility locus is located between D2S2278 and D2S168. This finding is strengthened by a recent report of linkage with marker D2S168 in a hypertensive sib-pair sample from China.

Chromosome Mapping↗

PubMed1995

Health as an objective value.

Variants on two approaches to the concept of health have dominated the philosophy of medicine, here referred to as 'reductionist' and 'relativist'. These two approaches share the basic assumption that the concept of health cannot be both based on an empirical biological foundation and be evaluative, and thus adopt either the view that it is 'objective' or evaluative. It is here argued that there are a subset of value concepts that are formed in recognition of certain fundamental facts about living organisms, among which is the concept of health. These are not yet moral concepts, but they are 'normative' or 'evaluative'. The view is defended that health, so understood, is a fundamental concept in the process of medical diagnosis and treatment.

Attitude to Health↗

PubMed1998

PSA screening for prostate cancer: the current controversy--a viewpoint. Patient Outcomes Research Team for Prostatic Diseases.

Prostate cancer is an important health problem. Randomized trials have not yet proven whether or not screening with prostate-specific antigen measurements reduces morbidity or mortality. The potential for overtreatment of prostate cancers not destined to cause future mortality, the uncertainty about the benefits of aggressive treatment of screen-detected cancers, and the relatively high costs of prostate cancer screening programs are all areas of concern. A shared approach to decisions about screening individual patients pending better evidence is one strategy for clinicians to consider in dealing with this controversial problem.

Aged↗

PubMed2002

Partners in healing: home care, hospice, and parish nurses.

A creative way to support patients in self-care strategies is to work with the parish nurse as a practice partner. This article shares approaches and innovative ideas on how home care and hospice nurses can work effectively with parish nurses.

Community Health Nursing↗

PubMed2004

Challenges in end-of-life care in the ICU: statement of the 5th International Consensus Conference in Critical Care: Brussels, Belgium, April 2003: executive summary.

OBJECTIVE: The purpose of the conference was to provide clinical practice guidance in end-of-life care in the ICU via answers to previously identified questions relating to variability in practice, inadequate predictive models for death, elusive knowledge of patient preferences, poor communication between staff and surrogates, insufficient or absent training of healthcare providers, the use of imprecise and insensitive terminology and incomplete documentation in the medical record. PARTICIPANTS: Presenters and jury were selected by the sponsoring organizations (American Thoracic Society, European Respiratory Society, European Society of Intensive Care Medicine, Society of Critical Care Medicine, Société de Réanimation de Langue Française). Presenters were experts on the question they addressed. Jury members were general intensivists without special expertise in the areas considered. Experts presented in an open session to jurors and other healthcare professionals. EVIDENCE: Experts prepared review papers on their specific topics in advance of the conference for the jury's reference in developing the consensus statement. CONSENSUS PROCESS: Jurors heard experts' presentations over 2 days and asked questions of the experts during the open sessions. Jury deliberation with access to the review papers occurred for 2 days following the conference. A writing committee drafted the consensus statement for review by the entire jury. The 5 sponsoring organizations reviewed the document and suggested revisions to be incorporated into the final statement. CONCLUSIONS: Strong recommendations for research to improve end-of-life care were made. The jury advocates a shared approach to end-of-life decision-making involving the caregiver team and patient surrogates. Respect for patient autonomy and the intention to honor decisions to decline unwanted treatments should be conveyed to the family. The process is one of negotiation, and the outcome will be determined by the personalities and beliefs of the participants. Ultimately, it is the attending physician's responsibility, as leader of the team, to decide on the reasonableness of the planned action. If a conflict cannot be resolved, an ethics consultation may be helpful. The patient must be assured of a pain-free death. The jury subscribes to the moral and legal principles that prohibit administering treatments specifically designed to hasten death. The patient must be given sufficient analgesia to alleviate pain and distress; if such analgesia hastens death, this "double-effect" should not detract from the primary aim to ensure comfort.

Belgium↗

PubMed2005

Advances in chemical genetics.

Chemical genetics is an emerging approach for studying biological systems using chemical tools. This strategy aims to reveal the macromolecules responsible for regulating biological systems; thus, the approach shares much in common with genetics. In both strategies, one must (a) develop an assay that reports on a biological process of interest, (b) perturb this process systematically (with mutations or small molecules), and (c) determine the target of each perturbation to reveal macromolecules (i.e., proteins and genes) regulating the process of interest. In this review, we discuss advances and challenges in this field that have emerged over the past four years. Several technologies have converged, raising the hope that it may be possible to systematically apply chemical probes to biological processes.

Combinatorial Chemistry Techniques↗

PubMed2005

Haplotype-sharing analysis for alcohol dependence based on quantitative traits and the Mantel statistic.

Haplotype-based methods have become increasingly popular in the last decade because shared lengths in haplotypes can be used for disease localization. In this contribution, we propose a novel linkage-based haplotype-sharing approach for quantitative traits based on the class of Mantel statistics which is closely related to the weighted pair-wise correlation statistic. Because these statistics are known to be liberal, we propose a permutation test to evaluate significance. We applied the Mantel statistic to the autosomal data from the genome-wide scan of the Collaborative Study on the Genetics of Alcoholism with the Affymetrix Genotype 10 K array that was provided for the Genetic Analysis Workshop 14. Four regions on chromosome 4, 8, 16, and 20 showed p-values less than 0.005 with a minimum p-value of < 0.0001 on chromosome 16 (tsc0520638 at 72.8 cM). Three of these four regions located on chromosome 4, 16, and 20 have been reported previously in the Genetic Analysis Workshop 11.

Alcoholism↗

PubMed2005

PSA testing for prostate cancer: an online survey of the views and reported practice of General Practitioners in the UK.

BACKGROUND: The role of Prostate Specific Antigen (PSA) testing in the early detection of prostate cancer is controversial. Current UK policy stipulates that any man who wishes to have a PSA test should have access to the test, provided he has been given full information about the benefits and limitations of testing. This study aimed to determine UK GPs' current reported practice regarding PSA testing, and their views towards informed decision-making and PSA testing. METHOD: Online questionnaire survey, with a sample of 421 GPs randomly selected from a database of GPs across the UK. RESULTS: 95% (400/421) of GPs responded. 76% of GPs reported having performed a PSA test for an asymptomatic man at least once in the previous three months, with 13% reported having tested more than five men in this period. A majority of GPs reported they would do a PSA test for men presenting with a family history and requesting a test, for asymptomatic men requesting a test and also for men presenting with lower urinary tract symptoms. Reported testing rates were highest for men with a family history. Amongst men with lower urinary tract symptoms and men with no symptoms, reported testing rates were significantly higher for older than younger men. The majority of GPs expressed support for the current policy (67%), and favoured both the general practitioner and the man being involved in the decision making process (83%). 90% of GPs indicated that they would discuss the benefits and limitation of testing with the man, with most (61%) preferring to ask the man to make a further appointment if he decides to be tested. CONCLUSION: This study indicates that PSA testing in asymptomatic men is a regular occurrence in the UK, and that there is general support from GPs for the current policy of making PSA tests available to 'informed' men who are concerned about prostate cancer. While most GPs indicated they would discuss the benefits and limitations prior to PSA testing, and most GPs favoured a shared approach to decision making, it is not known to what extent men are actually being informed. Research is needed to evaluate the most effective approach to assisting men in making an informed decision about whether or not to have a PSA test.

Adult↗

PubMedDate not supplied

The male menopause: possible causes, symptoms and treatment.

This article discusses the controversial concept of the male menopause, by explaining what the literature reveals about this condition. It does not wish to put forward a case for treating men with the male menopause with hormone replacement therapy, merely to provide information to nurses who may nurse men with the symptoms associated with the disorder. Definitions of key terms, i.e. male menopause, are considered and the endocrinological changes that occur with ageing are outlined. Assessment of the extent of the problem is confounded by the concept of definition. Some middle-aged men often describe similar symptoms that women describe associated with the menopause; therefore it may be reasonable to suggest that an andropause with an endocrine basis does exist. The investigations undertaken to make a diagnosis are described and treatments available are discussed. A shared approach to the care for men with menopausal symptoms is advocated. The role the nurse plays is described and recommendations for practice suggested. Finally, a conclusion is offered and a call is made for further empirical investigations to be made available, to ensure that men are provided with safe effective care based on the best available evidence.

Aging↗

PubMed2007

A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism.

BACKGROUND: HIV protease inhibitor (PI) therapy results in the rapid selection of drug resistant viral variants harbouring one or two substitutions in the viral protease. To combat PI resistance development, two approaches have been developed. The first is to increase the level of PI in the plasma of the patient, and the second is to develop novel PI with high potency against the known PI-resistant HIV protease variants. Both approaches share the requirement for a considerable increase in the number of protease mutations to lead to clinical resistance, thereby increasing the genetic barrier. We investigated whether HIV could yet again find a way to become less susceptible to these novel inhibitors. METHODS AND FINDINGS: We have performed in vitro selection experiments using a novel PI with an increased genetic barrier (RO033-4649) and demonstrated selection of three viruses 4- to 8-fold resistant to all PI compared to wild type. These PI-resistant viruses did not have a single substitution in the viral protease. Full genomic sequencing revealed the presence of NC/p1 cleavage site substitutions in the viral Gag polyprotein (K436E and/or I437T/V) in all three resistant viruses. These changes, when introduced in a reference strain, conferred PI resistance. The mechanism leading to PI resistance is enhancement of the processing efficiency of the altered substrate by wild-type protease. Analysis of genotypic and phenotypic resistance profiles of 28,000 clinical isolates demonstrated the presence of these NC/p1 cleavage site mutations in some clinical samples (codon 431 substitutions in 13%, codon 436 substitutions in 8%, and codon 437 substitutions in 10%). Moreover, these cleavage site substitutions were highly significantly associated with reduced susceptibility to PI in clinical isolates lacking primary protease mutations. Furthermore, we used data from a clinical trial (NARVAL, ANRS 088) to demonstrate that these NC/p1 cleavage site changes are associated with virological failure during PI therapy. CONCLUSIONS: HIV can use an alternative mechanism to become resistant to PI by changing the substrate instead of the protease. Further studies are required to determine to what extent cleavage site mutations may explain virological failure during PI therapy.

Amino Acid Sequence↗

PubMed2006

Microarray technology as a universal tool for high-throughput analysis of biological systems.

Over the last years microarray technology has become one of the principal platform technologies for the high-throughput analysis of biological systems. Starting with the construction of first DNA microarrays in the 1990s, microarray technology has flourished in the last years and many different new formats have been developed. Peptide and protein microarrays are now applied for the elucidation of interaction partners, modification sites and enzyme substrates. Antibody microarrays are envisaged to be of high importance for the high-throughput determination of protein abundances in translational profiling approaches. First cell microarrays have been constructed to transform microarray technology from an in vitro technology to an in vivo functional analysis tool. All of these approaches share a common prerequisite: the solid support on which they are generated. The demands on this solid support are thereby as manifold as the applications themselves. This review is aimed to display the recent developments in surface chemistry and derivatization, and to summarize the latest developments in the different application areas of microarray technology.

Antibodies, Monoclonal↗

PubMed1978

Decision-sharing in elementary school children: effects on body-concept and anxiety.

To determine the effects of teacher-directed and decision-sharing models of instruction on the development of body-concept and reduction of anxiety 99 Greensboro public school children in Grades 3 and 4 participated in either a movement program in which the teacher made all the decisions or in a program where they shared in the decision-making. The Cheffers adaptation of Flanders' Interaction Analysis System was used to verify the two treatments. The dependent variables were measured by Osgood's semantic differential for body-concept measures, and Sarason's General Anxiety Scale for Children. There was no significant difference between the groups for improvement in body-concept. Also, girls have more positive concepts about their bodies than do boys. Anxiety scores indicated that levels in fourth-grade children appear to be reduced when exposed to a teacher-directed model. However, a decision-sharing approach had a significant effect on reducing anxiety levels in third-grade children.

Anxiety↗

PubMed2002

The rising generation: laying claim to the health of adolescents in English Canada, 1920-70.

During the opening years of "Canada's Century," adolescents came to constitute a "youth problem," another of the often-overlapping "social problems" of the day. Medical doctors formed a significant cohort among those authorized to identify such potential threats to the national health, in its every sense. As they successfully professionalized, modernized, and took the reins of a burgeoning child welfare movement, doctors became increasingly interested in adolescents. This essay considers the medicalization of adolescence in English Canada between 1920 and 1970. During this half-century, doctors and other "experts" shaped and shared approaches to the all-encompassing "health" of the young, in collectively theorizing a modern adolescence.

Adolescent↗