The utility of the implementation science framework “Integrated Promoting Action on Research Implementation in Health Services” (i-PARIHS) and the facilitator role for introducing patient-reported outcome measures (PROMs) in a medical oncology outpatient department

Quality of Life Research - We evaluated the utility of the implementation science framework “Integrated Promoting Action on Research Implementation in Health Services” (i-PARIHS) for...     

Neurotensin-like Peptides in the CNS of Lampreys: Chromatographic Characterization and Immunohistochemical Localization with Reference to Aminergic Markers

Neurotensin (NT)-like peptides in the CNS of the lamprey Lampetra fluviatilis were studied by radioimmunoassay (C-terminal specific NT antiserum), reverse-phase HPLC and immunohistochemistry. Multiple peaks of NT-immunoreactive (-ir) material were observed upon HPLC, of which a major peak eluted in the position of bovine NT. Immunofluorescence histochemistry showed that a monoclonal antibody recognizing the N-terminal (1 - 11) fragment of NT, as well as two polyclonal NT antisera labelled a large number of cell bodies in the periventricular area of hypothalamus, including the postinfundibular commissural nucleus and the ventral and dorsal hypothalamic nuclei. Additional groups of NT-ir cells were observed in the preoptic nucleus, the postoptic commissural nucleus, the mesencephalic tegmentum (L.fluviatilis), and in the spinal cord (L.fluviatilis and Ichtyomyzon unicuspis). Dense NT-ir fibre plexuses were present in the caudal hypothalamus, corpus striatum, ventral mesencephalon, and in the dorsal horn and lateral margin of the spinal cord. At the ultrastructural level the lateral spinal margin showed NT-ir terminal structures, which in most cases were not associated with synaptic specializations, although occasional synaptic contacts with unlabelled elements were found. The relation between NT-ir and monoamine-containing cells was examined with immunofluorescence double-staining, using antisera to tyrosine hydroxylase (TH), 5-hydroxytryptamine (5-HT), and histamine respectively. In the periventricular nuclei of hypothalamus numerous TH-, 5-HT-, as well as histamine-ir cells were located in close association with NT-ir cells, but none of the aminergic markers could be detected within NT-ir neurons. The chemical properties as well as the anatomical distribution of lamprey NT-like peptides show several similarities with those present in mammals, suggesting that NT-containing neuronal systems in the CNS developed early in vertebrate phylogeny.     

A clinical comparison of indices of pulmonary gas exchange with changes in the inspired oxygen concentration

Several indices have been introduced as convenient alternatives to calculation of the physiological shunt fraction (Qs/QT) for the assessment of pulmonary gas exchange. These include: the arterial-alveolar oxygen tension ratio (a/APO2), the arterial oxygen tension-inspired oxygen concentration ratio (PaO2/FIO2), the respiratory index (RI), [A-a)DO2/PaO2) and the alveolar-arterial oxygen tension difference [A-a)Do2). These indices are in use clinically despite the fact that they may not accurately predict gas exchange in situations where FIO2, Qs/QT or arterial-venous oxygen content is changing. The clinical stability of each of these indices, relative to the behaviour of the physiological shunt, was therefore investigated prospectively in ten mechanically ventilated postoperative adults as FIO2 was varied from 0.30 to 1.00. None of the indices studied reliably reflected the behaviour of the physiological shunt. As FIO2 was increased incrementally from 0.30 to 1.00, 42 to 55 per cent of the measured changes in these indices were opposite in direction to the corresponding changes in the physiological shunt. The maximum magnitudes of the opposite changes were substantial; 24 and 22 per cent for the a/APO2 and PaO2/FIO2 ratio respectively, 67 per cent for the RI and 101 per cent for the (A-a)DO2. We conclude that the use of any of these indices for clinical assessment of a patient's gas exchange defect when FIO2 is varying can be substantially misleading.     

An analysis of multinucleated blastomere formation in human embryos

Human embryos were disaggregated into component blastomeres42–72 h after insemination. The blastomeres were scoredfor the number of nuclei present and blastomeres of known nuclearmorphology were returned to individual culture drops for 16–20h, after which they were scored for cleavage and nuclear morphology.In all, 48% of mononucleated blastomeres cleaved during thisperiod, but only 76% of these produced two mononucleated daughterblastomeres; in the remainder, one or more of the blastomereswas abnormally nucleated. During overnight culture, 30% of multinucleatedblastomeres and 30% of anucleate blastomeres cleaved, the majorityproducing abnormally nucleated daughter blastomeres. The majorityof blastomeres which showed no sign of cleavage after overnightculture retained the same nuclear morphology as when originallydisaggregated. However, a small number of mononucleated blastomerescontained two nuclei after culture, indicating that karyokinesismay have taken place in the absence of cytokinesis. Overall,30% of blastomeres with more than one nucleus seemed to ariseby this mechanism, the remainder probably arising by errorsof chromosome segregation and/or packaging at mitosis. In addition,25/111 mononucleated daughter cells arose either after abnormaldivision of mononucleated parent cells or after division ofmultinucleated cells, suggesting that 23% of newly formed mononucleatedcells might be chromosomally abnormal. The results of DNA quantitationindicated that very few (12/131, 9.2%) blastomeres (whetheruni-or multinucleated) had a DNA content outside the 2-4C range.The embryos used for these studies had been cultured in oneof three commonly used in-vitro fertilization (IVF) media: modifiedT6, Earle's balanced salts or Universal IVF medium (a commercialmedium from Medi-Cult). A retrospective analysis was carriedout of the number of embryos containing multinucleated blastomeresat disaggregation and of the total proportion of isolated blastomereswhich were multinucleated in three groups of embryos, each ofwhich had been cultured in one of the IVF media. Both theseparameters were found to vary between cohorts of embryos culturedin the different media. The mechanism(s) by which culture mediumcomposition might affect multinucleation of human blastomeresis discussed, as is the significance of these data for reliablepreimplantation diagnosis of genetic status. aberrant cleavage/acytokinesis/culture medium/multinucleated blastomeres     

Public involvement in health care priority setting: an economic perspective

Background  Public involvement in health care decision making and priority setting in the UK is being promoted by recent policy initiatives. In 1993, the British Medical Association called for public consultation where rationing of services was to be undertaken. The approach to priority setting advocated by many health economists is the maximization of quality adjusted life years (QALYs). Typically, for a particular health care programme, the QALY calculation takes account of four features: (1) the number of patients receiving the programme, (2) the survival gain, (3) the gain in quality of life and, (4) the probability of treatment success. Only one feature, that relating to quality of life, is based upon public preferences. If the QALY is to be used as a tool for health care resource allocation at a societal level then it should incorporate broader societal preferences.
Methods  This study used an interview-based survey of 91 members of the general public to explore whether the traditional QALY maximization model is a good predictor of public responses to health care priority setting choices.
Results and conclusions  Many respondents did not choose consistently in line with a QALY maximization objective and were most influenced by quality of life concerns. There was little support for health care programmes that provided a prognostic improvement but left patients in relatively poor states of health. The level of respondent engagement in the survey exercise was not sensitive to the provision of supporting clinical information.     

Medicine misuse or drug abuse? A critical appraisal of current issues and research in the UK

During the last decade consumption of licit medications and illicit drugs has risen substantially. It is estimated that the 100 000–200 000 severely dependent drug misusers in the UK generate social costs of 3–4 billion annually, while the cost of prescribed medicines for the entire population is currently 5 billion. Although attitudes and behaviours have been extensively researched, they remain complex and often contradictory. In particular, little is known of how perceptions of the benefits and risks of chemical substances influence behaviour. At an epidemiological level, new methods such as capture–recapture are being used to delineate forms of drug abuse which have previously not been detected in household surveys. There are few current data on the extent of inappropriate medicine prescribing, although there are various initiatives to promote rational and cost-effective prescribing. Reasons for inappropriate medicine use include patient expectations, prescribers' perceptions of patients and drug company marketing. Advances in basic science are revealing hitherto unsuspected consequences of both licit and illicit drug use. Examples include (1) the role of analgesics in causing severe headache and (2) suppression of immune functioning due to Ecstasy. One illustration of changing attitudes, as a result of public and medical pressure, is the growing call for the licensing of cannabis for medicinal use, particularly for intractable conditions such as multiple sclerosis. With the recently announced drug strategy promising a shift towards evidence-based decision-making, innovative research is required to improve the currently fragmentary view of the general population's attitudes and behaviour in relation to medicines and drugs.