Guidance on guidelines: Understanding the evidence on the uptake of health care guidelines

Rationale Regardless of health issue, health sector, patient condition, or treatment modality, the chances are that provision is supported by “a guideline” making professionally endorsed recommendations on best practice. Against this background, research has proliferated seeking to evaluate how effectively such guidance is followed. These investigations paint a gloomy picture with many a guideline prompting lip service, inattention, and even opposition. This predicament has prompted a further literature on how to improve the uptake of guidelines, and this paper considers how to draw together lessons from these inquiries. Methods This huge body of material presents a considerable challenge for research synthesis, and this paper produces a critical, methodological comparison of 2 types of review attempting to meet that task. Firstly, it provides an overview of the current orthodoxy, namely, “thematic reviews,” which aggregate and enumerate the “barriers and facilitators” to guideline implementation. It then outlines a “realist synthesis,” focussing on testing the “programme theories” that practitioners have devised to improve guideline uptake. Results Thematic reviews aim to provide a definitive, comprehensive catalogue of the facilitators and barriers to guideline implementation. As such, they present a restatement of the underlying problems rather than an improvement strategy. The realist approach assumes that the incorporation of any guideline into current practice will produce unintended system strains as different stakeholders wrestle over responsibilities. These distortions will prompt supplementary revisions to guidelines, which in turn beget further strains. Realist reviews follow this dynamic understanding of organisational change. Conclusions Health care decision makers operate in systems that are awash with guidelines. But guidelines only have paper authority. Managers do not need a checklist of their pros and cons, because the fate of guidelines depends on their reception rather than their production. They do need decision support on how to engineer and reengineer guidelines so they dovetail with evolving systems of health care delivery

Skin-derived fibroblasts from long-lived species are resistant to some, but not all, lethal stresses and to the mitochondrial inhibitor rotenone

Fibroblast cell lines were developed from skin biopsies of eight species of wild-trapped rodents, one species of bat, and a group of genetically heterogeneous laboratory mice. Each cell line was tested in vitro for their resistance to six varieties of lethal stress, as well as for resistance to the nonlethal metabolic effects of the mitochondrial inhibitor rotenone and of culture at very low glucose levels. Standard linear regression of species-specific lifespan against each species mean stress resistance showed that longevity was associated with resistance to death induced by cadmium and hydrogen peroxide, as well as with resistance to rotenone inhibition. A multilevel regression method supported these associations, and suggested a similar association for resistance to heat stress. Regressions for resistance to cadmium, peroxide, heat, and rotenone remained significant after various statistical adjustments for body weight. In contrast, cells from longer-lived species did not show significantly greater resistance to ultraviolet light, paraquat, or the DNA alkylating agent methylmethanesulfonate. There was a strong correlation between species longevity and resistance to the metabolic effects of low-glucose medium among the rodent cell lines, but this test did not distinguish mice and rats from the much longer-lived little brown bat. These results are consistent with the idea that evolution of long-lived species may require development of cellular resistance to several forms of lethal injury, and provide justification for evaluation of similar properties in a much wider range of mammals and bird species.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73523/1/j.1474-9726.2006.00255.x.pd

Altered growth characteristics of skin fibroblasts from wild-derived mice, and genetic loci regulating fibroblast clone size

Mouse fibroblast senescence in vitro is an important model for the study of aging at cellular level. However, common laboratory mouse strains may have lost some important allele variations related to aging processes. In this study, growth in vitro of tail skin fibroblasts (TSFs) derived from a wild-derived stock, Pohnpei (Pohn) mice, differed from growth of control C57BL/6 J (B6) TSFs. Pohn TSFs exhibited higher proliferative ability, fewer apoptotic cells, decreased expression of Cip1 , smaller surface areas, fewer cells positive for senescence associated-β-galactosidase (SA-β-gal) and greater resistance to H 2 O 2 -induced SA-β-gal staining and Cip1 expression. These data suggest that TSFs from Pohn mice resist cellular senescence-like changes. Using large clone ratio (LCR) as the phenotype, a quantitative trait locus (QTL) analysis in a Pohn/B6 backcross population found four QTLs for LCR: Fcs1 on Chr 3 at 55 cm; Fcs2 on Chr X at 50 cm; Fcs3 on Chr 4 at 51 cm and Fcs4 on Chr 10 at 25 cm. Together, these four QTLs explain 26.1% of the variations in LCRs in the N2 population. These are the first QTLs reported that regulate fibroblast growth. Glutathione S transferase mu ( GST-mu ) genes are overrepresented in the 95% confidence interval of Fcs1 , and Pohn TSFs have higher H 2 O 2 -induced GST-mu 4 , 5 and 7 mRNA levels than B6 TSFs. These enzymes may protect Pohn TSFs from oxidation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71416/1/j.1474-9726.2006.00208.x.pd

Despite the presence of UVB-induced DNA damage, HLA-DR+ cells from ex vivo UVB-exposed human skin are able to migrate and show no impaired allostimulatory capacity

In this study, we investigated the effect of ultraviolet B radiation on human Langerhans cell function. Normal human skin was irradiated ex vivo with single doses of ultraviolet B. For assessment of T-cell stimulatory function, cells that spontaneously migrated from epidermal sheets were used, whereas full-thickness skin biopsies were used to investigate alterations in migratory properties. The cells migrating from ultraviolet B-exposed epidermal sheets demonstrated a decrease in the percentage of HLA-DR positive Langerhans cells, as well as a reduced capacity to induce proliferation of allogeneic T cells, when compared with cells migrating from nonexposed sheets. When a correction was made for the decreased number of HLA-DR positive Langerhans cells migrating from ultraviolet B-exposed epidermis, however, it appeared that the capacity to induce T-cell proliferation was identical for Langerhans cells migrating from ultraviolet B-exposed and nonexposed epidermis. The presence of ultraviolet B-induced DNA damage could be demonstrated in the Langerhans cells from ultraviolet B-treated skin, indicating that the cells had received significant doses of ultraviolet B. As regards the effect of ultraviolet B on migratory properties of Langerhans cells, we found not only that reduced numbers of CD1a-positive Langerhans cells migrated from the ultraviolet B-exposed full-thickness skin, but also that there was a reduction in CD1a-positive Langerhans cells in the epidermis. This implies that ultraviolet B induces death of Langerhans cells as well as loss of cell surface molecules rather than altering Langerhans cells migration, whereas the Langerhans cells that were still able to migrate fully retained the capacity to activate allogeneic T cells

Building Babies - Chapter 16

In contrast to birds, male mammals rarely help to raise the offspring. Of all mammals, only among rodents, carnivores, and primates, males are sometimes intensively engaged in providing infant care (Kleiman and Malcolm 1981). Male caretaking of infants has long been recognized in nonhuman primates (Itani 1959). Given that infant care behavior can have a positive effect on the infant’s development, growth, well-being, or survival, why are male mammals not more frequently involved in “building babies”? We begin the chapter defining a few relevant terms and introducing the theory and hypotheses that have historically addressed the evolution of paternal care. We then review empirical findings on male care among primate taxa, before focusing, in the final section, on our own work on paternal care in South American owl monkeys (Aotus spp.). We conclude the chapter with some suggestions for future studies.Deutsche Forschungsgemeinschaft (HU 1746/2-1) Wenner-Gren Foundation, the L.S.B. Leakey Foundation, the National Geographic Society, the National Science Foundation (BCS-0621020), the University of Pennsylvania Research Foundation, the Zoological Society of San Dieg

The TopClosure® 3S System, for skin stretching and a secure wound closure

The principle of stretching wound margins for primary wound closure is commonly practiced and used for various skin defects, leading at times to excessive tension and complications during wound closure. Different surgical techniques, skin stretching devices and tissue expanders have been utilized to address this issue. Previously designed skin stretching devices resulted in considerable morbidity. They were invasive by nature and associated with relatively high localized tissue pressure, frequently leading to necrosis, damage and tearing of skin at the wound margins. To assess the clinical effectiveness and performance and, to determine the safety of TopClosure® for gradual, controlled, temporary, noninvasive and invasive applications for skin stretching and secure wound closing, the TopClosure® device was applied to 20 patients for preoperative skin lesion removal and to secure closure of a variety of wound sizes. TopClosure® was reinforced with adhesives, staples and/or surgical sutures, depending on the circumstances of the wound and the surgeon’s judgment. TopClosure® was used prior to, during and/or after surgery to reduce tension across wound edges. No significant complications or adverse events were associated with its use. TopClosure® was effectively used for preoperative skin expansion in preparation for dermal resection (e.g., congenital nevi). It aided closure of large wounds involving significant loss of skin and soft tissue by mobilizing skin and subcutaneous tissue, thus avoiding the need for skin grafts or flaps. Following surgery, it was used to secure closure of wounds under tension, thus improving wound aesthetics. A sample case study will be presented. We designed TopClosure®, an innovative device, to modify the currently practiced concept of wound closure by applying minimal stress to the skin, away from damaged wound edges, with flexible force vectors and versatile methods of attachment to the skin, in a noninvasive or invasive manner

Management of patients with persistent medically unexplained symptoms: a descriptive study

Background: In 2013 the Dutch guideline for management of medically unexplained symptoms (MUS) was published. The aim of this study is to assess medical care for patients with persistent MUS as recorded in their electronic medical records, to investigate if this is in line with the national guideline for persistent MUS and whether there are changes in care over time. Methods: We conducted an observational study of adult primary care patients with MUS. Routinely recorded health care data were extracted from electronic medical records of patients participating in an ongoing randomised controlled trial in 30 general practices in the Netherlands. Data on general practitioners’ (GPs’) management strategies during MUS consultations were collected in a 5-year period for each patient prior. Management strategies were categorised according to the options offered in the Dutch guideline. Changes in management over time were analysed. Results: Data were collected from 1035 MUS consultations (77 patients). Beside history-taking, the most frequently used diagnostic strategies were physical examination (24.5%) and additional investigations by the GP (11.1%). Frequently used therapeutic strategies were prescribing medication (24.6%) and providing explanations (11.2%). As MUS symptoms persisted, GPs adjusted medication, discussed progress and scheduled follow-up appointments more frequently. The least frequently used strategies were exploration of all complaint dimensions (i.e. somatic, cognitive, emotional, behavioural and social) (3.5%) and referral to a psychologist (0.5%) or psychiatrist (0.1%). Conclusions: Management of Dutch GPs is partly in line with the Dutch guideline. Medication was possibly prescribed more frequently than recommended, whereas exploration of all complaint dimensions, shared problem definition and referral to mental health care were used less

Facility Configuration Study of the High Temperature Gas-Cooled Reactor Component Test Facility

A test facility, referred to as the High Temperature Gas-Cooled Reactor Component Test Facility or CTF, will be sited at Idaho National Laboratory for the purposes of supporting development of high temperature gas thermal-hydraulic technologies (helium, helium-Nitrogen, CO2, etc.) as applied in heat transport and heat transfer applications in High Temperature Gas-Cooled Reactors. Such applications include, but are not limited to: primary coolant; secondary coolant; intermediate, secondary, and tertiary heat transfer; and demonstration of processes requiring high temperatures such as hydrogen production. The facility will initially support completion of the Next Generation Nuclear Plant. It will secondarily be open for use by the full range of suppliers, end-users, facilitators, government laboratories, and others in the domestic and international community supporting the development and application of High Temperature Gas-Cooled Reactor technology. This pre-conceptual facility configuration study, which forms the basis for a cost estimate to support CTF scoping and planning, accomplishes the following objectives: • Identifies pre-conceptual design requirements • Develops test loop equipment schematics and layout • Identifies space allocations for each of the facility functions, as required • Develops a pre-conceptual site layout including transportation, parking and support structures, and railway systems • Identifies pre-conceptual utility and support system needs • Establishes pre-conceptual electrical one-line drawings and schedule for development of power needs

Sex differential in mortality trends of old-aged Danes: a nation wide study of age, period and cohort effects

Objective Over the last half century the mortality rates in Denmark for females above age 80 have declined dramatically whereas the decline for males have been modest, resulting in a change in sex-ratio for centenarians from 2 to 5. Here we investigate whether this mortality pattern is mainly explained by period effects, cohort effects or both. This can provide clues for where to search for causes behind the changes in sex differential in mortality seen in many Western countries during the last decades. Methods Age-period-cohort study of mortality for all Danish women and men aged 79–98 during the period 1949–2006. Outcome measures Relative risks for deaths and second order differences for exploration of the nonlinear variation. Results Both the overall trends in mortality differences and the fluctuations in mortality for both men and women were better explained by period effects than by cohort effects. The observed rates were better described by the age, period and cohort model than by other models. Conclusions Our results suggest that causes for both the overall increased difference in mortality and the short term fluctuations in mortality rates are primarily to be found in the period dimension. Cohort effects on the mortality of the oldest Danish women and men played a significant but minor role compared to period effects