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The relation between systematic reviews and practice guidelines.

Clinical practice guidelines have been developed to improve the process and outcomes of health care and to optimize resource utilization. By addressing such issues as prevention, diagnosis, and treatment, they can aid in health care decision making at many levels. Several other decision aids are cast in the guideline lexicon, regardless of their focus, formulation, or format; this can foster misunderstanding of the term "guideline." Whether created or adapted locally or nationally, most guidelines are an amalgam of clinical experience, expert opinion, and research evidence. Approaches to practice guideline development vary widely. Given the resources required to identify all relevant primary studies, many guidelines rely on systematic reviews that were either previously published or created de novo by guideline developers. Systematic reviews can aid in guideline development because they involve searching for, selecting, critically appraising, and summarizing the results of primary research. The more rigorous the review methods used and the higher the quality of the primary research that is synthesized, the more evidence-based the practice guideline is likely to be. Summaries of relevant research incorporated into guideline documents can help to keep practitioners up to date with the literature. Systematic reviews have also been published on the dissemination and implementation strategies most likely to change clinician behavior and improve patient outcomes. These can be useful in more effectively translating research evidence into practice.

Evidence-Based Medicine↗

A JAVA-based multimedia tool for clinical practice guidelines.

We have developed a specific language for the representation of Clinical Practice Guidelines (CPGs) and Windows C++ and platform independent JAVA applications for multimedia presentation and edition of electronically stored CPGs. This approach facilitates translation of guidelines and protocols from paper to computer-based flowchart representations. Users can navigate through the algorithm with a friendly user interface and access related multimedia information within the context of each clinical problem. CPGs can be stored in a computer server and distributed over the World Wide Web, facilitating dissemination, local adaptation, and use as a reference element in medical care. We have chosen the Agency for Health Care and Policy Research's heart failure guideline to demonstrate the capabilities of our tool.

Computer Communication Networks↗

[Congenital corneal anesthesia in children: diagnostic and therapeutic problems].

Congenital corneal anesthesia (CCA) is an uncommon condition difficult to diagnose. We report the case of a 9-month-old girl who presented bilateral congenital corneal anesthesia. The child had a corneal ulcer which had been unresponsive to adapted local treatment. Self-inflicted corneal injuries were present. Local treatment and arm splints led to quick healing. CCA occurs either alone or in association with neurological diseases (familial dysautonomia) or systemic congenital abnormalities (Goldenhar Gorlin syndrome). It is important to search for corneal anesthesia in children with chronic ulcerations of the cornea and self-inflicted injuries. Early diagnosis is important due to the risk for the visual prognosis. Short and longterm prevention of self-inflicted corneal injuries should be associated with a local treatment to assure rapid healing and a relapse free outcome.

Corneal Diseases↗

Prescribing and dispensing activities at the health facilities of a non-governmental organization.

BACKGROUND: Prescribing and dispensing surveys are pre-requisites to achieving rational drug use. There is a dearth of such studies in India, particularly in the non-governmental organization sector. METHODS: We carried out a survey at the outpatient facilities maintained by the Southern Health Improvement Samity, a non-governmental organization in the South 24 Parganas district of West Bengal. Data were collected prospectively by interviewing patients immediately after patient-physician and patient-dispenser encounters. Pre-designed forms were used to collect data pertaining to World Health Organization drug-use indicators and some additional indices. The calculations of cost of therapy involved some approximation. RESULTS: Of the 312 prescriptions analysed, the majority were signed, legible and complete with respect to age/gender data; 95.5% used Latin abbreviations and 7.7% mentioned neither signs and symptoms nor diagnosis. The average number of drugs per encounter was 3.2; only 2 patients were treated without drugs; 46.2% of drugs were prescribed by generic name. Use of antibiotics (72.8% of encounters) and irrational fixed dose combinations (45.6% of prescribed drugs) were frequent, but injection use (3.9% of prescriptions) was low. The average drug cost per encounter was Rs 74.19, of which antibiotics comprised 37.1%. The availability of first-line antitubercular drugs was adequate but other key drugs were in limited supply. Essential drugs lists and formularies were not followed. Only 45.7% of prescribed drugs conformed to the World Health Organization model list of essential drugs. Only 12 preparations accounted for 70.9% of the prescribed drugs, including therapeutically doubtful ones such as cough syrups, multivitamins and carminative syrups. For the dispensing survey, 301 prescriptions were analysed separately. All the prescribed drugs were supplied for only 11.6% of prescriptions. There were no serious errors in dispensing but 43.8% of dispensed products were inadequately labelled. Patients knew the correct mode of use for 64.5% of dispensed drugs. The average consultation and dispensing times were 3.7 and 3.1 minutes, respectively. CONCLUSION: Frequent use of antibiotics, irrational fixed dose combinations and preparations of uncertain efficacy, inadequate labelling of dispensed drugs and lack of access to standard tools for rational drug use such as locally adapted essential drugs list, formularies and standard treatment guidelines were some of the problematic prescribing and dispensing trends identified through this survey. Educational interventions are required to rectify these problems.

Adult↗

Explaining stasis: microevolutionary studies in natural populations.

Microevolution, defined as a change in the genetic constitution of a population over time, is considered to be of commonplace occurrence in nature. Its ubiquity can be inferred from the observation that quantitative genetic divergence among populations usually exceeds that to be expected due to genetic drift alone, and from numerous observations and experiments consistent with local adaptation. Experimental manipulations in natural populations have provided evidence that rapid evolutionary responses may occur in the wild. However, there are remarkably few cases where direct observations of natural populations have revealed microevolutionary changes occurring, despite the frequent demonstration of additive genetic variation and strong directional selection for particular traits. Those few cases where responses congruent with expectation have been demonstrated are restricted to changes over one generation. In this article we focus on possible explanations as to why heritable traits under apparently strong directional selection often fail to show the expected evolutionary response. To date, few of these explanations for apparent stasis have been amenable to empirical testing. We describe new methods, derived from procedures developed by animal breeding scientists, which can be used to address these explanations, and illustrate the approach with examples from long-term studies of collared flycatchers (Ficedula albicollis) and red deer (Cervus elaphus). Understanding why most intensively studied natural populations do not appear to be evolving is an important challenge for evolutionary biology.

Animals↗

High gene flow levels lead to gamete wastage in a desert spider system.

Field censuses, breeding experiments, and a quantitative model are used to obtain insight into the extent and consequences of genetic mixing between locally adapted populations of a desert spider. Typically, 9% of the matings of desert riparian spiders (non-aggressive phenotype) in native habitat involve an arid-land partner (aggressive phenotype). Mating was found to be random with respect to behavioral phenotype, but linearly related to both the rate of immigration and survival of immigrants from surrounding arid habitats in the riparian area. Genetic mixing between riparian and arid-land spiders produces offspring that exhibit lower rates of survival in riparian habitat. Two extreme behavioral phenotypes were also observed in the field studies: approximately 5% of the female spiders attacked all males they encountered while another 22% ran from all potential mates. Punnett square analyses of the potential genotypes produced by introgression between arid- and riparian-adapted spiders indicate that these extreme phenotypes appear in F2 generation hybrids and backcrosses. Because there is a costly wastage of gametes in the case of mixed phenotype mating, model results indicate that within three generations of the cessation of gene flow, the riparian population would be free of mixed genotypes and moving towards genetic differentiation.

Alleles↗

[Effects of immunization on proteinase-inhibitor balance in the lacrimal fluid and blood serum in alkaline burns of the cornea (an experimental study)].

Proteinase-inhibitor balance in the lacrimal fluid in eye burns was studied in rabbits with modified and intact immune status. Stimulation of the immune system was induced by complete Freund's adjuvant. Clinical picture of the disease was studied in parallel. Immunization accelerated the local adaptive and defense reaction of the proteolytic enzymes and their inhibitors, which was paralleled by a more benign course of burn disease of the eyes, in comparison with that in non-immunized animals.

Alkalies↗

Improving the effectiveness of smoking cessation in primary care: lessons learned.

AIMS: The 'Smokescreen' smoking cessation programme was introduced in Christchurch in 1995, with an initial study showing six-month, self-reported quit rates of 10% and 17% (with a validated deception rate) in primary and secondary care settings. Substantial modifications were made to try to improve this rate in the primary care setting and the programme has been implemented widely. Our primary aim was to estimate programme utilisation and six-month quit rates for enrolled patients in this general primary care setting. We also aimed to use a wide range of patient, practice and environmental variables to estimate any predictive effect on outcome. METHODS: Prospective longitudinal cohort study. The nicotine replacement therapy (NRT) -based programme was implemented by Pegasus Health, an independent practitioner association (IPA) situated in the Christchurch urban area, to which the majority of Christchurch-based GPs belong. A cohort of 516 patients enrolling in the programme over a two-month period were contacted six months after their nominated quit date. The main outcome measure was the six-month, self-reported quit rate. RESULTS: Of the 516 participants, 334 (65%) were contacted by mail or telephone. The overall six-month quit rate was 36% (95% Confidence Interval (CI) 31-41). Univariate analysis initially showed duration of NRT (p = 0.03) and age band (p = 0.004) were significant predictors of quitting, while living with a smoker (p = 0.02), having made no previous quit attempts (p = 0.02) and having heart disease (p = 0.01) were all significant predictors of continued smoking at six months. Factors that did not predict whether respondents were smoking at six months included previous use of NRT, sex, ethnicity, who delivered the intervention, years of smoking, cigarette dose, and NZDep96 score. However, there was interaction between these factors as after multivariate analysis the only significant predictors of outcome were having others living in the house who smoked (odds ratio (OR) 0.55, 95% CI 0.33--0.93, p = 0.03) and having made no previous quit attempts (OR 0.29, 95% CI 0.12-0.71, p = 0.02). Both these factors were significantly associated with continuing to smoke. CONCLUSIONS: This programme compares favourably with six-month quit rates for NRT-based programmes reported in the international literature of 14-22%. The effectiveness of an NRT-based smoking cessation programme in a general primary care setting appears to have been significantly enhanced by local adaptation, the flexibility of a primary-care-team approach and subsidisation of NRT, together with facilitation responsive to individual practice needs. The success of this programme in helping individual patients quit, as well as its successful implementation in a wide primary care setting, suggests General Practice can play an important role in smoking cessation in a country with a high burden of disease from smoking-related illnesses. The programme is congruent with the current, national, smoking cessation guidelines endorsed by the RNZCGP. Widespread adoption of this kind of model in IPA/primary health organisation (PHO) settings throughout New Zealand should be encouraged and supported.

Adolescent↗

Hypothetical performance of syndrome-based management of acute paediatric admissions of children aged more than 60 days in a Kenyan district hospital.

OBJECTIVE: To investigate whether the outpatient, syndrome-based approach of the Integrated Management of Childhood Illness (IMCI) protocol could be extended to the inpatient arena to give clear and simple minimum standards of care for poorly resourced facilities. METHODS: A prospective, one-year admission cohort retrospectively compared hypothetical performance of syndrome-based management with paediatrician-defined final diagnosis. Admission syndrome definitions were based on local adaptations to the IMCI protocol that encompassed 20 clinical features, measurement of oxygen saturation, and malaria microscopy. FINDINGS: After 315 children with clinically obvious diagnoses (e.g. sickle cell disease and burns) were excluded, 3705 admission episodes were studied. Of these, 2334 (63%) met criteria for at least one severe syndrome (mortality 8% vs <1% for "non-severe" cases), and half of these had features of two or more severe syndromes. No cases of measles were seen. Syndrome-based treatment would have been appropriate (sensitivity >95%) for severe pneumonia, severe malaria, and diarrhoea with severe dehydration, and probably for severe malnutrition (sensitivity 71%). Syndrome-directed treatment suggested the use of broad-spectrum antibiotics in 75/133 (56% sensitivity) children with bacteraemic and 63/71 (89% sensitivity) children with meningitis. CONCLUSIONS: Twenty clinical features, oxygen saturation measurements, and results of malaria blood slides could be used for inpatient, syndrome-based management of acute paediatric admissions. The addition of microscopy of the cerebrospinal fluid and haemoglobin measurements would improve syndrome-directed treatment considerably. This approach might rationalize admission policy and standardize inpatient paediatric care in resource-poor countries, although the clinical detection of bacteraemia remains a problem.

Acute Disease↗

Clinical guidelines: a study of staff awareness of Internet resources.

Clinical guidelines (CGs) are widely used in community hospitals. The advantages and limitations of CGs are well understood by nurses and therapists. There are effective human dissemination routes using local training of link nurses and cascade learning. Practice development nurses are a useful resource for locating CGs. However there is a universal lack of awareness of Internet based national CGs in this sample of ward nurses and therapists. Access to these national CGs via the Internet would make local adaptation of CGs more effective and efficient. Access to Internet PCs on the wards backed up with staff training was recommended, and is ongoing.

Awareness↗

Assessing the potential for an ongoing arms race within and between the sexes: selection and heritable variation.

In promiscuous species, sexual selection generates two opposing male traits: offense (acquiring new mates and supplanting stored sperm) and defense (enforcing fidelity on one's mates and preventing sperm displacement when this fails). Coevolution between these traits requires both additive genetic variation and associated natural selection. Previous work with Drosophila melanogaster found autosomal genetic variation for these traits among inbred lines from a mixture of populations, but only nonheritable genetic variation was found within a single outbred population. These results do not support ongoing antagonistic coevolution between offense and defense, nor between either of these male traits and female reproductive characters. Here we use a new method (hemiclonal analysis) to study genomewide genetic variation in a large outbred laboratory population of D. melanogaster. Hemiclonal analysis estimates the additive genetic variation among random, genomewide haplotypes taken from a large, outbred, locally adapted laboratory population and determines the direction of the selection gradient on this variation. In contrast to earlier studies, we found low but biologically significant heritable variation for defensive and offensive offspring production as well as all their components (P1, fidelity, P2, and remating). Genetic correlations between these traits were substantially different from those reported for inbred lines. A positive genetic correlation was found between defense and offense, demonstrating that some shared genes influence both traits. In addition to this common variation, evidence for unique genetic variation for each trait was also found, supporting an ongoing coevolutionary arms race between defense and offense. Reproductive conflict between males can strongly influence female fitness. Correspondingly, we found genetic variation in both defense and offense that affected female fitness. No evidence was found for intersexual conflict in the context of male defense, but we found substantial intersexual conflict in the context of male offensive sperm competitive ability. These results indicate that conflict between competing males also promotes an associated arms race between the sexes.

Analysis of Variance↗

[Clinical guidelines: what are the viewpoints of physicians and housestaff working in hospital medical departments?].

BACKGROUND: Factors facilitating use of clinical guidelines by physicians working in French public hospitals are unknown. We wanted to ascertain the desires of physicians and housestaff working in medical departments. METHODS: A cross-sectional survey using a self-administered questionnaire with closed-ended questions and free comment was conducted in the two academic regional hospitals and the 20 district hospitals of Brittany. The following items were noted: individual and professional characteristics, use of and opinion about clinical guidelines, perceived usefulness of specific attributes of guidelines or implementation efforts. The results are shown separately for physicians and housestaff. The statistical significance of associations between physician characteristics and their opinions was tested by using the chi-square test. RESULTS: 390 out of 783 responded (50%). Nine housestaff and eight physicians out of ten responders found more positive than negative points to guidelines (decision making tool, standardization of practices, versus rigidity, lack of freedom in practice). One out of three reported using them regularly. Guidelines focusing on general medicine, covering both diagnosis and treatment, developed at the national level with local adaptation, synthetic and pocket-sized guide-book given directly to the housestaff by the department's physicians, were more likely to be used. One physician out of two would use more guidelines from specialty organizations, or would use them as a self-training tool in practices evaluation. CONCLUSION: Implementation of guidelines in hospital medical departments should take into account the housestaff demands as well as the need for the physicians' implication.

Adult↗

Major histocompatibility alleles associated with local resistance to malaria in a passerine.

Malaria parasites are a major cause of human mortality in tropical countries and a potential threat for wildlife, as witnessed by the malaria-induced extinction of naive Hawaiian avifauna. Identifying resistance mechanisms is therefore crucial both for human health and wildlife conservation. Patterns of malaria resistance are known to be highly polygenic in both humans and mice, with marked contributions attributed to major histocompatibility (Mhc) genes. Here we show that specific Mhc variants are linked to both increased resistance and susceptibility to malaria infection in a wild passerine species, the house sparrow (Passer domesticus). In addition, links between host immunogenetics and resistance to malaria involved population-specific alleles, suggesting local adaptation in this host-parasite interaction. This is the first evidence for a population-specific genetic control of resistance to malaria in a wild species.

Alleles↗

Comparative analyses of population structure in two subspecies of Nigella degenii: evidence for diversifying selection on pollen-color dimorphisms.

Flower color can be a major determinant of plant fitness, not only because of preferential visitation by pollinators but also because of pleiotropic relationships between the expression of floral pigments and biochemically related compounds that influence vegetative performance variables. Different environments may therefore favor different pigmentation phenotypes. We examined whether spatially varying selection has played a major role in shaping large-scale patterns of differentiation in two subspecies of Nigella degenii (Ranunculaceae), with particular emphasis on pollen color. The two subspecies appear to have been genetically isolated for substantial periods of time and, therefore, provide a "replicated test" for the effect of natural selection. Estimates of population structure based on a suite of floral and vegetative characters were compared with the corresponding data for amplified fragment length polymorphism (AFLP) markers, which were assumed to be selectively neutral. We found low levels of genetic structure within the subspecies using both the AFLP markers (FST < or = 0.05) and quantitative characters (QST < or = 0.15), with no statistically significant differences between the two measures. There is, therefore, no evidence of diversifying selection being important in structuring variation in quantitative characters within each of the two subspecies. In contrast, estimates of differentiation in pollen color (FST > or = 0.10) significantly exceeded the neutral expectations (estimated from AFLP data), suggesting that local adaptation has played a key role in the evolution of this monogenic character.

Analysis of Variance↗

Minimal selfing, few clones, and no among-host genetic structure in a hermaphroditic parasite with asexual larval propagation.

Little is known about actual mating systems in natural populations of parasites or about what constitutes the limits of a parasite deme. These parameters are interesting because they affect levels of genetic diversity, opportunities for local adaptation, and other evolutionary processes. We expect that transmission dynamics and the distribution of parasites among hosts should have a large effect on mating systems and demic structure, but currently we have mostly speculation and very few data. For example, infrapopulations (all the parasites in a single host) should behave as demes if parasite offspring are transmitted as a clump from host to host over several generations. However, if offspring are well mixed, then the parasite component population (all the parasites among a host population) would function as the deme. Similarly, low mean intensities or a high proportion of worms in single infections should increase the selfing rate. For species having an asexual amplification stage, transmission between intermediate and definitive (final) hosts will control the variance in clonal reproductive success, which in turn could have a large influence on effective sizes and rates of inbreeding. We examined demic structure, selfing rates, and the variance in clonal reproductive success in natural populations of Plagioporus shawi, a hermaphroditic trematode that parasitizes salmon. Overall levels of genetic diversity were very high. An a posteriori inference of population structure overwhelmingly supports the component population as the deme, rather than individual infrapopulations. Only a single pair of 597 adult individuals was identified as clones. Thus, the variance in clonal reproductive success was almost zero. Despite being hermaphroditic, P. shawi appears to be almost entirely outcrossing. Genetic estimates of selfing (<5%) were in accordance with the proportion of parasites from single infections. Thus, it appears that individual flukes outcross whenever possible and only resort to selfing when alone. Finally, our data support the hypothesis that aquatic transmission and the use of several intermediate hosts promotes high genetic diversity and well-mixed infrapopulations.

Animals↗

[An auto-extraction method of spectral line for normal galaxy spectra].

Spectral line extraction for normal galaxy spectra is the most difficult task in spectral line auto-extraction of celestial spectra. The present paper presents a novel technique of spectral line auto-extraction for normal galaxy spectra. Firstly, the Max operator of two spectra is defined, and the operator produces a new spectrum whose intensity at each wavelength is the maximum of intensities of the two spectra; Secondly, the continuum is fitted in an iterative way, where in each iteration, the traditional wavelet method is performed for the spectrum obtained by the Max operation of the original spectrum, and the continuum is fitted in the last iteration; Finally, adaptive local thresholding associated with the universal thresholding is used to extract spectral lines. Experiments show that this method is superior to the traditional wavelet method. It will be helpful to the spectral line based automated spectral classification and parameter measurement.

English Abstract↗

Population differentiation and genetic variation in host choice among pea aphids from eight host plant genera.

Habitat choice plays a critical role in the processes of host range evolution, specialization, and ecological speciation. Pea aphid, Acyrthosiphon pisum, populations from alfalfa and red clover in eastern North America are known to be genetically differentiated and show genetic preferences for the appropriate host plant. This species feeds on many more hosts, and here we report a study of the genetic variation in host plant preference within and between pea aphid populations collected from eight genera of host plants in southeastern England. Most host-associated populations show a strong, genetically based preference for the host plant from which they were collected. Only in one case (populations from Vicia and Trifolium) was there little difference in the plant preference spectrum between populations. All populations showed a significant secondary preference for the plant on which all the aphid lines were reared: broad bean, Vicia faba, previously suggested to be a "universal host" for pea aphids. Of the total genetic variance in host preference within our sample, 61% could be attributed to preference for the collection host plant and a further 9% to systematic differences in secondary preferences with the residual representing within-population genetic variation between clones. We discuss how a combination of host plant preference and mating on the host plant may promote local adaptation and possibly ecological speciation, and whether a widely accepted host could oppose speciation by mediating gene flow between different populations.

Animals↗

[Effect of phytohemagglutinins on cell proliferation of the small intestine epithelium of rats].

Twenty male rats, were divided into two groups of ten animals each: E group, which received solid diet containing 4% of phytohemagglutinin and P group iso-caloric par-fed control, which received the same diet but the phytohemagglutinin was inactivated by heat. Water was offered ad libitum to all groups. The animals were weighed every day and the consumption of diet and water was registered. In the fourteenth day of experiment, the animals were sacrificed and the fragments of jejunum and ileum were removed to morphokinetic study. The results showed that the hydric ingestion was the same in both groups, the body weight of the E group was significant smaller than P group, the villus cell population from the jejunum of the E group was statistically smaller than P group and the contrary happened with ileum samples, wherein the E group was statistically larger than P. The jejunum villus height from E group was similar with P group, but in the ileum of the E group was larger than P. The depth, the cell population and cell production rate of crypt of E group were larger than P, in the jejunum and in the ileum. In conclusion, these results in the present study supply evidence that the intake of the phytohemagglutinin provokes injury of jejunal mucosa, reducing the villus cell population and stimulating the crypt hyperplasia, developing local adaptation. This adaptative model is similar to the one that occurs in celic disease. This proximal lesion stimulate crypt-villus unit hyperplasia of the ileal epithelium, developing distal adaptation. These adaptations occurred in animals that ingested phytohemagglutinin, even though with multicarencial malnutrition.

Animals↗