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1.  Effect of clinical guidelines in nursing, midwifery, and the therapies: a systematic review of evaluations 
Quality in Health Care : QHC  1998;7(4):183-191.
BACKGROUND: Although nursing, midwifery, and professions allied to medicine are increasingly using clinical guidelines to reduce inappropriate variations in practice and ensure higher quality care, there have been no rigorous overviews of their effectiveness, 18 evaluations of guidelines were identified that meet Cochrane criteria for scientific rigor. METHODS: Guideline evaluations conducted since 1975 which used a randomised controlled trial, controlled before and after, or interrupted time series design were identified through a combination of database and hand searching. RESULTS: 18 studies met the inclusion criteria. Three studies evaluated guideline dissemination or implementation strategies, nine compared use of a guideline with a no guideline state; six studies examined skill substitution: performance of nurses operating according to a guideline were compared with standard care, generally provided by a physician. Significant changes in the process of care were found in six out of eight studies measuring process and in which guidelines were expected to have a positive impact on performance. In seven of the nine studies measuring outcomes of care, significant differences in favour of the intervention group were found. Skill substitution studies generally supported the hypothesis of no difference between protocol driven by nurses and care by a physician. Only one study included a formal economic evaluation, with equivocal findings. CONCLUSIONS: Findings from the review provide some evidence that care driven by a guideline can be effective in changing the process and outcome of care. However, many studies fell short of the criteria of the Cochrane Effective Practice and Organisation of Care Group (EPOC) for methodological quality.
PMCID: PMC2483618  PMID: 10339020
2.  Issues of recruitment and maintaining high response rates in a longitudinal study of older hospital patients in England--pathways through care study. 
STUDY OBJECTIVES: To describe and discuss the methods used to recruit and maintain an unbiased sample of older discharged hospital patients in a study of the process and outcomes of hospital care. DESIGN: Prospective longitudinal interview study of consecutive patients admitted to hospital over a 12 month period and followed up for six months. Interviews took place in hospital five days after admission, at home 10 days after discharge, and six months after admission. SETTING: Six hospital locations: three in the north of England and three in the south. PARTICIPANTS: People aged 65 and over admitted to hospital with a new stroke or fractured neck of femur, their significant other, and nursing staff caring for them. MAIN RESULTS: Of 3105 patients referred to the study, 2111 were eligible and 1671 (79%) were recruited. Recruited stroke patients were younger than those not recruited and rates differed between locations for both stroke and fractured neck of femur. By six months after admission 25% had died. Outcome data were obtained for 85% of the surviving patients. Patients who died were older and frailer before admission. Among survivors, outcome data for stroke patients were less likely to be obtained for men, those more able initially, and those who were married. Response rates to each interview differed according to respondent types. Interviews were more likely to be obtained with significant others than patients. Patients who were not able to be interviewed were older and frailer; significant others were less likely to be interviewed if the patients were younger and more able. CONCLUSIONS: High response rates can be achieved with very frail older people if strategies are adopted to maintain their interest and if self reported data are supplemented by interviewing significant others.
PMCID: PMC1060541  PMID: 9425465
3.  Effect of beta-lactams on peptidoglycan metabolism of Haemophilus influenzae grown in animals. 
Antimicrobial Agents and Chemotherapy  1992;36(10):2147-2155.
We have examined bacterial determinants that influence beta-lactam activity in Haemophilus influenzae cells cultivated in a system that reproduces in vivo growth conditions. Bacteria grown in diffusion chambers were recovered from the peritoneal cavities of rats, and their cell properties were compared with those of bacteria grown in broth cultures by various tests performed in vitro. The rate of peptidoglycan synthesis was measured as the incorporation of [14C]alanine into cell wall material in the presence of chloramphenicol. The total incorporation of [14C]alanine into peptidoglycan was markedly increased in cells grown in rats prior to the assay but was efficiently reduced by the beta-lactams. The extent of cross-linking was lower in the peptidoglycan of in vivo-grown bacteria, as estimated by sodium dodecyl sulfate- to trichloroacetic acid-insoluble radioactive cell wall material ratios. A whole-cell labeling assay with 125I-penicillin was used to characterize the penicillin-binding proteins (PBPs). Four PBPs showed a striking reduction in the binding of the labeled penicillin in cells grown in rats. Such changes resembled the PBP alterations seen in beta-lactamase-negative clinical strains that were resistant to the beta-lactams. Although ampicillin and moxalactam showed delayed inhibitory activities in vitro for cells collected from rats, cells recovered from beta-lactam-treated rats showed evidence of antibiotic effectiveness (binding of the beta-lactams to PBPs in vivo and altered morphology), and the killing of cells exposed to antibiotics in broth or in peritoneal fluid was equally good. Finally, the frequencies of spontaneous resistance or tolerance to ampicillin or moxalactam were estimated, and there was no significant difference for in vitro- or in vivo-grown cells. These data demonstrated that the cultivation of H. influenzae in animals created changes in PBPs and the overall peptidoglycan metabolism. Such alterations did not impair the bactericidal activities of the beta-lactams, although they resulted in delayed bacterial inhibition, a phenomenon that may have important consequences in antibiotherapy.
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PMCID: PMC245469  PMID: 1444294
4.  Molecular basis of the non-beta-lactamase-mediated resistance to beta-lactam antibiotics in strains of Haemophilus influenzae isolated in Canada. 
A study recently conducted across Canada showed that 64 of 2,503 clinical isolates of Haemophilus influenzae were resistant to beta-lactams without production of a beta-lactamase (L. D. Tremblay, J. L'Ecuyer, P. Provencher, M. G. Bergeron, and Canadian Study Group, Can. Med. Assoc. J. 143:895-900, 1990). The beta-lactamase-negative strains formed three distinct groups, with ampicillin MICs of 0.5 to 1, 2 to 4, and greater than or equal to 8 micrograms/ml for groups I, II, and III, respectively. We have investigated the mechanisms of resistance for eight strains originating from different infections and geographic areas. These strains were representative of groups I to III. Five strains were nontypeable, two were type B, and one was non-B. Chromosomal DNA extracted from each strain was used to transform the laboratory strain Rd. Transformants were selected on beta-lactam-containing plates and showed the same level of resistance to ampicillin as the donor strains. Differences in outer membrane proteins, porins, and lipopolysaccharide profiles on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) did not change with resistance. Functional analyses of purified porins in artificial lipid bilayer experiments did not explain resistance. Peptidoglycan synthesis was measured by incorporation of [14C]alanine into trichloroacetic acid-insoluble cell wall material in the presence of chloramphenicol. The growth rate and the rate of peptidoglycan synthesis observed for the transformants of the isogenic set did not correlate with resistance. Whole-cell labeling with 125I-penicillin revealed modifications in penicillin-binding proteins (PBPs) among the transformants. In particular, PBPs 3A and 3B (65 and 63 kDa, respectively) showed a decrease in affinity for beta-lactams in all transformants (groups I, II, and III) and correlated with an increased MIC except in the transformant of group III, which showed higher levels of resistance. Partial purification and proteolytic digestion of 125I-penicillin-labeled PBP 3B led to two types of CnBr peptide profiles on SDS-PAGE, the profiles of the transformed strains from groups I and II being different from those of the control group and group III. Finally, electron microscopy revealed a distinct cell filamentation for the group III transformants. These data clearly indicate that changes in PBPs are a common mechanism that results in a significant level of non-beta-lactamase-mediated beta-lactam resistance in H. influenzae despite serotype, origin of isolation, or geographic distribution.
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PMCID: PMC191612  PMID: 1510447
5.  Nucleotide sequence of an heterochromatic segment recognized by the antibodies to Z-DNA in fixed metaphase chromosomes. 
Nucleic Acids Research  1986;14(8):3197-3214.
The purpose of this work was to analyse at the molecular level the DNA recognized by the antibodies to Z-DNA in in situ experiments. Antibodies to Z-DNA interact strongly with R-band positive heterochromatic segments of fixed metaphase chromosomes of Cebus (Viegas-Pequignot et al., 1983). These segments are constituted of a satellite DNA the repeat unit of which is about 1520 base pairs long. The base sequence of the repeat unit has been determined. It contains a (AC)n rich region which, in vitro, adopts the Z conformation under topological constraints. Experiments with nuclei suggest that this sequence is not predominantly in the Z conformation in vivo. The polymorphic structure of the (AC)n rich region argues for an active recombination sequence.
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PMCID: PMC339742  PMID: 3010230

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