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Biomedical subjects

L Griffith

Publications and source records attributed to L Griffith.

At least 19 recordsLinked to original sources

Minimizing errors of omission: behavioural reenforcement of heparin to avert venous emboli: the BEHAVE study.

OBJECTIVE: To improve patient safety by increasing heparin thromboprophylaxis for medical-surgical intensive care unit patients using a multiple-method approach to evidence-based guideline development and implementation. DESIGN: Prospective longitudinal observational study. SETTING: Medical-surgical intensive care unit. PARTICIPANTS: Multidisciplinary clinicians caring for critically ill patients in a 15-bed medical-surgical closed intensive care unit. INTERVENTIONS: Phase 1 was a 3-month baseline period during which we documented anticoagulation and mechanical thromboprophylaxis. Phase 2 was a 1-yr period in which we implemented a thromboprophylaxis guideline using a) interactive multidisciplinary educational in-services; b) verbal reminders to the intensive care unit team; c) computerized daily nurse recording of thromboprophylaxis; d) weekly graphic feedback to individual intensivists on guideline adherence; and e) publicly displayed graphic feedback on group performance. Phase 3 was a 3-month follow-up period 10 months later, during which we documented thromboprophylaxis. Computerized daily nurse recording of thromboprophylaxis continued in this period. MEASUREMENTS AND MAIN RESULTS: Intensive care unit and hospital mortality rates were similar across phases, although patients in phase 2 had higher Acute Physiology and Chronic Health Evaluation II scores than patients in phases 1 and 3. The proportion (median % [interquartile range]) of intensive care unit patient-days of heparin thromboprophylaxis in phases 1, 2, and 3 was 60.0 (0, 100), 90.9 (50, 100), and 100.0 (60, 100), respectively (p=.01). The proportion (median % [interquartile range]) of days during which heparin thromboprophylaxis was omitted in error in phases 1, 2, and 3 was 20 (0, 53.8), 0 (0, 6.3), and 0 (0, 0), respectively (p<.001). CONCLUSIONS: After development and implementation of an evidence-based thromboprophylaxis guideline, we found significantly more patients receiving heparin thromboprophylaxis. Guideline adherence was maintained 1 yr later. Further research is needed on which are the most effective strategies to implement patient safety initiatives in the intensive care unit.

Aged↗

Calcium supplementation on bone loss in postmenopausal women.

BACKGROUND: Although calcium is one the simplest and least expensive strategies for preventing osteoporotic fractures calcium supplementation is nevertheless not without controversy (Kanis 1989; Nordin 1990). The Food and Drug Administration in the US has permitted a bone health claim for calcium-rich foods, and the NIH in its Consensus Development Process approved a statement that high calcium intake reduces the risk of osteoporosis. OBJECTIVES: To assess the effects of calcium on bone density and fractures in postmenopausal women. SEARCH STRATEGY: We searched Cochrane Controlled Register, MEDLINE and EMBASE up to 2001, and examined citations of relevant articles and proceedings of international meetings. SELECTION CRITERIA: Trials that randomized postmenopausal women to calcium supplementation or usual calcium intake in the diet and reported bone mineral density of the total body, vertebral spine, hip, or forearm or recorded the number of fractures, and followed patients for at least one year were considered for inclusion. DATA COLLECTION AND ANALYSIS: Three independent reviewers assessed the methodologic quality and extracted data for each trial. For each bone density site (lumbar spine, total body, combined hip and combined forearm), we calculated the weighted mean difference in bone density between treatment and control groups using the percentage change from baseline. We constructed regression models in which the independent variables were year and dose, and the dependent variable was the effect size. This regression was used to determine the years across which pooling was appropriate. Heterogeneity was assessed. For each fracture analysis we calculated a risk ratio. MAIN RESULTS: Fifteen trials, representing 1806 participants, were included. Calcium was more effective than placebo in reducing rates of bone loss after two or more years of treatment. The pooled difference in percentage change from baseline was 2.05% (95% CI 0.24 to 3.86) for total body bone density, 1.66% (95% CI 0.92 to 2.39) for the lumbar spine at 2 years, 1.60% (95% CI 0.78 to 2.41) for the hip, and 1.91% (95% CI 0.33 to 3.50) for the distal radius. The relative risk of fractures of the vertebrae was 0.79 (95% CI 0.54 to 1.09); the relative risk for non-vertebral fractures was 0.86 (95% CI 0.43 to 1.72). REVIEWER'S CONCLUSIONS: Calcium supplementation alone has a small positive effect on bone density. The data show a trend toward reduction in vertebral fractures, but it is unclear if calcium reduces the incidence of non vertebral fractures.

Bone Density↗

Calcium supplementation on bone loss in postmenopausal women.

BACKGROUND: Although calcium is one the simplest and least expensive strategies for preventing osteoporotic fractures calcium supplementation is nevertheless not without controversy (Kanis 1989; Nordin 1990). The Food and Drug Administration in the US has permitted a bone health claim for calcium-rich foods, and the NIH in its Consensus Development Process approved a statement that high calcium intake reduces the risk of osteoporosis. OBJECTIVES: To assess the effects of calcium on bone density and fractures in postmenopausal women. SEARCH STRATEGY: We searched Cochrane Controlled Register, MEDLINE and EMBASE up to 2001, and examined citations of relevant articles and proceedings of international meetings. SELECTION CRITERIA: Trials that randomized postmenopausal women to calcium supplementation or usual calcium intake in the diet and reported bone mineral density of the total body, vertebral spine, hip, or forearm or recorded the number of fractures, and followed patients for at least one year were considered for inclusion. DATA COLLECTION AND ANALYSIS: Three independent reviewers assessed the methodologic quality and extracted data for each trial. For each bone density site (lumbar spine, total body, combined hip and combined forearm), we calculated the weighted mean difference in bone density between treatment and control groups using the percentage change from baseline. We constructed regression models in which the independent variables were year and dose, and the dependent variable was the effect size. This regression was used to determine the years across which pooling was appropriate. Heterogeneity was assessed. For each fracture analysis we calculated a risk ratio. MAIN RESULTS: Fifteen trials, representing 1806 participants, were included. Calcium was more effective than placebo in reducing rates of bone loss after two or more years of treatment. The pooled difference in percentage change from baseline was 2.05% (95% CI 0.24 to 3.86) for total body bone density, 1.66% (95% CI 0.92 to 2.39) for the lumbar spine at 2 years, 1.60% (95% CI 0.78 to 2.41) for the hip, and 1.91% (95% CI 0.33 to 3.50) for the distal radius. The relative risk of fractures of the vertebrae was 0.79 (95% CI 0.54 to 1.09); the relative risk for non-vertebral fractures was 0.86 (95% CI 0.43 to 1.72). REVIEWER'S CONCLUSIONS: Calcium supplementation alone has a small positive effect on bone density. The data show a trend toward reduction in vertebral fractures, but it is unclear if calcium reduces the incidence of non vertebral fractures.

Bone Density↗

Interventions to reduce unintended pregnancies among adolescents: systematic review of randomised controlled trials.

OBJECTIVE: To review the effectiveness of primary prevention strategies aimed at delaying sexual intercourse, improving use of birth control, and reducing incidence of unintended pregnancy in adolescents. DATA SOURCES: 12 electronic bibliographic databases, 10 key journals, citations of relevant articles, and contact with authors. STUDY SELECTION: 26 trials described in 22 published and unpublished reports that randomised adolescents to an intervention or a control group (alternate intervention or nothing). DATA EXTRACTION: Two independent reviewers assessed methodological quality and abstracted data. DATA SYNTHESIS: The interventions did not delay initiation of sexual intercourse in young women (pooled odds ratio 1.12; 95% confidence interval 0.96 to 1.30) or young men (0.99; 0.84 to 1.16); did not improve use of birth control by young women at every intercourse (0.95; 0.69 to 1.30) or at last intercourse (1.05; 0.50 to 2.19) or by young men at every intercourse (0.90; 0.70 to 1.16) or at last intercourse (1.25; 0.99 to 1.59); and did not reduce pregnancy rates in young women (1.04; 0.78 to 1.40). Four abstinence programmes and one school based sex education programme were associated with an increase in number of pregnancies among partners of young male participants (1.54; 1.03 to 2.29). There were significantly fewer pregnancies in young women who received a multifaceted programme (0.41; 0.20 to 0.83), though baseline differences in this study favoured the intervention. CONCLUSIONS: Primary prevention strategies evaluated to date do not delay the initiation of sexual intercourse, improve use of birth control among young men and women, or reduce the number of pregnancies in young women.

Adolescent↗

Epidermal growth factor (EGF)-like repeats of human tenascin-C as ligands for EGF receptor.

Signaling through growth factor receptors controls such diverse cell functions as proliferation, migration, and differentiation. A critical question has been how the activation of these receptors is regulated. Most, if not all, of the known ligands for these receptors are soluble factors. However, as matrix components are highly tissue-specific and change during development and pathology, it has been suggested that select growth factor receptors might be stimulated by binding to matrix components. Herein, we describe a new class of ligand for the epidermal growth factor (EGF) receptor (EGFR) found within the EGF-like repeats of tenascin-C, an antiadhesive matrix component present during organogenesis, development, and wound repair. Select EGF-like repeats of tenascin-C elicited mitogenesis and EGFR autophosphorylation in an EGFR-dependent manner. Micromolar concentrations of EGF-like repeats induced EGFR autophosphorylation and activated extracellular signal-regulated, mitogen-activated protein kinase to levels comparable to those induced by subsaturating levels of known EGFR ligands. EGFR-dependent adhesion was noted when the ligands were tethered to inert beads, simulating the physiologically relevant presentation of tenascin-C as hexabrachion, and suggesting an increase in avidity similar to that seen for integrin ligands upon surface binding. Specific binding to EGFR was further established by immunofluorescence detection of EGF-like repeats bound to cells and cross-linking of EGFR with the repeats. Both of these interactions were abolished upon competition by EGF and enhanced by dimerization of the EGF-like repeat. Such low affinity behavior would be expected for a matrix-"tethered" ligand; i.e., a ligand which acts from the matrix, presented continuously to cell surface EGF receptors, because it can neither diffuse away nor be internalized and degraded. These data identify a new class of "insoluble" growth factor ligands and a novel mode of activation for growth factor receptors.

Binding, Competitive↗

Effect of RGD coating on osteocompatibility of PLGA-polymer disks in a rat tibial wound.

Osteocompatibility of porous polylactic-glycolic acid (PLGA) disks coated with synthetic peptides was assessed in 5-mm diameter unicortical tibial osseous wounds in rats. The coatings consisted of various ratios of peptides including the tripeptide arginine-glycine-aspartic acid (RGD) and the inactive arginine-glycine-glutamic acid (RGE). When left empty, the tibial wounds healed spontaneously with proliferation of intramedullary woven bone within 1 week. The reactive bone was resorbed, and by 3 weeks, the cortical wound was healed with lamellar bone, and the medullary space was repopulated with marrow. When PLGA disks were implanted there was a delay in repair with reduced bone fill and no bone bridging at 3 weeks. When disks were coated with increasing amounts of RGD peptide, there was a biphasic effect on osteocompatibility and on osseous ingrowth. Evaluation at 10 days showed a dose-dependent increase, with 1.5-fold greater osteocompatibility (p < 0.05) and 1.6-fold more osseous ingrowth into the polymer (p < 0.01) than uncoated disks. With more RGD and with undiluted RGE, osteocompatibility and osseous ingrowth were the same as with uncoated disks. At 3 weeks, there were no significant differences among all the groups. These data indicate that RGD coating enhanced early stages of osteocompatibility and ingrowth.

Animals↗

Etidronate for treating and preventing postmenopausal osteoporosis.

OBJECTIVES: To systematically review the efficacy of etidronate on bone density, fractures and toxicity in postmenopausal women. SEARCH STRATEGY: We searched MEDLINE from 1966 to December 1998, examined citations of relevant articles, and the proceedings of international osteoporosis meetings. We contacted osteoporosis investigators to identify additional studies, primary authors, and pharmaceutical industry sources for unpublished data. SELECTION CRITERIA: We included thirteen trials (with 1010 participants) that randomized women to etidronate or an alternative (placebo or calcium and/or vitamin D) and measured bone density for at least one year. DATA COLLECTION AND ANALYSIS: For each trial, three independent reviewers assessed the methodological quality and abstracted data. MAIN RESULTS: The data suggested a reduction in vertebral fractures with a pooled relative risk of 0.60% (95% CI 0.41 to 0.88). There was no effect on non-vertebral fractures (pooled relative risk 1.00, (95% CI 0.68 to 1.42)). Etidronate, relative to control, increased bone density after three years of treatment in the lumbar spine by 4.27% (95% CI 2.66 to 5.88), in the femoral neck by 2.19% (95% CI 0.43, 3.95) and in the total body by 0.97% (95% CI 0.39, 1.55). Effects were larger at 4 years, though the number of patients followed was much smaller. REVIEWER'S CONCLUSIONS: Etidronate increases bone density in the lumbar spine and femoral neck. The pooled estimates of fracture reduction with etidronate are consistent with a reduction in vertebral fractures, but no effect on non-vertebral fractures.

Bone Density↗

A deceptive case of amyloid myopathy: clinical and magnetic resonance imaging features.

Amyloid myopathy is a well-described, increasingly recognized clinical entity. Similar to inflammatory myopathies, amyloid myopathy presents with proximal muscle weakness and can be associated with elevated levels of muscle enzymes. We report the case of a 58-year-old woman who, at presentation to her physician with proximal muscle weakness and congestive heart failure, was antinuclear antibody positive and had muscle biopsy findings "consistent with inflammatory myopathy." She was referred to Johns Hopkins University Medical Center with the diagnosis of polymyositis. Further investigation revealed a monoclonal gammopathy, a unique patterning of subcutaneous fat reticulation and hypodense bone marrow changes on magnetic resonance imaging (MRI), and an endocardial biopsy sample that was positive for light chain amyloid deposition. Paraffin sections of the muscle biopsy sample from the time of her original presentation were obtained, and Congo red staining showed diffuse amyloid deposition throughout the sample, but no inflammation. This case not only illustrates that proximal muscle weakness due to primary amyloid myopathy (as found in light chain amyloidosis and transthyretin amyloidosis) can mimic that of polymyositis, but also shows that unique findings on MRI can alert the clinician to the diagnosis of amyloidosis prior to muscle biopsy.

Amyloidosis↗

A meta-analysis of etidronate for the treatment of postmenopausal osteoporosis.

The aim of the study was to review the effect of etidronate on bone density and fractures in postmenopausal women. We searched MEDLINE from 1966 to 1998, examined citations of relevant articles, and the proceedings of international osteoporosis meetings. We contacted osteoporosis investigators to identify additional studies, primary authors, and pharmaceutical industry sources for unpublished data. We included 13 trials that randomized women to etidronate or an alternative (placebo or calcium and/or vitamin D) and measured bone density for at least 1 year. For each trial, three independent reviewers assessed the methodologic quality and abstracted data. The data suggested a reduction in vertebral fractures with a pooled relative risk of 0.63 (95% CI 0.44 to 0.92). There was no effect on nonvertebral fractures (relative risk 0.99, (95% CI 0.69 to 1.42). Etidronate, relative to control, increased bone density after 1-3 years of treatment in the lumbar spine by 4.06% (95% CI 3.12 to 5.00), in the femoral neck by 2.35% (95% CI 1.66 to 3.04) and in the total body by 0.97% (95% CI 0.39 to 1.55). Effects were larger at 4 years, though the number of patients followed much smaller. Etidronate increases bone density in the lumbar spine and femoral neck for up to 4 years. The pooled estimates of fracture reduction with etidronate suggest a reduction in vertebral fractures, but no effect on nonvertebral fractures.

Aged↗

Problems of HRQL assessment: how much is too much?

Few investigations have explored the extent to which a number of less serious problems contribute to health-related quality of life (HRQL) impairment beyond a smaller number of more serious problems. Our study examined the relative impact of the number and severity of patient problems on HRQL. This study analyzed results from 100 patients with irritable bowel syndrome (IBS) and 100 women with polycystic ovary syndrome (PCOS). We compared an aggregation method that generated scores using all items that could affect HRQL as the denominator (all items) to a second method that considered only items that patients experienced as problems (problem items). For each IBS and PCOS questionnaire domain, we used regression analysis to examine the relative contribution of scores from the all-items and problem-items approaches to prediction of scores on the other instruments. Of 57 correlations between IBS domains and scores on the other questionnaires, the all-items method explained a statistically significant additional proportion of the variance beyond the problem items in 29 cases and the problem items a significant additional proportion of the variance between the all items in 7 (p < 0.001). Of the 28 correlations between the PCOS and the other questionnaires, the all-items approach explained a significant additional proportion of the variance in 21 cases and the problem items approach in 5 (p < 0.001). With IBS and PCOS, including all potential items in calculating a domain score provided a more accurate portrayal of HRQL than a selected approach focusing on problem items

Adult↗

Predicting success in weaning from mechanical ventilation.

We identified 65 observational studies of weaning predictors that had been reported in 70 publications. After grouping predictors with similar names but different thresholds, the following predictors met our relevance criteria: heterogeneous populations, 51; COPD patients, 21; and cardiovascular ICU patients, 45. Many variables were of no use in predicting the results of weaning. Moreover, few variables had been studied in > 50 patients or had results presented to generate estimates of predictive power. For stepwise reductions in mechanical support, the most promising predictors were a rapid shallow breathing index (RSBI) < 65 breaths/min/L (measured using the ventilator settings that were in effect at the time that the prediction was made) and a pressure time product < 275 cm H2O/L/s. The pooled likelihood ratios (LRs) were 1.1 (95% confidence interval [CI], 0.95 to 1.28) for a respiratory rate [RR] of < 38 breaths/min and 0.32 (95% CI, 0.06 to 1.71) for an RR of > 38 breaths/min, which indicate that an RR of < 38 breaths/min leaves the probability of successful weaning virtually unchanged but that a value of > 38 breaths/min leads to a small reduction in the probability of success in weaning the level of mechanical support. For trials of unassisted breathing, the most promising weaning predictors include the following: RR; RSBI; a product of RSBI and occlusion pressure < 450 cm H2O breaths/min/L; maximal inspiratory pressure (PImax) < 20 cm H2O; and a knowledge-based system for adjusting pressure support. Pooled results for the power of a positive test result for both RR and RSBI were limited (highest LR, 2.23), while the power of a negative test result was substantial (ie, LR, 0.09 to 0.23). Summary data suggest a similar predictive power for RR and RSBI. In the prediction of successful extubation, an RR of < 38 breaths/min (sensitivity, 88%; specificity, 47%), an RSBI < 100 or 105 breaths/min/L (sensitivity, 65 to 96%; specificity, 0 to 73%), PImax, and APACHE (acute physiology and chronic health evaluation) II scores that are obtained at hospital admission appear to be the most promising. After pooling, two variables appeared to have some value. An RR of > 38 breaths/min and an RSBI of > 100 breaths/min/L appear to reduce the probability of successful extubation, and PImax < 0.3, for which the pooled LR is 2.23 (95% CI, 1.15 to 4.34), appears to marginally increase the likelihood of successful extubation. Judging by areas under the receiver operator curve for all variables, none of these variables demonstrate more than modest accuracy in predicting weaning outcome. Why do most of these tests perform so poorly? The likely explanation is that clinicians have already considered the results when they choose patients for trials of weaning.

APACHE↗

Trials comparing alternative weaning modes and discontinuation assessments.

We identified 16 randomized controlled trials (RCTs) of methods for weaning patients from mechanical ventilation, 8 of which were trials of discontinuation assessment strategies, 5 of which were trials of stepwise reduction in mechanical ventilatory support, and 3 of which were trials comparing alternative ventilation modes for weaning periods lasting < 48 h. We found that different thresholds for deciding when a patient is ready for a trial of spontaneous breathing, different criteria for a successful trial, and different thresholds for extubation may overwhelm the impact of alternative ventilation strategies. Nevertheless, the results of these studies suggest the possibility that multiple daily T-piece weaning or pressure support may be superior to synchronized intermittent mandatory ventilation. Other RCTs suggest that early extubation with the back-up institution of noninvasive positive-pressure ventilation as needed may be a useful strategy in selected patients.

Evidence-Based Medicine↗

Trials comparing early vs late extubation following cardiovascular surgery.

We identified 10 randomized trials that compared alternative management approaches to patient care during and following cardiovascular surgery. One overall strategy involved a modification of anesthesia, in particular, a reduction in the dosage of fentanyl and benzodiazepine or the substitution of fentanyl for propofol (five randomized controlled trials [RCTs]). Pooled results show a shorter duration of ventilation (7 h) and a shorter duration of hospital stay (approximately 1 day) associated with lower anesthetic doses. The second strategy involved early vs late extubation once patients were admitted to the ICU (five RCTs). Pooled results show a shorter duration of ventilation (13 h) and a shorter duration of ICU stay (half a day) associated with early extubation. An additional 8 nonrandomized trials had findings that were consistent with the 10 RCTs. Reintubation, complications, and mortality rates were too low to draw conclusions about these outcomes. Overall, these studies indicate that anesthetic, sedation, and early-extubation strategies in selected cardiac surgery patients are associated with a shorter duration of mechanical ventilation and shorter lengths of ICU and hospital stays.

Cardiac Surgical Procedures↗

Development, dissemination, implementation and evaluation of a clinical pathway for oxygen therapy.

BACKGROUND: Oxygen is commonly administered to patients in hospital, but prescribing and monitoring of such therapy may be suboptimal. The objective of this study was to develop, disseminate, implement and evaluate a multidisciplinary clinical pathway for the administration of oxygen. METHODS: The authors developed a clinical pathway for the ordering, titration and discontinuation of oxygen, which was disseminated through teaching sessions, in-service training sessions and information posters in a medical clinical teaching unit (CTU). Implementation of the pathway was ensured by means of reminders and patient-centred audit and feedback to CTU nurses and house staff. During a 3-month intervention phase, consecutive patients requiring supplemental oxygen were treated according to the pathway. During a 1-month "wash-out" phase followed by a 3-month non-intervention phase, patients were treated at the discretion of the CTU team. Clinical and economic data were collected in both phases. RESULTS: In the 2 phases, patient characteristics, the concentration and duration of oxygen prescribed, the frequency of oxygen saturation monitoring, the frequency of arterial blood gas testing and the clinical outcomes were similar. However, there were more discontinuation orders in the intervention phase (p < 0.001). In the intervention phase, costs were higher for monitoring of oxygen saturation ($44.95/patient v. $36.17/patient, p = 0.048) and for order transcription ($2.71/patient v. $1.28/patient, p < 0.001); total costs, including those for personnel, were also higher in the intervention phase ($76.93/patient v. $56.67/patient, p = 0.02). The cost of education about the oxygen pathway was $45.71/patient. When the education cost was included, the total cost of oxygen therapy during the intervention phase was $122.64/patient; this was significantly higher than the total cost of oxygen therapy during the non-intervention phase ($56.67/patient) (p < 0.001). INTERPRETATION: This multidisciplinary, multimethod oxygen pathway led to changes in oxygen-prescribing behaviour, consumed more resources than standard management and was not associated with changes in patient outcome. Appropriate management of oxygen prescribing and monitoring by physicians and nurses take time and costs money.

Aged↗

Randomized trials versus observational studies in adolescent pregnancy prevention.

The objective of this study is to compare the results of randomized trials and observational studies of interventions to prevent adolescent pregnancy. We identified published and unpublished reports through computerized searches of CATLINE, CINAHL, CONFERENCE PAPERS INDEX, DISSERTATION ABSTRACTS ONLINE, EMBASE, ERIC, MEDLINE, NTIS, POPLINE, PsycINFO, and SOCIOLOGICAL ABSTRACTS; manual searches of eight relevant journals; reference lists from primary articles; and contact with content experts. We included randomized trials and observational studies that evaluated the impact of primary prevention interventions including sex education classes, school-based clinics, free-standing clinics, physician/nurse practitioner practice-based service, improved access, and community-based programs on four outcomes: sexual intercourse, birth control use, responsible sexual behavior, or pregnancy in adolescents. One investigator abstracted the data and a second conducted a detailed review of the abstraction. We identified 13 randomized trials and 17 observational studies. We generated estimates of the impact of the interventions separately for males and females for all four outcomes for both observational studies and randomized trials. For six of the eight outcomes the summary odds ratios for the observational studies showed a significant intervention benefit (P<0.05) while the randomized trials did not show a benefit for any outcome in either females or males. The difference between the results of the observational studies and randomized trials was statistically significant in two of the eight outcomes (P<0.05 for initiation of intercourse and pregnancy in females). Observational studies yield systematically greater estimates of treatment effects than randomized trials of adolescent pregnancy prevention interventions. Public policy or individual patient treatment decisions should be based on observational studies only when randomized trials are unavailable and only with careful consideration of possible biases.

Adolescent↗

Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group.

OBJECTIVE: To evaluate the incidence and risk factors for clinically important upper gastrointestinal bleeding in critically ill patients requiring mechanical ventilation. DESIGN: In duplicate, blinded adjudicators determined the presence of clinically important gastrointestinal bleeding using a priori criteria, evaluating relevant clinical, laboratory, and diagnostic data. Cox proportional hazards regression analyses were used to examine baseline and time-dependent risk factors for bleeding. SETTING: Sixteen university-affiliated intensive care units (ICUs) in Canada. PATIENTS: A total of 1,077 critically ill ICU patients ventilated for at least 48 hrs. INTERVENTIONS: Patients were randomized to stress ulcer prophylaxis with intravenous ranitidine or nasogastric sucralfate; otherwise, management was at the discretion of the ICU team. MEASUREMENTS AND MAIN RESULTS: Demographic data included patient characteristics, Acute Physiology and Chronic Health Evaluation II score, and multiple organ dysfunction (MOD) score. Each day in the ICU, physiologic measurements including MOD score, feeding, and other treatment variables were recorded. The significant risk factors for upper gastrointestinal bleeding in the univariable analyses were low platelet count, maximum serum creatinine, maximum MOD score, maximum pulmonary component of the MOD score, maximum hepatic component of the MOD score, maximum renal component of the MOD score, enteral nutrition, and stress ulcer prophylaxis with ranitidine. The only independent predictors of bleeding in the multivariable analysis were maximum serum creatinine (relative risk = 1.16 [95% confidence interval = 1.02-1.32]), enteral nutrition (relative risk = 0.30 [95% confidence interval = 0.13-0.67]), and ranitidine administration (relative risk = 0.39 [95% confidence interval = 0.17-0.83]). CONCLUSIONS: In critically ill ventilated patients, renal failure was independently associated with an increased risk of clinically important gastrointestinal bleeding, whereas enteral nutrition and stress ulcer prophylaxis with ranitidine conferred significantly lower bleeding rates.

APACHE↗