Clinical effectiveness of a silicone foam dressing for the prevention of heel pressure ulcers in critically ill patients: Border II Trial.

OBJECTIVE: Critically ill patients are at high risk of developing pressure ulcers (PU), with the sacrum and heels being highly susceptible to pressure injuries. The objective of our study was to evaluate the clinical effectiveness of a new multi-layer, self-adhesive soft silicone foam heel dressing to prevent PU development in trauma and critically ill patients in the intensive care unit (ICU). METHOD: A cohort of critically ill patients were enrolled at the Royal Melbourne Hospital. Each patient had the multi-layer soft silicone foam dressing applied to each heel on admission to the emergency department. The dressings were retained with a tubular bandage for the duration of the patients' stay in the ICU. The skin under the dressings was examined daily and the dressings were replaced every three days. The comparator for our cohort study was the control group from the recently completed Border Trial. RESULTS: Of the 191 patients in the initial cohort, excluding deaths, loss to follow-up and transfers to another ward, 150 patients were included in the final analysis. There was no difference in key demographic or physiological variables between the cohorts, apart from a longer ICU length of stay for our current cohort. No PUs developed in any of our intervention cohort patients compared with 14 patients in the control cohort (n=152; p<0.001) who developed a total of 19 heel PUs. CONCLUSION: We conclude, based on our results, that the multi-layer soft silicone foam dressing under investigation was clinically effective in reducing ICU-acquired heel PUs. The findings also support previous research on the clinical effectiveness of multi-layer soft silicone foam dressings for PU prevention in the ICU.

A novel magnetic approach to enhance the efficacy of cell-based gene therapies.

Attempts have been made to use various forms of cellular vectors to deliver therapeutic genes to diseased tissues like malignant tumours. However, this approach has proved problematic due to the poor uptake of these vectors by the target tissue. We have devised a novel way of using magnetic nanoparticles (MNPs) to enhance the uptake of such 'therapeutically armed' cells by tumours. Monocytes naturally migrate from the bloodstream into tumours, so attempts have been made to use them to deliver therapeutic genes to these sites. However, transfected monocytes injected systemically fail to infiltrate tumours in large numbers. Using a new in vitro assay for assessing monocyte extravasation, we show that the ability of transfected human monocytes to migrate across a human endothelial cell layer into a 3D tumour spheroid is markedly increased when cells are pre-loaded with MNPs and a magnetic force is applied close to the spheroid. Furthermore, systemic administration of such 'magnetic' monocytes to mice bearing solid tumours led to a marked increase in their extravasation into the tumour in the presence of an external magnet. This new magnetic targeting approach could be used to increase the targeting, and thus the efficacy, of many cell-based gene therapies in vivo.

Meta-analyses in orthopaedic surgery. A systematic review of their methodologies.

BACKGROUND: The number and quality of well-designed scientific studies in the orthopaedic literature are limited. The purpose of this review was to determine the methodological qualities of published meta-analyses on orthopaedic-surgery-related topics. METHODS: A systematic review of meta-analyses was conducted. A search of the Medline database provided lists of meta-analyses in orthopaedics published from 1969 to 1999. Extensive manual searches of major orthopaedic journals, bibliographies of major orthopaedic texts, and personal files identified additional studies. Of 601 studies identified, forty met the criteria for eligibility. Two investigators each assessed the quality of the studies under blinded conditions, and they abstracted relevant data. RESULTS: More than 50% of the meta-analyses included in this review were published after 1994. We found that 88% had methodological flaws that could limit their validity. The main deficiency was a lack of information on the methods used to retrieve and assess the validity of the primary studies. Regression analysis revealed that meta-analyses authored in affiliation with an epidemiology department and those published in nonsurgical journals were associated with higher scores for quality. Meta-analyses with lower scores for quality tended to report positive findings. The meta-analyses that focused upon fracture treatment and degenerative disease (hip, knee, or spine) had significantly lower mean quality scores than did meta-analyses that examined thrombosis prevention and diagnostic tests (p < 0.05). CONCLUSIONS: The majority of meta-analyses on orthopaedic-surgery-related topics have methodological limitations. Limitation of bias and improvement in the validity of the meta-analyses can be achieved by adherence to strict scientific methodology. However, the ultimate quality of a meta-analysis depends on the quality of the primary studies on which it is based. A meta-analysis is most persuasive when data from high-quality randomized trials are pooled.

Establishment of creatinine clearance reference values for older women.

Age-adjusted reference ranges for creatinine clearance were determined in 279 women, ages 40-95 years, who were housed in a metabolic research unit and consumed a meat-free diet. Creatinine clearance, but not serum creatinine, declined with age by 0.63 mL/min per 1.73 m2 per year. Serum and urine creatinine concentrations, used to calculate clearances, were analyzed by a kinetic Jaffé procedure. In a subset of 100 subjects, fasting serum creatinine values averaged 8.3 +/- 5.2 (SD) mumol/L higher when measured by the kinetic Jaffé procedure than by an enzymatic method (creatinine PAP). The Cockcroft-Gault formula for estimating creatinine clearance from serum creatinine in women was validated, and the modification factor for the male equation was determined to be 0.84 (95% confidence interval 0.83-0.86) confirming the suggested 15% correction. A prediction formula derived from this population was similar in accuracy to the Cockcroft-Gault formula.

Assessment of the safety of high-dose, short-term supplementation with vitamin E in healthy older adults.

The effect of daily supplementation of 800 mg dl alpha-tocopheryl acetate for 30 d on general health, nutrient status, hepatic and renal function, intermediary metabolism, hematological status, plasma nutrients and antioxidant status, thyroid hormones, and urinary creatinine concentrations was studied in 32 healthy elderly (> 60 y) people who participated in a double-blind, placebo-controlled, residential trial. The subjects reported no side effects due to the supplements. Supplementation had no effect on body weight, plasma total protein, albumin, glucose, total cholesterol and triglycerides, conjugated and unconjugated bilirubin, alkaline phosphatase, indicators of hepatic and renal function, hematologic status, thyroid hormones, or serum and urinary creatinine concentrations and creatinine clearance. Supplementation did cause a significant increase in serum vitamin E, and a small (5%) but significant (P < 0.05) increase in plasma zinc in the vitamin E-supplemented group. Thus, short-term supplementation with 800 mg vitamin E/d has no adverse effect on healthy older adults.

Nutritional correlates of atrophic glossitis: possible role of vitamin E in papillary atrophy.

Atrophy of the filiform papillae of the tongue is a sign of malnutrition. However, papillary atrophy has not been correlated with laboratory indices of nutritional status. We studied photographs of tongues from 30 elderly subjects and determined the percentage of normal papillary development (%NPD) relative to a reference photograph. We also determined 16 nutritional blood levels and used stepwise multiple linear regression to examine their relationship to %NPD. We found that %NPD correlated significantly (p < 0.0031) with levels of vitamin E and prealbumin, but not with 14 other laboratory indices. Subjects with overt atrophic glossitis (%NPD < 50%) tended to have multiple nutritional deficiencies. The high correlation of plasma vitamin E levels with %NPD may be related to its role as an antioxidant and in the maintenance of cellular membrane integrity.

Relationships between acetone, cataracts, and ascorbate in hairless guinea pigs.

Acetone is one of the most commonly used industrial solvents. Recent literature indicated that in guinea pigs, but not rabbits, acetone is cataractogenic and that elevated acetone exposure is also associated with depressed aqueous ascorbate levels. Other work indicated that aqueous and lens levels of ascorbate are closely linked and that depressed ascorbate status is related to cataract. Taken together, these papers suggested that acetone exposure, depressed ascorbate levels, and cataract are related, possibly causally. While the possibility that acetone is cataractogenic presented a major health concern, it also presented an opportunity to develop a new model of cataract in which hypotheses regarding anticataractogenic effects of ascorbate could be tested. Albino hairless guinea pigs are immunocompetent animals derived from albino Hartley guinea pigs. Animals were fed diets containing low (4.9 mg/day) and high (55 mg/day) levels of ascorbate. This resulted in distinct groups of animals, one with high tissue ascorbate levels and the other with low, but nonscorbutic ascorbate levels. The tissue levels of ascorbate and the relationship between tissue ascorbate levels and dietary intake indicate that with respect to ascorbate uptake, transport, and concentration, these animals are identical to the standard albino Hartley animals. Daily exposure to acetone was extended for 6 months, with a total applied dose of 65 ml. Absorption of the solvent was maximized by the use of hairless animals. Despite exposure of the animals to higher levels of acetone, in no case (n = 20) were cataracts observed over a 2-year period. This is consistent with results using rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Vascular disease risk factors, urinary free cortisol, and health histories in older adults: shyness and gender interactions.

We studied relationships between shyness and health during a health screening survey of older adults (ages 50-88) living in an active retirement community in the southwestern United States (n = 232). As in previous studies of infants, older individuals with hay fever, insomnia and constipation were more shy than those without these problems. Shy persons overall showed higher sitting systolic blood pressure and a larger fall in orthostatic systolic blood pressure on standing; shy men had a greater prevalence of hypertension histories than did low-shy men. Shy subjects of both sexes had lower HDL cholesterol and higher triglycerides than did low-shy subjects; shy women tended to have higher LDL cholesterol than did low-shy women. In contrast with findings of elevated salivary cortisol in extremely inhibited children of both sexes, only shy women had higher 24 h urinary free cortisol excretion than did low-shy women; men showed the opposite pattern, possibly related to suppression of aggression. Shy men also tended to report a higher prevalence of thyroid disease history than did low-shy men (20% versus 6%). Notably, autoimmune thyroiditis has previously been linked with panic and depression, disorders which in turn have been associated with shyness. Taken together with previous work in shy children and their families, the data raise the possibility of (a) increased risk for arteriosclerotic vascular disease; and (b) increased risk of adrenal- and/or thyroid-related diseases in certain shy older adults.

Plasma homocysteine in vascular disease and in nonvascular dementia of depressed elderly people.

Depression among elderly people with reversible cognitive loss often manifests with concomitant vascular disease and can also precede the development of nonvascular degenerative dementia. Little is known about etiological factors for reversible or irreversible dementias in older depressed people. The amino acid homocysteine (HC), which is both a vascular disease risk factor and a precursor of the excitotoxic amino acids cysteine and homocysteic acid, could play a role in the pathophysiology of such individuals. Twenty-seven depressed elderly acute inpatients by DSM-III-R criteria had significantly higher plasma homocysteine levels and lower cognitive screening test scores than did 15 depressed young adult inpatients. HC was highest in the older patients who had concomitant vascular diseases (n = 14). HC was lowest in the older depressives who had neither vascular illnesses nor dementia (n = 8), comparable to the young adult depressives. Higher HC correlated significantly with poorer cognition only in the nonvascular geriatric patients (rs = -0.53). The findings extend earlier work showing higher HC in vascular patients from general medical populations, and also suggest a possible metabolic factor in certain dementias associated with late-life depression.