Impaired hospitalized patient mobility is associated with nurse injuries.

BACKGROUND: Staff injuries adversely affect the health of staff members as well the ability of health care teams to effectively care for patients. Identifying patients who pose an increased risk of injury may allow for the planning of risk mitigation strategies, but few studies have examined patient factors associated with staff injury risk. AIMS: Examine the relationship between staff injury and patient mobility, which has been linked to other key hospital outcomes. METHODS: Linking occupational health and electronic medical record data, we examined documented patient mobility levels, based on the Activity Measure for Post-Acute Care (AM-PAC) and the Johns Hopkins Highest Level of Mobility (JH-HLM) Scale, on the day prior to injury. In addition, we created a matched cohort of control patients not associated with staff injury to examine the influence of patient mobility on the odds of staff injury. RESULTS: We identified 199 staff injuries associated with 181 patients with 1063 matched controls. Patients had median scores of 11 and 3 on the AM-PAC and JH-HLM, respectively, indicating moderate-severe mobility impairments. In addition, scores in the lowest AM-PAC tertile (6-15) and lowest JH-HLM tertile (1-4) were associated with a 4.46-fold and 2.90-fold increase in the odds of nurse injury, respectively. CONCLUSIONS: These results indicate that moderate-severe mobility impairments are associated with increased risk of nurse injury. Hospitals and clinical care teams should consider documenting mobility routinely and utilizing these values to identify patients who pose an increased risk of nurse injury.

Psychosocial predictors of weight loss by race and sex.

This paper examined the psychosocial predictors of weight loss among race and sex subgroups. Analyses included overweight and obese participants from the PREMIER study, a previously published randomized trial that examined the effects of two multi-component lifestyle interventions on blood pressure among pre-hypertensive and stage 1 hypertensive adults. Both intervention conditions received behavioural recommendations for weight loss and group sessions. Weight and psychosocial measures of self-efficacy and social support for diet and exercise were assessed at baseline and at 6 months. There were 157 African-American (AA) women, 46 AA men, 203 non-AA women and 182 non-AA men with an average age of 50 years and average body mass index of 34 at baseline. Multiple predictor regression models were performed individually by race and sex subgroup. Among AA women, increases in diet self-efficacy were associated with weight loss. Among AA men, increases in diet-related social support and self-efficacy, along with increases in family support to exercise, were associated with weight loss (all Ps <0.05). Among non-AA women, increases in friends' support to exercise and exercise-related self-efficacy were associated with weight loss, and among non-AA men only increases in diet self-efficacy were associated with weight loss (all Ps <0.05). These results emphasize the need for targeted interventions based on race and sex to optimize the impact of lifestyle-based weight loss programmes.

TNF-alpha and melphalan-based isolated limb perfusion: no evidence supporting the early destruction of tumour vasculature.

BACKGROUND: Isolated limb perfusion with TNF-alpha and melphalan (TM-ILP) is a highly effective treatment for locally advanced tumours of the extremities. Previous research suggests an almost immediate disintegration of the blood supply of the tumour. The aim of the present study was to verify this hypothesis using non-invasive measurements of microvascular perfusion and tissue oxygenation. METHODS: A total of 11 patients were included in the study. TM-ILP was performed under mildly hyperthermic conditions (39 °C) in the extremities via proximal vascular access. Capillary-venous microvascular blood flow, haemoglobin level (Hb) and oxygen saturation (SO2) were determined using laser Doppler and white-light spectroscopy, respectively, before TM-ILP and at 30 min, 4 h, 1 day, 4 days, 1 week, 2 weeks and 6 weeks after TM-ILP from tumour and healthy muscle tissues. RESULTS: Blood flow and Hb were mostly higher, whereas SO2 was lower, in tumour tissue compared with muscle tissue. In both tumour and muscle tissues, blood flow significantly increased immediately after TM-ILP and remained elevated for at least 2 weeks, followed by a return to the initial values 6 weeks after the procedure. CONCLUSION: No signs were found of early destruction of the tumour vasculature. The observations suggest that an inflammatory reaction is one of the key elements of TM-ILP.

Women's attitudes towards a pre-conception healthy lifestyle programme.

Nearly half of US women begin pregnancy overweight or obese and more than half of overweight or obese pregnant women experience excessive gestational weight gain. Recent lifestyle intervention programmes have helped women avoid excessive weight gain during pregnancy, but helping women lose weight before pregnancy may be a more effective way to improve pregnancy outcomes. This study assessed women's attitudes towards pre-conception diet and weight management interventions. An anonymous survey was conducted in patients waiting in a health maintenance organization's obstetrics and primary care waiting rooms. It focused on attitudes towards participating in a pre-conception, lifestyle change programme. Eighty percent of the 126 women surveyed were pregnant or considering pregnancy within 5 years. Of the 126 respondents, 60 (48%) were overweight or obese. Of these, 96% rated healthy diet and healthy weight before pregnancy as very important or important and 77% favoured a healthy lifestyle programme (diet, weight management and physical activity) before becoming pregnant. Likewise, overweight or obese women reported being likely or highly likely to participate in specific intervention programme aspects such as keeping phone appointments (77%), using a programme website (70%) and keeping food and exercise records (63%). Survey results show that women in this population believe that adopting a healthy lifestyle and losing weight are important before pregnancy and that they are enthusiastic about programmes that will help them achieve those goals in preparation for pregnancy.

Behavioral mediators of treatment effects in the weight loss maintenance trial.

BACKGROUND: The Weight Loss Maintenance Trial tested strategies for maintenance of weight loss. Personal contact was superior to interactive technology and self-directed conditions. PURPOSE: We aimed to identify behavioral mediators of the superior effect of personal contact vs. interactive technology and of personal contact vs. self-directed arms. METHODS: Overweight/obese adults at risk for cardiovascular disease (n = 1,032) who lost at least 4 kg were randomized to personal contact, interactive technology, or self-directed. After 30 months, 880 participants had data on weight and behavioral strategies. RESULTS: Reported increase of intake of fruits and vegetables and physical activity and more frequent self-weighing met criteria as mediators of the better outcome of personal contact vs. interactive technology. Increased intake of fruits and vegetables, more frequent self-weighing, and decreased dessert consumption were mediators of the difference between personal contact vs. self-directed. CONCLUSION: Inducing changes in the identified behaviors might yield better outcomes in future weight loss maintenance trials.

The effects of weight cycling on lifespan in male C57BL/6J mice.

OBJECTIVE: With the increasing rates of obesity, many people diet in an attempt to lose weight. As weight loss is seldom maintained in a single effort, weight cycling is a common occurrence. Unfortunately, reports from clinical studies that have attempted to determine the effect of weight cycling on mortality are in disagreement, and to date, no controlled animal study has been performed to assess the impact of weight cycling on longevity. Therefore, our objective was to determine whether weight cycling altered lifespan in mice that experienced repeated weight gain and weight loss throughout their lives. METHODS: Male C57BL/6J mice were placed on one of three lifelong diets: a low-fat (LF) diet, a high-fat (HF) diet or a cycled diet in which the mice alternated between 4 weeks on the LF diet and 4 weeks on the HF diet. Body weight, body composition, several blood parameters and lifespan were assessed. RESULTS: Cycling between the HF and LF diet resulted in large fluctuations in body weight and fat mass. These gains and losses corresponded to significant increases and decreases, respectively, in leptin, resistin, GIP, IGF-1, glucose, insulin and glucose tolerance. Surprisingly, weight cycled mice had no significant difference in lifespan (801±45 days) as compared to LF-fed controls (828±74 days), despite being overweight and eating a HF diet for half of their lives. In contrast, the HF-fed group experienced a significant decrease in lifespan (544±73 days) compared with LF-fed controls and cycled mice. CONCLUSIONS: This is the first controlled mouse study to demonstrate the effect of lifelong weight cycling on longevity. The act of repeatedly gaining and losing weight, in itself, did not decrease lifespan and was more beneficial than remaining obese.

Impact of sleep, screen time, depression and stress on weight change in the intensive weight loss phase of the LIFE study.

BACKGROUND: The LIFE study is a two-phase randomized clinical trial comparing two approaches to maintaining weight loss following guided weight loss. Phase I provided a nonrandomized intensive 6-month behavioral weight loss intervention to 472 obese (body mass index 30-50) adult participants. Phase II is the randomized weight loss maintenance portion of the study. This paper focuses on Phase I measures of sleep, screen time, depression and stress. METHODS: The Phase I intervention consisted of 22 group sessions led over 26 weeks by behavioral counselors. Recommendations included reducing dietary intake by 500 calories per day, adopting the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and increasing physical exercise to at least 180 min per week. Measures reported here are sleep time, insomnia, screen time, depression and stress at entry and post-weight loss intervention follow-up. RESULTS: The mean weight loss for all participants over the intensive Phase I weight loss intervention was 6.3 kg (s.d. 7.1). Sixty percent (N=285) of participants lost at least 4.5 kg (10 lbs) and were randomized into Phase II. Participants (N=472) attended a mean of 73.1% (s.d. 26.7) of sessions, completed 5.1 (s.d. 1.9) daily food records/week, and reported 195.1 min (s.d. 123.1) of exercise per week. Using logistic regression, sleep time (quadratic trend, P=0.030) and lower stress (P=0.024) at entry predicted success in the weight loss program, and lower stress predicted greater weight loss during Phase I (P=0.021). In addition, weight loss was significantly correlated with declines in stress (P=0.048) and depression (P=0.035). CONCLUSION: Results suggest that clinicians and investigators might consider targeting sleep, depression and stress as part of a behavioral weight loss intervention.

Granulovacuolar degeneration (GVD) bodies of Alzheimer's disease (AD) resemble late-stage autophagic organelles.

AIMS: Granulovacuolar degeneration involves the accumulation of large, double membrane-bound bodies within certain neurones during the course of Alzheimer's disease (AD) and other adult-onset dementias. Because of the two-layer membrane morphology, it has been proposed that the bodies are related to autophagic organelles. The aim of this study was to test this hypothesis, and determine the approximate stage at which the pathway stalls in AD. METHODS: Spatial colocalization of autophagic and endocytic markers with casein kinase 1 delta, a marker for granulovacuolar degeneration (GVD) bodies, was evaluated in hippocampal sections prepared from post mortem Braak stage IV and V AD cases using double-label confocal fluorescence microscopy. RESULTS: GVD bodies colocalized weakly with early-stage autophagy markers LC3 and p62, but strongly with late-stage marker lysosome-associated membrane protein 1 (LAMP1), which decorated their surrounding membranes. GVD bodies also colocalized strongly with charged multivesicular body protein 2B (CHMP2B), which colocalized with the core granule, but less strongly with lysosomal marker cathepsin D. CONCLUSIONS: The resultant immunohistochemical signature suggests that granulovacuolar degeneration bodies (GVBs) do contain late-stage autophagic markers, and accumulate at the nexus of autophagic and endocytic pathways. The data further suggest that failure to complete autolysosome formation may be an important correlate of GVB accumulation.

Imaging as a strategy for premortem diagnosis and staging of tauopathies.

Alzheimer's disease is diagnosed by postmortem detection of pathological lesions that accumulate in specific brain regions. Although the presence of both beta-amyloid plaques and tau-bearing neurofibrillary lesions defines Alzheimer's disease, the distribution of neurofibrillary lesions alone correlates strongly with neurodegeneration and cognitive decline. A whole-brain imaging test capable of detecting these lesions in premortem cases could have great potential for staging and differentially diagnosing Alzheimer's disease. Here we discuss the challenges in developing a whole-brain imaging approach for detection of this intracellular target.

Genetic and pharmacologic evidence that Rac1 GTPase is involved in regulation of platelet secretion and aggregation.

BACKGROUND: Rac1 GTPase, a member of the Ras-related Rho GTPase family, is the major Rac isoform present in platelets and has been shown to be involved in cell actin cytoskeleton reorganization and adhesion. Agonists that induce platelet secretion and aggregation also activate Rac1 GTPase, raising the possibility that Rac1 GTPase may be involved in regulation of platelet function. OBJECTIVES: To rigorously define the role of Rac1 in platelet regulation. METHODS: We have used a dual approach of gene targeting in mice and pharmacologic inhibition of Rac1 by NSC23766, a rationally designed specific small molecule inhibitor, to study the role of Rac1 in platelet function. RESULTS: Platelets from mice as well as human platelets treated with NSC23766 exhibited a significant decrease in: (i) active Rac1 species and phosphorylation of the Rac effector, p21-activated kinase; (ii) expression of P-selectin and secretion of adenosine triphosphate induced by thrombin or U46619; and (iii) aggregation induced by adenosine 5'-diphosphate, collagen, thrombin and U46619, a stable analog of thromboxane A(2). NSC23766 did not alter the cAMP or cGMP levels in platelets. Consistent with the requirement of Rac1 for normal platelet function, the bleeding times in Rac1(-/-) mice or mice given NSC23766 were significantly prolonged. CONCLUSIONS: Our data show that deficiency or inhibition of Rac1 GTPase blocks platelet secretion. The inhibition of secretion, at least in part, is responsible for diminished platelet aggregation and prolonged bleeding times observed in Rac1 knockout or Rac1 inhibitor-treated mice.

Hermaphroditism in a Sprague-Dawley rat.

A spontaneous case of unilateral true hermaphroditism was observed during the routine necropsy of a 9-week-old presumed female Sprague-Dawley rat on a repeat-dose toxicity study. There were no drug-related effects observed. True hermaphroditism is rare in rats, and despite the large numbers of rats examined annually, few cases are reported in the literature.

Effects of oral glucosamine and chondroitin sulfate alone and in combination on the metabolism of SHR and SD rats.

Glucosamine (G), often combined with chondroitin sulfate (CS), is a popular natural supplement used widely to treat osteoarthritis. However, use of glucosamine has been linked to development of insulin resistance. To assess the association between glucosamine and insulin resistance more closely, we challenged two rat strains highly sensitive to sugar-induced insulin resistance-Sprague-Dawley (SD) and Spontaneously Hypertensive (SHR) rats. Since elevations of systolic blood pressure (SBP) have been found to be an early and highly sensitive sign of insulin resistance in these two rat strains, we used this parameter as our primary endpoint. Four groups of both rat strains received either no agent (control), G, CS, or a combination of both for 9 weeks. The intake of each agent was calculated to be approximately 3-7 times comparable to human dose. Throughout the study, SBP of both strains consuming the two ingredients alone and in combination were not elevated. Rather, they were significantly lower than control, contrary to what is found in glucose-induced insulin resistance in rats. Over the study period, body weights of the four groups of SD and SHR did not vary significantly. Furthermore, no consistent trends in circulating glucose concentrations were found among the four different groups in the two strains after oral challenge with glucose. Finally, no significant histological differences were found in hearts, kidneys, and livers among the various groups of SHR and SD. From the above result, we conclude that glucosamine and chondroitin sulfate given alone or together do not produce insulin resistance or other related perturbations in two rat strains highly sensitive to sugar-induced insulin resistance.

Total synthesis and antifungal evaluation of cyclic aminohexapeptides.

The need for new therapies to treat systemic fungal infections continues to rise. Naturally occurring hexapeptide echinocandin B (1) has shown potent antifungal activity via its inhibition of the synthesis of beta-1,3 glucan, a key fungal cell wall component. Although this series of agents has been limited thus far based on their physicochemical characteristics, we have found that the synthesis of analogues bearing an aminoproline residue in the 'northwest' position imparts greatly improved water solubility (> 5 mg/mL). The synthesis and structure-activity relationships (SAR) based on whole cell and upon in vivo activity of the series of compounds are reported.

Propofol and alfentanil prevent the increase in intraocular pressure caused by succinylcholine and endotracheal intubation during a rapid sequence induction of anesthesia.

The increase in intraocular pressure (IOP) associated with succinylcholine (Sch) has made its use in patients with open globe injuries controversial. Studies that have examined techniques to prevent the increase in IOP due to Sch have shown a larger increase in IOP from the stimulus of laryngoscopy and endotracheal intubation. The purpose of our study was to examine whether the combination of propofol and alfentanil would prevent the increase in IOP due to Sch as well as endotracheal intubation during a rapid sequence induction of anesthesia. Sixty patients were randomized to receive either thiopental 5 mg/kg and Sch 1.5 mg/kg (Group I), propofol 2 mg/kg and Sch 1.5 mg/kg (Group II), or propofol 2 mg/kg, alfentanil 40 micrograms/kg, and Sch 1.5 mg/kg (Group III). The IOP was measured continuously from baseline awake (control) values until 15 s after successful intubation. All three groups had a significant decrease in IOP with the induction of anesthesia. Succinylcholine produced a consistent increase in IOP from the postinduction low in Groups I and II, but this increase was not significantly higher than baseline. The postintubation IOPs in Groups I and II were significantly higher than baseline (P < 0.001). During the entire study period, the IOP in Group III never increased above baseline. The IOP in Groups I and II had already begun to decline by 15 s postintubation, suggesting that laryngoscopy and intubation have the greatest effect on increasing IOP. We conclude that the combination of propofol and alfentanil prevents the increase in IOP from Sch as well as the increase associated with endotracheal intubation during a rapid sequence induction of anesthesia.

Clinical significance of reported changes in pain severity.

STUDY OBJECTIVE: To determine the amount of change in pain severity, as measured by a visual analog scale, that constitutes a minimum clinically significant difference. METHODS: Patients 18 years of age or older who presented with acute pain resulting from trauma were enrolled in this prospective, descriptive study. The setting was an urban county hospital emergency department with a Level 1 trauma center. In the course of a brief interview, patients were asked to indicate their current pain severity with a single mark through a standard 100-mm visual analog scale. At intervals of 20 minutes for the next 2 hours, patients were asked to repeat this measurement and, in addition, to contrast their present pain severity with that at the time of the previous measurement. They were to indicate whether they had "much less," "a little less," "about the same," "a little more," or "much more" pain. All contrasts were made without reference to prior visual analog scale measurements. A maximum of six measurements of pain change were recorded per patient. Measurements ended when the patient left the ED or when the patient reported a pain score of zero. The minimum clinically significant change in visual analog scale pain score was defined as the mean difference between current and preceding visual analog scale scores when the subject noted a little less or a little more pain. RESULTS: Forty-eight subjects were enrolled, and 248 pain contrasts were recorded. Of these contrasts, 41 were rated as a little less and 39 as a little more pain. The mean difference between current and preceding visual analog scale scores in these 80 contrasts was 13 mm (95% confidence interval, 10 to 17 mm). CONCLUSION: The minimum clinically significant change in patient pain severity measured with a 100-mm visual analog scale was 13 mm. Studies of pain experience that report less than a 13-mm change in pain severity, although statistically significant, may have no clinical importance.

Improving malnutrition documentation enhances reimbursement.

Diagnosis coding for malnutrition can positively affect hospital reimbursements. Our goal was to quantify the possible increase in reimbursements when the diagnosis of malnutrition was identified and appropriately coded. A sample of 234 cases representing 14% of Medicare patients seen from March 1991 through February 1992 at Allenmore Hospital in Tacoma, Wash, was retrospectively reviewed. Malnutrition diagnoses (using ICD-9-CM codes) were assessed according to established criteria. Ninety-four cases (39.7%) met the criteria for malnutrition. Seven demonstrated increased reimbursement, totaling $12,326 for the sample. Length of hospital stay was significantly longer in the malnourished group (P = .001). The results indicated a need for an improved system of documenting and coding malnutrition diagnoses for improved identification and reimbursement enhancement purposes. An example of criteria used for each malnutrition ICD-9-CM diagnosis code and a policy defining the criteria usage are shown. A nutrition assessment form, which includes each malnutrition ICD-9-CM code title for enhanced interdisciplinary communication leading to improved coding of malnutrition diagnoses, is also shown. We conclude that effective identification of malnutrition leading to enhanced reimbursement strengthens the leadership potential of hospital dietitians and improves hospital revenues. Additionally, we suggest that such a system initiates a process that may lead to improved, cost-effective treatment of persons identified as being malnourished and provide a foundation for surviving within the future health care reform environment.

Activity of coagulation and fibrinolysis parameters in animals.

Using diagnostics for the determination of clotting factors and fibrinolytic parameters in human plasma, samples from rat, guinea pig, rabbit, cat, dog, sheep, cattle, horse, pig, and monkey were analysed. The human system was employed even for standard curves and controls. Results obtained in this way are relative values in relation to pooled fresh human plasma of healthy donors which is defined to contain 100% of the norm or 1 unit of each factor per 1 ml. Under these conditions, marked differences between the human clotting system and those of different animal species appear. Thus, rabbits have an about 50 times higher activity of factor V than humans and guinea pigs only 6% of the factor VII activity of human plasma. Plasma levels of fibrinogen, alpha 2-antiplasmin and antithrombin III in plasma samples of the investigated animal species are in the range of human plasma. Differences in the plasma level of single factors as compared to human plasma are reflected by clotting times of the screening tests. For the determination of plasminogen, streptokinase was used as activator of the fibrinolytic system. Hence, the results obtained by this method merely reflect the activatability of the animal plasminogen in comparison to the human system, however, do not allow statements concerning the real plasminogen content of the plasma sample from the animal species. For pharmacological investigations a proper selection of the animal species is important to prevent wrong conclusions.