Prevention of fall-related injuries in long-term care: a randomized controlled trial of staff education

BACKGROUND: Fall-related injuries, a major public health problem in long-term care, may be reduced by interventions that improve safety practices. Previous studies have shown that safety practice interventions can reduce falls; however, in long-term care these have relied heavily on external funding and staff. The aim of this study was to test whether a training program in safety practices for staff could reduce fall-related injuries in long-term care facilities. METHODS: A cluster randomization clinical trial with 112 qualifying facilities and 10,558 study residents 65 years or older and not bedridden. The intervention was an intensive 2-day safety training program with 12-month follow-up. The training program targeted living space and personal safety; wheelchairs, canes, and walkers; psychotropic medication use; and transferring and ambulation. The main outcome measure was serious fall-related injuries during the follow-up period. RESULTS: There was no difference in injury occurrence between the intervention and control facilities (adjusted rate ratio, 0.98; 95% confidence interval, 0.83-1.16). For residents with a prior fall in facilities with the best program compliance, there was a nonsignificant trend toward fewer injuries in the intervention group (adjusted rate ratio, 0.79; 95% confidence interval, 0.57-1.10). CONCLUSION: More intensive interventions are required to prevent fall-related injuries in long-term care facilities.     

Role of endothelial progenitors and other bone marrow-derived cells in the development of the tumor vasculature

Increasing evidence suggests the importance of bone marrow-derived cells for blood vessel formation (neovascularization) in tumors, which can occur in two mechanisms: angiogenesis and vasculogenesis. Angiogenesis results from proliferation and sprouting of existing blood vessels close to the tumor, while vasculogenesis is believed to arise from recruitment of circulating cells, largely derived from the bone marrow, and de novo clonal formation of blood vessels from these cells. Although bone marrow-derived cells are crucial for neovascularization, current evidence suggests a promotional role of these cells on the existing blood vessels rather than de novo neovascularization in tumors. This is believed to be due to the highly proangiogenic features of these cells. The bone marrow-derived cells are heterogeneous, consisting of many different cell types including endothelial progenitor cells, myeloid cells, lymphocytes, and mesenchymal cells. These cells are highly orchestrated under the influence of the specific tumor microenvironment, which varies depending on the tumor type, thereby tightly regulating neovascularization in the tumors. In this review, we highlight some of the recent findings on each of these cell types by outlining some of the essential proangiogenic cytokines that these cells secrete to promote tumor angiogenesis and vasculogenesis.     

Adverse Drinking-Related Consequences Among Lower Income, Racial, and Ethnic Minority Drinkers: Cross-Sectional Results

Objective:  To examine factors associated with adverse consequences of alcohol consumption among a community sample of drinkers in a low-income, racial, and ethnic minority community.
Methods:  A sample of 329 drinkers was recruited from 17 randomly selected off-sell alcohol outlets in South Los Angeles. Respondents were interviewed by trained research personnel on their demographic characteristics, income, drinking patterns and preferences, and alcohol-related adverse consequences (using the Drinkers Inventory of Consequences—DrInC), among other items. We developed logistic regression models predicting high scores on DrInC total score and subscales (impulse control, interpersonal, intrapersonal, physical, and social responsibility).
Results:  In this sample, we found drinking patterns—bingeing, drinking outdoors, drinking in the morning—to be significantly associated with total DrInC scores and some subscales. Malt liquor beverage (MLB) use was significantly associated with total DrInC score and interpersonal and social responsibility subscales. Previous alcohol treatment predicted all but 1 DrInC subscale and total score.
Conclusions:  A diverse array of factors predicted high DrInC total and subscale scores. More research on the association between MLB use and consequences is required. In addition, studies with community samples are likely to further enrich our understanding of the interactions between drinking patterns and preferences, settings, and negative consequences.     

Absence of opiate and histamine H2 receptor-mediated effects of clonidine

The possibility that clonidine might exert some of its effects via opiate or histamine H2 receptors has been suggested from observations in animals and man. We undertook a double-blind, randomized study in six normal subjects, comparing the effects of 0.2 mg intravenous clonidine after pretreatment with 300 mg cimetidine, 0.8 mg naloxone, and saline. There was no attenuation of the hypotension, bradycardia, sedation, inhibition of salivary flow, or reduction in plasma catecholamines after cimetidine and naloxone, but the fall in plasma catecholamines ater clonidine correlated with blood pressure, sedation, and salivary flow, suggesting a central adrenergic mechanism for these effects. It is not known whether cimetidine can cross the blood-brain barrier after short-term dosing. We conclude that in normotensive subjects the short-term effects of intravenous clonidine are probably not mediated by an action at peripheral histamine H2 or central opiate receptors.     

G protein-coupled receptor kinase 4 gene variants in human essential hypertension

Essential hypertension has a heritability as high as 30-50%, but its genetic cause(s) has not been determined despite intensive investigation. The renal dopaminergic system exerts a pivotal role in maintaining fluid and electrolyte balance and participates in the pathogenesis of genetic hypertension. In genetic hypertension, the ability of dopamine and D(1)-like agonists to increase urinary sodium excretion is impaired. A defective coupling between the D(1) dopamine receptor and the G protein/effector enzyme complex in the proximal tubule of the kidney is the cause of the impaired renal dopaminergic action in genetic rodent and human essential hypertension. We now report that, in human essential hypertension, single nucleotide polymorphisms of a G protein-coupled receptor kinase, GRK4gamma, increase G protein-coupled receptor kinase (GRK) activity and cause the serine phosphorylation and uncoupling of the D(1) receptor from its G protein/effector enzyme complex in the renal proximal tubule and in transfected Chinese hamster ovary cells. Moreover, expressing GRK4gammaA142V but not the wild-type gene in transgenic mice produces hypertension and impairs the diuretic and natriuretic but not the hypotensive effects of D(1)-like agonist stimulation. These findings provide a mechanism for the D(1) receptor coupling defect in the kidney and may explain the inability of the kidney to properly excrete sodium in genetic hypertension.     

Pharmacokinetics of Cefovecin in Cynomolgus Macaques (Macaca fascicularis), Olive Baboons (Papio anubis), and Rhesus Macaques (Macaca mulatta)

Cefovecin sodium is a long-acting, third-generation, cephalosporin antibiotic approved for the treatment of skin infections in dogs and cats. The pharmacokinetic properties of cefovecin were evaluated in cynomolgus macaques (Macaca fascicularis), olive baboons (Papio anubis), and rhesus macaques (Macaca mulatta) by using a single-dose (8 mg/kg SC) dosing regimen. Plasma cefovecin concentrations were determined by using ultra-performance liquid chromatography with tandem mass spectrometry, and a noncompartmental model was used to determine pharmacokinetic parameters. The half-life of cefovecin was 4.95 ± 1.47 h in cynomolgus macaques, 9.17 ± 1.84 h in olive baboons, and 8.40 ± 2.53 h in rhesus macaques. These values are considerably lower than the half-lives previously published for dogs (133 h) and cats (166 h). The extended half-life of cefovecin in dogs and cats is speculated to be due to active reabsorption of drug in the kidney tubules because plasma clearance is well below the normal glomerular filtration rate. In nonhuman primates, renal clearance rates approximated plasma clearance rates, suggesting that active renal reabsorption of cefovecin does not occur in these species. The pharmacokinetic properties of cefovecin in nonhuman primates are vastly different from the pharmacokinetic properties in dogs and cats, precluding its use as a long-acting antibiotic in nonhuman primates. This study highlights the importance of performing pharmacokinetic studies prior to extralabel drug usage.Abbreviation: AUC, area under the drug concentration–time curve.Cefovecin sodium (Convenia, Pfizer Animal Health, New York, NY) is a recently developed third-generation cephalosporin antibiotic labeled for the treatment of skin infections in dogs and cats.¹¹ Cephalosporins are bactericidal, β-lactam antibiotics that act by interfering with bacterial cell-wall synthesis, and are active against a wide range of organisms.¹² In particular, third-generation cephalosporins have excellent broad-spectrum antimicrobial activity.¹² Cefovecin is administered to both dogs and cats as a single, subcutaneous dose of 8 mg/kg.¹¹ After injection, therapeutic drug concentrations are maintained in dogs for 7 d for Staphylococcus intermedius infections and for 14 d for Staphylococcus canis (group G) infections, whereas therapeutic concentrations are maintained in cats for approximately 7 d for Pasteurella multocida infections.¹¹A long-acting antibiotic such as cefovecin would be advantageous for treating nonhuman primates, among which animals may be housed in group cages or large outdoor corrals and access to individual animals for daily dosing is problematic. Injectable medications often are preferred over oral dosing in nonhuman primates because oral administration is dependent on appetite and individual taste preferences, making this route of administration less reliable.³ A long-acting injectable antibiotic would decrease the stress placed on animals otherwise requiring daily or even more frequent dosing. For these reasons, we investigated the possibility of using cefovecin against pathogenic bacteria in nonhuman primates. We hypothesized that the pharmacokinetics of cefovecin in nonhuman primates might be similar to those in dogs and cats, thereby supporting its use as a long-acting antibiotic in nonhuman primates. We therefore conducted a pharmacokinetics study of cefovecin in 3 species of nonhuman primates commonly used in research.     

Racial differences in oxidative stress and inflammation: in vitro and in vivo

African American race is an independent risk factor for enhanced oxidative stress and inflammation. We sought to examine whether oxidative-stress and inflammatory markers that are typically measured in humans also differ by race in cell culture. We compared levels between African American and Caucasian young adults and then separately in human umbilical vein endothelial cells (HUVECs) from both races. We found heightened oxidative stress and inflammation in the African Americans both in vitro and in vivo. African American HUVECs showed higher nitric oxide (NO) levels (10.8 ± 0.4 vs. 8.8 ± 0.7 μmol/L/mg, p = 0.03), Interleukin-6 (IL-6) levels (61.7 ± 4.2 vs. 23.9 ± 9.0 pg/mg, p = 0.02), and lower superoxide dismutase activity (15.6 ± 3.3 vs. 25.4 ± 2.8 U/mg, p = 0.04), and also higher protein expression (p < 0.05) of NADPH oxidase subunit p47phox, isoforms NOX2 and NOX4, endothelial nitric oxide synthase (NOS), inducible NOS, as well as IL-6. African American adults had higher plasma protein carbonyls (1.1 ± 0.1 vs. 0.8 ± 0.1 nmol/mg, p = 0.01) and antioxidant capacity (2.3 ± 0.2 vs. 1.1 ± 0.3 mM, p = 0.01). These preliminary translational data demonstrate a racial difference in HUVECs much like that in humans, but should be interpreted with caution given its preliminary nature. It is known that racial differences exist in how humans respond to development and progression of disease, therefore these data suggest that ethnicity of cell model may be important to consider with in vitro clinical research.     

The unit of analysis error in studies about physicians’ patient care behavior

Objective:To estimate the frequency with which patients are incorrectly used as the unit of analysis among statistical calculations in published studies of physicians’ patient care behavior. Design:Retrospective review of studies published during 1980–1990. Articles:54 articles retrieved by a computerized search using medical subject beadings for physicians and study characteristics. Article selection criteria included the requirement that the physician should have been the correct unit of analysis. Intervention:Presence of the error was determined by consensus using published criteria. Main results:The error was present in 38 articles (70%). The number of study physicians was reported in 35 articles (65%). The error was found in 57% of articles that reported the number of study physicians and in 95% of those that did not. The error rate was not lower among articles published more recently nor among those published in journals with higher rates of article citations in the medical literature. Conclusion:The unit of analysis error occurs frequently and can generate artificially low p values. Failure to report the number of study physicians can be a clue that this type of error has been made.     

In vitro binding of gibberellin A(4) to extracts of cucumber measured by using DEAE-cellulose filters

A rapid method for assaying [³H]gibberellin A₄ bound to a soluble protein from cucumber hypocotyls by using DEAE-cellulose filter discs is described. The binding is saturable, reversible with unlabeled gibberellin A₄, and has a half-life of association under nonequilibrium conditions at 0-4°C of 6-7 min. By using this assay, the dissociation constant (K_d) was estimated to be 70 nM and the number of binding sites, 0.4 pmol mg^-1 of soluble protein or 0.69 pmol g^-1 (fresh weight) of hypocotyls. The speed and reliability of the assay make it invaluable for kinetic studies involving competitors. Thus, it has been possible to show that gibberellins that are biologically active in a cucumber bioassay compete for binding to the same protein and their calculated affinity constants bear a direct relationship to their known activities in the cucumber bioassay. Gibberellins that are inactive in this bioassay and other plant hormones, such as indoleacetic acid, abscisic acid, and kinetin, show a noncompetitive interaction.