Health disparities associated with access to disability evaluations for toddlers in Early Head Start.

BACKGROUND: The aim of this investigation was to examine developmental, sociodemographic and familial factors associated with parent reported access to an evaluation in an Early Head Start sample. Children with developmental disabilities often require evaluations to access early interventions, which can improve their long-term outcomes. METHODS: This study (n = 191) examined how developmental, sociodemographic and parent factors at age 2 were associated with parent reporting the child being evaluated by age 3. Two logistic regression analyses were conducted. The first model included children at age 2 with scores at least in the monitoring zone of developmental risk, and the second model included children with high developmental risk. RESULTS: The first model found that children in the monitoring zone of developmental risk were more likely to be evaluated per parent report if they were born preterm, male, with increased behaviour problems, higher economic risk, increased maternal education, increased parental depressive symptoms and in urban areas and less likely if they were of Black or Hispanic/Latino ethnicity, had no health insurance or more home disorganisation. The second model found that children with high developmental risk were less likely to be evaluated per parent report if they were female, of Hispanic/Latino ethnicity, had better language skills and increased home disorganisation and more likely if their parents reported increased depressive symptoms or less economic risk. CONCLUSIONS: This study highlights barriers associated with access to developmental and disability evaluations for children in at-risk families. Health disparities are negatively associated with children's access to evaluations, even when supported by systems like Early Head Start.

[Delayed incision time of the first case : Analysis of incidences and causes and the effect of list planning instability]. / Verzögerungen der Schnittzeit des ersten Falles : Analyse von Inzidenzen und Ursachen sowie des Effektes von Planinstabilität.

BACKGROUND: Delays in beginning operations in the morning lead to a loss of valuable operating time and can cause frustration among the medical personnel involved. OBJECTIVE: So far there are no prospective, multicentric investigations of the incidence and reasons for delayed first incision times in the morning. The effect of planning list instability of first cases on late operating room starts has not yet been evaluated. MATERIAL AND METHODS: In this multicenter prospective study delays in surgical incision time in all first cases of the day were investigated in 36 German and Swiss hospitals (14 surgical specialties) over a period of 2 weeks. RESULTS: A total of 3628 first of the day cases were included in the study. Looking at all subspecialties combined 50.8% of the first cases of the day were delayed by more than 5 min and in 30.2% of cases longer than 15 min. Incidences of delayed surgical incision time >5 min ranged from 40.0% (gynecology) to 66.8% (neurosurgery). The main reasons for delays in ascending order were prolonged induction of anesthesia compared to the planned time, the delayed appearance of the surgeon and prolonged preparation for surgery. The incidence of delays in incision times for planning list instability was increased by 10% and the average delay increased by 7 min. CONCLUSION: Delays in surgical incision times of the first operation of the day have a high incidence in most surgical specialties; however, the reasons for delays are manifold. Plan instability of operating room lists with respect to the first cases has a negative effect on the punctuality of the incision time and should therefore be avoided.

High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients.

BACKGROUND: The combination of one non-nucleoside reverse transcriptase inhibitor (NNRTI) with two nucleoside reverse transcriptase inhibitors is a validated first-line antiretroviral (ARV) therapy. The once-daily combination of lamivudine, tenofovirDF and nevirapine has not been evaluated in a clinical trial. METHODS: Randomized, open-label, multicentre, non-inferiority trial comparing lamivudine, tenofovirDF and nevirapine once daily (Group 2) with zidovudine/lamivudine and nevirapine twice daily (Group 1), in naive HIV-1-infected patients with a CD4 count <350/mm(3). We planned to enroll 250 patients. RESULTS: As of May 2006, 71 patients had been enrolled (35 in Group 1 and 36 in Group 2) and an unplanned interim analysis was done. The groups were comparable at baseline: median CD4 count was 195 and 191/mm(3) and median plasma viral load was 4.9 log(10) and 5.01 log(10), respectively, in Groups 1 and 2. Eight early non-responses (22.2%) were observed, all in Group 2, while two later viral rebounds occurred. Resistance genotypes for the nine Group 2 failing patients showed the mutations M184V/I (n = 3), K65R (n = 6), one or more NNRTI resistance mutations in all cases. At baseline, the nine Group 2 patients who failed had higher median plasma viral load (5.4 log(10)) and lower median CD4 count (110/mm(3)) than the other Group 2 patients (4.7 log(10), P = 0.002 and 223/mm(3), P = 0.004). Nevirapine trough concentrations were not different between the two groups, nor between patients with full viral suppression or those who failed in Group 2. Due to slow recruitment, and those results, the steering committee decided to stop the trial at 12 months. CONCLUSIONS: In ARV-naive HIV-1-infected patients, the once-daily lamivudine, tenofovirDF and nevirapine regimen resulted in a high rate of early virological failures. The reasons for the failures remain unclear.

[Evaluation of the efficacy of a drug: from discovery to market]. / Evaluation de l'efficacité d'un médicament: de la découverte à la mise sur le marché.

To move from a chemical entity to a real drug, preclinical trials have to be followed by phase I human studies to evaluate human toxicity, phase II studies to demonstrate the pharmacological activity in healthy volunteers and patients, followed by phase III studies to evaluate the real therapeutic efficacy. Then new drug authorization is granted for a product that shows good pharmaceutical quality and a positive risk-benefit ratio. However, full knowledge of a new drug is available only after several years of clinical use.

Endoscopic evaluation of the gastrotolerance of short-term antalgic treatment with low dose k-diclofenac: a comparison of ibuprofen and aspirin.

In a short-term gastro-duodenal endoscopic study in 12 healthy volunteers, the gastrotoxicity was not different after intake of diclofenac-K 12.5 mg (0.33) or ibuprofen 200 mg (0.42, P=0.66) but significantly higher after aspirin 500 mg (2.67, P=0.002).

Interaction between aspirin and ACE inhibitors in patients with heart failure.

Both aspirin (acetylsalicylic acid) and ACE inhibitors are often used concomitantly, especially in patients with both heart failure and ischaemic heart disease, which is the most common underlying cause of heart failure. The safety of the association has been questioned because both drugs affect a related prostaglandin-mediated pathway. Thanks to their vasodilating properties, prostaglandins play an important role in heart failure where peripheral vasoconstriction occurs. Some of the beneficial effects of ACE inhibitors might be related to reduced degradation of bradykinin that enhances the synthesis of prostaglandins, while aspirin, through inhibiting the enzyme cyclo-oxygenase, inhibits the production of prostaglandins. To date no prospective study has been conducted to investigate the effect of long term aspirin treatment in the postinfarction period allowing the possible impact of the interaction between aspirin and ACE inhibitors upon survival to be confirmed or negated. However, the practitioner needs to know how to optimise the treatment of his or her patients. In order to stimulate arguments for and against the use of aspirin in patients with heart failure receiving ACE inhibitors, we searched MEDLINE from 1960 to 2000 using the key words heart failure, aspirin, and ACE inhibitors for English language articles and conducted a review of the available data. We report on the potential mechanisms of the interaction and the results of experimental studies on haemodynamic parameters. Results of retrospective clinical studies, subgroup analysis that were undertaken to evaluate the overall action upon haemodynamic parameters and survival of the association are summarised. Conflicting conclusions have been reported in the literature. Many explanations can be advanced to try to understand these conflicting conclusions: differences in study design (results of retrospective trials have to be interpreted with caution); differences in the choice of the evaluation parameter (problem of the clinical relevance of haemodynamic parameters); differences in the characteristics of the patient (different underlying cardiopathy, e.g. heart failure, hypertension or ischaemic cardiopathy); and differences in the type and the dosage of each treatment (especially ACE inhibitors and aspirin since an interaction might occur more often with dosage of aspirin greater than 250mg).

[Survey of the negativation of bacteriologic tests in patients with active pulmonary tuberculosis: how long should the isolation be?]. / Etude de la négativation des examens bactériologiques chez les patients présentant une tuberculose pulmonaire bacillifère: quelle doit être la durée de l'isolement?

The risk of contamination by contact with patients with tuberculosis is reduced by isolation of patients until negativation of direct sputum analysis for the research of tuberculosis bacilli. To evaluate the efficacy of this isolation, we compared, in 32 patients with active tuberculosis, the results of direct examination and culture of the sputum and the clinical outcome. Thirty-two successive patients hospitalized in the same internal medicine unit, received antituberculosis drugs and had 3 sputum examinations per week with direct analysis and culture until negativation of the 3 direct examinations. Then, isolation ended. At the time of direct-negativation, 14 of the 32 patients kept positive cultures. In the 18 remaining subjects, the cultures became negative, about seven days before direct-negativation. Patients with negative cultures had more frequently weight increase (83% versus 71%), were more rapidly without fever (11 days versus 19 days), had less cough and had less severe radiologic disease (50% versus 75%) compared to patients with positive cultures but these differences were not statistically significant due to the small sample size. In tuberculosis patients, 3 successive negative direct sputum examinations do not eliminate the risk of tuberculosis transmission, specially to hospitalized or immunocompromised patients. The risk of contamination in these cases, although unknown, may be weak. Terminating isolation should not be based on sputum examination alone, but also on other factors such as the clinical course (resolution of cough and fever, weight), the initial number of bacilli, and the severity of the radiological lesions.

Plant diversity and productivity experiments in european grasslands

At eight European field sites, the impact of loss of plant diversity on primary productivity was simulated by synthesizing grassland communities with different numbers of plant species. Results differed in detail at each location, but there was an overall log-linear reduction of average aboveground biomass with loss of species. For a given number of species, communities with fewer functional groups were less productive. These diversity effects occurred along with differences associated with species composition and geographic location. Niche complementarity and positive species interactions appear to play a role in generating diversity-productivity relationships within sites in addition to sampling from the species pool.

Impediments to writing do-not-resuscitate orders.

BACKGROUND: Physicians are frequently unaware of their patients' desires regarding end-of-life care. Consequently, opportunities to implement do-not-resuscitate (DNR) orders are often missed. OBJECTIVE: To determine the reasons attending physicians do not write DNR orders when patients face increased mortality. METHODS: Over 4 months, the medical records of all inpatients on the General Medicine Service were reviewed at the time of discharge to identify patients with conditions predicting increased mortality. These cases were presented to a 5-member panel who decided if a DNR order was indicated. Reasons for missing DNR orders were discussed with the attending physicians. RESULTS: Of 613 consecutive admissions, the panel identified 149 patients (24%) for whom DNR orders were indicated. In 88 (59%) of these, DNR orders were absent. The lack of a DNR order did not correlate with age (P = .95), sex (P = .61), or race (P = .80). The attending physicians' explanations for not writing DNR orders in these 88 cases included the belief that the patient was not in imminent danger of death (n = 49 [56%]), the belief that the primary physician should discuss DNR issues (n = 43 [49%]), and the lack of an appropriate opportunity to discuss end-of-life issues (n = 38 [43%]). In 11 (12%) of the 88 cases, patients or their families did not accept the recommendation for a DNR order. No physicians expressed concerns regarding the morality of DNR orders, discomfort discussing end-of-life issues, or the threat of litigation as reasons for not writing a DNR order. CONCLUSIONS: Limitations in the extent and depth of the physician-patient relationship appear to be the most frequent impediments to writing DNR orders in our institution.

Intraspecific brood parasitism: a strategy for floating females in the European starling.

In many bird species, there is a floating population of females that are excluded from breeding because of competition for limited breeding resources. Female floaters may enhance their reproductive success by engaging in intraspecific brood parasitism. We studied female floaters in a population of European starlings, Sturnus vulgaris, in order to determine their identity and potential parasitic behaviour. Females were caught after being attracted to nestboxes with artificial nests during 1993-1995. None of the females was known to have a nest of her own at capture but 47% of the females either laid an egg in the nest or carried a fully developed egg within the reproductive tract, indicating that they were intraspecific brood parasites. The floating females were significantly younger and smaller than breeding females. Of 13 females equipped with radiotransmitters and followed daily, all but one started a breeding attempt of their own after 3-8 days and the majority settled as secondary females or mated with males where the original female had disappeared. This suggests that females that are unable to compete successfully for nest sites or males early in the breeding season may use intraspecific brood parasitism to enhance reproductive success during the period that they are constrained from breeding. The importance of settling rapidly because of a seasonal decline in reproductive success may also promote the evolution of intraspecific brood parasitism in the starling. The relative reproductive success of combining egg dumping with breeding compared with traditional breeding will depend on the costs of delaying breeding as well as the probability of finding a mate later in the breeding season. Copyright 1999 The Association for the Study of Animal Behaviour.

Thrombolytic and antithrombotic efficacy of the platelet GPIIb-IIIa antagonist DMP728.

OBJECTIVE: This study was undertaken to determine the antithrombotic and thrombolytic efficacy of DMP728 alone and in conjunction with thrombolytic agents. BACKGROUND: Coronary artery reocclusion continues to be a significant clinical problem after thrombolytic therapy or balloon angioplasty, with incidence rates of 5-20% regardless of thrombolytic intervention. To date, no adjunctive therapy has been shown to eliminate the incidence of rethrombosis after thrombolysis. DMP728, a novel small-molecular-weight platelet GPIIb-IIIa receptor antagonist, has been shown to prevent rethrombosis after thrombolysis in various arterial thrombosis models in dogs. It might therefore have potential utility in optimizing the clinical outcome of currently available thrombolytic agents. The present investigation was designed to examine the thrombolytic potential of DMP728 alone and in conjunction with different thrombolytic agents. METHODS: The deaggregatory effect of DMP728 in reversing human platelet aggregation after initiation of platelet aggregation by 10 mumol/l adenosine 5'-diphosphate was determined using light-transmittance aggregometry. The in-vitro efficacy of DMP728, alone and in combination with thrombolytic drugs, in dispersing a preformed platelet-rich clot was determined using a clot-dispersion assay. In addition, the in-vivo thrombolytic effects of DMP728, alone and in conjunction with streptokinase, were examined in an electrolytically induced femoral artery thrombosis model in dogs. RESULTS: DMP728 had concentration-dependent deaggregatory and thrombolytic effects in reversing aggregates and in dispersing a preformed platelet-rich thrombus in vitro. Furthermore, it exhibited significant potentiation (P < 0.01) when combined with different thrombolytic drugs such as streptokinase, tissue-type plasminogen activator (t-PA) and urokinase in lysing platelet-rich thrombus. DMP728 had significant in-vivo thrombolytic effects along with synergy in fully restoring arterial flow upon its concomitant use with subeffective to ineffective doses of streptokinase in an electrolytically induced femoral artery thrombosis model in dogs. It also reduced the time to reperfusion and prevented the incidence of rethrombosis after streptokinase. CONCLUSIONS: These findings suggest the potential utility and benefits of DMP728, not only in preventing arterial thrombosis but also in optimizing the efficacy of thrombolytic drugs.

Antiplatelet and antithrombotic efficacy of DMP 728, a novel platelet GPIIb/IIIa receptor antagonist.

BACKGROUND: Currently used antiplatelet drugs, including aspirin, ticlopidine, and others, are effective against certain but not all of the many endogenous platelet activators. Because of their limited efficacy, a significant number of serious thromboembolic complications still occur, highlighting the need for a more effective therapy. Thus, we have identified a systemically active peptide analogue (DMP 728) of the arginine-glycine-aspartic acid (RGD) recognition sequence that mediates the binding of ligands such as fibrinogen to the platelet glycoprotein (GP) IIb/IIIa receptors. The goals of the present study were to determine the antiplatelet and antithrombotic efficacies of DMP 728 in various arterial thrombosis models. METHODS AND RESULTS: DMP 728 demonstrated antiplatelet efficacy in vitro in inhibiting ADP-induced human platelet aggregation (IC50, 46 +/- 2 nmol/L) and fibrinogen binding to human platelets (IC50, 2.3 +/- 0.8 nmol/L) or purified human GPIIb/IIIa receptors (IC50, 0.6 +/- 0.1 nmol/L). DMP 728 demonstrated high affinity and specificity for human platelet GPIIb/IIIa over other adhesion molecules. In anesthetized mongrel dogs, DMP 728 at 0.001 to 1.0 mg/kg IV produced dose-dependent antiplatelet effects in inhibiting ex vivo platelet aggregation induced by ADP and in prolonging template bleeding time. DMP 728 effects on bleeding time prolongation were more rapidly reversible than those on platelet aggregation inhibition. A maximal antiplatelet effect for DMP 728 was demonstrated at 0.01 mg/kg IV bolus. The antithrombotic efficacy of DMP 728 was examined in vitro and in vivo after IV administration at different doses in various models of arterial thrombosis. In the coronary artery Folts model in dogs, DMP 728 demonstrated maximal antithrombotic efficacy at 0.01 mg/kg IV bolus with an ED50 of 0.005 mg/kg IV bolus in inhibiting cyclic flow reductions. Additionally, DMP 728 demonstrated 100% prevention of primary thrombosis and rethrombosis (P < .01) after treatment with different thrombolytics, including tissue plasminogen activator and streptokinase, in an electrolytically induced femoral artery thrombosis model in dogs. CONCLUSIONS: Acute intravenous DMP 728 administration (0.001 to 1.0 mg/kg) has dose-dependent antiplatelet and antithrombotic effects in different arterial thrombosis models. These data suggest that DMP 728, a low-molecular-weight GPIIb/IIIa receptor antagonist, may have therapeutic potential as an effective antithrombotic agent in coronary and peripheral artery thromboembolic disorders.

Comparison of recombinant plasminogen activator inhibitor-1 and epsilon amino caproic acid in a hemorrhagic rabbit model.

A rabbit ear model of blood loss was developed to compare the effects of an active form of recombinant plasminogen activator inhibitor-1 (rPAI-1) with epsilon amino caproic acid (EACA) in antagonizing tissue-type plasminogen activator (r-tPA)-induced blood loss. The antagonism of both rebleeding, which occurs as a result of hemostatic plug degradation, and r-tPA-induced hemorrhage, where rabbits lose approximately 30% of their blood volume, was studied. rPAI-1 (1 mg/kg i.v.) or EACA (70 mg/kg i.v.) antagonized the rebleeding induced by r-tPA (10 micrograms kg-1 min-1) to a similar extent. In the hemorrhagic studies, rPAI-1 effectively antagonized the r-tPA-induced hemorrhage with an ED50 of 3 mg/kg i.v., while the ED50 obtained for EACA was 230 mg/kg i.v. rPAI-1 may be of value in reversing r-tPA-induced blood loss during thrombolytic therapy or in clinical situations where excessive fibrinolysis contributes to bleeding.

Leaf life spans in wild perennial herbaceous plants: a survey and attempts at a functional interpretation.

Leaf longevity in 29 herbaceous plant species of Central Europe was studied by inspecting tagged leaves at weekly intervals. About half of the species are elements of the lowland meadow flora, the other half comprises a representative sample of species from the highest sites where vascular plants grow in the Alps. Shaded and water-stressed sites were avoided. Overall mean leaf longevity did not differ significantly between sites and amounted to 71±5 days at low and 68±4 days at high altitude. Leaf life spans ranged (with no clear altitudinal trend) from 41 to 95 days. Low-altitude forbs and grasses produced several leaf cohorts during their growth period, while most alpine species produced only one. Correlations were found between leaf duration and percent nitrogen content and carbon-cost/carbon-gain ratios, but not with leaf dry mass per unit leaf area and photosynthetic capacity alone. As leaf life spans increase, more C tends to be invested per unit CO2 uptake and less N is invested per unit invested C. Thus, mass relationships rather than area relationships seem to be linked to leaf life span in these species, suggesting that leaf duration is associated with properties other than the efficiency of light utilization (e.g. mechanical strength, herbivory or pathogen resistance). It seems that the explanations of leaf duration that have been developed for evergreen/deciduous plants and for plants along steep light gradients do not apply to the variable life spans in leaves of perennial herbaceous plants of open habitats.

Antiarrhythmic, electrophysiologic and hemodynamic effects of ACC-9358.

The antiarrhythmic, electrophysiologic and hemodynamic effects of a new antiarrhythmic agent, ACC-9358, were evaluated. In anesthetized dogs, ACC-9358 converted ouabain-induced ventricular tachycardia to normal sinus rhythm at a cumulative dose equal to encainide or flecainide and less than disopyramide. In 24-hr coronary artery ligated dogs, ACC-9358 suppressed spontaneous ventricular arrhythmias for up to 6 hr after oral or i.v. administration. The antiarrhythmic effect and plasma concentrations of ACC-9358 correlated well for both oral (r = 0.88) and i.v. (r = 0.87) administration. ACC-9358, flecainide and disopyramide were equieffective in converting crush-stimulation-induced atrial flutter in anesthetized dogs to normal sinus rhythm. In alpha-chloralose-anesthetized, closed-chest dogs, ACC-9358 slowed impulse conduction through the atria, atrioventricular node, His-Purkinje system and ventricles and prolonged atrial functional refractory period. In conscious dogs, ACC-9358 increased heart rate, reduced stroke volume and had no effect on mean arterial pressure, systemic vascular resistance or cardiac output. In alpha-chloralose-anesthetized dogs, ACC-9358-induced sinus tachycardia was unaffected by propranolol but was blocked by hexamethonium or vagotomy. In isolated cat ventricular muscle, the IC50 for the negative inotropic effect of ACC-9358 was significantly greater than flecainide or disopyramide. These results indicate that ACC-9358 is a potent, broad-spectrum, long-acting, orally and intravenously active class Ic antiarrhythmic agent that 1) may be devoid of active metabolites, 2) exerts little or no vascular effects and 3) has less direct cardiodepressant activity than flecainide or disopyramide.