Minimum Baseline Research Articles

Report of an International Workshop to Standardize Baseline Evaluation and Response Criteria for Primary CNS Lymphoma

Standardized guidelines for the baseline evaluation and response assessment of primary CNS lymphoma (PCNSL) are critical to ensure comparability among clinical trials for newly diagnosed patients. The relative rarity of this tumor precludes rapid completion of large-scale phase III trials and, therefore, our reliance on the results of well-designed phase II trials is critical. To formulate this recommendation, an international group of experts representing hematologic oncology, medical oncology, neuro-oncology, neurology, radiation oncology, neurosurgery, and ophthalmology met to review current standards of reporting and to formulate a consensus opinion regarding minimum baseline evaluation and common standards for assessing response to therapy. The response guidelines were based on the results of neuroimaging, corticosteroid use, ophthalmologic examination, and CSF cytology. A critical issue that requires additional study is the optimal method to assess the neurocognitive impact of therapy and address the quality of life of PCNSL survivors. We hope that these guidelines will improve communication among investigators and comparability among clinical trials in a way that will allow us to develop better therapies for patients.

Skin Reactions in Patients with Influenza Treated with Oseltamivir: A Retrospective Cohort Study

Oseltamivir phosphate is an FDA-approved treatment for influenza that has been available for prescription use in the USA since 1999. The present report describes findings from a post-marketing safety study of skin reactions associated with oseltamivir use. All patients in the claims-derived Ingenix Research Database with a physician diagnosis of influenza and/or a dispensing of oseltamivir between 1 December 1999 and 31 March 2002 were identified. Cohort eligibility criteria included minimum baseline enrolment duration of 3 months, age of at least 1 year and no influenza vaccination on the date of influenza diagnosis or oseltamivir dispensing. Patients were classified into two primary cohorts, influenza diagnosis and oseltamivir dispensing on the same day, and influenza diagnosis but no oseltamivir at any time, and a cohort included for secondary analyses comprising patients who received an oseltamivir dispensing without an influenza diagnosis on the same day. Outcomes included general skin reactions and several specific skin reactions. Events occurring during the 30 days following the date of influenza diagnosis or oseltamivir dispensing were examined using Cox proportional hazards models. Model covariates included age, use of another influenza drug, month and year of index date, and use of antitussives. Adjusted rate ratios for the general class of skin reactions among the primary cohort of oseltamivir users versus non-users were 1.05 (95% CI: 0.88-1.24) for incident cases and 0.98 (95% CI: 0.77-1.24) among patients with a history of a skin reaction. Similar results were seen for the other skin reaction categories, and secondary analyses investigating the oseltamivir users without influenza revealed no elevation in risk. It is concluded that oseltamivir use does not appear to be associated with an increased risk of skin reactions.

Monitoring amiodarone's toxicities: recommendations, evidence, and clinical practice.

We sought to develop an explicit evidence-based model of medication monitoring and to evaluate monitoring practices and adverse drug events in patients taking amiodarone at one institution. We searched MEDLINE (1966 through 2000) for English-language publications providing specific monitoring recommendations for amiodarone. A cross-sectional retrospective chart review of 99 outpatients receiving amiodarone therapy between Jan 1, 2000, and Jan 1, 2001, at a large tertiary-care hospital was performed to assess monitoring practices. Adverse drug events were identified by use of structured implicit reviews. The main outcome measure was the proportion of patients receiving the monitoring recommended in the literature and having amiodarone-related adverse drug events. Forty-three articles were identified that provided specific monitoring recommendations, although no studies were found that compared the outcomes of patients managed with different monitoring regimens. Overall, 70% of the recommended monitoring criteria were satisfied, although only 9 patients (9%; 95% confidence interval [95% CI], 3%-15%) received all of the recommended monitoring. Variability in monitoring practices was identified at all stages of the monitoring model. Of the patients, 52 (52%; 95% CI, 42%-62%) received minimum baseline evaluations, 22 (22%; 95% CI, 14%-31%) underwent ongoing surveillance, 75 (75%; 95% CI, 61%-89%) had appropriate responses to abnormal surveillance results, and 71 (71%; 95% CI, 62%-80%) had timely follow-up visits. Of the patients, 8 (8%; 95% CI, 3%-13%) had 9 amiodarone-related adverse drug events, of which 3 were judged to be preventable. Interrater agreement for monitoring processes (kappa = 0.83) and adverse drug events (kappa = 0.67) was good. Current standards for amiodarone toxicity monitoring are based on expert opinion with limited evidence to support most recommendations. Monitoring practices appear to vary significantly, with few patients receiving all of the recommended monitoring. Some amiodarone-related adverse drug events may be preventable and patient safety might be improved with a better understanding of monitoring processes.

Optimizing Regulation of Electronic Commerce

The impressive growth of Internet markets has been accompanied by an important academic debate on how to regulate them. Commentators have suggested traditional top-down or bottom-up regulatory approaches based largely on ideological grounds. To date, there has been no rigorous analysis of the various proposals for e-commerce regulation. In this article, the authors analyze the advantages and shortcomings of each regime and propose a mixed solution that maximizes net social welfare. The authors first present a model of the institutional background of an economic system and provide evidence of its functioning on the Internet, which permits an evaluation of market functioning on the Internet as compared to real world markets. This evaluation indicates that the Internet is a system technologically different from real life markets, and thus government and private sector initiatives have a different impact on its structure. The authors also examine the economic and political implications of Internet regulation, discuss the various bottom-up and top-down approaches to this regulation, and conclude that a pure regulatory system is not viable and that a cooperative result is welfare improving. The authors then construct a game theoretic model in order to analyze the different regimes proposed for Internet regulation. Based on this analysis, the authors propose a new, optimal regulatory regime based on tacit cooperation between the government and private sector regulators and show how such a regime maximizes net social welfare for both consumers and firms and avoids the drawbacks of the top-down or bottom-up regulatory approaches. In this tacit, public-private cooperative solution, the authors identify a role for government in setting minimum baseline standards for problems such as online privacy, preventing the capture of private regulators through meaningful oversight, increasing the participation of firms in private regulatory initiatives, and also serving as the enforcer of last resort. Finally, the authors perform two, thorough case studies of private third-party regulation - regulation of online privacy by BBBOnLine and regulation of online consumer fraud by the Federal Trade Commission (FTC). The authors demonstrate how both private self-regulatory and top-down government regulation can be improved significantly by incorporating specific insights drawn from their optimal regulatory regime.

Researchers Identify Best Times For Effective Light Therapy

Researchers Identify Best Times For Effective Light Therapy

Use of Periodic Excitation to Enhance Airfoil Performance at Low Reynolds Numbers

throughout the entire cycle because of attachment of the  ow to the  ap. In contrast,however, instantaneousdCL=d® is not signiŽ cantly affected. In addition to lift increases, the light-moment stall is eliminated, resulting in a 20% reduction in moment excursions, while excitation induces a further mean nose-down pitching moment of CM;mean » 0:05: Although intrinsically different from the preceding case, a similar control strategy was applied for  ap-shoulder excitation. Here, excitation is initiated soon after the commencement of pitchup and terminated in the region where the continuous excitationdownstroke lift data begin to increase.As indicated in the Ž gure, this control strategybroughtabout the maximumpossiblelift excursions, namely between the minimum baseline and maximum excitation limits (CL ;exc D 0:8). In addition, the light-moment stall, which was effectively eliminated by continuous excitation, is also eliminated by intermittent excitation.

The impact of restrictive entry criterion during the placebo lead-in period.

In the study of depression, most randomized clinical trials have design features that attempt to sample from a stable patient population. One commonly used design feature is to require patients to maintain some minimum baseline symptom severity score during a placebo lead-in period. One intent of this design feature is to evaluate the behavior of patients prior to administration of active medication. If, during the lead-in period, patients do not maintain minimum symptom severity, the patients are excluded from the remainder of the study, the theory being that the excluded patients are not part of a stable patient population and hence are not likely to demonstrate efficacy of a truly effective treatment. This presentation investigates the effectiveness of a restrictive entry criterion and proposes an alternative explanation for what is usually defined as placebo response.

A 2-year follow-up of mandibular posture following an increase in occlusal vertical dimension beyond the clinical rest position with fixed restorations.

While resting mandibular posture is continuously changing, repeatable relations of 'physiologic rest position' (PRP) and 'clinical rest position' (CRP) are described in the literature. The PRP is defined as a position of minimal muscle activity and CRP as a more closed clinical reference relation. Relaxed resting posture (RRP) is a repeatable postural range obtained by operator-induced relaxation techniques. This article reports on measurements of mandibular posture in a patient group following an increase in occlusal vertical dimension (OVD) with fixed restorations beyond CRP over 2 years. The relationship of CRP and RRP in the restored and a non-restored control group is compared. The relationship of RRP and corresponding masseteric EMG values to baseline minimal EMG levels is reported for both groups. Resting face height adapted to the increased OVD and remained consistent over 1 and 2 years. The RRP was greater and significantly different from CRP in both groups (P = 0.0001). Results indicated that both CRP and RRP were postural ranges and not specific postural positions. The RRP occurred at minimum baseline EMG levels for both groups and appears to be consistent with physiologic rest position. The possibility of achieving minimal EMG levels at varying interocclusal rest space relations is discussed.

Large slow potential shifts occur during halothane anaesthesia in gerbils.

Continuous recordings were made of slow potential shift activity occurring at six locations on the surface of the cerebral cortex of seizure-prone and non seizure-prone gerbils. Measurements were made for 80-s epochs of recordings of frequency, maximum and minimum slow shift amplitude and baseline potential of the brain during periods of normal inactivity and subsequently during halothane anaesthesia. Induction of anaesthesia initially provoked large (millivolt) slow (3-4 s) oscillations in all animals, larger in amplitude than any recorded prior to anaesthesia. With increasing depth of anaesthesia, all animals also showed a reduction in the amplitude of this spontaneous slow potential shift activity. The effect was most pronounced in seizure-prone animals, and subsequent to anaesthetic-induced behavioural immobility, these animals also showed a regional resistance to the depression of spontaneous slow potential shift oscillations. Slow potential shift activity during anaesthesia represents ionic fluxes which may normally be involved in modulation of neuronal responsiveness. It was suggested that glia may be targets for anaesthetics and that seizure susceptibility may confer some degree of resistance to the depressant effects of such substances.

Azelastine Eye Drops in the Treatment of Seasonal Allergic Conjunctivitis or Rhinoconjunctivitis in Young Children

SummaryIn a randomised, multicentre study, the effect of azelastine eye drops (n = 51 patients) was compared in a double-blind manner with placebo eye drops (n = 30 patients) and in an open manner with levocabastine eye drops (n = 32 patients) during a 14-day treatment period involving 113 children (aged 4 to 12 years) suffering from seasonal allergic conjunctivitislrhinoconjunctivitis. The primary variable was the response rate defined as the number of patients showing an improvement after three days of treatment of at least three score points, from a minimum baseline score of six, in the main ocular symptoms of itching, conjunctival redness and lacrimation (each assessed on a four-point scale). Patients discontinuing due to inefficacy were regarded as non-responders.The mean response rate in the azelastine eye drops group (74%) was significantly higher (p < 0.01) than that in the placebo group (39%) and comparable with that in the levocabastine group. The response rates assessed by the patients in their diaries were very similar. Significant differences (p < 0.01) for azelastine compared with placebo were observed on days 3 and 14 in the mean sum scores for the three main symptoms and for a total of eight eye symptoms. The overall assessment of efficacy confirmed the superiority of both active treatments compared with placebo.Adverse drug reactions were reported in 23% of placebo-, 35% of azelastine- and 38% of levocabastine-treated patients. These were mainly local irritant effects. Overall tolerability was assessed as very good or good in 80%, 84% and 91% of placebo-, azelastine- and levocabastine-treated patients, respectively.Azelastine eye drops are effective and well-tolerated in children with seasonal allergic conjunctivitis.

Evaluation of the antimicrobial effects in vivo of Triaz® Gel (benzoyl peroxide special gel), Cleocin-T® Lotion (clindamycin phosphate lotion), and Azelex® Cream (azelaic acid cream) in humans

This single-blind, 4-week study compared the in vivo antimicrobial efficacy of three topical antimicrobial products used to treat acne: Triaz® 10% Gel (benzoyl peroxide special gel), Azelex® Cream (azelaic acid cream), and 2% Cleocin-T® Lotion (clindamycin phosphate lotion). There were three parallel groups, each containing males and females with minimum baseline Propionibacterium acnes of 10 000 colony forming units per cm2. Each product was applied twice daily for 4 weeks and P. acnes was sampled using the scrub procedures of Williamson and Kligman on the forehead and both cheeks, at baseline and at 2 and 4 weeks. The results showed that Triaz Gel produced substantial and significantly superior reductions in P. acnes, compared with those produced by Cleocin-T Lotion and Azelex Cream as early as 2 weeks and continuing through 4 weeks of treatment (P=<0.01). Further, while Triaz Gel and Cleocin-T Lotion produced significant reductions in P. acnes compared with baseline after 2 and 4 weeks, Azelex Cream appeared to produce no reduction in P. acnes at either time point.

Wide area differential GPS (WADGPS): future navigation system

Conventional differential Global Positioning System (DGPS) usually has accuracies of 1-3 within 100 km of the reference station wide area differential GPS (WADGPS) can achieve the same accuracy as DGPS in much wider area while reducing the number of reference stations and increasing the integrity substantially. Test results have shown 1.5-4 m positioning accuracy for a dual frequency user with 10-20 s of age using WADGPS, which in this case has six monitor stations with a 1632 km minimum baseline.

The effects of adrenergic agents on oxygen delivery and oxygen consumption in normal dogs.

This study measured changes in whole body Do2 and Vo2 caused by the administration of exogenous adrenergic agents given at physiologically relevant doses. Using 25-kg nonseptic dogs, we calculated Do2 and directly measured Vo2 in six groups (saline control, colloid fluid challenge, dopamine, dobutamine, norepinephrine, and epinephrine). The dogs were anesthetized with isoflurane, paralyzed, and maintained at a minimum baseline temperature of 37 degrees C. Measurements were taken at six time points: baseline, after each of four successively larger doses of drug, and after a recovery period. Our results demonstrated no significant changes in Vo2 in either the saline control or colloid challenge groups over the 6-hour experiment despite marked increases in cardiac output and oxygen delivery during colloid challenge. At the maximum dose used, adrenergic agents increased Vo2 by the following: dopamine, 56%; dobutamine, 51%; norepinephrine, 43%; epinephrine, 61%. We conclude that adrenergic agents cause a significant increase in whole body Vo2 at moderate doses in normal dogs.

A multicentre double‐blind comparative trial of fluvoxamine versus lorazepam in mixed anxiety and depression treated in general practice

Fluvoxamine, a selective serotonin reuptake inhibitor, was compared with lorazepam in a multicentre double-blind, parallel group study in 112 general practice patients with mixed anxiety and depression. For inclusion, patients were required to have minimum baseline scores of 21 on the Montgomery-Asberg Depression Rating Scale (MADRS) and 11 on the Clinical Anxiety Scale (CAS). Treatment was for 6 weeks. There were no significant differences between treatments at any point except in an elderly subgroup in whom anxiety improved more rapidly with lorazepam. There were significant improvements in MADRS, CAS and global ratings compared with baseline at all subsequent assessments. Improvement continued during the whole treatment period. Lorazepam produced more sedation, whilst fluvoxamine produced significantly more nausea and vomiting; this was usually early in onset and, if tolerated, resolved during the course of the study. As it is now widely recognized that benzodiazepines should only be given in short courses of 2-4 weeks, the continued improvement up to 6 weeks has implications regarding choice of treatment.

18 cm VLBI Network

The Soviet VLBI network includes parabolic 70-m antennas located near Usuriisk and Eupatoria, a 64-m antenna in Bear Lake, 22-m antennas in Pushino and Simeiz, and a 25-m antenna near Ulan-Ude. The maximum baseline length in the E–W direction is equal to about 7000 km, and in the N–S direction is equal to 1300 km. The minimum baseline length is equal to about 100 km.

Miniature ion mobility spectrometer cell

A miniature ion mobility spectrometer call using resistive coated ceramic electrodes is described. Its construction, performance and results of parametric studies are reported. The cell has a total ion current in the range 1 to 8*10-10 A and a minimum baseline ion current of 1.9*10-11 A. The total ion current less baseline ion current difference affects sensitivity through scaling relationships with the reactant and product ion currents. Because a membrane inlet is used for sample introduction, the carrier and drift gas flow rates both affect sensitivity. Although protonated quasi-molecular ions of sample molecules are found to be stable in the cell, protonated dimer ions dissociate in the higher electric fields which can be applied to the cell. Resolution of ion mobility peaks scales as the two-thirds power of the drift length squared divided by the gate width applied to the shutter grid. A microprocessor-controlled environmental monitoring system has been assembled using the cell as a sensor.

Solvent degassing and other factors affecting liquid chromatographic detector stability

We have measured the absorbance of methanol in the region 200–300 nm as a function of dissolved helium, nitrogen and air, and shown that a 1% change in oxygen level can cause a 4·10 −3 a.u. change at 210 nm. We have also measured the amount of oxygen that can be removed from different solvents by the degassing techniques of refluxing, helium sparging, vacuum degassing and ultrasonic agitation. Using these results we have determined the operating conditions for minimum baseline drift in high-performance liquid chromatographic detection at 0.005 a.u.f.s. sensitivity in the range 190–220 nm. We observed a residual change in the absorbance of methanol, related to temperature, even after removal of oxygen.