Randomized trial of daily versus weekly administration of 2-chlorodeoxyadenosine in patients with hairy cell leukemia: a multicenter phase III trial (SAKK 32/98)

Daily administration of 2-chlorodeoxyadenosine (Cladribine, CDA) is a standard treatment for hairy cell leukemia, but may cause severe neutropenia and neutropenic fever. This trial compared toxicity and efficacy of weekly versus daily CDA administration. One hundred patients were randomized to receive standard (CDA 0.14 mg/kg/day day 1-5 [Arm A]) or experimental treatment (CDA 0.14 mg/kg/day once weekly for 5 weeks [Arm B]). The primary endpoint was average leukocyte count within 6 weeks from randomization. Secondary endpoints included response rates, other acute hematotoxicity, acute infection rate, hospital admission, remission duration, event-free, and overall survival. There was no significant difference in average leukocyte count. Response rate (complete + partial remission) at week 10 was 78% (95% confidence interval (CI) 64-88%) in Arm A and 68% (95% CI 54-80%) in Arm B (p = 0.13). Best response rates during follow-up were identical (86%) in both arms. No significant difference was found in the rate of grade 3+4 leukocytopenia (94%vs. 84%), grade 3+4 neutropenia (90%vs. 80%), acute infection (44%vs. 40%), hospitalization (38%vs. 34%), and erythrocyte support (22%vs. 30%) within 10 weeks. Overall, these findings indicate that there are no apparent advantages in toxicity and efficacy by giving CDA weekly rather than daily.

Once daily dosing of netilmicin in neonatal and pediatric intensive care

OBJECTIVE: To examine a once daily dosing regimen of netilmicin in critically ill neonates and children. DESIGN AND SETTING: Open, prospective study on 81 antibiotic courses in 77 critically ill neonates and children, hospitalized in a multidisciplinary pediatric/neonatal intensive care unit. For combined empiric therapy (aminoglycoside and beta-lactam), netilmicin was given intravenously over 5 min once every 24 h. The dose ranged from 3.5-6 mg/kg, mainly depending upon gestational and postnatal age. Peak levels were determined by immunoassay 30 min after the second dose and trough levels 1 h before the third and fifth dose or after adaptation of dosing. RESULTS: All peak levels (n = 28) were clearly above 12 mumol/l (mean 22, range 13-41 mumol/l). Eighty-nine trough levels were within desired limits (< 4 mumol/l) and 11 (11%) above 4 mumol/l, mostly in conjunction with impaired renal function. CONCLUSIONS: Optimal peak and trough levels of netilmicin can be achieved by once daily dosing, adapted to gestational/postnatal age and renal function.

Daily monetary impulses and security prices

This paper uses Swiss data to study the real long-run effects of monetary policy. Daily unexpected changes in the monetary base are found to be negatively correlated with security price changes. This result is unaffected when, implicitly following Geske and Roll (1983), we try to measure the autonomous component of monetary policy by taking into account a reaction function of monetary policy to changes in real variables.

[Cone beam computed tomography in endodontics: a review for daily clinical practice]

Since the introduction of cone beam computed tomography (CBCT), this 3-dimensional diagnostic imaging technique has been established in a growing number of fields in dental medicine. It has become an important tool for both diagnosis and treatment planning, and is also able to support endodontic treatments. However, the higher effective dose of ionizing radiation compared to conventional 2-dimensional radiographs is not justifiable in every case. CBCT allows for a more precise diagnosis of periapical lesions, root fractures as well as external and internal resorptions. Concerning the utility of CBCT in treatment planning decisions, the gain of information through 3-dimensional imaging for any of these pathologies has to be evaluated carefully on an individual basis. Moreover, radioopaque materials such as root canal filling and posts often create artefacts, which may compromise diagnosis. The aim of this review is to summarize the possibilities and limits of CBCT imaging in endodontology as well as introduce guidelines for daily clinical practice. Furthermore, the article presents possible therapeutic advantages of preexisting CBCT scans for root canal treatments.

Ecological validity of virtual reality daily living activities screening for early dementia: longitudinal study

Background: Dementia is a multifaceted disorder that impairs cognitive functions, such as memory, language, and executive functions necessary to plan, organize, and prioritize tasks required for goal-directed behaviors. In most cases, individuals with dementia experience difficulties interacting with physical and social environments. The purpose of this study was to establish ecological validity and initial construct validity of a fire evacuation Virtual Reality Day-Out Task (VR-DOT) environment based on performance profiles as a screening tool for early dementia. Objective: The objectives were (1) to examine the relationships among the performances of 3 groups of participants in the VR-DOT and traditional neuropsychological tests employed to assess executive functions, and (2) to compare the performance of participants with mild Alzheimer’s-type dementia (AD) to those with amnestic single-domain mild cognitive impairment (MCI) and healthy controls in the VR-DOT and traditional neuropsychological tests used to assess executive functions. We hypothesized that the 2 cognitively impaired groups would have distinct performance profiles and show significantly impaired independent functioning in ADL compared to the healthy controls. Methods: The study population included 3 groups: 72 healthy control elderly participants, 65 amnestic MCI participants, and 68 mild AD participants. A natural user interface framework based on a fire evacuation VR-DOT environment was used for assessing physical and cognitive abilities of seniors over 3 years. VR-DOT focuses on the subtle errors and patterns in performing everyday activities and has the advantage of not depending on a subjective rating of an individual person. We further assessed functional capacity by both neuropsychological tests (including measures of attention, memory, working memory, executive functions, language, and depression). We also evaluated performance in finger tapping, grip strength, stride length, gait speed, and chair stands separately and while performing VR-DOTs in order to correlate performance in these measures with VR-DOTs because performance while navigating a virtual environment is a valid and reliable indicator of cognitive decline in elderly persons. Results: The mild AD group was more impaired than the amnestic MCI group, and both were more impaired than healthy controls. The novel VR-DOT functional index correlated strongly with standard cognitive and functional measurements, such as mini-mental state examination (MMSE; rho=0.26, P=.01) and Bristol Activities of Daily Living (ADL) scale scores (rho=0.32, P=.001). Conclusions: Functional impairment is a defining characteristic of predementia and is partly dependent on the degree of cognitive impairment. The novel virtual reality measures of functional ability seem more sensitive to functional impairment than qualitative measures in predementia, thus accurately differentiating from healthy controls. We conclude that VR-DOT is an effective tool for discriminating predementia and mild AD from controls by detecting differences in terms of errors, omissions, and perseverations while measuring ADL functional ability.

Does work stress make you shorter? An ambulatory field study of daily work stressors, job control, and spinal shrinkage

Body height decreases throughout the day due to fluid loss from the intervertebral disk. This study investigated whether spinal shrinkage was greater during workdays compared with nonwork days, whether daily work stressors were positively related to spinal shrinkage, and whether job control was negatively related to spinal shrinkage. In a consecutive 2-week ambulatory field study, including 39 office employees and 512 days of observation, spinal shrinkage was measured by a stadiometer, and calculated as body height in the morning minus body height in the evening. Physical activity was monitored throughout the 14 days by accelerometry. Daily work stressors, daily job control, biomechanical workload, and recreational activities after work were measured with daily surveys. Multilevel regression analyses showed that spinal disks shrank more during workdays than during nonwork days. After adjustment for sex, age, body weight, smoking status, biomechanical work strain, and time spent on physical and low-effort activities during the day, lower levels of daily job control significantly predicted increased spinal shrinkage. Findings add to knowledge on how work redesign that increases job control may possibly contribute to preserving intervertebral disk function and preventing occupational back pain.

Inter- and intraindividual associations between volitional processes and daily smoking during a quit attempt

Background: The Health Action Process Approach (HAPA) assumes that volitional processes are important for effective behavioral change. This study examined the associations of volitional predictors and daily smoking in quitters at the inter- and intraindividual level. Method: Overall, 105 smokers completed daily electronic questionnaires 10 days before and 21 days after a self-set quit date, assessing intentions, self-efficacy, planning, action control and numbers of cigarettes smoked. Findings: Multilevel analyses showed that mean levels of volitional predictors across the 32 days were negatively associated with numbers of cigarettes smoked. Moreover, on days with higher intentions, self-efficacy, planning and action control than usual, less cigarettes were smoked. These effects were stronger after the quit date than before the quit date. Intentions and action control emerged as most powerful predictors at the intraindividual level. Discussion: Findings emphasize the importance of volitional processes at the intraindividual level in the context of quitting smoking.

Predicting daily smoking around a quit date : Volitional processes at the inter- and intraindividual level

Background: The health action process approach (hapa) is a well-established model in predicting health behavior and assumes that volitional processes are important for effective behavioral change. however, only few studies have so far tested associations on the intraindividual level. thus, this study examined the inter- and intraindividual associations between volitional predictors and daily smoking around a quit attempt. method: overall, 105 smokers completed daily electronic questionnaires 10 days before and 21 days after a self-set quit date, including measures of intentions, self-efficacy, planning, action control and numbers of cigarettes smoked. multilevel analysis was applied. findings: at the interindividual level, higher mean levels of volitional predictors across the 32 days were associated with less numbers of cigarettes smoked. negative associations emerged also at the intraindividual level, indicating that on days with higher intentions, self-efficacy, planning and action control than usual, less cigarettes were smoked. moreover, these effects were stronger after the quit date than before the quit date. intentions and action control emerged as most powerful predictors at the intraindividual level. discussion: findings confirm assumptions of the hapa and emphasize the importance of volitional processes at the inter- and intraindividual level in the context of quitting smoking.