Timing and directions for administration of questionnaires affect outcomes measurement

We used data from two pilot studies to compare the change in patients' self-reported health-related quality of life after participation in two nearly identical Department of Veterans Affairs (VA) Blind Rehabilitation Center (BRC) programs, the Southwestern BRC in Tucson, Arizona, and the BRC at the VA hospital in Hines, Illinois. Researchers at the Southwestern BRC administered the National Eye Institute Visual Functioning Questionnaire as directed by the developer. Researchers at the Hines BRC modified the directions to consider use of low-vision devices. Interval person-ability and item-difficulty measures estimated from patient responses pre- and postrehabilitation were compared with these same measures obtained at follow-up. At the Southwestern BRC, no change was reported in either person or item measures 3 months after rehabilitation. At the Hines BRC, improvement was seen in both the person and item measures when measurements were made immediately following rehabilitation. Because a temporary halo effect may explain the higher ratings at discharge, veterans from the Hines cohort were contacted by telephone and administered the same instrument 3 years later. For these subjects, the improvement noted in the person measure disappeared at follow-up, while the improvement in the item measure was maintained.     

Neural prostheses for restoring functions lost after spinal cord injury

<正>Spinal cord injury(SCI)is a debilitating condition that affects more than 2.5 million individuals worldwide(Thuret et al.,2006).In addition to its devastating effects on the individual,this disease is a heavy burden to the society in terms of health     

Limbic encephalitis and hyperactive foci on PET scan.

Two cases of patients with paraneoplastic limbic encephalitis, difficult to control seizures, and unilateral hippocampal hypermetabolism on positron emission tomography (PET) are described. Two women aged 33 and 61 presented with uncontrolled complex partial seizures, profound memory loss and cognitive decline. One was later diagnosed with breast cancer and the other with lung cancer. Video-EEG on the first patient recorded multifocal sharp waves and bilateral independent seizure onsets. The second patient had no epileptiform discharges and bitemporal ictal onset, even though the clinical seizures suggested a right temporal onset. Magnetic resonance imaging (MRI) was normal in both patients. PET scans obtained in the interictal state showed right hippocampal hypermetabolism in both patients. In the second patient, the lung cancer was irradiated with resolution of seizures and improvement of memory function. A PET scan six months later was normal. Subsequent seizure recurrence and worsening of memory led to the discovery of widespread metastases. Limbic encephalitis should be considered in the differential diagnosis of intractable partial epilepsy, particularly if accompanied by severe memory loss and cognitive decline. Treatment of the underlying cancer may be lead to improved seizure control. Hippocampal hypermetabolism may be a common feature on PET, and may indicate subclinical seizure activity.     

Limited sampling strategy using Bayesian estimation for estimating individual exposure of the once-daily prolonged-release formulation of tacrolimus in kidney transplant children

Background

A limited sampling strategy (LSS) for estimating the area under the curve (AUC) of the prolonged-release formulation of tacrolimus (tacrolimus^PR) is not available in pediatric patients, although the method is of real benefit to children. The objective of this study was to develop and validate a reliable and clinically applicable LSS using Bayesian estimation for estimating tacrolimus^PR AUC in pediatric kidney transplant patients

Methods

The original tacrolimus pharmacokinetic dataset consisted of 22 full profiles from 22 pediatric kidney transplant patients. The Bayesian estimation method was used to develop the LSS. External validation was performed in an independent validation group which consisted of 20 full pharmacokinetic profiles from 12 pediatric kidney transplant patients.

Results

Bayesian estimator using C_0h C_2h and C_3h gave the best predictive performance with a mean prediction error of 2.2 % in the external validation dataset. There was no correlation between the prediction error and age. The Bland–Altman analysis showed that the mean difference between the reference and Bayesian-estimated AUC_0-24 was 3.5 (95 % confidence interval ?3.5–10.5) ng h/mL

Conclusions

A reliable and clinically applicable LSS for estimating AUC_0–24 of tacrolimus^PR was determined and validated in children. The prediction was unbiased and precise. It can be used as a routine procedure to perform AUC-based tacrolimus^PR dosage optimization in pediatric renal transplant patients.     

Morale and job perception of community mental health professionals in Berlin and London

Abstract Introduction Morale and job perception of staff in community mental health care may influence feasibility and quality of care, and some research has suggested particularly high burnout of staff in the community. The aims of this study were to: a) assess morale, i. e. team identity, job satisfaction and burnout, in psychiatrists, community psychiatric nurses and social workers in community mental health care in Berlin and London; b) compare findings between the groups and test whether personal characteristics, place of working and professional group predict morale; and c) explore what tasks, obstacles, skills, enjoyable and stressful aspects interviewees perceived as important in their jobs. Methods In all, 189 mental health professionals (a minimum of 30 in each of the six groups) responded to a postal survey and reported activities per week using pre-formed categories. Perception of professional role was assessed on the Team Identity Scale, job satisfaction on the Minnesota Job Satisfaction Scale, and burnout on the Maslach Burnout Inventory. Seven simple open questions were used to elicit the main tasks, skills that staff did and did not feel competent in, aspects that they did and did not enjoy in their job, and obstacles and factors that caused pressure. Answers were subjected to content analysis using a posteriori formed categories. Results Weekly activities and morale varied between sites and professional groups. Some mean scores for groups in London exceeded the threshold for a burnout syndrome, and are particularly less favourable for social workers. Working in London predicted higher burnout, lower job satisfaction and lower team identity. Being a psychiatrist predicted higher team identity, whilst being a social worker was associated with higher burnout and lower job satisfaction. Male gender predicted lower burnout and higher team identity. However, professional group and site interacted in predicting burnout and job satisfaction. Psychiatrists in London had much more favourable scores than the other two groups, whilst this did not hold true in Berlin. Answers to open questions revealed universal aspects, such as enjoying direct patient contact and disliking bureaucracy, but also various views that were specific to a site or professional group or both. Conclusions Burnout remains a problem for some, but not all, professional groups in community mental health care, and social workers in London appear to be a group with particularly low morale. Differences between professional groups depend on the location, and it remains unclear to what extent job-related and general factors impact on the morale of mental health professionals. Answers to open questions reveal general as well as specific aspects of the job perception of the professional groups, some of which may be relevant for service development, training and supervision. More conceptual and methodological work and more extensive studies are required to develop a better understanding of how community mental health professionals perceive their job and how morale may be improved.     

TGF-alpha sustains clonal expansion by promoter-dependent, chemically initiated rat hepatocytes

A series of promoting and non-promoting barbiturates and hydantoins were examined for their ability to sustain the growth of a phenobarbital (PB)-dependent hepatocyte line in cell culture. The effective liver tumor promoters, pentobarbital, allobarbital and 5- ethyl-5-phenylhydantoin, replaced PB and supported 6/27C1 hepatocyte colony formation in vitro at 52-87% of the level induced by PB. The weak promoters secobarbital and amobarbital supported colony formation at only 11-19% of the PB control. A significant correlation was observed for in vivo and in vitro promotion activities of barbiturates and hydantoins, indicating that clonal expansion by 6/27C1 hepatocytes was promoter-dependent. Cell density also appeared to influence hepatocyte growth in vitro. Hepatocyte colonies acquired the ability to grow in the absence of PB, such that after 10 days incubation with PB, approximately 50% of colonies continued to grow in the absence of promoter. This phenomenon of clone-size-dependent hepatocyte growth suggested the operation of an autocrine growth factor pathway. Addition of the hepatocyte mitogen and autocrine growth factor, transforming growth factor-alpha (TGF-alpha), to culture medium lacking PB induced a dose-dependent increase in 6/27C1 hepatocyte colony formation. At the optimal concentration of 3 ng/ml, TGF-alpha sustained hepatocyte clonal expansion at 84% of the level induced by 2 mM PB. Individual 6/27C1 colonies that grew from single cells in the presence of TGF-alpha were tested for promoter-dependent colony formation. Either PB or TGF-alpha supported colony formation by these cells at similar levels and when combined at optimal concentrations, the response appeared to be saturated. When these factors were tested in combination at suboptimal concentrations, the two compounds were additive for supporting colony formation by the parental 6/27C1 line. The ability of TGF-alpha to replace PB and sustain hepatocyte clonal expansion was confirmed with the tumorigenic 6/15 hepatocyte line. These results suggest that TGF- alpha and PB may promote hepatocarcinogenesis by stimulating a common signal transduction pathway.      

Tacrolimus nephrotoxicity: beware of the association of diarrhea, drug interaction and pharmacogenetics

Tacrolimus is known to potentially lead to adverse events in recipients with diarrhoea and/or calcium channel blocker (CCB) co-administration. We report a renal transplant recipient who suffered from severe nephrotoxicity related to a toxic tacrolimus trough concentration in both conditions, diarrhoea and CCB co-administration, and with genotyped CYP3A system and P-glycoprotein (P-gp) polymorphisms. To our knowledge, this is the first case to be investigated for such polymorphisms. Clinicians should be reminded of the possibility of highly increased levels of tacrolimus in situations of diarrhoea and/or co-administration of CCBs. It also highlights the key role in tacrolimus pharmacokinetics of the CYP3A system and P-gp polymorphisms, and their influence in high-risk situations when enzyme activity is already affected by enterocyte damage due to diarrhoea and CCB competition.     

Upfront consolidation treatment with 131I-mIBG followed by myeloablative chemotherapy and hematopoietic stem cell transplantation in high-risk neuroblastoma

Importance::131I-metaiodobenzylguanidine ( 131I-mIBG) has a significant targeted antitumor effect for neuroblastoma. However, currently there is a paucity...     

Obstructive sleep apnea syndrome: an experience in Chinese adults in Hong Kong

OBJECTIVE: Epidemiologic studies in Caucasian populations suggested that symptomatic obstructive sleep apnea (OSA) occurred at a prevalence of 1-10%. The condition has been increasingly recognised among the Chinese in Hong Kong. We therefore, summarize our experience with OSA at the Department of Medicine, The University of Hong Kong at Queen Mary Hospital from 1985-1996. METHODS: All clinic records concerning demographic data, anthropometric data, clinical features, polysomnographic findings and treatment were reviewed. RESULTS: One hundred and twenty-two patients were diagnosed to have OSA. Demographic and clinical features were similar to Caucasian data with a male predominance of 84%, a mean age of about 50 years, and obesity as a risk factor at a mean body mass index of 30.4, which was higher than that of the average local population, although lower than that of OSA patients in Caucasian series. About 27% of the patients have a body mass index (BMI) similar to or below the population average. Nearly all were habitual snorers, and the majority had excessive daytime sleepiness. On polysomnography, the mean apnea-hypopnea index was 38. Common associated medical conditions were hypertension (34%), diabetes mellitus (10%), ischemic heart disease (9%), hyperlipidemia (6%). Most patients were managed successfully with nasal continuous positive airway pressure. Treatment with oral appliances for milder cases is being explored. CONCLUSIONS: OSA has been increasingly recognised among Chinese adults in Hong Kong in the past decade. Demographic features were similar to Caucasian data. The majority of patients were overweight, although 27% were not, and further investigation on the contribution of faciomaxillary morphology to OSA in this group is warranted.