Epilepsy and the impact of an epileptology clinic for patients with mental retardation and associated disabilities in an institutional setting

Summary:  Purpose: Epilepsy is a common problem in institutionalized patients with multiple handicaps. Limited data exist on the characteristics of epilepsy in this patient population and the impact of systematic evaluation by an epilepsy service.
Methods: We evaluated 138 patients with epilepsy, institutionalized at a facility that cares for 324 patients with multiple handicaps. Evaluation included EEG, MRI, and video-EEG monitoring. The medication regimen was changed according to seizure diagnosis and the status of seizure control. Follow-up was available for ≥6 months in 110 patients, 1 year for 89, and 1.5 years for 49 patients. We analyzed the seizure and epilepsy diagnosis in this population, as well as the seizure frequency after evaluation and treatment
Results: The 76 male and 62 female patients' ages ranged from 14 to 73 years. Seventy-three patients had fewer than one seizure per month, whereas 29 patients had at least one seizure per month. Of 131 patients taking antiepileptic drugs (AEDs), 62 were receiving monotherapy, and 69 were receiving two or more AEDs. At the last follow-up, overall 55% of patients had reduced seizure frequency, including 23% who became seizure free. Two of 36 patients had spontaneous seizure recurrence after being seizure free with no AEDs for 4 months in one patient and 3 years for the other. Attempts were made to discontinue phenobarbital, primidone, and clonazepam in 21 patients. However, these were discontinued in only five patients.
Conclusions: Epilepsy is heterogeneous in institutionalized patients with multiple handicaps. It is often responsive to medical therapy. Evaluation and treatment by epilepsy specialists had an overall favorable impact on seizure control.     

A limited sampling strategy to estimate individual pharmacokinetic parameters of methotrexate in children with acute lymphoblastic leukemia

Purpose The objectives of this study were to characterize the population pharmacokinetics of MTX in patients with acute lymphoblastic leukemia (ALL) with ages ranging from 2 to 16 years and to propose a limited sampling strategy to estimate individual pharmacokinetic parameters. Methods Seventy-nine children were enrolled in this study; they received 1–4 courses of chemotherapy. MTX was administered at a dose of 5 g/m2. MTX population parameters were estimated from 61 patients (231 courses; age range: 2–16 years). The data were analyzed by nonlinear mixed-effect modeling with use of a two-compartment structural model. The interoccasion variability was taken into account in the model. Eighteen additional patients (70 courses) were used to evaluate the predictive performances of the Bayesian approach and to devise a limited sampling strategy. Results The following population parameters were obtained: total clearance (CL) = 8.8 l/h (inter-individual variability: 43%), initial volume of distribution (V ₁) = 17.3 l (48%), k ₁₂ = 0.0225 h⁻¹ (41%), and k ₂₁ = 0.0629 h⁻¹ (24%). The inter-individual variability in the initial volume of distribution was partially explained by the fact that this parameter was weight-dependent. Intercourse variability was limited, with a mean variation of 13.2%. The protocol involving two sampling times, 24 and 48 h after the beginning of infusion, allows precise and accurate determination of individual pharmacokinetic parameters and consequently, it was possible to predict the time at which the MTX concentration reached the predicted threshold (0.2 μM) below which the administration of folinic acid could be stopped. Conclusion The results of this study combine the relationships between the pharmacokinetic parameters of MTX and patient covariates that may be useful for dose adjustment, with a convenient sampling procedure that may aid in optimizing pediatric patient care. An erratum to this article can be found at     

Undetected chronic obstructive pulmonary disease and asthma in people over 50 years with persistent cough

Background

Chronic obstructive pulmonary disease (COPD) and asthma are underdiagnosed in primary care.

Aim

To determine how often COPD or asthma are present in middle-aged and older patients who consult their GP for persistent cough.

Design of study

A cross-sectional study in 353 patients older than 50 years, visiting their GP for persistent cough and not known to have COPD or asthma.

Setting

General practice in the Netherlands.

Method

All participants underwent extensive diagnostic work-up, including symptoms, signs, spirometry, and body plethysmography. All results were studied by an expert panel to diagnose or exclude COPD and/or asthma. The reproducibility of the panel diagnosis was assessed by calculation of Cohen''s κ statistic in a sample of 41 participants.

Results

Of the 353 participants, 102 (29%, 95% confidence interval [CI] = 24 to 34%) were diagnosed with COPD. In 14 of these 102 participants, both COPD and asthma were diagnosed (4%, 95% CI = 2 to 7%). Asthma (without COPD) was diagnosed in 23 (7%, 95% CI = 4 to 10%) participants. Mean duration of cough was 93 days (median 40 days). The reproducibility of the expert panel was good (Cohen''s κ = 0.90).

Conclusion

In patients aged over 50 years who consult their GP for persistent cough, undetected COPD or asthma is frequently present.     

Reduced levels of hydroxylated, polyunsaturated ultra long-chain fatty acids in the serum of colorectal cancer patients: implications for early screening and detection

Background

There are currently no accurate serum markers for detecting early risk of colorectal cancer (CRC). We therefore developed a non-targeted metabolomics technology to analyse the serum of pre-treatment CRC patients in order to discover putative metabolic markers associated with CRC. Using tandem-mass spectrometry (MS/MS) high throughput MS technology we evaluated the utility of selected markers and this technology for discriminating between CRC and healthy subjects.

Methods

Biomarker discovery was performed using Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). Comprehensive metabolic profiles of CRC patients and controls from three independent populations from different continents (USA and Japan; total n = 222) were obtained and the best inter-study biomarkers determined. The structural characterization of these and related markers was performed using liquid chromatography (LC) MS/MS and nuclear magnetic resonance technologies. Clinical utility evaluations were performed using a targeted high-throughput triple-quadrupole multiple reaction monitoring (TQ-MRM) method for three biomarkers in two further independent populations from the USA and Japan (total n = 220).

Results

Comprehensive metabolomic analyses revealed significantly reduced levels of 28-36 carbon-containing hydroxylated polyunsaturated ultra long-chain fatty-acids in all three independent cohorts of CRC patient samples relative to controls. Structure elucidation studies on the C28 molecules revealed two families harbouring specifically two or three hydroxyl substitutions and varying degrees of unsaturation. The TQ-MRM method successfully validated the FTICR-MS results in two further independent studies. In total, biomarkers in five independent populations across two continental regions were evaluated (three populations by FTICR-MS and two by TQ-MRM). The resultant receiver-operator characteristic curve AUCs ranged from 0.85 to 0.98 (average = 0.91 ± 0.04).

Conclusions

A novel comprehensive metabolomics technology was used to identify a systemic metabolic dysregulation comprising previously unknown hydroxylated polyunsaturated ultra-long chain fatty acid metabolites in CRC patients. These metabolites are easily measurable in serum and a decrease in their concentration appears to be highly sensitive and specific for the presence of CRC, regardless of ethnic or geographic background. The measurement of these metabolites may represent an additional tool for the early detection and screening of CRC.     

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.     

Feasibility and limitations of oxcarbazepine monitoring using salivary monohydroxycarbamazepine (MHD)

The purpose of this study is to determine the feasibility of using 10-hydroxy-10,11-dihydrocarbazepine (MHD) concentration in saliva as an alternative to serum for the therapeutic monitoring of oxcarbazepine (OXC) treatment. Investigators identified subjects seen in neurology clinics at the University of Kentucky Chandler Medical Center. Patients were eligible if they agreed to participate in this study, were taking oxcarbazepine, and if a serum MHD concentration had been ordered by their physician. Unstimulated saliva specimens (0.25 mL minimum) were collected in the clinic and frozen until analysis. Blood samples were obtained by phlebotomy. Serum specimens were analyzed by a reference laboratory. Saliva MHD concentrations were determined by high-performance liquid chromatography in the Clinical Laboratory at the Cincinnati Children's Hospital Medical Center. Linear regression analysis was used to evaluate correlations. Saliva and blood specimens were collected from 28 epilepsy patients, but usable samples were obtained from only 23. The mean serum MHD concentration was 23.9 +/- 10.0 microg/mL, and the mean saliva concentration was 23.1 +/- 10.1 microg/mL. There was a significant positive correlation between the serum and saliva concentrations: saliva (y) = 0.95 serum (x) + 0.39; r = 0.941; n = 23; P < 0.001). The mean saliva:serum MHD concentration ratio was 0.96 +/- 0.15. The results of the current study indicate that the relationship between freely flowing (unstimulated) saliva and serum concentrations of MHD is sufficient for therapeutic drug monitoring. A limitation of saliva MHD monitoring is that individuals who have difficulty producing small quantities of saliva or who have viscous saliva should generally be avoided for this type of monitoring. It is also recommended to avoid saliva collection within 8 hours after OXC dosing to allow complete absorption and transformation of the parent drug.     

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.     

Comparative analysis of 8-oxo-2' -deoxyguanosine in DNA by 32P- and 33P- postlabeling and electrochemical detection

8-Oxo-2'-deoxyguanosine (8-oxo-dG) is emerging as a useful marker for oxidative DNA damage. Reported basal levels determined by 32P- postlabeling (PPL) method were 10-fold or more higher than those obtained with HPLC/electrochemical detection (ECD). This discrepancy was investigated. In commercial calf thymus DNA, levels of 4 +/- 1 and 64 +/- 14 8-oxo-dG per 10(6) 2'-deoxynucleosides (dN) were measured by the standard HPLC/ECD and PPL methods, respectively. DNA digestion by micrococcal nuclease/spleen phosphodiesterase and nuclease P1 (as used in the standard PPL method), followed by ECD analysis resulted in a level of 8 +/- 3. In calf thymus DNA spiked with chemically synthesized 8-oxo-dGp to give an increment of 9 8-oxo-dG/10(6) dN, the added standard produced a significant increase with HPLC/ECD but not PPL. After spiking the DNA with 90 8-oxo-dG/10(6) dN, the added 8-oxo-dGp was detectable also with PPL, with a labeling efficiency of 65%. In order to investigate the role of ionizing radiation from 32P for the higher 8-oxo-dG levels in PPL, incubation times and amounts of radioactivity in the phosphorylation reaction with commercial dGp were increased, and external irradiation of commercial dG with 32P was investigated. All modifications resulted in higher values of 8-oxo-dG measured, but the effect was not large enough to fully explain the discrepancy between PPL and HPLC/ECD. Using [gamma-33P]ATP instead of [gamma-32P]ATP or adding [33P]phosphate to a 32P-PPL assay resulted in even higher levels of 8-oxo-dG measured. The increase in 8-oxo-dG levels during the PPL workup is attributed to the presence and oxidation of unmodified dGp in the reaction mixture. For a determination of true basal levels, the PPL method will have to be modified, including the removal of dGp prior to the phosphorylation reaction.