Comparison of glomerular function tests in children with cancer

Evaluation of renal function should be performed as part of the follow-up during and after chemotherapy in pediatric cancer patients. The aim of this study was to compare an isotope clearance method [isotope glomerular filtration rate (iGFR)] with alternative methods to determine GFR in such patients. Isotope GFR [^99mTc-labeled diethylene triaminopentoacetic acid (DTPA) or ⁵¹Cr-labeled ethylenediaminetetra-acetate (EDTA)] was measured in 36 children (112 studies) and compared with simultaneously measured creatinine clearance (CrCl), serum creatinine (SCr), and cystatin C (CysC) concentrations, as well as the results of Schwartz, Counahan–Barratt, and Cockroft–Gault formulae, using general linear mixed models. Our results showed a significant association between iGFR and CysC concentrations (p < 0.001). No linear relationship was observed between CrCl and iGFR (p = 0.7). As expected, the results of height-based formulae (Counahan–Barratt and Schwartz) had significantly (p = 0.004) better correlation to iGFR than the results of a formula based on weight (Cockroft–Gault) (p = 0.19). Despite significant linear correlation, intraclass correlation coefficients showed poor agreement. Tests of similarity between iGFR estimates showed differences between average values of GFR. Therefore, determination of iGFR remains the method of choice in estimation of GFR in cancer patients. In our study population, assay of serum CysC was the most reliable alternative method to measure glomerular function.     

Effect of spinal cord abnormalities on the function of the lower urinary tract in patients with anorectal abnormalities

PURPOSE: We evaluated the effect of spinal cord abnormalities on lower urinary tract function in patients with anorectal abnormalities. MATERIALS AND METHODS: We examined 30 patients with anorectal anomalies mainly because of fecal or urinary incontinence. All patients underwent spinal magnetic resonance imaging and urodynamic investigation. RESULTS: Major lumbosacral abnormalities were detected in 57% of patients, including 13, 4 and 3 with a tethered cord, syringomyelia and caudal regression, respectively. Significant dysfunction of the lower urinary tract in 57% of the cases involved an overactive detrusor in 11, detrusor-sphincter dyssynergia in 4, distended bladder in 4 and lazy bladder in 1. When the spinal cord was normal, 54% of the patients had abnormal urodynamic findings but when the spinal cord was abnormal, 59% had abnormal urodynamics. When the bony spine was normal, 33% of the patients had an abnormal spinal cord but when the bony spine was abnormal, 69% had an abnormal spinal cord. CONCLUSIONS: Patients with anorectal abnormalities and fecal or urinary incontinence problems often have an abnormal spinal cord and abnormal urodynamic findings. However, the state of the spinal cord is not the only factor explaining lower urinary tract function. Thus, the possibility of lower urinary tract dysfunction should be considered in each patient with anorectal abnormalities. If the patient has symptoms or findings suggesting abnormal lower urinary tract function urodynamic evaluation should be performed.     

Effects of ospemifene and raloxifene on biochemical markers of bone turnover in postmenopausal women

Ospemifene is a novel selective estrogen receptor modulator (SERM) that is initially being developed for the treatment of vaginal atrophy in postmenopausal women. However, it also shows promise in the prevention and treatment of osteoporosis. As a part of a phase II trial, we compared the effects of ospemifene and raloxifene on bone turnover in postmenopausal women. The study was conducted as a randomized, double-blind study in which 118 healthy postmenopausal women received 30 (n = 29), 60 (n = 30), or 90 mg (n = 30) ospemifene or 60 mg (n = 29) raloxifene for 3 months. Bone resorption was assessed by measuring the urinary outputs of N- and C-terminal cross-linking telopeptides of type I collagen (NTX and CTX, respectively). Bone formation was assessed by measuring bone-specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I N propeptide (PINP), and procollagen type I C propeptide (PICP) in serum. All markers were studied before and at 3 months and 2–4 weeks after cessation of the medication. Urine NTX outputs decreased in all study groups, and the only statistically significant difference in NTX was observed between raloxifene and 30 mg ospemifene, which was reduced more in the raloxifene group. The output of CTX decreased most clearly in 60- and 90-mg ospemifene groups, but no significant differences between study groups emerged. A significant difference was found between the 90-mg ospemifene group and raloxifene in PINP in favor of ospemifene. No other differences in bone formation markers emerged between ospemifene and raloxifene. The study confirms the bone-restoring activity of ospemifene, which is comparable to that of raloxifene.     

Quantitative ADME Proteomics – CYP and UGT Enzymes in the Beagle Dog Liver and Intestine

Pharmaceutical Research - Beagle dogs are used to study oral pharmacokinetics and guide development of drug formulations for human use. Since mechanistic insight into species differences is needed...     

Health-related quality of life in adults with hearing impairment before and after hearing-aid rehabilitation in Finland

Objective: The aim of this study was to evaluate health-related quality of life (HRQoL) in adults with hearing impairment in Finland before and after hearing rehabilitation. Design: The study was prospective with hearing-aid rehabilitation as the intervention. The data was collected, using the 15D instrument, before and six months after hearing-aid rehabilitation. The data was analysed using t-tests and multiple linear regression methods. Study sample: The study sample included 949 adults with hearing impairment, and the control group included a sample of age- and gender-standardized general population. Results: The study population had significantly poorer HRQoL on most dimensions of the 15D when compared to the control group both before and after hearing-aid rehabilitation. Hearing-aid rehabilitation resulted in improved mean scores on the dimensions of hearing and in the overall 15D score that were statistically significant, although the mean improvement in the overall score was marginal. Self-reported hearing ability can better predict the change in HRQoL, as a result of a hearing aid, when compared with measured hearing sensitivity. Conclusions: The study supports the hypothesis that on average, use of a unilateral hearing aid results in improved subjective hearing and marginal improvement in HRQoL in adults with hearing impairment.     

Physicians’ views on patient participation in choice of oral anticoagulants in atrial fibrillation—a qualitative study

Direct oral anticoagulants provide an alternative to vitamin K antagonists for the anticoagulation therapy in atrial fibrillation (AF). The availability of several treatment options with different attributes makes shared decision‐making appropriate for the choice of anticoagulation therapy. The aim of this study was to understand how physicians choose an oral anticoagulant (OAC) for patients with AF and how physicians view patients’ participation in this decision. Semi‐structured interviews with 17 Finnish physicians (eight general practitioners and nine specialists) working in the public sector were conducted. An interview guide on experience, prescribing and opinions about oral anticoagulants was developed based on previous literature. The data were thematically analysed using deductive and inductive approaches. Based on the interviews, patient's opinion was the most influential factor in decision‐making when there were no clinical factors limiting the choice between OACs. Of patient's preferences, the most important was the attitude towards co‐payments of OACs. Patients’ opinions on monitoring of treatment, dosing and antidote availability were also mentioned by the interviewees. The choice of an OAC in AF was patient‐centred as all interviewees expressed that patient's opinion affects the choice.     

Comparison of spherical and realistically shaped boundary element head models for transcranial magnetic stimulation navigation

Objective

MRI-guided real-time transcranial magnetic stimulation (TMS) navigators that apply electromagnetic modeling have improved the utility of TMS. However, their accuracy and speed depends on the assumed volume conductor geometry. Spherical models found in present navigators are computationally fast but may be inaccurate in some areas. Realistically shaped boundary-element models (BEMs) could increase accuracy at a moderate computational cost, but it is unknown which model features have the largest influence on accuracy. Thus, we compared different types of spherical models and BEMs.

Methods

Globally and locally fitted spherical models and different BEMs with either one or three compartments and with different skull-to-brain conductivity ratios (1/1–1/80) were compared against a reference BEM.

Results

The one-compartment BEM at inner skull surface was almost as accurate as the reference BEM. Skull/brain conductivity ratio in the range 1/10–1/80 had only a minor influence. BEMs were superior to spherical models especially in frontal and temporal areas (up to 20 mm localization and 40% intensity improvement); in motor cortex all models provided similar results.

Conclusions

One-compartment BEMs offer a good balance between accuracy and computational cost.

Significance

Realistically shaped BEMs may increase TMS navigation accuracy in several brain areas, such as in prefrontal regions often targeted in clinical applications.     

Carotid artery intima-media thickness and elasticity in relation to glucose tolerance

The association between diabetes and subclinical atherosclerosis is well established. The effect of non-diabetic glucose intolerance on early atherosclerosis is not as straightforward, and the data regarding sex-related differences in this matter are limited. Therefore, our aim was to investigate these associations in men and women separately. We studied 1,304 Finnish men and women over 45?years of age who participated in the Finnish Health 2000 Survey. Ultrasonically determined carotid artery intima-media thickness and elasticity were used as markers of early atherosclerosis. Glucose tolerance was categorized according to the American Diabetes Association criteria for diabetes mellitus. Age-adjusted means for carotid artery intima-media thickness and elasticity indices were significantly (P?<?0.05) associated with glucose tolerance status in both sexes. There was a trend of increasing early atherosclerosis with the worsening of glucose tolerance in men and women. These associations were weakened in both sexes after further adjustments for other cardiovascular risk factors. In women, but not in men, significant (P?<?0.05) associations between glucose tolerance status and carotid artery elasticity were seen even after these further adjustments. Diabetes and non-diabetic glucose intolerance are associated with increased early carotid atherosclerosis compared with normal glucose tolerance in both sexes. Our results suggest that women with glucose intolerance may be in greater risk than men.     

Health-related quality of life of hospitalized patients with burns—Comparison with general population and a 2-year follow-up

Objective

Health-related quality of life (HRQoL) has gained increasing interest as an important indicator of adaptation after a burn injury. Our objective was to compare HRQoL of medium severity hospitalized burn victims with no need for intensive care treatment with that of the general population.

Methods

The 15D HRQoL questionnaire at discharge, and 6, 12 and 24 months thereafter.

Results

44 patients filled in the baseline questionnaire between June 2007 and December 2009. At discharge the mean (SD) HRQoL score (on a scale of 0–1) of the patients was worse in comparison with that of the general population (0.839 (0.125) vs. 0.936 (0.071)), p < 0.001. The most striking differences (p < 0.001) were seen on the dimensions of sleeping, usual activities, discomfort and symptoms, and sexual activity. At the 2-year follow-up the mean HRQoL score had increased from 0.835 (0.121) to 0.856 (0.149), but the difference was not statistically significant. Of the dimensions, moving and usual activities improved statistically significantly.

Conclusions

HRQoL of patients hospitalized for treatment of burns is, at discharge, compromised compared with that of the general population. During follow-up HRQoL showed slight improvement but remained at a clearly lower level.     

High stromal versican expression predicts unfavourable outcome in oral squamous cell carcinoma

BACKGROUND: Versican, an extracellular matrix proteoglycan, has been noted to be expressed in several malignant tumours and has been suggested to play an important role in cancer development and tumour growth. AIMS: To investigate whether the versican expression level in the peritumoural stromal tissue of primary oral squamous cell carcinoma (OSCC) predicts relapse-free or disease-specific survival. Also, to study the associations between versican expression and several other clinicopathological variables, as well as tumour cell proliferation. METHODS: Immunohistochemistry was used to study the expression of versican and tumour cell proliferative activity in 139 OSCCs. All pertinent clinical data were collected retrospectively from the hospital records. RESULTS: In this cohort, versican expression did not correlate with the clinicopathological factors or tumour cell proliferation. In univariate analyses, higher risk for disease recurrence was associated with higher stromal versican expression score (p = 0.02), positive neck node status (p = 0.02), lower Karnofsky performance status (p = 0.03) and higher tumour cell proliferation index (p = 0.04). Increased disease-specific risk of death was associated with high stromal versican expression score (p = 0.005) higher T class (p = 0.002), positive neck node status (p<0.001), higher stage (p<0.001), poorer histological differentiation (p = 0.005), worse general condition of the patient (p = 0.049) and increased tumour cell proliferative index (p = 0.02). In multivariate disease-specific survival analysis, high stromal versican expression score (p = 0.048), poorer histological differentiation (p = 0.047) and higher stage (p = 0.002) independently predicted poorer disease outcome. CONCLUSIONS: In this cohort, increased stromal versican expression correlated with both increased risk for disease recurrence and shortened survival. High stromal versican expression may thus be considered an independent and adverse prognostic marker in OSCC.