Erythrocytapheresis versus phlebotomy in the maintenance treatment of HFE hemochromatosis patients: results from a randomized crossover trial.

BACKGROUND: Phlebotomy is standard maintenance treatment of patients with hereditary hemochromatosis (HH). Erythrocytapheresis, which selectively removes red blood cells, provides a new, potentially more effective treatment option. Our aim was to evaluate the effectiveness of erythrocytapheresis over phlebotomy for maintenance therapy in patients with HH. STUDY DESIGN AND METHODS: We conducted a two-treatment-arms, randomized, crossover clinical trial, involving 46 patients, treated for 1 year with either erythrocytapheresis or phlebotomy to keep the ferritin level at not more than 50 µg/L. After 1 year, patients were switched to the other treatment modality. Primary endpoint was the number of treatment procedures per treatment year. Secondary endpoints were intertreatment intervals, several aspects of health-related quality of life, costs, and patient discomfort as well as preference for one of both treatments. RESULTS: The mean number of required treatment procedures per treatment year was significantly higher using phlebotomy versus erythrocytapheresis (3.3 vs. 1.9; mean difference, 1.4; 95% confidence interval, 1.1-1.7). The median intertreatment time was 2.3 times longer for erythrocytapheresis. There was no significant difference in overall health assessed by SF-36 and EQ-5D, respectively, between both treatments arms. The number of self-reported swollen joints was significantly higher during phlebotomy treatment. The mean treatment costs of one treatment year were 235€ for phlebotomy versus 511€ for erythrocytapheresis. Eighty percent of patients preferred erythrocytapheresis as treatment method. CONCLUSION: Erythrocytapheresis significantly reduced the number of treatment procedures per treatment year, although the mean treatment costs per year are higher in our health care system. It is the preferred treatment for the majority of patients.

Introducing an integrated intermediate care unit improves ICU utilization: a prospective intervention study.

BACKGROUND: Improvement of appropriate bed use and access to intensive care (ICU) beds is essential in optimizing utilization of ICU capacity. The introduction of an intermediate care unit (IMC) integrated in the ICU care may improve this utilization. METHOD: In a before-after prospective intervention study in a university hospital mixed ICU, the impact of introducing a six-bed mixed IMC unit supervised and staffed by ICU physicians was investigated. Changes in ICU utilization (length of stay, frequency of mechanical ventilation use), nursing workload assessed byTISS-28 score, as well as inappropriate bed use, accessibility of the ICU (number of referrals), and clinical outcome indicators (readmission and mortality rates) were measured. RESULTS: During 17 months, data of 1027 ICU patients were collected. ICU utilization improved significantly with an increased appropriate use of ICU beds. However, the number of referrals, readmissions to the ICU and mortality rates did not decrease after the IMC was opened. CONCLUSION: The IMC contributed to a more appropriate use of ICU facilities and did result in a significant increase in mean nursing workload at the ICU.

Erythrocytapheresis versus phlebotomy in the initial treatment of HFE hemochromatosis patients: results from a randomized trial.

BACKGROUND: Standard treatment of newly diagnosed HFE hemochromatosis patients is phlebotomy. Erythrocytapheresis provides a new therapeutic modality that can remove up to three times more red blood cells per single procedure and could thus have a clinical and economic benefit. STUDY DESIGN AND METHODS: To compare the number of treatment procedures between erythrocytapheresis and phlebotomy needed to reach the serum ferritin (SF) target level of 50 µg/L, a two-treatment-arms, randomized trial was conducted in which 38 newly diagnosed patients homozygous for C282Y were randomly assigned in a 1:1 ratio to undergo either erythrocytapheresis or phlebotomy. A 50% decrease in the number of treatment procedures for erythrocytapheresis compared to phlebotomy was chosen as the relevant difference to detect. RESULTS: Univariate analysis showed a significantly lower mean number of treatment procedures in the erythrocytapheresis group (9 vs. 27; ratio, 0.33; 95% confidence interval [CI], 0.25-0.45; Mann-Whitney p < 0.001). After adjustments for the two important influential factors initial SF level and body weight, the reduction ratio was still significant (0.43; 95% CI, 0.35-0.52; p < 0.001). Cost analysis showed no significant difference in treatment costs between both procedures. The costs resulting from productivity loss were significantly lower for the erythrocytapheresis group. CONCLUSION: Erythrocytapheresis is highly effective treatment to reduce iron overload and from a societal perspective might potentially also be a cost-saving therapy.

Effect of supervised exercise therapy for intermittent claudication in patients with diabetes mellitus.

BACKGROUND: Primary treatment for patients with intermittent claudication is exercise therapy. Diabetes mellitus (DM) is a frequently occurring comorbidity in patients with intermittent claudication, and in these patients, exercise tolerance is decreased. However, there is little literature about the increase in walking distance after supervised exercise therapy (SET) in patients with both intermittent claudication and DM. The objective of this study was to determine the effectiveness of SET for intermittent claudication in patients with DM. METHODS: Consecutive patients with intermittent claudication who started SET were included. Exclusion criteria were Rutherford stage 4 to 6 and the inability to perform the standardized treadmill test. SET was administered according to the guidelines of the Royal Dutch Society for Physiotherapy. At baseline and at 1, 3, and 6 months of follow-up, a standardized treadmill exercise test was performed. The primary outcome measurement was the absolute claudication distance (ACD). RESULTS: We included 775 patients, of whom 230 had DM (29.7%). At 6 months of follow-up, data of 440 patients were available. Both ACD at baseline and at 6 months of follow-up were significantly lower in patients with DM (P < 0.001). However, increase in ACD after 6 months of SET did not differ significantly (P = 0.48) between the DM group and the non-DM group (270 m and 400 m, respectively). CONCLUSION: In conclusion, SET for patients with intermittent claudication is equally effective in improving walking distance for both patients with and without DM, although ACD remains lower in patients with DM.

Early loss of peritubular capillaries after kidney transplantation.

Inflammation, interstitial fibrosis (IF), and tubular atrophy (TA) precede chronic transplant dysfunction, which is a major cause of renal allograft loss. There is an association between IF/TA and loss of peritubular capillaries (PTCs) in advanced renal disease, but whether PTC loss occurs in an early stage of chronic transplant dysfunction is unknown. Here, we studied PTC number, IF/TA, inflammation, and renal function in 48 patients who underwent protocol biopsies. Compared with before transplantation, there was a statistically significant loss of PTCs by 3 months after transplantation. Fewer PTCs in the 3-month biopsy correlated with high IF/TA and inflammation scores and predicted lower renal function at 1 year. Predictors of PTC loss during the first 3 months after transplantation included donor type, rejection, donor age, and the number of PTCs at the time of implantation. In conclusion, PTC loss occurs during the first 3 months after renal transplantation, associates with increased IF and TA, and predicts reduced renal function.

A multicenter, randomized, dose-finding study of mechanochemical ablation using ClariVein and liquid polidocanol for great saphenous vein incompetence.

BACKGROUND: The purpose of the present study was to identify the ideal polidocanol (POL) concentration for mechanochemical ablation (MOCA) of the great saphenous vein (GSV) using the ClariVein system (Merit Medical, South Jordan, Utah). METHODS: We performed a multicenter, randomized, controlled, single-blind trial with a follow-up period of 6 months. Patients with symptomatic primary truncal GSV incompetence were randomized to MOCA + 2% POL liquid (2% group) or MOCA + 3% POL liquid (3% group). The primary outcome was technical success (TS), defined as an open part of the treated vein segment of ≤10 cm in length. The secondary outcomes were alternative TS, defined as ≥85% occlusion of the treated vein segment, postoperative pain, venous clinical severity scores, Aberdeen varicose vein questionnaire scores, and short-form 36-item health survey questionnaire scores, and complications. RESULTS: From 2012 to 2018, 364 patients (375 limbs) were included, of which, 189 limbs were randomly allocated to the 2% group and 186 to the 3% group. The TS rate at 6 months was 69.8% in the 2% group vs 78.0% in the 3% group (P = .027). A higher overall TS rate was seen in GSVs of ≤5.9 mm compared with GSVs >5.9 mm (84.3% vs 59.5%, respectively; P < .001). The alternative TS rate at 6 months was 61.4% in the 2% group and 67.7% in the 3% group (P = .028). The venous clinical severity scores, Aberdeen varicose vein questionnaire scores, and most short-form 36-item health survey questionnaire domains had improved in both groups (P < .002). Postprocedural pain was low. Two pulmonary embolisms and two deep vein thromboses were seen. Superficial venous thrombosis had occurred more often in the 3% group (18 vs 8 in the 2% group; P = .033). CONCLUSIONS: The results from the present study showed a higher success rate for MOCA with 3% POL liquid than for MOCA with 2% POL liquid at 6 months of follow-up. However, the difference in quality of life was not significant. Long-term follow-up studies are required to investigate whether these results will be sustained in the future.

The effect of pulse rate changes on the clinical outcome of sacral neuromodulation.

PURPOSE: We evaluated the effect of pulse rate changes on the clinical response to and stimulation related pain symptoms of sacral neuromodulation treatment. MATERIALS AND METHODS: In this pilot study we evaluated the effect of 4 pulse rates, including 5.2, 10, 21 and 40 Hz, in patients with a suboptimal response to sacral neuromodulation. The effect of each frequency was evaluated during a 6-day test period. To avoid the carryover effect stimulation was discontinued for 24 hours between consecutive test periods. On the last 3 days of each test period a voiding diary and questionnaire were completed. Changes in the clinical response and pain symptoms were compared between the 4 pulse rates using multivariate analysis. RESULTS: Of the 50 patients included in the study 40 (80%) were female. Mean ± SD age was 55.5 ± 12.3 years. Of the patients 41 (82%) had overactive bladder symptoms and 9 (18%) were in chronic nonobstructive urinary retention. No significant difference was found in clinical outcome on the voiding diary and questionnaire between the pulse rates and none of the 4 rates was significantly related to sacral neuromodulation associated pain. However, individuals appeared to benefit from changing the pulse rate in terms of treatment efficacy and stimulation related pain. CONCLUSIONS: On the group level none of the 4 pulse rates appeared to have a significantly different effect on clinical outcome or sacral neuromodulation related pain. However, an individualized approach to optimize treatment efficacy by changing the pulse rate appears to be useful.

During IVF treatment patient preference shifts from singletons towards twins but only a few patients show an actual reversal of preference.

BACKGROUND: Knowledge of patients' preferences for elective single embryo transfer (eSET) or double embryo transfer (DET) and for singletons or twins is of great importance in counselling for embryo transfer (ET) strategies. In this study, the stability of IVF patients' preferences over time for either a healthy single child or healthy twins was measured and we investigated which factors could explain preference shifts. METHODS: Infertile women (n = 177) who participated in an RCT comparing one cycle eSET with one cycle DET were included. A satisfaction questionnaire was developed to measure patient preferences and attitudes at two moments in time, i.e. at 2 weeks before ET and at 2 weeks following ET, after the results of the pregnancy test. Regression analysis examined the effect of several variables on preference shifts. RESULTS: Before ET, most patients expressed a preference for a singleton, whereas most patients were indifferent 2 weeks after ET, resulting in an overall preference shift towards twins (P = 0.002; n = 145). Overall, 62% of patients showed a preference shift. Preference shifts were explained by patients' global satisfaction of the information given by the fertility clinic staff received by the fertility clinic staff, and an interaction between the occurrence of pregnancy and transfer policy (eSET or DET). CONCLUSIONS: In general, patients' preferences for a singleton or twins are not stable during IVF treatment. Possible explanations of a shift in preference are that pregnant patients attuned their preferences to what they expect their pregnancy to result in, whereas non-pregnant patients shifted towards a preference for twins in order to be able to fulfil their ultimate child wish.

Bone metabolic activity in hyperostosis cranialis interna measured with 18F-fluoride PET.

PURPOSE: (18)F-Fluoride PET/CT is a relatively undervalued diagnostic test to measure bone metabolism in bone diseases. Hyperostosis cranialis interna (HCI) is a (hereditary) bone disease characterised by endosteal hyperostosis and osteosclerosis of the skull and the skull base. Bone overgrowth causes entrapment and dysfunction of several cranial nerves. The aim of this study is to compare standardised uptake values (SUVs) at different sites in order to quantify bone metabolism in the affected anatomical regions in HCI patients. METHODS: Nine affected family members, seven non-affected family members and nine non-HCI non-family members underwent (18)F-fluoride PET/CT scans. SUVs were systematically measured in the different regions of interest: frontal bone, sphenoid bone, petrous bone and clivus. Moreover, the average (18)F-fluoride uptake in the entire skull was measured by assessing the uptake in axial slides. Visual assessment of the PET scans of affected individuals was performed to discover the process of disturbed bone metabolism in HCI. RESULTS: (18)F-Fluoride uptake is statistically significantly higher in the sphenoid bone and clivus regions of affected family members. Visual assessment of the scans of HCI patients is relevant in detecting disease severity and the pattern of disturbed bone metabolism throughout life. CONCLUSION: (18)F-Fluoride PET/CT is useful in quantifying the metabolic activity in HCI and provides information about the process of disturbed bone metabolism in this specific disorder. Limitations are a narrow window between normal and pathological activity and the influence of age. This study emphasises that (18)F-fluoride PET/CT may also be a promising diagnostic tool for other metabolic bone disorders, even those with an indolent course.

Psychological and psychiatric factors as predictors for success in sacral neuromodulation treatment.

UNLABELLED: What's known on the subject? and What does the study add? Sacral neuromodulation (SNM) is a well-established treatment for patients with chronic LUTS. The selection of eligible candidates could be improved by identifying factors that can predict a successful response. In the present study, we evaluated the role of various psychological and psychiatric factors in relation to SNM treatment. OBJECTIVE: • To evaluate if psychological and psychiatric factors can predict the outcome of test stimulation or permanent treatment with sacral neuromodulation (SNM). PATIENTS AND METHODS: • Between 2006 and 2009, patients with overactive bladder syndrome or non-obstructive urinary retention who were eligible for test stimulation were included. • All patients completed the Amsterdam Biographic Questionnaire (ABQ), which measures the personality traits of the patient, and the Symptom Check-List-90-Revised (SCL-90-R), which is a screening instrument for neuroticism, and for current level of complaints. • The results of the questionnaires were compared with the outcomes of test stimulation and permanent treatment. • In addition to the questionnaires, we also included the psychiatric history as a potential predictive factor. RESULTS: • On univariate analysis there was no relationship between the psychological characteristics and the outcome of test stimulation or the occurrence of adverse events (AEs) with permanent treatment. • A history of psychiatric disease was not related to the outcome of test stimulation, but was shown to be a positive predictor for the occurrence of AEs with permanent SNM treatment. CONCLUSIONS: • In the present study there was no evidence that psychological screening with the ABQ or SCL-90-R can predict the outcome of SNM treatment. • Patients with a medical history of psychiatric disease appear to be more likely to encounter AEs with permanent SNM treatment.

Health-related quality of life after fast-track treatment results from a randomized controlled clinical equivalence trial.

PURPOSE: This randomized clinical equivalence trial was designed to evaluate health-related quality of life (HRQoL) after fast-track treatment for low-risk coronary artery bypass (CABG) patients. METHODS: Four hundred and ten CABG patients were randomly assigned to undergo either short-stay intensive care treatment (SSIC, 8 h of intensive care stay) or control treatment (care as usual, overnight intensive care stay). HRQoL was measured at baseline and 1 month, and one year after surgery using the multidimensional index of life quality (MILQ), the EQ-5D, the Beck Depression Inventory and the State-Trait Anxiety Inventory. RESULTS: At one month after surgery, no statistically significant difference in overall HRQoL was found (MILQ-score P-value=.508, overall MILQ-index P-value=.543, EQ-5D VAS P-value=.593). The scores on the MILQ-domains, physical, and social functioning were significantly higher at one month postoperatively in the SSIC group compared to the control group (P-value=.049; 95%CI: 0.01-2.50 and P-value=.014, 95% CI: 0.24-2.06, respectively). However, these differences were no longer observed at long-term follow-up. CONCLUSIONS: According to our definition of clinical equivalence, the HRQoL of SSIC patients is similar to patients receiving care as usual. Since safety and the financial benefits of this intervention were demonstrated in a previously reported analysis, SSIC can be considered as an adequate fast-track intensive care treatment option for low-risk CABG patients.

Recurrence and functional results after open versus conventional laparoscopic versus robot-assisted laparoscopic rectopexy for rectal prolapse: a case-control study.

PURPOSE: This study was designed to evaluate recurrence and functional outcome of three surgical techniques for rectopexy: open (OR), laparoscopic (LR), and robot-assisted (RR). A case-control study was performed to study recurrence after the three operative techniques used for rectal procidentia. The secondary aim of this study was to examine the differences in functional results between the three techniques. MATERIALS AND METHODS: All consecutive patients who underwent a rectopexy between January 2000 and September 2006 enrolled in this study. Peri-operative data were collected from patient records and functional outcome was assessed by telephonic questionnaire. RESULTS: Eighty-two patients (71 females, mean age 56.4 years) underwent a rectopexy for rectal procidentia. Nine patients (11%) had a recurrence; one (2%) after OR, four (27%) after LR, and four (20%) after RR. RR showed significantly higher recurrence rates when controlled for age and follow-up time compared to OR, (p = 0.027), while LR showed near-significant higher rates (p = 0.059). Functional results improved in all three operation types, without a difference between them. CONCLUSIONS: LR and RR are adequate procedures but have a higher risk of recurrence. A RCT is needed assessing the definitive role of (robotic assistance in) laparoscopic surgery in rectopexy.

Using EQ-5D in children with asthma, rheumatic disorders, diabetes, and speech/language and/or hearing disorders.

OBJECTIVES: This study explores several variables of the EQ-5D child version, a multi-attribute utility instrument, in children with chronic conditions. METHODS: A convenience sample was selected from hospital outpatient records and school records. The sample included children aged 7-18 years with the following chronic conditions: asthma, rheumatic disorders, diabetes, and speech/language and/or hearing disorders. The practicality, convergent validity, and discriminant power were compared with a generic quality of life questionnaire for children (TACQOL) and the 2-week test-retest reliability was assessed. RESULTS: A total of 182 children or their parents completed the first questionnaire and 161 children/parents completed both questionnaires. The practicality of the EQ-5D was good. Low to moderate correlations were found between the utilities and VAS scores and the TACQOL scales. The discriminant power of the EQ-5D items was low overall and was greater for children with a rheumatic disorder than for children with the other conditions. In the subset of children who experienced no health change between the test and the retest, the reliability of the EQ-5D was moderate to high. CONCLUSIONS: The EQ-5D seems suitable for children, although the use of an additional disease-specific questionnaire is still recommended. The EQ-5D seems the most suitable for children with a chronic physical condition and appears to be reliable for children with a stable health status.

Long-term effects of motherfit group therapy in pre-(MOTHERFIT1) and post-partum women (MOTHERFIT2) with stress urinary incontinence compared to care-as-usual: study protocol of two multi-centred, randomised controlled trials.

BACKGROUND: Stress urinary incontinence (SUI) is highly prevalent during pregnancy and after delivery. It is often associated with a failing pelvic floor, sphincteric and/or supportive system. Pelvic-floor-muscle training (PFMT) peri-partum has been proven effective for up to 1 year post-partum; however, its long-term effects are unknown. Group PFMT, given by a physiotherapist, has been proven to be as equally effective as individual therapy. Motherfit is a group-PFMT therapy with an emphasis on pelvic floor exercises, adherence and general fitness. Care-as-usual (CAU), if guideline driven, should, as first treatment option, consist of PFMT. Cost-effective strategies are of relevance, given the rise of health care costs. Motherfit group therapy has the potential to be cost-effective in women with urinary incontinence. Therefore, the objectives of the two current studies are: (1) to investigate whether intensive, supervised, pre-partum (MOTHERFIT1) or post-partum (MOTHERFIT2) pelvic-floor-muscle group therapy reduces 18-month post-partum severity of SUI compared to CAU and (2) whether MOTHERFIT1 OR MOTHERFIT 2 is more (cost-)effective compared to CAU. METHODS: Two multi-centred, randomised controlled trials (MOTHERFIT1, n = 150, MOTHERFIT2, n = 90) will be performed. Participants will be recruited by their midwife or gynaecologist during their routine check. Participants with SUI will receive either motherfit group therapy or CAU. Motherfit group therapy consists of eight group sessions of 60 min each, instructed and supervised by a registered pelvic physiotherapist. Motherfit group therapy includes instructions on pelvic floor anatomy and how to contract, relax and train the pelvic-floor muscles correctly and is combined with general physical exercises. Adherence during and after motherfit will be stimulated by reinforcement techniques and a mobile app. The primary outcome measure is the absence of self-reported SUI based on the severity sum score of the International Consultation on Incontinence Questionnaire Short Form (ICIQ-UI-SF) at 18 months post-partum. Secondary outcomes evaluate quality of life, subjective improvement and health care costs. DISCUSSION: The motherfit studies are, to our knowledge, the first studies that evaluate both long-term results and health care costs compared to CAU in pregnant and post-partum women with SUI. If motherfit is shown to be (cost-)effective, implementation in peri-partum care should be considered. TRIAL REGISTRATION: Netherlands Trial Register, ID: NL5816 . Registered on 18 July 2016.

Changes in hospital costs after introducing an intermediate care unit: a comparative observational study.

INTRODUCTION: The high cost of critical care resources has resulted in strategies to reduce the costs of ruling out low-risk patients by developing intermediate care units (IMCs). The aim of this study was to compare changes in total hospital costs for intensive care patients before and after the introduction of an IMC at the University Hospital Maastricht. METHODS: The design was a comparative longitudinal study. The setting was a university hospital with a mixed intensive care unit (ICU), an IMC, and general wards. Changes in total hospital costs were measured for patients who were admitted to the ICU before and after the introduction of the IMC. The comparison of interest was the opening of a six-bed mixed IMC. RESULTS: The mean total hospital cost per patient increased significantly. Before the introduction of the IMC, the total hospital cost per patient was n12,961 (+/- n14,530) and afterwards it rose to n16,513 (+/- n17,718). Multiple regression analysis was used to determine to what extent patient characteristics explained these higher hospital costs using mortality, type of stay, diagnostic categories, length of ICU and ward stay, and the Therapeutic Intervention Scoring System (TISS) as predictors. More surgical patients, greater requirements of therapeutic interventions on the ICU admission day, and longer ICU stay in patients did explain the increase in hospital costs, rather than the introduction of the IMC. CONCLUSION: After the introduction of the IMC, the higher mean total hospital costs for patients with a high TISS score and longer ICU stay explained the cost increase.

Prediction of peak pressure from clinical and radiological measurements in patients with diabetes.

BACKGROUND: Various structural and functional factors of foot function have been associated with high local plantar pressures. The therapist focuses on these features which are thought to be responsible for plantar ulceration in patients with diabetes. Risk assessment of the diabetic foot would be made easier if locally elevated plantar pressure could be indicated with a minimum set of clinical measures. METHODS: Ninety three patients were evaluated through vascular, orthopaedic, neurological and radiological assessment. A pressure platform was used to quantify the barefoot peak pressure for six forefoot regions: big toe (BT) and metatarsals one (MT-1) to five (MT-5). Stepwise regression modelling was performed to determine which set of the clinical and radiological measures explained most variability in local barefoot plantar peak pressure in each of the six forefoot regions. Comprehensive models were computed with independent variables from the clinical and radiological measurements. The difference between the actual plantar pressure and the predicted value was examined through Bland-Altman analysis. RESULTS: Forefoot pressures were significant higher in patients with neuropathy, compared to patients without neuropathy for the whole forefoot, the MT-1 region and the MT-5 region (respectively 138 kPa, 173 kPa and 88 kPa higher: mean difference). The clinical models explained up to 39 percent of the variance in local peak pressures. Callus formation and toe deformity were identified as relevant clinical predictors for all forefoot regions. Regression models with radiological variables explained about 26 percent of the variance in local peak pressures. For most regions the combination of clinical and radiological variables resulted in a higher explained variance. The Bland and Altman analysis showed a major discrepancy between the predicted and the actual peak pressure values. CONCLUSION: At best, clinical and radiological measurements could only explain about 34 percent of the variance in local barefoot peak pressure in this population of diabetic patients. The prediction models constructed with linear regression are not useful in clinical practice because of considerable underestimation of high plantar pressure values. Identification of elevated plantar pressure without equipment for quantification of plantar pressure is inadequate. The use of quantitative plantar pressure measurement for diabetic foot screening is therefore advocated.

The functional, metabolic, and anabolic responses to exercise training in renal transplant and hemodialysis patients.

BACKGROUND: Exercise intolerance is common in hemodialysis (HD) and renal transplant (RTx) patients and is related to muscle weakness. Its pathogenesis may vary between these groups leading to a different response to exercise. The aim of the study was to compare intrinsic muscular parameters between HD and RTx patients and controls, and to assess the response to exercise training on exercise capacity and muscular structure and function in these groups. METHODS: Quadriceps function (isokinetic dynamometry), body composition (dual-energy x-ray absorptiometry), and vastus lateralis muscle biopsies were analyzed before and after a 12-week lasting training-program in 35 RTx patients, 16 HD patients, and 21 healthy controls. RESULTS: At baseline, myosin heavy chain (MyHC) isoform composition and enzyme activities were not different between the groups. VO2peak and muscle strength improved significantly and comparably over the training-period in RTx, HD patients and controls (p(time)<0.05). The proportion of MyHC type I isoforms decreased (p(time)<0.001) and type IIa MyHC isoforms increased (p(time)<0.05). The 3-hydroxyacyl-CoA-dehydrogenase activity increased (p(time)=0.052). Intrinsic muscular changes were not significantly different between groups. In the HD group, changes in lean body mass were significantly related to changes in muscle insulin-like growth factor (IGF)-II and IGF binding protein-3. CONCLUSIONS: Abnormalities in metabolic enzyme activities or muscle fiber redistribution do not appear to be involved in muscle dysfunction in RTx and HD patients. Exercise training has comparable beneficial effects on functional and intrinsic muscular parameters in RTx patients, HD patients, and controls. In HD patients, the anabolic response to exercise training is related to changes in the muscle IGF system.

Assessment of vascularity in irradiated and nonirradiated maxillary and mandibular minipig alveolar bone using laser doppler flowmetry.

PURPOSE: The purpose of this animal study was to confirm that laser Doppler flowmetry (LDF) is a reproducible method for the assessment of maxillary and mandibular alveolar bone vascularity and that there is less vascularity in irradiated mandibular and maxillary bone compared to nonirradiated bone. MATERIALS AND METHODS: All maxillary and mandibular premolars and molars of 6 Göttingen minipigs were extracted. After a 3-month healing period, 3 minipigs received irradiation at a total dose of 24 Gy. Three months after irradiation, 5 holes were drilled in the residual alveolar ridge of each edentulous site in each minipig. Local microvascular blood flow around all 120 holes was recorded by LDF prior to implant placement. In 1 irradiated and 1 nonirradiated minipig, an additional hole was drilled in a right maxillary site to enable repeated LDF recordings. RESULTS: The alveolar bone appeared less vascularized in irradiated than in nonirradiated minipigs. The effect of radiation appeared more pronounced in the mandible than in the maxilla. LDF was demonstrated to be a reproducible method for assessing alveolar bone vascularity. However, recordings varied by edentulous site as well as by minipig. CONCLUSION: The authors' hypotheses regarding LDF and vascularity were supported. Further research validating the use of LDF in human beings, especially in those who have undergone radiation therapy for head and neck cancer, is necessary.

Effect of calcium, vitamins K1 and D3 on bone in galactosemia.

Classical galactosemia is an inherited disorder of galactose metabolism. Recently, diminished bone mineral content (BMC) in children and adolescents has been found. The aim of this study was to evaluate the effect of calcium, vitamins K(1) and D(3) supplementation on bone in children with galactosemia. A 2-year randomized, double-blind, placebo-controlled clinical trial was undertaken in which 40 children with classical galactosemia (13 males and 27 females, aged 3-17 years) were included to receive daily either 750 mg calcium, 1.0 mg vitamin K(1) and 10.0 microg vitamin D(3) or placebo. BMC of femoral neck, lumbar spine and total body and body composition data were determined by dual energy X-ray absorptiometry (DXA) at baseline and after 1 and 2 years. Diet was assessed using a food frequency questionnaire and a 3-day food diary. Biochemical measurements were determined at baseline and after 1 and 2 years. In the children receiving treatment, carboxylated osteocalcin (cOC) concentration significantly increased (P < 0.001) and undercarboxylated osteocalcin (ucOC) concentration significantly decreased (P = 0.001) when compared to the children receiving placebo. Furthermore, there was a statistically significant increase in BMC of lumbar spine (P = 0.001), lean tissue mass (LTM: P = 0.016) and fat mass (FM: P = 0.014) in the treatment group when compared to the placebo group. The significant increase in cOC and decrease in ucOC concentration in the treatment group were present in prepubertal (P < 0.001 and P = 0.006 respectively) and pubertal children (P = 0.004 and P = 0.042 respectively). The significant increase in BMC of lumbar spine in the treatment group was present only in the prepubertal children (P = 0.015). Supplementation of calcium, vitamins K(1) and D(3) given in this dose (750 mg, 1.0 mg and 10.0 mug respectively) is likely to have a role in the treatment of BMC abnormalities in galactosemia.

Statins associated with reduced mortality in patients admitted for congestive heart failure.

BACKGROUND: Statins may be of potential benefit in patients with congestive heart failure (CHF) due to modulation of neurohormones and their antioxidant, antiinflammatory, and antifibrotic properties. To test this hypothesis, we performed a case-control study by using a prospective registry of patients admitted to our hospital for CHF. METHODS AND RESULTS: The Maastricht Registry of Congestive Heart Failure consists of a cohort of all patients who were admitted to the University Hospital Maastricht because of CHF for the first time between 1998 and 2000. Elective admissions were not included in the database. Drug treatment was left at the discretion of the attending physician. From a total of 840 patients admitted, we selected patients with an uncomplicated survival for at least 1 month after hospital discharge. For each survivor a nonsurvivor was matched for age, sex, left ventricular ejection fraction, and renal function. Drugs were considered in use only if they were administered for at least 90% of follow-up time. Five hundred twenty-four patients were included with a mean follow-up after discharge of 31 +/- 18 months. Twenty percent used statins. In Cox multivariate regression analysis, the use of statins remained significantly associated with decreased mortality independent of the cause of CHF. However, there appeared no additional benefit of statins in patients using beta-blockers. Mortality rates were constant over time after discharge. Statins were as effective in ischemic as in nonischemic heart failure and in patients with depressed as well as preserved LVEF. CONCLUSION: Statins appear associated with improved survival in CHF independent of its etiology. No additional benefit was seen in patients treated with beta-blockers.