Effect of large doses of parenteral vitamin D on glycaemic control and calcium/phosphate metabolism in patients with stable type 2 diabetes mellitus: a randomised, placebo-controlled, prospective pilot study.

OBJECTIVE Vitamin D (D₃) status is reported to correlate negatively with insulin production and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). However, few placebo-controlled intervention data are available. We aimed to assess the effect of large doses of parenteral D3 on glycosylated haemoglobin (HbA(₁c)) and estimates of insulin action (homeostasis model assessment insulin resistance: HOMA-IR) in patients with stable T2DM. MATERIALS AND METHODS We performed a prospective, randomised, double-blind, placebo-controlled pilot study at a single university care setting in Switzerland. Fifty-five patients of both genders with T2DM of more than 10 years were enrolled and randomised to either 300,000 IU D₃ or placebo, intramuscularly. The primary endpoint was the intergroup difference in HbA(₁c) levels. Secondary endpoints were: changes in insulin sensitivity, albuminuria, calcium/phosphate metabolism, activity of the renin-aldosterone axis and changes in 24-hour ambulatory blood pressure values. RESULTS After 6 months of D₃ supply, there was a significant intergroup difference in the change in HbA(₁c) levels (relative change [mean ± standard deviation] +2.9% ± 1.5% in the D₃ group vs +6.9% ± 2.1% the in placebo group, p = 0.041) as HOMA-IR decreased by 12.8% ± 5.6% in the D₃ group and increased by 10% ± 5.4% in the placebo group (intergroup difference, p = 0.032). Twenty-four-hour urinary albumin excretion decreased in the D₃ group from 200 ± 41 to 126 ± 39, p = 0.021). There was no significant intergroup difference for the other secondary endpoints. CONCLUSIONS D₃ improved insulin sensitivity (based on HOMA-IR) and affected the course of HbA(₁c) positively compared with placebo in patients with T2DM.

Neural change following different memory training approaches in very preterm born children - A pilot study.

OBJECTIVE There is mixed evidence regarding neural change following cognitive training. Brain activation increase, decrease, or a combination of both may occur. We investigated training-induced neural change using two different memory training approaches. METHODS Very preterm born children (aged 7-12 years) were randomly allocated to a memory strategy training, an intensive working memory practice or a waiting control group. Before and immediately after the trainings and the waiting period, brain activation during a visual working memory task was measured using fMRI and cognitive performance was assessed. RESULTS Following both memory trainings, there was a significant decrease of fronto-parietal brain activation and a significant increase of memory performance. In the control group, no neural or performance change occurred after the waiting period. CONCLUSION These pilot data point towards a training-related decrease of brain activation, independent of the training approach. Our data highlight the high training-induced plasticity of the child's brain during development.

A pilot test of the new Swiss regulatory procedure for categorizing clinical trials by risk: A randomized controlled trial

BACKGROUND/AIMS Several countries are working to adapt clinical trial regulations to align the approval process to the level of risk for trial participants. The optimal framework to categorize clinical trials according to risk remains unclear, however. Switzerland is the first European country to adopt a risk-based categorization procedure in January 2014. We assessed how accurately and consistently clinical trials are categorized using two different approaches: an approach using criteria set forth in the new law (concept) or an intuitive approach (ad hoc). METHODS This was a randomized controlled trial with a method-comparison study nested in each arm. We used clinical trial protocols from eight Swiss ethics committees approved between 2010 and 2011. Protocols were randomly assigned to be categorized in one of three risk categories using the concept or the ad hoc approach. Each protocol was independently categorized by the trial's sponsor, a group of experts and the approving ethics committee. The primary outcome was the difference in categorization agreement between the expert group and sponsors across arms. Linear weighted kappa was used to quantify agreements, with the difference between kappas being the primary effect measure. RESULTS We included 142 of 231 protocols in the final analysis (concept = 78; ad hoc = 64). Raw agreement between the expert group and sponsors was 0.74 in the concept and 0.78 in the ad hoc arm. Chance-corrected agreement was higher in the ad hoc (kappa: 0.34 (95% confidence interval = 0.10-0.58)) than in the concept arm (0.27 (0.06-0.50)), but the difference was not significant (p = 0.67). LIMITATIONS The main limitation was the large number of protocols excluded from the analysis mostly because they did not fit with the clinical trial definition of the new law. CONCLUSION A structured risk categorization approach was not better than an ad hoc approach. Laws introducing risk-based approaches should provide guidelines, examples and templates to ensure correct application.

Localization of Hidden Insulinomas with 68Ga-DOTA-Exendin-4 PET/CT: A Pilot Study.

UNLABELLED (111)In-DOTA-exendin-4 SPECT/CT has been shown to be highly efficient in the detection of insulinomas. We aimed at determining whether novel PET/CT imaging with [Nle(14),Lys(40)(Ahx-DOTA-(68)Ga)NH2]exendin-4 ((68)Ga-DOTA-exendin-4) is feasible and sensitive in detecting benign insulinomas. METHODS (68)Ga-DOTA-exendin-4 PET/CT and (111)In-DOTA-exendin-4 SPECT/CT were performed in a randomized cross-over order on 5 patients with endogenous hyperinsulinemic hypoglycemia. The gold standard for comparison was the histologic diagnosis after surgery. RESULTS In 4 patients histologic diagnosis confirmed a benign insulinoma, whereas one patient refused surgery despite a positive (68)Ga-DOTA-exendin-4 PET/CT scan. In 4 of 5 patients, previously performed conventional imaging (CT or MR imaging) was not able to localize the insulinoma. (68)Ga-DOTA-exendin-4 PET/CT correctly identified the insulinoma in 4 of 4 patients, whereas (111)In-DOTA-exendin-4 SPECT/CT correctly identified the insulinoma in only 2 of 4 patients. CONCLUSION These preliminary data suggest that the use of (68)Ga-DOTA-exendin-4 PET/CT in detecting hidden insulinomas is feasible.

Higher Visual Functions in the Upper and Lower Visual Fields: a pilot study in healthy subjects

Visual perception is not identical in the upper and lower visual hemifields. The mechanisms behind this difference can be found at the retinal, cortical, or higher attentional level. In this study, a new visual test battery, that involves real-time comparisons of complex visual stimuli, such as shape of objects, and speed of moving dot patterns, in the upper and lower visual hemifields, is presented. This study represents, to our knowledge, the first to implement such a visual test battery in an immersive environment composed of a hemisphere, in order to present visual stimuli in precise regions of the visual field. Ten healthy volunteers were tested in this pilot study. The results showed a higher accuracy in the image matching when the visual test was performed in the lower visual hemifield.

A brief project completion report of "Pilot project on participatory planning of sustainable land use in Chancho Obi Kebele"

Description of project activities and accountancy report.

Titanium and hydroxyapatite coating of polyetheretherketone and carbon fiber-reinforced polyetheretherketone: A pilot study in sheep

Purpose: The purpose of this study was to evaluate the bone formation capability of polyetheretherketone (PEEK) and carbon fiber-reinforced PEEK (CFR-PEEK) implants coated with different titanium and hydroxyapatite plasma-sprayed layers after 2 and 12 weeks. Methods: In six sheep 108 implants were placed in the pelvis. Altogether six different surface modifications were tested. After 2 and 12 weeks, n = 3 implants per group were examined histologically and n = 6 implants per group were tested by a pull-out test. Results: Biomechanically (p = 0.001) as well as histologically (p > 0.05) surface coating of PEEK/CFR-PEEK led to an increase of osseointegration from 2 to 12 weeks. After 12 weeks, coated implants demonstrated significant (p < 0.001) higher pull-out values in comparison to uncoated implants. Overall, the double coating (titanium bond layer and hydroxyapatite top layer) showed the most favorable results after 2 and 12 weeks. Conclusions: Plasma-sprayed titanium and hydroxyapatite coatings on PEEK or CFR-PEEK demonstrated a significant improvement of osseointegration.

Human 3β-hydroxysteroid dehydrogenase deficiency seems to affect fertility but may not harbor a tumor risk: lesson from an experiment of nature.

CONTEXT 3β-hydroxysteroid dehydrogenase deficiency (3βHSD) is a rare disorder of sexual development and steroidogenesis. There are two isozymes of 3βHSD, HSD3B1 and HSD3B2. Human mutations are known for the HSD3B2 gene which is expressed in the gonads and the adrenals. Little is known about testis histology, fertility and malignancy risk. OBJECTIVE To describe the molecular genetics, the steroid biochemistry, the (immuno-)histochemistry and the clinical implications of a loss-of-function HSD3B2 mutation. METHODS Biochemical, genetic and immunohistochemical investigations on human biomaterials. RESULTS A 46,XY boy presented at birth with severe undervirilization of the external genitalia. Steroid profiling showed low steroid production for mineralocorticoids, glucocorticoids and sex steroids with typical precursor metabolites for HSD3B2 deficiency. The genetic analysis of the HSD3B2 gene revealed a homozygous c.687del27 deletion. At pubertal age, he showed some virilization of the external genitalia and some sex steroid metabolites appeared likely through conversion of precursors secreted by the testis and converted by unaffected HSD3B1 in peripheral tissues. However, he also developed enlarged breasts through production of estrogens in the periphery. Testis histology in late puberty revealed primarily a Sertoli-cell-only pattern and only few tubules with arrested spermatogenesis, presence of few Leydig cells in stroma, but no neoplastic changes. CONCLUSIONS The testis with HSD3B2 deficiency due to the c.687del27 deletion does not express the defective protein. This patient is unlikely to be fertile and his risk for gonadal malignancy is low. Further studies are needed to obtain firm knowledge on malignancy risk for gonads harboring defects of androgen biosynthesis.

Real-time computer-based visual feedback improves visual acuity in downbeat nystagmus - a pilot study.

BACKGROUND Patients with downbeat nystagmus syndrome suffer from oscillopsia, which leads to an unstable visual perception and therefore impaired visual acuity. The aim of this study was to use real-time computer-based visual feedback to compensate for the destabilizing slow phase eye movements. METHODS The patients were sitting in front of a computer screen with the head fixed on a chin rest. The eye movements were recorded by an eye tracking system (EyeSeeCam®). We tested the visual acuity with a fixed Landolt C (static) and during real-time feedback driven condition (dynamic) in gaze straight ahead and (20°) sideward gaze. In the dynamic condition, the Landolt C moved according to the slow phase eye velocity of the downbeat nystagmus. The Shapiro-Wilk test was used to test for normal distribution and one-way ANOVA for comparison. RESULTS Ten patients with downbeat nystagmus were included in the study. Median age was 76 years and the median duration of symptoms was 6.3 years (SD +/- 3.1y). The mean slow phase velocity was moderate during gaze straight ahead (1.44°/s, SD +/- 1.18°/s) and increased significantly in sideward gaze (mean left 3.36°/s; right 3.58°/s). In gaze straight ahead, we found no difference between the static and feedback driven condition. In sideward gaze, visual acuity improved in five out of ten subjects during the feedback-driven condition (p = 0.043). CONCLUSIONS This study provides proof of concept that non-invasive real-time computer-based visual feedback compensates for the SPV in DBN. Therefore, real-time visual feedback may be a promising aid for patients suffering from oscillopsia and impaired text reading on screen. Recent technological advances in the area of virtual reality displays might soon render this approach feasible in fully mobile settings.

Combining qualitative and quantitative methods to analyze serious games outcomes: A pilot study for a new cognitive screening tool

Computer games for a serious purpose - so called serious games can provide additional information for the screening and diagnosis of cognitive impairment. Moreover, they have the advantage of being an ecological tool by involving daily living tasks. However, there is a need for better comprehensive designs regarding the acceptance of this technology, as the target population is older adults that are not used to interact with novel technologies. Moreover given the complexity of the diagnosis and the need for precise assessment, an evaluation of the best approach to analyze the performance data is required. The present study examines the usability of a new screening tool and proposes several new outlines for data analysis.

Virtual Patients in continuing medical education and residency training: a pilot project for acceptance analysis in the framework of a residency revision course in pediatrics.

AIM Virtual patients (VPs) are a one-of-a-kind e-learning resource, fostering clinical reasoning skills through clinical case examples. The combination with face-to-face teaching is important for their successful integration, which is referred to as "blended learning". So far little is known about the use of VPs in the field of continuing medical education and residency training. The pilot study presented here inquired the application of VPs in the framework of a pediatric residency revision course. METHODS Around 200 participants of a pediatric nephology lecture ('nephrotic and nephritic syndrome in children') were offered two VPs as a wrap-up session at the revision course of the German Society for Pediatrics and Adolescent Medicine (DGKJ) 2009 in Heidelberg, Germany. Using a web-based survey form, different aspects were evaluated concerning the learning experiences with VPs, the combination with the lecture, and the use of VPs for residency training in general. RESULTS N=40 evaluable survey forms were returned (approximately 21%). The return rate was impaired by a technical problem with the local Wi-Fi firewall. The participants perceived the work-up of the VPs as a worthwhile learning experience, with proper preparation for diagnosing and treating real patients with similar complaints. Case presentations, interactivity, and locally and timely independent repetitive practices were, in particular, pointed out. On being asked about the use of VPs in general for residency training, there was a distinct demand for more such offers. CONCLUSION VPs may reasonably complement existing learning activities in residency training.

[Pilot Project: Improved Lung Deposition via a New Nasal Inhalation Procedure].

INTRODUCTION Inhaled drugs can only be effective if they reach the middle and small airways. This study introduces a system that combines a trans-nasal application of aerosols with noninvasive pressure support ventilation. METHODS In a pilot study, 7 COPD patients with GOLD stages II and III inhaled a radiolabeled marker dissolved in water via a trans-nasal route. The mean aerosol particle size was 5.5 µm. Each patient took part in two inhalation sessions that included two application methods and were at least 70 hours apart. During the first session ("passive method"), the patient inhaled the aerosol through an open tube system. The second session ("active method") included pressure support ventilation during the inhalation process. A gamma camera and planar scintigraphy was used to determine the distribution of aerosol particles in the patient's body and lung. RESULTS The pressure supported inhalation ("active method") results in an increased aerosol lung deposition compared to the passive method. Above all, we could demonstrate deposition in the lung periphery with relatively large aerosol particles (5.5 µm). DISCUSSION The results prove that the combination of trans-nasal inhalation with noninvasive pressure support ventilation leads to significantly increased particle deposition in the lung.

Hysteroscopic outpatient metroplasty to expand dysmorphic uteri (HOME-DU technique): a pilot study.

The new classification system of uterine anomalies from the European Society of Human Reproduction and Embryology and the European Society for Gynaecological Endoscopy defines T-shaped and tubular-shaped infantilis uteri as 'dysmorphic'. Such malformations have been proven to be associated with poor reproductive performance. A prospective observational study was conducted with 30 infertile women with dysmorphic uterus who underwent the novel Hysteroscopic Outpatient Metroplasty to Expand Dysmorphic Uteri (HOME-DU ) technique. Incisions are made on the uterine walls with a 5 Fr bipolar electrode. The procedure was conducted in outpatients under conscious sedation, using a 5-mm office hysteroscope. The technique was successful in all cases without complications. A net increase of uterine volume was found, as measured at hysteroscopy and three-dimensional transvaginal ultrasound (P < 0.001). Uterine morphology improved in all patients but one. At mean follow-up of 15 months, clinical pregnancy rate was 57% and term delivery rate 65%. These early data support HOME-DU as safe and effective in expanding the volume and normalizing the appearance of the uterine cavity of dysmorphic uteri. Although the cohort was small, pregnancy and live births outcomes were favourable in this poor-prognosis group, implying desirable benefits, which should be compared with other techniques.

Everolimus-Eluting Bioresorbable Vascular Scaffold System in the Treatment of Cardiac Allograft Vasculopathy: the CART (Cardiac Allograft Reparative Therapy) Prospective Multicenter Pilot Study.

Cardiac allograft vasculopathy (CAV) is a form of accelerated atherosclerosis, which represents the leading cause of late morbidity and mortality after heart transplantation. The recent bioresorbable vascular scaffold (BVS) technology represents a potential novel therapeutic tool, in the context of CAV, by allowing transient scaffolding and concomitant vessel healing. Eligible subjects will be treated by using the Absorb Everolimus-Eluting BVS (Abbott Vascular, Santa Clara, CA, USA), and evaluated at pre-determined time points, up to 3 years since the index procedure. Both clinical and imaging data will be collected in dedicated case report forms (CRF). All imaging data will be analyzed in an independent core laboratory. The primary aim of the study is to evaluate the angiographic performance at 1 year of second-generation Absorb BVS, in heart transplant recipients affected by CAV.