nils-herrmann/clean_scirepeval huggingface dataset:
Clinical effect of bisphosphonate and vitamin D on osteoporosis: reappraisal of a multicenter double-blind clinical trial comparing etidronate and alfacalcidol

As inhibitors of bone resorption, bisphosphonates and vitamin D derivatives have been extensively used for the treatment of osteoporosis in various parts of the world, but the clinical effects of these two groups of agents have rarely been compared in detail. A multicenter, prospective, double-blind controlled study was started comparing the effects of etidronate and alfacalcidol (1-alpha-hydroxycholecalciferol) in 414 patients with established osteoporosis from 36 centers. Among these patients, 135 were given 400 mg etidronate daily at bedtime for 2 weeks followed by 10 weeks off treatment, and this cycle was repeated four times along with a placebo indistinguishable from the alfacalcidol capsule daily throughout the 48 weeks of study (Group A, High Dose Etidronate Group). In 133 patients, 200 mg etidronate was used instead of 400 mg (Group B, Low Dose Etidronate Group). In 138 patients, 1 µg alfacalcidol was given daily throughout the 48-week study period along with a placebo indistinguishable from the etidronate tablet in four separate periods of 2 weeks (Group C, Control Group). Dual-energy X-ray absorptiometry of the lumbar spine (L2–L4) was performed before the beginning of the study and every 12 weeks thereafter. Changes in spinal deformity were also assessed based on the lateral thoracic and lumbar spine X-ray films taken before and after the study. The lumbar spine bone mineral density (BMD) changes were +3.4% ± 0.6% (mean ± SEM) in Group A, +2.4% ± 0.5% in Group B, and −0.5% ± 0.4% in Group C, the former two being significantly higher than the last. New occurrence of spinal compression fracture was also significantly reduced in Group A compared to Group C. In patients without previous fracture at entry, incident fracture was 10.2% in Group C, but 0% in Groups A and B. In patients with prevalent fracture at entry, corresponding figures were 21.5% (Group C), 12.0% (Group A), and 13.2% (Group B), respectively. Alfacalcidol maintained lumbar spine BMD, preventing a decrease for 48 weeks, and etidronate significantly increased it further, demonstrating its usefulness in the treatment of established osteoporosis.
Computerized planning for multiprobe cryosurgery using a force-field analogy.

Cryosurgery is the destruction of undesired biological tissues by freezing. For internal organs, multiple cryoprobes are inserted into the tissue with the goal of maximizing cryoinjury within a predefined target region, while minimizing cryoinjury to the surrounding tissues. The objective of this study is to develop a computerized planning tool to determine the best locations to insert the cryoprobes, based on bioheat transfer simulations. This tool is general and suitable for all available cooling techniques and hardware. The planning procedure employs a novel iterative optimization technique based on a force-field analogy. In each iteration, a single transient bioheat transfer simulation of the cryoprocedure is computed. At the end of the simulation, regions of tissue that would have undesired temperatures apply "forces" to the cryoprobes directly moving them to better locations. This method is more efficient than traditional numerical optimization techniques, because it requires significantly fewer bioheat transfer simulations for each iteration of planning. For demonstration purposes, 2D examples on cross sections typical of prostate cryosurgery are given.
Cognitive behavioural intervention for adults with anxiety complications of asthma: prospective randomised trial.

High levels of asthma-related fear and panic exacerbate asthma symptoms and complicate the management of asthma. Asthma-specific fear may be reduced by a cognitive behavioural intervention. We aimed to test if there is a reduction in asthma-specific fear after cognitive behavioural intervention compared with routine treatment.



Adults with asthma registered with family doctors in Sheffield UK were screened for anxiety and 94 highly anxious patients were randomly allocated to receive either a cognitive behavioural intervention to improve self-management of their anxiety (n = 50) or routine clinical care (n = 44). Asthma-specific fear at the end of treatment and at six month follow up were the primary endpoints. Service usage in the six months prior to and six months following the intervention was monitored to allow estimation of costs. Data were analysed by intention to treat.



At the end of treatment, there was a significantly greater reduction in asthma-specific fear for people in the CBT group compared with controls. At six months after treatment the reduction in asthma-specific fear in the CBT group was increased and the difference between treatment and control group was statistically significant. Service use costs were not reduced in the CBT group.



A brief cognitive behavioural intervention was found to have efficacy in reducing asthma-specific panic fear immediately after treatment and at 6 months follow up. There was no cost advantage to cognitive behavioural treatment.
UK Renal Registry 11th Annual Report (December 2008): Chapter 15 The UK Renal Registry, UKRR database, validation and methodology.

The UK Renal Registry receives encrypted data extracts quarterly from each centre providing Renal Replacement Therapy (RRT) in England, Wales and Northern Ireland. Summary data is received from the Scottish Renal Registry to allow national statistics to be compiled. Data from patients receiving haemodialysis in satellite units or at home are reported through the main renal centre. Data from patients with functioning kidney transplants are reported through the centre providing routine clinical follow-up. The data are extracted from a variety of IT systems with varying functionality and no common messaging system, necessitating extensive data validation and cleaning prior to analysis. Growing confidence in the analyses since the inception of the Registry in 1995 has allowed de-anonymised centre-specific analyses of all outcomes, including survival, to be published, although incomplete data returns for primary renal diagnosis and comorbidity at start of RRT limit ability to adjust for case-mix.
Three-dimensional reconstructed rotational digital subtraction angiography in planning treatment of intracranial aneurysms

We evaluated three-dimensional (3D) reconstructions of 200 ° rotational digital subtraction angiography (DSA) images for their contributions to improving the safety of endovascular embolization of intracranial aneurysms. Standard DSA and 200 ° rotational DSA were performed in 40 adult patients (aged 21–77 years) with 45 intracranial aneurysms. Information obtainable from standard DSA and 3D-DSA images about aneurysm shape and size was compared. In 40 (89 %) of the 45 aneurysms 3D-DSA gave additional information about the anatomy of the aneurysm. In 17 (43 %) of these cases aneurysm anatomy could be visualized better on 3D-DSA than on standard DSA images. In three cases only 3D-DSA images showed blood vessels originating from the aneurysm. Reconstructed 3D images were also helpful in visualizing partially clipped aneurysms. On maximum-intensity projection images it was even possible to depict previously embolized aneurysms. Blood vessels originating from the aneurysm are visible on 3D-DSA images, and even previously clipped aneurysms can be visualized well. Rotational DSA with 3D reconstruction is a helpful tool in the assessment of intracranial aneurysms.
Functional diffusion map: a noninvasive MRI biomarker for early stratification of clinical brain tumor response.

Assessment of radiation and chemotherapy efficacy for brain cancer patients is traditionally accomplished by measuring changes in tumor size several months after therapy has been administered. The ability to use noninvasive imaging during the early stages of fractionated therapy to determine whether a particular treatment will be effective would provide an opportunity to optimize individual patient management and avoid unnecessary systemic toxicity, expense, and treatment delays. We investigated whether changes in the Brownian motion of water within tumor tissue as quantified by using diffusion MRI could be used as a biomarker for early prediction of treatment response in brain cancer patients. Twenty brain tumor patients were examined by standard and diffusion MRI before initiation of treatment. Additional images were acquired 3 weeks after initiation of chemo- and/or radiotherapy. Images were coregistered to pretreatment scans, and changes in tumor water diffusion values were calculated and displayed as a functional diffusion map (fDM) for correlation with clinical response. Of the 20 patients imaged during the course of therapy, 6 were classified as having a partial response, 6 as stable disease, and 8 as progressive disease. The fDMs were found to predict patient response at 3 weeks from the start of treatment, revealing that early changes in tumor diffusion values could be used as a prognostic indicator of subsequent volumetric tumor response. Overall, fDM analysis provided an early biomarker for predicting treatment response in brain tumor patients.
Serum levels of intercellular adhesion molecule-1 and E-selectin in patients with acute ischaemic stroke

To investigate the role of circulating intercellular adhesion molecule-1 (ICAM-1) and E-selectin in ischaemic stroke, serum levels of ICAM-1 and E-selectin were measured by ELISA in 51 patients with acute ischaemic stroke within 24 h, and in 25 age-matched healthy controls and 10 young healthy volunteers. Carotid Doppler ultrasonography showed a significant stenosis (>50%) of the carotid or vertebrobasilar artery in 11 of 51 stroke patients. Serum levels of ICAM-1 [mean (SE)] were higher (P <0.01) in patients with ischaemic stroke [381 (30) ng/ ml] than in age-matched controls [271 (27) ng/ml] and young controls [246 (6) ng/ml]. There was no significant difference in serum E-selectin levels [mean (SE)] among stroke patients, age-matched and young controls [47 (6), 39 (3), and 41 (3) ng/ ml, respectively; P = NS]. The leucocyte count [mean (SD)] was higher (P < 0.01) in patients with ischaemic stroke [8310 (2800)] than in age-matched controls [6040 (930)]. Serum levels of ICAM-1 and E-selectin did not significantly differ between patients with or without abnormal carotid or vertebrobasilar artery disease. In conclusion, serum ICAM-1 level and leucocyte count were elevated in acute ischaemic stroke within 24 h, while the E-selectin level did not change significantly. This finding suggests that adhesion molecules may play an important role in the post-rolling process of leucocyte-endothelial cell interaction in acute ischaemic stroke.
A randomised, blinded, placebo-controlled, dose escalation study of the tolerability and efficacy of filgrastim for haemopoietic stem cell mobilisation in patients with severe active rheumatoid arthritis

Autologous haemopoietic stem cell transplantation (HSCT) represents a potential therapy for severe rheumatoid arthritis (RA). As a prelude to clinical trails, the safety and efficacy of haemopoietic stem cell (HSC) mobilisation required investigation as colony-stimulating factors (CSFs) have been reported to flare RA. A double-blind, randomised placebo-controlled dose escalation study was performed. Two cohorts of eight patients fulfilling strict eligibility criteria for severe active RA (age median 40 years, range 24–60 years; median disease duration 10.5 years, range 2–18 years) received filgrastim (r-Hu-methionyl granulocyte(G)-CSF) at 5 and 10 μg/kg/day, randomised in a 5:3 ratio with placebo. Patients were unblinded on the fifth day of treatment and those randomised to filgrastim underwent cell harvesting (leukapheresis) daily until 2 × 106/kg CD34+ cells (haemopoietic stem and progenitor cells) were obtained. Patients were assessed by clinical and laboratory parameters before, during and after filgrastim administration. RA flare was defined as an increase of 30% or more in two of the following parameters: tender joint count, swollen joint count or pain score. Efficacy was assessed by quantitation of CD34+ cells and CFU-GM. One patient in the 5 μg/kg/day group and two patients in the 10 μg/kg/day group fulfilled criteria for RA flare, although this did not preclude successful stem cell collection. Median changes in swollen and tender joint counts were not supportive of filgrastim consistently causing exacerbation of disease, but administration of filgrastim at 10 μg/kg/day was associated with rises in median C-reactive protein and median rheumatoid factor compared with placebo. Other adverse events were well recognised for filgrastim and included bone pain (80%) and increases in alkaline phosphatase (four-fold) and lactate dehydrogenase (two-fold). With respect to efficacy, filgrastim at 10 μg/kg/day was more efficient with all patients (n = 5) achieving target CD34+ cell counts with a single leukapheresis (median = 2.8, range = 2.3–4.8 × 106/kg, median CFU-GM = 22.1, range = 4.2–102.9 × 104/kg), whereas 1–3 leukaphereses were necessary to achieve the target yield using 5 μg/kg/day. We conclude that filgrastim may be administered to patients with severe active RA for effective stem cell mobilisation. Flare of RA occurs in a minority of patients and is more likely with 10 than 5 μg/kg/day. However, on balance, 10 μg/kg/day remains the dose of choice in view of more efficient CD34+ cell mobilisation.
Measuring continuity of care in diabetes mellitus: an experience-based measure.

Continuity is an important attribute of health care, but appropriate measures are not currently available. We developed an experience-based measure of continuity of care in type 2 diabetes.



A 19-item measure of experienced continuity of care for diabetes mellitus (ECC-DM) was developed from qualitative patient interview data with 4 continuity subdomains: longitudinal, flexible, relational, and team and cross-boundary continuity. The measure was implemented in a survey of 193 patients with type 2 diabetes from 19 family practices. Associations of ECC-DM scores with clinician organizational characteristics were estimated.



Potential ECC-DM scores ranged from 0 to 100 with an observed mean of 62.1 (SD 16.0). The average inter-item correlation was 0.343 and Cronbach's alpha was 0.908. Factor analysis found 4 factors that were generally consistent with the proposed subdomains. Patients' mean scores varied significantly between practices (P = .001), ranging from 46 to 78 at different family practices. Experienced continuity was lower for patients receiving only hospital clinic care than for those receiving some diabetes care from their family practice (difference 13.7; 95% confidence interval [CI], 8.2-19.2; P <.001). Patients had higher ECC-DM scores if their family practice had a designated lead doctor for diabetes (difference 8.2; 95% CI, 2.7-13.6; P = .003).



The results provide evidence for the reliability, construct validity, and criterion validity of the experienced continuity-of-care measure. The measure may be used in research and monitoring to evaluate patient-centered outcomes of diabetes care. Patients' experiences of continuity of care vary between health care organizations and are influenced by the organizational arrangements for care.
Prevention of mother-to-child transmission of HIV in Kenya: challenges to implementation

The prevention of mother-to-child transmission of human immunodeficiency virus (HIV) is lauded as one of the more successful HIV prevention measures. However, despite some gains in the prevention of mother-to-child transmission of HIV (PMTCT) in sub-Saharan Africa, mother-to-child transmission rates are still high. In Kenya, mother-to-child transmission is considered one of the greatest health challenges and scaling up PMTCT services is crucial to its elimination by 2015. However, guideline implementation faces barriers that challenge scale-up of services. The objective of this paper is to identify barriers to PMTCT implementation in the context of a randomized control trial on the use of structured mobile phone messages in PMTCT.



The preliminary analysis presented here is based on survey data collected during enrolment in PMTCT services at one of two health facilities in Nairobi, Kenya, with overall number of antenatal care (ANC) visits determined from 48 hour follow up data.



Data was collected for 503 women. Despite significant differences in the type of facility and sample characteristics between sites, all women presented to care at 20 weeks gestation or later and 88.8% attended less than four ANC visits. PMTCT counselling at first visit had high coverage (86%), however less than a third of women (31.34%) reported receiving contraception counselling. Although 60.8% of women had reportedly disclosed their status to their partners, only 40% were aware of their partner's status. Very few women had been tested for TB (10%) or received single dose nevirapine during their first antenatal care appointment (20%).



Revised PMTCT guidelines aim to reduce the inequity between PMTCT services in high and low resource settings in efforts to eliminate mother-to-child transmission. However, guideline implementation in low resource settings continues to be confronted with challenges related to late presentation, less than four ANC visits, low screening rates for opportunistic infections, and limited contraception counselling. These challenges are further complicated by lack of disclosure to partners. Effective scale up and implementation of PMTCT services requires that such ongoing program challenges be identified and appropriately addressed within the local context.
Design for an ipriflavone multicenter European fracture study

In order to investigate the efficacy of ipriflavone (IP) on the prevention of vertebral fractures and the effect on bone mineral density (BMD) in women with postmenopausal osteoporosis, a large multicentric European study was designed and is presently ongoing. Included in the study were 460 Caucasian, nonobese postmenopausal women aged < 45 and < 75 years, menopaused for at least 12 months. Inclusion was on the basis of a lumbar bone mineral density (BMD) lower than 2 SD compared with healthy women aged 50 years, corresponding to values below 0.860 g/cm2 (antero-posterior measurement) by Hologic QDR 1000. Women with prevalent vertebral fractures were excluded as well as those presenting secondary osteoporosis or having been treated with medications that could affect bone metabolism. This study was designed as a 3-year, doubleblind, placebo-controlled, parallel group study that randomized the women to the oral administration of either 3 × 200 mg/day of IP or placebo. All patients received a daily supplement of 500 mg calcium. The primary purpose of the study was to evaluate the efficacy of IP in preventing vertebral nontraumatic fractures. Fracture is defined here as a ≤20% decrease in any anterior, central, or posterior T4-L4 vertebral height. Blinded vertebral X-ray readings and vertebral morphometry have been centralized in an independent Center, with standardized evaluation of two experts. Power calculations have been based on the hypothesis that 21% of placebo-treated patients would fracture within 3 years and that treatment with IP would lead to a 50% reduction in the incidence of fracture. Statistical tests have been designed to have a power of 80%, with a type I error equal to 5%. Secondary endpoints were changes in vertebral, radial, and femoral BMD. Centralized controls on 100% BMD scans would ensure the good quality of BMD readings. This study should verify the hypothesis that IP significantly decreases the risk of vertebral fracture in postmenopausal, osteoporotic women.
Endothelial repair capacity and apoptosis are inversely related in obstructive sleep apnea

To investigate the impact of obstructive sleep apnea (OSA) on endothelial repair capacity and apoptosis in the absence of potentially confounding factors including obesity.



Sixteen patients with a body mass index <30 and newly diagnosed OSA and 16 controls were studied. Circulating levels of endothelial progenitor cells, a marker of endothelial repair capacity, and endothelial microparticles, a marker of endothelial apoptosis, were quantified before and after four-week therapy with continuous positive airway pressure (CPAP). Endothelial cell apoptotic rate was also quantified in freshly harvested venous endothelial cells. Vascular reactivity was measured by flow-mediated dilation.



Before treatment, endothelial microparticle levels were greater and endothelial progenitor cell levels were lower in patients with OSA than in controls (P < 0.001 for both). Levels of endothelial microparticles and progenitors cells were inversely related (r = -0.67, P < 0.001). Endothelial progenitor cell levels increased after effective treatment (P = 0.036).



In the absence of any co-morbid conditions including obesity, OSA alone impairs endothelial repair capacity and promotes endothelial apoptosis. These early endothelial alterations may underlie accelerated atherosclerosis and increased cardiovascular risk in OSA.
Low-dose of statin treatment improves cerebrovascular reactivity in patients with ischemic stroke: single photon emission computed tomography analysis.

Statins, 3-hydroxy-3-methylglutaryl-coenzymeA reductase inhibitors, have pleiotropic effects that are independent of their cholesterol-lowering activities. For example, they improve vascular endothelial function and exert anti-inflammatory effects. In large clinical trials they reduced the incidence of stroke and myocardial infarction; however, little is currently known regarding the mechanism or mechanisms underlying their clinically confirmed stroke protection.



We assessed 10 patients who had experienced a stroke at least 6 months earlier; they received low-dose (5 mg) simvastatin. Using our triple-injection technetium 99m-ethylcysteinate dimer method, we determined their cerebral blood flow and cerebrovascular reactivity. A second assessment of at-rest cerebral blood flow and cerebrovascular reactivity was performed 4 or more months (mean 6 months) after the start of statin administration. We used acetazolamide (1 g) as the vasodilator. The region of interest was the middle cerebral artery territory on a 3-dimensional stereotaxic region of interest template.



Statin administration did not significantly affect the regional cerebral blood flow at rest. Before statin treatment, the patients' vasoreactivity, determined by the triple-injection technetium 99m-ethylcysteinate dimer method, demonstrated delayed, poor, or near-normal response patterns. Statin treatment improved vasoreactivity in all patients. Their mean serum total cholesterol level before statin administration was 200 mg/dL (range 187-256 mg/dL). Statin treatment significantly reduced their mean serum total cholesterol to 180 mg/dL (range 128-220 mg/dL) (P < .01).



The clinically confirmed stroke protection activity exerted by statins may be attributable to improved cerebrovascular reactivity.