nils-herrmann/clean_scirepeval huggingface dataset:
The effect on bone mass and bone markers of different doses of ibandronate — A new bisphosphonate for prevention and treatment of postmenopausal osteoporosis. A 1-year, randomized, double-blind, placebo-controlled dose-finding study

The present article describes the results from a phase II dose finding study of the effect of ibandronate, a new, third generation bisphosphonate, in postmenopausal osteoporosis. One hundred and eighty postmenopausal, white women, at least 10 years past a natural menopause, with osteopenia defined as a bone mineral density (BMD) in the distal forearm at least 1.5 SD below the premenopausal mean, entered and 141 (78%) completed a 12 months randomized, double-blind, placebo-controlled study. The women received 0.25, 0.5, 1.0, 2.5, or 5.0 mg ibandronate daily or placebo. All women received a daily calcium supplementation of 1000 mg Ca2+. Bone mass and biochemical markers of bone turnover were measured every 3 months throughout the study period. The average changes in bone mass showed positive outcome in all regions in the groups receiving ibandronate 2.5 and 5.0 mg. The responses in the two groups were not significantly different, although there was a tendency toward a higher response in bone mass in the group receiving ibandronate 2.5 mg, where the increase in BMD was 4.6 +/- 3.1% (SD) in the spine (p < 0.001), 1.3 +/- 3.0% (SD) to 3.5 +/- 5.3% (SD) in the different regions of the proximal femur (p < 0.03 to p < 0.002), and 2.0 +/- 1.9% (SD) in total body bone mineral content (BMC) (p < 0.001). There was no significant changes in bone mass in the group receiving calcium (placebo) and ibandronate 0.25 mg. Dose-related responses were found in all biochemical markers of bone turnover. In average, serum osteocalcin decreased 13 +/- 14% (SD) (placebo) and 35 +/- 14% (SD) (5.0 mg). Urinary excretions of breakdown products of type I collagen decreased 35 +/- 21% (SD) (placebo) and 78 +/- 28% (SD) (5.0 mg), p < 0.001 in all groups. In conclusion, the results suggest that ibandronate treatment increases bone mass in all skeletal regions in a dose dependent manner with 2.5 mg being the most effective dose. Ibandronate treatment reduces bone turnover to premenopausal levels and is well tolerated.
Usefulness of perflubutane microbubble-enhanced ultrasound in imaging and detection of prostate cancer: phase II multicenter clinical trial

To explore the possibility of targeted biopsy (TBx) using transrectal ultrasound (US) with perflubutane microbubbles, we studied the findings of different cancerous tissue imaging modalities and evaluated needle biopsy in prostate cancer (PCa) using contrast-enhanced US (CEUS) in a multicenter clinical trial. Seventy-one patients undergoing prostate biopsy received intravenous injection of perflubutane microbubbles (Sonazoid®). We evaluated and compared images obtained by CEUS. The safety observation period was 2 days after contrast administration. Among the 30 patients with cancer, one or more sites with findings suggestive of cancer in CEUS were detected in 23 patients (32.4%) by TBx. Although 22 patients had positive cores of cancer by systematic biopsy (SBx), 8 patients had positive cores of cancer in TBx alone (11.3%). There was a significant difference in cancer detection rate by TBx between two cohorts with PSA < 10 ng/mL (22.9%) and PSA ≥ 10 ng/mL (52.2%) (P < 0.02). Close observation of various CEUS findings with Sonazoid® enabled targeting of cancerous areas, and consequently, a significant difference (P < 0.05) in the detection rate of cancer was recognized in the transition zone (TZ): SBx; 21/120 (17.5%) and TBx; 17/55 (30.9%). The incidence of adverse events was 6.7% and that of adverse reactions was 4%. CEUS with Sonazoid® improved the detection rate of PCa by visualizing cancerous lesions. More detailed examination of CEUS images provided efficient characterization especially in the TZ area. TBx according to this procedure is expected to enable a lower number of biopsies and more accurate diagnosis of PCa.
Costs of chronic obstructive pulmonary disease in urban areas of China: a cross-sectional study in four cities

The economic burden of COPD has not been well studied in China. This study investigated the total costs caused by COPD and the influencing factors for the high economic burden in urban areas of China.



A cross-sectional study was carried out among 678 COPD patients in four cities in China in 2011. The average annual direct medical costs (DMCs), direct nonmedical costs (DNMCs), and indirect costs (ICs) on COPD were measured by median and mean (± standard deviation). Logistic regression model was used to explore factors related to high total costs on COPD.



The median annual DMCs, DNMCs, and ICs per COPD patient were RMB 5565 Yuan (US$ 862), 0 Yuan (US$ 0), and 0 Yuan (US$ 0), respectively, and the mean annual DMCs, DNMCs, and ICs per COPD patient were RMB 11968 (±22422) Yuan [US$ 1853 (±3472)], 539 (±2092) Yuan [US$ 83 (±324)], and 2087 (±8110) Yuan [US$ 323 (±1256)], respectively. The annual DMCs, DNMCs, and ICs for diagnosed COPD patients were RMB 195.70 billion Yuan (US$ 30.30 billion), 8.78 billion Yuan (US$ 1.36 billion), and 34.10 billion Yuan (US$ 5.28 billion), respectively, in China. Hospitalization accounted for 56.7% of the total costs. High economic burden was significantly related to age, acute exacerbations, and disease severity in COPD patients.



COPD posed a heavy economic burden in China. Measures to delay the disease progression and to reduce the risks of acute exacerbation and hospitalization will help substantially lower the costs for COPD care.
Long-acting inhaled anticholinergic therapy improves sleeping oxygen saturation in COPD.

Oxygen desaturation occurs during sleep in severe chronic obstructive pulmonary disease (COPD), especially during rapid eye movement (REM) sleep, due to hypoventilation and ventilation-perfusion mismatching, but the possible contribution of airflow limitation is unclear. In a randomised, placebo-controlled, double-blind study of severe, stable COPD patients, the authors compared 4 weeks treatment with a long-acting inhaled anticholinergic agent (tiotropium), taken in the morning (tiotropium-AM), or in the evening (tiotropium-PM), on sleeping arterial oxygen saturation (Sa,O2) and sleep quality. Overnight polysomnography was performed at baseline and after 4 weeks treatment. A total of 95 patients with awake resting arterial oxygen tension < or = 9.98 kPa (75 mmHg) were randomised, with a mean age of 66.4 yrs and mean forced expiratory volume in one second (FEV1) of 32% predicted. A total of 80 patients completed the study, of which 56 fulfilled the polysomnographic criterion of at least 2 h sleep in both sleep study nights and represent the group analysed. Tiotropium significantly improved spirometry compared with placebo. Both tiotropium-AM and tiotropium-PM groups had higher Sa,O2 during REM than placebo (+2.41% and +2.42%, respectively, and both pooled and tiotropium-PM groups had higher Sa,O2 during total sleep time (+2.49% and +3.06%, respectively). End-of-treatment FEV1 correlated with Sa,O2 during REM sleep, however, tiotropium did not change sleep quality. Sustained anticholinergic blockade improves sleeping arterial oxygen saturation without affecting sleep quality.
Two-dose versus monthly intermittent preventive treatment of malaria with sulfadoxine-pyrimethamine in HIV-seropositive pregnant Zambian women.

Intermittent preventive treatment of malaria during pregnancy (IPTp) reduces placental infection, maternal anemia, and low birth weight (LBW). However, the optimal dosing regimen in settings in which human immunodeficiency virus (HIV) is highly prevalent among pregnant women remains controversial.



We conducted a randomized, double-blind, placebo-controlled study of IPTp comparing the standard 2-dose sulfadoxine-pyrimethamine (SP) regimen with monthly IPTp among a cohort of HIV-positive pregnant Zambian women. Primary outcomes included placental malaria (by smear and histology) and maternal peripheral parasitemia at delivery.



There were no differences between monthly IPTp (n=224) and standard IPTp (n=232) in placental malaria by histopathology (26% vs. 29%; relative risk [RR], 0.90 [95% confidence interval {CI}, 0.64-1.26]) or placental parasitemia (2% vs. 4%; RR, 0.55 [95% CI, 0.17-1.79]). There also were no differences in maternal anemia, stillbirths, preterm delivery, LBW, or all-cause mortality of infants at 6 weeks.



In an area of mesoendemicity in Zambia, monthly SP IPTp was not more efficacious than the standard 2-dose regimen for the prevention of placental malaria or adverse birth outcomes. IPTp policy recommendations need to take into account local malaria transmission patterns and the prevalence of HIV.
The effects of multisystemic therapy on diabetes stress among adolescents with chronically poorly controlled type 1 diabetes: findings from a randomized, controlled trial.

The goal of this study was to determine whether multisystemic therapy (MST), an intensive, home-based psychotherapy, could decrease diabetes-related stress among adolescents with chronically poorly controlled type 1 diabetes. Stress was also evaluated as a mediator of the effect of MST on adherence and metabolic control.



A randomized, controlled trial was conducted with 127 adolescents with type 1 diabetes mellitus and chronically poor metabolic control (hemoglobin A1c levels of > or =8% at study enrollment and for the past 1 year) who received their diabetes care in a children's hospital located in a major Midwestern city. Participants assigned randomly to MST received treatment for approximately 6 months. Data were collected at baseline and at a 7-month posttest (ie, treatment termination). Changes in diabetes-related stress, as measured with a self-report questionnaire, were assessed. Structural equation models were used to test the degree to which changes in stress levels mediated the ability of the MST intervention to improve adherence and metabolic control.



In intent-to-treat analyses, participation in MST was associated with significant reductions in diabetes-related stress. Tests for moderation found no significant effects of age, gender, or ethnicity, which suggests that the intervention was equally effective in reducing diabetes stress for all participants. However, structural equation modeling did not provide support for diabetes stress as the mechanism through which MST improved health outcomes. Rather, the final model suggested that MST improved metabolic control through increased regimen adherence.



Intensive, home-based psychotherapy reduces diabetes-related stress among adolescents with chronically poorly controlled type 1 diabetes. Such stress reductions are important for the psychological wellbeing of a subset of youths with diabetes who are at high risk for future health complications.
Systematic care for asthma in Australian general practice: a randomised controlled trial.

To evaluate whether systematic asthma care involving a register-recall system, postcard prompts for review, and education for general practitioners and staff in Australian general practice improves the quality of care and health outcomes for adult patients with moderate to severe asthma.



Cluster randomised controlled trial in 40 general practices in urban and rural South Australia and New South Wales over the 2 years 2004 and 2005; practices were randomly allocated to the intervention or control group.



565 adult patients of these randomly allocated practices who had doctor-diagnosed moderate to severe asthma and were taking inhaled corticosteroids.



Clinical asthma indicators, quality of care, acceptability of the intervention to patients, quality of life, and asthma self-management skills at baseline, 6 months and 12 months.



Although 46% of patients in the intervention group practices responded to the postcard prompts, only 32% actually attended for their asthma review. At 12 months, there was a statistically significant difference in provision of written asthma action plans (rate ratio, 1.9; 95% CI, 1.0-3.5; P = 0.04) for intervention group patients compared with control group patients; there was no significant difference in other indicators.



We found little objective evidence of improvement in patient management and outcomes resulting from a systematic model of asthma care.
Factors that influence fatigue status in patients with severe rheumatoid arthritis (RA) and good disease outcome following 6 months of TNF inhibitor therapy: a comparative analysis

The objective of the present study is to determine the factors associated with persistent fatigue in patients with severe rheumatoid arthritis (RA) and good disease response to 6 months of tumour necrosis factor inhibitor therapy. Eligible patients with either persistent (PF) or no fatigue (NF) were compared. Using validated questionnaires and bivariate analysis, this cross-sectional survey explored if clinical characteristics, pain, self-efficacy, sleep and mood/depression differed between groups. Patients with PF (PF; NF) (n = 28; 28) reported significantly more overall pain (11.3 ± 9.4 (0–33); 6.9 ± 8.9 (0–33)), more recent and current pain intensity (41.4 ± 26.6 (0–80) 24.4 ± 26.6 (0–100) and depression (11.8 ± 7.5 (1–35); 8.2 ± 6.6 (0–26)), than the NF group. There was no significant difference between groups in self-efficacy and both groups experienced poor sleep quality (Pittsburgh Sleep Quality Index >5). Despite having good disease response, the PF group had significantly higher rheumatoid factor incidence, disease activity score-28, early morning stiffness duration and lower incidence of ever-failing disease-modifying anti-rheumatic drugs than the NF group. These findings enhance the fatigue literature in patients with RA prescribed tumour necrosis factor (TNF) inhibition therapy, identifying the potentially modifiable factors of pain and depression, previously demonstrated to be strongly associated with fatigue in non-biologic populations. In addition, this study highlights the association between persistent fatigue and an on-going state of low disease activity. This infers that more judicious disease management could minimise the symptom burden of pain and depression and consequentially fatigue.
What Is theBestWay toEstimateHospital QualityOutcomes ? ASimulation Approach

To test the accuracy of alternative estimators of hospital mortality quality using aMonte Carlo simulation experiment.  Data are simulated to create an admission-level analytic dataset. The simulated data are validated by comparing distributional parameters (e.g., mean and standard deviation of 30-day mortality rate, hospital sample size) with the same parameters observed inMedicare data for acute myocardial infarction (AMI) inpatient admissions.  We perform a Monte Carlo simulation experiment in which true quality is known to test the accuracy of the Observed-over-Expected estimator, the Risk StandardizedMortality Rate (RSMR), the Dimick and Staiger (DS) estimator, the Hierarchical Poisson estimator, and the Moving Average estimator using hospital 30-day mortality for AMI as the outcome. Estimator accuracy is evaluated for all hospitals and for small, medium, and large hospitals.  Data are simulated.  Significant and substantial variation is observed in the accuracy of the tested outcome estimators. The DS estimator is the most accurate for all hospitals and for small hospitals using both accuracy criteria (root mean squared error and proportion of hospitals correctly classified into quintiles).  The mortality estimator currently in use by Medicare for public quality reporting, the RSMR, has been shown to be less accurate than the DS estimator, although the magnitude of the difference is not large. Pending testing and validation of our findings using current hospital data, CMS should reconsider the decision to publicly report mortality rates using the RSMR.
Effect of different seated positions on lung volume and oxygenation in acute respiratory distress syndrome

Lung volume available for ventilation is markedly decreased during acute respiratory distress syndrome. Body positioning may contribute to increase lung volume and partial verticalization is simple to perform. This study evaluated whether verticalization had parallel effects on oxygenation and end expiratory lung volume (EELV). Prospective multicenter study in 40 mechanically ventilated patients with ALI/ARDS in five university hospital MICUs. We evaluated four 45-min successive trunk position epochs (supine slightly elevated at 15°; semi recumbent with trunk elevated at 45°; seated with trunk elevated at 60° and legs down at 45°; back to supine). Arterial blood gases, EELV measured using the nitrogen washin/washout, and static compliance were measured. Responders were defined by a PaO2/FiO2 increase >20 % between supine and seated position. Results are median [25th–75th percentiles]. With median PEEP = 10 cmH2O, verticalization increased lung volume but only responders (13 patients, 32 %) had a significant increase in EELV/PBW (predicted body weight) compared to baseline. This increase persisted at least partially when patients were positioned back to supine. Responders had a lower EELV/PBW supine [14 mL/kg (13–15) vs. 18 mL/kg (15–27) (p = 0.005)] and a lower compliance [30 mL/cmH2O (22–38) vs. 42 (30–46) (p = 0.01)] than non-responders. Strain decreased with verticalization for responders. EELV/PBW increase and PaO2/FiO2 increase were not correlated. Verticalization is easily achieved and improves oxygenation in approximately 32 % of the patients together with an increase in EELV. Nonetheless, effect of verticalization on EELV/PBW is not predictable by PaO2/FiO2 increase, its monitoring may be helpful for strain optimization.
Efficacy of corticosteroids in community-acquired pneumonia: a randomized double-blinded clinical trial.

Some studies have shown a beneficial effect of corticosteroids in patients with community-acquired pneumonia (CAP), possibly by diminishing local and systemic antiinflammatory host response.



To assess the efficacy of adjunctive prednisolone treatment in patients hospitalized with CAP.



Hospitalized patients, clinically and radiologically diagnosed with CAP using standard clinical and radiological criteria, were randomized to receive 40 mg prednisolone for 7 days or placebo, along with antibiotics. Primary outcome was clinical cure at Day 7. Secondary outcomes were clinical cure at Day 30, length of stay, time to clinical stability, defervescence, and C-reactive protein. Disease severity was scored using CURB-65 (a severity index for community-acquired pneumonia evaluating Confusion, blood Urea nitrogen, Respiratory rate, Blood pressure, and age 65 or older) and Pneumonia Severity Index.



We enrolled 213 patients. Fifty-four (25.4%) patients had a CURB-65 score greater than 2, and 93 (43.7%) patients were in Pneumonia Severity Index class IV-V. Clinical cure at Days 7 and 30 was 84/104 (80.8%) and 69/104 (66.3%) in the prednisolone group and 93/109 (85.3%) and 84/109 (77.1%) in the placebo group (P = 0.38 and P = 0.08). Patients on prednisolone had faster defervescence and faster decline in serum C-reactive protein levels compared with placebo. Subanalysis of patients with severe pneumonia did not show differences in clinical outcome. Late failure (>72 h after admittance) was more common in the prednisolone group (20 patients, 19.2%) than in the placebo group (10 patients, 6.4%; P = 0.04). Adverse events were few and not different between the two groups.



Prednisolone (at 40 mg) once daily for a week does not improve outcome in hospitalized patients with CAP. A benefit in more severely ill patients cannot be excluded. Because of its association with increased late failure and lack of efficacy prednisolone should not be recommended as routine adjunctive treatment in CAP.
Quantifying freezing of gait in Parkinson's disease during the instrumented timed up and go test

Over half of patients with PD eventually develop freezing of gait (FoG), an intermittent failure to initiate or maintain walking that is often associated with trembling of the legs. We tested 21 PD with FoG, 27 PD without FoG, and 21 healthy elderly people in a clinic with the Intrumented Timed Up and Go test (ITUG). FoG was quantified from the power spectral density of the antero-posterior shank acceleration from which a Frequency Ratio was calculated as the square of the total power in the 3-8 Hz band, divided by the square of the total power in the .5-3 Hz band. Spatiotemporal gait parameters calculated from synchronized gyroscopes on the two legs were also measured in these subjects. The Frequency Ratio was significantly larger in freezers than in non-freezers or control subjects. It better differentiated gait disorders between PD subjects with and without FoG than traditional gait measures such as stride length, stride velocity and double support time. The Frequency Ratio was validated as significantly correlated with self-perceived severity of gait and balance confidence. This Freezing Ratio will be useful to quantify FoG during a simple ITUG, a popular clinical test of mobility.
The pharmacokinetics of nebulized nanocrystal budesonide suspension in healthy volunteers.

Nanocrystal budesonide (nanobudesonide) is a suspension for nebulization in patients with steroid-responsive pulmonary diseases such as asthma. The pharmacokinetics and safety of the product were compared to those of Pulmicort Respules. Sixteen healthy volunteers were administered nanobudesonide 0.5 and 1.0 mg, Pulmicort Respules 0.5 mg, and placebo in a four-way, randomized crossover design. All nebulized formulations were well tolerated, with no evidence of bronchospasm. Nebulization times were significantly shorter for nanobudesonide compared to Pulmicort Respules. Because of a low oral bioavailability, plasma concentration of budesonide is a good marker of lung-delivered dose. The pharmacokinetics of nanobudesonide 0.5 and 1.0 mg were approximately dose proportional with respect to Cmax, AUC(0-t), and AUC(0-infinity). Nanobudesonide 0.5 mg and Pulmicort Respules 0.5 mg exhibited similar AUCs, suggesting a similar extent of pulmonary absorption. A higher Cmax was noted with nanobudesonide 0.5 mg, and the tmax was significantly different, suggesting a more rapid rate of drug delivery of nanobudesonide 0.5 mg than Pulmicort Respules. In conclusion, nebulized nanobudesonide 0.5 mg was safe in healthy volunteers, with a similar extent of absorption as Pulmicort Respules.
Single blind randomised controlled trial of GAME (Goals - Activity - Motor Enrichment) in infants at high risk of cerebral palsy.

Cerebral palsy (CP) is caused by a lesion in the developing infant brain. Recent neuroplasticity literature suggests that intensive, task-specific intervention ought to commence early, during the critical period of neural development.



To determine whether "GAME" (Goals - Activity - Motor Enrichment), a motor learning, environmental enrichment intervention, is effective for improving motor skills in infants at high risk of CP.



Single blind randomised controlled trial of GAME versus standard care. Primary outcome was motor skills on the Peabody Developmental Motor Scales-2 (PDMS-2). Secondary outcomes included Canadian Occupational Performance Measure (COPM), Bayley Scales of Infant and Toddler Development (BSID-III) and Gross Motor Function Measure-66 (GMFM-66). Outcome assessors were masked to group allocation and data analyzed with multiple regression.



All n=30 infants enrolled received the assigned intervention until 16 weeks post enrolment. At 12 months of age, n=26 completed assessments. Significant between group differences were found in raw scores on the PDMS-2 in favour of GAME (B=20.71, 95%CI 1.66-39.76, p=0. 03) and at 12 months on the total motor quotient (B=8.29, 95%CI 0.13-16.45,p =0.05). Significant between group differences favored GAME participants at 12 months on the cognitive scale of the BSID-III and satisfaction scores on the COPM.



GAME intervention resulted in advanced motor and cognitive outcomes when compared with standard care.