nils-herrmann/clean_scirepeval huggingface dataset:
Ten-year fracture probability identifies women who will benefit from clodronate therapy—additional results from a double-blind, placebo-controlled randomised study

Fracture risk prediction can be enhanced by the concurrent assessment of other clinical risk factors. This study demonstrates that the estimation of an individual’s 10-year probability of fracture by the FRAX® algorithm identifies patients at high risk of fracture who will respond to bisphosphonate therapy. Treatments for osteoporosis are targeted largely to patients with low bone density (BMD) or a prior fragility fracture. Fracture risk prediction can be enhanced by the concurrent assessment of other clinical risk factors, but it is important to determine whether the risk so identified can be reduced by intervention. We determined the effect of a bisphosphonate on fracture rates when risk was calculated using a new risk algorithm (FRAX®). Women aged 75 years or more were recruited to a randomised, double-blind controlled trial of 800 mg oral clodronate (Bonefos®) daily over 3 years. Baseline clinical risk factors were entered in the FRAX® model to compute the 10-year probability of major osteoporotic fractures with or without input of femoral neck BMD. The interaction between fracture probability and treatment efficacy was examined by Poisson regression. In 3,974 women, the interaction between fracture probability and treatment efficacy was significant when probability was assessed without BMD (p = 0.043), but not when BMD was included (p = 0.10). Efficacy was more evident in those deemed at highest risk. For example women lying at the 75th percentile of fracture probability in the absence of BMD (10-year probability 24%) treatment reduced fracture risk by 27% (HR 0.73, 95%CI 0.58–0.92). In those with a fracture probability of 30% (90th percentile), the fracture risk reduction was 38% (HR 0.62, 0.46–0.84). The estimation of an individual’s 10-year probability of fracture by the FRAX® algorithm identifies patients at high risk of fracture who will respond to bisphosphonate therapy.
Predictors of mortality in 6975 patients with chronic heart failure in the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico-Heart Failure trial: proposal for a nomogram.

We developed a prognostic model to assess the risk of all-cause mortality in patients with chronic heart failure.



We examined 6975 patients with chronic heart failure enrolled in the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico-Heart Failure (GISSI-HF) trial (3.9 years follow-up). Multivariable Cox regression models were developed to predict mortality (1969 deaths). By stepwise selection, the full final model included 25 predictors. A reduced model, considering the most significant variables ranked according to the Wald χ(2) (P<0.0001) accounted for most of the prognostic information. Internal validation of the model was performed with bootstrap techniques. The discrimination ability of the reduced model constituted by 12 factors (concordance probability estimate, 0.693) was as good as the full final model (concordance probability estimate, 0.70). Among the first 12 independent risk factors emerging in the reduced model, the 3 most powerful predictors were older age, higher New York Heart Association class, and lower estimated glomerular filtration rate. Other independent predictors that increased risk included lower left ventricular ejection fraction, chronic obstructive pulmonary disease, lower systolic blood pressure, diabetes mellitus, male sex, higher uricemia, lower body mass index, lower hemoglobin, and aortic stenosis. The reduced model was used to build a nomogram to estimate the risk of death in individual patients. In a subgroup of patients, the 2 well-known biomarkers (high-sensitivity cardiac troponin T and N-terminal pro-brain natriuretic peptide) emerged as the most powerful predictors of outcome.



In a large contemporary population with chronic heart failure, this model offers good ability to assess the risk of death, confirming most of the risk factors that have emerged in recent trials.
Mycophenolate mofetil (MMF) as therapy for refractory chronic GVHD (cGVHD) in children receiving bone marrow transplantation

Mycophenolate mofetil (MMF) is an alternative immunosuppressant which inhibits the proliferation of T and B lymphocytes. The purpose of the present study was to evaluate the safety and efficacy of MMF as salvage therapy for chronic GVHD (cGVHD) in children receiving allogeneic bone marrow transplantation. Fifteen children, 3–16 years of age, who had received grafts from HLA-compatible siblings (n = 8), partially matched related donors (n = 2) or matched unrelated donors (n = 5), developed extensive cGVHD which had proved unresponsive to standard immunosuppressive therapy. Patients were treated with MMF at the dose of 15–40 mg/kg/day in combination with other immunosuppressive therapy for a median of 4 months (range 1–15 months). The overall response rate (complete or partial response) was 60%. Thirteen percent had only minor responses, whereas 27% of patients had progressive disease. Best responses were seen in patients with GI tract (60% of complete responses) or mouth (33% of complete responses) cGVHD and skin involvement (43% of complete responses) that did not include sclerodermatous manifestations. Once MMF was started, improvements in the clinical manifestations of cGVHD allowed a significant reduction of steroids in 45% of patients and discontinuation in 27% of cases. Six patients (40%) experienced adverse events, with gastrointestinal symptoms predominating. Five patients experienced opportunistic infections. MMF was discontinued after 35–180 days in six patients for the following reasons: parents choice (n = 2), liver toxicity (n = 1), poor compliance (n = 2), and no response (n = 1). In conclusion, these preliminary results suggest that MMF in combination with other immunosuppressive agents may have a role to play in patients with cGVHD. Prospective clinical trials are needed to establish exact indications for therapy and dosage scheduling. Bone Marrow Transplantation (2000) 25, 1067–1071.
The development of artificial neural networks to predict virological response to combination HIV therapy.

When used in combination, antiretroviral drugs are highly effective for suppressing HIV replication. Nevertheless, treatment failure commonly occurs and is generally associated with viral drug resistance. The choice of an alternative regimen may be guided by a drug-resistance test. However, interpretation of resistance from genotypic data poses a major challenge.



As an alternative to current interpretation systems, we have developed artificial neural network (ANN) models to predict virological response to combination therapy from HIV genotype and other clinical information.



ANN models trained with genotype, baseline viral load and time to follow-up viral load (1154 treatment change episodes from multiple clinics), produced predictions of virological response that were highly significantly correlated with actual responses (r2 = 0.53; P < 0.00001) using independent test data from clinics that contributed training data. Augmented models, trained with the additional variables of baseline CD4+ T-cell count and four treatment history variables, were more accurate, explaining 69% of the variance in virological response. Models trained with the full input dataset, but only those data involving highly active antiretroviral therapy (three or more full-dose antiretroviral drugs in combination), performed at an intermediate level, explaining 61% of the variance. The augmented models performed less well when tested with data from unfamiliar clinics that had not contributed data to the training dataset, explaining 46% of the variance in response.



These data indicate that ANN models can be quite accurate predictors of virological response to HIV therapy even for patients from unfamiliar clinics. ANN models therefore warrant further development as a potential tool to aid treatment selection.
Early clearance of peripheral blasts measured by flow cytometry during the first week of AML induction therapy as a new independent prognostic factor: a GOELAMS study

An early appreciation of treatment efficacy could be very useful in acute myeloblastic leukemia (AML), and a prognostic value has been suggested for the morphological assessment of decrease in blasts during induction therapy. More sensitive, multiparametric flow cytometry (FCM) can detect far lower blast counts, allowing for a precise and reliable calculation of blast cell decrease rate (BDR). Such a multiparametric FCM four-colours/single-tube protocol, combining CD11b, CD45-ECD and CD16-PC5, was applied to peripheral blood samples from 130 AML patients, collected daily during induction chemotherapy. Normalized blast cell percentages were used to calculate the relevant decrease slopes. Slope thresholds (<−25, −25 to −15 and >−15), or the time required to reach 90% depletion of the peripheral blast load (<5, 5 or >5 days), was strongly associated with the achievement of complete remission (P<0.0001). Log-rank test and Cox model showed that they also carried high statistical significance (P<0.0001) for disease-free survival. The prognostic value of cytogenetic features, confirmed in this series, was refined by BDR, which allowed to discriminate between good- and poor-risk patients among those with intermediate or normal karyotypes. This simple FCM protocol allows for an accurate prognostic sequential approach adapted to the determination of decrease in peripheral blast cells during induction chemotherapy.
Potential new diagnostic tool for Alzheimer's disease using a linear discriminant function for Fourier domain optical coherence tomography.

We calculated and validated a linear discriminant function (LDF) for Fourier domain optical coherence tomography (OCT) to improve the diagnostic ability of retinal and retinal nerve fiber layer (RNFL) thickness parameters in the detection of Alzheimer's disease (AD).



We enrolled AD patients (n = 151) and age-matched, healthy subjects (n = 61). The Cirrus and Spectralis OCT systems were used to obtain retinal measurements and circumpapillary RNFL thickness for each participant. An LDF was calculated using all retinal and RNFL OCT measurements. Receiver operating characteristic (ROC) curves were plotted and compared among the LDF and the standard parameters provided by OCT devices. Sensitivity and specificity were used to evaluate diagnostic performance. A validating set was used in an independent population to test the performance of the LDF.



The optimal function was calculated using the RNFL thickness provided by Spectralis OCT, using the 768 points registered during peripapillary scan acquisition (grouped to obtain 24 uniformly divided locations): 18.325 + 0.056 × (315°-330°) - 0.122 × (300°-315°) - 0.041 × (285°-300°) + 0.091 × (255°-270°) + 0.041 × (225°-240°) + 0.183 × (195°-210°) - 0.108 × (150°-165°) - 0.092 × (75°-90°) + 0.051 × (30°-45°). The largest area under the ROC curve was 0.967 for the LDF. At 95% fixed specificity, the LDF yielded the highest sensitivity values.



Measurements of RNFL thickness obtained with the Spectralis OCT device differentiated between healthy and AD individuals. Based on the area under the ROC curve, the LDF was a better predictor than any single parameter.
FORCe: Fully Online and Automated Artifact Removal for Brain-Computer Interfacing

A fully automated and online artifact removal method for the electroencephalogram (EEG) is developed for use in brain-computer interfacing (BCI). The method (FORCe) is based upon a novel combination of wavelet decomposition, independent component analysis, and thresholding. FORCe is able to operate on a small channel set during online EEG acquisition and does not require additional signals (e.g., electrooculogram signals). Evaluation of FORCe is performed offline on EEG recorded from 13 BCI particpants with cerebral palsy (CP) and online with three healthy participants. The method outperforms the state-of the-art automated artifact removal methods Lagged Auto-Mutual Information Clustering (LAMIC) and Fully Automated Statistical Thresholding for EEG artifact Rejection (FASTER), and is able to remove a wide range of artifact types including blink, electromyogram (EMG), and electrooculogram (EOG) artifacts.
A multifaceted intervention to improve blood pressure control: The Guideline Adherence for Heart Health (GLAD) study.

Although high blood pressure is associated with significant morbidity and mortality, the proportion reaching the goal blood pressures as outlined in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, Treatment of High Blood Pressure (JNC 7) is low. We conducted a randomized trial in primary care practices of a multifactorial intervention targeted to improve providers' adherence to hypertension guidelines.



A total of 61 primary care practices in North Carolina were randomized to receive either a multifactorial intervention (guideline dissemination via a continuing medical education session, academic detailing sessions, audit and feedback on preintervention rates of adherence, and automated blood pressure machines) or an attention control of similar magnitude but targeted at a different guideline. Outcomes were determined through review of patient charts conducted by an independent masked quality assurance organization.



We found no difference between the 2 groups in any of the adherence measures including no difference in the percentage of patients at goal (intervention 49.2%, control 50.6%), with undiagnosed hypertension (18.1% vs 13.6%), average systolic (126 vs 125.1 mm Hg), or diastolic blood pressure (73.1 vs 73.4 mm Hg). Similarly, there was no difference in provider adherence to treatment recommendations (use of thiazide-type diuretic as first-line therapy: 32% vs 29.5%; use of 2-drug therapy in stage 2 hypertension: 11.3% vs 10.4%).



An intensive, multifactorial intervention did not improve adherence to national hypertension guidelines among community-based primary care. Efforts should be focused on other types of interventions to improve rates of control of hypertension.
Agreement of visual estimation of coronary artery calcium from low-dose CT attenuation correction scans in hybrid PET/CT and SPECT/CT with standard Agatston score.

We sought to evaluate the accuracy and reproducibility of visual estimation of coronary artery calcium (CAC) from computed tomography attenuation correction (CTAC) scans performed for hybrid positron emission tomography (PET)/computed tomography (CT) and single-photon emission computed tomography (SPECT)/CT myocardial perfusion imaging (MPI).



At the time of MPI, hybrid systems obtain a low-dose, non-electrocardiogram (ECG)-gated CT scan that is used to perform attenuation correction. Utility of this CTAC scan in estimating actual CAC as measured by Agatston score (AS) on standard ECG-gated scans has not been previously studied.



A total of 492 patients, from 3 centers, receiving both MPI with CTAC and a standard CAC scan were studied. At each site, experienced readers blinded to AS reviewed CTAC images, visually estimating CAC on a 6-level scale: classifying patients as estimated AS of 0, 1 to 9, 10 to 99, 100 to 300, 400 to 999, or ≥1,000. Agreement between visually estimated coronary artery calcium (VECAC) on CTAC and AS, measured standardly and converted to the same scale, was evaluated, as was inter-reader agreement.



Although CTAC images are low dose and nongated, a high degree of association was observed between VECAC and AS, with 63% of VECACs in the same category as the AS category and 93% within 1 category. Weighted kappa was 0.89 (95% confidence interval: 0.88 to 0.91, p < 0.0001). High weighted kappa statistics were observed for each site, scanner type, and sex. Readers reported identical scores in 65% of cases and scores within 1 category in 93%.



CAC can be visually assessed from low-dose CTAC scans with high agreement with AS. CTAC scans should be routinely assessed for VECAC.
Elderly patients with epileptic seizures: In-patient observational study of two French community hospitals

Epileptic seizures (ESs) in the elderly are recognized as frequent, and potentially difficult to diagnose. Their clinical features and relevant diagnostic problems still remain poorly investigated in hospital populations outside the setting of tertiary referral centres. In this study we attempted to improve the understanding of these aspects in community institutions. We conducted a four-year retrospective observational study of 104 consecutive elderly patients with the diagnosis of ES, in 2 French community hospitals. Most ESs were partial (n=50; 48.07%) but generalized ESs were also clinically frequent (n=41; 39.42%). Brain imaging was highly contributive for the diagnosis of partial ESs by demonstrating causative focal structural lesions. ESs were often unprovoked (n=82; 78.84%). Fifty six of these (68.29%) were symptomatic. Stroke lesions were the most identified cause (n=17; 20.73%). In 26 patients (31.70%) aetiology was unknown. Various diagnostic problems were identified. Inter-observer agreement between neurologists and non-neurologists based on clinical judgement was only "fair" (kappa coefficient: 0.28; 95% CI; p=0.002). ESs were initially misdiagnosed in 28 patients (26.92%). The misdiagnosis rate was higher among non-neurologists (n=25; 89.28%) as compared to neurologists (n=8; 28.57%) (p<0.0001). The presence of focal neurological abnormalities was an important diagnostic indicator of a positive diagnosis of ES. In conclusion, ESs in the elderly are generally partial, unprovoked and symptomatic, and caused by stroke-related lesions. Many are still overlooked, highlighting the important role of specialist input and rigorous clinical evaluation for diagnostic confirmation.
Short-course antiretroviral therapy in primary HIV infection.

Short-course antiretroviral therapy (ART) in primary human immunodeficiency virus (HIV) infection may delay disease progression but has not been adequately evaluated.



We randomly assigned adults with primary HIV infection to ART for 48 weeks, ART for 12 weeks, or no ART (standard of care), with treatment initiated within 6 months after seroconversion. The primary end point was a CD4+ count of less than 350 cells per cubic millimeter or long-term ART initiation.



A total of 366 participants (60% men) underwent randomization to 48-week ART (123 participants), 12-week ART (120), or standard care (123), with an average follow-up of 4.2 years. The primary end point was reached in 50% of the 48-week ART group, as compared with 61% in each of the 12-week ART and standard-care groups. The average hazard ratio was 0.63 (95% confidence interval [CI], 0.45 to 0.90; P=0.01) for 48-week ART as compared with standard care and was 0.93 (95% CI, 0.67 to 1.29; P=0.67) for 12-week ART as compared with standard care. The proportion of participants who had a CD4+ count of less than 350 cells per cubic millimeter was 28% in the 48-week ART group, 40% in the 12-week group, and 40% in the standard-care group. Corresponding values for long-term ART initiation were 22%, 21%, and 22%. The median time to the primary end point was 65 weeks (95% CI, 17 to 114) longer with 48-week ART than with standard care. Post hoc analysis identified a trend toward a greater interval between ART initiation and the primary end point the closer that ART was initiated to estimated seroconversion (P=0.09), and 48-week ART conferred a reduction in the HIV RNA level of 0.44 log(10) copies per milliliter (95% CI, 0.25 to 0.64) 36 weeks after the completion of short-course therapy. There were no significant between-group differences in the incidence of the acquired immunodeficiency syndrome, death, or serious adverse events.



A 48-week course of ART in patients with primary HIV infection delayed disease progression, although not significantly longer than the duration of the treatment. There was no evidence of adverse effects of ART interruption on the clinical outcome. (Funded by the Wellcome Trust; SPARTAC Controlled-Trials.com number, ISRCTN76742797, and EudraCT number, 2004-000446-20.).
Intradiscal electrothermal therapy (IDET) provides effective symptom relief in patients with discogenic low back pain.

Single-arm, prospective clinical trial.



To evaluate back pain severity, physical function, and quality of life outcomes in highly selected patients with lumbar discogenic pain treated with intradiscal electrothermal therapy (IDET).



Degeneration and disruption of the intervertebral disc can be the source of severe low back pain and the associated physical dysfunction. IDET is a minimally invasive treatment option in the continuum of care between conservative nonoperative management and spinal surgery.



Using magnetic resonance imaging, pressure-controlled discography, and postdiscogram computed tomography findings, 56 patients with lumbar discogenic pain were identified, underwent IDET treatment and followed for 20.5+/-4.4 months, on average. Outcomes included assessments of back pain severity by visual analog scale, sitting, standing, and walking tolerances, and health-related quality of life using the SF-36.



Mean pain severity scores (visual analog scale) improved from 6.1+/-1.8 pretreatment to 2.4+/-2.6 at final follow-up (P=0.0001). Mean tolerance times (minutes) improved from 40.9+/-40.6 to 84.5+/-54.4, 46.8+/-42.9 to 84.4+/-54.2, and 39.2+/-39.6 to 77.9+/-50.8 between baseline and final follow-up for sitting, standing, and walking, respectively (P=0.0001 for all comparisons). Seven of 8 quality of life domains showed significant (P=0.0001 for all comparisons) improvement over baseline. Forty-two patients (75%) were classified as a treatment success by virtue of a >or=2-point improvement in pain severity or a >or=10-point improvement in either the physical functioning or bodily pain domain of the SF-36.



The findings of this study suggest that durable clinical improvements can be realized after IDET in highly selected patients with mild disc degeneration, confirmatory imaging evidence of annular disruption, and concordant pain provocation by low pressure discography.
Neural tissue management provides immediate clinically relevant benefits without harmful effects for patients with nerve-related neck and arm pain: a randomised trial.

What are the benefits and harms of neural tissue management in the short term for treating nerve-related neck and arm pain?



Randomised controlled trial.



Sixty participants with non-traumatic nerve-related neck and unilateral arm pain were randomised to experimental (n=40) or control (n=20) groups.



Both groups were advised to continue usual activities. The experimental group also received education, manual therapy, and nerve gliding exercises in 4 treatments over 2 weeks.



Primary outcomes were participant-reported improvement and worsening on a Global Rating of Change scale. Secondary outcomes were neck pain, arm pain, the Neck Disability Index, the Patient-Specific Functional Scale, and adverse events related to treatment. Follow-up occurred 3-4 weeks after baseline.



Numbers needed to treat favoured the experimental intervention for participant-reported improvement (2.7, 95% CI 1.7 to 6.5), neck pain (3.6, 95% CI 2.1 to 10), arm pain (3.6, 95% CI 2.1 to 10), Neck Disability Index (4.3, 95% CI 2.4 to 18.2), and Patient-Specific Functional Scale (3.0, 95% CI 1.9 to 6.7). The prevalence of worsening in the experimental (13%) and control (20%) groups were not different (RD -7%, 95% CI -28 to 13). Adverse events had minimal impact on daily activities and did not reduce the chance of improving with the experimental intervention (RR = 1.03, 95% CI 0.58 to 1.84).



These results enable physiotherapists to inform patients that neural tissue management provides immediate clinically relevant benefits beyond advice to remain active with no evidence of harmful effects.