nils-herrmann/clean_scirepeval huggingface dataset:
Dose-response and efficacy of spinal manipulation for care of chronic low back pain: a randomized controlled trial.

There have been no full-scale trials of the optimal number of visits for the care of any condition with spinal manipulation.



To identify the dose-response relationship between visits to a chiropractor for spinal manipulation and chronic low back pain (cLBP) outcomes and to determine the efficacy of manipulation by comparison with a light massage control.



Practice-based randomized controlled trial.


PATIENT SAMPLE
Four hundred participants with cLBP.



The primary cLBP outcomes were the 100-point modified Von Korff pain intensity and functional disability scales evaluated at the 12- and 24-week primary end points. Secondary outcomes included days with pain and functional disability, pain unpleasantness, global perceived improvement, medication use, and general health status.



One hundred participants with cLBP were randomized to each of four dose levels of care: 0, 6, 12, or 18 sessions of spinal manipulation from a chiropractor. Participants were treated three times per week for 6 weeks. At sessions when manipulation was not assigned, they received a focused light massage control. Covariate-adjusted linear dose effects and comparisons with the no-manipulation control group were evaluated at 6, 12, 18, 24, 39, and 52 weeks.



For the primary outcomes, mean pain and disability improvement in the manipulation groups were 20 points by 12 weeks and sustainable to 52 weeks. Linear dose-response effects were small, reaching about two points per six manipulation sessions at 12 and 52 weeks for both variables (p<.025). At 12 weeks, the greatest differences from the no-manipulation control were found for 12 sessions (8.6 pain and 7.6 disability points, p<.025); at 24 weeks, differences were negligible; and at 52 weeks, the greatest group differences were seen for 18 visits (5.9 pain and 8.8 disability points, p<.025).



The number of spinal manipulation visits had modest effects on cLBP outcomes above those of 18 hands-on visits to a chiropractor. Overall, 12 visits yielded the most favorable results but was not well distinguished from other dose levels.
Comparison of Three Tracheal Intubation Techniques in Thyroid Tumor Patients with a Difficult Airway: A Randomized Controlled Trial

To investigate the effectiveness of the Shikani optical stylet (SOS) and GlideScope video laryngoscope (GVL) for tracheal intubation of thyroid tumor patients with a difficult airway.



One hundred and twenty thyroid tumor patients with a difficult airway, who were undergoing elective surgery requiring general anesthesia, were enrolled in the study. They were randomly allocated to 3 groups (n = 40 each) who underwent direct laryngoscopy (DL), SOS or GVL. The outcomes recorded were time to intubation, first-attempt success rate, mean artery pressure (MAP), heart rate (HR) and incidence of complications.



The mean time to intubation in the SOS group (group S; 42.4 ± 24.1 s) and the GLV group (group G; 29.8 ± 22.3 s) was significantly less than that in the DL group (group D) (68.8 ± 26.6 s). The first-attempt success rate in group S (90.0%) and group G (97.5%) was significantly higher than that in group D (75.0%; all p < 0.05). The HR and MAP at 1 min after intubation were lowest in group S (76.4 ± 9.2 beats/min and 12.9 ± 1.1 kPa), followed by group G (79.9 ± 9.3 beats/min and 13.0 ± 0.9 kPa) and then group D (90.4 ± 8.1 beats/min and 16.6 ± 1.2 kPa). The difference was statistically significant (all p < 0.05). The incidence of lip or mucosal trauma was lowest in group S, followed by group G and then group D.



The SOS and the GLV had advantages over the DL in the management of thyroid tumor patients with a difficult airway in terms of a shorter time to intubation, a higher first-attempt success rate and a reduced incidence of complications. Thus, a rational choice of one of these techniques may be better for the perioperative safety of thyroid tumor patients with a difficult airway.
Serum levels of selenium and smoking habits at age 50 influence long term prostate cancer risk; a 34 year ULSAM follow-up

Serum selenium level (s-Se) has been associated with prostate cancer (PrCa) risk. We investigated the relation between s-Se, smoking and non-screening detected PrCa and explored if polymorphisms in two DNA repair genes: OGG1 and MnSOD, influenced any effect of s-Se. ULSAM, a population based Swedish male cohort (n = 2322) investigated at age 50 for s-Se and s-Se influencing factors: serum cholesterol, erythrocyte sedimentation rate and smoking habits. At age 71 a subcohort, (n = 1005) was genotyped for OGG1 and MnSOD polymorphisms. In a 34-year-follow-up, national registries identified 208 PrCa cases further confirmed in medical records. Participants with s-Se in the upper tertile had a non-significantly lower risk of PrCa. Smokers with s-Se in the two lower tertiles (≤80 μg/L) experienced a higher cumulative incidence of PrCa than smokers in the high selenium tertile (Hazard Ratio 2.39; 95% CI: 1.09-5.25). A high tertile selenium level in combination with non-wt rs125701 of the OGG1 gene in combination with smoking status or rs4880 related variation of MnSOD gene appeared to protect from PrCa. S-Se levels and smoking habits influence long-term risk of PrCa. Smoking as a risk factor for PrCa in men with low s-Se is relevant to explore further. Exploratory analyses of variations in OGG1 and MnSOD genes indicate that hypotheses about patterns of exposure to selenium and smoking combined with data on genetic variation in genes involved in DNA repair can be valuable to pursue.
Bortezomib (Velcade) for progressive myeloma after autologous stem cell transplantation and thalidomide.

Twenty-one patients with multiple myeloma, all relapsed after frontline autologous stem cell transplantation and all relapsed again after or resistant to thalidomide (employed as second line treatment) received bortezomib (1.3 mg/m(2) body surface twice weekly for 2 weeks followed by an interval of 10-12 days) without adjunct of steroids as third line therapy. Three patients died of progressive disease during the first 2 cycles with bortezomib. Eighteen patients received at least 2 cycles and were evaluated for response. According to EBMT criteria, two complete (negative immunofixation) and seven partial (reduction of M-component > 50-75%) remissions were achieved (ITT response rate 42.8%). Duration of response lasted from 2 to 14+ months. Grades 3-4 toxicities (thrombocytopenia, leucopenia, peripheral neuropathy and vasculitis) were observed in seven patients, but no patient interrupted the treatment due to side effects. We conclude that bortezomib alone may induce high quality responses as third line salvage therapy with acceptable toxicity in a significant proportion of homogeneously pre-treated myeloma patients with progressive disease after autologous transplantation and thalidomide.
Efficacy of atorvastatin for the treatment of nonalcoholic steatohepatitis with dyslipidemia.

Nonalcoholic steatohepatitis (NASH) is the hepatic manifestation of the metabolic syndrome. Currently, there is no established therapy for NASH. The aim of the present study was to evaluate the efficacy of atorvastatin in the treatment of NASH associated with hyperlipidemia. This prospective study included 31 patients with biopsy-proven NASH with hyperlipidemia. Body mass index, serum lipids, liver function tests, fibrosis markers, and adipocytokines (adiponectin, leptin, tumor necrosis factor-alpha) were measured periodically during an open-label study of atorvastatin (10 mg daily) for 24 months. Standard weight-loss counseling was continued during the treatment period. Oral glucose tolerance test and liver density assessed by computerized tomography were performed before and after treatment. Follow-up liver biopsy was performed in 17 patients. All 31 patients had high cholesterol levels at baseline, and 20 also presented high triglyceride levels. The body mass index and serum glucose levels did not change during the treatment. After treatment, 23 patients (74.2%) presented normal transaminase levels. Adiponectin levels were significantly increased, and the levels of tumor necrosis factor-alpha were significantly decreased. However, leptin levels were not changed significantly. The concentration of long-chain fatty acids was decreased; and significant decreases were observed in C18:2,n-6 (linoleic acid, -21%) and C20:4,n-6 (arachidonic acid, -22%). Liver steatosis and nonalcoholic fatty liver disease activity score were significantly improved, whereas 4 patients had increased fibrosis stage. The NASH-related metabolic parameters improved with therapy, including fibrosis in some patients. However, 4 of 17 patients had progression of fibrosis over the 2-year period, with 3 of them progressing to stage 3. It is unclear whether this divergent response represents sampling error, heterogeneity in the population, or untreated postprandial hyperglyceridemia. Controlled trials are needed to further investigate and resolve this.
Implications of IV monoclonal antibody infusion reaction for the patient, caregiver, and practice: results of a multicenter study

Targeted monoclonal antibodies (MoAbs) have become a promising treatment option for patients with cancer. However, there is a risk of developing infusion reactions (IRs) with MoAbs. This study was conducted to evaluate the impact of IRs on staff time and costs among patients receiving an initial infusion of cetuximab (Erbitux®) and rituximab (Rituxan®). A prospective multicenter study involving time and motion and activity sampling methods was conducted among patients with cancer receiving their first outpatient infusion of cetuximab or rituximab. Patients were observed from initiation of MoAb infusion to the end of the clinic visit. IRs were classified as absent, mild/moderate, and severe/life threatening. Staff time and costs were estimated for preparation and administration of MoAb, other chemotherapy agents, and for management of IRs. Resource costs were compared across IR groups within each MoAb. Among 161 patients enrolled, 32% of 71 patients on cetuximab and 39% of 90 patients on rituximab experienced IRs. Treatment of patients who experienced IRs required more staff time (31–80% more time) and resulted in higher human resource costs (increase of 17–65 US dollars) than patients who did not experience IRs. IRs following cetuximab and rituximab administration are common and are associated with measurably increased costs of care. The frequency of IRs suggests the importance of identifying clinical guidelines for intervention and management.
Common SNPs in LEP and LEPR associated with birth weight and type 2 diabetes-related metabolic risk factors in twins

n 179 217 107 125 Birth weight (g) 2540±443 2456±488 0.11 2690±446 2572±474 0.002 Gestational age (weeks) 36.9±2.2 36.8±2.6 0.98 37.4±2.2 37.5±2.3 0.82 Age (years) 25.0±4.6 24.8±4.7 0.68 25.5±4.7 25.6±4.6 0.88 Body height (cm) 178.0±5.9 165.3±6.5 o0.0001 178.5±6.7 166.5±6.5 o0.0001 Body mass (kg) 69.3±9.1 60.2±9.9 o0.0001 70.1±10.1 60.7±10.0 o0.0001 BMI (kg/m) 21.7±1.1 21.8±1.2 0.78 21.9±1.1 21.7±1.1 0.84 Fat mass (kg) 11.3±1.5 16.7±1.3 o0.0001 12.2±1.5 16.6±1.3 o0.0001 Lean body mass (kg) 57.0±6.2 42.8±5.2 o0.0001 57.0±6.5 43.5±5.9 o0.0001 S4SF (mm) 34.9±1.5 56.2±1.4 o0.0001 34.2±1.5 52.2±1.4 o0.0001 WHR (%) 82.9±5.3 73.2±4.5 o0.0001 82.6±5.1 72.3±4.2 o0.0001 IGFBP-1 (ng ml ) 10.9±1.8 16.3±2.0 o0.0001 12.2±1.8 19.1±2.3 o0.0001 Fasting insulin (pmol l ) 32.5±1.5 37.8±1.6 0.005 31.6±1.6 40.6±1.5 o0.0001 Fasting glucose (mmol l ) 5.0±0.4 4.6±0.4 o0.0001 4.8±0.4 4.6±0.4 o0.0001 Leptin (ng ml ) 1.6±3.1 11.8±2.1 o0.0001 1.6±2.8 11.4±1.9 o0.0001 Total cholesterol (mmol l ) 4.8±1.0 5.1±0.8 0.003 5.0±1.1 5.2±1.0 0.08 LDL cholesterol (mmol l ) 3.0±0.9 2.9±0.8 0.43 3.1±1.0 2.9±0.8 0.03 HDL cholesterol (mmol l ) 1.4±0.3 1.8±0.4 o0.0001 1.4±0.4 1.9±0.4 o0.0001 Triacylglycerol (mmol l ) 0.8±1.5 0.9±1.5 0.04 0.9±1.5 0.9±1.5 0.81 NEFA (mmol l ) 0.5±0.2 0.7±0.2 o0.0001 0.5±0.2 0.7±0.2 o0.0001
Maintenance treatment with medroxyprogesterone acetate in patients with advanced breast cancer responding to chemotherapy: results of a randomized trial

The purpose of this randomized phase III trial was to study whether medroxyprogesterone acetate (MPA) maintenance treatment prolongs the time to progression in advanced breast cancer patients responding to an induction chemotherapy. Patients with progressive advanced breast cancer previously untreated with anthracylines and progestins were given epirubicin (30 mg/m2) and ifosfamide (2 g/m2) on days 1 and 8 at 3‐weekly intervals. Patients without disease progression after 6 cycles of chemotherapy were randomly assigned to receive, until progression, either no treatment or MPA at a daily total dose of 500 mg. Ninety patients were randomized: 46 to the MPA arm and 44 to the observation arm. Median time to progression was longer in the MPA arm: 4.9 months versus 3.7 months in the intent‐to‐treat analysis (p=0.02), and 4.9 months versus 3.0 months in the secondary efficacy analysis (p=0.012). Seven patients were removed from MPA due to side effects. The changes in patient‐rated quality of life scores were similar in both groups. The median length of survival from randomization was 17.4 months for patients receiving MPA and 18.3 months for patients randomized to observation (p=0.39). In conclusion, in patients with advanced breast cancer achieving remission or non‐progression with 6 cycles of epirubicin and ifosfamide chemotherapy, MPA maintenance treatment led to a significant, though modest, prolongation of the time to progression without affecting overall survival of the study patients.
Associations between Vitamin D Status and Type 2 Diabetes Measures among Inuit in Greenland May Be Affected by Other Factors.

Epidemiological studies have provided evidence of an association between vitamin D insufficiency and type 2 diabetes. Vitamin D levels have decreased among Inuit in Greenland, and type 2 diabetes is increasing. We hypothesized that the decline in vitamin D could have contributed to the increase in type 2 diabetes, and therefore investigated associations between serum 25(OH)D3 as a measure of vitamin D status and glucose homeostasis and glucose intolerance in an adult Inuit population.



2877 Inuit (≥18 years) randomly selected for participation in the Inuit Health in Transition study were included. Fasting- and 2hour plasma glucose and insulin, C-peptide and HbA1c were measured, and associations with serum 25(OH)D3 were analysed using linear and logistic regression. A subsample of 330 individuals who also donated a blood sample in 1987, were furthermore included.



After adjustment, increasing serum 25(OH)D3 (per 10 nmol/L) was associated with higher fasting plasma glucose (0.02 mmol/L, p = 0.004), 2hour plasma glucose (0.05 nmol/L, p = 0.002) and HbA1c (0.39%, p<0.001), and with lower beta-cell function (-1.00 mmol/L, p<0.001). Serum 25(OH)D3 was positively associated with impaired fasting glycaemia (OR: 1.08, p = 0.001), but not with IGT or type 2 diabetes.



Our results did not support an association between low vitamin D levels and risk of type 2 diabetes. Instead, we found weak positive associations between vitamin D levels and fasting- and 2hour plasma glucose levels, HbA1c and impaired fasting glycaemia, and a negative association with beta-cell function, underlining the need for determination of the causal relationship.
Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD): study design and protocol

Studies suggest that in addition to blood glucose concentrations, thiazolidinediones such as rosiglitazone improve some cardiovascular (CV) risk factors and surrogate markers, that are abnormal in type 2 diabetes. However, fluid retention might lead to cardiac failure in a minority of people. The aim of the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) study is to evaluate the long-term impact of these effects on CV outcomes, as well as on long-term glycaemic control, in people with type 2 diabetes. RECORD is a 6-year, randomised, open-label study in type 2 diabetic patients with inadequate blood glucose control (HbA1c 7.1–9.0%) on metformin or sulphonylurea alone. The study is being performed in 327 centres in Europe and Australasia. After a 4-week run-in, participants were randomised by current treatment stratum to add-on rosiglitazone, metformin or sulphonylurea, with dose titration to a target HbA1c of ≤7.0%. If confirmed HbA1c rises to ≥8.5%, either a third glucose-lowering drug is added (rosiglitazone-treated group) or insulin is started (non-rosiglitazone group). The same criterion for failure of triple oral drug therapy in the rosiglitazone-treated group is used for starting insulin in this group. The primary endpoint is the time to first CV hospitalisation or death, blindly adjudicated by a central endpoints committee. The study aim is to evaluate non-inferiority of the rosiglitazone group vs the non-rosiglitazone group with respect to CV outcomes. Safety, tolerability and study conduct are monitored by an independent board. All CV endpoint and safety data are held and analysed by a clinical trials organisation, and are not available to the study investigators while data collection is open. Over a 2-year period a total of 7,428 people were screened in 25 countries. Of these, 4,458 were randomised; 2,228 on background metformin, 2,230 on background sulphonylurea. Approximately half of the participants are male (52%) and almost all are Caucasian (99%). The RECORD study should provide robust data on the extent to which rosiglitazone, in combination with metformin or sulphonylurea therapy, affects CV outcomes and progression of diabetes in the long term.
A Cancer Vaccine Induces Expansion of NY-ESO-1-Specific Regulatory T Cells in Patients with Advanced Melanoma

Cancer vaccines are designed to expand tumor antigen-specific T cells with effector function. However, they may also inadvertently expand regulatory T cells (Treg), which could seriously hamper clinical efficacy. To address this possibility, we developed a novel assay to detect antigen-specific Treg based on down-regulation of surface CD3 following TCR engagement, and used this approach to screen for Treg specific to the NY-ESO-1 tumor antigen in melanoma patients treated with the NY-ESO-1/ISCOMATRIX™ cancer vaccine. All patients tested had Treg (CD25(bright) FoxP3(+) CD127(neg)) specific for at least one NY-ESO-1 epitope in the blood. Strikingly, comparison with pre-treatment samples revealed that many of these responses were induced or boosted by vaccination. The most frequently detected response was toward the HLA-DP4-restricted NY-ESO-1(157-170) epitope, which is also recognized by effector T cells. Notably, functional Treg specific for an HLA-DR-restricted epitope within the NY-ESO-1(115-132) peptide were also identified at high frequency in tumor tissue, suggesting that NY-ESO-1-specific Treg may suppress local anti-tumor immune responses. Together, our data provide compelling evidence for the ability of a cancer vaccine to expand tumor antigen-specific Treg in the setting of advanced cancer, a finding which should be given serious consideration in the design of future cancer vaccine clinical trials.
Atrial Fibrillation Complexity Parameters Derived From Surface ECGs Predict Procedural Outcome and Long-Term Follow-Up of Stepwise Catheter Ablation for Atrial Fibrillation.

The success rate of catheter ablation for persistent atrial fibrillation (AF) is still far from satisfactory. Identification of patients who will benefit from ablation is highly desirable. We investigated the predictive value of noninvasive AF complexity parameters derived from standard 12-lead ECGs for AF termination and long-term success of catheter ablation and compared them with clinical predictors.



The study included a training (93 patients) and a validation set (81 patients) of patients with persistent AF undergoing stepwise radiofrequency ablation. In the training set AF terminated in 81% during catheter ablation, 77% were in sinus rhythm after 6 years and multiple ablations. ECG-derived complexity parameters were determined from a baseline 10-s 12-lead ECG. Prediction of AF termination was similar using only ECG (cross-validated mean area under the curve [AUC], 0.76±0.15) or only clinical parameters (mean AUC, 0.75±0.16). The combination improved prediction to a mean AUC of 0.79±0.13. Using a combined model of ECG and clinical parameters, sinus rhythm at long-term follow-up could be predicted with a mean AUC of 0.71±0.12. In the validation set AF terminated in 57%, 61% were in sinus rhythm after 4.6 years. The combined models predicted termination with an AUC of 0.70 and sinus rhythm at long-term follow-up with an AUC of 0.61. Overall, fibrillation-wave amplitude provided the best rhythm prediction.



The predictive performance of ECG-derived AF complexity parameters for AF termination and long-term success of catheter ablation in patients with persistent AF is at least as good as known clinical predictive parameters, with fibrillation-wave amplitude as the best predictor.
Blood oxygen level dependent and adenosine-perfusion imaging correlates to invasive measurement of fractional flow reserve

It has been shown that blood oxygen level dependent (BOLD) cardiac magnetic resonance imaging (CMR) is able to detect myocardial perfusion differences. However, validation of BOLD CMR against myocardial perfusion reserve (MPR) and fractional flow reserve (FFR) is lacking. We sought to analyze the potential diagnostic accuracy of BOLD CMR in comparison to invasively measured FFR which served as the standard reference.
A phase II trial of ixabepilone in Asian patients with advanced gastric cancer previously treated with fluoropyrimidine-based chemotherapy

The highest rates of gastric cancer occur in Eastern Asia. Fluoropyrimidine-based therapy is used initially in unresectable and metastatic disease, but no single standard of care exists following disease progression. Ixabepilone, an epothilone B analog, is a non-taxane microtubule-stabilizing agent with clinical activity across multiple tumor types approved by the United States Food and Drug Administration for treatment of metastatic breast cancer. Asian patients with unresectable or metastatic gastric adenocarcinoma who had failed fluoropyrimidine-based chemotherapy received ixabepilone 40 mg/m2 by 3-h intravenous infusion every 3 weeks. The primary endpoint was objective response rate (ORR). Fifty-two patients were treated (65.4 % men; median age: 56.5 years). The ORR was 15.4 % (95 % confidence interval [CI] 6.9–28.1); 8 patients achieved partial responses for a median duration of 3.1 months (95 % CI 2.6–4.1 months) and 26 patients (50.0 %) had stable disease. Median progression-free survival was 2.8 months (95 % CI 2.1–3.5 months). The most common grade 3 non-hematological toxicities were fatigue (9.6 %), decreased appetite (7.7 %), sensory neuropathy (5.8 %), and diarrhea (5.8 %). Grade 3/4 neutropenia occurred in 46.2 % of patients. Ixabepilone is active in Asian patients with advanced gastric cancer and shows a toxicity profile similar to those previously reported in other tumor types.