nils-herrmann/clean_scirepeval huggingface dataset:
Omitting elective nodal irradiation and irradiating postinduction versus preinduction chemotherapy tumor extent for limited-stage small cell lung cancer: interim analysis of a prospective randomized noninferiority trial.

Controversies exist with regard to thoracic radiotherapy volumes for limited-stage small cell lung cancer (SCLC). This study compared locoregional progression and overall survival between limited-stage SCLC patients who received thoracic radiotherapy to different target volumes after induction chemotherapy.



Chemotherapy consisted of 6 cycles of etoposide and cisplatin. After 2 cycles of etoposide and cisplatin, patients were randomly assigned to receive thoracic radiotherapy to either the postchemotherapy or prechemotherapy tumor extent as study arm or control. Elective nodal irradiation was omitted for both arms. Forty-five Gy/30Fx/19 days thoracic radiotherapy was administered concurrently with cycle 3 chemotherapy. Prophylactic cranial irradiation was administered to patients who achieved complete remission. An interim analysis was planned when the first 80 patients had been followed for at least 6 months, for consideration of potential inferiority in the study arm.



Forty-two and 43 patients were randomly assigned to a study arm and a control, respectively. The local recurrence rates were 31.6% (12 of 38) and 28.6% (12 of 42), respectively (P = .81). The isolated nodal failure rates were 2.6% (1 of 38) and 2.4% (1 of 42), respectively (P = 1.00). All isolated nodal failure sites were in the ipsilateral supraclavicular fossa. Mediastinal N3 was the only factor to predict isolated nodal failure (P = .004; odds ratio [OR], 29.33; 95% CI, 2.94-292.38). One-year and 3-year overall survival rates were 80.6%, 36.2%, and 78.9%, 36.4%, respectively (P = .54).



Preliminary results indicated that irradiated postchemotherapy tumor extent and omitted elective nodal irradiation did not decrease locoregional control in the study arm, and the overall survival difference was not statistically significant between the 2 arms. Further investigation is warranted.
Facilitated bone mineral density testing versus hospital-based case management to improve osteoporosis treatment for hip fracture patients: additional results from a randomized trial.

We previously demonstrated that a case manager intervention improved osteoporosis (OP) treatment within 6 months of hip fracture compared with usual care. The second phase of the randomized trial compared a less intensive intervention, facilitated bone mineral density (BMD) testing, with usual care and the case manager intervention.



We initially randomized 220 hip fracture patients to either an OP case manager intervention or usual care. After completing the original trial at 6 months postfracture, usual care patients were reallocated to facilitated BMD testing; BMD tests were arranged and results sent to primary care physicians. Main outcomes (bisphosphonate treatment, BMD tests, receipt of appropriate care) were reascertained 1 year following hip fracture and compared with outcomes achieved by the OP case manager intervention and usual care.



Compared with usual care, facilitated BMD testing increased testing from 29% to 68% (P < 0.001), bisphosphonate use from 22% to 38% (P < 0.001), and receipt of appropriate care from 26% to 45% (P < 0.001). The more intensive (70 versus 30 minutes) and expensive ($56 versus $24 Canadian per patient) OP case manager intervention led to significantly higher bisphosphonate use (54% versus 38%; P = 0.03), receipt of appropriate care (71% versus 45%; P < 0.001), and more BMD testing (80% versus 68%; P = 0.06) than usual care followed by facilitated BMD testing.



Compared with usual care, 2 different inexpensive interventions resulted in significant increases in appropriate management of OP after hip fracture. The magnitude of improvements achieved was directly related to the intensity of the interventions.
Annexin and survivin in locally advanced rectal cancer: indicators of resistance to preoperative chemoradiotherapy?

The aim of preoperative chemoradiotherapy is improvement of local control in patients with locally advanced rectal cancer (LARC). Recent studies have shown that annexin and survivin are involved in the resistance capability of tumours. We sought to determine whether survivin, annexin A4 or annexin A5 expression predict resistance to preoperative chemoradiotherapy.



Biopsies of tumour and normal rectal tissue were taken from 38 patients with LARC (cT3/4Nx or Tx/N+) before the start of chemoradiotherapy and during surgery. mRNA expression of annexin A4/A5 and survivin was measured by real-time polymerase chain reaction (RT-PCR) and correlated with down-staging and progression-free survival (PFS).



Significantly higher mRNA levels of survivin, and annexin A4/A5 were detected in untreated tumour compared with normal mucosa. After chemoradiotherapy, this difference disappeared for survivin and annexin A4. Annexin A5 expression in the tumour increased during chemoradiotherapy. No correlation between the mRNA levels of survivin, annexin A4/A5 and tumour down-staging or PFS was noticed.



In the present analysis of 38 patients with LARC undergoing neoadjuvant chemoradiotherapy, the expression levels of survivin and annexin A4 and A5 did not correlate with down-staging. Moreover, with regard to PFS, none of these markers was found to be prognostically relevant.
The follow-up of the efficacy of antiviral therapy at patients with chronic hepatitis C.

Hepatitis C virus infection can cause progressive liver injury and lead to fibrosis and eventually cirrhosis. Peginterferon alfa-2a represents a significant advance in the treatment of patients with chronic hepatitis C. The aim of the study was to investigate the efficacy, safety and tolerability of the therapy with Peginterferon alfa-2a plus Ribavirin in patients with chronic hepatitis C. The study was made on a number of 37 patients with chronic hepatitis C, admitted in Medical Clinic no. 1, Emergency County Hospital Craiova. The diagnosis of chronic hepatitis was established by means of clinical, biological and morphological investigations. Patients received 180 mug subcutaneously of Pegasys, once weekly, along with either 1000 or 1200 mg/day of Copegus, depending on their weight, for 48 weeks, with 24 weeks of treatment -- free follow-up. We evaluated: sustained virological response, histological response and adverse events. All patients were monitored using blood tests, control of viremia and liver functional tests. Analysis viral response revealed that 11 patients (29.72%) achieved sustained virological response. Histological response was obtained in 20 cases (54.05%) with chronic hepatitis C. The adverse events for Pegasys and Copegus combination therapy were reported in 21 cases (56.72%). Antiviral therapy had positive effect on subjective symptoms in almost half of patients included in our study. An improvement of liver functional tests was noted in the most cases. A third of patients who received Peginterferon alfa-2a plus Ribavirin had sustained virological response. Histological response was noted both at patients with sustained virological response and with unsustained virological response. The side effects of the antiviral treatment are frequent and the severe ones, which require dose reduction, are present at a low number of patients.
Additional effect of pulsed electromagnetic field therapy on knee osteoarthritis treatment: a randomized, placebo-controlled study

The aim of this study was to evaluate if pulsed electromagnetic field therapy (PEMF) has additional effect on the classical physical treatment of knee osteoarthritis (OA) composed of hot pack, therapeutic ultrasound, and terminal isometric exercises. Forty patients (29 women and 11 men), ages 44 to 78 (mean age was 61.3 ± 7.8 years) were included in our study. Patients with knee osteoarthritis [Kellgren–Lawrence criteria grade 2 and above and an average pain intensity of 40 or more on a 100-mm visual analog scale (VAS)] recruited from outpatient physical medicine and rehabilitation clinic were randomly assigned to receive PEMF or sham PEMF treatment in addition to their physical therapy. Both the PEMF and sham PEMF treatments being evaluated were 55 min/session, five sessions per week for 2 weeks. Each session comprise 20-min hot pack, 5-min therapeutic ultrasound, and 30-min PEMF or sham PEMF treatment applied to the knee of the patients. Patients were evaluated by the Western Ontario and McMasters Universities Osteoarthritis (WOMAC) Index and VAS at the baseline and at the end of treatment. Both PEMF and sham PEMF treatment groups showed statistically significant improvement in WOMAC pain and functional scores at the end of treatment (p < 0.001 in both groups). There were no statistically significant differences between groups in WOMAC pain, stiffness, and physical function scores after treatment (p = 0.906, p = 0.855, p = 0.809, respectively). There was neither difference in concomitant used acetaminophen dose in both groups (p = 0.289). The results of this study show that PEMF does not have additional effect on the classical physical treatment in reducing symptoms of knee OA.
The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial.

Transcranial Doppler ultrasound (TCD) and magnetic resonance angiography (MRA) can identify intracranial atherosclerosis but have not been rigorously validated against the gold standard, catheter angiography. The WASID trial (Warfarin Aspirin Symptomatic Intracranial Disease) required performance of angiography to verify the presence of intracranial stenosis, allowing for prospective evaluation of TCD and MRA. The aims of Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial were to define abnormalities on TCD/MRA to see how well they identify 50 to 99% intracranial stenosis of large proximal arteries on catheter angiography.



SONIA standardized the performance and interpretation of TCD, MRA, and angiography. Study-wide cutpoints defining positive TCD/MRA were used. Hard copy TCD/MRA were centrally read, blind to the results of angiography.



SONIA enrolled 407 patients at 46 sites in the United States. For prospectively tested noninvasive test cutpoints, positive predictive values (PPVs) and negative predictive values (NPVs) were TCD, PPV 36% (95% CI: 27 to 46); NPV, 86% (95% CI: 81 to 89); MRA, PPV 59% (95% CI: 54 to 65); NPV, 91% (95% CI: 89 to 93). For cutpoints modified to maximize PPV, they were TCD, PPV 50% (95% CI: 36 to 64), NPV 85% (95% CI: 81 to 88); MRA PPV 66% (95% CI: 58 to 73), NPV 87% (95% CI: 85 to 89). For each test, a characteristic performance curve showing how the predictive values vary with a changing test cutpoint was obtained.



Both transcranial Doppler ultrasound and magnetic resonance angiography noninvasively identify 50 to 99% intracranial large vessel stenoses with substantial negative predictive value. The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis trial methods allow transcranial Doppler ultrasound and magnetic resonance angiography to reliably exclude the presence of intracranial stenosis. Abnormal findings on transcranial Doppler ultrasound or magnetic resonance angiography require a confirmatory test such as angiography to reliably identify stenosis.
Methylphenidate reduces mental fatigue and improves processing speed in persons suffered a traumatic brain injury.

Post-traumatic brain injury symptoms, such as mental fatigue, have considerable negative impacts on quality-of-life. In the present study the effects of methylphenidate in two different dosages were assessed with regard to mental fatigue, pain and cognitive functions in persons who had suffered a traumatic brain injury.



Fifty-one subjects were included and 44 completed the study. The treatment continued for 12 weeks, including three treatment periods with no medication for 4 weeks, administration of low dose methylphenidate (up to 5 mg × 3) for 4 weeks and normal dose methylphenidate (up to 20 mg × 3) for a further 4 weeks. The patients were randomized into three groups where all groups were given all treatments.



Significantly reduced mental fatigue, assessed with the Mental Fatigue Scale (MFS) and increased information processing speed (coding, WAIS-III), were detected. The SF-36 vitality and social functioning scales were also improved significantly. Pain was not reduced by methylphenidate. The positive effects of treatment were dose-dependent, with the most prominent effects being at 60 mg methylphenidate/day spread over three doses. Observed side-effects were increased blood pressure and increased heart rate.



Methylphenidate was generally well-tolerated and it improved long-lasting mental fatigue and processing speed after traumatic brain injury.
Positive anti-citrullinated protein antibody status and small joint arthritis are consistent predictors of chronic disease in patients with very early arthritis: results from the NOR-VEAC cohort

The current 1987 American College of Rheumatology (ACR) classification criteria for rheumatoid arthritis (RA) have proven less useful in early arthritis. The objective of this study was to identify and compare predictors of three relevant outcomes of chronic arthritis in a cohort of very early arthritis patients.



The Norwegian Very Early Arthritis Cohort (NOR-VEAC) includes adult patients with at least one swollen joint of < or = 16 weeks' duration. Patients are followed for 2 years with comprehensive clinical and laboratory examinations. Logistic regression analyses were performed to determine independent predictors of three outcomes: persistent synovitis, prescription of disease-modifying anti-rheumatic drugs (DMARDs), and established clinical RA diagnosis within one year.



Of 384 patients eligible for one year follow-up (56.3% females, mean (SD) age 45.8 (14.7) years, median (IQR) duration of arthritis 31 (10-62) days), 14.4% were anti-CCP2 positive, and 11.2% were IgM RF positive. 98 patients (25.5%) had persistent synovitis, 106 (27.6%) had received DMARD treatment during follow-up, while 68 (17.7%) were diagnosed with RA. Consistent independent predictors across all three outcomes were positive anti-citrullinated protein antibody (ACPA) status (odds ratio (OR) 3.2, 5.6 and 19.3), respectively, and small joint arthritis (proximal interphalangeal joint (PIP), metacarpo-phalangeal joint (MCP), and/or metatarso-phalangeal joint (MTP) joint swelling) (OR 1.9, 3.5, and 3.5, respectively).



Positive ACPA status and small joint arthritis were consistent predictors of three relevant outcomes of chronic arthritis in very early arthritis patients. This consistency supports DMARD prescription as a valid surrogate endpoint for chronic arthritis. Importantly, this surrogate is used in ongoing efforts to develop new diagnostic criteria for early RA.
Exploring differences in referrals to a hospice at home service in two socio-economically distinct areas of Manchester, UK.

In order to provide equitable access to hospice at home palliative care services, it is important to identify the socio-economic factors associated with poorer access. In this population-based study we aimed to test the inverse care law by exploring how socio-economic status and other key demographic indicators were associated with referral rates in two distinct areas (Salford and Trafford) served by the same service. Secondary data from the UK National Census 2001, North West Cancer Intelligence Service (2004) and hospice at home service referral data (2004-06) was collated for both areas. Descriptive analysis profiled electoral ward characteristics whilst simple correlations and regression modelling estimated associations with referral rates. Referral rates were lower and cancer mortality higher in the most deprived areas (Salford). Referral rates were significantly associated with deprivation, particularly multiple deprivation, but not significantly associated with cancer mortality (service model and resources available were held constant). At the population level, the socio-economic characteristics of those referred to hospice at home rather than service provision strongly predicted referral rates. This has implications for the allocation and targeting of resources and contributes important findings to future work exploring equitable access at organizational and professional levels.
Sequence of the human homologue of a mitochondrially encoded murine transplantation antigen in patients with multiple sclerosis

There is some evidence that mitochondrial genes may contribute to susceptibility to multiple sclerosis (MS), and a mitochondrial DNA-encoded peptide, the N-terminal portion of NADH-dehydrogenase subunit 1, acts as a transplantation antigen in mice. We have analysed the DNA sequence of the corresponding region of human mitochondria) DNA in 87 patients with MS, 10 with Leber's hereditary optic neuropathy in association with an MS like illness, and 31 control subjects. This sequence appears to be highly conserved. Only three base pair changes were identified, each being found once only in one control and two patients, and these are likely to be harmless polymorphisms. There is thus no evidence that polymorphism in this region contributes to genetic susceptibility in MS.
Usefulness of proteinuria as a prognostic marker of mortality and cardiovascular events among patients undergoing percutaneous coronary intervention (data from the Evaluation of Oral Xemilofiban in Controlling Thrombotic Events [EXCITE] trial).

Proteinuria was associated with cardiovascular events and mortality in community-based cohorts. The association of proteinuria with mortality and cardiovascular events in patients undergoing percutaneous coronary intervention (PCI) was unknown. The association of urinary dipstick proteinuria with mortality and cardiovascular events (composite of death, myocardial infarction, or nonhemorrhagic stroke) in 5,835 subjects of the EXCITE trial was evaluated. Dipstick urinalysis was performed before PCI, and proteinuria was defined as trace or greater. Subjects were followed up for 210 days/7 months after enrollment for the occurrence of events. Multivariate Cox regression analysis evaluated the independent association of proteinuria with each outcome. Mean age was 59 years, 21% were women, 18% had diabetes mellitus, and mean estimated glomerular filtration rate was 90 ml/min/1.73 m(2). Proteinuria was present in 750 patients (13%). During follow-up, 22 subjects (2.9%) with proteinuria and 54 subjects (1.1%) without proteinuria died (adjusted hazard ratio 2.83, 95% confidence interval [CI] 1.65 to 4.84, p <0.001). The severity of proteinuria attenuated the strength of the association with mortality after PCI (low-grade proteinuria, hazard ratio 2.67, 95% CI 1.50 to 4.75; high-grade proteinuria, hazard ratio 3.76, 95% CI 1.24 to 11.37). No significant association was present for cardiovascular events during the relatively short follow-up, but high-grade proteinuria tended toward increased risk of cardiovascular events (hazard ratio 1.45, 95% CI 0.81 to 2.61).In conclusion, proteinuria was strongly and independently associated with mortality in patients undergoing PCI. These data suggest that such a relatively simple and clinically easy to use tool as urinary dipstick may be useful to identify and treat patients at high risk of mortality at the time of PCI.
Consumption of Dairy Products and Cognitive Functioning: Findings from the SU.VI.MAX 2 Study.

Research concerning the link between dairy product intake and cognition is scant while experimental studies suggest links through various biological mechanisms. This study's objective was to examine the cross-time associations of total and specific dairy product consumption with cognitive performance in aging adults. We also explored compliance with dairy intake recommendations in France.



The study was based on the «Supplémentation en Vitamines et Minéraux Antioxydants» randomized trial (SU.VI.MAX, 1994-2002) and the SU.VI.MAX 2 observational follow-up study (2007-2009).



A general-population cohort in France.



N=3,076 participants included in both the SU.VI.MAX and SU.VI.MAX 2 studies.



Dairy product consumption was estimated using repeated 24h records (1994-1996; mean=10 records, SD=3). Cognitive performance was assessed by neuropsychologists after an average of 13 years post-baseline via a battery of six validated tests. Mean age at the time of the cognitive function evaluation was 65.5 (SD=4.6) years. Principal component analysis revealed factors for verbal memory and working memory. Associations of energy-adjusted dairy product consumption and compliance with the respective dietary guidelines with subsequent cognitive impairment were examined using ANCOVA, providing mean differences (95% confidence intervals, CI) according to tertiles (T), adjusted for confounders including overall dietary patterns.



Total dairy product consumption was not associated with cognitive function. However, milk intake was negatively associated with verbal memory performance: mean difference T3 versus T1= -0.99 (-1.83, -0.15). Among women, consuming more than the recommended amount of dairy was negatively associated with working memory performance: excess versus adequate = -1.52 (-2.93, -0.11).



Our results indicate that dairy products consumption and especially compliance with dietary guidelines regarding dairy product intake are differentially associated with performance in specific cognitive domains after a comprehensive adjustment for lifestyle factors, health status markers and dietary patterns. Further longitudinal research is needed given the limited data available.
Safety and tolerability of the novel inhaled corticosteroid fluticasone furoate in combination with the β2 agonist vilanterol administered once daily for 52 weeks in patients ≥12 years old with asthma: a randomised trial

The inhaled corticosteroid fluticasone furoate (FF) in combination with the long-acting β2 agonist vilanterol (VI) is in development for asthma and chronic obstructive pulmonary disease.



To assess the safety and tolerability of FF/VI over 52 weeks in patients with asthma.



Patients (aged ≥12 years; on inhaled corticosteroid) were randomised (2:2:1) to FF/VI 100/25 µg or FF/VI 200/25 µg once daily in the evening, or fluticasone propionate (FP) 500 µg twice daily. Safety evaluations included adverse events (AEs), non-fasting glucose, potassium, 24-h urinary cortisol excretion, ophthalmic assessments, heart rate and pulse rate.



On-treatment AEs were similar across groups (FF/VI 66-69%; 73% FP). Oral candidiasis/oropharyngeal candidiasis was more common with FF/VI (6-7%) than FP (3%). Twelve serious AEs were reported; one (worsening hepatitis B on FP) was considered drug related. Statistically significant cortisol suppression was seen with FP compared with both FF/VI groups at Weeks 12 and 28 (ratios [95% CI] to FP ranged from 1.43 [1.11 to 1.84] to 1.67 [1.34 to 2.08]; p≤0.006), but not at Week 52 (ratios to FP were 1.05 [0.83 to 1.33] for FF/VI 100/25 µg and 1.09 [0.87 to 1.38] for FF/VI 200/25 µg). No clinically important changes in non-fasting glucose, potassium, QT interval corrected using Fridericia's formula (QTc[F]) or ophthalmic assessments were reported. Pulse rate (10 min post dose [Tmax], Week 52) was significantly increased with FF/VI versus FP (3.4 bpm, 95% CI 1.3 to 5.6; p=0.002 [FF/VI 100/25 µg]; 3.4 bpm, 95% CI 1.2 to 5.6; p=0.003 [FF/VI 200/25 µg]). Mean heart rate (24-h Holter monitoring) decreased from screening values in all groups (0.2-1.1 bpm FF/VI vs 5 bpm FP; Week 52).



FF/VI (100/25 µg or 200/25 µg) administered once daily over 52 weeks was well tolerated by patients aged ≥12 years with asthma. The overall safety profile of FF/VI did not reveal any findings of significant clinical concern.