nils-herrmann/clean_scirepeval huggingface dataset:
Delay in diagnosis of lung cancer in general practice.

Lung cancer is a common cancer disease; nevertheless, in Denmark a GP only sees one new case of lung cancer per year. The core symptoms of lung cancer, cough and dyspnoea, are on the other hand very common in general practice. This represents a challenge to the diagnostic process and increases the risk of diagnostic delay.



To explore diagnostic delay in primary health care among patients with lung cancer.



A population based observational case series of 84 lung cancer patients' delay.



The County of Aarhus, Denmark.



From county-based registers of all histological and cytological tests we identified all patients in the County of Aarhus with lung cancer diagnosed during a 6 month period in 2003. Inclusion was verified by contacting the departments involved in the treatment of lung cancer. Data were based on telephone interviews with patients' GPs. A review of delay was made starting with the first symptom until referral to secondary care.



The overall median delay in primary health care was 32.5 days (interquartile interval (IQI) = 12-68 days). One-third of the patients were referred to the diagnostic investigation after their first consultation. Important reasons for delay in primary care were: symptoms not related to the lungs, chest X-ray without suspicion of cancer, comorbidity, waiting times for investigations and lack of explicit follow-up appointment. Prolonged delay was often due to a combination of these factors.



When diagnosing lung cancer, it is important that GPs are aware of the low sensitivity of chest X-ray. Shorter waiting times for investigations could reduce delay considerably.
Feasibility and efficacy of simultaneous integrated boost intensity-modulated radiation therapy in patients with limited-disease small cell lung cancer

To evaluate the feasibility and efficacy of simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT) in patients with limited-disease small-cell lung cancer (LD-SCLC).



Patients with LD-SCLC were treated with SIB-IMRT within 1 week after completion of 2 cycles of induction chemotherapy. Then 2-4 cycles of adjuvant chemotherapy were administered within 1 week after SIB-IMRT. Irradiation was given accelerated hyper-fractionated with the prescribed dose 57Gy at 1.9Gy twice daily to the gross tumor volume (GTV) , 51Gy at 1.7Gy twice daily to the clinical tumor volume (CTV) and 45Gy at 1.5Gy twice daily to the planning target volume (PTV). The chemotherapy regimen consisted of platinum plus etoposide. Prophylactic cranial radiation (25Gy in 10 fractions) was administered to patients who got complete response (CR) or near complete response (nCR). The primary endpoint of this study was the frequency of grade 3 or higher acute non-hematologic treatment-related toxicities. Secondary end points included objective response, overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRFS).



A cohort of 35 patients were enrolled in the study, the biological equivalent dose (BED) of the GTV in the SIB-IMRT was 59.16Gy. Grade 1, 2, and 3 esophagitis were observed in 11 (31%), 12 (34%), and 6 (17%) patients, respectively; Grade 1 and 2 pneumonitis were observed in 8 (23%) and 4 (11%) patients, respectively. The median OS and PFS of the whole group were 37.7 months and 29.3 months, respectively. The 1- and 2-year OS was 94.1% and 68.5%, respectively. The 1- and 2-year PFS was 76.8% and 40.7%, respectively. The 1- and 2-year LRFS was 87.7% and 73.8%, respectively.



SIB-IMRT was feasible and well-tolerated in patients with LD-SCLC, and worth further evaluating in a large prospective clinical trial.
Factors associated with condom use problems during vaginal sex with main and non-main partners.

Incorrect condom use is a common problem that can undermine their prevention impact. We assessed the prevalence of 2 condom use problems, breakage/slippage and partial use, compared problems by partnership type, and examined associations with respondent, partner, and partnership characteristics.



Data were collected at 3-month intervals during a 12-month period (1999-2000) among urban sexually transmitted disease (STD) clinic users. Condom use problems were compared between partnership types using z tests for equality of proportions. Logistic generalized estimating equations modeling accounted for within-participant correlation of repeated measures.



Overall 3297 respondents reported 9304 main and 6793 non-main partnerships; condoms were used at least once in 4942 (53.0%) and 4523 (66.6%) of these partnerships, respectively. Condom breakage/slippage was reported during 6.0% of uses (5.1% main, 9.4% non-main) and partial use during 12.5% of uses (12.8% main, 11.5% non-main). The proportion of respondents experiencing any condom use problem in the prior 3 months was higher among main compared with non-main partnerships: 39.1% versus 29.9% had either problem; 22.5% versus 19.0% had breakage/slippage only; 21.8% versus 18.7% had partial use; and 8.7% versus 7.1% had both use problems. In multivariable analysis, factors associated with condom use problems varied by partnership type and respondent sex. The most common predictors of problems across models were sex while high and inconsistent condom use.



This study highlights the diverse set of risk factors for condom use problems at the individual, partner, and partnerships levels.
The effects of progressive-resisted exercises on muscle strength and health-related quality of life in persons with HIV-related poly-neuropathy in Zimbabwe.

Distal symmetrical poly-neuropathy (DSP) is a neurological complication associated with HIV/AIDS and stavudine (d4T) containing antiretroviral therapy. People with DSP experience pain, numbness and muscle weakness, which affect their quality of life (QOL). The purpose of this study was to establish the effect of a progressive-resisted exercise (PRE) intervention on health-related quality of life (HR-QOL) in people living with HIV/AIDS-related DSP. An assessor-blinded randomised controlled trial was conducted, with participants sourced from 10 clinics with HIV services, the family care clinic at Wilkins Hospital and 2 large hospitals in Harare, Zimbabwe. A 12-week PRE intervention was conducted twice weekly for 80 participants, while the control group with 80 participants continued with usual daily activities. The main outcome variable was HR-QOL for which we controlled for demographic and clinical measures in generalised estimating equation population-averaged models. Data were summarised and analysed using an intention to treat analysis approach using the Stata v10 program. Mean age of participants was 42.2 years (SD = 8.5). While d4T was used by 59% (n = 94), an equal proportion of the participants also had moderate to severe neuropathy. PRE was found to significantly improve HR-QOL in the intervention group based on the mean difference between the intervention group mean change and the mean change in the control group (F ratio 4.24; p = .04). This study established that PREs have positive effects on HR-QOL for people living with HIV/AIDS-related DSP.
Idiotype-pulsed antigen-presenting cells following autologous transplantation for multiple myeloma may be associated with prolonged survival.

Vaccines are attractive as consolidation therapy after autologous stem cell transplantation (ASCT) for multiple myeloma (MM). We report the results of a phase II trial of the immunotherapeutic, APC8020 (Mylovenge), given after ASCT for MM. We compared the results with that of other patients with MM who underwent ASCT at Mayo Clinic during the same time period. Twenty-seven patients were enrolled on the trial between July, 1998 and June, 2001, and the outcomes were compared to that of 124 consecutive patients transplanted during the same period, but not enrolled on the trial. The median (range) follow-up for patients still alive from the vaccine trial is 6.5 (2.9-8 years), and 7.1 (6-8 years) in the control group. The median age was 57.4 range (36.1-71.3) in the DB group and 56.4 (range, 30-69) in the trial group. Known prognostic factors including PCLI, B2M, and CRP were comparable between the groups. The median overall survival for the trial patients was 5.3 years (95% CI: 4.0 years-N/A) compared to 3.4 years (95% CI: 2.7-4.6 years) for the DB group (P = 0.02). The median time to progression and progression-free survival for the trial group was similar to the DB group. Although not a controlled trial, the vaccines given after ASCT appear to be associated with improved overall survival compared to historical controls. This approach warrants further investigation to confirm this and define the role of vaccine therapy in myeloma.
Prospective cohort study of ultrasound-ultrasound and ultrasound-MR enterography agreement in the evaluation of pediatric small bowel Crohn disease

There is a paucity of published literature describing ultrasound (US)-US and US-MR enterography (MRE) inter-radiologist agreement in pediatric small bowel Crohn disease. To prospectively assess US-US and US-MRE inter-radiologist agreement in pediatric small bowel Crohn disease.  Board approval and informed consent/assent were obtained for this HIPAA-compliant prospective cohort study of children with newly diagnosed distal small bowel Crohn disease (July 2012 to December 2014). Enrolled subjects (n = 29) underwent two small bowel US examinations performed by blinded independent radiologists both before and at multiple time points after initiation of medical therapy (231 unique US examinations, in total); 134 US examinations were associated with concurrent MRE. The MRE examination was interpreted by a third blinded radiologist. The following was documented on each examination: involved length of ileum (cm); maximum bowel wall thickness (mm); amount of bowel wall and mesenteric Doppler signal, and presence of stricture, penetrating disease and/or abscess. Inter-radiologist agreement was assessed with single-measure, three-way, mixed-model intra-class correlation coefficients (ICC) and prevalence-adjusted, bias-adjusted kappa statistics (κ). Numbers in brackets are 95% confidence intervals. Ultrasound-US agreement was moderate for involved length (ICC: 0.41 [0.35-0.49]); substantial for maximum bowel wall thickness (ICC: 0.67 [0.64-0.70]); moderate for bowel wall Doppler signal (ICC: 0.53 [0.48-0.59]); slight for mesenteric Doppler signal (ICC: 0.25 [0.18-0.42]), and moderate to almost perfect for stricture (κ: 0.54), penetrating disease (κ: 0.80), and abscess (κ: 0.96). US-MRE agreement was moderate for involved length (ICC: 0.42 [0.37-0.49]); substantial for maximum bowel wall thickness (ICC: 0.66 [0.65-0.69]), and substantial to almost perfect for stricture (κ: 0.61), penetrating disease (κ: 0.72) and abscess (κ: 0.88). Ultrasound-US agreement was similar to US-MRE agreement for assessing pediatric small bowel Crohn disease. Discrepancies in US-US and US-MRE reporting question the utility of US as an accurate, reproducible radiologic biomarker for assessing response to medical therapy and disease-related complications.
Steroid pulse therapy for rheumatoid arthritis: effect on lymphocyte subsets and mononuclear cell adhesion.

Eighteen patients with clinically active rheumatoid arthritis, satisfying the ARA criteria, were admitted to hospital for i.v. methylprednisolone pulse therapy. Studies of circulating lymphocyte subsets 1 h before and 24 h after pulsing were carried out together with studies on their adhesion to endothelium-containing lamina propria of porcine gut at various time points. Additionally, circulating VCAM-1 was estimated pre- and post-pulse by ELISA. We observed a marked fall (59%) in mononuclear cell adhesion 24 h post-pulse therapy (P < 0.001). Accompanying this was a significant, though slight, fall in circulating mononuclear cells (P < 0.01), mainly involving T cells. However, the degree of reduction in cell adhesion did not appear to reflect change in any particular circulating subset, but was more likely due to changes in adhesion molecule expression of several subsets. No significant change in circulating VCAM-1 was observed. It would appear, therefore, that the early beneficial effect of steroid pulsing in rheumatoid arthritis coincides with a demonstrable reduction in cell adhesion to gut. This may have implications for the pathogenesis of this disease.
Phase 1 clinical results with tandutinib (MLN518), a novel FLT3 antagonist, in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome: safety, pharmacokinetics, and pharmacodynamics.

Tandutinib (MLN518/CT53518) is a novel quinazoline-based inhibitor of the type III receptor tyrosine kinases: FMS-like tyrosine kinase 3 (FLT3), platelet-derived growth factor receptor (PDGFR), and KIT. Because of the correlation between FLT3 internal tandem duplication (ITD) mutations and poor prognosis in acute myelogenous leukemia (AML), we conducted a phase 1 trial of tandutinib in 40 patients with either AML or high-risk myelodysplastic syndrome (MDS). Tandutinib was given orally in doses ranging from 50 mg to 700 mg twice daily The principal dose-limiting toxicity (DLT) of tandutinib was reversible generalized muscular weakness, fatigue, or both, occurring at doses of 525 mg and 700 mg twice daily. Tandutinib's pharmacokinetics were characterized by slow elimination, with achievement of steady-state plasma concentrations requiring greater than 1 week of dosing. Western blotting showed that tandutinib inhibited phosphorylation of FLT3 in circulating leukemic blasts. Eight patients had FLT3-ITD mutations; 5 of these were evaluable for assessment of tandutinib's antileukemic effect. Two of the 5 patients, treated at 525 mg and 700 mg twice daily, showed evidence of antileukemic activity, with decreases in both peripheral and bone marrow blasts. Tandutinib at the MTD (525 mg twice daily) should be evaluated more extensively in patients with AML with FLT3-ITD mutations to better define its antileukemic activity.
Resurfacing hemiarthroplasty compared to stemmed hemiarthroplasty for glenohumeral osteoarthritis: a randomised clinical trial

The aim of this study was to conduct a randomised, clinical trial comparing stemmed hemiarthroplasty and resurfacing hemiarthroplasty in the treatment of glenohumeral osteoarthritis. A total of 40 shoulders (35 patients) were randomised to stemmed hemiarthroplasty or resurfacing hemiarthroplasty and evaluated three and 12 months postoperatively using the Constant-Murley score (CMS) and Western Ontario Osteoarthritis of the Shoulder (WOOS) index. There were no statistically significant differences in age, gender or pre-operative scores except for WOOS at baseline. Two patients were lost to follow-up. Significant improvements in CMS and WOOS were observed at one year after both arthroplasty designs. At one year, the mean CMS was 48.9 (range 6–80) after resurfacing hemiarthroplasty and 59.1 (range 0–88) after stemmed hemiarthroplasty {mean difference 10.2 [95 % confidence interval (CI) −3.3 to 23.6], P = 0.14}. The mean WOOS was 59.2 (range 5.2–100.0) and 79.4 (range 12.8–98.6), respectively [mean difference 20.2 (95 % CI 3.4–36.9), P = 0.02]. No major complications occurred and there were no revisions. The effects of resurfacing hemiarthroplasty tended to be inferior to those of stemmed hemiarthroplasty. It is unclear whether this reflects a real difference in effect or baseline differences due to the limited number of randomised patients. We suggest there is a need for a larger, more definitive trial.
Accelerated biological ageing in HIV-infected individuals in South Africa: a case–control study

Little is known about the impact of HIV infection on biological ageing in sub-Saharan Africa. The study aimed to assess biological ageing in South African HIV-infected adults and HIV-seronegative individuals using two validated biomarkers, telomere length and CDKN2A expression (a mediator of cellular senescence).



A case-control study.



Two hundred and thirty-six HIV-infected adults aged at least 30 years and 250 age and sex frequency matched HIV-seronegative individuals were recruited from clinics in township communities in Cape Town. Biological ageing was evaluated by measurement of telomere length and CDKN2A expression in peripheral blood leukocytes.



The median ages of the HIV-infected and HIV-seronegative participants were 39 and 40 years, respectively. Among HIV-infected participants, 87.1% were receiving antiretroviral therapy (ART), their median CD4⁺ cell count was 468 cells/μl and 84.3% had undetectable viral load. Both biomarkers were validated against chronological age in HIV-seronegative individuals. Telomere length was significantly shorter in HIV-infected individuals than in HIV-seronegative individuals (mean relative T/S ratio ±SE:0.91 ± 0.007 vs. 1.07 ± 0.008, P < 0.0001). CD2NKA expression was higher in HIV-infected participants than in HIV-seronegative individuals (mean expression: 0.45 ± 0.02 vs. 0.36 ± 0.03, P = 0.003). Socioeconomic factors were not associated with biological ageing in HIV-infected participants. However, in participants on ART with undetectable viral load, biomarker levels indicated greater biological ageing in those with lower current CD4⁺ cell counts.



Telomere length and CDKN2A expression were both consistent with increased biological ageing in HIV-infected individuals. Prospective studies of the impact of HIV on biological ageing in sub-Saharan Africa are warranted.
Phase I trial of split-dose induction docetaxel, cisplatin, and 5-fluorouracil (TPF) chemotherapy followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1)

Induction chemotherapy (ICT) with docetaxel, cisplatin and fluorouracil (TPF) followed by radiotherapy is an effective treatment option for unresectable locally advanced head and neck cancer. This phase I study was designed to investigate the safety and tolerability of a split-dose TPF ICT regimen prior to surgery for locally advanced resectable oral and oropharyngeal cancer. Patients received TPF split on two dosages on day 1 and 8 per cycle for one or three 3-week cycles prior to surgery and postoperative radiotherapy or radiochemotherapy. Docetaxel was escalated in two dose levels, 40 mg/m2 (DL 0) and 30 mg/m2 (DL −1), plus 40 mg/m2 cisplatin and 2000 mg/m2 fluorouracil per week using a 3 +3 dose escalation algorithm. Eighteen patients were enrolled and were eligible for toxicity and response. A maximum tolerated dose of 30 mg/m2 docetaxel per week was reached. The most common grade 3+ adverse event was neutropenia during ICT in 10 patients. Surgery reached R0 resection in all cases. Nine patients (50%) showed complete pathologic regression. A split-dose regime of TPF prior to surgery is feasible, tolerated and merits additional investigation in a phase II study with a dose of 30 mg/m docetaxel per week. NCT01108042 (ClinicalTrials.gov Identifier)
Multiplexed Serum Biomarkers for the Detection of Lung Cancer

Currently, there is no available biomarker for lung cancer diagnosis. Here we recruited 844 lung cancer patients and 620 healthy participants from six hospitals. A total of four serum proteins was identified and subsequently assessed in the training and validation cohorts. The concentrations of four serum proteins were found to be significantly higher in lung cancer patients compared with healthy participants. The area under the curve (AUC) for the 4-biomarker were 0.86 in the training cohort, and 0.87 in the validation cohort. The classification improved to a corrected AUC of 0.90 and 0.89 respectively following addition of sex, age and smoking status. Similar results were observed for early-stage lung cancer. Remarkably, in a blinded test with a suspicious pulmonary nodule, the adjusted prediction model correctly discriminated the patients with 86.96% sensitivity and 98.25% specificity. These results demonstrated the 4-biomarker panel improved lung cancer prediction beyond that of known risk factors. Moreover, the biomarkers were valuable in differentiating benign nodules which will remain indolent from those that are likely to progress and therefore might serve as an adjuvant diagnosis tool for LDCT scanning.
Effects of trauma, hemorrhage and resuscitation in aged rats

Traumatic brain injury (TBI) is a leading cause of death in the elderly and the incidence of mortality and morbidity increases with age. This study tested the hypothesis that, after TBI followed by hemorrhagic hypotension (HH) and resuscitation, cerebral blood flow (CBF) would decrease more in aged compared with young rats. Young adult (4-6 months) and aged (20-24 months) male Sprague-Dawley rats were anesthetized with isoflurane, prepared for parasagittal fluid percussion injury (FPI) and randomly assigned to receive either moderate FPI (2.0 atm) only, moderate FPI+severe HH (40 mm Hg for 45 min) followed by return of shed blood, or sham FPI. Intracranial pressure (ICP), CBF, and mean arterial pressure (MAP) were measured and, after twenty-four hours survival, the rats were euthanized and their brains were sectioned and stained with Fluoro-Jade (FJ), a dye that stains injured neurons. After moderate FPI, severe HH and reinfusion of shed blood, MAP and CBF were significantly reduced in the aged group, compared to the young group. Both FPI and FPI+HH groups significantly increased the numbers of FJ-positive neurons in hippocampal cell layers CA1, CA2 and CA3 (p<0.05 vs Sham) in young and aged rats. Despite differences in post-resuscitation MAP and CBF, there were no differences in the numbers of FJ-positive neurons in aged compared to young rats after FPI, HH and blood resuscitation. Although cerebral hypoperfusion in the aged rats was not associated with increased hippocampal cell injury, the trauma-induced reductions in CBF and post-resuscitation blood pressure may have resulted in damage to brain regions that were not examined or neurological or behavioral impairments that were not assessed in this study. Therefore, the maintenance of normal blood pressure and cerebral perfusion would be advisable in the treatment of elderly patients after TBI.
Effect of thigh strength on incident radiographic and symptomatic knee osteoarthritis in a longitudinal cohort.

To assess whether knee extensor strength or hamstring:quadriceps (H:Q) ratio predicts risk for incident radiographic tibiofemoral and incident symptomatic whole knee osteoarthritis (OA) in adults ages 50-79 years.



We followed 1,617 participants (2,519 knees) who, at the baseline visit of the Multicenter Osteoarthritis (MOST) Study, did not have radiographic tibiofemoral OA and 2,078 participants (3,392 knees) who did not have symptomatic whole knee OA (i.e., did not have the combination of radiographic OA and frequent knee symptoms). Isokinetic strength was measured at baseline, and participants were followed for development of incident radiographic tibiofemoral OA, or incident symptomatic whole knee OA at 30 months. Generalized estimating equations accounted for 2 knees per subject, and multivariable models adjusted for age, body mass index (BMI), hip bone mineral density, knee surgery or pain, and physical activity score.



In the studies of incident radiographic and incident symptomatic knee OA, mean +/- SD ages were 62.4 +/- 8.0 years and 62.3 +/- 8.0 years, respectively, and mean +/- SD BMI scores were 30.6 +/- 5.8 kg/m(2) and 30.2 +/- 5.5 kg/m(2), respectively. Knee extensor strength and H:Q ratio at baseline significantly differed between men and women. Neither knee extensor strength nor the H:Q ratio was predictive of incident radiographic tibiofemoral OA. Compared with the lowest tertile, the highest tertile of knee extensor strength protected against development of incident symptomatic whole knee OA in both sexes (adjusted odds ratio 0.5-0.6). Q ratio was not predictive of incident symptomatic whole knee OA in either sex.



Thigh muscle strength does not appear to predict incident radiographic OA, but does seem to predict incident symptomatic knee OA.