nils-herrmann/clean_scirepeval huggingface dataset:
Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression.

Several non-Hodgkin lymphoma (NHL) subtypes, including diffuse large B-cell lymphoma (DLBCL), variably express CD30. This phase 2, open-label study evaluated the efficacy of brentuximab vedotin, an anti-CD30 antibody-drug conjugate, in relapsed/refractory CD30(+) NHL. This planned subset analysis of B-cell NHLs includes 49 patients with DLBCL and 19 with other B-cell NHLs. Objective response rate was 44% for DLBCL, including 8 (17%) complete remissions (CRs) with a median duration of 16.6 months thus far (range, 2.7 to 22.7+ months). There was no statistical correlation between response and level of CD30 expression; however, all responding patients had quantifiable CD30 by computer-assisted assessment of immunohistochemistry. DLBCL patients were generally refractory to first-line (76%) and most recent therapies (82%), and 44% of these refractory patients responded (15% CRs). Patients with other B-cell lymphomas also responded: 1 CR, 2 partial responses (PRs) of 6 with gray zone, 1 CR of 6 with primary mediastinal B-cell, and 1 CR of 3 with posttransplant lymphoproliferative disorder. Adverse events were consistent with known toxicities. The combination of brentuximab vedotin with rituximab was generally well tolerated and had activity similar to brentuximab vedotin alone. Overall, significant activity with brentuximab vedotin was observed in relapsed/refractory DLBCL, and responses occurred across a range of CD30 expression.
A phase II study of an herbal decoction that includes Astragali radix for cancer-associated anorexia in patients with advanced cancer.

Anorexia and cancer cachexia produce significant loss of adipose tissue and muscle mass and eventually reduce survival in cancer patients.



This phase II study was conducted to assess the efficacy and the safety of an herbal decoction with Astragali radix in patients with anorexia in advanced cancer.



All patients with histologic evidence of an incurable malignancy had a weight loss of at least 5% during the preceding 6 months and a patient-estimated severe anorexia.The herbal decoction was administered 30 minutes after meals, three times a day for 3 weeks.The score of appetite, body weight, the cytokines, IL-1beta, IL-6, TNF-alpha, and anthropometric measurements were assessed. For the assessment of anorexia, a visual analog scale (VAS: 0 mm = no anorexia, 100 mm = maximal anorexia) was used.



Eleven patients were recruited from January, 2007 to January, 2009. The mean age was 59.8 years old. The change in anorexia from baseline with the herbal decoction was significantly different and anorexia was improved (anorexia VAS score, 60 mm vs. 40 mm, p = 0.008). The mean value of the maximal body weight was 55.6 kg and differed significantly from the 54.6 kg at baseline (p = 0.009). Changes in cytokine levels and anthropometric measurements from baseline to the 3rd week were not significant. All toxicities were manageable.



Appetite and body weight were improved with the herbal decoction. This herbal decoction shows some potential for management of cancer-related anorexia.
Prospective comparison of a conventional and an accelerated protocol for programmed ventricular stimulation in patients with coronary artery disease.

This study compared the sensitivity, specificity, and efficiency of a "conventional" and "accelerated" programmed stimulation protocol in 293 patients with coronary artery disease who had a history of sustained or nonsustained monomorphic ventricular tachycardia (VT).



In the conventional protocol, one and two extrastimuli were introduced during sinus rhythm and during basic drive trains at cycle lengths of 600 and 400 msec at the right ventricular apex and then at the outflow tract or septum. In the accelerated protocol, one, two, and then three extrastimuli were introduced at each of three basic drive train cycle lengths (350, 400, and 600 msec) at the right ventricular apex; the procedure was repeated at a second right ventricular site. Six hundred thirty-four electrophysiological tests were performed using one of these two protocols either in the baseline state (293 tests) or during drug testing (341 tests). The yield of sustained, monomorphic VT was 89% with the conventional protocol and 92% with the accelerated protocol during baseline tests in patients who had a history of sustained VT (p = 0.05); 20% and 34%, respectively, during baseline tests in patients with a history of nonsustained VT (p = 0.06); and 70% and 77%, respectively, during drug testing (p = 0.2). To induce sustained, monomorphic VT, 10.1 +/- 5.0 (mean +/- SD) protocol steps and 14.4 +/- 8.7 minutes were required with the conventional protocol, compared with 4.0 +/- 3.7 steps and 5.6 +/- 6.1 minutes with the accelerated protocol (p less than 0.001 for each comparison). Among the tests in which sustained, monomorphic VT was induced, sustained polymorphic VT or ventricular fibrillation was induced more often with the conventional protocol (3.6%) than with the accelerated protocol (0.9%, p = 0.05).



The efficiency of programmed stimulation can be improved by the early use of a basic drive train cycle length of 350 msec and three extrastimuli. Compared with a conventional stimulation protocol, the accelerated protocol used in this study reduces the number of protocol steps and duration of time required to induce monomorphic VT by an average of more than 50% and improves the specificity of programmed stimulation without impairing the yield of monomorphic VT.
The Maintaining Musculoskeletal Health (MAmMOTH) Study: Protocol for a randomised trial of cognitive behavioural therapy versus usual care for the prevention of chronic widespread pain

Cognitive behavioural therapy (CBT) has been shown to improve outcomes for patients with fibromyalgia, and its cardinal feature chronic widespread pain (CWP). Prediction models have now been developed which identify groups who are at high-risk of developing CWP. It would be beneficial to be able to prevent the development of CWP in these people because of the high cost of symptoms and because once established they are difficult to manage. We will test the hypothesis that among patients who are identified as at high-risk, a short course of telephone-delivered CBT (tCBT) reduces the onset of CWP. We will further determine the cost-effectiveness of such a preventative intervention.



The study will be a two-arm randomised trial testing a course of tCBT against usual care for prevention of CWP. Eligible participants will be identified from a screening questionnaire sent to patients registered at general practices within three Scottish health boards. Those returning questionnaires indicating they have visited their doctor for regional pain in the last 6 months, and who have two of, sleep problems, maladaptive behaviour response to illness, or high number of somatic symptoms, will be invited to participate. After giving consent, participants will be randomly allocated to either tCBT or usual care. We aim to recruit 473 participants to each treatment arm. Participants in the tCBT group will have an initial assessment with a CBT therapist by telephone, then 6 weekly sessions, and booster sessions 3 and 6 months after treatment start. Those in the usual care group will receive no additional intervention. Follow-up questionnaires measuring the same items as the screening survey questionnaire will be sent 3, 12 and 24 months after start of treatment. The main outcome will be CWP at the 12 month questionnaire.



This will be the first trial of an intervention aimed at preventing fibromyalgia or CWP. The results of the study will help to inform future treatments for the prevention of chronic pain, and aetiological models of its development.


 Please check that the following URLs are working. If not, please provide alternatives: NCT02668003Alternative is: https://www.clinicaltrials.gov/ct2/show/NCT02668003> .
Human Immunodeficiency Virus nef signature sequences are associated with pulmonary hypertension.

Severe pulmonary hypertension (PH) associated with vascular remodeling is a long-term complication of HIV infection (HIV-PH) affecting 1/200 infected individuals vs. 1/200,000 frequency in the uninfected population. Factors accounting for increased PH susceptibility in HIV-infected individuals are unknown. Rhesus macaques infected with chimeric SHIVnef virions but not with SIV display PH-like pulmonary vascular remodeling suggesting that HIV-Nef is associated with PH; these monkeys showed changes in nef sequences that correlated with pathogenesis after passage in vivo. We further examined whether HIV-nef alleles in HIV-PH subjects have signature sequences associated with the disease phenotype. We evaluated specimens from participants with and without HIV-PH from European Registries and validated results with samples collected as part of the Lung-HIV Studies in San Francisco. We found that 10 polymorphisms in nef were overrepresented in blood cells or lung tissue specimens from European HIV-PH individuals but significantly less frequent in HIV-infected individuals without PH. These polymorphisms mapped to known functional domains in Nef. In the validation cohort, 7/10 polymorphisms in the HIV-nef gene were confirmed; these polymorphisms arose independently from viral load, CD4(+) T cell counts, length of infection, and antiretroviral therapy status. Two out of 10 polymorphisms were previously reported in macaques with PH-like pulmonary vascular remodeling. Cloned recombinant Nef proteins from clinical samples down-regulated CD4, suggesting that these primary isolates are functional. This study offers new insights into the association between Nef polymorphisms in functional domains and the HIV-PH phenotype. The utility of these polymorphisms as predictors of PH should be examined in a larger population.
Eculizumab for dense deposit disease and C3 glomerulonephritis.

The principle defect in dense deposit disease and C3 glomerulonephritis is hyperactivity of the alternative complement pathway. Eculizumab, a monoclonal antibody that binds to C5 to prevent formation of the membrane attack complex, may prove beneficial.



In this open-label, proof of concept efficacy and safety study, six subjects with dense deposit disease or C3 glomerulonephritis were treated with eculizumab every other week for 1 year. All had proteinuria >1 g/d and/or AKI at enrollment. Subjects underwent biopsy before enrollment and repeat biopsy at the 1-year mark.



The subjects included three patients with dense deposit disease (including one patient with recurrent dense deposit disease in allograft) and three patients with C3 glomerulonephritis (including two patients with recurrent C3 glomerulonephritis in allograft). Genetic and complement function testing revealed a mutation in CFH and MCP in one subject each, C3 nephritic factor in three subjects, and elevated levels of serum membrane attack complex in three subjects. After 12 months, two subjects showed significantly reduced serum creatinine, one subject achieved marked reduction in proteinuria, and one subject had stable laboratory parameters but histopathologic improvements. Elevated serum membrane attack complex levels normalized on therapy and paralleled improvements in creatinine and proteinuria.



Clinical and histopathologic data suggest a response to eculizumab in some but not all subjects with dense deposit disease and C3 glomerulonephritis. Elevation of serum membrane attack complex before treatment may predict response. Additional research is needed to define the subgroup of dense deposit disease/C3 glomerulonephritis patients in whom eculizumab therapy can be considered.
Effects of resuscitation with crystalloid fluids on cardiac function in patients with severe sepsis

The use of hypertonic crystalloid solutions, including sodium chloride and bicarbonate, for treating severe sepsis has been much debated in previous investigations. We have investigated the effects of three crystalloid solutions on fluid resuscitation in severe sepsis patients with hypotension.



Ninety-four severe sepsis patients with hypotension were randomly assigned to three groups. The patients received the following injections within 15 min at initial treatment: Ns group (n = 32), 5 ml/kg normal saline; Hs group (n = 30), with 5 ml/kg 3.5% sodium chloride; and Sb group (n = 32), 5 ml/kg 5% sodium bicarbonate. Cardiac output (CO), systolic blood pressure, mean arterial pressure (MAP), body temperature, heart rate, respiratory rate and blood gases were measured.



There were no differences among the three groups in CO, MAP, heart rate or respiratory rate during the 120 min trial or the 8 hour follow-up, and no significant differences in observed mortality rate after 28 days. However, improvement of MAP and CO started earlier in the Sb group than in the Ns and Hs groups. Sodium bicarbonate increased the base excess but did not alter blood pH, lactic acid or [HCO3]- values; and neither 3.5% hypertonic saline nor 5% sodium bicarbonate altered the Na+, K+, Ca2+ or Cl- levels.



All three crystalloid solutions may be used for initial volume loading in severe sepsis, and sodium bicarbonate confers a limited benefit on humans with severe sepsis.
Keto acid-supplemented low-protein diet for treatment of adult patients with hepatitis B virus infection and chronic glomerulonephritis.

An open-label, randomized, controlled, single-centre clinical trial to evaluate the effects of low-protein intake, with or without keto acid supplementation, on nutritional status and proteinuria, in patients with hepatitis B virus (HBV) and early stage chronic glomerulonephritis.



Patients with chronic glomerulonephritis and HBV infection were randomized to receive a low-protein diet (0.6-0.8 g/kg ideal body weight [IBW] per day) either without (LP group) or with (sLP group) keto acid supplementation (0.1 g/kg IBW per day), for 12 months. Nutritional, clinical and safety parameters were recorded.



The study included 17 patients (LP group n = 9; sLP group n = 8). Proteinuria and microalbuminuria were significantly lower in the sLP group at 6 and 12 months compared with baseline, and at 12 months compared with the LP group. There were no significant differences in serum creatinine level or estimated glomerular filtration rate. Nutritional parameters (serum albumin and prealbumin) were significantly improved at 12 months, compared with baseline, in the sLP group.



Restriction of dietary protein intake to 0.6-0.8 g/kg IBW per day appears to have an acceptable safety profile. Supplementation with keto acids is associated with decreased urine protein excretion.
Incidence of recurrent venous thromboembolism of patients after termination of treatment with ximelagatran

Recurrent thromboembolic events may occur after termination of anticoagulant therapy for acute venous thromboembolism (VTE) using oral direct thrombin inhibitor ximelagatran. Patients with VTE recruited at the German study centres were followed-up for an additional 18 months, treated initially with 2×36 mg ximelagatran daily or with enoxaparin/warfarin over 6 months (THRIVE Treatment study) and 2×24 mg ximelagatran daily or placebo over 18 months (THRIVE III study). Recurrent VTE and the combined outcome events consisting of recurrent VTE, other thrombotic complication, major bleeding and mortality were analysed. In the THRIVE Treatment study, no patient suffered from a recurrent VTE, but 1 patient randomised to enoxaparin/warfarin experienced major bleeding. During follow-up, 4/32 and 3/32 patients initially randomised to ximelagatran and enoxaparin/warfarin developed recurrent VTE (p=0.7024). No major bleed occurred. One patient in each group died. The incidences of the combined outcome events were not different (p=0.9326). In the THRIVE III study, 0/9 versus 5/14 patients randomised to ximelagatran and placebo developed recurrent VTE including 1 fatal pulmonary embolism (p=0.0501). During follow-up, 3/9 and no patients initially randomised to ximelagatran and placebo developed recurrent VTE. One and 3 other outcome events occurred in patients initially randomised to ximelagatran or placebo. During follow-up, recurrent VTE (p=0.6893) and combined outcome events (p=0.3642) were not different between the groups. The results of the follow-up studies suggest that thromboembolic events may re-occur in patients with acute VTE after termination of treatment with both vitamin K-antagonists and ximelagatran.
Negative chest X-rays in primary care patients with lung cancer.

The main investigation for suspected lung cancer in primary care is a chest X-ray. Reports from secondary care show that some patients with normal chest X-rays transpire to have lung cancer. The assumption is that this occurs rarely in primary care.



The aim of this study was to examine the frequency of misleading chest X-rays in primary care, and whether there were any particular symptoms associated with them.



Retrospective cohort study of the primary care records of 247 lung cancer patients diagnosed between 1998-2002.



All general practices in Exeter Primary Care Trust, Devon, UK.



All chest X-rays and all common symptoms of lung cancer reported to primary care were identified from the medical records. X-ray results were categorised into three groups by the radiologist's report: normal; abnormal but no malignancy suspected (together classified as negative X-rays); or abnormal with possible malignancy.



Of the 247 patients, 164 (66%) had a chest X-ray taken in primary care during the year before diagnosis: 126 of these (77%) were abnormal with possible malignancy; 21 (13%) were abnormal but with no malignancy suspected; in 17 (10%) the X-ray was reported as normal. Thus, 38 of 164 patients (23%; 95% confidence interval = 16 to 32%) had a negative X-ray. Negative X-rays were less common in the 90 days before diagnosis. No particular symptoms were significantly associated with negative X-rays.



Nearly a quarter of chest X-rays requested from primary care in lung cancer patients are negative. Further investigation is warranted with continuing or changing symptoms, even if the X-ray is not suggestive of malignancy.
Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study.

The aim of the study was to evaluate tolerance and efficacy of preoperative treatment with capecitabine in combination with radiation therapy (RT) in patients with locally advanced, resectable, rectal cancer.



Fifty-three patients with potentially resectable T3, N0-2 (87%) and T4, N0-2 (13%) rectal cancer were treated with capecitabine (825 mg/m2, twice daily for 7 days/week) and concomitant RT (50.4 Gy/28 fractions). Patients underwent surgery after 6-8 weeks followed, upon physician's indications, by 4-months adjuvant capecitabine. The primary end point was to determine the rate of pathologic complete response. Secondary end points were to assess the rate of clinical response and the safety profile.



All patients but two completed the RT programme and 47 (89%) received 81%-100% of the capecitabine dose (100% of dose in 72% patients, 81%-95% in 17% patients and 48%-74% in 11% of patients). No patient had grade 4 toxicity. Grade 3 toxicity occurred in six patients (11%) and consisted mainly of leucopenia (4%) and hand-foot syndrome (4%). Mild or moderate toxicity was common and included leucopenia (72%), diarrhea (40%), proctitis (34%) and skin toxicity (20%). The overall clinical response rate was 58% and the downstaging rate was 57%, with a pathologic complete response rate of 24%. Among 34 patients with low-lying tumors (<or=5 cm from anal verge), 20 (59%) had a sphincter-saving operation.



Preoperative chemoradiation with capecitabine and RT appeared to be effective in locally advanced resectable, rectal cancer. The favorable safety profile of the combination might warrant the use of capecitabine and RT with other effective new drugs.
Effectiveness of weekly cognitive stimulation therapy for people with dementia and the additional impact of enhancing cognitive stimulation therapy with a carer training program

Cognitive stimulation therapy (CST) is a widely used, evidence-based intervention for people with dementia (PwD). Although designed as a 14 session, twice weekly intervention, many services in the UK deliver CST once a week for 14 weeks. However, this method of delivery has yet to be evaluated. In addition, CST does not include any formal carer training. This study aimed to evaluate the effectiveness of once weekly CST and determine any additional impact when enhanced with a carer training program.



A single blind, randomized controlled trial was conducted. Sixty eight PwD and their carers were recruited through three community Memory Assessment Services. PwD and their carers were randomized to one of three conditions: CST plus carer training, CST only, or a wait list control. PwD were administered standardized measures of cognition, quality of life, and quality of relationship with carer at baseline and the 15 week follow-up.



There were no baseline differences across the three groups. At follow-up, there were no significant differences between PwD in the three groups on any outcomes.



Weekly CST with or without carer training may not be an effective form of delivery. Several possible explanations for the outcomes are proposed. Weekly CST may not offer the necessary "dose" required to combat decline, and equally the carer training may have been too brief to have made a difference. Services currently offering weekly CST should collect routine outcome data to support its use and provide practice-based evidence.
A phase 2 study of sequential neoadjuvant chemotherapy with gemcitabine and doxorubicin followed by gemcitabine and cisplatin in patients with large or locally advanced operable breast cancer: results from long-term follow-up.

Neoadjuvant chemotherapy (NACT) is being increasingly used for patients with large-size operable breast cancer. This phase 2 study of sequential NACT with gemcitabine and doxorubicin (Gem + Dox) followed by gemcitabine and cisplatin (Gem + Cis) was conducted in women with large or locally advanced breast cancer. The objectives were to evaluate the pathological complete response (pCR) rate, toxicity, pathological and genetic markers predicting response, the proportion of patients undergoing breast conservation surgery, progression-free survival (PFS) and overall survival (OS) after 5 years, and time to treatment failure (TtTF). In this manuscript, we report the long-term OS, PFS, and TtTF results.



Female patients aged at least 18 years with large T2 (at least 3 cm) or locally advanced (T3, T4, or N2) breast carcinoma were included. Treatment consisted of 4 cycles of Gem + Dox (gemcitabine 1,200 mg/m(2) on days 1 and 8 plus doxorubicin 60 mg/m(2) on day 1 of each 21-day cycle), followed by 4 cycles of Gem + Cis (gemcitabine 1,000 mg/m(2) on days 1 and 8 plus cisplatin 70 mg/m(2) on day 1 of each 21-day cycle), and then surgery.



Sixty-five patients were enrolled. The pCR rate was 20%. The 5-year OS probability was 71% (95% CI 56-82%), and the 4-year PFS and TtTF probabilities were 63% (95% CI 48-74%) and 45% (95% CI 32-57%), respectively.



NACT with Gem + Dox followed by Gem + Cis was efficacious in patients with operable breast cancer.