nils-herrmann/clean_scirepeval huggingface dataset:
Phase 2 trial of clofarabine in combination with etoposide and cyclophosphamide in pediatric patients with refractory or relapsed acute lymphoblastic leukemia.

The outcomes in children with refractory/relapsed (R/R) acute lymphoblastic leukemia (ALL) are dismal. The efficacy and safety of intravenous clofarabine 40 mg/m(2) per day, cyclophosphamide 440 mg/m(2) per day, and etoposide 100 mg/m(2) per day for 5 consecutive days in pediatric patients with R/R ALL was evaluated in this phase 2 study. The primary endpoint was overall response rate (complete remission [CR] plus CR without platelet recovery [CRp]). Among the 25 patients (median age, 14 years; pre-B cell ALL, 84%; ≥ 2 prior regimens: 84%; refractory to previous regimen: 60%), the overall response rate was 44% (7 CR, 4 CRp) with a 67.3-week median duration or remission censored at last follow-up. Most patients proceeded to alternative therapy, and 10 patients (40%) received hematopoietic stem cell transplantation. Six patients (24%) died because of treatment-related adverse events associated with infection, hepatotoxicity, and/or multiorgan failure. The study protocol was amended to exclude patients with prior hematopoietic stem cell transplantation after 4 of the first 8 patients developed severe hepatotoxicity suggestive of veno-occlusive disease. No additional cases of veno-occlusive disease occurred. The regimen offered encouraging response rates and sustained remission in R/R patients. Future investigation should include exploration of patient selection, dosing, and supportive care.
Comparison of two different loading doses of digoxin in severe renal impairment

The correct loading dose of digoxin in patients with advanced renal failure is still a matter of discussion. The effect has been studied of loading doses of digoxin 0.625 mg or 1.25 mg given over 48 h according to randomized crossover design to healthy volunteers and to two different groups of patients with renal impairment and the same mean endogenous creatinine clearance of about 15 ml/min. The subsequent maintenance dose for 4 days was digoxin 0.25 mg in the volunteers and 0.125 mg in both groups of patients. The minimum plasma digoxin concentrations before each dose was measured by radioimmunoassay and the plasma levels in the different groups have been compared. In the healthy volunteers no significant difference was found during the study, despite wide variation in the plasma digoxin concentration. In contrast, in patients with renal failure, the group with the higher loading dose showed significantly higher plasma concentrations 24, 36 and 48 h after drug administration, reaching the highest mean value of 2.2 ng/ml at 48 h. However, after 120 h of maintenance therapy a mean digoxin concentration of 1.3 mg/ml was found in both groups. Thus, despite different loading doses identical plasma concentrations were reached during administration of the same maintenance therapy. The higher plasma digoxin concentration obtained during administration of a higher loading dose might be the cause of arrythmias in individual patients.
Intracranial blood-flow velocity and pressure measurements using an intra-arterial dual-sensor guidewire.

Hemodynamics is thought to play a role in the growth and rupture of intracranial aneurysms. In 4 patients, we obtained local pressure and BFV by using a dual-sensor pressure and Doppler velocity wire within and in vessels surrounding unruptured aneurysms. Local BFVs can serve as boundary conditions for computational fluid dynamics, whereas pressure recordings provide direct information on the mechanical load imposed on the aneurysm. Both measurements may thus add to patient-specific rupture-risk assessment.
The Effect of Targeted and Tailored Patient Depression Engagement Interventions on Patient–Physician Discussion of Suicidal Thoughts: A Randomized Control Trial

Despite improvements in the diagnosis and treatment of depression, primary care provider (PCP) discussion regarding suicidal thoughts among patients with depressive symptoms remains low. To determine whether a targeted depression public service announcement (PSA) video or an individually tailored interactive multimedia computer program (IMCP) leads to increased primary care provider (PCP) discussion of suicidal thoughts in patients with elevated risk for clinical depression when compared to an attention control. Randomized control trial at five different healthcare systems in Northern California; two academic, two Veterans Affairs (VA), and one group-model health maintenance organization (HMO). Eight-hundred sixty-seven participants, with mean age 51.7; 43.9 % women, 43.4 % from a racial/ethnic minority group. The PSA was targeted to gender and socio-economic status, and designed to encourage patients to seek depression care or request information regarding depression. The IMCP was an individually tailored interactive health message designed to activate patients to discuss possible depressive symptoms. The attention control was a sleep hygiene video. Clinician reported discussion of suicidal thoughts. Analyses were stratified by depressive symptom level (Patient Health Questionnaire [PHQ-9] score < 9 [mild or lower] versus ≥ 10 [at least moderate]). Among patients with a PHQ-9 score ≥ 10, PCP discussion of suicidal thoughts was significantly higher in the IMCP group than in the control group (adjusted odds ratio = 2.33, 95 % confidence interval = 1.5, 5.10, p = 0.03). There were no significant effects of either intervention on PCP discussion of suicidal thoughts among patients with a PHQ-9 score < 9. Exposure of patients with at least moderate depressive symptoms to an individually tailored intervention designed to increase patient engagement in depression care led to increased PCP discussion of suicidal thoughts.
Combination therapy with mizoribine for severe childhood IgA nephropathy: a pilot study

In two previous randomized controlled trials we showed that treatment of severe childhood immunoglobulin A nephropathy (IgA-N) using prednisolone, azathioprine, heparin–warfarin, and dipyridamole prevented any increase of sclerosed glomeruli and that prednisolone alone did not prevent a further increase of sclerosed glomeruli. Accordingly, the immunosuppressant is considered to be important. Often, however, we were unable to complete azathioprine regimen due to toxicity. Therefore, a different but effective immunosuppressant may be worth trying. Mizoribine, like azathioprine, is an antimetabolite that exerts its immunosuppressant effect by inhibiting lymphocyte proliferation. In this pilot study, we administered mizoribine instead of azathioprine as part of the combination therapy for treating 23 children with severe IgA-N and evaluated the efficacy and safety. Eighteen patients reached the primary endpoint (urine protein/creatinine ratio <0.2) during the 2-year treatment period. The cumulative disappearance rate of proteinuria determined by Kaplan–Meier was 80.4%. Median protein excretion was reduced from 1.19 g/m2/day to 0.05 g/m2/day (p < 0.0001). After treatment, the median percentage of glomeruli showing sclerosis was unchanged in comparison with that before treatment. No patients required a change of treatment. In conclusion, the efficacy and safety of the mizoribine combination seems to be acceptable for treating children with severe IgA-N.
Monotherapy with lopinavir/ritonavir versus standard of care in HIV-infected patients virologically suppressed while on treatment with protease inhibitor-based regimens: results from the MoLo study.

This study compared the cost-efficacy ratios of lopinavir/ritonavir monotherapy (LPV/r-MT) and of standard of care in virologically suppressed HIV-infected patients. The results of the efficacy and safety analyses are presented. We conducted a multicentre, randomised, open-label trial of HIV-infected adults on stable treatment, with HIV- RNA <50 copies/mL, randomised to continue the ongoing regimen (cART-arm) or to switch to LPV/r (400/100 mg BID) MT (MT-arm). Time to virological rebound (VR = confirmed HIV-RNA ?50 copies/mL) was estimated by Ka- plan-Meier method and changes in laboratory values during follow-up were evaluated by univariate mixed-linear models. Ninety-four patients were randomised and analysed (43 in the MT-arm and 51 in the cART-arm). Five (four in the MT and 1 in the cART-arm; p=0.175) had VR, but time to VR did not statistically differ between the two arms (p=0.143). Major PI mutations were not detected at VR. Patients on MT had significant increases in total choles- terol [difference in mean change between MT and cART arm: 0.77 (±0.30) mg/dL per month; p=0.012] and eGFR [difference in mean change between MT and cART arm: 0.24 (±0.11) mL/min/1.73 m2 per month; p=0.029]. LPV/r-MT seems safe in most patients and should be considered in patients who have developed kidney toxicity from tenofovir.
Clustering of unconventional cardiovascular risk factors among Taiwanese hemodialysis patients.

Cardiovascular disease (CAVD) is the most common cause of mortality for chronic hemodialysis (HD) patients, yet the risk factors for the events have not been well established.



We conducted a multicenter cross-sectional survey in 995 chronic HD patients recruited from 12 HD centers in Taiwan to investigate the prevalence of CAVD, including coronary heart disease (CHD), cerebrovascular disease (CVD), and peripheral vascular disease (PVD), and related them to 30 different parameters.



The mean age of 995 patients (499 males/496 females) was 56.4 +/- 12.3 years, and average HD duration was 59.8 +/- 51.2 months. The prevalence rates of CHD, CVD, and PVD were 24.0, 6.0, and 5.3%, respectively. Results of our multivariate logistic regression analysis showed that out of the conventional CAVD risk factors, only old age and diabetes could be significantly associated with CAVD. Meanwhile, we found some novel clinical correlates, including low apolipoprotein A-I and creatinine for CHD, low uric acid for CVD, and low hematocrit and low diastolic blood pressure for PVD. Interestingly, left ventricular hypertrophy was found to be an independent correlate for all three: CHD, CVD, and PVD.



Our study suggests that consideration of conventional cardiovascular risk factors as well as unconventional risk factors might better assess the risk for CAVD among HD patients.
Pneumoconiosis increases the risk of congestive heart failure

The purpose of the study was to determine the relationship between pneumoconiosis and congestive heart failure (CHF).We collected data from the National Health Insurance Research Database in Taiwan. The study sample comprised 8923 patients with pneumoconiosis and 35,692 nonpneumoconiosis controls enrolled from 2000 to 2011. Patients were followed up until the end of 2011 to evaluate the incidence of CHF. The risk of CHF was analyzed using Cox proportional hazard regression models, and the analysis accounted for factors such as sex, age, comorbidities, and air pollutants (μg/m).The overall incidence of CHF was higher in the pneumoconiosis cohort (15.7 per 1000 person-y) than in the nonpneumoconiosis cohort (11.2 per 1000 person-y), with a crude hazard ratio (HR) of 1.40 (P < 0.001). The HR for CHF was 1.38-fold greater in the pneumoconiosis cohort than in the nonpneumoconiosis cohort (P < 0.001) after the model was adjusted for age, sex, various comorbidities, and air pollutants (μg/m). The relative risk for CHF in the sex-specific pneumoconiosis cohort compared with the nonpneumoconiosis cohort was significant for men (adjusted HR = 1.40, 95% confidence interval = 1.21-1.62, P < 0.001). The incidence density rates of CHF increased with age; pneumoconiosis patients had a higher relative risk of CHF for all age group.Patients with pneumoconiosis were at higher risk for developing CHF than patients in the nonpneumoconiosis cohort, particularly in cases with coexisting coronary artery disease, hypertension, and chronic obstructive pulmonary disease.
Cardiac vagal control in the severity and course of depression: the importance of symptomatic heterogeneity.

Impaired cardiac vagal control (CVC), as indexed by respiratory sinus arrhythmia, has been investigated as a risk factor for major depressive disorder (MDD), but prior findings are mixed with respect to whether impaired CVC predicts greater global depression severity and/or a more severe course of disorder. One possible explanation for mixed findings is that CVC abnormalities in MDD are related more closely to specific depression symptoms than to the syndrome as a whole.



Depression severity (both global and symptom-specific indices) and electrocardiogram measures of resting CVC were obtained from 151 diagnosed MDD participants at intake, before randomization to a novel treatment for depression (acupuncture), and again after 8 and 16 weeks.



Resting CVC did not predict global indices of depression in cross-sectional or longitudinal analyses. In symptom-specific analyses, resting CVC was positively related to sad mood and crying and inversely related to middle and late insomnia. Improvement in late insomnia was related to increases in CVC over time.



Relationships between CVC and MDD were studied only within the clinical range of severity. Symptom analyses were exploratory and hence did not correct for Type I error.



Resting CVC did not exhibit concurrent or prospective relations with overall depression severity but a few specific symptoms did. Symptomatic heterogeneity across samples may account for mixed findings within the CVC-depression literature.
How mindfulness changed my sleep: focus groups with chronic insomnia patients

Chronic insomnia is a major public health problem affecting approximately 10% of adults. Use of meditation and yoga to develop mindful awareness ('mindfulness training') may be an effective approach to treat chronic insomnia, with sleep outcomes comparable to nightly use of prescription sedatives, but more durable and with minimal or no side effects. The purpose of this study was to understand mindfulness training as experienced by patients with chronic insomnia, and suggest procedures that may be useful in optimizing sleep benefits.



Adults (N = 18) who completed an 8-week mindfulness-based stress reduction (MBSR) program as part of a randomized, controlled clinical trial to evaluate MBSR as a treatment for chronic insomnia were invited to participate in post-trial focus groups. Two groups were held. Participants (n = 9) described how their sleep routine, thoughts and emotions were affected by MBSR and about utility (or not) of various mindfulness techniques. Groups were audio-recorded, transcribed and analyzed using content analysis.



Four themes were identified: the impact of mindfulness on sleep and motivation to adopt a healthy sleep lifestyle; benefits of mindfulness on aspects of life beyond sleep; challenges and successes in adopting mindfulness-based practices; and the importance of group sharing and support. Participants said they were not sleeping more, but sleeping better, waking more refreshed, feeling less distressed about insomnia, and better able to cope when it occurred. Some participants experienced the course as a call to action, and for them, practicing meditation and following sleep hygiene guidelines became priorities. Motivation to sustain behavioral changes was reinforced by feeling physically better and more emotionally stable, and seeing others in the MBSR class improve. The body scan was identified as an effective tool to enable falling asleep faster. Participants described needing to continue practicing mindfulness to maintain benefits.



First-person accounts are consistent with published trial results of positive impacts of MBSR on sleep measured by sleep diary, actigraphy, and self-report sleep scales. Findings indicate that mindfulness training in a group format, combined with sleep hygiene education, is important for effective application of MBSR as a treatment for chronic insomnia.
A randomised controlled trial of a theory-based intervention to improve sun protective behaviour in adolescents ('you can still be HOT in the shade'): study protocol

Most skin cancers are preventable by encouraging consistent use of sun protective behaviour. In Australia, adolescents have high levels of knowledge and awareness of the risks of skin cancer but exhibit significantly lower sun protection behaviours than adults. There is limited research aimed at understanding why people do or do not engage in sun protective behaviour, and an associated absence of theory-based interventions to improve sun safe behaviour. This paper presents the study protocol for a school-based intervention which aims to improve the sun safe behaviour of adolescents. Approximately 400 adolescents (aged 12-17 years) will be recruited through Queensland, Australia public and private schools and randomized to the intervention (n = 200) or 'wait-list' control group (n = 200). The intervention focuses on encouraging supportive sun protective attitudes and beliefs, fostering perceptions of normative support for sun protection behaviour, and increasing perceptions of control/self-efficacy over using sun protection. It will be delivered during three × one hour sessions over a three week period from a trained facilitator during class time. Data will be collected one week pre-intervention (Time 1), and at one week (Time 2) and four weeks (Time 3) post-intervention. Primary outcomes are intentions to sun protect and sun protection behaviour. Secondary outcomes include attitudes toward performing sun protective behaviours (i.e., attitudes), perceptions of normative support to sun protect (i.e., subjective norms, group norms, and image norms), and perceived control over performing sun protective behaviours (i.e., perceived behavioural control). The study will provide valuable information about the effectiveness of the intervention in improving the sun protective behaviour of adolescents.
Bowel obstruction after laparoscopic and open colon resection for cancer: Results of 5 years of follow-up in a randomized trial

Postoperative bowel obstruction caused by intra-abdominal adhesions occurs after all types of abdominal surgery. It has been suggested that the laparoscopic technique should reduce the risk for adhesion formation and thus for postoperative bowel obstruction. This study was designed to compare the incidence of bowel obstruction in a randomized trial where laparoscopic and open resection for colon cancer was compared. A retrospective analysis was performed, collecting data of episodes of bowel obstruction with or without surgery. Only episodes treated in the hospital where the index surgery took place were included. Data for 786 patients were collected for the 5-year period after cancer surgery. Baseline characteristics for the evaluated laparoscopic (n = 383) and open (n = 403) groups were comparable. The cumulative obstruction percentages at 5 years for the open and laparoscopic groups were 6.5 and 5.1% respectively and did not significantly differ from each other. Tumor stage seemed to influence the risk for bowel obstruction: 2.8% in stage I, 6.6% in stage II, and 7% in stage III, but the differences were not significant. This analysis does not support the hypothesis that laparoscopy leads to fewer episodes of bowel obstruction compared with open surgery.
The potential immunogenicity of the TK suicide gene does not prevent full clinical benefit associated with the use of TK-transduced donor lymphocytes in HSCT for hematologic malignancies.

Gene therapy is a promising therapeutic strategy for genetic and acquired hematologic diseases. With the improvements in gene transfer and expression, factors affecting safety and efficacy of gene therapy can now be evaluated to establish the best clinical benefit-to-risk ratio. The induction of immune responses against gene therapy components is one of the potential limitations. We studied the occurrence of such event in 23 patients treated with donor lymphocyte infusions (DLIs), with lymphocytes transduced to express the HSV-TK suicide gene for relapse of hematologic malignancies occurring after allogeneic hematopoietic stem cell transplantation (HSCT). The suicide gene was used to selectively control graft-versus-host disease (GvHD). Seven patients given infusions late after HSCT developed an immune response against the transgene. Immunization involved appearance of thymidine kinase (TK)-specific CD8(+) effectors and required a level of immunocompetence at the time of TK-DLI that can be achieved only several months after transplantation. This did not prevent graft-versus-leukemia (GvL) effect of the TK-DLI, since 5 of 7 immunized patients maintained the complete remission achieved prior to immunization. We suggest that appropriate study designs taking into account the immune suppression of the patient and time-kinetics of GvL mediated by TK-transduced donor lymphocytes may allow the full exploitation of TK-DLI.
The Nkateko health service trial to improve hypertension management in rural South Africa: study protocol for a randomised controlled trial

South Africa has a high and rising prevalence of hypertension. Many affected individuals are not using medication, and few have controlled blood pressure. Until recently, primary care clinics focused on maternal and child health and management of acute conditions, but new government initiatives have shifted the focus to chronic diseases, including HIV/AIDS and hypertension.



The Nkateko trial will test the effectiveness of clinic-based lay health workers (LHWs) in supporting hypertension management. It is a pragmatic, cluster randomised controlled trial based in the Agincourt subdistrict of northeast South Africa, and it is underpinned by long-term health and demographic surveillance. Eight primary care facilities, with their catchment communities, are randomised to usual care or the addition of LHWs focused on chronic care. All clinics (intervention and control) will be provided with a clerk to collect information on clinic attendees and will match them to preexisting surveillance records. Intervention clinics will have LHWs working alongside nursing staff and focusing on health care for people with chronic conditions, particularly hypertension. The LHWs will be supported by an implementation manager, who will work with clinic staff to develop the most effective role for the LHWs. Control clinics will continue to provide usual care. The primary outcome will be the change between two population surveys conducted before and after the intervention in the proportion of the population with uncontrolled hypertension and a risk profile indicating at least moderate risk of cardiovascular disease. A process evaluation will be based on a realist approach using patient exit interviews, clinic observations and interviews with health professionals, LHWs and patients to document the intervention and its implementation.



There are challenges in the design of this trial. Assessing change through population surveys may reduce measurable effects; however, we feel this is appropriate because we aim to attract those who currently do not use clinics, and we hope to improve care for clinic users. Clinics were randomised at an open meeting because we were concerned that a remote process of randomisation would not be trusted by the community. We are constantly working to achieve an effective balance between the intervention and process evaluations.