nils-herrmann/clean_scirepeval huggingface dataset:
A phase I trial of the bombesin/gastrin-releasing peptide (BN/GRP) antagonist RC3095 in patients with advanced solid malignancies

Bombesin/gastrin-releasing peptides (BN/GRP) were shown to bind selectively to cell surface receptors, stimulating the growth of various types of malignancies in murine and human models. The novel BN/GRP synthetic receptor antagonist, RC-3095, was able to produce long-lasting tumor regressions in murine and human tumor models in vitro and in vivo. Animal toxicology studies showed no detectable organ toxicity apart from local irritation at the injection site. The purpose of this study was to determine the safety and feasibility of the administration of RC-3095 by daily subcutaneous injections in patients with advanced and refractory solid malignancies. Twenty-five patients received RC-3095 once or twice-daily at doses ranging from 8 to 96 ug/kg. Dose was escalated in groups of 3–5 patients per dose level. The only toxicity observed was local discomfort in the injection site at the highest doses. A single dose administration of RC-3095 at the highest dose level (96 ug/kg) was tested in a clearly hypergastrinemic individual with the Zollingen-Ellison syndrome and produced a decrease in plasma gastrin down to 50% of basal levels in 6 h. There was no objective tumor responses in patients included in the study. A short-lasting minor tumor response was observed in a patient with a GRP-expressing progressive medullary carcinoma of the thyroid. Due to problems with the analytical method, plasma pharmacokinetic data was obtained only from two patients included at the highest dose level. In these patients, RC-3095 reached plasma concentrations >100 ng/mL for about 8 h, which were within therapeutic levels on the basis of prior data obtained in mice and rats. The plasma elimination half-life was between 8.6–10.9 h. Due to the occurrence of local toxicity at the injection site, the dose escalation procedure could not be fully evaluated up to a maximum tolerated dose. Thus, a recommended dose of RC-3095 for Phase II trials could not be clearly established. Considering the novelty of its mechanism of action and impressive preclinical anti-tumor activity, further studies exploiting new formulations of RC-3095 for human use, such as slow-release preparations, and analogues with a more favorable pharmacokinetics are warranted.
Opioid maintenance therapy in Switzerland: an overview of the Swiss IMPROVE study.

Switzerland's drug policy model has always been unique and progressive, but there is a need to reassess this system in a rapidly changing world. The IMPROVE study was conducted to gain understanding of the attitudes and beliefs towards opioid maintenance therapy (OMT) in Switzerland with regards to quality and access to treatment. To obtain a "real-world" view on OMT, the study approached its goals from two different angles: from the perspectives of the OMT patients and of the physicians who treat patients with maintenance therapy. The IMPROVE study collected a large body of data on OMT in Switzerland. This paper presents a small subset of the dataset, focusing on the research design and methodology, the profile of the participants and the responses to several key questions addressed by the questionnaires.



IMPROVE was an observational, questionnaire-based cross-sectional study on OMT conducted in Switzerland. Respondents consisted of OMT patients and treating physicians from various regions of the country. Data were collected using questionnaires in German and French. Physicians were interviewed by phone with a computer-based questionnaire. Patients self-completed a paper-based questionnaire at the physicians' offices or OMT treatment centres.



A total of 200 physicians and 207 patients participated in the study. Liquid methadone and methadone tablets or capsules were the medications most commonly prescribed by physicians (60% and 20% of patient load, respectively) whereas buprenorphine use was less frequent. Patients (88%) and physicians (83%) were generally satisfied with the OMT currently offered. The current political framework and lack of training or information were cited as determining factors that deter physicians from engaging in OMT. About 31% of OMT physicians interviewed were ≥60 years old, indicating an ageing population. Diversion and misuse were considered a significant problem in Switzerland by 45% of the physicians.



The subset of IMPROVE data presented gives a present-day, real-life overview of the OMT landscape in Switzerland. It represents a valuable resource for policy makers, key opinion leaders and drug addiction researchers and will be a useful basis for improving the current Swiss OMT model.
Midazolam for acute emesis refractory to dexamethasone and granisetron after highly emetogenic chemotherapy: a phase II study

To assess whether the addition of midazolam to dexamethasone and granisetron could ameliorate the refractory acute nausea and/or vomiting caused by a highly emetogenic platinum-based chemotherapy. Enrolled in the study were 30 consecutive adult patients with refractory acute emesis. Nausea and vomiting were assessed by physicians and graded according to the NCI common toxicity criteria. Nausea was further self-assessed by patients using a visual analogue scale. Statistical analysis was performed by nonparametric tests. With the introduction of midazolam, 73% of patients had a reduction of at least one grade in nausea and vomiting intensity in comparison with the previous cycle of chemotherapy. From the second cycle, six patients (23%) had complete control of acute vomiting, a benefit that usually persisted in the subsequent cycles. Five more patients achieved complete control of acute vomiting during the third course; this effect persisted in the subsequent courses as well. The average relative reduction in acute nausea and vomiting grade from the first to the second course was 48% (95% CI 34–62%) and 48% (95% CI 31–65%), respectively. A significant difference in acute nausea and vomiting over all the six courses of chemotherapy administered was recorded (Friedman ANOVA, P <0.0001). Comparing each course with any subsequent course, a significant reduction in acute nausea and vomiting was observed between the first and second course, the first and third course, and the first and fourth course. Our results suggest that midazolam may be a useful adjunct to standard antiemetic drugs for patients receiving highly emetogenic cisplatin-based chemotherapy. A randomized trial is warranted to confirm these results.
Very low birth weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, January 1993 through December 1994.

Our purpose was to determine the mortality and morbidity rates for infants weighing 501 to 1500 g according to gestational age, birth weight, and gender.



Perinatal data were collected prospectively on an inborn cohort from January 1993 through December 1994 by 12 participating centers of the National Institute of Child Health and Human Development Neonatal Research Network and were compared with the corresponding data from previous reports. Sociodemographic factors, perinatal events, and the neonatal course to 120 days of life, discharge, or death were evaluated.



Eighty-three percent of infants survived until discharge to home or to a long- term care facility (compared with 74% in 1988). Survival to discharge was 49% for infants weighing 501 to 750 g at birth, 85% for those 751 to 1000 g, 93% for those 1001 to 1250 g, and 96% for those 1251 to 1500 g. The majority of deaths occurred within the first 3 days of life. Mortality rates were greater for male than for female infants. Respiratory distress syndrome was the most frequent pulmonary disease (52%). Chronic lung disease (defined as an oxygen requirement at 36 weeks after conception) developed in 19%. Thirty-two percent of infants had evidence of intracranial hemorrhage. Periventricular leukomalacia was noted in 6% of infants who had ultrasonography after 2 weeks. The average duration of hospitalization for survivors was 68 days (122 days for surviving infants weighing 501 to 750 g, compared with an average of 43 days for surviving infants 1251 to 1500 g). Among infants who died, the average length of stay was 19 days.



The mortality rate for infants weighing between 501 and 1500 g at birth continues to decline. This increase in survival is not accompanied by an increase in medical morbidity. There are interactions between birth weight, gestational age, sex, and survival rates.
Correlation between gastric acid secretion and severity of acid reflux in children.

The purpose of our study was to systematically evaluate gastric acid output in children with long-lasting gastro-esophageal reflux (GER) in order to assess its mechanism and the need for anti-acid treatment. The investigation was carried out in 20 males and 10 females, aged 7.5 +/- 3.8 years, with prolonged (>15 months) clinical manifestations of GER. All underwent routine ambulatory 24-h esophageal pH-monitoring and measurement of gastric acid secretion including gastric basal (BAO) (micromol/kg/h), maximal (MAO) and peak acid outputs (PAO) after pentagastrin (6 microg/kg sec) stimulation. Children with heartburn or abdominal pain underwent upper fiber-endoscopy. In group A (moderate GER, n=12), patients had a normal reflux index (pH<4 below 5.2% of total recording time) despite abnormal Euler and Byrne scoring (median 57, 95% confidence interval 53.5-73.4). In group B (severe GER, n=18, among whom 5 were with grade III esophagitis), reflux index was >5.2%. When considering all children, esophageal pH (%) was significantly correlated with MAO and PAO, r=0.33, p=0.05 and r=0.37, p=0.04, respectively. Children of group B exhibited significantly higher BAO (75, 53.96-137.81), MAO (468, 394.1-671.3) and PAO (617, 518.8-782.3) than those of group A, BAO (27, 10.8-38.5), MAO (266, 243.2-348.2) and PAO (387, 322.5-452.7), p<0.05). The five children of group B with severe esophagitis exhibited significantly higher BAO, MAO and PAO than the other 13 children from the same group and those of group A, p<0.05. Children with long-lasting and severe GER hyper-secrete gastric acid. Individual variations in gastric acid secretion probably account for variations in gastric acid inhibitor requirements. Anti-secretory treatment is justified in children with long-lasting GER and high pH-metric reflux index.
Is self-monitoring of blood glucose appropriate for all type 2 diabetic patients? The Fremantle Diabetes Study.

We sought to determine whether self-monitoring of blood glucose (SMBG) is associated with better glycemic control in type 2 diabetes.



We used cross-sectional and longitudinal data from type 2 diabetic participants in the observational, community-based Fremantle Diabetes Study (FDS) who reported SMBG status at study entry (n = 1,286) and annual reviews over 5 years (n = 531).



At study entry, 70% of patients performed SMBG, with a median of four tests per week (interquartile range two to seven). Patients with shorter diabetes duration; who were attending diabetes education, diabetes-related clinics, or medical specialists; who were taking insulin with or without oral hypoglycemic agents (OHAs); and who were self-reporting hypoglycemic events were more likely to use SMBG. Both cross-sectional and longitudinal FDS data showed that HbA(1c) (A1C) was not significantly different between SMBG users and nonusers, either overall or within diabetes treatment groups (diet, OHAs, and insulin with or without OHAs). There was also no independent cross-sectional relationship between A1C and SMBG frequency. The average annual societal cost of using SMBG (in year 2000 Australian dollars [Adollars], excluding glucometers) was 162 Australian dollars per type 2 diabetic patient or 51 million Australian dollars when projected to the Australian diagnosed type 2 diabetic population.



Neither SMBG testing nor its frequency was associated with glycemic benefit in type 2 diabetic patients regardless of treatment. Our data did not include methods of SMBG delivery and application, factors that require further assessment in the evaluation of SMBG utility in non-insulin-treated type 2 diabetes. SMBG may be still of value in the identification and prevention of hypoglycemia and in dose adjustment in insulin-treated patients.
Evaluation of a randomised controlled trial of adult asthma education in a hospital setting.

Although patient education is a key step in the Australian Asthma Management Plan, its impact has not been assessed in a hospital outpatient asthma clinic.



A controlled trial was undertaken in 125 adults with asthma recruited from the Alfred Hospital Asthma and Allergy Clinic and randomly allocated to an intervention (n = 64) or control (n = 61) group. Subjects in the intervention group attended three education sessions, each of 90 minutes duration, spread over three successive weeks. Asthma knowledge, quality of life, self-management skills, and attitudes and beliefs about asthma were assessed by questionnaires at baseline and after six months. The intervention group was also assessed immediately after the three education sessions. The control group was evaluated after six months of usual care.



Asthma knowledge improved significantly in the intervention group after three education sessions (p = 0.0001) and this was retained six months later (p = 0.03). The impact of asthma on quality of life decreased significantly immediately after intervention (p = 0.03) but this was not maintained six months later (p = 0.35). On the other hand, the intervention had little impact on self-management skills or attitudes and beliefs about asthma. However, the control group had also improved their knowledge, quality of life and self-management skills after six months of usual care. The difference in mean change in knowledge score at six months between the intervention and control groups was not significant (p = 0.51).



In contrast to some other studies, a limited asthma education programme in a hospital outpatient setting had a positive impact on patients' knowledge of asthma, but not on their quality of life, self-management skills, or attitudes and beliefs about asthma.
Abacavir/lamivudine versus tenofovir/emtricitabine in virologically suppressed patients switching from ritonavir-boosted protease inhibitors to raltegravir.

There are few clinical data on the combination abacavir/lamivudine plus raltegravir. We compared the outcomes of patients from the SPIRAL trial receiving either abacavir/lamivudine or tenofovir/emtricitabine at baseline who had taken at least one dose of either raltegravir or ritonavir-boosted protease inhibitors. For the purpose of this analysis, treatment failure was defined as virological failure (confirmed HIV-1 RNA ≥50 copies/ml) or discontinuation of abacavir/lamivudine or tenofovir/emtricitabine because of adverse events, consent withdrawal, or lost to follow-up. There were 143 (72.59%) patients with tenofovir/emtricitabine and 54 (27.41%) with abacavir/lamivudine. In the raltegravir group, there were three (11.11%) treatment failures with abacavir/lamivudine and eight (10.96%) with tenofovir/emtricitabine (estimated difference 0.15%; 95% CI -17.90 to 11.6). In the ritonavir-boosted protease inhibitor group, there were four (14.81%) treatment failures with abacavir/lamivudine and 12 (17.14%) with tenofovir/emtricitabine (estimated difference -2.33%; 95% CI -16.10 to 16.70). Triglycerides decreased and HDL cholesterol increased through the study more pronouncedly with abacavir/lamivudine than with tenofovir/emtricitabine and differences in the total-to-HDL cholesterol ratio between both combinations of nucleoside reverse transcriptase inhibitors (NRTIs) tended to be higher in the raltegravir group, although differences at 48 weeks were not significant. While no patient discontinued abacavir/lamivudine due to adverse events, four (2.80%) patients (all in the ritonavir-boosted protease inhibitor group) discontinued tenofovir/emtricitabine because of adverse events (p=0.2744). The results of this analysis do not suggest that outcomes of abacavir/lamivudine are worse than those of tenofovir/emtricitabine when combined with raltegravir in virologically suppressed HIV-infected adults.
Secondary prevention in coronary artery disease. Achieved goals and possibilities for improvements.

To describe presence of risk indicators of recurrence 6 months after hospitalisation due to coronary artery disease at a university clinic.



The presence of risk indicators, including tobacco use, lipid levels, blood pressure and glucometabolic status, including 24-hour blood pressure monitoring and an oral glucose-tolerance test, was analysed.



Of 1465 patients who were screened, 402 took part in the survey (50% previous myocardial infarction and 50% angina pectoris). Mean age was 64 years (range 40-85 years) and 23% were women. Present medications were: lipid lowering drugs (statins; 94%), beta-blockers (85%), aspirin or warfarin (100%) and ACE-inhibitors or angiotensin II blockers (66%). Values above target levels recommended in guidelines were: a) low density lipoprotein (LDL) in 40%; b) mean blood pressure (day or night) in 38% and c) smoking in 13%. Of all patients, 66% had at least one risk factor (LDL or blood pressure above target levels or current smoking). An abnormal glucose-tolerance test was found in 59% of patients without known diabetes. If no history of diabetes, 85% had either LDL or blood pressure above target levels, current smoking or an abnormal glucose-tolerance test. However, with treatment intensification to patients with elevated risk factors 56% reached target levels for blood pressure and 79% reached target levels for LDL.



Six months after hospitalisation due to coronary artery disease, despite the high use of medication aimed at prophylaxis against recurrence, the majority were either above target levels for LDL or blood pressure or continued to smoke.
The high-risk discectomy patient: prevention of reherniation in patients with large anular defects using an anular closure device

With lumbar discectomy for disc herniation, surgeons must choose between limited nucleus removal associated with higher reherniation risk or more aggressive nucleus removal associated with increased back pain and disc degeneration. This trade-off is particularly challenging in patients with large anular defects, which carry the highest risk of reherniation. We examined the effect of an anular closure device on reherniation and clinical outcomes. Seventy-five primary discectomy patients had a limited discectomy followed by implantation of an anular closure device and were followed-up to 2 years. Anular defect size and volume of removed nucleus was recorded at surgery. Reherniations were reported, pain and function were monitored throughout, and imaging was performed at annual visits. The overall symptomatic reherniation rate was 1.4 %, and the asymptomatic reherniation rate was 1.5 % at 12 months and 5.1 % at 24 months. Both rates compare favorably with literature reports which include symptomatic rates ranging between 2 and 18 % (up to 27 % for patients with large anular defects) and an asymptomatic rate of 13 %. The low reherniation rate in patients at high-risk of reherniation based on anular defect size, despite discectomy being only limited, suggests that an anular closure device may reduce reherniation risk. Clinical outcomes for pain and function at 1 and 2 years post-operatively compared favorably with literature reports. Further study in a randomized controlled trial is required to confirm these results.
CROSS-CULTURAL VALIDATION OF THE PORTUGUESE VERSION OF THE EDUCATIONAL NEEDS ASSESSMENT TOOL (PortENAT).

To undertake a cross-cultural adaptation and validation of the educational needs assessment tool (ENAT) into Portuguese.



The first phase of this research (cross-cultural adaptation) utilised a well-established translation method comprising five sequential steps: forward-translation, synthesis of translations, back-translation, expert committee and field-testing of the adapted version. The second phase involved collecting data from 123 patients and subjecting them to Rasch analysis for validity testing including cross-cultural invariance.



The translation and field-testing phase went smoothly giving rise to minor adjustments in the phrasing of some items. The preliminary analysis of the 39 items, revealed some deviations from the model with the overall item-person interaction fit statistics 2(df) = 56.025 (39), p = 0.038. Significant item-item correlations caused artificial inflation of the internal consistency, therefore violating the model assumption of local independence of items. To correct this, all locally dependent items were then grouped into their respective domains, creating a 7 testlet-scale which demonstrated a good fit to the Rasch model, 2(df) = 2.625 (7), p = 0.917 and internal consistency PSI = 0.975. Analysis of the pooled (Portuguese and the English) data revealed cross-cultural DIF, requiring adjustments in two testlets: 'treatments' and 'support' which ensured cross-cultural equivalence.



This study confirms the Portuguese ENAT is a robust unidimensional tool with which to assess the educational needs of Portuguese people with RA. Cross-cultural adjustments are required only if the data from Portugal and the UK are pooled or compared. The tool is now available for use in clinical practice and research.
Dose intensification of methotrexate and cytarabine during intensified continuation chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: POG 9406: a report from the Children's Oncology Group.

To determine the efficacy and toxicity of higher dose versus standard dose intravenous methotrexate (MTX) and pulses of high-dose cytosine arabinoside with asparaginase versus standard dose cytosine arabinoside and teniposide during intensified continuation therapy for higher risk pediatric B-precursor acute lymphoblastic leukemia (ALL).



From 1994 to 1999, the Pediatric Oncology Group conducted a randomized phase III clinical trial in higher risk pediatric B-precursor ALL. A total of 784 patients were randomized in a 2×2 factorial design to receive MTX 1 g/m versus 2.5 g/m and to cytosine arabinoside/teniposide versus high-dose cytosine arabinoside/asparaginase during intensified continuation therapy.



Patients receiving standard dose MTX had a 5-year disease-free survival (DFS) of 71.8±2.4%; patients receiving higher dose MTX had a 5-year DFS of 71.7±2.4% (P=0.55). Outcomes on cytosine arabinoside/teniposide (DFS of 70.4±2.4) were similar to higher dose cytosine arabinoside/asparaginase (DFS of 73.1±2.3%) (P=0.41). Overall survival rates were not different between MTX doses or cytosine arabinoside/teniposide versus cytosine arabinoside/asparaginase.



Increasing MTX dosing to 2.5 g/m did not improve outcomes in higher risk pediatric B-precursor ALL. Giving high-dose cytarabine and asparaginase pulses instead of standard dose cytarabine and teniposide produced nonsignificant differences in outcomes, allowing for teniposide to be removed from ALL therapy.