nils-herrmann/clean_scirepeval huggingface dataset:
A phase I dose-escalating study of ES-285, a marine sphingolipid-derived compound, with repeat dose administration in patients with advanced solid tumors

(Spisulosine) is a novel marine compound with antitumor activity in preclinical studies. A phase I study was performed in patients with advanced solid tumors to determine the maximum tolerated dose (MTD), establish a safety profile, and to evaluate pharmacokinetics and efficacy of the drug.  Thirty patients from two centers were treated with a three-hour ES-285 intravenous infusion for five consecutive days, every 3 weeks. Eleven dose levels were explored.  No dose-limiting toxicity (DLT) occurred from 2 to 81 mg/m²/day. Three patients had DLT, one each at dose levels 160, 120 and 100 mg/m²/day; all had grade 4 transaminase increases, one of whom (160 mg/m²/day) had concomitant grade 4 hepatitis and grade 3 bilirubin elevation. The MTD of this regimen was not reached due to early termination of the ES-285 phase I program, but was considered to be 80 to 100 mg/m²/day. Other toxicities included mild to moderate asthenia, nausea, vomiting, anemia, lymphopenia, and injection site reaction. Pharmacokinetic analyses showed dose proportionality on Days 1 and 5, a wide distribution and a long half-life. Seven patients (five with colorectal cancer) had stable disease (1.2–4.1 months), lasting for more than 3 months in three patients.  Liver enzyme elevations were dose limiting for ES-285 in this administration schedule. Low antitumor activity was observed.
Effect of azathioprine or mesalazine therapy on incidence of re-hospitalization in sub-occlusive ileocecal Crohn’s disease patients

Although the cost of Crohn's disease (CD) treatment differs considerably, hospitalization and surgery costs account for most of the total treatment cost. Decreasing hospitalization and surgery rates are pivotal issues in reducing health-care costs.  We evaluated the effect of azathioprine (AZA) compared with mesalazine on incidence of re-hospitalizations due to all causes and for CD-related surgeries. In this controlled, randomized study, 72 subjects with sub-occlusive ileocecal CD were randomized for AZA (2-3 mg/kg per day) or mesalazine (3.2 g per day) therapy during a 3-year period. The primary end point was the re-hospitalization proportion due to all causes, as well as for surgical procedures during this period evaluated between the groups.



On an intention-to-treat basis, the proportion of patients re-hospitalized within 36 months due to all causes was lower in patients treated with AZA compared to those on mesalazine (0.39 vs. 0.83, respectively; p=0.035). The AZA group had also significantly lower proportions of re-hospitalization for surgical intervention (0.25 vs. 0.56, respectively; p=0.011). The number of admissions (0.70 vs. 1.41, p=0.001) and the length of re-hospitalization (3.8 vs. 7.7 days; p=0.002) were both lower in AZA patients.



Patients with sub-occlusive ileocecal CD treated with AZA had lower re-hospitalization rates due to all causes and for surgical management of CD compared to those treated with mesalazine during a 3-year period. The long-term use of AZA in ileocecal CD patients recovering from a sub-occlusion episode can save healthcare costs.
Cardiopulmonary resuscitation

Diffuse hypoxic brain damage is rather common in patients with successful prehospital resuscitation by Emergency Medical System. The extent of revesible and irreversible neuropsychological lesions associated with hypoxia depends on age, preexisting diseases (e.g. cerebrovascular insufficiency) and duration of cardiorespiratory arrest . In those patients regaining consciousness despite persistent neu -ropsychological lesions the process of personality reorganization has little been studied. Personality reorganization was analysed in 20 patients with primarily deep coma after successful prehospital resuscitation (estimated mean duration of cardiac arrest 18 min.) followed by slow improvement of cerebral function and regaining "consciousness". Common features were reversible loss of short term memory and various kinds of acute exogenic reaction. Patients with possibly preexisting cerebral atrophy showed an apparently improved neuropsychological recovery. In 2 patients, personality reorganization showed striking similarities with earliest stages of childhood development. Careful analysis of personality reorganization may have most important implications for individualized rehabilitation strategies in patients after resuscitation.
Wormy wood?

Post thrombotic syndrome (PTS) is a burdensome and costly complication of deep venous thrombosis (DVT) that develops in 20–40% of patients within 1–2 years after symptomatic DVT. Affected patients have chronic leg pain and swelling and may develop ulcers. Venous valve disruption from the thrombus itself or thrombus-associated mediators of inflammation is considered to be a key initiating event for the development of venous hypertension that often underlies PTS. As existing treatments for PTS are extremely limited, strategies that focus on preventing the development of PTS in patients with DVT are more likely to be effective and cost-effective in reducing its burden. Elastic compression stockings (ECS) could be helpful in preventing PTS; however, data on their effectiveness are scarce and conflicting.  The SOX Trial is a randomized, allocation concealed, double-blind multicenter clinical trial. The objective of the study is to evaluate ECS to prevent PTS. A total of 800 patients with proximal DVT will be randomized to one of 2 treatment groups: ECS or placebo (inactive) stockings worn on the DVT-affected leg daily for 2 years. The primary outcome is the incidence of PTS during follow-up. Secondary outcomes are severity of PTS, venous thromboembolism (VTE) recurrence, death from VTE, quality of life and cost-effectiveness. Outcomes will be evaluated during 6 clinic visits and 2 telephone follow ups. At baseline, 1 and 6 months, blood samples will be obtained to evaluate the role of inflammatory mediators and genetic markers of thrombophilia in the development of PTS (Bio-SOX substudy).  The SOX Trial will be the largest study and the first with a placebo control to evaluate the effectiveness of ECS to prevent PTS. It is designed to provide definitive data on the effects of ECS on the occurrence and severity of PTS, as well as DVT recurrence, cost-effectiveness and quality of life. This study will also prospectively evaluate the predictive role of biomarkers that are reflective of putative underlying pathophysiological mechanisms in the development of clinical PTS. As such, our results will impact directly on the care of patients with DVT.
Mood stabilizer treatment increases serotonin type 1A receptor binding in bipolar depression.

Abnormal serotonin type 1A (5-HT1A) receptor function and binding have been implicated in the pathophysiology of mood disorders. Preclinical studies have consistently shown that stress decreases the gene expression of 5-HT1A receptors in experimental animals, and that the associated increase in hormone secretion plays a crucial role in mediating this effect. Chronic administration of the mood stabilizers lithium and divalproex (valproate semisodium) reduces glucocorticoid signaling and function in the hippocampus. Lithium has further been shown to enhance 5-HT1A receptor function. To assess whether these effects translate to human subject with bipolar disorder (BD), positron emission tomography (PET) and [18F]trans-4-fluoro-N-(2-[4-(2-methoxyphenyl) piperazino]-ethyl)-N-(2-pyridyl) cyclohexanecarboxamide ([(18)F]FCWAY) were used to acquire PET images of 5-HT1A receptor binding in 10 subjects with BD, before and after treatment with lithium or divalproex. Mean 5-HT1A binding potential (BPP) significantly increased following mood stabilizer treatment, most prominently in the mesiotemporal cortex (hippocampus plus amygdala). When mood state was also controlled for, treatment was associated with increases in BPP in widespread cortical areas. These preliminary findings are consistent with the hypothesis that these mood stabilizers enhance 5-HT1A receptor expression in BD, which may underscore an important component of these agents' mechanism of action.
Naproxen and celecoxib do not prevent AD in early results from a randomized controlled trial.

To evaluate the efficacy and safety of naproxen and celecoxib for the primary prevention of Alzheimer disease (AD).



Randomized, placebo-controlled, double-masked clinical trial conducted at six US dementia research clinics. Volunteers aged 70+ years, with cognitive screening scores above designated cut-offs and a family history of AD, were randomly assigned to celecoxib 200 mg BID, naproxen sodium 220 mg BID, or placebo. Enrollment began in early 2001. The main outcome measure was diagnosis of AD after randomization.



On December 17, 2004, treatments were suspended. Events while on treatment yielded hazard ratios vs placebo of 1.99 (95% CI 0.80 to 4.97; p = 0.14) for celecoxib and 2.35 (0.95 to 5.77; p = 0.06) for naproxen. Imperfect screening measures led to enrollment of 7 individuals with dementia and 46 others with milder cognitive syndromes. Their (prevalent) illness was detected at enrollment and diagnosed within 6 months following randomization. Secondary analyses that excluded the 7 cases of prevalent dementia showed increased hazard ratios for AD with both treatments. Neither treatment produced a notable effect on the incidence of milder cognitive syndromes.



These results do not support the hypothesis that celecoxib or naproxen prevent Alzheimer dementia, at least within the early years after initiation of treatment. Masked long-term follow-up of these participants will be essential.
Metabolic effects of carteolol and dilevalol in essential hypertension

As further classes of antihypertensive agents become available, more attention is being directed toward the ancillary pharmacological activities of the drugs, such as metabolic effects, fl-Adrenoceptor blockers are known to produce different effects on serum lipids, depending on their pharmacological characteristics [1, 2]; for example, non-cardioselective ffblockers without intrinsic sympathomimetic activity (ISA) have been reported to raise triglycerides and to lower HDL-cholesterol [3, 4], while cardioselective flz-blockers show less of this adverse effect , and/3-blockers with ISA appear to cause the least alteration in serum lipids . Nevertheless, the precise reasons why/3-blockers with ISA have a less unfavourable effect on lipid metabolism than those without ISA remains unclear. The present study was designed to assess whether a fl-blocker with partial selective ~-adrenoceptor agonism would have any advantageous metabolic effects when compared to a convectional/3-blocker with ISA. The metabolic effects of carteolol (10 mg, once daily), a/3-blocker with potent intrinsic sympathomimetic activity [7, 8], and dilevalol (100 mg, once daily), a/3-blocker with fl2-selective ISA , have been in compared 9 patients with untreated mild-to-moderate, otherwise uncomplicated, essential hypertension (WHO Classes I and II) in a randomised, two-way, cross-over trial, following a 2-week run-in control period. Blood samples for measurement of serum lipids, creatine phosphokinase (CK), uric acid and glycosylated haemoglobin Ale (HbAlc), an indicator of glycaemic control, were obtained from each of the patients after a 12-h overnight fast at the end of the 2-week run-in and of 6-week fixed maintenance periods of carteolol and dilevalol. The results are summarized in Table 1. Six-week oral monotherapy with carteolol and dilevalol significantly lowered (P<0.01) both systolic and diastolic blood pressure to a similar extent as compared to the predose values. Total serum cholesterol, triglycerides, low(LDL) and high-density lipoprotein (HDL) cholesterol and the LDL/HDL-cholesterol ratio were not altered by either drug. The serum CK level was significantly increased (P < 0.05) by carteolol ( + 23 %) and dilevalol ( + 27 %) as compared to the predose level. Serum uric acid and HbAzc remained unchanged
Autologous hematopoietic stem cell transplantation for relapsed follicular lymphoma: safety profile and clinical outcome in a single-center experience

Autologous hematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsed and recurrent follicular lymphoma (R/R FL); however, its value in the rituximab era remains to be elucidated. To evaluate the safety and clinical outcome of AHSCT for relapsed FL, we present a retrospective series of AHSCT for 30 FL patients (17 male and 13 female) at median age of 49 years. Patients were transplanted in second or subsequent complete or partial response after at least one therapeutic line including chemotherapy and rituximab. Overall, seven patients achieved second or higher complete response (CR) at AHSCT, whereas 23 were transplanted in partial response. Median overall survival (OS) was not reached, whereas progression-free survival (PFS) was 4.8 years. The estimated 10-year OS and PFS were found to be 60 and 33%, respectively. There was no significant difference in OS and PFS in terms of FLIPI score and disease status at transplant. Median follow-ups from diagnosis and from AHSCT were 4.9 years (range 1.5-18.4 years) and 1.7 years (range 0.03-16.5 years), respectively. Fifteen patients relapsed, and 11 out of them (73%) died of disease recurrence and chemoresistance. At the last contact, 19 patients are alive: 12 are in CR, whereas seven patients receive salvage regimens due to active lymphoma. AHSCT for relapsed FL patients who were pretreated with rituximab remains a safe procedure with low transplant-related mortality and long-term progression-free survival in about one-third of transplanted patients.
We're using the wrong name

One of the great joys in working with Ada is strong typing and wha t we call data abstraction. We create user-defined types such as DAY OF WEEK , because now we can spell out the values we mean such as MONDAY, BLUE, SECRET , ROUTINE, etc. Now as our code becomes much more readable for everyone (particularly the program author), we are less apt to make logic and codin g errors, and the compiler will rather firmly notify us if we attempt to mi x anything of type APPLES with something of type ORANGES. But do we want t o call this activity "data abstraction"? One definition my dictionary gives o f abstraction is : "Thought of or stated without reference to a specifi c instance". Of course our English language is very ambiguous, but after reading this definition five or six times, I think it pretty well describes wha t we are trying to do with types in Ada : we have specific instances of value s such as BLUE, RED, GREEN, etc ., and we abstract the common property of al l these specific values into a thing we call "type COLOR". Very good. But wait a minute. What we are doing in Ada with typing is to avoi d using numeric codes for non-numeric things, such as 1, 2, 3 for red, amber , When we do this kind of thing by creating type COLOR, or type SECURITY CLASSIFICATION , we are not performing an abstraction on the integers, we are doin g just the opposite! If "data abstraction" is truly what you want, I'll giv e you data abstraction, it is a higher abstraction on any enumeration type you might want to make : subtype ABSTRACT TYPE is INTEGER ; Here we abstract the values of DAY OF WEEK, COLOR, or whatever, int o a common type which turns out to be the integers. Type COLOR is indeed a n abstraction of the values BLUE, RED, GREEN, but using type COLOR and it s values is not an abstraction over using integer codes .
Tiludronate infusion in the treatment of bone spavin: a double blind placebo-controlled trial.

Tiludronate regulates bone remodelling through a decrease of the resorptive process and should therefore ameliorate the remodelling processes active in osteoarthritis of the distal tarsal joints ('bone spavin') and alleviate pain associated with abnormal bone lysis.



To confirm the efficacy of tiludronate, administered as a single infusion at a dose of 1 mg/kg bwt, in the treatment of bone spavin in the horse.



A double blind placebo controlled trial on 108 clinical cases of bone spavin was undertaken. The lameness score of the lamest limb was assessed following distal tarsal analgesia of the contralateral limb and followed-up using the same procedure throughout the study. Bone spavin in the lamest limb was confirmed by distal tarsal analgesia and radiography. Horses were treated at Day 0 and reassessed 60 days later after controlled exercise. A second nonblinded treatment was given to unresponsive horses and all horses were re-examined at Day 120. Exercise levels were recorded at each examination.



Eighty-seven horses completed the trial as per the protocol. The tiludronate horses were significantly less lame than the placebo horses (P = 0.0318). Horses treated at Day 60 with tiludronate showed further improvement in lameness at Day 120 (P = 0.0096 and P = 0.0034 for horses treated with tiludronate and placebo at Day 0, respectively). The only significant difference in radiographic findings between tiludronate and placebo was for presence of periarticular osteophytes (P = 0.006).



Tiludronate treatment is proven to be effective in bone spavin in horses in association with a controlled exercise programme.



Tiludronate in combination with controlled exercise offers an alternate medical treatment for bone spavin.
Ambulatory blood pressure in untreated and treated hypertensive patients at high altitude: the High Altitude Cardiovascular Research-Andes study.

Blood pressure increases during acute exposure to high altitude in healthy humans. However, little is known on altitude effects in hypertensive subjects or on the treatment efficacy in this condition. hour ambulatory blood pressure in hypertensive subjects and to assess antihypertensive treatment efficacy in this setting. One hundred untreated subjects with mild hypertension (screening blood pressure, 144.1±9.8 mm Hg systolic, 92.0±7.5 mm Hg diastolic) were randomized to double-blind placebo or to telmisartan 80 mg+modified release nifedipine 30 mg combination. Twenty-four-hour ambulatory blood pressure monitoring was performed off-treatment, after 6 weeks of treatment at sea level, on treatment during acute exposure to high altitude (3260 m) and immediately after return to sea level. Eighty-nine patients completed the study (age, 56.4±17.6 years; 52 men/37 women; body mass index, 28.2±3.5 kg/m(2)). Twenty-four-hour systolic blood pressure increased at high altitude in both groups (placebo, 11.0±9 mm Hg; P<0.001 and active treatment, 8.1±10.4 mm Hg; P<0.001). Active treatment reduced 24-hour systolic blood pressure both at sea level and at high altitude (147.9±11.1 versus 132.6±12.4 mm Hg for placebo versus treated; P<0.001; 95% confidence interval of the difference 10.9-19.9 mm Hg) and was well tolerated. Similar results were obtained for diastolic, for daytime blood pressure, and for nighttime blood pressure. Treatment was well tolerated in all conditions. Our study demonstrates that (1) 24-hour blood pressure increases significantly during acute high-altitude exposure in hypertensive subjects and (2) treatment with angiotensin receptor blocker-calcium channel blocker combination is effective and safe in this condition.
Enhancing cognitive-behavioural therapy for recurrent headache: design of a randomised controlled trial

We have argued against the traditional approach of counselling avoidance of all triggers of headaches and migraine. Problems with this approach include the impossibility of avoiding all triggers and the high costs associated with trying to do so, and that avoidance could lead to reduced tolerance for the triggers. We have developed an alternative approach called Learning to Cope with Triggers (LCT) that encourages avoidance of triggers that are detrimental to health and wellbeing, but uses exposure to other triggers to desensitise headache sufferers to the triggers. This approach has been shown to be more effective than advising avoidance of all triggers. Trigger management is only one component of a comprehensive treatment program and the current study is designed to evaluate a new approach to treating headaches in which LCT has been integrated into an established cognitive-behavioural therapy (CBT) package (LCT/CBT).



A target sample of 120 adult participants who suffer from migraine or tension-type headache, at least six days per month, and have done so for at least 12 months will be recruited. Participants will be randomly assigned to one of three groups: LCT/CBT; Avoid/CBT (CBT combined with instructions to avoid all triggers); and waiting-list control. Measures will include: daily diaries for recording headaches, triggers and medication consumption; headache disability and quality of life; trigger avoidance; locus of control and self-efficacy; and coping strategies. Treatment will involve 12 60-minute sessions scheduled weekly. Assessment will be completed before and after treatment, and at 4 and 12 month follow-up. The data will be analysed to determine which approach is most effective, and predictors of response to treatment.



Migraine and tension-type headache are common and can be disabling. CBT has been demonstrated to be an efficacious treatment for both disorders. However, there is room for improvement. This study aims to increase the efficacy of behavioural approaches and identify factors predictive of a positive response.
Homeopathic medical practice: Long-term results of a cohort study with 3981 patients

On the range of diagnoses, course of treatment, and long-term outcome in patients who chose to receive homeopathic medical treatment very little is known. We investigated homeopathic practice in an industrialized country under everyday conditions.



In a prospective, multicentre cohort study with 103 primary care practices with additional specialisation in homeopathy in Germany and Switzerland, data from all patients (age > 1 year) consulting the physician for the first time were observed. The main outcome measures were: Patient and physician assessments (numeric rating scales from 0 to 10) and quality of life at baseline, and after 3, 12, and 24 months.



A total of 3,981 patients were studied including 2,851 adults (29% men, mean age 42.5 +/- 13.1 years; 71% women, 39.9 +/- 12.4 years) and 1,130 children (52% boys, 6.5 +/- 3.9 years; 48% girls, 7.0 +/- 4.3 years). Ninety-seven percent of all diagnoses were chronic with an average duration of 8.8 +/- 8 years. The most frequent diagnoses were allergic rhinitis in men, headache in women, and atopic dermatitis in children. Disease severity decreased significantly (p < 0.001) between baseline and 24 months (adults from 6.2 +/- 1.7 to 3.0 +/- 2.2; children from 6.1 +/- 1.8 to 2.2 +/- 1.9). Physicians' assessments yielded similar results. For adults and young children, major improvements were observed for quality of life, whereas no changes were seen in adolescents. Younger age and more severe disease at baseline were factors predictive of better therapeutic success.



Disease severity and quality of life demonstrated marked and sustained improvements following homeopathic treatment period. Our findings indicate that homeopathic medical therapy may play a beneficial role in the long-term care of patients with chronic diseases.