nils-herrmann/clean_scirepeval huggingface dataset:
Co-occurrence of IBS and symptoms of anxiety or depression, among Norwegian twins, is influenced by both heredity and intrauterine growth

Environmental and genetic factors contribute to variation in irritable bowel syndrome (IBS), anxiety and depression. Comorbidity between these disorders is high. A previous investigation of our population-based twin cohort revealed that low birth weight increased the risk for development of IBS, with environmental influences in utero as the most relevant contributing factor. We hypothesise that both intrauterine and genetic factors influence the co-occurrence of IBS and symptoms of anxiety and depression.



A postal questionnaire sent to 12700 Norwegian twins born between 1967 and 1979 comprised a checklist of 31 illnesses and symptoms, including IBS and symptoms of anxiety and depression. The influence of genetic factors and intrauterine growth on comorbidity between these disorders were analysed in the full sample and compared to those based on only monozygotic (MZ) twin pairs discordant for IBS (95 pairs) in birth weight group < 2500 g and ≥ 2500 g.



In the co-twin analyses restricted growth (birth weight < 2500 g) was significantly associated with anxiety and depression (average birth weight difference of 181.0 g (p <0.0001) and 249.9 g (p < 0.0001), respectively). The analysis of the full sample revealed that IBS was significantly associated with symptoms of anxiety (adjusted OR = 2.5, 95% CI: 1.9, 3.3) and depression (adjusted OR = 2.3. 95% CI: 1.8, 3.0). Analyses of MZ pairs discordant for IBS indicated significant associations between IBS and symptoms of anxiety (OR = 3.7, 95% CI: 1.3, 10.5) and between IBS and symptoms of depression (OR = 4.2, 95% CI: 1.7, 9.9) only in the birth weight group below 2500 g.



Our findings suggest that genetic factors partly explain the association between IBS and symptoms of anxiety and depression. In the low range of birth weight (<2500 g), restricted fetal growth seems to be a common contributing factor to the co-occurrence between these disorders.
[High versus moderate intense running exercise - effects on cardiometabolic risk-factors in untrained males].

The philosophy on how to improve cardiometabolic risk factors most efficiently by endurance exercise is still controversial. To determine the effect of high-intensity (interval) training (HI[I]T) vs. moderate-intensity continuous exercise (MICE) training on cardiometabolic risk factors we conducted a 16-week crossover randomized controlled trial. Methods | 81 healthy untrained middle aged men were randomly assigned to a HI(I)T-group and a control-group that started the MICE running program after their control status. HI(I)T consisted of running exercise around or above the individual anaerobic threshold (≈ 80- 100 % HRmax); MICE focused on continuous running exercise at ≈ 65-77.5 % HRmax. Both protocols were comparable with respect to energy consumption. Study endpoints were cardiorespiratory fitness (VO2max), left ventricular mass index (LVMI), metabolic syndrome Z-score (MetS-Z-score), intima-media-thickness (IMT) and body composition. Results | VO2max-changes in this overweighed male cohort significantly (p=0.002) differ between HIIT (14.7 ± 9.3 %, p=0.001) and MICE (7.9 ± 7.4 %,p=0.001). LVMI, as determined via magnetic resonance imaging, significantly increased in both exercise groups (HIIT: 8.5 ± 5.4 %, p=0.001 vs. MICE: 5.3 ± 4.0 %, p=0.001), however the change was significantly more pronounced (p=0.005) in the HIIT-group. MetS-Z-score (HIIT: -2.06 ± 1.31, p=0.001 vs. MICE: -1.60 ± 1.77, p=0.001) and IMT (4.6 ± 5.9 % p=0.011 vs. 4.4 ± 8.1 %, p=0.019) did not show significant group-differences. Reductions of fat mass (-4.9 ± 9.0 %, p=0.010 vs. -9.5 ± 9.4, p=0.001) were significantly higher among the MICE-participants (p=0.034), however, the same was true (p=0.008) for lean body mass (0.5 ± 2.3 %, p=0.381 vs. -1.3 ± 2.0 %, p=0.003).  In summary high-intensity interval training tends to impact cardiometabolic health more favorable compared with a moderate-intensity continuous endurance exercise protocol.
Sonographic monitoring of midline shift in space-occupying stroke: an early outcome predictor.

Transcranial color-coded duplex sonography (TCCS) allows bedside imaging of intracranial hemodynamics and parenchymal structures. It provides reliable information regarding midline shift (MLS) in space-occupying hemispheric stroke. We studied the value of MLS measurement to predict fatal outcome at different time points after stroke onset.



Forty-two patients with acute, severe hemispheric stroke were enrolled. Cranial computed tomography (CCT) and extracranial duplex sonography were performed on admission. TCCS was carried out 8+/-3, 16+/-3, 24+/-3, 32+/-3, and 40+/-3 hours after stroke onset. Lesion size was determined from follow-up CCT.



Twelve patients died as the result of cerebral herniation (group 1); 28 survived (group 2). Two patients received decompressive hemicraniectomy and were therefore excluded from further evaluation. MLS was significantly higher in group 1 as early as 16 hours after onset of stroke. Specificity and positive predictive values for death caused by cerebral herniation of MLS >/=2.5, 3.5, 4.0, and 5.0 mm after 16, 24, 32, and 40 hours were 1.0.



TCCS helps to estimate outcome as early as 16 hours after stroke onset and thus facilitates identification of patients who are unlikely to survive without decompressive craniectomy. Because of its noninvasive character and bedside suitability, sonographic monitoring of MLS might be a useful tool in management of critically ill patients who cannot undergo repeated CCT scans.
A phase II study of oportuzumab monatox: an immunotoxin therapy for patients with noninvasive urothelial carcinoma in situ previously treated with bacillus Calmette-Guérin.

A phase II study was performed to assess the efficacy and tolerability of intravesical oportuzumab monatox in patients with urothelial carcinoma in situ of the bladder. Bacillus Calmette-Guérin treatment had previously failed in all patients.



A total of 46 patients received 1 induction cycle of 6 (cohort 1) or 12 (cohort 2) weekly intravesical oportuzumab monatox (VB4-845) instillations of 30 mg, followed by up to 3 maintenance cycles of 3 weekly administrations every 3 months.



A complete response to oportuzumab monatox was seen in 9 of 22 patients (41%) in cohort 1 and 9 of 23 (39%) in cohort 2 at the 3-month evaluation. A total of 20 patients (44%) achieved a complete response. Two other patients without carcinoma in situ who achieved a complete response were not included in the study due to the development of noninvasive papillary (Ta) disease. Median time to recurrence in patients who achieved a complete response was 274 and 408 days in cohorts 1 and 2, respectively. Overall 7 patients (16%) remained disease-free. Post-study assessment demonstrated that these patients were still disease-free at last followup (18 to 25 months). The most common adverse events were mild to moderate reversible bladder symptoms.



Oportuzumab monatox was effective and well tolerated in patients with bacillus Calmette-Guérin refractory carcinoma in situ of the bladder. These results demonstrate the clinical benefit of oportuzumab monatox and support its continued development for the second line treatment of nonmuscle invasive bladder cancer.
Pilot induction regimen incorporating pharmacokinetically guided topotecan for treatment of newly diagnosed high-risk neuroblastoma: a Children's Oncology Group study.

To assess the feasibility of adding dose-intensive topotecan and cyclophosphamide to induction therapy for newly diagnosed high-risk neuroblastoma (HRNB).



Enrolled patients received two cycles of topotecan (approximately 1.2 mg/m(2)/d) and cyclophosphamide (400 mg/m(2)/d) for 5 days followed by four cycles of multiagent chemotherapy (Memorial Sloan-Kettering Cancer Center [MSKCC] regimen). Pharmacokinetically guided topotecan dosing (target systemic exposure with area under the curve of 50 to 70 ng/mL/hr) was performed. Peripheral-blood stem cell (PBSC) harvest and surgical resection of residual primary tumor occurred after cycles 2 and 5, respectively. Patients achieving at least a partial response received myeloablative chemotherapy with PBSC rescue and radiation to the presurgical primary tumor volume. Oral 13-cis-retinoic acid maintenance therapy was administered twice daily for 14 days in six 28-day cycles.



Thirty-one patients were enrolled onto the study. No deaths related to toxicity or dose-limiting toxicities occurred during induction. Mucositis rarely occurred after topotecan cycles (9.7%) in contrast to 30% after MSKCC cycles. Thirty patients underwent PBSC collection with median 31.1 × 10(6) CD34+ cells/kg (range, 1.8 to 541.8 × 10(6) CD34+ cells/kg), all negative for tumor contamination by immunocytochemical analysis. Targeted topotecan systemic exposure was achieved in 26 (84%) of 31 patients. At the end of induction, 26 patients (84%) had tumor response and one patient had progressive disease. In the overall cohort, 3-year event-free and overall survival were 37.8% ± 9.4% and 57.1% ± 9.4%, respectively.



This pilot induction regimen was well tolerated with expected and reversible toxicities. These data support investigation of efficacy in a phase III clinical trial for newly diagnosed HRNB.
Collaborative care for patients with bipolar disorder: a randomised controlled trial

Bipolar disorder is a severe mental illness with serious consequences for daily living of patients and their caregivers. Care as usual primarily consists of pharmacotherapy and supportive treatment. However, a substantial number of patients show a suboptimal response to treatment and still suffer from frequent episodes, persistent interepisodic symptoms and poor social functioning. Both psychiatric and somatic comorbid disorders are frequent, especially personality disorders, substance abuse, cardiovascular diseases and diabetes. Multidisciplinary collaboration of professionals is needed to combine all expertise in order to achieve high-quality integrated treatment. 'Collaborative Care' is a treatment method that could meet these needs. Several studies have shown promising effects of these integrated treatment programs for patients with bipolar disorder. In this article we describe a research protocol concerning a study on the effects of Collaborative Care for patients with bipolar disorder in the Netherlands.



The study concerns a two-armed cluster randomised clinical trial to evaluate the effectiveness of Collaborative Care (CC) in comparison with Care as usual (CAU) in outpatient clinics for bipolar disorder or mood disorders in general. Collaborative Care includes individually tailored interventions, aimed at personal goals set by the patient. The patient, his caregiver, the nurse and the psychiatrist all are part of the Collaborative Care team. Elements of the program are: contracting and shared decision making; psycho education; problem solving treatment; systematic relapse prevention; monitoring of outcomes and pharmacotherapy. Nurses coordinate the program. Nurses and psychiatrists in the intervention group will be trained in the intervention. The effects will be measured at baseline, 6 months and 12 months. Primary outcomes are psychosocial functioning, psychiatric symptoms, and quality of life. Caregiver outcomes are burden and satisfaction with care.



Several ways to enhance the quality of this study are described, as well as some limitations caused by the complexities of naturalistic treatment settings where not all influencing factors on an intervention and the outcomes can be controlled.
Cross-sectional study of 168 patients with hepatorenal tyrosinaemia and implications for clinical practice

Hepatorenal tyrosinaemia (Tyr 1) is a rare inborn error of tyrosine metabolism. Without treatment, patients are at high risk of developing acute liver failure, renal dysfunction and in the long run hepatocellular carcinoma. The aim of our study was to collect cross-sectional data.



Via questionnaires we collected retrospective data of 168 patients with Tyr 1 from 21 centres (Europe, Turkey and Israel) about diagnosis, treatment, monitoring and outcome. In a subsequent consensus workshop, we discussed data and clinical implications.



Early treatment by NTBC accompanied by diet is essential to prevent serious complications such as liver failure, hepatocellular carcinoma and renal disease. As patients may remain initially asymptomatic or develop uncharacteristic clinical symptoms in the first months of life newborn mass screening using succinylacetone (SA) as a screening parameter in dried blood is mandatory for early diagnosis. NTBC-treatment has to be combined with natural protein restriction supplemented with essential amino acids. NTBC dosage should be reduced to the minimal dose allowing metabolic control, once daily dosing may be an option in older children and adults in order to increase compliance. Metabolic control is judged by SA (below detection limit) in dried blood or urine, plasma tyrosine (<400 μM) and NTBC-levels in the therapeutic range (20-40 μM). Side effects of NTBC are mild and often transient. Indications for liver transplantation are hepatocellular carcinoma or failure to respond to NTBC. Follow-up procedures should include liver and kidney function tests, tumor markers and imaging, ophthalmological examination, blood count, psychomotor and intelligence testing as well as therapeutic monitoring (SA, tyrosine, NTBC in blood).



Based on the data from 21 centres treating 168 patients we were able to characterize current practice and clinical experience in Tyr 1. This information could form the basis for clinical practice recommendations, however further prospective data are required to underpin some of the recommendations.
Divalproex sodium for the treatment of PTSD and conduct disordered youth: a pilot randomized controlled clinical trial.

We examined the efficacy of divalproex sodium (DVP) for the treatment of PTSD in conduct disorder, utilizing a previous study in which 71 youth were enrolled in a randomized controlled clinical trial. Twelve had PTSD. Subjects (all males, mean age 16, SD 1.0) were randomized into high and low dose conditions. Clinical Global Impression (CGI) ratings for core PTSD symptoms (Intrusion, avoidance and hyper arousal) were primary outcome measures, weekly slopes of impulsivity secondary ones. Intent-to-treat analyses showed significant positive associations between receiving high dose of DVP CGI's. Parallel analyses comparing outcome by drug level achieved strengthened the results.
Design of a randomized clinical trial of concurrent treatment with vitamin K2 and risedronate compared to risedronate alone in osteoporotic patients: Japanese Osteoporosis Intervention Trial-03 (JOINT-03)

Concurrent treatments with bisphosphonates and vitamin K are promising given that bisphosphonates possibly interfere with vitamin K activation. This is a prospective, multi-center, open-labeled, randomized trial of the efficacy of concurrent treatment with vitamin K2 and risedronate compared with risedronate alone and to explore subsets of patients for which concurrent treatment is particularly efficacious (trial identification number UMIN000000991). Inclusion criteria are women who meet the criteria for pharmacological therapy for osteoporosis, aged ≥65 years, have any of pre-specified risk factors, can walk unassisted, and are able to answer questionnaires. Exclusion criteria are prior warfarin use, secondary osteoporosis or non-osteoporotic metabolic bone diseases, contraindication for vitamin K2 and risedronate, hyper- or hypoparathyroidism, mental disorders, prevalent vertebral fracture at ≥6 sites, severe degenerative spinal deformation between T4 and L4, serious heart, liver, or kidney disease, or bisphosphonate use within the previous 6 months. Patients were recruited from 123 institutes between January 2008 and February 2010, and allocated to vitamin K2 (45 mg/day) and risedronate (2.5 mg/day or 17.5 mg/week) or risedronate alone (2.5 mg/day or 17.5 mg/week) groups. Primary endpoint is a vertebral or non-vertebral fracture. Secondary endpoints are bone mineral density, height, undercarboxylated osteocalcin, JOQOL, EQ-5D and safety. A sample size of 910 subjects per group and 2-year follow-up will provide 80 % power to detect 35 % risk reduction for fracture, with a two-sided significance level of 5 %. Subgroup analysis stratified to adjustment factors for random allocation, body mass index, 25-hydroxyvitamin D, estimated glomerular filtration rate, grade of vertebral fracture, JOQOL, EQ-5D, and co-morbidity is pre-specified.
Effectiveness of an Intervention to Increase Pap Test Screening Among Chinese Women in Taiwan

This study assessed the effectiveness of a theory-based direct mail campaign in encouraging non-compliant women, aged 30 and older or younger if married, to obtain a Pap test. Participants were female family members of inpatients admitted to one of the major teaching hospitals in Taiwan during August–September 1999. A total of 424 women were recruited in the randomized intervention trial. Three months following implementation of the intervention, women in the intervention group reported a higher rate of Pap test screening than women in the comparison group (50% versus 32%) (p = 0.002). Women in the intervention group also showed higher perceived pros of a Pap test at follow-up (p = 0.031). Although women in both groups showed an increased knowledge and intention to obtain a Pap, only the intervention group had significantly higher follow-up scores on perceived pros and susceptibility. The results shows that the intervention was effective in increasing Pap test screening among Chinese women within three months. The results also support the use of Intervention Mapping, a systematic program development framework for planning effective interventions.
An observational study to assess the association between osteoporosis and periodontal disease

There is evidence to suggest osteoporosis may result in premature tooth loss. The pathology behind this relationship is poorly understood. A correlation with osteoporosis and greater susceptibility to periodontal disease has been suggested. To investigate the association between osteoporosis and periodontal disease, accounting for the effect of confounding variables of age, smoking status and oral hygiene. Three hundred and fifty-nine postmenopausal women aged 45-70 years were recruited from the Greater Manchester area between March 2008 and June 2010.Subjects and methods Data were collected on osteoporosis status, smoking status, pocket probing depths, suppuration, plaque, bleeding and calculus indices. Dental panoramic tomographs were taken and periodontal bone support assessed on all teeth. Data were analysed using SPSS software (version  Complete data were available for 348 patients. Twenty-six percent (91) of individuals were osteoporotic. Logistic regression was used. The relationship between osteoporosis status and moderate to severe periodontal disease of both molar teeth and the whole mouth was not significant (p = 0.088 and p = 0.296 respectively).Conclusions Osteoporosis is not a causal factor in the development of moderate to severe chronic periodontitis.
Safety and efficacy of lorcaserin: a combined analysis of the BLOOM and BLOSSOM trials.

Lorcaserin, a novel selective 5-HT2C receptor agonist, is approved by the US Food and Drug Administration (FDA) for weight management in combination with lifestyle modification for adults with obesity and adults with overweight and ≥ 1 weight-related comorbid condition. The safety and effectiveness of lorcaserin in adult patients without type 2 diabetes mellitus was established based on 2 phase III clinical trials of similar design: Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) and Behavioral Modification and Lorcaserin Second Study for Obesity Management (BLOSSOM). This report presents a prespecified analysis of pooled data from these trials.



Co-primary end points in this analysis include the proportion of patients with a reduction in baseline body weight of ≥ 5% and ≥ 10%, and a change in weight from baseline. Key secondary end points include changes from baseline values in lipid parameters, quality-of-life measures, glycemic indicators, and vital signs.



At week 52, more than twice as many lorcaserin-treated patients achieved a weight loss of ≥ 5% compared with placebo (lorcaserin, 47.1%; placebo, 22.6%), and lorcaserin-treated patients lost significantly more body weight (lorcaserin, -5.8%; placebo, -2.5%). A significantly greater proportion of lorcaserin-treated patients achieved a weight loss of ≥ 10% (lorcaserin, 22.4%; placebo, 8.7%). There were statistically significant improvements in lipid parameters, glycemic indicators, quality-of-life measures, and vital signs in the lorcaserin group compared with placebo. The most common adverse events associated with lorcaserin treatment were headache, upper respiratory tract infection, and nasopharyngitis. Lorcaserin-treated patients had a rate of FDA-defined valvulopathy similar to placebo.



This pooled analysis of the phase III BLOOM and BLOSSOM trials shows that lorcaserin 10 mg twice daily, in combination with diet and exercise, is safe and tolerable, and is associated with statistically significant weight loss and clinically relevant improvements in cardiometabolic parameters.
The ADO index as a predictor of two-year mortality in general practice-based chronic obstructive pulmonary disease cohorts.

Existing prediction models for mortality in chronic obstructive pulmonary disease (COPD) patients have not yet been validated in primary care, which is where the majority of patients receive care.



Our aim was to validate the ADO (age, dyspnoea, airflow obstruction) index as a predictor of 2-year mortality in 2 general practice-based COPD cohorts.



Six hundred and forty-six patients with COPD with GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages I-IV were enrolled by their general practitioners and followed for 2 years. The ADO regression equation was used to predict a 2-year risk of all-cause mortality in each patient and this risk was compared with the observed 2-year mortality. Discrimination and calibration were assessed as well as the strength of association between the 15-point ADO score and the observed 2-year all-cause mortality.



Fifty-two (8.1%) patients died during the 2-year follow-up period. Discrimination with the ADO index was excellent with an area under the curve of 0.78 [95% confidence interval (CI) 0.71-0.84]. Overall, the predicted and observed risks matched well and visual inspection revealed no important differences between them across 10 risk classes (p = 0.68). The odds ratio for death per point increase according to the ADO index was 1.50 (95% CI 1.31-1.71).



The ADO index showed excellent prediction properties in an out-of-population validation carried out in COPD patients from primary care settings.
A new applicator design for endocavitary brachytherapy of cancer in the nasopharynx.

In attempting to improve local tumor control by higher doses of radiation, there has been a resurgence of interest in the implementation of brachytherapy in the management of primary and recurrent cancers of the nasopharynx. Brachytherapy with its steep dose fall-off is of particular interest because of the proximity of critical dose limiting structures. Recent developments in brachytherapy, such as the introduction of pulsed-dose-rate and high-dose-rate computerized afterloaders, have encouraged further evolution of brachytherapy techniques.



We have designed an inexpensive, re-usable and flexible silicone applicator, tailored to the shape of the soft tissues of the nasopharynx, which can be used with either low-dose-rate brachytherapy or high (pulsed)-dose-rate remote controlled afterloaders.



This Rotterdam nasopharynx applicator proved to be easy to introduce, patient friendly and can remain in situ for the duration of the treatment (2-6 days). The design, technique of application and the first consecutive 5 years of clinical experience in using this applicator are presented.