nils-herrmann/clean_scirepeval huggingface dataset:
Long-term safety and effectiveness of lopinavir/ritonavir in antiretroviral-experienced HIV-1-infected children.

To evaluate the long-term safety and effectiveness of lopinavir/ritonavir (LPV/r) in a population-based cohort of HIV-1-infected children.



All children enrolled in the Swiss Mother and Child HIV Cohort Study, treated with LPV/r-based combination antiretroviral treatment (cART) between November 2000 and October 2008, were included.



88 children (25 (28%) protease inhibitor (PI)-naive, 16 (18%) ART-naive) were analysed (251 patient-years on LPV/r). After 48 weeks on LPV/r, 70 children had a median (interquartile range (IQR)) decrease in HIV-1 viral load of 4.25 log (5.45-3.17; PI-naive, n=17) and 2.53 (3.68-1.38; PI-experienced, n=53). Median (IQR) increase in CD4 count was 429 (203-593; PI-naive) and 177 (21-331; PI-experienced) cells/microl. These effects remained stable throughout 192 weeks for 25 children. Treatment was stopped for viral rebound in seven and suspected toxicity in 12 children.



Long-term treatment with LPV/r-based cART is safe and effective in HIV-1-infected children.
Effects of motivational interviewing-based adherence therapy for schizophrenia spectrum disorders: a randomized controlled trial

Non-adherence to antipsychotic medication is commonly found in schizophrenia and other psychotic disorders, thus forming a major obstacle to long-term maintenance treatment and contributing to high relapse rates. With limited evidence on the success of interventions in enhancing medication adherence, this controlled trial was designed to test and evaluate the effectiveness of an adherence therapy (AT) for outpatients with schizophrenia spectrum disorders, based on a motivational interviewing approach over a six-month follow-up period.



A single-blind, randomized controlled trial with a repeated-measures, two parallel groups design was conducted in a random sample of 114 participants with schizophrenia spectrum disorders in one community psychiatric nursing service. After pre-test, the participants were randomly assigned to either an eight-session course of AT plus usual care or usual psychiatric care (n = 57 per group). The main outcomes, including medication adherence, symptom severity, insight into treatment, hospitalization rate, and functioning, were measured at baseline and immediately and six months post-intervention.



A total of 110 participants completed this trial and thus the attrition rate was 3.5%. Results of repeated-measures analysis of variance followed by Helmert's contrasts test indicated that the AT participants reported significantly greater improvements in their insight into illness and/or treatment, psychosocial functioning, symptom severity, number of re-hospitalizations, and medication adherence (F = 5.01 to 7.45, P = 0.007 to 0.030) over six months follow-up, when compared with usual care.



Motivational interviewing-based AT for people with schizophrenia can be effective to reduce symptom severity and re-hospitalizations, and improve medication adherence, functioning, and insight into illness and/or treatment over a medium term (six months) period of follow-up. Further study on the effects of AT in people with psychotic disorders in terms of diverse sociodemographic and illness characteristics, and a longer term (for example, over 12 months) follow-up period is recommended.
A quantitative skin impedance test to diagnose spinal cord injury

The purpose of this study was to develop a quantitative skin impedance test that could be used to diagnose spinal cord injury (SCI) if any, especially in unconscious and/or non-cooperative SCI patients. To achieve this goal, initially skin impedance of the sensory key points of the dermatomes (between C3 and S1 bilaterally) was measured in 15 traumatic SCI patients (13 paraplegics and 2 tetraplegics) and 15 control subjects. In order to classify impedance values and to observe whether there would be a significant difference between patient and subject impedances, an artificial neural network (ANN) with back-propagation algorithm was employed. Validation results of the ANN showed promising performance. It could classify traumatic SCI patients with a success rate of 73%. By assessing the experimental protocols and the validation results, the proposed method seemed to be a simple, objective, quantitative, non-invasive and non-expensive way of assessing SCI in such patients.
Inhibition of adipose tissue lipolysis increases intramuscular lipid use in type 2 diabetic patients

In the present study, we investigated the consequences of adipose tissue lipolytic inhibition on skeletal muscle substrate use in type 2 diabetic patients. We studied ten type 2 diabetic patients under the following conditions: (1) at rest; (2) during 60 min of cycling exercise at 50% of maximal workload capacity and subsequent recovery. Studies were done under normal, fasting conditions (control trial: CON) and following administration of a nicotinic acid analogue (low plasma non-esterified fatty acid trial: LFA). Continuous [U-13C]palmitate and [6,6 -2H2]glucose infusions were applied to quantify plasma NEFA and glucose oxidation rates, and to estimate intramuscular triacylglycerol (IMTG) and glycogen use. Muscle biopsies were collected before and after exercise to determine net changes in lipid and glycogen content specific to muscle fibre type. Following administration of the nicotinic acid analogue (Acipimox), the plasma NEFA rate of appearance was effectively reduced, resulting in lower NEFA concentrations in the LFA trial (p<0.001). Plasma NEFA oxidation rates were substantially reduced at rest, during exercise and subsequent recovery in the LFA trial. The lower plasma NEFA oxidation rates were compensated by an increase in IMTG and endogenous carbohydrate use (p<0.05). Plasma glucose disposal rates did not differ between trials. In accordance with the tracer data, a greater net decline in type I muscle fibre lipid content was observed following exercise in the LFA trial (p<0.05). This study shows that plasma NEFA availability regulates IMTG use, and that adipose tissue lipolytic inhibition, in combination with exercise, could be an effective means of augmenting intramuscular lipid and glycogen use in type 2 diabetic patients in an overnight fasted state.
Diagnosis of HIV-Associated Oral Lesions in Relation to Early versus Delayed Antiretroviral Therapy: Results from the CIPRA HT001 Trial

Oral mucosal lesions that are associated with HIV infection can play an important role in guiding the decision to initiate antiretroviral therapy (ART). The incidence of these lesions relative to the timing of ART initiation has not been well characterized. A randomized controlled clinical trial was conducted at the GHESKIO Center in Port-au-Prince, Haiti between 2004 and 2009. 816 HIV-infected ART-naïve participants with CD4 T cell counts between 200 and 350 cells/mm3 were randomized to either immediate ART initiation (early group; N = 408), or initiation when CD4 T cell count was less than or equal 200 cells/mm3 or with the development of an AIDS-defining condition (delayed group; N = 408). Every 3 months, all participants underwent an oral examination. The incidence of oral lesions was 4.10 in the early group and 17.85 in the delayed group (p-value <0.01). In comparison to the early group, there was a significantly higher incidence of candidiasis, hairy leukoplakia, herpes labialis, and recurrent herpes simplex in the delayed group. The incidence of oral warts in delayed group was 0.97 before therapy and 4.27 post-ART initiation (p-value <0.01). In the delayed group the incidence of oral warts post-ART initiation was significantly higher than that seen in the early group (4.27 versus 1.09; p-value <0.01). The incidence of oral warts increased after ART was initiated, and relative to the early group there was a four-fold increase in oral warts if ART was initiated following an AIDS diagnosis. Based upon our findings, candidiasis, hairy leukoplakia, herpes labialis, and recurrent herpes simplex indicate immune suppression and the need to start ART. In contrast, oral warts are a sign of immune reconstitution following ART initiation.
Limited induction of tumor cross-reactive T cells without a measurable clinical benefit in early melanoma patients vaccinated with human leukocyte antigen class I-modified peptides.

The progressive immune dysfunctions that occur in patients with advanced melanoma make them unlikely to efficiently respond to cancer vaccines. A multicenter randomized phase II trial was conducted to test whether immunization with modified HLA class I tumor peptides in the context of adjuvant therapy results in better immunologic responses and improved clinical outcomes in patients with early melanoma (stages IIB/C-III).



Forty-three patients were enrolled to undergo vaccination (n = 22) or observation (n = 21). The vaccine included four HLA-A*0201-restricted modified peptides (Melan-A/MART-1([27L]), gp100([210M]), NY-ESO-1([165V]), and Survivin([97M])) emulsified in Montanide ISA51 and injected subcutaneously in combination with cyclophosphamide (300 mg/m(2)) and low-dose IL-2 (3 × 10(6) IU). The immune responses were monitored using ex vivo IFN-γ-ELISpot, HLA/multimer staining, and in vitro short-term peptide sensitization assays.



Vaccination induced a rapid and persistent increase in specific effector memory CD8(+) T cells in 75% of the patients. However, this immunization was not associated with any significant increase in disease-free or overall survival as compared with the observation group. An extensive immunologic analysis revealed a significantly reduced cross-recognition of the corresponding native peptides and, most importantly, a limited ability to react to melanoma cells.



Adjuvant setting is an appealing approach for testing cancer vaccines because specific CD8(+) T cells can be efficiently induced in most vaccinated patients. However, the marginal antitumor activity of the T cells induced by modified peptides in this study largely accounts for the observed lack of benefit of vaccination. These findings suggest reconsidering this immunization strategy, particularly in early disease.
Association between myocardial substrate, implantable cardioverter defibrillator shocks and mortality in MADIT-CRT.

The aim of the present study was to assess a possible association between myocardial substrate, implantable cardioverter defibrillator (ICD) shocks, and subsequent mortality.



Within the multicentre automatic defibrillator implantation trial-cardiac resynchronization therapy (MADIT-CRT) population (n = 1790), we investigated the association between myocardial substrate, ICD shocks and subsequent mortality using multivariate Cox regression analyses and landmark analyses at 1-year follow-up.



The 4-year cumulative probability of ICD shocks was 13% for appropriate shock and 6% for inappropriate shock. Compared with patients who never received ICD therapy, patients who received appropriate shock had an increased risk of mortality [HR = 2.3 (1.47-3.54), P < 0.001], which remained increased after adjusting for echocardiographic remodelling at 1 year (HR = 2.8, P = 0.001). Appropriate anti-tachycardia pacing (ATP) only was not associated with increased mortality (P = 0.42). We were not able to show an association between inappropriate shocks (P = 0.53), or inappropriate ATP (P = 0.10) and increased mortality. Advanced myocardial structural disease, i.e. higher baseline echocardiographic volumes and lack of remodelling at 1 year, was present in patients who received appropriate shocks but not in patients who received inappropriate shocks or no shocks.



In the MADIT-CRT study, receiving appropriate ICD shocks was associated with an increased risk of subsequent mortality. This association was not evident for appropriate ATP only. These findings, along with advanced cardiac structural disease in the patients who received appropriate shocks, suggest that the compromised myocardium is a contributing factor to the increased mortality associated with appropriate ICD shock therapy.
The delta-shaped anastomosis in laparoscopic distal gastrectomy: analysis of the initial 100 consecutive procedures of intracorporeal gastroduodenostomy

We developed a new method of intracorporeal gastroduodenostomy, the delta-shaped anastomosis, in which only endoscopic linear staplers are used. In this report, we present the short- and long-term outcomes of our initial experience with this procedure. We retrospectively analyzed 100 consecutive gastric cancer patients who underwent the delta-shaped anastomosis procedure from May 2001 to November 2006. All of them underwent a laparoscopic distal gastrectomy with regional lymph node dissection. Quality of life was assessed with a questionnaire 6 months or more postoperatively, and the gastric remnant was evaluated by endoscopy one year following the surgery. Eight surgeons successfully performed the delta-shaped anastomosis without any conversion to laparotomy. The learning curve for all surgeons was steep and the mean time for the anastomosis was 13 min. Only one patient developed an anastomotic leak, and the leak was minor. Sixty-five patients tolerated a 1500 kcal/day soft diet at the time of discharge. The mean follow-up period was 54.9 months. Only one patient reported symptoms indicative of dumping. Two patients were diagnosed with reflux esophagitis, and approximately 70% had evidence of bile reflux, but severe gastritis of the remnant stomach on endoscopy was uncommon. The wide lumen of the delta-shaped anastomosis led to early, adequate postoperative oral intake without a significant incidence of dumping syndrome. The delta-shaped anastomosis is safe and simple and provides satisfactory postoperative results.
Chronological age is not an independent predictor of clinical outcomes after radical nephroureterectomy

Higher chronological age has been suggested to confer worse prognosis in patients with upper tract urothelial carcinoma (UTUC). The aim of the current study was to test this hypothesis in a large multicenter external validation cohort of patients treated with radical nephroureterectomy (RNU) while controlling for patient performance status. We retrospectively reviewed the data from 1,169 patients treated with RNU for UTUC. Age at RNU was analyzed both as a continuous and categorical variable (<50 years, n = 66; 50–59.9 years, n = 185; 60–69.9 years, n = 367; 70–79.9 years, n = 419; ≥80 years, n = 132). Median follow-up was 37 months. Actuarial recurrence-free, cancer-specific, and all-cause survival estimates at 5 years after RNU were 69, 73, and 61%, respectively. Advanced age was associated with female gender, higher ECOG status, higher ASA score, and a lower probability of receiving adjuvant chemotherapy (all P values ≤ 0.02). In multivariable analyses, advanced age was associated with decreased recurrence-free (P = 0.021), cancer-specific (P = 0.002), and all-cause survival (P < 0.001) after controlling for the effects of gender, tumor location, number of lymph nodes removed, tumor grade, stage, architecture, necrosis, and lymphovascular invasion. After addition of ECOG status, age remained an independent predictor of only all-cause mortality (P > 0.001). We confirmed that advanced patient age at the time of RNU is associated with worse clinical outcomes after surgery. However, ECOG performance status abrogated the association. Furthermore, a large proportion of elderly patients were cured with RNU. This suggests that chronological age alone is an inadequate indicator criterion to predict response of older UTUC patients to RNU.
Exercise and obesity in fibromyalgia: beneficial roles of IGF-1 and resistin?

Severe fatigue is a major health problem in fibromyalgia (FM). Obesity is common in FM, but the influence of adipokines and growth factors is not clear. The aim was to examine effects of exercise on fatigue, in lean, overweight and obese FM patients.



In a longitudinal study, 48 FM patients (median 52 years) exercised for 15 weeks. Nine patients were lean (body mass index, BMI 18.5 to 24.9), 26 overweight (BMI 25 to 29.9) and 13 obese. Fatigue was rated on a 0 to 100 mm scale (fibromyalgia impact questionnaire [FIQ] fatigue) and multidimensional fatigue inventory (MFI-20) general fatigue (MFIGF). Higher levels in FIQ fatigue and MFIGF indicate greater degree of fatigue. Free and total IGF-1, neuropeptides, adipokines were determined in serum and cerebrospinal fluid (CSF).



Baseline FIQ fatigue correlated negatively with serum leptin (r=-0.345; P=0.016) and nerve growth factor (NGF; r=-0.412; P=0.037). In lean patients, baseline MFIGF associated negatively with serum resistin (r=-0.694; P=0.038). FIQ Fatigue associated negatively with CSF resistin (r=-0.365; P=0.073). Similarly, FIQ fatigue (r=-0.444; P=0.026) and MFIGF correlated negatively with CSF adiponectin (r=-0.508; P=0.01). In lean patients, FIQ fatigue (P=0.046) decreased after 15 weeks. After 30 weeks, MFIGF decreased significantly in lean ( P=0.017), overweight (MFIGF: P=0.001), and obese patients (MFIGF: P=0.016). After 15 weeks, total IGF-1 increased in lean (P=0.043) patients. ∆Total IGF-1 differed significantly between lean and obese patients (P=0.010). ∆Total IGF-1 related negatively with ∆MFIGF after 15 weeks (r=-0.329; P=0.050). After 30 weeks, ∆FIQ fatigue negatively correlated with ∆NGF (r=-0.463; P=0.034) and positively with ∆neuropeptide Y (NPY) (r=0.469; P=0.032). Resistin increased after 30 weeks (P=0.034). ∆MFIGF correlated negatively with ∆resistin (r=-0.346; P=0.031), being strongest in obese patients (r=-0.815; P=0.007). In obese patients, ∆FIQ fatigue after 30 weeks correlated negatively with ∆free IGF-1 (r=-0.711; P=0.032).



Exercise reduced fatigue in all FM patients, this effect was achieved earlier in lean patients. Baseline levels of resistin in both serum and CSF associated negatively with fatigue. Resistin was increased after the exercise period which correlated with decreased fatigue. Changes in IGF-1 indicate similar long-term effects in obese patients. This study shows reduced fatigue after moderate exercise in FM and indicates the involvement of IGF-1 and resistin in these beneficial effects.
Attenuation correction using asymmetric fanbeam transmission CT on two-head SPECT system.

For transmission computed tomography (TCT) systems using a centered transmission source with a fan-beam collimator, the transmission projection data are truncated. To achieve sufficiently large imaging field of view (FOV), we have designed the combination of an asymmetric fan-beam (AsF) collimator and a small uncollimated sheet-source for TCT, and implemented AsF sampling on a two-head SPECT system. The purpose of this study is to evaluate the feasibility of our TCT method for quantitative emission computed tomography (ECT) in clinical application. Sequential Tc-99m transmission and Tl-201 emission data acquisition were performed in a cardiac phantom (30 cm in width) with a myocardial chamber and a patient study. Tc-99m of 185 MBq was used as the transmission source. Both the ECT and TCT images were reconstructed with the filtered back-projection method after scatter correction with the triple energy window (TEW) method. The attenuation corrected transaxial images were iteratively reconstructed with the Chang algorithm utilizing the attenuation coefficient map computed from the TCT data. In this AsF sampling geometry, an imaging FOV of 50 cm was yielded. The attenuated regions appeared normal on the scatter and attenuation corrected (SAC) images in the phantom and patient study. The good quantitative accuracy on the SAC images was also confirmed by the measurement of the Tl-201 radioactivity in the myocardial chamber in the phantom study. The AsF collimation geometry that we have proposed in this study makes it easy to realize TCT data acquisition on the two-head SPECT system and to perform quantification on Tl-201 myocardial SPECT.
The validity of national hospital discharge register data on dementia: a comparative analysis using clinical data from a university medical centre.

Most information on the incidence and prognosis of dementia comes from small studies with limited precision and generalisability. Nationwide registers can be an alternative source of information, but only when the diagnosis is validly recorded. We assessed the validity of the Dutch Hospital Discharge Register (HDR).



HDR data on dementia diagnoses (ICD-9 codes 290.0; 290.1; 290.3; 290.4; 294.1; 331.0; 331.1; 331.82) in a university medical centre in the Netherlands were collected. Diagnoses were verified by using hospital medical records. Positive predictive values (PPVs) were calculated. Multivariate logistic regression models were used to evaluate determinants of inaccuracy in discharge diagnoses.



A sample of the HDR data was used for this study (n = 340). PPV was 93.2% for overall dementia, indicating confirmation of 93.2% of HDR dementia diagnoses by the medical records. The accuracy of the diagnosis of overall dementia in patients aged ≥ 65 years was significantly higher compared with younger patients (PPV 95.5 % vs. 67.9%; p = 0.0001). There was no difference in the accuracy of the diagnosis between men and women and accuracy was not influenced by type of admission, comorbidity and polypharmacy.



The results of this study show a high validity of the diagnosis of overall dementia in the HDR, making this register of great value for further nationwide research on dementia.
Citalopram neuropharmacological challenge in alcohol-dependent patients and controls: pharmacogenetic, endocrine and psychobehavioral results.

Alcoholism has been associated with long-lasting alterations in LHPA (limbic-hypothalamus-pituitary-adrenal) axis function, related to a dysfunction of the serotonergic neurotransmission. Functional polymorphisms of the serotonin system were previously reported to have significant influence on serotonin-induced neuroendocrine response. The aim of the study is to investigate in a double-blind, placebo-controlled approach, whether citalopram (a selective serotonin reuptake inhibitor, SSRI) would affect LHPA axis function as measured with ACTH (adrenocorticotrophic hormone) levels representing endocrine responsivity in 11 alcohol-dependent individuals compared to 12 controls. Furthermore we wanted to know whether functional polymorphisms (5-HTTLPR and 5HT2C Ser23Cys), have any influence on this responsivity.



Alcohol-dependent inpatients aged 36.45+/-7.7 years who were detoxified, without comorbid psychiatric/medical disorders or concurrent psychotropic medications, and 12 age-matched healthy controls aged 32.50+/-6.4 years were enrolled. Subjects also reported their subjective experiences like anxiety, craving and intoxication using visual analogue scales (VAS), side-effects were assessed by the serotonin syndrome scale (SSS). Measurements were taken at 8 timepoints at 30 mins interval, from -2 (60 mins pre-application) to +6 (180 mins post-application). Patients had a mean duration of illness of 8.91+/-3.4 years, consumed a mean of 326.36+/-220.8 g alcohol/day whereas control subjects consumed a mean of 32.50+/-41.4 g alcohol/day. A 0.4 mg citalopram/kg body weight dose was administered intravenously to patients (31.96+/-4.45 mg), and to controls (34.22+/-7.65 mg).



ACTH levels were higher for both groups in the verum compared to placebo administrations across timepoints. 5HT2C Ser23 alleles effected significantly higher ACTH responses under placebo administration but attenuated the responses under citalopram administration. Considering both groups together, no influence of 5-HTTLPR alleles was found on ACTH levels in either group under either regimen. While citalopram administration did not reduce craving in alcohol-dependent patients, it increased anxiety in patients and controls compared to placebo administration.



Despite the small differences in endocrine and subjective responses between alcoholic patients and controls, the effect of SSRI on endocrine response with respect to 5HT2C functional alleles deserves further investigation in larger samples to clarify whether this genetic variant constitutes a potential risk factor for changes in neuroendocrine functioning and subsequent psychiatric disorders.