nils-herrmann/clean_scirepeval huggingface dataset:
Validation and clinical application of a high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the quantitative determination of 10 anti-retrovirals in human peripheral blood mononuclear cells.

This paper reports the validation of a liquid chromatography tandem mass spectrometry (LC-MS/MS) method that allows the quantification of 10 antiretroviral (ARV) drugs in peripheral blood mononuclear cells (PBMCs) using 6 different isotopic internal standards (IS) and its clinical application. PBMCs are isolated from blood by density gradient centrifugation and drugs are extracted with a 60% methanol (MeOH) solution containing the 6 IS. The cell extract is then injected in the HPLC system and analytes are separated on a Symmetry Shield RP18 2.1 mm x 50 mm column. The different molecules are then detected by MS/MS in electrospray positive or negative ionisation modes and data are recorded using the multiple reaction monitoring (MRM) mode. Calibration curves are constructed in the range of 0.25-125 ng/ml of cell extract by a 1/x(2) weighted quadratic regression. The regression coefficients obtained are always greater than 0.99 and back calculated values always comprised in the range of +/-15% from their nominal concentration. Mean extraction recoveries are greater than 80% for all analytes and the method is accurate and precise with CV and bias lower than 9.4%. The lower limits of quantification (LLOQ) of the different drugs range from 0.0125 to 0.2 ng/ml of cell extract. This method was successfully applied to a cohort of 98 HIV-infected patients treated with Kaletra (400/100 mg of lopinavir/ritonavir (LPV/RTV) twice a day, n=48) or with Stocrin (600 mg once a day, n=50) and has been tested for cellular quantification of tipranavir (TPV) in 2 patients treated with Aptivus (500 mg twice a day). The patients treated by Kaletra showed mean cell-associated concentrations (CC) of 1819.0 and 917.2 ng/ml, for LPV and RTV, respectively. Patients treated with Stocrin showed mean CC of 2388.11 ng/ml while both patients under Aptivus showed TPV CC of 4322.7 and 1078.0 ng/ml, respectively. This method can be used to analyze ARV drug concentrations within the target tissue.
Sexual Risk, Serostatus and Intimate Partner Violence Among Couples During Pregnancy in Rural South Africa

The aim of this study was to describe sexual risk behavior among 239 couples during pregnancy and to examine the relationship of sexual risk behavior with HIV serostatus and intimate partner violence. One-third (31.8 %) of pregnant women and 20.9 % of male partners were HIV positive. HIV risk factors included lack of knowledge of partners’ HIV serostatus, unprotected sexual intercourse and multiple sexual partners. Among men, multivariate logistic regression identified awareness of HIV negative partner status, multiple sexual partners and low levels of partner violence and among women Zulu or Swati ethnicity were associated with unprotected intercourse. HIV positive concordance was associated with protected sex and in multilevel analysis of couples HIV positive status and awareness of the partner’s HIV positive status were associated with protected sex. High levels of HIV risk behaviour was found among couples during pregnancy calling for HIV risk reduction interventions. La meta de este estudio fue describir la conducta sexual de riesgo de 239 parejas durante el embarazo, y examinar la relación entre la conducta sexual de riesgo y VIH serostatus y la violencia doméstica. Un tercio (31.8 %) de las mujeres embarazadas y 20.9 % de las parejas masculinas eran VIH positivo. Los factores de riesgo de VIH incluyeron falta de conocimiento de VIH serostatus de la pareja, relación sexual sin protección y parejas sexuales múltiples. Entre los hombres, regresión logística multivariable identificó conciencia del estado de VIH negativo de la pareja, parejas sexuales múltiples y niveles bajos de violencia doméstica, y entre mujeres, la etnicidad Zulú o Swati fue asociada con relación sexual sin protección. Concordancia de VIH positivo fue asociada con sexo con protección, y en análisis de multiniveles de parejas, el estado VIH positivo y la conciencia del estado VIH positivo de la pareja fueron asociados con sexo con protección. Altos niveles de conducta de riesgo de VIH fueron encontrados entre parejas durante el embarazo, pidiendo intervenciones para reducir el riesgo de VIH.
Investigating the Experiences of Childhood Cancer Patients and Parents Participating in Optional Nontherapeutic Clinical Research Studies in the UK

While the majority of childhood cancer clinical trials are treatment related, additional optional research investigations may be carried out that do not directly impact on treatment. It is essential that these studies are conducted ethically and that the experiences of families participating in these studies are as positive as possible.



A questionnaire study was carried out to investigate the key factors that influence why families choose to participate in optional nontherapeutic research studies, the level of understanding of the trials involved, and the experiences of participation.



A total of 100 participants from six UK centers were studied; 77 parents, 10 patients >16 years, and 13 patients aged 8-15 years. Ninety-seven percent of parents and 90% of patients felt that information provided prior to study consent was of the right length, with 52% of parents and 65% of patients fully understanding the information provided. Seventy-four percent of parents participated in research studies in order to "do something important", while 74% of patients participated "to help medical staff". Encouragingly, <5% of participants felt that their clinical care would be negatively affected if they did not participate. Positive aspects of participation included a perception of increased attention from medical staff. Negative aspects included spending longer periods in hospital and the requirement for additional blood samples. Ninety-six percent of parents and 87% of patients would participate in future studies.



The study provides an insight into the views of childhood cancer patients and their parents participating in nontherapeutic clinical research studies. Overwhelmingly, the findings suggest that participation is seen as a positive experience.
Efficacy of Probiotic Escherichia coli Nissle 1917 in Patients with Irritable Bowel Syndrome: a Double Blind Placebo-controlled Randomized Trial.

to evaluate potential improvement effect for probiotic E. coliNissle 1917 in the management of refractory IBS in an Iranian population.



a double blind placebo controlled approach has been used in the current clinical trial. 139 confirmed IBS patients were included into the study, and were given probiotic E.coli Nissle 1917 for 6 weeks. 11 items Birmingham IBS Symptom Questionnairehas been used for evaluation of changes in the symptoms every 2 weeks.



sixty eight subjects (49%) were males. Mean±SD age of the participants was 38±13.3 years. 49(35.3%) of the patients were diarrhea-predominant. The total scores showed no significant difference between the intervention vs. control group(-6.7±6.8 vs. -6.7±6.5, respectively; p=0.95); neither did any of the questionnaire items any significant alterations in the two groups. After stratification of patients based on their IBS type, diarrhea-predominant patients showed a positive response to the probiotic improving their sleep (p=0.05 and 0.03 at weeks 2 and 6, respectively). Patients with constipation-predominant IBS showed no response to the probiotic; while patients with diarrhea-constipation mixed IBS showed unfavorable response to the probiotic in the need for strain to pass a motion compared to the placebo (p=0.03 and 0.02 at weeks 4 and 6, respectively).



probiotic therapy with E.coli Nissle 1917 was not able to induce significant improvement in the symptoms of patients with non-categorized IBS. Nevertheless, when IBS patients were recategorized to subgroups according to their main symptoms, evaluation of the efficacy of the probiotic on some individual items in the symptom list reached the significance level. Prospective clinical trials are recommended to confirm our findings.
Guided internet-based cognitive behavioural treatment for chronic back pain reduces pain catastrophizing: a randomized controlled trial.

The aim of this study was to investigate whether an Internet-based cognitive behavioural intervention would have an effect on the symptoms of chronic back pain.



Experimental design with a treatment group and a control group measured before and after a treatment period.



Participants who met the criteria for chronic back pain (n = 54).



All participants were screened in a live, structured interview before inclusion. The study period was 12 weeks and the treatment consisted of education, cognitive skills acquisition, behavioural rehearsal, generalization and maintenance. The main outcome of interest was the catastrophizing subscale of the Coping Strategies Questionnaire.



There were statistically significant reductions from pre- to post-treatment in catastrophizing in the treatment group, and an improvement in quality of life for the treatment group. However, most outcome measures did not indicate a positive treatment outcome. On a scale measuring pain catastrophizing, 58% (15/26) of the treated participants showed reliable improvement, compared with 18% (5/28) of the control group.



Internet-based cognitive behavioural therapy can serve as a complement for individuals with chronic pain who prefer this treatment and have difficulties accessing specialist treatment facilities.
Belgian Fabry study: prevalence of Fabry disease in a cohort of 1000 young patients with cerebrovascular disease.

Data on the prevalence of Fabry disease in patients with central nervous system pathology are limited and controversial. In this study, we assessed the prevalence of Fabry disease in young patients presenting with cerebrovascular disease in Belgium.



In this national, prospective, multicenter study, we screened for Fabry disease in 1000 patients presenting with ischemic stroke, transient ischemic attack, or intracranial hemorrhage; unexplained white matter lesions; or vertebrobasilar dolichoectasia. In male patients, we measured alpha-galactosidase A (alpha-GAL A) activity in dried blood spots. Female patients were screened for mutations by exonic DNA sequencing of the alpha-GAL A gene.



alpha-GAL A activity was deficient in 19 men (3.5%), although all had normal alpha-GAL A gene sequences. Enzymatic deficiency was confirmed on repeat assessment in 2 male patients (0.4%). We identified missense mutations in 8 unrelated female patients (1.8%): Asp313Tyr (n=5), Ala143Thr (n=2), and Ser126Gly (n=1). The pathogenicity of the 2 former missense mutations is controversial. Ser126Gly is a novel mutation that can be linked to late-onset Fabry disease.



alpha-GAL A deficiency may play a role in up to 1% of young patients presenting with cerebrovascular disease. These findings suggest that atypical variants of Fabry disease with late-onset cerebrovascular disease exist, although the clinical relevance is unclear in all cases.
Appropriateness of internal digital phantoms for monitoring the stability of the UBIS 5000 quantitative ultrasound device in clinical trials

In bone status assessment, proper quality assurance/quality control is crucial since changes due to disease or therapeutic treatment are very small, in the order of 2–5%. Unlike for dual X-ray absorptiometry, quality control procedures have not been extensively developed and validated for quantitative ultrasound technology, limiting its use in longitudinal monitoring. While the challenge of developing an ideal anthropometric phantom is still open, some manufacturers use the concept of the internal digital phantom mimicking human characteristics to check the stability of their device. The objective of the study was to develop a sensitive model of quality control suitable for the correction of QUS patient data. In order to achieve this goal, we simulated a longitudinal device lifetime with both correct and malfunctioning behaviors. Then, we verified the efficiency of digital phantoms in detecting those changes and subsequently established the in vitro/in vivo relationship. This is the first time that an attempt to validate an internal digital phantom has made, and that this type of validation approach is used. The digital phantom (DP) was designed to mimic normal bone (BUAP2) and osteoporotic bone (BUAP1) properties. The DP was studied using the UBIS 5000 ultrasound device (DMS, France). Diverse malfunctions of the UBIS-5000 were simulated. Several series of measurements were performed on both BUAP1 and 2 and on 12 volunteers at each grade of malfunction. The effect of each simulated malfunction on in vivo and in vitro results was presented graphically by plotting the average BUA values against the percentage change from baseline. The change from baseline in BUA was modeled using linear regression, and the in vivo/in vitro ratio was obtained from the model. All experimentations influenced the measure of BUAP1 and 2 as well as the measure of our 12 volunteers. However, the degree of significance varied as a function of the severity of the malfunction, and the results also differed substantially in magnitude between in vivo and in vitro. Indeed, the DP was about 10 times more sensitive to variations of the transfer function than was the in vivo measurement, which is very reassuring. The sensitivity of the digital phantoms was reliable in the determination of simulated malfunctions of the UBIS-5000. The digital phantoms provided an accurate evaluation of the acoustic performance of the scanner, including the fidelity of transducers. In light of these results, the QC approach of the UBIS-5000 will be extremely simple to implement compared with other devices. Indeed, since the digital phantom was automatically measured during every patient measurement, the QC approach could be built on an individual level basis rather than on an average basis.
Hop rho iso-alpha acids, berberine, vitamin D3 and vitamin K1 favorably impact biomarkers of bone turnover in postmenopausal women in a 14-week trial

Osteoporosis is a major health issue facing postmenopausal women. Increased production of pro-inflammatory cytokines resulting from declining estrogen leads to increased bone resorption. Nutrition can have a positive impact on osteoporosis prevention and amelioration. The objective of this study was to investigate the impact of targeted phytochemicals and nutrients essential for bone health on bone turnover markers in healthy postmenopausal women. In this 14-week, single-blinded, 2-arm placebo-controlled pilot study, all women were instructed to consume a modified Mediterranean-style low-glycemic-load diet and to engage in limited aerobic exercise; 17 randomized to the placebo and 16 to the treatment arm (receiving 200 mg hop rho iso-alpha acids, 100 mg berberine sulfate trihydrate, 500 IU vitamin D3 and 500 μg vitamin K1, twice daily). Thirty-two women completed the study. Baseline nutrient intake did not differ between arms. At 14 weeks, the treatment arm exhibited an estimated 31% mean reduction (P = 0.02) in serum osteocalcin (a marker of bone turnover), whereas the placebo arm exhibited a 19% increase (P = 0.03) compared to baseline. Serum 25-hydroxyvitamin D (25(OH)D) increased by 13% (P = 0.24) in the treatment arm and decreased by 25% (P < 0.01) in the placebo arm. The between-arm differences for OC and 25(OH)D were statistically significant. Serum IGF-I was increased in both arms, but the increase was more significant in the treatment arm at 14 weeks (P < 0.01). Treatment with hop rho iso-alpha acids, berberine sulfate trihydrate, vitamin D3 and vitamin K1 produced a more favorable bone biomarker profile that supports a healthy bone metabolism.
Prevalence of intra-abdominal hypertension in critically ill patients: a multicentre epidemiological study

Although intra-abdominal hypertension (IAH) can cause dysfunction of several organs and raise mortality, little information is available on the incidence and risk factors for IAH in critically ill patients. This study assessed the prevalence of IAH and its risk factors in a mixed population of intensive care patients. A multicentre, prospective 1-day point-prevalence epidemiological study conducted in 13 ICUs of six countries. None. Ninety-seven patients admitted for more than 24 h to one of the ICUs during the 1-day study period. Intra-abdominal pressure (IAP) was measured four times (every 6 h) by the bladder pressure method. Data included the demographics, medical or surgical type of admission, SOFA score, etiological factors such as abdominal surgery, haemoperitoneum, abdominal infection, massive fluid resuscitation, and ileus and predisposing conditions such as hypothermia, acidosis, polytransfusion, coagulopathy, sepsis, liver dysfunction, pneumonia and bacteraemia. We enrolled 97 patients, mean age 64±15 years, 57 (59%) medical and 40 (41%) surgical admission, SOFA score of 6.5±4.0. Mean IAP was 9.8±4.7 mmHg. The prevalence of IAH (defined as IAP 12 mmHg or more) was 50.5 and 8.2% had abdominal compartment syndrome (defined as IAP 20 mmHg or more). The only risk factor significantly associated with IAH was the body mass index, while massive fluid resuscitation, renal and coagulation impairment were at limit of significance. Although we found a quite high prevalence of IAH, no risk factors were reliably associated with IAH; consequently, to get valid information about IAH, IAP needs to be measured.
Low doses of TRH in amyotrophic lateral sclerosis and in other neurological diseases

30 subjects — 23 with amyotrophic lateral sclerosis (ALS), 4 with Charcot-Marie Tooth atrophy, 2 with progressive spinal muscle atrophy and 1 with radiation myelopathy —were given chronic low-dose TRH therapy. The effects of treatment were assessed on the scale of Norris et al. (1974). The outcome of the study, in agreement with some and at variance with other studies, was that TRH induced a statistically significant neurological improvement in 17 of the 23 ALS patients but little or none in the other ALS patients and in patients with other neurological diseases. 30 soggetti di cui 23 affetti da Sclerosi Laterale Amiotrofica, 4 dalla malattia di Charcot-Marie-Tooth, 2 affetti da Amiotrofia Spinale Progressiva, 1 affetto, da una Mielopatia da Raggi X, sono stati sottoposti ad un trattamento cronico con basse dosi di TRH. Gli effetti della terapia sulle performances neurologiche sono stati valutati con la scala di Norris et al. (1974). I risultati dello studio, in parte in accordo, in parte in contrasto con quelli di precedenti studi, mostrano che il TRH induce un miglioramento, statisticamente significativo, delle performances neurologiche in 17 dei 23 pazienti con SLA mentre determina modificazioni insignificanti o nessuna modificazione nei restanti casi di SLA e nei soggetti affetti da altre malattie neurologiche.
Body fat abnormality in HIV-infected children and adolescents living in Europe: prevalence and risk factors.

To estimate the prevalence of and identify risk factors for lipodystrophy syndrome (LS) and body fat abnormality in a population of HIV-infected children and adolescents.



Cross-sectional observational study.



HIV-infected subjects aged 2-18 years were recruited from 15 HIV centers in Belgium, Italy, and Poland between January 2007 and December 2008. Standardized assessments by the patient's long-term clinician were performed to establish the presence of abnormality. Risk factors were explored in logistic regression models for fat abnormality outcomes and LS (abnormality plus dyslipidemia).



Among 426 subjects (70% white), median age was 12.2 years (interquartile range: 9.0-15.0 years) and median duration of antiretroviral therapy was 5.2 years (interquartile range: 2.2-8.8 years). Prevalence was 57% (n = 235) for LS and 42% (n = 176) for fat abnormality; 90 subjects with abnormality were affected in ≥3 locations. Lipoatrophy occurred in 28% (n = 117) of subjects and lipohypertrophy in 27% (n = 115), most commonly in the face and trunk, respectively. In multivariable analysis, white ethnicity, body mass index, ritonavir/lopinavir, and nonnucleoside reverse transcriptase inhibitors were each associated with an increased risk of LS (P < 0.05). White ethnicity, history of Centers for Disease Control and Prevention-defined disease, and stavudine were associated with risk of lipoatrophy (P < 0.05). Increased risk of lipohypertrophy was associated with body mass index and prior HIV disease.



Fat abnormality was prevalent in close to half of children and adolescents, who had accumulated long treatment durations. Risk of fat abnormality was associated with specific drugs, including stavudine and ritonavir, and other variables. Our results underline the importance of continued surveillance of children treated with antiretroviral therapy.
A comprehensive care management program to prevent chronic obstructive pulmonary disease hospitalizations: a randomized, controlled trial.

Improving a patient's ability to self-monitor and manage changes in chronic obstructive pulmonary disease (COPD) symptoms may improve outcomes.



To determine the efficacy of a comprehensive care management program (CCMP) in reducing the risk for COPD hospitalization.



A randomized, controlled trial comparing CCMP with guideline-based usual care. 
Patients hospitalized for COPD in the past year.



The CCMP included COPD education during 4 individual sessions and 1 group session, an action plan for identification and treatment of exacerbations, and scheduled proactive telephone calls for case management. Patients in both the intervention and usual care groups received a COPD informational booklet; their primary care providers received a copy of COPD guidelines and were advised to manage their patients according to these guidelines. Patients were randomly assigned, stratifying by site based on random, permuted blocks of variable size.



The primary outcome was time to first COPD hospitalization. Staff blinded to study group performed telephone-based assessment of COPD exacerbations and hospitalizations, and all hospitalizations were blindly adjudicated. Secondary outcomes included non-COPD health care use, all-cause mortality, health-related quality of life, patient satisfaction, disease knowledge, and self-efficacy.



Of the eligible patients, 209 were randomly assigned to the intervention group and 217 to the usual care group. Citing serious safety concerns, the data monitoring committee terminated the intervention before the trial's planned completion after 426 (44%) of the planned total of 960 patients were enrolled. Mean follow-up was 250 days. When the study was stopped, the 1-year cumulative incidence of COPD-related hospitalization was 27% in the intervention group and 24% in the usual care group (hazard ratio, 1.13 [95% CI, 0.70 to 1.80]; P= 0.62). There were 28 deaths from all causes in the intervention group versus 10 in the usual care group (hazard ratio, 3.00 [CI, 1.46 to 6.17]; P= 0.003). Cause could be assigned in 27 (71%) deaths. Deaths due to COPD accounted for the largest difference: 10 in the intervention group versus 3 in the usual care group (hazard ratio, 3.60 [CI, 0.99 to 13.08]; P= 0.053).



Available data could not fully explain the excess mortality in the intervention group. Ability to assess the quality of the educational sessions provided by the case managers was limited.



A CCMP in patients with severe COPD had not decreased COPD-related hospitalizations when the trial was stopped prematurely. The CCMP was associated with unanticipated excess mortality, results that differ markedly from similar previous trials. A data monitoring committee should be considered in the design of clinical trials involving behavioral interventions.