nils-herrmann/clean_scirepeval huggingface dataset:
Plasma concentrations of generic lopinavir/ritonavir in HIV type-1-infected individuals.

Generic drugs can contribute to access to treatment for HIV-infected patients. However quality and safety remains an issue of concern. Therefore, we evaluated minimal plasma concentrations and short-term safety of a generic lopinavir/ritonavir 200/50 mg tablet formulation.



In a single-centre prospective pilot study, patients receiving protease-inhibitor-based antiretroviral treatment were switched to a generic lopinavir/ritonavir tablet at the standard dose (400/100 mg twice daily). Minimum drug concentrations (C(min)) of lopinavir and ritonavir were performed before switching (in 16 patients who were on Kaletra((R)) soft-gel capsules) and after 4 weeks (in all patients). Plasma levels of lopinavir and ritonavir were determined by a validated HPLC method. Either the Wilcoxon signed-rank or Mann-Whitney U test was used to compare the groups.



A total of 37 patients (18 females) were included in the study. Two stopped their study medications prematurely because of intolerance. The median (interquartile range) lopinavir C(min) was 7.2 mg/l (5.8-8.3) and no patients had subtherapeutic levels <1.0 mg/l. No significant difference of lopinavir C(min) levels was found between Kaletra((R)), and the generic product (P=0.224). By contrast, the C(min) of generic ritonavir was higher (P=0.012). Food did not affect the drug levels. Mild gastrointestinal complaints were reported in 12 patients.



The generic lopinavir/ritonavir tablet showed C(min) plasma concentrations similar to what is described for the branded product, with good stability, independent of food intake. These data support the efforts in scaling up access to generic second-line treatment in middle- and low-income countries.
Comment on: ‘Vitamin D supplements and cancer incidence and mortality: a meta-analysis'

Over 2–7 years of duration, vitamin D supplementations had little effect on total cancer incidence (400–1100 IU per day, summary relative risk (RR)1⁄4 1.00, 95% confidence interval (CI)1⁄4 0.94–1.06, I1⁄4 0%; four RCTs with combined 4333 cases), but significantly reduced total cancer mortality (400–833 IU per day, summary RR1⁄4 0.88, 95% CI1⁄4 0.78–0.98, I1⁄4 0%, three RCTs with combined 1190 deaths).
Effect of intracoronary streptokinase administered immediately after primary percutaneous coronary intervention on long-term left ventricular infarct size, volumes, and function.

The purpose of this study was to investigate the reflections of the improvement in microvascular perfusion provided by adjuvant intracoronary streptokinase (ICSK) on late-phase infarct size and left ventricular volumes and functions.



It has been shown that ICSK given immediately after primary percutaneous coronary intervention (PCI) improves myocardial perfusion in the early days of ST-segment elevation acute myocardial infarction.



Ninety-five patients undergoing primary PCI were randomized to ICSK 250 kU (n = 51) or no additional therapy (n = 44). Two days later, coronary hemodynamic indexes were measured to evaluate tissue-level perfusion. After 6 months, angiography, echocardiography, and technetium-99m single-photon emission computed tomography (SPECT) were performed.



At 2 days, all indexes of microvascular function were significantly better in the ICSK group than in the control group, including coronary flow reserve (2.5 vs. 1.7, p < 0.001) and index of microvascular resistance (20.2 vs. 34.2, p < 0.001). At 6 months, infarct size (22.7% vs. 32.9%; p = 0.003) and left ventricular end-systolic (41.1 ml vs. 60.9 ml; p = 0.009) and end-diastolic volumes (95.5 ml vs. 118.3 ml; p = 0.006) were significantly smaller, and the ejection fraction was significantly higher (57.2% vs. 51.8%; p = 0.018) in the ICSK group compared with the control group.



In this study, it has been demonstrated that low-dose ICSK given immediately after primary PCI significantly limits long-term infarct size and preserves left ventricular volumes and functions.
Physical therapy and chiropractic use among childhood cancer survivors with chronic disease: impact on health-related quality of life.

The use of rehabilitation services to address musculoskeletal, neurological and cardiovascular late effects among childhood cancer survivors could improve physical function and health-related quality-of-life (HRQL). We describe physical therapy (PT) and chiropractic utilization among childhood cancer survivors and their association with HRQL.



The sample included 5+ year survivors from the Childhood Cancer Survivor Study (N = 9,289). Questions addressing use of PT or chiropractic services and HRQL (Medical Outcomes Survey Short Form (SF-36)) were evaluated. Multivariable regression models compared PT and/or chiropractic utilization between survivors and siblings, and by diagnosis, treatment and demographic characteristics; associations between chronic disease, PT/chiropractic use, and HRQL were similarly evaluated.



Survivors were not more likely to use PT (OR 1.0; 95% CI 0.8-1.2) or chiropractic (OR 0.8; 95% CI 0.7-1.0) services than siblings. More survivors reported using chiropractic (12.4%) than PT (9.2%) services. Older age and having health insurance were associated with utilization of either PT or chiropractic services. Grade 3-4 chronic conditions and a CNS tumor or sarcoma history were associated with PT but not with chiropractic service utilization. Survivors with musculoskeletal (OR 1.8; 95% CI 1.1-2.9), neurological (OR 3.4; 95% CI 1.6-6.9), or cardiovascular (OR 3.3; 95% CI 1.6-6.9) chronic conditions who used PT/chiropractic services were more likely to report poor physical health than survivors who did not use services.



The reported prevalence of PT/chiropractic among survivors is consistent with that reported by siblings. Severity of late effects is associated with service use and with reporting poor physical health.



Long-term childhood cancer survivors do not appear to utilize rehabilitation services to optimize physical function and support increased HRQL.
Endoscopic and symptomatic assessment of anastomotic strictures following esophagectomy and cervical esophagogastrostomy

Dysphagia following esophagectomy with cervical esophagogastric anastomosis is common and often can be attributed to anastomotic stricture. The prevalence, risk factors, symptomatic and endoscopic severity, and response to dilation of such strictures, however, are poorly defined. In the present study the population consisted of 42 patients undergoing esophagectomy with gastric pull-up and cervical anastomosis. Any complaint of postoperative dysphagia was investigated with upper endoscopy. Patients undergoing endoscopy were entered into a prospective randomized trial of graduated balloon versus bougie-over-a-guidewire dilation that will be part of a future report. Dysphagia was assigned a standardized severity score, and stricture diameter pre-dilation was classified as minimal (>12 mm), mild (9–12 mm), moderate (5–8 mm), or severe (<5 mm). Outcome measures included the incidence, time to first dilation, symptomatic and endoscopic severity of anastomotic strictures, number of dilations, and influence of co-morbidities and anastomotic technique on stricture occurrence. Twenty-seven of 41 (66%) surviving patients underwent endoscopy and dilation. Median time to presentation was 2.4 months (min, 27 days; max, 11 months). Most patients (63%) with stricture complained of dysphagia with every meal. The majority (93%) of strictures were mild to moderate (5–12 mm), and there was no correlation between dysphagia frequency and stricture size. Tolerance of an unrestricted diet decreased with increasing stricture severity. In all, 98 dilation sessions were performed without complication. A higher stricture rate was noted following handsewn anastomoses as compared to combined stapled and handsewn anastomoses (85.7% versus 55.5%; p = 0.044). Most patients with symptomatic anastomotic strictures following esophagectomy with cervical esophagogastrostomy present within the first few months following surgery. Half of such strictures are minimal to mild as endoscopically assessed. Dilation is safe, and most patients experience symptomatic relief after only a few dilation sessions. A combined handsewn and stapled anastomosis may decrease the risk of stricture formation relative to a two-layer handsewn technique.
Effects of vildagliptin on postprandial markers of bone resorption and calcium homeostasis in recently diagnosed, well-controlled type 2 diabetes patients.

Bone metabolism is a dynamic process that is influenced by food ingestion. Endogenous incretins have been shown to be important regulators of bone turnover. The aim of the present study was to assess whether a dipeptidylpeptidase (DPP)-4 inhibitor affects markers of bone resorption and calcium homeostasis.



The present study was a single-center, double blind, randomized clinical trail. Fifty-nine drug-naïve patients with type 2 diabetes (T2D) were randomized to either 1 year treatment with the DPP-4 inhibitor vildagliptin (100 mg, once daily; n = 29) or placebo (n = 30). Patients received a standardized breakfast after measurement of serum concentrations of cross-linked C-terminal telopeptide (s-CTx), a bone resorption marker influenced by food intake, before and after 50 weeks treatment.



Vildagliptin did not change postprandial s-CTx concentrations compared with pretreatment levels (between-group ratio 1.15 ± 0.17; P = 0.320). Fasting serum alkaline phosphatase, calcium, and phosphate were also unaffected y 1 year treatment with vildagliptin.



Treatment with vildagliptin for 1 year was not associated with changes in markers of bone resorption and calcium homeostasis in drug-naïve patients with T2D and mild hyperglycemia.
The A 1 chieve study : a 60000-person , global , prospective , observational study of basal , mealtime , and biphasic insulin analogs in daily clinical practice

a Department of Endocrinology, S.L. Raheja Hospital, Mumbai, India b Hospital Italiano de Buenos Aires, Buenos Aires, Argentina c Endocrinology Section, Bader Medical Complex, Amman, Jordan d Novo Nordisk Region International Operations A/S, Zurich, Switzerland e National Centre for Diabetes & Endocrinology, Tripoli, Libya
Phase I trial of a novel human monoclonal antibody mAb216 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia.

This phase I trial was conducted to determine the safety and pharmacokinetics of monoclonal antibody 216, a human monoclonal Immunoglobulin M antibody targeting a linear B-cell lactosamine antigen, administered alone and in combination with vincristine in patients with relapsed or refractory B-cell acute lymphoblastic leukemia, and to preliminarily assess tumor targeting and efficacy.



Three cohorts of patients received escalating doses of monoclonal antibody 216 administered as an intravenous infusion. In the case of poor response to the first dose of monoclonal antibody 216 alone, defined as less than 75% reduction in peripheral blood blast count, a second dose of the antibody with vincristine was given between days 4 and 7. Responses were assessed weekly until day 35. Serum concentration of monoclonal antibody 216 was measured before and after infusion. Monoclonal antibody 216 targeting was determined with an anti-idiotypic antibody to monoclonal antibody 216 and preliminary efficacy was analyzed by changes in peripheral blood blasts.



Thirteen patients were enrolled. One episode of grade 3 epistaxis was the only dose-limiting toxicity observed. All patients showed a poor response to the first monoclonal antibody 216 infusion with a decrease in peripheral blasts from 6-65% in 9 patients. In 8 patients, addition of vincristine to monoclonal antibody 216 resulted in an average reduction of the peripheral blasts of 81%. One patient without peripheral blasts achieved a hypoplastic marrow without evidence of leukemia after one infusion of monoclonal antibody 216 and monoclonal antibody 216/vincristine each. Monoclonal antibody 216 was detected on peripheral blasts in all patients.



Treatment with monoclonal antibody 216 in combination with vincristine is feasible and well tolerated in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Binding of monoclonal antibody 216 to leukemic blasts was efficient, and favorable early responses were observed.
Effect of a universal anxiety prevention programme (FRIENDS) on children's academic performance: results from a randomised controlled trial

Evaluations of school-based anxiety prevention programmes have reported improvements in psychological functioning although little is known about their effect upon educational outcomes.



One thousand three hundred and sixty-two children from 40 primary schools in England took part in the randomised controlled trial, Preventing Anxiety in Children through Education in Schools. The trial investigated the effectiveness of a universal school-based cognitive behaviour therapy prevention programme, FRIENDS, delivered by health care staff or school staff compared with usual personal, social, health and education (PSHE) lessons. Self-report psychological outcomes and educational attainment on national standardised attainment tests in reading, writing and maths were collected 12 months postintervention. Analysis was performed at individual level using multivariable mixed effect models controlling for gender, type of intervention and school effect. 
At 12 months, anxiety reduced in the health-led FRIENDS group compared to school-led FRIENDS and PSHE. There were no between-group differences in academic performance regardless of gender, deprivation, ethnicity and additional educational needs.



School-based mental health interventions should assess psychological and educational outcomes. Further research should directly compare the effects of interventions led by health and school staff.
Effects of clarithromycin in patients with active rheumatoid arthritis.

To evaluate the clinical efficacy, safety, and tolerability of clarithromycin in patients with rheumatoid arthritis.



This was a 6-month, monocenter, randomized, double-blind, placebo-controlled study. A total of 81 patients with early rheumatoid arthritis were treated with either once-daily oral clarithromycin (500 mg) or daily oral placebo for 6 months.



The primary efficacy variable was the percentage of patients who had a 20% improvement according to American College of Rheumatology (ACR) criteria (an ACR 20 response) at 6-months. Secondary outcome measures were 50% improvement and 70% improvement according to ACR criteria (an ACR 50 response and an ACR 70 response, respectively).



A significantly greater percentage of patients treated with 500 mg clarithromycin met the ACR 20 response at 6 months compared with patients who received placebo (59 vs. 33%; p < 0.001). Greater percentages of patients treated with 500 mg clarithromycin also achieved ACR 50 responses (34 vs. 10%; p < 0.001) and ACR 70 responses (20 vs. 3%; p = 0.003) compared with patients who received placebo, respectively. Clarithromycin was well tolerated. There were no dose-limiting toxic effects.



In patients with early active rheumatoid arthritis, treatment with clarithromycin significantly improved the signs and symptoms of rheumatoid arthritis. Clarithromycin has been shown to be effective against rheumatoid arthritis.
Software version of Roland Morris Disability questionnaire for outcome assessment in low back pain.

Developing and using the software version of existing validated paper version of patient-related outcome can go a long way in saving cost, time and effort. However, the equivalence of paper version and software versions cannot be assumed. The aim of the study is to test the equivalence between paper version and software version of Roland Morris Disability Questionnaire and its acceptability among patients.



This is a within-subject cross over equivalence study. Fifty-five patients with back pain were asked to complete the paper and software version of RMDQ in random order. Patients were included from the Neuro Spinal surgery outpatient department of Lilavati Hospital and Research Center.



Statistical analysis of 52 patients who completed the study showed high agreement between the paper and software version of the questionnaire (intraclass correlation coefficient 0.994, 95% confidence interval (0.989-0.996)). High sensitivity and specificity of 84 and 88% of the software version was noted. About 69.2% patients preferred software version over paper version.



Our study shows that software version is comparable to the paper version. It may prove to be a useful tool for epidemiological studies and patient follow-up over longer period.
Rheumatoid Arthritis Risk Associated with Periodontitis Exposure: A Nationwide, Population-Based Cohort Study

The risk of periodontitis (PD) is increased in the patient group of rheumatoid arthritis (RA). RA and PD also shared some pathological mechanism. The aim of this study is to investigate the risk of RA associated with PD exposure.



This study identified 3 mutually exclusive cohorts using the 1999-2010 Taiwanese National Health Insurance Research Database (NHIRD) to investigate the association between PD and the risk of incident RA. All patients with PD in 2000 were identified from the database of all enrollees as the PD cohort. From the representative database of 1,000,000 enrollees randomly selected in 2010 (LHID2010), individuals without any periodontal disease (PO) during 1999-2010 were selected as the non-PO cohort. Individuals who were not included in the non-PO cohort and received dental scaling (DS) no more than two times per year during 1999-2010 were selected as the DS cohort from LHID2010. Using cox proportional regression analysis, hazard ratios (HRs) with 95% confidence intervals (Cis) were calculated to quantify the association between PD exposure and RA development. In the three-group comparison using the non-PO cohort as reference, we found that the risk of RA was higher in the PD and DS cohorts (HRs, 1.89 and 1.43; 95% CIs, 1.56-2.29 and 1.09-1.87, respectively). For comparisons between two cohorts, the PD cohort had a higher risk of RA than the non-PO and DS cohorts (HRs, 1.91 and 1.35; 95% CIs, 1.57-2.30 and 1.09-1.67, respectively).



PD was associated with an increased risk of RA development.
Comparison of patient and partner quality of life and health outcomes in the first year after an implantable cardioverter defibrillator (ICD)

Recovery following an implantable cardioverter defibrillator (ICD) impacts both the patient and partner, often in divergent ways. Patients may have had a cardiac arrest or cardiac arrhythmias, whereas partners may have to perform CPR and manage the ongoing challenges of heart disease therapy. Currently, support for post-ICD care focuses primarily on restoring patient functioning with few interventions available to partners who serve as primary support. This descriptive study examined and compared patterns of change for both patients and partners during the first year post-ICD implantation. For this longitudinal study, the sample included 42 of 55 (76.4 %) patient–partner dyads who participated in the ‘usual care’ group of a larger intervention RCT with patients following ICD implant for secondary prevention of cardiac arrest. Measures taken at across five time points (at hospital discharge and at 1, 3, 6 and 12 months follow up) tracked physical function (SF-12 PCS, symptoms); psychological adjustment (SF-12 MCS; State-Trait Anxiety Inventory; CES-D); relationship impact (Family Functioning, DOII; Mutuality and Interpersonal Sensitivity, MIS); and healthcare utilization (ED visits, outpatient visits, hospitalizations). Repeated measures analysis of variance was used to characterize and compare outcome trends for patients and partners across the first 12 months of recovery. Patients were 66.5 ± 11.3 (mean + SD) years old, predominately Caucasian male (91 %), with Charlson co-morbidities of 4.4 ± 2.4. Partners were 62.5 ± 11.1 years old, predominantly female (91 %) with Charlson co-morbidities of 2.9 ± 3.0. Patient versus partner differences were observed in the pattern of physical health (F = 10.8, p < 0.0001); patient physical health improved while partner health showed few changes. For partners compared to patients, anxiety, depression, and illness demands on family functioning tended to be higher. Patient mutuality was stable, while partner mutuality increased steadily (F = 2.5, p = 0.05). Patient sensitivity was highest at discharge and declined; partner sensitivity increased (F = 10.2, p < 0.0001) across the 12-month recovery. Outpatient visits for patients versus partners differed (F = 5.0, p = 0.008) due most likely to the number of required patient ICD visits. Total hospitalizations and ED visits were higher for patients versus partners, but not significantly. The findings highlight the potential reciprocal influences of patient and partner responses to the ICD experience on health outcomes. Warranted are new, sound and feasible strategies to counterbalance partner needs while simultaneously optimizing patient recovery outcomes.
Inhibition of the Ras/Raf/MEK/ERK and RET kinase pathways with the combination of the multikinase inhibitor sorafenib and the farnesyltransferase inhibitor tipifarnib in medullary and differentiated thyroid malignancies.

Ras/Raf/MAPK kinase/ERK and rearranged in transformation (RET) kinase pathways are important in thyroid cancer. We tested sorafenib, a B-Raf, RET, and vascular endothelial growth factor receptor kinase inhibitor, combined with tipifarnib, a farnesyltransferase inhibitor that inactivates Ras and other farnesylated proteins.



We treated 35 patients with differentiated thyroid cancer (DTC) and medullary thyroid cancer (MTC) in a phase I trial. Sorafenib and tipifarnib were given for 21 d with 7 d rest in each 28-d cycle.



We enrolled 22 patients with metastatic DTC (16 papillary, five follicular, and one poorly differentiated) and 13 patients with MTC, of whom 15 with DTC and 10 with MTC reached first restaging. When tissue was available, eight of 15 DTC patients (53%) had B-Raf mutations; eight of 13 MTC (61.5%) patients had RET mutations. MTC partial response rate was 38% (five of 13) (duration = 9+, 12, 13, 16+, and 34+ months), stable disease of at least 6 months was 31% (four of 13). The DTC partial response rate was 4.5% (one of 22), and stable disease of at least 6 months was 36% (eight of 22). Median progression-free survival for all 35 patients was 18 months (95% confidence interval, 14.6 to not reached months). Median overall survival has not been reached, with a median follow-up of 24 months with 80% overall survival. Grade 1-2 toxicities were mainly rash, fatigue, and diarrhea. The most common grade 3-4 toxicities were rash, rise in amylase/lipase, and fatigue.



Inhibiting the Ras/Raf/MAPK kinase/ERK and RET kinase pathways with sorafenib and tipifarnib is well tolerated and active against thyroid cancer.