nils-herrmann/clean_scirepeval huggingface dataset:
Design and methods of the MAINTAIN study: a randomized controlled clinical trial of micronutrient and antioxidant supplementation in untreated HIV infection.

Micronutrient deficiencies are common in HIV positive persons and are associated with a poorer prognosis, but the role of micronutrient supplementation in the medical management of HIV infection remains controversial, as some but not all studies show immunological and clinical benefit. Micronutrients supplementation could be a relatively low cost strategy to defer the initiation of expensive, potentially toxic and lifelong antiretroviral therapy. The MAINTAIN study is a Canadian multi-center randomized control double blind clinical trial to evaluate if micronutrient supplementation of HIV positive persons slows progression of immune deficiency and delays the need to start antiretroviral therapy and is safe, compared to standard multivitamins. Untreated asymptomatic HIV positive adults will receive a micronutrient and antioxidant preparation (n = 109) or an identical appearing recommended daily allowance multivitamin and mineral preparation (n = 109) for two years. Participants will be followed quarterly and monitored for time from baseline to CD4 T lymphocyte count <350 mm(3), or emergence of CDC-defined AIDS-defining illness, or the start of antiretroviral therapy. We will also compare safety and health related quality of life between groups. Primary analysis will compare the incidence of the composite primary outcome between study groups and will be by intention-to-treat. The study was originally expected to last three years, with accrual over one year and a minimum of two years follow up of the last enrolled participant. We discuss here the study design and methods, often used for evaluation of complementary and adjunctive treatments for health maintenance in HIV infection, which are common interventions.
Antibiotics in addition to systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease.

The role of antibiotics in acute exacerbations is controversial and their efficacy when added to systemic corticosteroids is unknown.



We conducted a randomized, placebo-controlled trial to determine the effects of doxycycline in addition to corticosteroids on clinical outcome, microbiological outcome, lung function, and systemic inflammation in patients hospitalized with an acute exacerbation of chronic obstructive pulmonary disease.



Of 223 patients, we enrolled 265 exacerbations defined on the basis of increased dyspnea and increased sputum volume with or without increased sputum purulence. Patients received 200 mg of oral doxycycline or matching placebo for 7 days in addition to systemic corticosteroids. Clinical and microbiological response, time to treatment failure, lung function, symptom scores, and serum C-reactive protein were assessed.



On Day 30, clinical success was similar in intention-to-treat patients (odds ratio, 1.3; 95% confidence interval, 0.8 to 2.0) and per-protocol patients. Doxycycline showed superiority over placebo in terms of clinical success on Day 10 in intention-to-treat patients (odds ratio, 1.9; 95% confidence interval, 1.1 to 3.2), but not in per-protocol patients. Doxycycline was also superior in terms of clinical cure on Day 10, microbiological outcome, use of open label antibiotics, and symptoms. There was no interaction between the treatment effect and any of the subgroup variables (lung function, type of exacerbation, serum C-reactive protein, and bacterial presence).



Although equivalent to placebo in terms of clinical success on Day 30, doxycycline showed superiority in terms of clinical success and clinical cure on Day 10, microbiological success, the use of open label antibiotics, and symptoms.
Microbiota benefits after inulin and partially hydrolized guar gum supplementation: a randomized clinical trial in constipated women.

Prebiotics positively affect gut microbiota composition, thus improving gut function. These properties may be useful for the treatment of constipation.



This study assessed the tolerance and effectiveness of a prebiotic inulin/partially hydrolyzed guar gum mixture (I-PHGG) for the treatment of constipation in females, as well as its influence on the composition of intestinal microbiota and production of short chain fatty acids.



Our study enrolled 60 constipated female health worker volunteers. Participants reported less than 3 bowel movements per week. Volunteers were randomized to treatment with prebiotic or placebo. Treatment consisted of 3 weeks supplementation with 15 g/d IPHGG (fiber group) or maltodextrin (placebo group). Abdominal discomfort, flatulence, stool consistency, and bowel movements were evaluated by a recorded daily questionnaire and a weekly interview. Changes in fecal bacterial population and short chain fatty acids were assessed by real-time PCR and gas chromatography, respectively.



There was an increased frequency of weekly bowel movements and patient satisfaction in both the fiber and placebo groups with no significant differences. Total Clostridium sp significantly decreased in the fiber group (p = 0.046) and increased in the placebo group (p = 0.047). There were no changes in fecal short chain fatty acid profile.



Consumption of I-PHGG produced clinical results comparable to placebo in constipated females, but had additional protective effects on gut microbiota by decreasing the amount of pathological bacteria of the Clostridium genera.
Increased risk of HIV-1 transmission in pregnancy: a prospective study among African HIV-1-serodiscordant couples.

Physiologic and behavioral changes during pregnancy may alter HIV-1 susceptibility and infectiousness. Prospective studies exploring pregnancy and HIV-1 acquisition risk in women have found inconsistent results. No study has explored the effect of pregnancy on HIV-1 transmission risk from HIV-1-infected women to male partners.



In a prospective study of African HIV-1-serodiscordant couples, we evaluated the relationship between pregnancy and the risk of HIV-1 acquisition among women and HIV-1 transmission from women to men.



Three thousand three hundred and twenty-one HIV-1-serodiscordant couples were enrolled, 1085 (32.7%) with HIV-1 susceptible female partners and 2236 (67.3%) with susceptible male partners. HIV-1 incidence in women was 7.35 versus 3.01 per 100 person-years during pregnant and nonpregnant periods [hazard ratio 2.34, 95% confidence interval (CI) 1.33-4.09]. This effect was attenuated and not statistically significant after adjusting for sexual behavior and other confounding factors (adjusted hazard ratio 1.71, 95% CI 0.93-3.12). HIV-1 incidence in male partners of infected women was 3.46 versus 1.58 per 100 person-years when their partners were pregnant versus not pregnant (hazard ratio 2.31, 95% CI 1.22-4.39). This effect was not attenuated in adjusted analysis (adjusted hazard ratio 2.47, 95% CI 1.26-4.85).



HIV-1 risk increased two-fold during pregnancy. Elevated risk of HIV-1 acquisition in pregnant women appeared in part to be explained by behavioral and other factors. This is the first study to show that pregnancy increased the risk of female-to-male HIV-1 transmission, which may reflect biological changes of pregnancy that could increase HIV-1 infectiousness.
Potential of Phosphorus Nuclear Magnetic Resonance Spectroscopy in Studies of the Energy Metabolism of Skeletal Muscles

The aim of the present study was to investigate the possibility of phosphorus magnetic resonance spectroscopy (MR spectroscopy) in the diagnosis of metabolic lesions of skeletal musculature in patients with intermittent claudication syndrome, chronic cardiac failure, and varicose diseases of the lower limbs. Studies included 50 males: 20 patients with intermittent claudication, 10 patients with chronic cardiac failure, and 10 patients with varicose veins. The control group consisted of 10 healthy volunteers. The following measures were determined: the phosphocreatinine index, the intracellular pH in the gastrocnemius muscle, and the half-recovery time for the phosphocreatinine index. The phosphocreatinine index and the pH at rest did not differ between study groups. Isotonic exercise produced no change in the phosphocreatinine index in the control group; patients with intermittent claudication showed a 26.1% decrease, patients with chronic cardiac failure showed an 8% decrease, and patients with varicose veins showed a 25.6% decrease. The only group showing a significant decrease in pH during exercise was the group of patients with intermittent claudication. This group also showed an inverse correlation between the pressure index and the extent of the decrease in the phosphocreatinine index. Thus, MR spectroscopy provides a non-invasive diagnostic method for lesions of energy metabolism in skeletal musculature in patients with deranged peripheral hemodynamics.
A CD8 T Cell/Indoleamine 2,3-Dioxygenase Axis Is Required for Mesenchymal Stem Cell Suppression of Human Systemic Lupus Erythematosus

Allogeneic mesenchymal stem cells (MSCs) exhibit therapeutic effects in human autoimmune diseases such as systemic lupus erythematosus (SLE), but the underlying mechanisms remain largely unknown. The aim of this study was to investigate how allogeneic MSCs mediate immunosuppression in lupus patients.



The effects of allogeneic umbilical cord-derived MSCs (UC-MSCs) on inhibition of T cell proliferation were determined. MSC functional molecules were stimulated with peripheral blood mononuclear cells from healthy controls and SLE patients and examined by real-time polymerase chain reaction. CD4+ and CD8+ T cells were purified using microbeads to stimulate MSCs in order to determine cytokine expression by MSCs and to further determine which cell subset(s) or which molecule(s) is involved in inhibition of MSC-mediated T cell proliferation. The related signaling pathways were assessed. We determined levels of serum cytokines in lupus patients before and after UC-MSC transplantation.



Allogeneic UC-MSCs suppressed T cell proliferation in lupus patients by secreting large amounts of indoleamine 2,3-dioxygenase (IDO). We further found that interferon-γ (IFNγ), which is produced predominantly by lupus CD8+ T cells, is the key factor that enhances IDO activity in allogeneic MSCs and that it is associated with IFNGR1/JAK-2/STAT signaling pathways. Intriguingly, bone marrow-derived MSCs from patients with active lupus demonstrated defective IDO production in response to IFNγ and allogeneic CD8+ T cell stimulation. After allogeneic UC-MSC transplantation, serum IDO activity increased in lupus patients.



We found a previously unrecognized CD8+ T cell/IFNγ/IDO axis that mediates the therapeutic effects of allogeneic MSCs in lupus patients.
Uremic Solutes in Chronic Kidney Disease and Their Role in Progression

To date, over 150 possible uremic solutes have been listed, but their role in the progression of CKD is largely unknown. Here, the association between a selected panel of uremic solutes and progression in CKD patients was investigated.



Patients from the MASTERPLAN study, a randomized controlled trial in CKD patients with a creatinine clearance between 20 and 70 ml/min per 1.73m2, were selected based on their rate of eGFR decline during the first five years of follow-up. They were categorized as rapid (decline >5 ml/min per year) or slow progressors. Concentrations of eleven uremic solutes were obtained at baseline and after one year of follow-up. Logistic regression was used to compare the odds for rapid to slow progression by uremic solute concentrations at baseline. Variability in uremic solute levels was assessed using scatter plots, and limits of variability were calculated.



In total, 40 rapidly and 40 slowly progressing patients were included. Uremic solutes were elevated in all patients compared to reference values for healthy persons. The serum levels of uremic solutes were not associated with rapid progression. Moreover, we observed substantial variability in solute levels over time.



Elevated concentrations of uremic solutes measured in this study did not explain differences in rate of eGFR decline in CKD patients, possibly due to lack of power as a result of the small sample size, substantial between patient variability, and variability in solute concentrations over time. The etiology of intra-individual variation in uremic solute levels remains to be elucidated.
Use of a standardized uptake value for parametric in vivo imaging of benzodiazepine receptor distribution on [11C]flumazenil brain PET

To simplify the acquisition protocol of carbon-11 labeled flumazenil (FMZ) positron emission tomography (PET) for distribution volume (DV) images, we attempted to obtain standardized uptake value (SUV) images compatible with DV images, and assessed the applicability of this method in patients with unilateral cerebrovascular diseases (CVD). [11C]FMZ PET was performed in ten normal subjects. A DV image and ten sequential 5-min SUV images were generated for each subject. We investigated the correlation coefficient (r) and standard estimation of error (SEE) between the latter ten static images and the DV image using the pixel-by-pixel method, thereby determining the optimum acquisition phase. The same FMZ PET procedure was performed in 15 patients with unilateral CVD. Twenty regions of interest (ROIs) were positioned both in lesioned areas and in symmetrical regions. DV and SUV in the optimum phase for each ROI were calculated to compare the lesion-to-normal (L/N) ratio of DV and that of SUV. The highest r and a low SEE (r=0.957, SEE=633) were observed from 30 to 35 min after tracer administration in the study of normal subjects. A high r (0.945) and a low SEE (0.0438) between the DV L/N ratio and the SUV L/N ratio were obtained in the study of patients. Our study suggests that SUV images acquired from 30 to 35 min after FMZ administration are a suitable alternative to DV images not only in normal subjects but also in patients with unilateral CVD. This simple method seems to be valuable for the identification of altered neuronal activity in patients with CVD.
Intra-articular Drain versus No Drain after Arthroscopic Anterior Cruciate Ligament Reconstruction: A Randomized Prospective Clinical Trial

In this study, forty consecutive arthroscopic ACL reconstruction patients were randomized alternately for either intra-articular suction drain group or non-drain group. All arthroscopic ACL reconstructions using a four strands hamstrings graft as auto graft were included in the trial. The outcome was evaluated in the first three days, first week, fourth week and eighth week. The results were evaluated through pain assessment, range of motion (ROM), and grade of haemoarthrosis.
Improved insulin sensitivity and adipose tissue dysregulation after short-term treatment with pioglitazone in non-diabetic, insulin-resistant subjects

We examined whether short-term treatment with a thiazolidinedione improves insulin sensitivity in non-obese but insulin-resistant subjects and whether this is associated with an improvement in dysregulated adipose tissue (reduced expression of IRS-1, GLUT4, PPARγ co-activator 1 and markers of terminal differentiation) that we have previously documented to be associated with insulin resistance. Ten non-diabetic subjects, identified as having low IRS-1 and GLUT-4 protein in adipose cells as markers of insulin resistance, underwent 3 weeks of treatment with pioglitazone. The euglycaemic–hyperinsulinaemic clamp technique was used to measure insulin sensitivity before and after treatment. Serum samples were analysed for glucose, insulin, lipids, total and high-molecular-weight (HMW) adiponectin levels. Biopsies from abdominal subcutaneous adipose tissue were taken, cell size measured, mRNA and protein extracted and quantified using real-time RT-PCR and Western blot. Insulin sensitivity was improved after 3 weeks treatment and circulating total as well as HMW adiponectin increased in all subjects, while no effect was seen on serum lipids. In the adipose cells, gene and protein expression of IRS-1 and PPARγ co-activator 1 remained unchanged, while adiponectin, adipocyte P 2, uncoupling protein 2, GLUT4 and liver X receptor-α increased. Insulin-stimulated tyrosine phosphorylation and p-ser-PKB/Akt increased, while no significant effect of thiazolidinedione treatment was seen on the inflammatory status of the adipose tissue in these non-obese subjects. Short-term treatment with pioglitazone improved insulin sensitivity in the absence of any changes in circulating NEFA or lipid levels. Several markers of adipose cell differentiation, previously shown to be reduced in insulin resistance, were augmented, supporting the concept that insulin resistance in these individuals is associated with impaired terminal differentiation of the adipose cells.
Phase I study of DMP 840 in pediatric patients with refractory solid tumors

The bis-naphthalimide DMP 840 has demonstrated high level antitumor activity in a number of preclinical models and has been evaluated in several Phase I studies in adults. We enrolled 10 patients with refractory pediatric solid tumors to this Phase I study of DMP 840 given intravenously by short infusion daily for 5 days. The most frequent and dose-limiting toxicity was myelosuppression. The maximum tolerated dose on this schedule was 8.6 mg/m2 daily for 5 days. One patient had a complete response; there were no measurable tumor responses among the remaining 9 patients.
The Effect of Methylphenidate on Fatigue in Advanced Cancer: An Aggregated N-of-1 Trial.

Fatigue is common in life-limiting cancer. Methylphenidate (MPH), a psychostimulant, may be a useful therapy. Gathering evidence in patients with advanced cancer can be challenging.



To determine if MPH improves cancer-related fatigue in people with advanced cancer.



N-of-1 trials are multicycle, double-blind, randomized, controlled crossover trials using standardized measures of effect in individuals. They are normally used to assess treatment effects in individuals. Aggregated N-of-1 trials from participants with end-stage cancer suffering fatigue were used to assess the group effect of MPH, producing an estimate of equivalent power to a parallel-group randomized controlled trial (RCT) but requiring less than half of the sample size. Up to three cycles of MPH 5 mg twice daily (three days) vs. identical placebo (three days) capsules were offered to participants. Primary outcome was improvement in fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue Scale and the Wu Cancer Fatigue Scale. Analysis used Bayesian statistical methods using intention-to-treat principles.



Forty-three participants completed 84 cycles of MPH and placebo in random order, exceeding sample size estimates. Overall, MPH did not improve fatigue (mean difference 3.2; 95% credible interval -2.0, 9.0; posterior probability of favorable effect 0.890). Eight participants showed important improvement, and one participant showed important worsening of fatigue on MPH. There were no features that distinguished participants whose fatigue responded to MPH compared with those who did not.



MPH does not improve fatigue in the population of patients with end-stage cancer. Aggregated N-of-1 trial methodology is feasible and produces population-based sample estimates with less than half the sample size required for the equivalent parallel-group RCT. It also identified individuals who did and did not respond to MPH, which is a feature difficult to achieve in a standard RCT. The study was registered with the Australian Clinical Trials Registry (12609000794202).
Mitochondrial proliferation, DNA depletion and adipocyte differentiation in subcutaneous adipose tissue of HIV-positive HAART recipients.

To examine the in vivo effects of highly active antiretroviral therapy (HAART) regimens on adipose tissue mitochondrial DNA (mtDNA) depletion, mitochondrial organellar proliferation, and markers of adipocyte differentiation and phenotype.



DNA and mRNA quantification using real-time PCR methods was performed on adipose tissue samples from 31 HIV-infected individuals, of whom 11 were treatment-naive and 20 were receiving HAART. mtDNA depletion was measured as mtDNA copies/cell, and mitochondrial proliferation by quantification of mitochondrial protein mass. Regulation of mitochondrial biogenesis was assessed by NRF-1 and mtTFA mRNA. PPARgamma, UCP2 and UCP1 mRNA expression was used to assess adipocyte differentiation and phenotype.



Stavudine-based HAART recipients (n=10) displayed significant mtDNA depletion (12.8% of control, P<0.001), mildly increased mitochondrial protein mass (2.6-fold of control, P=0.032) and decreased expression of PPARgamma (53.9% of control, P=0.021), UCP2 (62.2% of control, P=0.024) and UCP3 (51.8% of control, P=0.047) mRNA compared with controls. Zidovudine-based HAART recipients (n=7) also displayed significant mtDNA depletion (34.45% of control, P=0.031), increased mitochondrial protein mass (5.7-fold of control, P=0.009), and markedly increased UCP1 (18-fold of control, P=0.009) mRNA. Elevated UCP1 mRNA expression was found to be associated with non-stavudine (zidovudine or abacavir), protease inhibitor (PI)-containing HAART (95-fold of non-stavudine, non-PI-containing HAART, P=0.006).



Differential effects of stavudine and zidovudine therapy on mtDNA depletion and expression of adipocyte differentiation markers PPARgamma and UCP2 were observed, consistent with increased adipose tissue toxicity associated with stavudine therapy. Increased UCP1 mRNA, a marker of brown adipose tissue phenotype, was associated with non-stavudine, PI-containing HAART, and may represent an adaptive response to the increased fatty acid flux associated with PI therapy, and may contribute to the increased resting energy expenditure reported in such patients.
Activation of persons living with HIV for treatment, the great study

Patient empowerment represents a potent tool for addressing racial, ethnic and socioeconomic disparities in health care, particularly for chronic conditions such as HIV infection that require active patient engagement. This multimodal intervention, developed in concert with HIV patients and clinicians, aims to provide HIV patients with the knowledge, skills, attitudes and tools to become more activated patients.



Randomized controlled trial of a multimodal intervention designed to activate persons living with HIV. The intervention includes four components: 1) use of a web-enabled hand-held device (Apple iPod Touch) loaded with a Personal Health Record (ePHR) customized for HIV patients; 2) six 90-minute group-based training sessions in use of the device, internet and the ePHR; 3) a pre-visit coaching session; and 4) clinician education regarding how they can support activated patients. Outcome measures include pre- post changes in patient activation measure score (primary outcome), eHealth literacy, patient involvement in decision-making and care, medication adherence, preventive care, and HIV Viral Load.



We hypothesize that participants receiving the intervention will show greater improvement in empowerment and the intervention will reduce disparities in study outcomes. Disparities in these measures will be smaller than those in the usual care group. Findings have implications for activating persons living with HIV and for other marginalized groups living with chronic illness.