Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy and safety of sirolimus in lymphangioleiomyomatosis.

BACKGROUND Lymphangioleiomyomatosis (LAM) is a progressive, cystic lung disease in women; it is associated with inappropriate activation of mammalian target of rapamycin (mTOR) signaling, which regulates cellular growth and lymphangiogenesis. Sirolimus (also called rapamycin) inhibits mTOR and has shown promise in phase 1-2 trials involving patients with LAM. METHODS We conducted a two-stage trial of sirolimus involving 89 patients with LAM who had moderate lung impairment--a 12-month randomized, double-blind comparison of sirolimus with placebo, followed by a 12-month observation period. The primary end point was the difference between the groups in the rate of change (slope) in forced expiratory volume in 1 second (FEV(1)). RESULTS During the treatment period, the FEV(1) slope was -12±2 ml per month in the placebo group (43 patients) and 1±2 ml per month in the sirolimus group (46 patients) (P<0.001). The absolute between-group difference in the mean change in FEV(1) during the treatment period was 153 ml, or approximately 11% of the mean FEV(1) at enrollment. As compared with the placebo group, the sirolimus group had improvement from baseline to 12 months in measures of forced vital capacity, functional residual capacity, serum vascular endothelial growth factor D (VEGF-D), and quality of life and functional performance. There was no significant between-group difference in this interval in the change in 6-minute walk distance or diffusing capacity of the lung for carbon monoxide. After discontinuation of sirolimus, the decline in lung function resumed in the sirolimus group and paralleled that in the placebo group. Adverse events were more common with sirolimus, but the frequency of serious adverse events did not differ significantly between the groups. CONCLUSIONS In patients with LAM, sirolimus stabilized lung function, reduced serum VEGF-D levels, and was associated with a reduction in symptoms and improvement in quality of life. Therapy with sirolimus may be useful in selected patients with LAM. (Funded by the National Institutes of Health and others; MILES ClinicalTrials.gov number, NCT00414648.).
Primary Percutaneous Coronary Intervention in an Anomalous Right Coronary Artery in a Patient with Acute ST-Segment Elevation Myocardial Infarction

An anomalous right coronary artery (RCA) arising from the left sinus of Valsalva is a rare congenital coronary anomaly. Although there are reports of percutaneous coronary intervention (PCI) for atherosclerotic lesions of this unusual coronary anomaly, only four cases of acute ST-segment elevation myocardial infarction caused by thrombotic occlusion of an anomalous RCA managed with primary PCI have been documented previously. Herein, we describe a 65-year-old man who had successful PCI in an anomalous RCA in the clinical setting of acute myocardial infarction. The patient was discharged a few days later and has been well during OPD follow-up.
Anti-inhibitor coagulant complex prophylaxis in hemophilia with inhibitors.

BACKGROUND Patients with severe hemophilia A and factor VIII inhibitors are at increased risk for serious bleeding complications and progression to end-stage joint disease. Effective strategies to prevent bleeding in such patients have not yet been established. METHODS We enrolled patients with hemophilia A who were older than 2 years of age, had high-titer inhibitors, and used concentrates known as bypassing agents for bleeding in a prospective, randomized, crossover study comparing 6 months of anti-inhibitor coagulant complex (AICC), infused prophylactically at a target dose of 85 U per kilogram of body weight (±15%) on 3 nonconsecutive days per week, with 6 months of on-demand therapy (AICC at a target dose of 85 U per kilogram [±15%] used for bleeding episodes). The two treatment periods were separated by a 3-month washout period, during which patients received on-demand therapy for bleeding. The primary outcome was the number of bleeding episodes during each 6-month treatment period. RESULTS Thirty-four patients underwent randomization; 26 patients completed both treatment periods and could be evaluated per protocol for the efficacy analysis. As compared with on-demand therapy, prophylaxis was associated with a 62% reduction in all bleeding episodes (P<0.001), a 61% reduction in hemarthroses (P<0.001), and a 72% reduction in target-joint bleeding (≥3 hemarthroses in a single joint during a 6-month treatment period) (P<0.001). Thirty-three randomly assigned patients received at least one infusion of the study drug and were evaluated for safety. One patient had an allergic reaction to the study drug. CONCLUSIONS AICC prophylaxis at the dosage evaluated significantly and safely decreased the frequency of joint and other bleeding events in patients with severe hemophilia A and factor VIII inhibitors. (Funded by Baxter BioScience; Pro-FEIBA ClinicalTrials.gov number, NCT00221195.).
Stroke and bleeding in atrial fibrillation with chronic kidney disease.

BACKGROUND Both atrial fibrillation and chronic kidney disease increase the risk of stroke and systemic thromboembolism. However, these risks, and the effects of antithrombotic treatment, have not been thoroughly investigated in patients with both conditions. METHODS Using Danish national registries, we identified all patients discharged from the hospital with a diagnosis of nonvalvular atrial fibrillation between 1997 and 2008. The risk of stroke or systemic thromboembolism and bleeding associated with non-end-stage chronic kidney disease and with end-stage chronic kidney disease (i.e., disease requiring renal-replacement therapy) was estimated with the use of time-dependent Cox regression analyses. In addition, the effects of treatment with warfarin, aspirin, or both in patients with chronic kidney disease were compared with the effects in patients with no renal disease. RESULTS Of 132,372 patients included in the analysis, 3587 (2.7%) had non-end-stage chronic kidney disease and 901 (0.7%) required renal-replacement therapy at the time of inclusion. As compared with patients who did not have renal disease, patients with non-end-stage chronic kidney disease had an increased risk of stroke or systemic thromboembolism (hazard ratio, 1.49; 95% confidence interval [CI], 1.38 to 1.59; P<0.001), as did those requiring renal-replacement therapy (hazard ratio, 1.83; 95% CI, 1.57 to 2.14; P<0.001); this risk was significantly decreased for both groups of patients with warfarin but not with aspirin. The risk of bleeding was also increased among patients who had non-end-stage chronic kidney disease or required renal-replacement therapy and was further increased with warfarin, aspirin, or both. CONCLUSIONS Chronic kidney disease was associated with an increased risk of stroke or systemic thromboembolism and bleeding among patients with atrial fibrillation. Warfarin treatment was associated with a decreased risk of stroke or systemic thromboembolism among patients with chronic kidney disease, whereas warfarin and aspirin were associated with an increased risk of bleeding. (Funded by the Lundbeck Foundation.).
Inducible apoptosis as a safety switch for adoptive cell therapy.

BACKGROUND Cellular therapies could play a role in cancer treatment and regenerative medicine if it were possible to quickly eliminate the infused cells in case of adverse events. We devised an inducible T-cell safety switch that is based on the fusion of human caspase 9 to a modified human FK-binding protein, allowing conditional dimerization. When exposed to a synthetic dimerizing drug, the inducible caspase 9 (iCasp9) becomes activated and leads to the rapid death of cells expressing this construct. METHODS We tested the activity of our safety switch by introducing the gene into donor T cells given to enhance immune reconstitution in recipients of haploidentical stem-cell transplants. Patients received AP1903, an otherwise bioinert small-molecule dimerizing drug, if graft-versus-host disease (GVHD) developed. We measured the effects of AP1903 on GVHD and on the function and persistence of the cells containing the iCasp9 safety switch. RESULTS Five patients between the ages of 3 and 17 years who had undergone stem-cell transplantation for relapsed acute leukemia were treated with the genetically modified T cells. The cells were detected in peripheral blood from all five patients and increased in number over time, despite their constitutive transgene expression. A single dose of dimerizing drug, given to four patients in whom GVHD developed, eliminated more than 90% of the modified T cells within 30 minutes after administration and ended the GVHD without recurrence. CONCLUSIONS The iCasp9 cell-suicide system may increase the safety of cellular therapies and expand their clinical applications. (Funded by the National Heart, Lung, and Blood Institute and the National Cancer Institute; ClinicalTrials.gov number, NCT00710892.).
Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany.

BACKGROUND We describe an outbreak of gastroenteritis and the hemolytic-uremic syndrome caused by Shiga-toxin-producing Escherichia coli in Germany in May, June, and July, 2011. The consumption of sprouts was identified as the most likely vehicle of infection. METHODS We analyzed data from reports in Germany of Shiga-toxin-producing E. coli gastroenteritis and the hemolytic-uremic syndrome and clinical information on patients presenting to Hamburg University Medical Center (HUMC). An outbreak case was defined as a reported case of the hemolytic-uremic syndrome or of gastroenteritis in a patient infected by Shiga-toxin-producing E. coli, serogroup O104 or serogroup unknown, with an onset of disease during the period from May 1 through July 4, 2011, in Germany. RESULTS A total of 3816 cases (including 54 deaths) were reported in Germany, 845 of which (22%) involved the hemolytic-uremic syndrome. The outbreak was centered in northern Germany and peaked around May 21 to 22. Most of the patients in whom the hemolytic-uremic syndrome developed were adults (88%; median age, 42 years), and women were overrepresented (68%). The estimated median incubation period was 8 days, with a median of 5 days from the onset of diarrhea to the development of the hemolytic-uremic syndrome. Among 59 patients prospectively followed at HUMC, the hemolytic-uremic syndrome developed in 12 (20%), with no significant differences according to sex or reported initial symptoms and signs. The outbreak strain was typed as an enteroaggregative Shiga-toxin-producing E. coli O104:H4, producing extended-spectrum beta-lactamase. CONCLUSIONS In this outbreak, caused by an unusual E. coli strain, cases of the hemolytic-uremic syndrome occurred predominantly in adults, with a preponderance of cases occurring in women. The hemolytic-uremic syndrome developed in more than 20% of the identified cases.
Effects of Post-Election Violence on HIV patients care and Treatment in Selected Districts in Central, Nyanza and Rift Valley Provinces, Kenya, 2008.

Kenya, like other African countries, has been affected significantly by the HIV/AIDS epidemic. Kenya has been a leader in rapidly expanding access to HIV prevention, care and treatment, and great effort has been invested in developing national to facility-level systems to deliver prevention, care, and treatment services for HIV patients. In December 30, 2007; civil unrest broke out in several parts of the country after the presidential election results were announced. People fled their homes and health care services were disrupted. The effects of the post-election violence on HIV infected individuals and those on antiretroviral therapy (ART) are not clearly understood. A cross-sectional study was carried out to determine the effects of post-election violence on HIV patients care and treatment in selected districts in Central, Nyanza, and Rift Valley provinces, Kenya. A total of 35 health facilities from 18 districts were selected using person proportion to size method. HIV patients were interviewed and facility records reviewed to asses the effects of the post-election violence. A standardized questionnaire was administered to the study participants. Odds Ratio (OR) was used to assess the strength of association between various risk factors and missing ART and chi square to test for statistical significance.A total of 947 participants were interviewed. On analysis of factors that could have lead to patients missing treatment, there was significant increased risk of missing ART therapy among those who reported to have moved into different districts since December 30, 2007 (OR=2.6, p=0.002), unable to access health XVIcare during the post-election violence period (OR=9.5, p<0.0001), having experienced physical violence personally (OR=2.7, p=0.0055) and having witnessed acts of physical violence (OR=2.0, p=0.02). For participants who had remained at the hospital of normalcare they were less likely to miss ART (OR=0.3, p=0.002). A Logistic regression model of factors that lead to patients missing treatment showed two factors that remained independent. There was an increased risk of missing ART among those participants who were unable to access routine health care (OR=5.25, p<0.0001) and care when ill (OR=3.81 p<0.0001). The post-election violence had an effect on patients who were on ART. Inability to access health care and experiencing physical violence were important factors leading to participants missing ART treatment. This may have implications on ARV drug resistance and further research is needed.
Parenting interventions on a Mother and Baby Unit : an investigation

In this thesis the intricacies of service user and staff perceptions of psychological interventions for mental health difficulties were explored. Expanding upon this theme, mothers and staff on a Mother and Baby Unit (MBU) were asked about their views regarding the acceptability and feasibility of the implementation of a parenting intervention, Baby Triple P Positive Parenting Programme (Baby TP). This investigation is presented as four papers: a literature review, two empirical papers (a & b) and, a critical review and personal reflection of the research process.The literature review, a meta-synthesis of qualitative studies, explores service user and staff perceptions of psychological interventions for mental health difficulties. Twenty-eight studies were synthesised to develop comprehensive understanding of subtle, specific and overlapping elements involved in the implementation of psychological intervention. Guided by Noblit and Hare? s (1988) approach, 11 over-arching themes and 25 sub-ordinate themes emerged from the synthesis. Findings provide a detailed description of the concepts pertinent to both service users and staff. Implications are identified for service managers and clinicians in obtaining optimum efficiency and outcomes of psychological intervention. The empirical study is a Q-methodological investigation into service user and staff perceptions of the acceptability and feasibility of a parenting intervention, Baby TP, on a MBU. This study is split into two population-specific papers. Overall five main factors were identified (service users: three; staff: two), which provides new insights into the acceptable and feasible elements of a parenting intervention within this specialist setting. The findings highlight a positive consensus as to the acceptability and feasibility of Baby TP in a MBU setting alongside a number of identified needs pertinent to service users, staff and the setting. Clinical implications and recommendations are provided to address identified areas of need for both populations within this setting. The third paper is a critical review of the thesis illustrated through personal reflections of the research process.
Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening.

BACKGROUND Colonoscopy and fecal immunochemical testing (FIT) are accepted strategies for colorectal-cancer screening in the average-risk population. METHODS In this randomized, controlled trial involving asymptomatic adults 50 to 69 years of age, we compared one-time colonoscopy in 26,703 subjects with FIT every 2 years in 26,599 subjects. The primary outcome was the rate of death from colorectal cancer at 10 years. This interim report describes rates of participation, diagnostic findings, and occurrence of major complications at completion of the baseline screening. Study outcomes were analyzed in both intention-to-screen and as-screened populations. RESULTS The rate of participation was higher in the FIT group than in the colonoscopy group (34.2% vs. 24.6%, P<0.001). Colorectal cancer was found in 30 subjects (0.1%) in the colonoscopy group and 33 subjects (0.1%) in the FIT group (odds ratio, 0.99; 95% confidence interval [CI], 0.61 to 1.64; P=0.99). Advanced adenomas were detected in 514 subjects (1.9%) in the colonoscopy group and 231 subjects (0.9%) in the FIT group (odds ratio, 2.30; 95% CI, 1.97 to 2.69; P<0.001), and nonadvanced adenomas were detected in 1109 subjects (4.2%) in the colonoscopy group and 119 subjects (0.4%) in the FIT group (odds ratio, 9.80; 95% CI, 8.10 to 11.85; P<0.001). CONCLUSIONS Subjects in the FIT group were more likely to participate in screening than were those in the colonoscopy group. On the baseline screening examination, the numbers of subjects in whom colorectal cancer was detected were similar in the two study groups, but more adenomas were identified in the colonoscopy group. (Funded by Instituto de Salud Carlos III and others; ClinicalTrials.gov number, NCT00906997.).
Fucoidanases: distribution, properties, specificity and structure

In recent years, the research of fucoidans has steadily increased. The interest in these substances is due to their various biological activities. Despite a wide range of biological activity and the lack of oral toxicity, fucoidans remain relatively unexploited as a source of medicines because of their heterogeneity. Enzymes that degrade polyanionic polysaccharides are widely used for establishing their structures and structure-activity relationships. Sometimes, to obtain preparations of polysaccharides with standard characteristics, for example, medicines and food supplements, enzymatic treatment can be also applied. Only a few sources of enzymes with fucoidanase activity have been described and only a few studies regarding the isolation and characterisation of fucoidanases have been performed. The data on the specificity of fucoidanases: the type of cleaved glycoside bond, the relation between catalytic activity and the degree of substrate sulphation, is scarce. The review summarises achievements in the research of fucoidanases, mechanisms of enzymatic degradation of fucoidans, as well as of structures of sulphated fuco-oligosaccharides obtained under the action of fucoidanases.
Soluble triggering receptor expressed on myeloid cells‐1 is a biomarker of anti‐CCP‐positive, early rheumatoid arthritis

To assess serum soluble triggering receptor expressed on myeloid cells‐1 (sTREM‐1) levels in disease‐modifying antirheumatic drug (DMARD)‐naïve early rheumatoid arthritis (ERA), to investigate the association of sTREM‐1 levels with Disease Activity Score in 28 joints (DAS28) and seropositivity for anti‐cyclic citrullinated peptide (CCP) antibody and to determine the predictive value of sTREM‐1 with respect to clinical response to DMARD therapy.
Effect of Radiofrequency Denervation on Pain Intensity Among Patients With Chronic Low Back Pain: The Mint Randomized Clinical Trials

Importance Radiofrequency denervation is a commonly used treatment for chronic low back pain, but high-quality evidence for its effectiveness is lacking. Objective To evaluate the effectiveness of radiofrequency denervation added to a standardized exercise program for patients with chronic low back pain. Design, Setting, and Participants Three pragmatic multicenter, nonblinded randomized clinical trials on the effectiveness of minimal interventional treatments for participants with chronic low back pain (Mint study) were conducted in 16 multidisciplinary pain clinics in the Netherlands. Eligible participants were included between January 1, 2013, and October 24, 2014, and had chronic low back pain, a positive diagnostic block at the facet joints (facet joint trial, 251 participants), sacroiliac joints (sacroiliac joint trial, 228 participants), or a combination of facet joints, sacroiliac joints, or intervertebral disks (combination trial, 202 participants) and were unresponsive to conservative care. Interventions All participants received a 3-month standardized exercise program and psychological support if needed. Participants in the intervention group received radiofrequency denervation as well. This is usually a 1-time procedure, but the maximum number of treatments in the trial was 3. Main Outcomes and Measures The primary outcome was pain intensity (numeric rating scale, 0-10; whereby 0 indicated no pain and 10 indicated worst pain imaginable) measured 3 months after the intervention. The prespecified minimal clinically important difference was defined as 2 points or more. Final follow-up was at 12 months, ending October 2015. Results Among 681 participants who were randomized (mean age, 52.2 years; 421 women [61.8%], mean baseline pain intensity, 7.1), 599 (88%) completed the 3-month follow-up, and 521 (77%) completed the 12-month follow-up. The mean difference in pain intensity between the radiofrequency denervation and control groups at 3 months was −0.18 (95% CI, −0.76 to 0.40) in the facet joint trial; −0.71 (95% CI, −1.35 to −0.06) in the sacroiliac joint trial; and −0.99 (95% CI, −1.73 to −0.25) in the combination trial. Conclusions and Relevance In 3 randomized clinical trials of participants with chronic low back pain originating in the facet joints, sacroiliac joints, or a combination of facet joints, sacroiliac joints, or intervertebral disks, radiofrequency denervation combined with a standardized exercise program resulted in either no improvement or no clinically important improvement in chronic low back pain compared with a standardized exercise program alone. The findings do not support the use of radiofrequency denervation to treat chronic low back pain from these sources. Trial Registration trialregister.nl Identifier: NTR3531