Miracle-dz/UniFAR-FTUs huggingface dataset:
Once-weekly dalbavancin versus daily conventional therapy for skin infection.

BACKGROUND Dalbavancin, a lipoglycopeptide antibiotic agent that is active against gram-positive pathogens, has a long plasma half-life, allowing for once-weekly dosing. DISCOVER 1 and DISCOVER 2 were identically designed noninferiority trials of dalbavancin for the treatment of acute bacterial skin and skin-structure infection. METHODS We randomly assigned patients to receive dalbavancin intravenously on days 1 and 8 or vancomycin intravenously for at least 3 days with the option to switch to oral linezolid to complete 10 to 14 days of therapy. The primary end point, early clinical response, required the cessation of spread of infection-related erythema and the absence of fever at 48 to 72 hours. Secondary end points at the end of therapy included clinical status and investigator's assessment of outcome. RESULTS Analysis of the primary end point showed noninferiority of dalbavancin in both DISCOVER 1 and DISCOVER 2. In the pooled analysis, 525 of 659 patients (79.7%) in the dalbavancin group and 521 of 653 (79.8%) in the vancomycin-linezolid group had an early clinical response indicating treatment success (weighted difference, -0.1 percentage point; 95% confidence interval, -4.5 to 4.2). The outcomes were similar in the analyses by study and the pooled analyses of clinical status at the end of therapy and the investigator's assessment of outcome. For patients infected with Staphylococcus aureus, including methicillin-resistant S. aureus, clinical success was seen in 90.6% of the patients treated with dalbavancin and 93.8% of those treated with vancomycin-linezolid. Adverse events and study days with an adverse event were less frequent in the dalbavancin group than in the vancomycin-linezolid group. The most common treatment-related adverse events in either group were nausea, diarrhea, and pruritus. CONCLUSIONS Once-weekly intravenous dalbavancin was not inferior to twice-daily intravenous vancomycin followed by oral linezolid for the treatment of acute bacterial skin and skin-structure infection. (Funded by Durata Therapeutics; DISCOVER 1 and DISCOVER 2 ClinicalTrials.gov numbers, NCT01339091 and NCT01431339.).
THE EFFECT OF EDUCATION BASED ON HEALTH BELIEF MODEL (HBM) IN DECREASING DENTAL PLAQUE INDEX AMONG FIRST GRADE OF MIDDLE- SCHOOL GIRL STUDENTS IN HAMADAN

Background & Aims : Oral-dental health behaviors education to students is an important subject in the school to prevent dental problems. The use of suggested educational models and theories is a new way in health service fields. This study was done to determine the effect of health education based on HBM on the decreasing of dental plaque index among first grade of middle - school girl students in Hamadan. Materials & Methods : In this quasi-experimental study, 120 students were chosen through the stratified random sampling which were in 2 schools and 6 classrooms, and they were placed in the experimental (n=60) and control groups (n=60). Data collection tool was a questionnaire based on HBM constructs (perceived severity, susceptibility, benefits, barriers and self-efficacy) , knowledge, dental health behaviors and determine dental plaque by disclosing agent. The educational intervention included 4 educational sessions of 60 minutes.Two months after intervention, two groups were followed, and the data were analyzed by using SPSS 16 . Results: There were no statistically significant differences in demographic factors in two groups. Significant differences were observed in perceived severity (P<0.001), perceived barriers (P<0.001), self efficacy (P<0.001), perceived benefits (P=0.015), knowledge, health behaviors and dental plaque index between the two groups after intervention (P<0.001). There was no statistical significant difference between the two groups in perceived susceptibility (P=0.095). Finally, the optimal performance as well as decreasing dental plaque index was shown in experimental group comparing to control group. Conclusion: Findings showed that educational intervention based on HBM may be an effective method for promoting oral - dental health behaviors and decreasing dental plaque index in students.
A randomized trial of genotype-guided dosing of warfarin.

BACKGROUND The level of anticoagulation in response to a fixed-dose regimen of warfarin is difficult to predict during the initiation of therapy. We prospectively compared the effect of genotype-guided dosing with that of standard dosing on anticoagulation control in patients starting warfarin therapy. METHODS We conducted a multicenter, randomized, controlled trial involving patients with atrial fibrillation or venous thromboembolism. Genotyping for CYP2C9*2, CYP2C9*3, and VKORC1 (-1639G→A) was performed with the use of a point-of-care test. For patients assigned to the genotype-guided group, warfarin doses were prescribed according to pharmacogenetic-based algorithms for the first 5 days. Patients in the control (standard dosing) group received a 3-day loading-dose regimen. After the initiation period, the treatment of all patients was managed according to routine clinical practice. The primary outcome measure was the percentage of time in the therapeutic range of 2.0 to 3.0 for the international normalized ratio (INR) during the first 12 weeks after warfarin initiation. RESULTS A total of 455 patients were recruited, with 227 randomly assigned to the genotype-guided group and 228 assigned to the control group. The mean percentage of time in the therapeutic range was 67.4% in the genotype-guided group as compared with 60.3% in the control group (adjusted difference, 7.0 percentage points; 95% confidence interval, 3.3 to 10.6; P<0.001). There were significantly fewer incidences of excessive anticoagulation (INR ≥4.0) in the genotype-guided group. The median time to reach a therapeutic INR was 21 days in the genotype-guided group as compared with 29 days in the control group (P<0.001). CONCLUSIONS Pharmacogenetic-based dosing was associated with a higher percentage of time in the therapeutic INR range than was standard dosing during the initiation of warfarin therapy. (Funded by the European Commission Seventh Framework Programme and others; ClinicalTrials.gov number, NCT01119300.).
Association of Thyroid Hormone Therapy With Quality of Life and Thyroid-Related Symptoms in Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-analysis

Importance The benefit of thyroid hormone therapy for subclinical hypothyroidism is uncertain. New evidence from recent large randomized clinical trials warrants an update of previous meta-analyses. Objective To conduct a meta-analysis of the association of thyroid hormone therapy with quality of life and thyroid-related symptoms in adults with subclinical hypothyroidism. Data Sources PubMed, EMBASE, ClinicalTrials.gov, Web of Science, Cochrane Library, CENTRAL, Emcare, and Academic Search Premier from inception until July 4, 2018. Study Selection Randomized clinical trials that compared thyroid hormone therapy with placebo or no therapy in nonpregnant adults with subclinical hypothyroidism were eligible. Two reviewers independently evaluated eligibility based on titles and abstracts of all retrieved studies. Studies not excluded in this first step were independently assessed for inclusion after full-text evaluation by 2 reviewers. Data Extraction and Synthesis Two independent reviewers extracted data, assessed risk of bias (Cochrane risk-of-bias tool), and evaluated the quality of evidence (GRADE tool). For synthesis, differences in clinical scores were transformed (eg, quality of life) into standardized mean differences (SMDs; positive values indicate benefit of thyroid hormone therapy; 0.2, 0.5, and 0.8 correspond to small, moderate, and large effects, respectively). Random-effects models for meta-analyses were applied. Main Outcomes and Measures General quality of life and thyroid-related symptoms after a minimum follow-up of 3 months. Results Overall, 21 of 3088 initially identified publications met the inclusion criteria, with 2192 adults randomized. After treatment (range, 3-18 months), thyroid hormone therapy was associated with lowering the mean thyrotropin value into the normal reference range compared with placebo (range, 0.5-3.7 mIU/L vs 4.6 to 14.7 mIU/L) but was not associated with benefit regarding general quality of life (n = 796; SMD, −0.11; 95% CI, −0.25 to 0.03; I2=66.7%) or thyroid-related symptoms (n = 858; SMD, 0.01; 95% CI, −0.12 to 0.14; I2=0.0%). Overall, risk of bias was low and the quality of evidence assessed with the GRADE tool was judged moderate to high. Conclusions and Relevance Among nonpregnant adults with subclinical hypothyroidism, the use of thyroid hormone therapy was not associated with improvements in general quality of life or thyroid-related symptoms. These findings do not support the routine use of thyroid hormone therapy in adults with subclinical hypothyroidism.
Spread of artemisinin resistance in Plasmodium falciparum malaria.

BACKGROUND Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and now poses a threat to the control and elimination of malaria. Mapping the geographic extent of resistance is essential for planning containment and elimination strategies. METHODS Between May 2011 and April 2013, we enrolled 1241 adults and children with acute, uncomplicated falciparum malaria in an open-label trial at 15 sites in 10 countries (7 in Asia and 3 in Africa). Patients received artesunate, administered orally at a daily dose of either 2 mg per kilogram of body weight per day or 4 mg per kilogram, for 3 days, followed by a standard 3-day course of artemisinin-based combination therapy. Parasite counts in peripheral-blood samples were measured every 6 hours, and the parasite clearance half-lives were determined. RESULTS The median parasite clearance half-lives ranged from 1.9 hours in the Democratic Republic of Congo to 7.0 hours at the Thailand-Cambodia border. Slowly clearing infections (parasite clearance half-life >5 hours), strongly associated with single point mutations in the "propeller" region of the P. falciparum kelch protein gene on chromosome 13 (kelch13), were detected throughout mainland Southeast Asia from southern Vietnam to central Myanmar. The incidence of pretreatment and post-treatment gametocytemia was higher among patients with slow parasite clearance, suggesting greater potential for transmission. In western Cambodia, where artemisinin-based combination therapies are failing, the 6-day course of antimalarial therapy was associated with a cure rate of 97.7% (95% confidence interval, 90.9 to 99.4) at 42 days. CONCLUSIONS Artemisinin resistance to P. falciparum, which is now prevalent across mainland Southeast Asia, is associated with mutations in kelch13. Prolonged courses of artemisinin-based combination therapies are currently efficacious in areas where standard 3-day treatments are failing. (Funded by the U.K. Department of International Development and others; ClinicalTrials.gov number, NCT01350856.).
An experimental model for studies on delayed tooth replantation and ankylosis in rabbits.

AIM To develop an experimental in vivo model to study dentoalveolar ankylosis and osseous replacement resorption after delayed replantation. MATERIALS AND METHODS The maxillary right incisors of eight rabbits were extracted and replanted, while the maxillary left incisors served as controls. A special technique for extraction was used, luxating the incisor laterally prior to extraction. Extra-oral root canal treatment was performed. In four of the eight replanted teeth, periodontal ligament was removed using gauze. All teeth were replanted after one-hour dry storage. A horizontal line was drilled on the labial enamel surface of the incisors to enable registration of possible subsequent infraposition. The rabbits were sacrificed after 1 week or 4 weeks, respectively. Percussion test of the teeth was carried out and infraposition was registered. Histological processing and evaluation were performed. RESULTS Percussion sound was normal after 1 week and high in the 4 week group; infraposition was noted in all replanted teeth in the 4-week group. Fusion between the bone and dentin was seen in some areas on the root already after 1 week, but there was little or no osseous replacement. Larger areas of ankylosis were seen in the 4-week group although not significant, but deeper progressive osseous replacement was noted in this group. There was no significant difference in ankylosis with regard to periodontal ligament removal or not. Pulp and periodontal tissues were normal in all control teeth. CONCLUSION The rabbit tooth model may be useful for experimental in-vivo studies on delayed replantation, subsequent ankylosis, osseous replacement and infraposition.
Efficacy of high-dose versus standard-dose influenza vaccine in older adults.

BACKGROUND As compared with a standard-dose vaccine, a high-dose, trivalent, inactivated influenza vaccine (IIV3-HD) improves antibody responses to influenza among adults 65 years of age or older. This study evaluated whether IIV3-HD also improves protection against laboratory-confirmed influenza illness. METHODS We conducted a phase IIIb-IV, multicenter, randomized, double-blind, active-controlled trial to compare IIV3-HD (60 μg of hemagglutinin per strain) with standard-dose trivalent, inactivated influenza vaccine (IIV3-SD [15 μg of hemagglutinin per strain]) in adults 65 years of age or older. Assessments of relative efficacy, effectiveness, safety (serious adverse events), and immunogenicity (hemagglutination-inhibition [HAI] titers) were performed during the 2011-2012 (year 1) and the 2012-2013 (year 2) northern-hemisphere influenza seasons. RESULTS A total of 31,989 participants were enrolled from 126 research centers in the United States and Canada (15,991 were randomly assigned to receive IIV3-HD, and 15,998 to receive IIV3-SD). In the intention-to-treat analysis, 228 participants in the IIV3-HD group (1.4%) and 301 participants in the IIV3-SD group (1.9%) had laboratory-confirmed influenza caused by any viral type or subtype associated with a protocol-defined influenza-like illness (relative efficacy, 24.2%; 95% confidence interval [CI], 9.7 to 36.5). At least one serious adverse event during the safety surveillance period was reported by 1323 (8.3%) of the participants in the IIV3-HD group, as compared with 1442 (9.0%) of the participants in the IIV3-SD group (relative risk, 0.92; 95% CI, 0.85 to 0.99). After vaccination, HAI titers and seroprotection rates (the percentage of participants with HAI titers ≥ 1:40) were significantly higher in the IIV3-HD group. Conclusions: Among persons 65 years of age or older, IIV3-HD induced significantly higher antibody responses and provided better protection against laboratory-confirmed influenza illness than did IIV3-SD. (Funded by Sanofi Pasteur; ClinicalTrials.gov number, NCT01427309.).
Obesity, physical activity and traumatic dental injuries in adolescents from East London

BACKGROUND/AIMS Evidence on the interplay between obesity, physical activity and traumatic dental injuries (TDIs) is still inconclusive and heavily based on cross-sectional studies. The aim of this study was to explore the interrelationship of obesity and physical activity at age 11-12 years with TDI at age 15-16-years among schoolchildren from East London. MATERIALS AND METHOD Data were analysed regarding 598 adolescents who participated in phases I and III of the Research with East London Adolescents Community Health Survey (RELACHS), a longitudinal, school-based study of adolescents in East London. Participants reported their level of physical activity and their height and weight were measured to estimate body mass index Z-scores (according to the UK growth reference) when they were 11-12 years old. Oral clinical examinations were conducted to assess TDI, overjet and lip coverage when participants were 15-16 years old. The associations of obesity and physical activity with TDI were evaluated in crude and adjusted models using binary logistic regression. RESULTS Overall, 22.6% of adolescents were obese and 7.2% exercised for 7 h or more a week at baseline, while 18.1% of adolescents had experienced TDI by age 15-16 years. Physical activity (7+ hours per week) was significantly associated with TDI (odds ratio: 2.19; 95% confidence interval: 1.08-4.43) in the crude model. However, no significant associations were found between obesity and TDI (1.18; 95% CI: 0.72-1.93) or physical activity and TDI (1.96; 95% CI: 0.94-4.07) in adjusted models. CONCLUSION This study found no evidence of any associations of obesity and physical activity with TDI among adolescents from East London.
Spiroindolone KAE609 for falciparum and vivax malaria.

BACKGROUND KAE609 (cipargamin; formerly NITD609, Novartis Institute for Tropical Diseases) is a new synthetic antimalarial spiroindolone analogue with potent, dose-dependent antimalarial activity against asexual and sexual stages of Plasmodium falciparum. METHODS We conducted a phase 2, open-label study at three centers in Thailand to assess the antimalarial efficacy, safety, and adverse-event profile of KAE609, at a dose of 30 mg per day for 3 days, in two sequential cohorts of adults with uncomplicated P. vivax malaria (10 patients) or P. falciparum malaria (11). The primary end point was the parasite clearance time. RESULTS The median parasite clearance time was 12 hours in each cohort (interquartile range, 8 to 16 hours in patients with P. vivax malaria and 10 to 16 hours in those with P. falciparum malaria). The median half-lives for parasite clearance were 0.95 hours (range, 0.68 to 2.01; interquartile range, 0.85 to 1.14) in the patients with P. vivax malaria and 0.90 hours (range, 0.68 to 1.64; interquartile range, 0.78 to 1.07) in those with P. falciparum malaria. By comparison, only 19 of 5076 patients with P. falciparum malaria (<1%) who were treated with oral artesunate in Southeast Asia had a parasite clearance half-life of less than 1 hour. Adverse events were reported in 14 patients (67%), with nausea being the most common. The adverse events were generally mild and did not lead to any discontinuations of the drug. The mean terminal half-life for the elimination of KAE609 was 20.8 hours (range, 11.3 to 37.6), supporting a once-daily oral dosing regimen. CONCLUSIONS KAE609, at dose of 30 mg daily for 3 days, cleared parasitemia rapidly in adults with uncomplicated P. vivax or P. falciparum malaria. (Funded by Novartis and others; ClinicalTrials.gov number, NCT01524341.).
Effect of Human Recombinant Alkaline Phosphatase on 7-Day Creatinine Clearance in Patients With Sepsis-Associated Acute Kidney Injury: A Randomized Clinical Trial

Importance Sepsis-associated acute kidney injury (AKI) adversely affects long-term kidney outcomes and survival. Administration of the detoxifying enzyme alkaline phosphatase may improve kidney function and survival. Objective To determine the optimal therapeutic dose, effect on kidney function, and adverse effects of a human recombinant alkaline phosphatase in patients who are critically ill with sepsis-associated AKI. Design, Setting, and Participants The STOP-AKI trial was an international (53 recruiting sites), randomized, double-blind, placebo-controlled, dose-finding, adaptive phase 2a/2b study in 301 adult patients admitted to the intensive care unit with a diagnosis of sepsis and AKI. Patients were enrolled between December 2014 and May 2017, and follow-up was conducted for 90 days. The final date of follow-up was August 14, 2017. Interventions In the intention-to-treat analysis, in part 1 of the trial, patients were randomized to receive recombinant alkaline phosphatase in a dosage of 0.4 mg/kg (n = 31), 0.8 mg/kg (n = 32), or 1.6 mg/kg (n = 29) or placebo (n = 30), once daily for 3 days, to establish the optimal dose. The optimal dose was identified as 1.6 mg/kg based on modeling approaches and adverse events. In part 2, 1.6 mg/kg (n = 82) was compared with placebo (n = 86). Main Outcomes and Measures The primary end point was the time-corrected area under the curve of the endogenous creatinine clearance for days 1 through 7, divided by 7 to provide a mean daily creatinine clearance (AUC1-7 ECC). Incidence of fatal and nonfatal (serious) adverse events ([S]AEs) was also determined. Results Overall, 301 patients were enrolled (men, 70.7%; median age, 67 years [interquartile range {IQR}, 59-73]). From day 1 to day 7, median ECC increased from 26.0 mL/min (IQR, 8.8 to 59.5) to 65.4 mL/min (IQR, 26.7 to 115.4) in the recombinant alkaline phosphatase 1.6-mg/kg group vs from 35.9 mL/min (IQR, 12.2 to 82.9) to 61.9 mL/min (IQR, 22.7 to 115.2) in the placebo group (absolute difference, 9.5 mL/min [95% CI, −23.9 to 25.5]; P = .47). Fatal adverse events occurred in 26.3% of patients in the 0.4-mg/kg recombinant alkaline phosphatase group; 17.1% in the 0.8-mg/kg group, 17.4% in the 1.6-mg/kg group, and 29.5% in the placebo group. Rates of nonfatal SAEs were 21.0% for the 0.4-mg/kg recombinant alkaline phosphatase group, 14.3% for the 0.8-mg/kg group, 25.7% for the 1.6-mg/kg group, and 20.5% for the placebo group. Conclusions and Relevance Among patients who were critically ill with sepsis-associated acute kidney injury, human recombinant alkaline phosphatase compared with placebo did not significantly improve short-term kidney function. Further research is necessary to assess other clinical outcomes. Trial Registration ClinicalTrials.gov Identifier: NCT02182440
Retrospective studying of sociodemographic, clinical characteristics and extent of alcohol use disorder among patients applied by probation -

Objective: Aim of this study was to study sociodemographic, clinical characteristics and extent of alcohol use disorder (AUD) among patients applied by probation. Methods: The file records of the 215 cases who gave at least one urine-blood sample applied to Izmir Ataturk Education and Research Hospital Addiction Unit Probation Policlinic at February 2010 have been assessed retrospectively. Sociodemographic characteristics, clinical char-acteristics of substance use and CAGE (Cut down, Annoyed, Guilty, Eye-opener) scores and blood %CDT (carbo-hydrate-deficient transferrin) results of cases were used to detect AUD. SPSS 15.0 program has been used for the statistical assessment. Results: The average age of the sample was 29.4±9.1 year and most of the patients were male (%99.5). The lifetime prevalence of substances was cannabis %99.5, ecstasy %17.2, benzodiazepine %11.6, cocaine %5.6, heroin %0.9 and inhalants %0.9. %10.2 patients were positive for urine samples. %8.8 patient were positive for cannabis and %3.2 were positive for benzodiazepine. Urine samples positive group had higher unemployment rates (χ2=8.72, p=0.003) and higher CAGE scores (χ2=5.08, p=0.024). %37.2 patients had positive %CDT and %25.6 patients had positive CAGE scores. Discussion: The most important finding of this study is that higher unemployment rates in urine positive group and high AUD rates in all patients. The relation-ship between unemployment and substance use show that social and employment rehabilitation programs with medical treatment is important. High AUD rates show the importance of evaluating alcohol use in treatment.