pinecone/core-2020-05-10-deduplication huggingface dataset:
Does This Patient Have Acute Mountain Sickness?: The Rational Clinical Examination Systematic Review.

Acute mountain sickness (AMS) affects more than 25% of individuals ascending to 3500 m (11 500 ft) and more than 50% of those above 6000 m (19 700 ft). AMS may progress from nonspecific symptoms to life-threatening high-altitude cerebral edema in less than 1% of patients. It is not clear how to best diagnose AMS.
To systematically review studies assessing the accuracy of AMS diagnostic instruments, including the visual analog scale (VAS) score, which quantifies the overall feeling of sickness at altitude (VAS[O]; various thresholds), Acute Mountain Sickness-Cerebral score (AMS-C; ≥0.7 indicates AMS), and the clinical functional score (CFS; ≥2 indicates AMS) compared with the Lake Louise Questionnaire Score (LLQS; score of ≥5).
Searches of MEDLINE and EMBASE from inception to May 2017 identified 1245 publications of which 91 were suitable for prevalence analysis (66 944 participants) and 14 compared at least 2 instruments (1858 participants) using a score of 5 or greater on the LLQS as a reference standard. To determine the prevalence of AMS for establishing the pretest probability of AMS, a random-effects meta-regression was performed based on the reported prevalence of AMS as a function of altitude.
AMS prevalence, likelihood ratios (LRs), sensitivity, and specificity of screening instruments.
The final analysis included 91 articles (comprising 66 944 study participants). Altitude predicted AMS and accounted for 28% of heterogeneity between studies. For each 1000-m (3300-ft) increase in altitude above 2500 m (8200 ft), AMS prevalence increased 13% (95% CI, 9.5%-17%). Testing characteristics were similar for VAS(O), AMS-C, and CFS vs a score of 5 or greater on the LLQS (positive LRs: range, 3.2-8.2; P = .22 for comparisons; specificity range, 67%-92%; negative LRs: range, 0.30-0.36; P = .50 for comparisons; sensitivity range, 67%-82%). The CFS asks a single question: "overall if you had any symptoms, how did they affect your activity (ordinal scale 0-3)?" For CFS, moderate to severe reduction in daily activities had a positive LR of 3.2 (95% CI, 1.4-7.2) and specificity of 67% (95% CI, 37%-97%); no reduction to mild reduction in activities had a negative LR of 0.30 (95% CI, 0.22-0.39) and sensitivity of 82% (95% CI, 77%-87%).
The prevalence of acute mountain sickness increases with higher altitudes. The visual analog scale for the overall feeling of sickness at altitude, Acute Mountain Sickness-Cerebral, and clinical functional score perform similarly to the Lake Louise Questionnaire Score using a score of 5 or greater as a reference standard. In clinical and travel settings, the clinical functional score is the simplest instrument to use. Clinicians evaluating high-altitude travelers who report moderate to severe limitations in activities of daily living (clinical functional score ≥2) should use the Lake Louise Questionnaire Score to assess the severity of acute mountain sickness
Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial.

Tumor-treating fields (TTFields) is an antimitotic treatment modality that interferes with glioblastoma cell division and organelle assembly by delivering low-intensity alternating electric fields to the tumor.
To investigate whether TTFields improves progression-free and overall survival of patients with glioblastoma, a fatal disease that commonly recurs at the initial tumor site or in the central nervous system.
In this randomized, open-label trial, 695 patients with glioblastoma whose tumor was resected or biopsied and had completed concomitant radiochemotherapy (median time from diagnosis to randomization, 3.8 months) were enrolled at 83 centers (July 2009-2014) and followed up through December 2016. A preliminary report from this trial was published in 2015; this report describes the final analysis.
Patients were randomized 2:1 to TTFields plus maintenance temozolomide chemotherapy (n = 466) or temozolomide alone (n = 229). The TTFields, consisting of low-intensity, 200 kHz frequency, alternating electric fields, was delivered (≥ 18 hours/d) via 4 transducer arrays on the shaved scalp and connected to a portable device. Temozolomide was administered to both groups (150-200 mg/m2) for 5 days per 28-day cycle (6-12 cycles).
Progression-free survival (tested at α = .046). The secondary end point was overall survival (tested hierarchically at α = .048). Analyses were performed for the intent-to-treat population. Adverse events were compared by group.
Of the 695 randomized patients (median age, 56 years; IQR, 48-63; 473 men [68%]), 637 (92%) completed the trial. Median progression-free survival from randomization was 6.7 months in the TTFields-temozolomide group and 4.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.52-0.76; P &lt; .001). Median overall survival was 20.9 months in the TTFields-temozolomide group vs 16.0 months in the temozolomide-alone group (HR, 0.63; 95% CI, 0.53-0.76; P &lt; .001). Systemic adverse event frequency was 48% in the TTFields-temozolomide group and 44% in the temozolomide-alone group. Mild to moderate skin toxicity underneath the transducer arrays occurred in 52% of patients who received TTFields-temozolomide vs no patients who received temozolomide alone.
In the final analysis of this randomized clinical trial of patients with glioblastoma who had received standard radiochemotherapy, the addition of TTFields to maintenance temozolomide chemotherapy vs maintenance temozolomide alone, resulted in statistically significant improvement in progression-free survival and overall survival. These results are consistent with the previous interim analysis.
clinicaltrials.gov Identifier: NCT00916409
Effect of cervical pessary on spontaneous preterm birth in women with singleton pregnancies and short cervical length a randomized clinical trial

IMPORTANCE:\ud
Spontaneous preterm birth is a major cause of perinatal morbidity and mortality. It is unclear if a cervical pessary can reduce the risk of spontaneous preterm delivery.\ud
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OBJECTIVE:\ud
To test whether in asymptomatic women with singleton pregnancies and no prior spontaneous preterm birth but with short cervical length on transvaginal ultrasound, use of a cervical pessary would reduce the rate of spontaneous preterm birth at less than 34 weeks of gestation.\ud
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DESIGN, SETTING, AND PARTICIPANTS:\ud
Parallel-group, nonblinded, randomized clinical trial conducted from March 1, 2016, to May 25, 2017, at a single center in Italy. Asymptomatic women with singleton gestations, no previous spontaneous preterm births, and cervical lengths of 25 mm or less at 18 weeks 0 days to 23 weeks 6 days of gestation were eligible.\ud
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INTERVENTIONS:\ud
Patients were randomized 1:1 to receive either cervical pessary (n = 150) or no pessary (n = 150). The pessary was removed between 37 weeks 0 days and 37 weeks 6 days of gestation or earlier if clinically indicated. The control group received standard care. For cervical length of 20 mm or shorter, women in both groups were prescribed vaginal progesterone, 200 mg/d, until 36 weeks 6 days of gestation. No bed rest or activity restriction was recommended.\ud
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MAIN OUTCOMES AND MEASURES:\ud
The primary end point was spontaneous preterm birth at less than 34 weeks of gestation. Secondary outcomes were adverse events.\ud
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RESULTS:\ud
Among 300 women who were randomized (mean age, 29 [SD, 6.3] years; mean gestational age, 22 [SD, 1.3] weeks), 100% completed the trial. The primary end point occurred in 11 women (7.3%) in the pessary group and 23 women (15.3%) in the control group (between-group difference, -8.0% [95% CI, -15.7% to -0.4]; relative risk, 0.48 [95% CI, 0.24-0.95]). During follow-up, the pessary group had a higher rate of increased or new vaginal discharge (86.7% vs 46.0%; between-group difference, +40.7% [95% CI, +30.1%-+50.3%]; relative risk, 1.88 [95% CI, 1.57-2.27]).\ud
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CONCLUSIONS AND RELEVANCE:\ud
Among women without prior spontaneous preterm birth who had asymptomatic singleton pregnancies and short transvaginal cervical length, use of a cervical pessary, compared with no pessary use, resulted in a lower rate of spontaneous preterm birth at less than 34 weeks of gestation. The results of this single-center, nonblinded study among selected pregnant women require confirmation in multicenter clinical trials.\ud
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TRIAL REGISTRATION:\ud
clinicaltrials.gov Identifier: NCT02716909
Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies: The PRISMA-DTA Statement.

This is the final version of the article. Available from American Medical Association via the DOI in this record.Importance: Systematic reviews of diagnostic test accuracy synthesize data from primary diagnostic studies that have evaluated the accuracy of 1 or more index tests against a reference standard, provide estimates of test performance, allow comparisons of the accuracy of different tests, and facilitate the identification of sources of variability in test accuracy. Objective: To develop the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagnostic test accuracy guideline as a stand-alone extension of the PRISMA statement. Modifications to the PRISMA statement reflect the specific requirements for reporting of systematic reviews and meta-analyses of diagnostic test accuracy studies and the abstracts for these reviews. Design: Established standards from the Enhancing the Quality and Transparency of Health Research (EQUATOR) Network were followed for the development of the guideline. The original PRISMA statement was used as a framework on which to modify and add items. A group of 24 multidisciplinary experts used a systematic review of articles on existing reporting guidelines and methods, a 3-round Delphi process, a consensus meeting, pilot testing, and iterative refinement to develop the PRISMA diagnostic test accuracy guideline. The final version of the PRISMA diagnostic test accuracy guideline checklist was approved by the group. Findings: The systematic review (produced 64 items) and the Delphi process (provided feedback on 7 proposed items; 1 item was later split into 2 items) identified 71 potentially relevant items for consideration. The Delphi process reduced these to 60 items that were discussed at the consensus meeting. Following the meeting, pilot testing and iterative feedback were used to generate the 27-item PRISMA diagnostic test accuracy checklist. To reflect specific or optimal contemporary systematic review methods for diagnostic test accuracy, 8 of the 27 original PRISMA items were left unchanged, 17 were modified, 2 were added, and 2 were omitted. Conclusions and Relevance: The 27-item PRISMA diagnostic test accuracy checklist provides specific guidance for reporting of systematic reviews. The PRISMA diagnostic test accuracy guideline can facilitate the transparent reporting of reviews, and may assist in the evaluation of validity and applicability, enhance replicability of reviews, and make the results from systematic reviews of diagnostic test accuracy studies more useful.The research was supported by grant 375751 from the Canadian Institute for Health Research; funding from the Canadian Agency for Drugs and Technologies in Health; funding from the Standards for Reporting of Diagnostic Accuracy Studies Group; funding from the University of Ottawa Department of Radiology Research Stipend Program; and funding from the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care South West Peninsula
Effect of total laparoscopic hysterectomy vs total abdominal hysterectomy on disease-free survival among women with stage I endometrial cancer. A randomized clinical trial

<b>IMPORTANCE </b>\ud
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Current standard treatment for endometrial cancer involves removal of uterus, adnexa ± lymph nodes. Few randomized trials have compared disease-free survival outcomes for surgical approaches.  \ud
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<b>OBJECTIVE </b>\ud
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To investigate whether total laparoscopic hysterectomy (TLH) is equivalent to total abdominal hysterectomy (TAH) in women with treatment-naive endometrial cancer.\ud
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<b>DESIGN, SETTING, AND PARTICIPANTS  </b>\ud
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Multinational, randomized equivalence trial evaluating the laparoscopic approach to endometrial cancer (LACE). Between October 7, 2005 and June 30, 2010, 27 surgeons from 20 tertiary gynaecological cancer centres in Australia, New Zealand, and Hong Kong randomised 760 women with stage I endometrioid endometrial cancer to either TLH or TAH. Follow-up ended 3rd March 2016. \ud
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<b>INTERVENTIONS  </b>\ud
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353 patients were randomized to TAH, 407 to TLH. \ud
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<b>MAIN OUTCOMES AND MEASURES  </b>\ud
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Analysis according to intention-to-treat assessed the primary outcome of disease-free survival (DFS, time interval between surgery and date of first recurrence including any new localized or distant endometrial cancer recurrence or any new cancers, at 4.5 years post-randomization). The pre-specified equivalence boundary was ∆=±7%.  Among seven pre-specified secondary outcomes, disease recurrence and overall survival are reported.  \ud
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<b>RESULTS </b>\ud
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Patients were followed for a median of 4.5 years. Of 760 patients who were randomized (mean age 63 years), 679 (89%) completed the trial. At 4.5 years follow-up, DFS was 81.3% in the TAH and 81.6% in the TLH group. Equivalence was established with a DFS rate difference of 0.3% (favoring TLH) [95% CI: -5.53% to 6.13], p for equivalence =0.007. There was no statistical difference in endometrial cancer recurrences between the two groups (TAH 28 of 353 (7.9%) and TLH 33 of 407 (8.1%), risk difference 0.2%, 95% CI: -3.7 to 4.0%, p=0.93) or in overall survival (TAH 24 of 353 (6.8%) and TLH 30 of 407 (7.4%), risk difference 0.6%, 95% CI: -3.0 to 4.2%, p=0.76). \ud
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<b>CONCLUSIONS AND RELEVANCE </b>\ud
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Among women with stage I endometrioid endometrial cancer, the use of TAH compared with TLH resulted in equivalent DFS at 4.5 years and no difference in overall survival was observed. These findings support the use of laparoscopic hysterectomy for stage 1 endometrial cancer
Characteristics of pre-approval and post-approval studies for drugs granted accelerated approval by the US food and drug administration

Importance: Drugs treating serious conditions can receive US Food and Drug Administration (FDA) Accelerated Approval based on showing an effect in surrogate measures that are only reasonably likely to predict clinical benefit. Confirmatory trials are then required to determine whether these effects translate to clinical improvements.  Objective: To characterize pre-approval and confirmatory clinical trials of drugs granted Accelerated Approval.  Design and Setting: Publicly available FDA documents were surveyed to evaluate the pre-approval trials leading to Accelerated Approval between 2009 and 2013. Information on the status and findings of required confirmatory studies was extracted from the FDA’s database of postmarketing requirements and commitments, ClinicalTrials.gov, and matched publications. End date of follow up was 7 April 2017. Exposure: Granting of Accelerated Approval.  Main Outcomes and Measures: Characteristics of pre-approval and confirmatory studies were compared in terms of study design features (randomization, blinding, comparator, primary endpoint) and indications. Subsequent regulatory decisions and estimated time between Accelerated Approval and fulfillment of regulatory requirements were reviewed.  Results: FDA granted Accelerated Approval to 22 drugs for 24 indications in the study period. At a minimum 3 years of follow-up, 19 of 38 required confirmatory studies were completed (50%). The proportion of studies with randomized designs did not differ before and after Accelerated Approval (16%, 95% confidence interval [CI]: -15%-46%; P=0.31). Post-approval requirements were completed and demonstrated efficacy in 10 indications (42%) on the basis of trials that evaluated surrogate measures alone. Among the 14 indications (58%) that had not yet completed requirements, confirmatory studies failed to demonstrate clinical benefit in 2 (8%) indications; were terminated in 2 (8%); and were delayed by more than one year in 3 (13%) with no regulatory action. Studies were progressing according to target timelines for the remaining 7 indications (29%). Clinical benefit had not yet been confirmed for 7 indications that had been initially approved 5 or more years prior.  Conclusions and Relevance: Many drugs recently granted Accelerated Approval had had their efficacy confirmed in post-approval trials, although confirmatory trials have similar design elements to pre-approval trials, including reliance on surrogate measures as outcomes. Delays in completing post-approval confirmatory trials persisted for a minority of drugs
Effects of improvisational music therapy vs enhanced standard care on symptom severity among children with autism spectrum disorder: the TIME-A randomized clinical trial

IMPORTANCE Music therapymay facilitate skills in areas affected by autism spectrum disorder (ASD), such as social interaction and communication. OBJECTIVE To evaluate effects of improvisational music therapy on generalized social communication skills of children with ASD. DESIGN, SETTING, AND PARTICIPANTS Assessor-blinded, randomized clinical trial, conducted in 9 countries and enrolling children aged 4 to 7 years with ASD. Childrenwere recruited from November 2011 to November 2015, with follow-up between January 2012 and November 2016. INTERVENTIONS Enhanced standard care (n = 182) vs enhanced standard care plus improvisational music therapy (n = 182), allocated in a 1:1 ratio. Enhanced standard care consisted of usual care as locally available plus parent counseling to discuss parents’ concerns and provide information about ASD. In improvisational music therapy, trained music therapists sang or played music with each child, attuned and adapted to the child’s focus of attention, to help children develop affect sharing and joint attention. MAIN OUTCOMES AND MEASURES The primary outcomewas symptom severity over 5 months, based on the Autism Diagnostic Observation Schedule (ADOS), social affect domain (range, 0-27; higher scores indicate greater severity; minimal clinically important difference, 1). Prespecified secondary outcomes included parent-rated social responsiveness. All outcomes were also assessed at 2 and 12 months. RESULTS Among 364 participants randomized (mean age, 5.4 years; 83%boys), 314 (86%) completed the primary end point and 290 (80%) completed the last end point. Over 5 months, participants assigned to music therapy received a median of 19 music therapy, 3 parent counseling, and 36 other therapy sessions, compared with 3 parent counseling and 45 other therapy sessions for those assigned to enhanced standard care. From baseline to 5 months, mean ADOS social affect scores estimated by linear mixed-effects models decreased from 14.08 to 13.23 in the music therapy group and from 13.49 to 12.58 in the standard care group (mean difference, 0.06 [95%CI, −0.70 to 0.81]; P = .88), with no significant difference in improvement. Of 20 exploratory secondary outcomes, 17 showed no significant difference. CONCLUSIONS AND RELEVANCE Among children with autism spectrum disorder, improvisational music therapy, compared with enhanced standard care, resulted in no significant difference in symptom severity based on the ADOS social affect domain over 5 months. These findings do not support the use of improvisational music therapy for symptom reduction in children with autism spectrum disorder. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN7892396
A multifactorial system for equitable selection of cadaver kidney recipients

During 1986, a total of 270 cadaver renal transplantations were performed at the University of Pittsburgh. Kidneys were allocated by a point system that awarded points to recipients for waiting time, antigen matching, antibody analyses, medical urgency, and logistic practicality. Kidneys were given to patients with the highest point totals in 98% of cases. To our knowledge, this is the first such multifactorial system for cadaver kidney allocation. Possibly it may be modified for extrarenal organs
Effect of lifestyle changes on erectile dysfunction in obese men: a randomized controlled trial

Context: Healthy lifestyle factors are associated with maintenance of erectile function in men. Objective: To determine the effect of weight loss and increased physical activity on erectile and endothelial functions in obese men. Design, Setting, and Patients: Randomized, single-blind trial of 110 obese men (body mass index ≥30) aged 35 to 55 years, without diabetes, hypertension, or hyperlipidemia, who had erectile dysfunction that was determined by having a score of 21 or less on the International Index of Erectile Function (IIEF). The study was conducted from October 2000 to October 2003 at a university hospital in Italy. Interventions: The 55 men randomly assigned to the intervention group received detailed advice about how to achieve a loss of 10% or more in their total body weight by reducing caloric intake and increasing their level of physical activity. Men in the control group (n=55) were given general information about healthy food choices and exercise. Main Outcomes Measures: Erectile function score, levels of cholesterol and tryglycerides, circulating levels of interleukin 6, interleukin 8, and C-reactive protein, and endothelial function as assessed by vascular responses to L-arginine. Results: After 2 years, body mass index decreased more in the intervention group (from a mean [SD] of 36.9 [2.5] to 31.2 [2.1]) than in the control group (from 36.4 [2.3] to 35.7 [2.5]) (P<.001), as did serum concentrations of interleukin 6 (P=.03), and C-reactive protein (P=.02). The mean (SD) level of physical activity increased more in the intervention group (from 48 [10] to 195 [36] min/wk; P<.001) than in the control group (from 51 [9] to 84 [28] min/wk; P<.001). The mean (SD) IIEF score improved in the intervention group (from 13.9 [4.0] to 17 [5]; P<.001), but remained stable in the control group (from 13.5 [4.0] to 13.6 [4.1]; P=.89). Seventeen men in the intervention group and 3 in the control group (P=.001) reported an IIEF score of 22 or higher. In multivariate analyses, changes in body mass index (P=.02), physical activity (P=.02), and C-reactive protein (P=.03) were independently associated with changes in IIEF score. Conclusion: Lifestyle changes are associated with improvement in sexual function in about one third of obese men with erectile dysfunction at baseline