bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mild Cognitive Impairment and Risk of Critical Illness*
Authors: Teeters D. Alex , Moua Teng , Li Guangxi , Kashyap Rahul , Biehl Michelle , Kaur Rupinder , Gajic Ognjen , Boeve Bradley F. , St Louis Erik K. , Petersen Ronald C. , Caples Sean M. 
Published: July 2016

Objectives:
Approximately half of ICU admissions are comprised of patients older than 65 years old. Mild cognitive impairment is a common disorder affecting 10–20% of patients in the same age group. A need exists for exploring mild cognitive impairment and risk of critical illness. As mild cognitive impairment may be a contributor to poorer overall health or be a result of it, we sought to determine whether the presence of mild cognitive impairment independently increases the risk of critical illness admissions.

Design:
Data from the Mayo Clinic Study of Aging were analyzed. All study participants underwent prospective comprehensive cognitive testing and expert panel consensus diagnosis of both cognitive function and clinical state at baseline and subsequent visits. Comparisons were made between those with normal cognitive function and mild cognitive impairment regarding baseline health and frequency of critical illness.

Setting:
Single-center population-based cohort out of Olmsted County, MN.

Participants:
All individuals 70–89 years old were screened for prospective enrollment in the Mayo Clinic Study of Aging. Patients with preexisting dementia and ICU admission within 3 years of entry to the study were excluded from this analysis.

Interventions:
None.

Measurements and Main Results:
Of 2,425 patients analyzed from the Mayo Clinic Study of Aging, 1,734 patients (71%) were included in the current study. Clinical factors associated with baseline mild cognitive impairment included age, male gender, stroke, and poorer health self-rating. Using a Cox regression model adjusting for these and a priori variables of baseline health, the presence of mild cognitive impairment remained a significant predictor of ICU admission (hazard ratio, 1.50 [1.15–1.96]; p = 0.003).

Conclusions and Relevance:
The presence of mild cognitive impairment is independently associated with increased critical illness admission. Further prospective studies are needed to analyze the impact of critical illness on cognitive function.
Quality of Life and Recommendations for Further Care*
Authors: Putman Michael S. , Tak Hyo Jung , Curlin Farr A. , Yoon John D. 
Published: July 2016

Objectives:
Physician recommendations for further medical treatment or palliative treatment only at the end of life may influence patient decisions. Little is known about the patient characteristics that affect physician-assessed quality of life or how such assessments are related to subsequent recommendations.

Design, Setting, and Subjects:
A 2010 mailed survey of practicing U.S. physicians (1,156/1,878 or 62% of eligible physicians responded).

Measurements and Main Results:
Measures included an end of life vignette with five experimentally varied patient characteristics: setting, alimentation, pain, cognition, and communication. Physicians rated vignette patient quality of life on a scale from 0 to 100 and indicated whether they would recommend continuing full medical treatment or palliative treatment only. Cognitive deficits and alimentation had the greatest impacts on recommendations for further care, but pain and communication were also significant (all p < 0.001). Physicians who recommended continuing full medical treatment rated quality of life three times higher than those recommending palliative treatment only (40.41 vs 12.19; p < 0.01). Religious physicians were more likely to assess quality of life higher and to recommend full medical treatment.

Conclusions:
Physician judgments about quality of life are highly correlated with recommendations for further care. Patients and family members might consider these biases when negotiating medical decisions.
Neutrophil Fluorescence: A New Indicator of Cell Activation During Septic Shock–Induced Disseminated Intravascular Coagulation
Authors: Stiel Laure , Delabranche Xavier , Galoisy Anne-Cécile , Severac François , Toti Florence , Mauvieux Laurent , Meziani Ferhat , Boisramé-Helms Julie 
Published: July 2016

Objective:
To investigate the contribution of neutrophil activation as innate immune cells during septic shock–induced disseminated intravascular coagulation.

Design:
Prospective study.

Setting:
One University Hospital ICU.

Participants:
Hundred patients with septic shock. Thirty-five patients had disseminated intravascular coagulation according to Japanese Association for Acute Medicine 2006 score.

Intervention:
None.

Measurements and Main Results:
Neutrophil chromatin decondensation was assessed by measuring neutrophil fluorescence (NEUT-side-fluorescence light) labeled by a fluorochrome-based polymethine reagent using a routine automated flow cytometer Sysmex XN20 (Sysmex, Kobe, Japan) and neutrophil-derived CD66b microparticles by prothrombinase assay. Measurements in disseminated intravascular coagulation and no disseminated intravascular coagulation patients showed that a mean value of NEUT-side-fluorescence light above 57.3 arbitrary units had a sensitivity of 90.91% and a specificity of 80.60% for disseminated intravascular coagulation diagnosis. NEUT-side-fluorescence light was correlated to the CD66b microparticles/neutrophil count, a surrogate of neutrophil activation associated with septic shock–induced disseminated intravascular coagulation.

Conclusion:
NEUT-side-fluorescence light, routinely available, could prove an accurate biomarker of neutrophil activation.
Elevated Plasma Angiopoietin-2 Levels Are Associated With Fluid Overload, Organ Dysfunction, and Mortality in Human Septic Shock
Authors: Fisher Jane , Douglas James J. , Linder Adam , Boyd John H. , Walley Keith R. , Russell James A. 
Published: July 2016

Objectives:
Angiopoietins modulate endothelial permeability via endothelial cell junctions. Angiopoietin-2 blocks the angiopoietin-1/Tie-2 interaction that stabilizes these junctions, and elevated plasma angiopoietin-2 levels are associated with vascular leakage. We hypothesized that plasma angiopoietin-1 and angiopoietin-2 levels are associated with indirect markers of increased vascular permeability, organ dysfunction, mortality, and plasma proinflammatory cytokine levels in human septic shock.

Design:
Multicenter observational cohort study derived from a randomized controlled trial (Vasopressin and Septic Shock Trial of vasopressin versus norepinephrine in septic shock).

Setting:
ICUs of hospitals in Canada, Australia, and the United States.

Patients:
Three hundred forty-one patients in the randomized, controlled Vasopressin and Septic Shock Trial trial of vasopressin versus norepinephrine in septic shock.

Interventions:
None.

Measurement and Main Results:
We measured plasma levels of angiopoietin-1 and angiopoietin-2 at study baseline and determined their association with percent fluid overload and acute organ dysfunction and generated a receiver operating characteristic curve for plasma angiopoietin-2 levels versus acute kidney injury. We also determined the association of angiopoietin-1 and angiopoietin-2 levels with hemodynamics, mortality, and plasma cytokine levels. Plasma angiopoietin-2 levels were directly associated with percent fluid overload at baseline (r
s = 0.18; p = 0.0008) and at 6 hours (r
s = 0.13; p = 0.023), but not at 24 hours (r
s = 0.041; p = 0.46). Plasma angiopoietin-2 levels were associated with the development of hepatic (p < 0.0001) and coagulation (p < 0.0001) dysfunction and acute kidney injury (p < 0.0001). Receiver operating characteristic curve had an area under the curve of 0.73 for acute kidney injury. angiopoietin-2 levels were also inversely associated with days alive (r = –0.24; p = 0.010) and positively associated with increased 7-day (log-rank trend chi-square = 5.9; p = 0.015) and 28-day (log-rank chi square = 4.9; p = 0.027) mortality. A threshold of angiopoietin-2 levels above the first quartile (> 5,807 pg/mL) was observed to be associated with increased mortality risk, which aligns with prior studies. Plasma angiopoietin-2 levels were positively associated with plasma cytokine levels, including tumor necrosis factor-α and interleukin-6 at baseline (r
s = 0.39; p < 0.0001 and r
s = 0.51; p < 0.0001) and at 24 hours (r
s = 0.29; p < 0.0001 and r
s = 0.41; p < 0.0001).

Conclusions:
Increased plasma angiopoietin-2 levels are associated with increased fluid overload, hepatic and coagulation dysfunction, acute kidney injury, mortality, and plasma cytokines in human septic shock. angiopoietin-2 activation may increase vascular leakage leading to increased fluid requirements, organ dysfunction, and death from septic shock.
An Algorithm for Systemic Inflammatory Response Syndrome Criteria–Based Prediction of Sepsis in a Polytrauma Cohort*
Authors: Lindner Holger A. , Balaban Ümniye , Sturm Timo , Weiϐ Christel , Thiel Manfred , Schneider-Lindner Verena 
Published: July 2016

Objectives:
Lifesaving early distinction of infectious systemic inflammatory response syndrome, known as “sepsis,” from noninfectious systemic inflammatory response syndrome is challenging in the ICU because of high systemic inflammatory response syndrome prevalence and lack of specific biomarkers. The purpose of this study was to use an automatic algorithm to detect systemic inflammatory response syndrome criteria (tachycardia, tachypnea, leukocytosis, and fever) in surgical ICU patients for ICU-wide systemic inflammatory response syndrome prevalence determination and evaluation of algorithm-derived systemic inflammatory response syndrome descriptors for sepsis prediction and diagnosis in a polytrauma cohort.

Design:
Cross-sectional descriptive study and retrospective cohort study.

Setting:
Electronic medical records of a tertiary care center’s surgical ICU, 2006–2011.

Patients:
All ICU admissions and consecutive polytrauma admissions.

Interventions:
None.

Measurements and Main Results:
Average prevalence of conventional systemic inflammatory response syndrome (≥ 2 criteria met concomitantly) from cross-sectional application of the algorithm to all ICU patients and each minute of the study period was 43.3%. Of 256 validated polytrauma patients, 85 developed sepsis (33.2%). Three systemic inflammatory response syndrome descriptors summarized the 24 hours after admission and before therapy initiation: 1) systemic inflammatory response syndrome criteria average for systemic inflammatory response syndrome quantification over time, 2) first-to-last minute difference for trend detection, and 3) change count reflecting systemic inflammatory response syndrome criteria fluctuation. Conventional systemic inflammatory response syndrome for greater than or equal to 1 minute had 91% sensitivity and 19% specificity, whereas a systemic inflammatory response syndrome criteria average cutoff value of 1.72 had 51% sensitivity and 77% specificity for sepsis prediction. For sepsis diagnosis, systemic inflammatory response syndrome criteria average and first-to-last minute difference combined yielded 82% sensitivity and 71% specificity compared with 99% sensitivity and only 31% specificity of conventional systemic inflammatory response syndrome from a nested case-control analysis.

Conclusions:
Dynamic systemic inflammatory response syndrome descriptors improved specificity of sepsis prediction and particularly diagnosis, rivaling established biomarkers, in a polytrauma cohort. They may enhance electronic sepsis surveillance once evaluated in other patient populations.
A Phase II Study to Prevent Radiation-induced Rectal Injury With Lovastatin
Authors: Anscher Mitchell S. , Chang Michael G. , Moghanaki Drew , Rosu Mihaela , Mikkelsen Ross B. , Holdford Diane , Skinner Vicki , Grob Baruch M. , Sanyal Arun , Wang Aiping , Mukhopadhyay Nitai D. 
Published: July 2016

Purpose:
Physician reported symptomatic late rectal injury occurs in about 5% to 25% of patients treated with radiation therapy for prostate cancer, depending on the treatment technique. Patients, however, report clinically meaningful declines in bowel/rectal function regardless of the technique used. Lovastatin has been shown to protect mice from late radiation injury. This study was designed to determine if lovastatin might reduce the incidence of late rectal injury in patients receiving radiation therapy for prostate cancer.

Materials and Methods:
Patients with adenocarcinoma of the prostate receiving radiotherapy with curative intent were eligible. A portion of the rectum had to receive at least 60 Gy. Gastrointestinal functioning was assessed using both physician-reported and patient-reported instruments at baseline and at prescribed intervals during and after treatment. Lovastatin (20 to 80 mg/d) was started on day 1 of radiation and continued for 12 months. Patients were followed for an additional 12 months. The primary endpoint was physician-reported rectal toxicity ≥grade 2 during the first 2 years after treatment.

Results:
A total of 20/53 (38%) patients developed grade 2 or higher toxicity during the 2-year follow-up period. Seventeen patients had 1 or more unresolved gastrointestinal symptom at the end of 2 years, 3 (6%) of which were grade 2 and none were of higher grade.

Conclusions:
The primary endpoint of the study was not met. Lovastatin, as administered in this trial, did not reduce the incidence of grade 2 or higher rectal toxicity compared with historical controls.
Hormone therapy and clinical and surrogate cardiovascular endpoints in women with chronic kidney disease: a systematic review and meta-analysis
Authors: Ramesh Sharanya , Mann Michelle C. , Holroyd-Leduc Jayna M. , Wilton Stephen B. , James Matthew T. , Seely Ellen W. , Ahmed Sofia B. 
Published: July 2016

Abstract

Objective:
Women with chronic kidney disease (CKD) experience kidney dysfunction-mediated premature menopause. The role of postmenopausal hormone therapy (HT) in this population is unclear. We sought to summarize current knowledge regarding use of postmenopausal HT and cardiovascular (CV) outcomes, and established surrogate measures of CV risk in women with CKD.

Methods:
This is a systematic review and meta-analysis of adult women with CKD. We searched electronic bibliographic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials) (inception to 2014 December), relevant conference proceedings, tables of contents of journals, and review articles. Randomized controlled trials and observational studies examining postmenopausal HT compared with either placebo or untreated control groups were included. The intervention of interest was postmenopausal HT, and the outcome measures were all-cause and CV mortality, nonfatal CV event (myocardial infarction, stroke), and surrogate measures of CV risk (serum lipids, blood pressure).

Results:
Of 12,482 references retrieved, four randomized controlled trials and two cohort studies (N = 1,666 participants) were identified. No studies reported on CV outcomes or mortality. Compared with placebo, postmenopausal HT was associated with decreased low-density lipoprotein cholesterol (−13.2 mg/dL [95% CI, −23.32 to −3.00 mg/dL]), and increased high-density lipoprotein (8.73 mg/dL [95% CI, 4.72-12.73 mg/dL]) and total cholesterol (7.96 mg/dL [95% CI, 0.07-15.84 mg/dL]). No associations were observed between postmenopausal HT triglyceride levels and blood pressure.

Conclusions:
Studies examining the effect of postmenopausal HT on CV outcomes in women with CKD are lacking. Further prospective study of the role of postmenopausal HT in this high-risk group is required.
Relationship between changes in vasomotor symptoms and changes in menopause-specific quality of life and sleep parameters
Authors: Pinkerton JoAnn V. , Abraham Lucy , Bushmakin Andrew G. , Cappelleri Joseph C. , Komm Barry S. 
Published: July 2016

Abstract

Objective:
This study characterizes and quantifies the relationship of vasomotor symptoms (VMS) of menopause with menopause-specific quality of life (MSQOL) and sleep parameters to help predict treatment outcomes and inform treatment decision-making.

Methods:
Data were derived from a 12-week randomized, double-blind, placebo-controlled phase 3 trial that evaluated effects of two doses of conjugated estrogens/bazedoxifene on VMS in nonhysterectomized postmenopausal women (N = 318, mean age = 53.39) experiencing at least seven moderate to severe hot flushes (HFs) per day or at least 50 per week. Repeated measures models were used to determine relationships between HF frequency and severity and outcomes on the Menopause-Specific Quality of Life questionnaire and the Medical Outcomes Study sleep scale. Sensitivity analyses were performed to check assumptions of linearity between VMS and outcomes.

Results:
Frequency and severity of HFs showed approximately linear relationships with MSQOL and sleep parameters. Sensitivity analyses supported assumptions of linearity. The largest changes associated with a reduction of five HFs and a 0.5-point decrease in severity occurred in the Menopause-Specific Quality of Life vasomotor functioning domain (0.78 for number of HFs and 0.98 for severity) and the Medical Outcomes Study sleep disturbance (7.38 and 4.86) and sleep adequacy (−5.60 and −4.66) domains and the two overall sleep problems indices (SPI: 5.17 and 3.63; SPII: 5.82 and 3.83).

Conclusions:
Frequency and severity of HFs have an approximately linear relationship with MSQOL and sleep parameters—that is, improvements in HFs are associated with improvements in MSQOL and sleep. Such relationships may enable clinicians to predict changes in sleep and MSQOL expected from various VMS treatments.
Measuring hot flash phenomenonology using ambulatory prospective digital diaries
Authors: Fisher William I. , Thurston Rebecca C. 
Published: July 2016

Abstract

Objective:
This study provides the description, protocol, and results from a novel prospective ambulatory digital hot flash phenomenon diary.

Methods:
This study included 152 midlife women with daily hot flashes who completed an ambulatory electronic hot flash diary continuously for the waking hours of three consecutive days. In this diary, women recorded their hot flashes and accompanying characteristics and associations as the hot flashes occurred.

Results:
Self-reported hot flash severity on the digital diaries indicated that the majority of hot flashes were rated as mild (41.3%) or moderate (43.7%). Severe (13.1%) and very severe (1.8%) hot flashes were less common. Hot flash bother ratings were rated as mild (43%), or moderate (33.5%), with fewer hot flashes reported bothersome (17.5%) or very bothersome (6%). The majority of hot flashes were reported as occurring on the face (78.9%), neck (74.7%), and chest (61.3%). Of all reported hot flashes, 32% occurred concurrently with prickly skin, 7% with anxiety, and 5% with nausea. A novel finding from the study was that 38% of hot flashes were accompanied by a premonitory aura.

Conclusions:
A prospective electronic digital hot flash diary allows for a more precise quantitation of hot flashes while overcoming many of the limitations of commonly used retrospective questionnaires and paper diaries. Unique insights into the phenomenology, loci, and associated characteristics of hot flashes were obtained using this device. The digital hot flash phenomenology diary is recommended for future ambulatory studies of hot flashes as a prospective measure of the hot flash experience.
Anthropometric and cardiovascular responses to hypertrophic resistance training in postmenopausal women
Authors: Shaw Brandon S. , Gouveia Monique , McIntyre Shannon , Shaw Ina 
Published: July 2016

Abstract

Objective:
Menopause induces a phase of decreased physical fitness and altered body composition characterized by increased total and abdominal fat and reduced lean mass. It is, however, inconclusive which specific resistance training (RT) subtypes can reverse these deleterious changes in postmenopausal women.

Methods:
Thirty-seven postmenopausal women were randomized to a 6-week nonexercising control group (n = 18) or hypertrophic RT group (n = 19) that engaged in two 40-minute sessions weekly using three sets of 12 repetitions at 67% to 85% one-repetition maximum for 10 whole-body exercises.

Results:
RT significantly improved resting heart rate (69.05 ± 11.19-63.80 ± 4.94 bpm, P = 0.017), systolic blood pressure (125.85 ± 4.86-124.05 ± 3.98 mm Hg, P < 0.0001), diastolic blood pressure (81.20 ± 7.50-77.90 ± 6.85 mm Hg, P < 0.0001), rate-pressure product (8,712.40 ± 1,408.21-7,952.90 ± 782.72, P = 0.003), blood glucose concentration (6.06 ± 0.52-5.70 ± 0.52 mmol/L, P = 0.009), fat mass (21.53 ± 7.07-19.75 ± 6.40 kg, P = 0.001), percentage body fat (30.66% ± 5.08%-25.49% ± 9.89%, P = 0.026), body mass index (24.50 ± 3.85-24.27 ± 4.04 kg/m2, P = 0.050), waist circumference (80.04 ± 8.57-73.19 ± 18.44 cm, P = 0.045), sum of skinfolds (22.91 ± 6.05-20.72 ± 5.26 mm, P < 0.0001), upper-body muscle strength (20.12 ± 5.65-23.77 ± 7.10 kg, P < 0.0001), and lower-body (16.28 ± 5.47-16.44 ± 5.62 kg, P = 0.001) muscle strength.

Conclusions:
A 6-week hypertrophic RT program, performed even twice weekly, produces substantial simultaneous improvements in multiple anthropometric, cardiovascular, and muscle strength variables in postmenopausal women. This program can be recommended for inclusion in any exercise training regime or as an adjunct lifestyle approach in combination with other treatments in postmenopausal women.
Timing and persistence of effect of conjugated estrogens/bazedoxifene in postmenopausal women
Authors: Kagan Risa , Komm Barry S. , Ryan Kelly A. , Lavenberg Joanne , Yu Ching-Ray , Pinkerton JoAnn V. 
Published: July 2016

Abstract

Objective:
The aim of the study was to determine the time course of effect with conjugated estrogens/bazedoxifene (CE/BZA) in nonhysterectomized postmenopausal women in five phase 3 trials.

Methods:
This post hoc analysis identified when CE 0.45 mg/BZA 20 mg and CE 0.625 mg/BZA 20 mg first achieved a statistically significant difference (P < 0.05) versus placebo in individual trials and the duration the difference persisted for prespecified efficacy endpoints.

Results:
CE/BZA significantly reduced hot flush frequency beginning at weeks 2 to 4 and severity at weeks 3 to 6; benefits were maintained through month 24. Significant improvements in lumbar spine, total hip, femoral neck, and femoral trochanter bone mineral density were evident at month 6 or 12 and changes in bone turnover markers at month 3 or 6; benefits were maintained throughout the studies (12 or 24 mo). In symptomatic women with less than 5% vaginal superficial cells at baseline, vaginal maturation index was significantly improved by week 4. Reductions in parabasal cells were maintained throughout the studies (through months 3 and 24), but superficial cell count changes persisted only with the higher CE/BZA dose. Menopause-Specific Quality of Life total and vasomotor domain scores were improved at all assessments, from months 3 through 24. Some measures of sleep, especially quality and time to fall asleep, improved during weeks 4 to 8 and were maintained in a majority of weeks thereafter.

Conclusions:
In the context of studies designed primarily to evaluate efficacy at final study endpoints, both doses of CE/BZA achieved significance versus placebo at early assessments for most outcomes, and benefits were well maintained.