Evaluation of the Danish Aerospace Corporation Portable Pulmonary Function System

A research project designed to investigate changes in maximal oxygen consumption (VO2max) during and following long duration flight on the International Space Station (ISS) has recently been completed. The device used to measure VO2 on board ISS, the Portable Pulmonary Function System (PPFS) manufactured by the Danish Aerospace Corporation (DAC), is based on previous-generation devices manufactured by DAC, but the PPFS has not been validated for analyzing metabolic gases or measuring cardiac output (Qc). The purpose of the present evaluation is to compare PPFS metabolic gas analysis measurements to measurements obtained using a clinically-validated system (ParvoMedics TrueOne(c) 2400 system; Parvo). In addition, Qc data collected with the PPFS were compared to Qc measurements from echocardiography. METHODS: Ten subjects completed three cycle exercise tests to maximal exertion. The first test was conducted to determine each subject's VO2max and set the work rates for the second and third (comparison) tests. The protocol for the two comparison tests consisted of three 5-minute stages designed to elicit 25%, 50%, and 75% VO2max (based upon results from the initial test), followed by 1-minute stages of increasing work rate (25 watt/minute) until the subject reached maximal effort. During one of the two comparison tests, metabolic gases and Qc were assessed with the PPFS; metabolic gases and Qc were assessed with the Parvo and by echocardiography, respectively, during the other test. The order of the comparison tests was counterbalanced. VO2max and maximal work rate during the comparison tests were compared using t tests. Mixed-effects regression modeling was used to analyze submaximal data. RESULTS: All of the data were within normal physiological ranges. The PPFS-measured values for VO2max were 6% lower than values obtained with the Parvo (PPFS: 3.11 +/- 0.75 L/min; Parvo: 3.32 +/- 0.87 L/min; mean +/- standard deviation; P = 0.02); this difference is probably due to flow restriction imposed by the PPFS Qc accessories. Submaximal VO2 values were slightly lower when measured with the PPFS, although differences were not physiologically relevant. The PPFS-measured values of submaximal carbon dioxide production (VCO2) were lower than the data obtained from Parvo, which could be attributed to lower fractions of expired carbon dioxide measured by the PPFS. The PPFS Qc values tended to be lower than echocardiography-derived values. CONCLUSIONS: The results of the present study indicate a need to further examine the PPFS and to better quantify its reproducibility; however, none of the findings of the current evaluation indicate that the PPFS needs to be replaced or modified

Reliability of the Danish Aerospace Corporation Portable Pulmonary Function System

Metabolic gas analysis is a critical component of investigations that measure cardio-pulmonary exercise responses during and after long-duration spaceflight. The primary purpose of the current study was to determine the reliability and intra-subject repeatability of a metabolic gas analysis device, the Portable Pulmonary Function System (PPFS), designed for use on the International Space Station (ISS). The second objective of this study was to directly compare PPFS measurements of expired oxygen and carbon dioxide (FEO2 and FECO2) to values obtained from a well-validated clinical metabolic gas analysis system (ParvoMedics TrueOne (c) [PM]). Eight subjects performed four peak cycle tests to maximal exertion. The first test was used to prescribe work rates for the subsequent test sessions. Metabolic gas analysis for this test was performed by the PM, but samples of FEO2 and FECO2 also were simultaneously collected for analysis by the PPFS. Subjects then performed three additional peak cycle tests, consisting of three 5-min stages designed to elicit 25%, 50%, and 75% maximal oxygen consumption (VO2max) followed by stepwise increases of 25 W/min until subjects reached volitional exhaustion. Metabolic gas analysis was performed using the PPFS for these tests. Intraclass correlation coefficients (ICC), within-subject standard deviations (WS SD), and coefficients of variation (CV%) were calculated for the repeated exercise tests. Mixed model regression analysis was used to compare paired FEO2 and FECO2 values obtained from the PPFS and the PM during the initial test. The ICC values for oxygen consumption (VO2), carbon dioxide production (VCO2), and ventilation (VE) indicate that the PPFS is highly reliable (0.79 to 0.99) for all exercise levels tested; however, ICCs for respiratory exchange ratio (RER) were low ( 0.11 - 0.51), indicating poor agreement between trials during submaximal and maximal exercise. Overall, CVs ranged from 1.6% to 6.7% for all measurements, a finding consistent with reported values that were obtained using other metabolic gas analysis techniques. The PPFS and PM produced comparable FEO2 data; however, there was less agreement between measures of FECO2 obtained from the two devices, particularly at lower CO2 concentrations. The PPFS appears, in practically all respects, to yield highly reliable metabolic gas analysis data. Lower reliability of RER measurements reported in the literature and likely is not a function of the PPFS device. Further examination of PPFS CO2 data is warranted to better understand the limitations of these PPFS measurements. Overall, the PPFS when used for repeated measures of cardio-pulmonary exercise should provide accurate and reliable data for studies of human adaptation to spaceflight

Peak Oxygen Uptake during and after Long-duration Space Flight

Aerobic capacity (VO2peak) previously has not been measured during or after long-duration spaceflight. PURPOSE: To measure VO2peak and submaximal exercise responses during and after International Space Station (ISS) missions. METHODS: Astronauts (9 M, 5 F: 49 +/- 5 yr, 175 +/- 7 cm, 77.2 +/- 15.1 kg, 40.6 +/- 6.4 mL/kg/min [mean +/-SD]) performed graded peak cycle tests ~90 days before spaceflight, 15 d (FD15) after launch and every ~30 d thereafter during flight, and 1 (R+1), 10 (R+10), and 30 d (R+30) after landing. Oxygen consumption (VO2) and heart rate (HR) were measured from rest to peak exercise, while cardiac output (Q), stroke volume (SV), and arterial-venous oxygen difference (a-vO2diff) were measured only during rest and submaximal exercise. Data were analyzed using mixed-model linear regression. Body mass contributed significantly to statistical models, and thus results are reported as modeled estimates for an average subject. RESULTS: Early inflight (FD15) VO2peak was 17% lower (95% CI = - 22%, -13%) than preflight. VO2peak increased during spaceflight (0.001 L/min/d, P = 0.02) but did not return to preflight levels. On R+1 VO2peak was 15% (95% CI = -19%, -10%) lower than preflight but recovered to within 2% of preflight by R+30 (95% CI = -6%, +3%). Peak HR was not significantly different from preflight at any time. Inflight submaximal VO2 and a-vO2diff were generally lower than preflight, but the Q vs. VO2 slope was unchanged. In contrast, the SV vs. VO2 slope was lower (P < 0.001), primarily due to elevated SV at rest, and the HR vs. VO2 slope was greater (P < 0.001), largely due to elevated HR during more intense exercise. On R+1 although the relationships between VO2 and Q, SV, and HR were not statistically different than preflight, resting and submaximal exercise SV was lower (P < 0.001), resting and submaximal exercise HR was higher (P < 0.002), and a-vO2diff was unchanged. HR and SV returned to preflight levels by R+30. CONCLUSION: In the average astronaut VO2peak was reduced during spaceflight and immediately after landing but factors contributing to lower VO2peak may be different during spaceflight and recovery. Maintaining Q while VO2 is reduced inflight may be suggestive of an elevated blood flow to vascular beds other than exercising muscles, but decreased SV after flight likely reduces Q at peak exertion

Pathologist Concordance for Ovarian Carcinoma Subtype Classification and Identification of Relevant Histologic Features Using Microscope and Whole Slide Imaging.

CONTEXT.—: Despite several studies focusing on the validation of whole slide imaging (WSI) across organ systems or subspecialties, the use of WSI for specific primary diagnosis tasks has been underexamined. OBJECTIVE.—: To assess pathologist performance for the histologic subtyping of individual sections of ovarian carcinomas using a light microscope and WSI. DESIGN.—: A panel of 3 experienced gynecologic pathologists provided reference subtype diagnoses for 212 histologic sections from 109 ovarian carcinomas based on optical microscopy review. Two additional attending pathologists provided diagnoses and also identified the presence of a set of 8 histologic features important for ovarian tumor subtyping. Two experienced gynecologic pathologists and 2 fellows reviewed the corresponding WSI images for subtype classification and feature identification. RESULTS.—: Across pathologists specialized in gynecologic pathology, concordance with the reference diagnosis for the 5 major ovarian carcinoma subtypes was significantly higher for a pathologist reading on a microscope than each of 2 pathologists reading on WSI. Differences were primarily due to more frequent classification of mucinous carcinomas as endometrioid with WSI. Pathologists had generally low agreement in identifying histologic features important to ovarian tumor subtype classification with either an optical microscopy or WSI. This result suggests the need for refined histologic criteria for identifying such features. Interobserver agreement was particularly low for identifying intracytoplasmic mucin with WSI. Inconsistencies in evaluating nuclear atypia and mitoses with WSI were also observed. CONCLUSIONS.—: Further research is needed to specify the reasons for these diagnostic challenges and to inform users and manufacturers of WSI technology

Handoffs and Transitions in Critical Care (HATRICC): Protocol for a Mixed Methods Study of Operating Room to Intensive Care Unit Handoffs

Background: Operating room to intensive care unit handoffs are high-risk events for critically ill patients. Studies in selected patient populations show that standardizing operating room to intensive care unit handoffs improves information exchange and decreases errors. To adapt these findings to mixed surgical populations, we propose to study the implementation of a standardized operating room to intensive care unit handoff process in two intensive care units currently without an existing standard process. Methods/Design: The Handoffs and Transitions in Critical Care (HATRICC) study is a hybrid effectiveness- implementation trial of operating room to intensive care unit handoffs. We will use mixed methods to conduct a needs assessment of the current handoff process, adapt published handoff processes, and implement a new standardized handoff process in two academic intensive care units. Needs assessment: We will use non-participant observation to observe the current handoff process. Focus groups, interviews, and surveys of clinicians will elicit participants’ impressions about the current process. Adaptation and implementation: We will adapt published standardized handoff processes using the needs assessment findings. We will use small group simulation to test the new process’ feasibility. After simulation, we will incorporate the new handoff process into the clinical work of all providers in the study units. Evaluation: Using the same methods employed in the needs assessment phase, we will evaluate use of the new handoff process. Data analysis: The primary effectiveness outcome is the number of information omissions per handoff episode as compared to the pre-intervention period. Additional intervention outcomes include patient intensive care unit length of stay and intensive care unit mortality. The primary implementation outcome is acceptability of the new process. Additional implementation outcomes include feasibility, fidelity and sustainability. Discussion: The HATRICC study will examine the effectiveness and implementation of a standardized operating room to intensive care unit handoff process. Findings from this study have the potential to improve healthcare communication and outcomes for critically ill patients. Trial registration: ClinicalTrials.gov identifier: NCT02267174. Date of registration October 16, 2014

Impact of a ring fitted cap on insertion time and adenoma detection: a randomized controlled trial

Background and Aims: Devices for flattening colon folds can improve polyp detection at colonoscopy. However, there are few data on the endoscopic ring fitted cap (EndoRings, EndoAid, Caesarea, Israel). We sought to compare adenoma detection with EndoRings with that of standard high-definition colonoscopy. Methods: A single-center randomized controlled trial of 562 patients (284 randomized to EndoRings and 278 to standard colonoscopy) at 2 outpatient endoscopy units in the Indiana University Hospital system. Adenoma detection was the primary outcome measured as adenoma detection rate (ADR) and adenomas per colonoscopy (APC). We also compared sessile serrated polyp detection rate (SSPDR), insertion times, withdrawal times, and ease of passage through the sigmoid colon. Results: EndoRings was superior to standard colonoscopy in terms of APC (1.46 vs 1.06, p=0.025) but there were no statistically significant differences in ADR or SSPDR. Mean withdrawal time (in patients with no polyps) was shorter and insertion time (all patients) was longer in the EndoRings arm by 1.8 minutes and 0.75 minutes, respectively. One provider had significantly higher detection with EndoRings and contributed substantially to the overall results. Conclusions: EndoRings can increase adenoma detection without significant increase in procedure time, but the effect varies between operators. EndoRings slows colonoscope insertion

Psychological well-being, cardiorespiratory fitness, and long-term survival

BACKGROUND: Psychological well-being is associated with mortality/survival. Although cardiorespiratory fitness (CRF) is one of the strongest predictors of mortality, studies examining the relationship between well-being and survival seldom account for the possible effects of CRF. PURPOSE: This study examined the independent associations of psychological well-being components (low level of negative emotion and high level of positive emotion) and CRF, as well as their combined effects, with survival. METHODS: Participants (N=4888) were examined in 1988-1997 and followed up for a median period of ∼15 years (212 deaths, 4.3%). CRF was assessed by a maximal exercise test on a treadmill. Low-level negative emotion was defined as the minimum score of the negative emotion subscale of the CES-D scale and high-level positive emotion as the maximum score of the positive emotion subscale. Results are presented as hazard ratios (95% CIs). Data were analyzed in 2009. RESULTS: After adjustment for a set of established risk factors, men and women with low levels of negative emotion had lower risk of death than those with higher levels of negative emotion, 0.66 (95% CI=0.50, 0.87). The association persisted after additional adjustment for CRF and positive emotion. High level of positive emotion was not associated with survival. A high level of CRF independently predicted lower risk of death, 0.54 (95% CI=0.37, 0.79), compared to a low level of CRF. The risk of death in participants with both a low level of negative emotion and a high level of CRF was 0.37 (95% CI=0.22, 0.63), compared to their peers with higher levels of negative emotion/low levels of CRF. CONCLUSIONS: Low levels of negative emotion and high levels of CRF are independent predictors of long-term survival in men and women. A strong combined effect was observed, as individuals with both a low level of negative emotion and a high level of CRF had a 63% lower risk of premature death than those with higher levels of negative emotion and a low level of CRF.This study was supported by NIH grants AG06945 and HL62508, and in part by an unrestricted research grant from The Coca-Cola Company. The study also was supported in part by Robert Wood Johnson Foundation's Pioneer Portfolio (grant number 63597); the Spanish Ministry of Education (EX-2008-0641, EX-2007-1124); the Swedish Council for Working Life and Social Research; and the Swedish Heart-Lung Foundation (20090635)

Role of Sleep Disturbance in Chronic Hepatitis C Infection

Chronic infection with the hepatitis C virus (CHC) is associated with physical and mental symptoms including fatigue and depression that adversely affect quality of life. A related complaint, sleep disturbance, has received little attention in the literature, with the exception of sleep changes noted in cirrhosis and end-stage liver disease. We present an overview of studies indicating sleep problems in patients with CHC, with about 60% to 65% of individuals reporting such complaints. Evidence suggests that impairments in sleep quality exist independent of antiviral therapy with interferon-α and prior to advanced stages of liver disease. Further investigation of sleep disturbance in CHC patients with a mild stage of liver disease may provide important information on disease course as well as allow additional opportunities for patient support

Autonomous Seawater \u3ci\u3ep\u3c/i\u3eCO\u3csub\u3e2\u3c/sub\u3e and pH Time Series From 40 Surface Buoys and the Emergence of Anthropogenic Trends

Ship-based time series, some now approaching over 3 decades long, are critical climate records that have dramatically improved our ability to characterize natural and anthropogenic drivers of ocean carbon dioxide (CO2) uptake and biogeochemical processes. Advancements in autonomous marine carbon sensors and technologies over the last 2 decades have led to the expansion of observations at fixed time series sites, thereby improving the capability of characterizing sub-seasonal variability in the ocean. Here , we present a data product of 40 individual autonomous moored surface ocean pCO2 (partial pressure of CO2) time series established between 2004 and 2013, 17 also include autonomous pH measurements. These time series characterie a wide range of surface ocean carbonate conditions in diffferent oceanic (17 sites), coastal (13 sites), and coral reef (10 sites) regimes. A time of trend emergence (ToE) methodology applied ot the time series that exhibit well-constrained daily to interannual variability and an estimate of decadal variability indicates that the length of sustained observations necessary to detect statistically significant anthropogenic trends varies by marine environment. The ToE estisites, and 9 to 22 years at the coral reef sites. Only two open ocean pCO2 and pH range from 8 to 15 years at the open ocean sites, 16 to 41 years at the coastal sites, and 9 to 22 years at the coral reef sites. Only two open ocean pCO2 time series, Woods Hole Oceanographic Institution Hawaii Ocean Time-series Station (WHOTS) in the subtropical North Pacific and Stratus n the South Pacific gyre, have been deployed longer than the estimated trend detection time and, for these, deseasoned monthly means show estimated anthropogenic trends of 1.9 ± 0.3 and 1.6 ± 0.3 μatm yr-1, respectively. In the future, it is possible that updates to this product will allow for the estimation of anthropogenic trends at more sites; however, the product currently provides a valuable tool in an accessible format for evaluating climatology and natural variability of surface ocean carbonate chemistry in a variety of regions. Data are available at https://doi.org/10.7289/V5DB8043 and https://www.nodc.noaa.gov/ocads/oceans/Moorings/ndp097.html (Sutton et al., 2018)

Acute kidney injury in patients treated with immune checkpoint inhibitors

Background: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. Methods: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. Results: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. Conclusions: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery