Crossed Cerebellar Diaschisis Has an Adverse Effect on Functional Outcome in the Subacute Rehabilitation Phase of Stroke: A Case-Control Study

ObjectiveTo investigate whether crossed cerebellar diaschisis (CCD) is associated with functional outcome in the subacute rehabilitation phase of stroke.DesignRetrospective case-control study.SettingHospital-based cohort.ParticipantsThe study enrolled participants who underwent brain single-photon emission computed tomography (N=48). Patients with CCD were identified (n=24). Twenty-four controls were selected for each case-patient by matching age, stroke type (ischemic or hemorrhagic), lesion laterality, and lesion location.InterventionNot applicable.Main Outcome MeasuresThe functional ambulation category (FAC), modified Barthel Index (MBI), and Mini-Mental State Examination (MMSE) were administered at the initial (initiation of rehabilitation therapy) and the follow-up (4wk after rehabilitation therapy) assessments.ResultsThe CCD group had lower MMSE, FAC, MBI, and MMSE scores at the initial assessment (P=.032, .016, and .001, respectively) and lower FAC and MBI scores at the follow-up assessment, than the non-CCD group (P=.001 and .036, respectively). Although CCD was not associated with cognitive impairment, nonambulatory status, and dependent activities of daily living (ADL) at the initial assessment (P=.538, .083, and >.99, respectively), the CCD group had a higher risk of cognitive impairment (adjusted odds ratio [aOR]=4.044; 95% confidence interval [CI], 1.071-15.270; P=.039), nonambulatory status (aOR=7.000; 95% CI, 1.641-29.854; P=.009) and dependent ADL (aOR=13.500; 95% CI, 1.535-118.692; P=.019) at the follow-up assessment.ConclusionsCCD is associated with severe functional impairment and may have an adverse effect on functional outcomes related to cognition, ambulatory function, and ADL during the subacute rehabilitation phase of stroke. This suggests that CCD may be a valuable predictor of functional outcome in the subacute rehabilitation phase of stroke.     

Unilateral Strength Training of the Less Affected Hand Improves Cortical Excitability and Clinical Outcomes in Patients With Subacute Stroke: A Randomized Controlled Trial

ObjectivesTo investigate whether unilateral strength training helps improve cortical excitability and clinical outcomes after stroke.DesignRandomized controlled trial.SettingRehabilitation sciences research center.ParticipantsPatients with subacute stroke (N=26) were randomly assigned to a control group (n=13) or the experimental group (n=13).InterventionsParticipants in both groups received conventional physiotherapy. The experimental group also received unilateral strength training of the less affected wrist extensors. Interventions were applied for 4 weeks (12 sessions, 3 d/wk).Main Outcome MeasuresCortical excitability in both the ipsilesional hemisphere (ipsiH) and contralesional hemisphere (contraH) was assessed by measuring resting motor threshold (RMT), active motor threshold (AMT), motor evoked potential (MEP), and cortical silent period (CSP) at baseline and after the 4-week intervention period. Clinical outcomes were obtained by evaluating wrist extension strength in both the more affected and less affected hands, upper extremity motor function, activities of daily living (ADL), and spasticity.ResultsThe experimental group showed greater MEP amplitude (P=.001) in the ipsiH and shorter CSP duration in both the ipsiH (P=.042) and contraH (P=.038) compared with the control group. However, the reductions in RMT and AMT in both hemispheres were not significantly different between groups. Improvements in wrist extension strength in the more affected (P=.029) and less affected (P=.001) hand, upper extremity motor function (P=.04), and spasticity (P=.014) were greater in the experimental group. No significant difference in ADLs was detected between groups.ConclusionsA combination of unilateral strength training and conventional physiotherapy appears to be a beneficial therapeutic modality for improving cortical excitability and some clinical outcomes in patients with stroke.     

Control of Linear Head and Trunk Acceleration During Gait After Unilateral Vestibular Deficits

ObjectiveTo use clinically available inertial measurement units to quantify the control of linear accelerations at the head and trunk during gait in different sensory conditions in individuals with unilateral vestibular loss.DesignObservational study.SettingOutpatient research laboratory.ParticipantsIndividuals (n=13; mean age, 47.6±13.7y; 69% women) 6 weeks after vestibular schwannoma resection surgery and vestibular healthy participants (n=16; mean age, 29.7±5.9y; 56% women).InterventionNot applicable.Main Outcome MeasuresWalking speed normalized, root mean square values of cranial-caudal, medial-lateral, and anterior-posterior directed linear accelerations at the head and the trunk while walking in 2 visual sensory conditions (eyes open and eyes closed).ResultsLinear mixed models for each root mean square value were fit on the effects of group, condition, and group by condition. The group by condition effect was used to examine the primary hypothesis that individuals with vestibular loss would experience greater change in triplanar root mean square values at the head and trunk from the eyes open to eyes closed condition compared with the vestibular healthy group. The group by condition effect was found to be significant at the head in the cranial-caudal (β=0.39; P=.002), medial-lateral (β=0.41; P<.001), and anterior-posterior (β=0.43; P<.001) directions. The group by condition effect was also significant in the cranial-caudal (β=0.39; P=.002), medial-lateral (β=0.39; P<.001), and anterior-posterior (β=0.23; P=.002) directions at the trunk.ConclusionsParticipants who underwent vestibular schwannoma resection were more impaired in their ability to control accelerations at the head and trunk without visual sensory information than vestibular healthy participants. These impairments were detectable using clinically available inertial measurement units.     

Age-Related 2-Year Mortality After Transcatheter Aortic Valve Replacement: the YOUNG TAVR Registry

ObjectiveTo comparatively assess the natural history of patients of different ages undergoing transcatheter aortic valve replacement (TAVR).Patients and MethodsFor this study, we used the YOUNG TAVR, an international, multicenter registry investigating mortality trends up to 2 years in patients with aortic valve stenosis treated by TAVR, classified according to 3 prespecified age groups: 75 years or younger (n=179), 76 to 86 years (n=602), and older than 86 years (n=221). A total of 1002 patients undergoing TAVR were included. Demographic, clinical, and outcome data in the youngest group were compared with those of patients 76 to 86 years and older than 86 years. Patients were followed up for up to 2 years.ResultsCompared with patients 75 years or younger (reference group), patients aged 76 to 86 years and older than 86 years had nonsignificantly different 30-day mortality (odds ratio, 0.76; 95% CI, 0.41-1.38; P=.37 and odds ratio, 1.27; 95% CI, 0.62-2.60; P=.51, respectively) and 1-year mortality (hazard ratio (HR), 0.72; 95% CI, 0.48-1.09; P=.12 and HR, 1.11; 95% CI, 0.88-1.40; P=.34, respectively). Mortality at 2 years was significantly lower among patients aged 76 to 86 years (HR, 0.62; 95% CI, 0.42-0.90; P=.01) but not among the older group (HR, 1.06; 95% CI, 0.68-1.67; P=.79). The Society of Thoracic Surgeons 30-day mortality score was lower in younger patients who, however, had a significantly higher prevalence of chronic obstructive pulmonary disease (P=.005 vs the intermediate group and P=.02 vs the older group) and bicuspid aortic valves (P=.02 vs both older groups), larger left ventricles, and lower ejection fractions.ConclusionIn the present registry, mortality at 2 years after TAVR among patients 75 years or younger was higher compared with that of patients aged 75 to 86 years and was not markedly different from that of patients older than 86 years. The findings are attributable at least in part to a greater burden of comorbidities in the younger age group that are not entirely captured by current risk assessment tools.     

Early Detection of Pancreatic Cancer in Patients With Chronic Liver Disease Under Hepatocellular Carcinoma Surveillance

ObjectiveTo evaluate whether patients with hepatitis B virus (HBV)– and hepatitis C virus (HCV)–related chronic liver disease were diagnosed as having pancreatic cancer (PC) at an early stage during abdominal imaging surveillance for hepatocellular carcinoma (HCC).Patients and MethodsWe retrospectively examined 447 patients with PC diagnosed at Ehime University Hospital and affiliated centers (2011-2013). Data were collected regarding HBV and HCV status, likelihood of PC diagnosis, and Union for International Cancer Control (UICC) stage. Intergroup comparisons were performed using the χ² test.ResultsThe UICC stage distribution in the HCC surveillance group (n=16) was stage 0 (n=2, 12.5%), stage IA (n=3, 18.8%), stage IB (n=2, 12.5%), stage IIA (n=2, 12.5%), stage IIB (n=2, 12.5%), stage III (n=1, 6.3%), and stage IV (n=4, 25%). The UICC stage distribution in the nonsurveillance group (n=431) was stage 0 (n=4, 0.9%), stage IA (n=28, 6.5%), stage IB (n=27, 6.3%), stage IIA (n=86, 20.0%), stage IIB (n=48, 11.1%), stage III (n=56, 13.0%), and stage IV (n=182, 42.2%). The HCC surveillance group had significantly more patients with stage 0 disease than with stages IA through IV (P=.02). Similar results were observed when including stages IA (P=.007) and IB (P=.004) as early stages but not stage IIA (P=.10). A dilated pancreatic duct led to a PC diagnosis in all 6 patients with stage 0 disease.ConclusionPatients with HBV- and HCV-related chronic liver disease had an early PC diagnosis during HCC surveillance. Careful evaluation of the pancreas is warranted during HCC surveillance.     

Dosage and Effectiveness of Aerobic Training on Cardiorespiratory Fitness,Functional Capacity,Balance, and Fatigue in People With Multiple Sclerosis: A Systematic Review and Meta-Analysis

ObjectivesTo evaluate the benefits of aerobic training (AT) programs on cardiorespiratory fitness, functional capacity, balance, and fatigue in individuals with multiple sclerosis (MS) and to identify the optimal dosage of AT programs for individuals with MS via a systematic review with meta-analysis.Data sourcesTwo electronic databases were searched until March 2020 (PubMed-Medline and Web of Science).Study SelectionStudies examining the effect of AT program on cardiorespiratory fitness, functional capacity, balance, and fatigue were included.Data ExtractionAfter applying the inclusion and exclusion criteria, we included 43 studies. A total sample of 1070 individuals with MS (AT group, n=680; control group, n=390) were analyzed.Data SynthesisThe AT group demonstrated a significant increase in cardiorespiratory fitness (standardized mean difference [SMD], 0.29; P=.002), functional capacity (timed Up and Go Test: SMD, –1.14; P<.001; gait speed: SMD, –1.19; P<.001; walking endurance: SMD, 0.46; P<.001), and balance (SMD, 3.49; P<.001) after training. Fatigue perception also decreased (SMD, –0.45; P<.001). However, no significant differences were observed when compared with the control group in either cardiorespiratory fitness (SMD, 0.14; P=.19) or fatigue perception. Nevertheless, we observed significant differences between the AT and control groups in balance (P=.02), gait speed (P=.02), and walking endurance (P=.03), favoring the participants who performed AT. Regarding the subgroup analysis, no significant differences were observed between subgroups in any of the variables studied except for gait speed, for which a greater increase in posttraining was observed when the AT program applied the continuous method (χ²=7.75; P=.005) and the exercises were performed by walking (χ²=9.36; P=.002).ConclusionsAerobic training improves gait speed, walking endurance, and balance. Cardiorespiratory fitness and fatigue perception also improved after AT, but we found no differences with the control group. In addition, subgroup analysis suggested that training using continuous and walking methods could optimize gait speed.     

Repeat Coronary Bypass Surgery or Percutaneous Coronary Intervention After Previous Surgical Revascularization

ObjectiveTo assess long-term survival with repeat coronary artery bypass grafting (RCABG) or percutaneous coronary intervention (PCI) in patients with previous CABG.MethodsFrom January 1, 2000, through December 31, 2013, 1612 Mayo Clinic patients underwent RCABG (n=215) or PCI (n=1397) after previous CABG. The RCABG cohort was grouped by use of saphenous vein grafts only (n=75), or with additional arterial grafts (n=140); the PCI cohort by, bare metal stents (BMS; n=628), or drug-eluting stents (DES; n=769), and by the treated target into native coronary artery (n=943), bypass grafts only (n=338), or both (n=116). Multivariable regression and propensity score analysis (n=280 matched patients) were used.ResultsIn multivariable analysis, the 30-day mortality was increased in RCABG versus PCI patients (hazard ratio [HR], 5.32; 95%CI, 2.34-12.08; P<.001), but overall survival after 30 days improved with RCABG (HR, 0.72; 95% CI, 0.55-0.94; P=.01). Internal mammary arteries were used in 61% (129 of 215) of previous CABG patients and improved survival (HR, 0.82; 95% CI, 0.69-0.98; P=.03). Patients treated with drug-eluting stent had better 10-year survival (HR, 0.74; 95% CI, 0.59-0.91; P=.001) than those with bare metal stent alone. In matched patients, RCABG had improved late survival over PCI: 48% vs 33% (HR, 0.57; 95% CI, 0.35-0.91; P=.02). Compared with RCABG, patients with PCI involving bypass grafts (n=60) had increased late mortality (HR, 1.62; 95% CI, 1.10-2.37; P=.01), whereas those having PCI of native coronary arteries (n=80) did not (HR, 1.09; 95% CI, 0.75-1.59; P=.65).ConclusionRCABG is associated with improved long-term survival after previous CABG, especially compared with PCI involving bypass grafts.     

Comparison of Rest to Aerobic Exercise and Placebo-like Treatment of Acute Sport-Related Concussion in Male and Female Adolescents

ObjectiveTo compare a sample of adolescents with sport-related concussion (SRC) who were prescribed rest with 2 arms of a randomized controlled trial comparing aerobic exercise with placebo-like stretching. We also compared sex differences across the 3 approaches to treatment.DesignQuasi-experimental trial.SettingUniversity concussion management clinics.ParticipantsAdolescent athletes (aged 13-18 years) presenting within 10 days of SRC (mean, 5 days after injury) received a recommendation for rest (rest group [RG], n=48, 15.4±1y, 25% female). Their outcomes were compared with matched samples of adolescents assigned to aerobic exercise (exercise group [EG], n=52, 15.3±2y, 46% female) or placebo-like stretching (placebo group [PG], n=51, 15.4±2y, 47% female) (N=151).Main Outcome MeasuresThe primary outcome was median days from injury to recovery. The secondary outcome was proportion classified as normal recovery (<30d) or delayed recovery (≥30d).ResultsThe RG recovered in 16 days (interquartile range, 9.25-23.25d), which was significantly delayed (P=.020) compared with EG (13d; interquartile range, 10-18.5d). The PG recovered in 17 days (interquartile range, 13-23d). Four percent of the EG, 14% of the PG, and 13% of the RG had delayed recovery (P=.190). There was no difference in recovery time or delayed recovery between male participants and female participants across groups. Female participants prescribed rest experienced an increase in symptoms vs the other groups (P=.013).ConclusionRelative rest and a placebo-like stretching program were very similar in days to recovery and symptom improvement pattern after SRC. Both conditions were less effective than subsymptom threshold aerobic exercise. Female adolescents appear to be susceptible to symptom increase when prescribed rest.     

Association Between Public Trust and Provider Specialty Among Physicians With Financial Conflicts of Interest

ObjectivesTo characterize public perception of physicians’ conflicts of interest (COIs) across medical and surgical specialties.Patients and MethodsA cross-sectional 6-arm randomized survey of a nonprobability sample from Amazon’s Mechanical Turk occurred on December 11 to 16, 2018. Survey respondents were randomly assigned to vignettes that varied the physician specialty with COI. The primary outcome was mean difference in Mayer Trust, and the secondary outcome included the proportion who desire to discontinue care.ResultsThere were 1729 of 1920 respondents who completed the experiment (90.1% completion rate). Respondents were male (52.5%; n=907), white (71.4%; n=1234), and between the ages of 25 and 44 years (70.9%; n=1227). Mean ± SD Mayer Trust across the 6 specialties was 3.7±.60, with the only between-specialty differences observed for psychiatry compared with the other specialties (F=5.4; P<.001). The median dollar amount that would affect respondents’ trust in a physician was $5000 (interquartile range, $100-$100,000). A total of 75.1% (n=1298) of respondents desired COI information, with 41.6% (n=720) discontinuing care. Age older than 34 years (adjusted odds ratio [aOR], 0.7; 95%, CI, 0.49-0.99; P=.047), nonwhite race (aOR, 1.3; 95% CI, 1.02-1.6; P=.03), educational attainment of 4 or more years of college (aOR, 1.31; 95% CI, 1.05-1.6; P=.016), and physician specialty as a psychiatrist (aOR, 1.5; 95% CI, 1.03-2.2; P=.034) were predictors for discontinuing care.ConclusionPublic COI disclosure is a common method for managing financial conflicts. Although survey respondents were more likely to discontinue care with a physician with COI, they will act on this knowledge of COI differently depending on the specialty of the physician. The finding that psychiatry is an outlier may be a chance finding that warrants further confirmation. Continued efforts to ensure best practices for disclosure are required.     

Does Unilateral Lower Limb Amputation Influence Ankle Joint Torque in the Intact Leg?

ObjectiveTo investigate ankle torque and steadiness in the intact leg of transtibial and transfemoral unilateral amputees.DesignComparative study.SettingMedical rehabilitation centers.ParticipantsFifteen persons with a unilateral transfemoral amputation, 8 persons with a transtibial amputation, and 14 able-bodied male participants volunteered to participate in this study (N=37).InterventionsNot applicable.Main Outcomes MeasuresMaximal isometric torque performed during ankle plantarflexion and dorsiflexion in the intact limb of amputees and in the dominant limb of able-bodied persons. The coefficient of variation (CV) of the plantarflexion torque was calculated over 5 seconds during a submaximal isometric contraction (15%) in order to assess torque steadiness. Furthermore, electromyographic activity (the root mean square amplitude) of the gastrocnemius medialis and tibialis anterior muscles was analyzed.ResultsPlantarflexion maximal torque was significantly higher for the able-bodied group (115±39 Nm) than for the group with a transfemoral amputation (77±34 Nm) (P<.01), and did not differ between able-bodied group and the group with a transtibial amputation (97±26 Nm) (P=.25). Furthermore, the transfemoral amputee group was 29% less steady than the able-bodied group (P=.01). However, there were no significant differences in torque steadiness between the able-bodied group and transtibial amputee group (P=.26) or between transtibial and transfemoral amputee groups (P=.27). The amputation had no significant effect between groups on dorsiflexion maximal torque (P=.10), gastrocnemius medialis electromyography (EMG) (P=.85), tibialis anterior coactivation (P=.95), and coactivation ratio (P=.75).ConclusionThe present study suggests that as the level of amputation progresses from below the knee to above the knee, the effect on the intact ankle is progressively more negative.     

Effect of an mHealth Wheelchair Skills Training Program for Older Adults: A Feasibility Randomized Controlled Trial

ObjectiveTo evaluate the effect of an mHealth wheelchair skills training program on clinical outcomes among older adult manual wheelchair users.Design2×2 factorial randomized controlled trial.SettingCommunity setting in 2 Canadian cities.ParticipantsConvenience sample of manual wheelchair users 50 years and older living in the community who were able to self-propel with both hands and communicate in English. Participants (N=18) were randomized into either a mHealth treatment (n=10) or tablet gaming control (n=8) group.InterventionsAll participants received 2 in-person sessions with their trainer and engaged in a 4-week monitored home training program with a computer tablet. The Enhancing Participation In the Community by improving Wheelchair Skills program provided wheelchair skills training; the control program included 9 dexterity and cognitive training games.Main Outcome MeasuresThe primary outcome was wheelchair skill capacity. Secondary outcomes included safety, self-efficacy, activity participation, mobility, divided-attention, and health-related quality of life.ResultsData collection was blinded to group allocation. Capacity improved by 2 skills but with no statistically significant between-group difference. The mHealth training program had a significant effect on participation (P=.03) and self-efficacy (P=.06) with large effect sizes (η_p²=0.22-0.29). Mobility, safety with skill performance, and divided attention measures demonstrated medium effect size changes, but only safety with skill performance was statistically significant. The program was more beneficial for participants with <1 year of wheelchair experience.ConclusionEnhancing Participation In the Community by improving Wheelchair Skills participants demonstrated good program adherence and clinical benefits were evident in community participation and wheelchair self-efficacy. Wheelchair safety and mobility were positively affected, while skill capacity showed a small, nonsignificant improvement. Future study should investigate benefit retention over time.     

Long-Term Specialized Physical Therapy in Cervical Dystonia: Outcomes of a Randomized Controlled Trial

ObjectiveTo evaluate the effectiveness of a specialized physical therapy (SPT) program on disability in cervical dystonia (CD) compared to regular physical therapy (RPT).DesignA single-blinded randomized controlled trial.SettingThis study was performed by a physical therapist in a primary health care setting. Measurements were performed at baseline, 6 and 12 months in the botulinum toxin (BoNT) outpatient clinic of the neurology department.ParticipantsPatients with primary CD and stable on BoNT treatment for 1 year (N=96).Main Outcome MeasuresThe primary outcome was disability assessed with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Secondary outcomes were pain, anxiety, depression, quality of life (QOL), and health related costs over 12 months.ResultsA total of 72 participants (30 men, 42 women) finished the study: 40 received SPT, 32 RPT. No significant between group differences were found after 12 months of treatment (P=.326). Over these 12 months both groups improved significantly (P<.001) on the TWSTRS disability scale compared to baseline (SPT 1.7 points, RPT 1.0 points). Short Form 36 (SF-36) General Health Perceptions (P=.046) and self-perceived improvement (P=.007) showed significantly larger improvements after 12 months in favor of SPT. Total health related costs after 12 months were $1373±556 for SPT compared to $1614±917 for RPT.ConclusionSPT revealed no significant differences compared to RPT after 12 months of treatment on the TWSTRS disability scale. Both groups showed similar improvements compared to baseline. Positive results in the SPT group were higher patient perceived effects and general health perception. Treatment costs were lower in the SPT group. With lower costs and similar effects, the SPT program seems to be the preferred program to treat CD.     

Gait Function in Adults Aged 50 Years and Older With Spina Bifida

ObjectiveTo study gait function among individuals with spina bifida (SB) aged 50 years or older.DesignA cross-sectional study conducted in 2017.SettingHome-dwelling participants from all regions in Norway.ParticipantsIndividuals between the ages of 51 and 76 years (N=26; 16 women) categorized as independent walkers (n=9), walkers with aids (n=10) and nonwalkers (n=7).InterventionsNot applicable.Main Outcome MeasuresQuestionnaire, pain assessment, anthropometry, Falls Efficacy Scale International (FES-I), objective gait analysis, 6-minute walk test (6MWT), and timed Up and Go (TUG).ResultsWalking speed correlated with SB severity (ρ=–.59; P=.008). Individuals who walked slower than 0.81 m/s had a higher body mass index (BMI) than those who walked faster (P=.008). Independent walkers walked slower than healthy age-matched walkers (P=.046); spatiotemporal variables showed that this was owing to shorter steps rather than cadence. The mean TUG was 10.6±2.6 seconds in independent walkers and 20.2±6.5 in walkers with aids (P<.01). The mean 6MWT was 504±126 meters in independent walkers and 316±88 in walkers with aids (P<.01). The mean pain intensity (numeric rating scale) was 4.9±2.2 in independent walkers and 4.2±1.6 in walkers with aids, but the difference was not statistically significant. FES-I was significantly lower among independent walkers (mean, 23.6±3.9) than walkers with aids (mean, 31.4±10.0) (P=.042).ConclusionsParticipants commonly experienced an early onset deterioration in gait function, and walking speed was influenced by SB severity and BMI. This highlights the importance of early monitoring and weight management during follow-up for SB.     

Artificial Intelligence–Enabled Electrocardiogram for Atrial Fibrillation Identifies Cognitive Decline Risk and Cerebral Infarcts

ObjectiveTo investigate whether artificial intelligence–enabled electrocardiogram (AI-ECG) assessment of atrial fibrillation (AF) risk predicts cognitive decline and cerebral infarcts.Patients and MethodsThis population-based study included sinus-rhythm ECG participants seen from November 29, 2004 through July 13, 2020, and a subset with brain magnetic resonance imaging (MRI) (October 10, 2011, through November 2, 2017). The AI-ECG score of AF risk calculated for participants was 0-1. To determine the AI-ECG-AF relationship with baseline cognitive dysfunction, we compared linear mixed-effects models with global and domain-specific cognitive z-scores from longitudinal neuropsychological assessments. The AI-ECG-AF score was logit transformed and modeled with cubic splines. For the brain-MRI subset, logistic regression evaluated correlation of the AI-ECG-AF score and the high-threshold, dichotomized AI-ECG-AF score with infarcts.ResultsParticipants (N=3729; median age, 74.1 years) underwent cognitive analysis. Adjusting for age, sex, education, and APOE ?4-carrier status, the AI-ECG-AF score correlated with lower baseline and faster decline in global-cognitive z-scores (P=.009 and P=.01, respectively, non–linear-based spline-models tests) and attention z-scores (P<.001 and P=.01, respectively). Sinus-rhythm-ECG participants (n=1373) underwent MRI. As a continuous measure, the AI-ECG-AF score correlated with infarcts but not after age and sex adjustment (P=.52). For dichotomized analysis, an AI-ECG-AF score greater than 0.5 correlated with infarcts (OR, 4.61; 95% CI, 2.45-8.55; P<.001); even after age and sex adjustment (OR, 2.09; 95% CI, 1.06-4.07; P=.03).ConclusionThe AI-ECG-AF score correlated with worse baseline cognition and gradual global cognition and attention decline. High AF probability by AI-ECG-AF score correlated with MRI cerebral infarcts. However, most infarcts observed in our cohort were subcortical, suggesting that AI-ECG not only predicts AF but also detects other non-AF cardiac disease markers and correlates with small vessel cerebrovascular disease and cognitive decline.     

Host Factors and Outcomes in Hospitalizations for Pneumocystis Jirovecii Pneumonia in the United States

ObjectiveTo assess host factors in pneumocystis jirovecii pneumonia (PCP)–related hospitalizations and compare outcomes between HIV and non-HIV patients.MethodsUsing the National Inpatient Sample database, we identified 3384 hospitalizations with PCP (International Classification of Diseases, Ninth Revision, Clinical Modification code: 136.3) as the primary discharge diagnosis from 2005 to 2014. We evaluated hospitalizations for the following host factors: HIV, malignancies, organ transplantation, rheumatologic diseases, and vasculitides. We compared the prevalence of individual host factors among PCP hospitalizations over time, and compared intervention rates and outcomes between HIV and non-HIV patients with PCP.ResultsAmong all hospitalizations for PCP, malignancy was the most prevalent host factor (46.0%, n=1559), followed by HIV (17.8%, n=604); 60.7% (n=946) of malignancies were hematologic. The prevalence of HIV among hospitalizations for PCP decreased from 25.1% in 2005 to 9.2% in 2014 (P<.001), whereas the prevalence of non-HIV immunocompromising conditions increased. Compared with HIV patients, PCP patients without HIV had higher rates of bronchoscopy (52.3% vs 26.7%, P<.001) and endotracheal intubation (17.0% vs 7.9%, P<.001), prolonged hospitalizations (11.5 vs 8.7 days, P<.001), higher hospitalization costs (86.8 vs 48.2×10³ USD, P<.001) and increased in-hospital mortality (16.0% vs 5.0%, P<.001). After adjusting for age, sex, and smoking status, there was no difference in mortality between non-HIV and HIV patients with PCP (adjusted odds ratio, 1.4; 95% CI, 0.9 to 2.3).ConclusionThe epidemiology of PCP has shifted with an increase in the prevalence of non-HIV patients who have higher intubation rates and prolonged hospitalizations compared with matched HIV patients.     

Energy Expenditure and Oxygen Consumption During Activities of Daily Living in People With Multiple Sclerosis and Healthy Subjects: An Ecological Approach to Estimate Real-Life Fatigue and Fatigability

ObjectiveTo compare oxygen consumption and energy expenditure (EE) of the activities of daily living (ADL) in people with multiple sclerosis (PwMS) and healthy subjects.DesignCross-sectional observational study.SettingOutpatient care facilities.ParticipantsTwenty-four moderately impaired PwMS and 21 healthy controls (N=45).InterventionNot applicable.Main Outcome MeasuresOxygen consumption, EE rate, and total EE assessed by portable open-circuit spirometry during the accomplishment of a comprehensive set of 14 ADL. Body composition was also assessed with bioelectrical impedance analysis. Body cell mass was used to normalize metabolic rates between groups.ResultsPwMS exhibited significantly higher oxygen consumption than controls in transfer and mobility tasks (walking with stairs: +10.4%, P=.04; without stairs: +15.2%, P=.002; driving: +10.4%, P=.04) and higher EE rates for walking (+13.6%, P=.01). ADL completion took significantly longer in PwMS. Consequently, when total EE to complete each ADL was considered, PwMS used significantly more energy in 10 of the 14 ADL. Of these, “climb stairs” and walking with or without stairs showed the largest differences (+100%, +99.5%, +79.3%, respectively; all P values<.0005), followed by “dressing” (+48.8%; P=.002), “laundry” (+41.7%; P=.007), and “shopping” (+40.1%; P=.003).ConclusionsModerately disabled PwMS display oxygen consumption and EE rates during ADL that are comparable to those of matched healthy subjects, except for the activities that involve walking. Although metabolic rates were not different for the majority of ADL, PwMS showed higher total EE to complete the same activities at a comparable work intensity, which may contribute to the burden of “real-life” tiredness and fatigue typically described in this population. Importantly, the subjective Modified Fatigue Impact Scale score significantly correlated to EE and oxygen consumption of selected ADL, such as “make a bed,” “driving,” “clean surfaces,” and “climb stairs.” The joint employment of open-circuit spirometry during ADL and body composition analysis allows an accurate metabolic characterization of PwMS, who frequently complain of fatigue.     

Pain Manifestations of COVID-19 and Their Association With Mortality: A Multicenter Prospective Observational Study

ObjectivesTo determine the prevalence and breakdown of pain symptoms among patients with coronavirus disease 2019 (COVID-19) infection admitted for nonpain symptoms and the association between the presence of pain and intensive care unit (ICU) admission and death.Patients and MethodsIn this multicenter prospective study, data on the intensity and type of pain were collected on 169 patients with active severe acute respiratory syndrome coronavirus 2 infection at 2 teaching hospitals in the United States and Korea and on 8 patients with acute pain at another large teaching hospital between February 1, 2020, and June 15, 2020.ResultsSixty-five of 169 patients (38.5%) reported an active pain condition. Among the 73 patients with pain, the most common pain symptoms were headache (n=22; 30.1%), chest pain (n=17; 23.3%), spinal pain (n=18; 24.7%), myalgia (n=13; 17.8%), abdominal or pelvic pain (n=13; 17.8%), arthralgia (n=11; 15.1%), and generalized pain (n=9; 12.3%). Those reporting headache as their main symptom were less likely to require ICU admission (P=.003). Acetaminophen or nonsteroidal anti-inflammatory drugs were prescribed to 80.8% (n=59), opioids to 17.8% (n=13), adjuvants to 8.2% (n=6), and ketamine to 5.5% (n=4) of patients with pain. When age 65 years and older and sex were controlled for in multivariable analysis, the absence of pain was associated with ICU admission (odds ratio, 2.92; 95% CI, 1.42 to 6.28; P=.004) and death (odds ratio, 3.49; 95% CI, 1.40 to 9.76; P=.01).ConclusionAcute pain is common during active COVID-19 infection with the most common manifestations being headache, chest pain and spine pain. Individuals without pain were more likely to require intensive care and expire than those with pain. Reasons why pain may be associated with reduced mortality include that an intense systemic stimulus (eg, respiratory distress) might distract pain perception or that the catecholamine surge associated with severe respiratory distress might attenuate nociceptive signaling.     

Effect of the Renin-Angiotensin System Inhibitors on Inflammatory Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials

ObjectiveTo synthesize more conclusive evidence on the anti-inflammatory effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs).MethodsPubMed, Scopus, and Embase were searched from inception until March 1, 2021. We included randomized controlled trials (RCTs) that assessed the effect of ACEIs or ARBs, compared with placebo, on any of the following markers: C-reactive protein (CRP), interleukin 6 (IL-6), or tumor necrosis factor α (TNF-α). Mean changes in the levels of these markers were pooled as a weighted mean difference (WMD) with a 95% CI.ResultsThirty-two RCTs (n=3489 patients) were included in the final analysis. Overall pooled analysis suggested that ACEIs significantly reduced plasma levels of CRP (WMD, ?0.54 [95% CI, ?0.88 to ?0.21]; P=.002; I²=96%), IL-6 (WMD, ?0.84 [95% CI, ?1.03 to ?0.64]; P<.001; I²=0%), and TNF-α (WMD, ?12.75 [95% CI, ?17.20 to ?8.29]; P<.001; I²=99%). Moreover, ARBs showed a significant reduction only in IL-6 (WMD, ?1.34 [95% CI, ?2.65 to ?0.04]; P=.04; I²=85%) and did not significantly affect CRP (P=.15) or TNF-α (P=.97) levels. The lowering effect of ACEIs on CRP levels remained significant with enalapril (P=.006) and perindopril (P=.01) as well as with a treatment duration of less than 24 weeks (WMD, -0.67 [95% CI, ?1.07 to -0.27]; P=.001; I²=94%) and in patients with coronary artery disease (WMD, ?0.75 [95% CI, ?1.17 to ?0.33]; P<.001; I²=96%).ConclusionBased on this meta-analysis, ACEIs showed a beneficial lowering effect on CRP, IL-6, and TNF-α, whereas ARBs were effective as a class in reduction of IL-6 only.     

Continuous Renal Replacement Therapy Liberation and Outcomes of Critically Ill Patients With Acute Kidney Injury

ObjectiveTo examine the association between continuous renal replacement therapy (CRRT) liberation and clinical outcomes among patients with acute kidney injury (AKI) requiring CRRT.MethodsThis single-center, retrospective cohort study included adult patients admitted to intensive care units with AKI and treated with CRRT from January 1, 2007, to May 4, 2018. Based on the survival and renal replacement therapy (RRT) status at 72 hours after the first CRRT liberation, we classified patients into liberated, reinstituted, and those who died. We observed patients for 90 days after CRRT initiation to compare the major adverse kidney events (MAKE₉₀).ResultsOf 1135 patients with AKI, 228 (20%), 437 (39%), and 470 (41%) were assigned to liberated, reinstituted, and nonsurvival groups, respectively. The MAKE₉₀, mortality, and RRT independence rates of the cohort were 62% (707 cases), 59% (674 cases), and 40% (453 cases), respectively. Compared with reinstituted patients, the liberated group had a lower MAKE₉₀ (29% vs 39%; P=.009) and higher RRT independence rate (73% vs 65%; P=.04) on day 90, but without significant difference in 90-day mortality (26% vs 33%; P=.05). After adjustments for confounders, successful CRRT liberation was not associated with lower MAKE₉₀ (odds ratio, 0.71; 95% CI, 0.48 to 1.04; P=.08) but was independently associated with improved kidney recovery at 90-day follow-up (hazard ratio, 1.81; 95% CI, 1.41 to 2.32; P<.001).ConclusionOur study demonstrated a high occurrence of CRRT liberation failure and poor 90-day outcomes in a cohort of AKI patients treated with CRRT.