Effect of the COVID-19 Pandemic on Postacute Care Decision Making.

The response to the coronavirus disease 2019 (COVID-19) pandemic in the United States has resulted in rapid modifications in the delivery of health care. Key among them has been surge preparation to increase both acute care hospital availability and staffing while using state and federal waivers to provide appropriate and efficient delivery of care. As a large health system in New York City, the epicenter of the pandemic in the United States, we were faced with these challenges early on, including the need to rapidly transition patients from acute care beds to provide bed capacity for the acute care hospitals. Rehabilitation medicine has always played an essential role in the continuum of care, establishing functional goals while identifying patients for postacute care planning. During this crisis, this expertise and the overwhelming need to adapt and facilitate patient transitions resulted in a collaborative process to efficiently assess patients for postacute care needs. We worked closely with our skilled nursing facility, home care partners, and an acute inpatient rehabilitation hospital to adapt their admissions processes to the patient population with COVID-19, all the while grappling with varying access to vital supplies, testing, and manpower. As the patient criteria were established, rapid pathways were created to postacute care, and we were able to create much needed bed capacity in our acute care hospitals.

What Now for Rehabilitation Specialists? Coronavirus Disease 2019 Questions and Answers.

Recognizing a need for more guidance on the coronavirus disease 2019 (COVID-19) pandemic, members of the Archives of Physical Medicine and Rehabilitation Editorial Board invited several clinicians with early experience managing the disease to collaborate on a document to help guide rehabilitation clinicians in the community. This consensus document is written in a "question and answer" format and contains information on the following items: common manifestations of the disease; rehabilitation recommendations in the acute hospital setting, recommendations for inpatient rehabilitation and special considerations. These suggestions are intended for use by rehabilitation clinicians in the inpatient setting caring for patients with confirmed or suspected COVID-19. The text represents the authors' best judgment at the time it was written. However, our knowledge of COVID-19 is growing rapidly. The reader should take advantage of the most up-to-date information when making clinical decisions.

High attenuation areas on chest computed tomography in community-dwelling adults: the MESA study.

Evidence suggests that lung injury, inflammation and extracellular matrix remodelling precede lung fibrosis in interstitial lung disease (ILD). We examined whether a quantitative measure of increased lung attenuation on computed tomography (CT) detects lung injury, inflammation and extracellular matrix remodelling in community-dwelling adults sampled without regard to respiratory symptoms or smoking.We measured high attenuation areas (HAA; percentage of lung voxels between -600 and -250 Hounsfield Units) on cardiac CT scans of adults enrolled in the Multi-Ethnic Study of Atherosclerosis.HAA was associated with higher serum matrix metalloproteinase-7 (mean adjusted difference 6.3% per HAA doubling, 95% CI 1.3-11.5), higher interleukin-6 (mean adjusted difference 8.8%, 95% CI 4.8-13.0), lower forced vital capacity (FVC) (mean adjusted difference -82 mL, 95% CI -119--44), lower 6-min walk distance (mean adjusted difference -40 m, 95% CI -1--80), higher odds of interstitial lung abnormalities at 9.5 years (adjusted OR 1.95, 95% CI 1.43-2.65), and higher all cause-mortality rate over 12.2 years (HR 1.58, 95% CI 1.39-1.79).High attenuation areas are associated with biomarkers of inflammation and extracellular matrix remodelling, reduced lung function, interstitial lung abnormalities, and a higher risk of death among community-dwelling adults.

Analysis of Skeletal Muscle Torque Capacity and Circulating Ceramides in Patients with Advanced Heart Failure.

BACKGROUND: Heart failure (HF)-related exercise intolerance is thought to be perpetuated by peripheral skeletal muscle functional, structural, and metabolic abnormalities. We analyzed specific dynamics of muscle contraction in patients with HF compared with healthy, sedentary controls. METHODS: Isometric and isokinetic muscle parameters were measured in the dominant upper and lower limbs of 45 HF patients and 15 healthy age-matched controls. Measurements included peak torque normalized to body weight, work normalized to body weight, power, time to peak torque, and acceleration and deceleration to maximum strength times. Body morphometry (dual energy X-ray absorptiometry scan) and circulating fatty acids and ceramides (lipodomics) were analyzed in a subset of subjects (18 HF and 9 controls). RESULTS: Extension and flexion time-to-peak torque was longer in the lower limbs of HF patients. Furthermore, acceleration and deceleration times in the lower limbs were also prolonged in HF subjects. HF subjects had increased adiposity and decreased lean muscle mass compared with controls. Decreased circulating unsaturated fatty acids and increased ceramides were found in subjects with HF. CONCLUSIONS: Delayed torque development suggests skeletal muscle impairments that may reflect abnormal neuromuscular functional coupling. These impairments may be further compounded by increased adiposity and inflammation associated with increased ceramides.

Impact of pulmonary hypertension on exercise performance in patients with interstitial lung disease undergoing evaluation for lung transplantation.

BACKGROUND AND OBJECTIVE: Pulmonary hypertension (PH) is a known complication in patients with interstitial lung disease (ILD). Cardiopulmonary exercise testing (CPET) is an essential tool for the assessment of patients with cardiac and pulmonary diseases due to its prognostic and therapeutic implications. Few studies have evaluated the relationship between CPET response and mean pulmonary artery pressures (mPAP) in ILD. The purpose of the present study was to determine and compare the potential correlations between CPET, 6-min walk test (6MWT), pulmonary function testing (PFT) and PH in patients with ILD being evaluated for lung transplantation. METHODS: The present study reviewed patients with ILD who received lung transplantations and had CPETs within 2 years before transplantation, right heart catheterizations, PFTs and 6MWTs within 4 months of CPET. RESULTS: A total of 72 patients with ILD were analysed; 36% had PH. There were significant correlations between mPAP and CPET parameters in patients with PH; but mPAP had no impact on percent of predicted diffusion capacity of the lung for carbon monoxide or 6-min walk distance (6MWD). CPET parameters were able to detect differences between levels of severity of PH through the use of the ratio of minute ventilation to rate of carbon dioxide production (VE/VCO2) and the partial pressure of end-tidal carbon dioxide. CONCLUSIONS: This is the first study that analyses 6MWD, PFT and CPET in patients with ILD awaiting lung transplantation with and without PH. The present study demonstrates the significant impact of PH on exercise capacity and performance in patients with ILD awaiting lung transplantation.

Comparing cardiopulmonary exercise testing in severe COPD patients with and without pulmonary hypertension.

PURPOSE: To determine; (i) the effect of PH on exercise capacity, gas exchange and oxygen pulse; (ii) the variables that correlate with mean pulmonary artery pressure (mPAP) in severe COPD patients. METHODS: We reviewed 98 severe COPD patients who had pulmonary function, right heart catheterisation, and cardiopulmonary exercise testing (CPET) performed within six months of each other. PH was defined by a resting mPAP > 25 mmHg. COPD patients with and without PH were compared using the independent samples t-test and Mann-Whitney U test. Pearson correlation coefficients were used to assess the relationship between continuous variables. RESULTS: PH was present in 32% of patients and the majority of PH was mild (mPAP, 25-35 mmHg). Peak workload, oxygen uptake and oxygen pulse on CPET were significantly lower in the PH group. Mean PAP was found to inversely correlate with peak oxygen uptake, with a tendency towards lower six-minute walk distance. No difference between two groups was seen in any of the gas exchange variables. CONCLUSION: In severe COPD, there is a relatively high percentage of PH which causes a decrease in exercise capacity and oxygen pulse without significantly altered ventilation as measured by CPET. Lower than expected exercise performance without a change in pulmonary function may indicate a need for evaluation for possible PH.

Distinguishing pulmonary hypertension in interstitial lung disease by ventilation and perfusion defects measured by cardiopulmonary exercise testing.

BACKGROUND: Pulmonary hypertension (PH) is common in interstitial lung disease (ILD). Since cardiopulmonary exercise testing (CPET) is useful in understanding the pathophysiology of respiratory disorders and can distinguish between ventilation and perfusion (V/Q) defects, it may have a role in the detection of PH in ILD. We evaluated whether CPET can detect PH through analysis of V/Q defects in ILD. OBJECTIVES: We aimed to use CPET to determine if there are changes in the ventilation and the activity pattern of mixed-expired carbon dioxide pressure (PECO2) and end-tidal carbon dioxide pressure (PetCO2) in ILD patients with and without PH. METHODS: A retrospective chart review was done of all patients who received lung transplants at the Columbia University Medical Center between 2000 and 2011 with the diagnosis of ILD. CPETs were performed during the 2 years prior to transplantation; right heart catheterizations and pulmonary function tests were performed within 4 months of CPET. RESULTS: The ILD patients with PH demonstrated significantly lower PetCO2 and PECO2 during certain levels of exercise with a distinctive activity pattern for PECO2/PetCO2. CONCLUSIONS: Evaluation of V/Q defects through the PECO2 and PetCO2 patterns on CPET in ILD patients can distinguish between patients with and without PH.

Exercise capacity and ventilatory response during exercise in COPD patients with and without ß blockade.

BACKGROUND: Although ß blockade (BB) in patients with chronic obstructive pulmonary disease (COPD) does not show signs of worsening pulmonary function or respiratory symptoms, the effects on cardiopulmonary exercise testing (CPET) remain unclear. The aim of this study was to determine whether BB affects exercise capacity, gas exchange, and hemodynamic responses in patients with COPD. METHODS: Twenty-four COPD subjects on BB were matched to 24 COPD subjects without BB according to age, gender, body mass index, and severity of COPD. All subjects underwent resting pulmonary function and symptom-limited CPET. RESULTS: Comparing COPD patients with and without BB revealed that percent peak oxygen consumption and VE/VCO2 nadir were not significantly different (45 ± 16 vs. 51 ± 23 %, p = 0.30, and 35.1 ± 8.5 vs. 36.2 ± 11.6 %, p = 0.69). Systolic blood pressure and heart rate at peak exercise were significantly decreased in COPD patients with BB (168 ± 16 vs. 185 ± 20 mmHg, and 109 ± 16 vs. 122 ± 14 bpm, respectively, p < 0.05). CONCLUSION: Exercise capacity and gas exchange remain unaffected in patients with COPD in the presence of BB, although heart rate and blood pressure are lower. These findings imply that BB does not adversely affect functional capacity in patients with COPD.

Baroreceptor sensitivity after Valsalva maneuver in women with chronic obstructive pulmonary disease.

PURPOSE: Reduced baroreceptor sensitivity (BRS) results in changes in autonomic modulation. Patients with chronic obstructive pulmonary disease (COPD) may have altered BRS. Therefore, we compared BRS between COPD patients and normal controls. METHODS: We compared 14 COPD patients [mean (±SD) age, 62 ± 8 years] to 14 healthy controls [mean (±SD) age, 59 ± 6 years] for the loss of BRS. All patients received ß(2)-agonist therapy but were free from any other type of medication that would interfere with autonomic responses, all controls were free from cardiopulmonary disease, and none was taking medications. All participants were female, post-menopausal, had no known cardiac disease and were ex-smokers. Reduced baroreceptor sensitivity was determined using the slope of the magnitude of R-R widening over the increase in systolic blood pressure following Valsalva maneuver. RESULTS: The mean BRS in controls versus COPD patients showed a mean value of 6.15 ± 2.26 versus 1.91 ± 2.92 ms/mmHg (p < 0.001). CONCLUSIONS: These findings are consistent with other abnormalities of autonomic disruption as previously reported, and demonstrate a severe blunting of the baroreceptor response in individuals with COPD. The cause of this altered BRS response in COPD is not fully clear, we postulate that air trapping with persistent elevation of intrathoracic pressure may lead to a subsequent blunting of the sensitivity of the baroreceptors.

Sildenafil for chronic obstructive pulmonary disease: a randomized crossover trial.

RATIONALE: Pulmonary hypertension with exercise is common in chronic obstructive pulmonary disease (COPD) and may contribute to exercise limitation in this disease. We aimed to determine the effects of treatment with sildenafil on exercise capacity in patients with COPD and emphysema. METHODS: We performed a randomized, double-blind, placebo-controlled 2-period crossover trial of sildenafil thrice daily in ten adults with COPD and emphysema on CT scan without pulmonary hypertension. We randomized study participants to 4 weeks of sildenafil (or placebo) followed by a 1-week washout and then 4 weeks of placebo (or sildenafil). The 2 primary outcomes were the 6-minute walk distance and oxygen consumption at peak exercise. RESULTS: Sildenafil had no effect on 6-minute walk distance (placebo-corrected difference = -7.8 m, 95% confidence interval, -23.2 to 7.5 m, p = 0.35) or oxygen consumption at peak exercise (placebo-corrected difference = -0.1 ml/kg/min, 95% confidence interval -2.1 to 1.8 ml/kg/min, p = 0.89). Sildenafil increased the alveolar-arterial oxygen gradient (p = 0.02), worsened symptoms (p = 0.04), and decreased quality-of-life (p = 0.03). Adverse events were more frequent while receiving sildenafil (p = 0.005). CONCLUSIONS: Routine sildenafil administration did not have a beneficial effect on exercise capacity in patients with COPD and emphysema without pulmonary hypertension. Sildenafil significantly worsened gas exchange at rest and quality of life. (clinicaltrials.gov NCT00104637).

Rehabilitation and In-Hospital Mortality in COVID-19 Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) guidelines endorse early rehabilitation to improve outcomes in hospitalized patients, but the evidence base to support this recommendation is lacking. We examined the association between early rehabilitation and in-hospital deaths in COVID-19 patients. METHOD: A single-center retrospective study, involving 990 COVID-19 patients (42.4% women, mean age 67.8 years) admitted between March 1, 2020 and May 31, 2020 to a community hospital, was conducted. Association of rehabilitation during hospitalization with in-hospital mortality was examined using logistic regression analysis adjusted for demographics, length of stay, body mass index, comorbid illnesses, functional status as well as for COVID-19 presentations, treatments, and complications. RESULTS: Over the 3-month study period, 475 (48.0%) inpatients were referred for rehabilitation. Patients who received rehabilitation were older (73.7 ± 14.0 vs 62.3 ± 17.2). There were 61 hospital deaths (12.8%) in the rehabilitation group and 165 (32.0%) in the nonrehabilitation group. Receiving rehabilitation was associated with an 89% lower in-hospital mortality (odds ratio [OR]: 0.11, 95% confidence interval [CI]: 0.06-0.19) after adjusting for multiple confounders and COVID-19 disease markers. In sensitivity analyses, the results were significant in subpopulations defined by age group, sex, race, length of hospitalization, or pulmonary presentations. Each additional rehabilitation session was associated with a 29% lower risk of in-hospital mortality (OR per session: 0.71, 95% CI: 0.64-0.79) in the fully adjusted model. CONCLUSION: Among hospitalized COVID-19 patients, receiving early rehabilitation was associated with lower in-hospital mortality. Our findings support implementation of rehabilitation services for COVID-19 patients in acute care settings, but further research from randomized clinical trials is needed.

Impaired autonomic function in normotensive obese children.

PURPOSE: To evaluate baroreflex sensitivity and autonomic control in a cohort of normotensive obese (OB) children. METHOD: A cross-sectional investigation, in which, baroreflex sensitivity and autonomic control were evaluated using transfer function and power spectral density analysis (PSDA) of the electrocardiogram and beat-to-beat blood pressures in normotensive OB children and normal weight normotensive controls. All methods used were noninvasive and data were captured while seated and at rest. RESULTS: The OB and control subjects non-obese (NO) were of similar age (OB 9.1±1.9 years vs. NO 9.2±1.4 years). The OB group was classified as having a BMI greater than the 95th percentile adjusted for age and gender, and a NO group with a BMI at or less than the 95th percentile (BMI percentile OB. 97.5±1.3 vs. NO 58.5±24.1). Both groups had similar normotensive blood pressures. T tests revealed that baroreflex sensitivity and HFRR were significantly reduced in the OB 9.2±2.7 vs. 15.2±4.7 (ms/mmHg) and 6.7±1.1 vs. 8.2±1.1 ms2, respectively, while LFSBP and LF/HF ratio were significantly increased in the OB 11.9±5.6 vs. 8.2±4.7 mmHg2 and 1.2±0.7 vs. 0.54±0.3, respectively. CONCLUSIONS: Normotensive OB children exhibited significantly reduced baroreflex sensitivity, parasympathetic control as well as increased sympathetic control when compared with healthy, NO controls. Findings in this investigation raise the awareness that autonomic dysfunction is present in young OB normotensive children.

Psychosis risk individuals show poor fitness and discrepancies with objective and subjective measures.

Exercise is a promising intervention for individuals at clinical high-risk for psychosis (CHR). However, these youth may not be reliable reporters on fitness. There have been no investigations that utilized objective fitness assessment in this population. The present study objectively characterizes the level of fitness in CHR youth, compares the accuracy of self-report measures to objective fitness indices, and explores clinical factors that may influence the accuracy of self-reported measures of fitness. Forty CHR individuals completed an exercise survey and objective indices of fitness (i.e., VO2max and BMI). Forty healthy volunteers completed objective indices of fitness and a structured clinical interview ruling out the presence of psychiatric illness. CHR youth showed greater BMI and lowered VO2max compared to healthy volunteers. In the CHR group, self-report items (perceived fitness) did not reflect objective indices of fitness, whereas specific exercise behaviors (intensity of exercise) showed stronger correlations with objective fitness measurements. Exploratory analyses suggested that symptoms (grandiosity and avolition) related to errors in self-perception. Results indicate that CHR individuals are less fit than controls as indexed by objective measures of fitness and that it is important to consider unique population clinical characteristics when employing self-report data.

Challenges and Lessons Learned for Acute Inpatient Rehabilitation of Persons With COVID-19: Clinical Presentation, Assessment, Needs, and Services Utilization.

OBJECTIVE: The aim of the study was to present: (1) physiatric care delivery amid the SARS-CoV-2 pandemic, (2) challenges, (3) data from the first cohort of post-COVID-19 inpatient rehabilitation facility patients, and (4) lessons learned by a research consortium of New York and New Jersey rehabilitation institutions. DESIGN: For this clinical descriptive retrospective study, data were extracted from post-COVID-19 patient records treated at a research consortium of New York and New Jersey rehabilitation inpatient rehabilitation facilities (May 1-June 30, 2020) to characterize admission criteria, physical space, precautions, bed numbers, staffing, employee wellness, leadership, and family communication. For comparison, data from the Uniform Data System and eRehabData databases were analyzed. The research consortium of New York and New Jersey rehabilitation members discussed experiences and lessons learned. RESULTS: The COVID-19 patients (N = 320) were treated during the study period. Most patients were male, average age of 61.9 yrs, and 40.9% were White. The average acute care length of stay before inpatient rehabilitation facility admission was 24.5 days; mean length of stay at inpatient rehabilitation facilities was 15.2 days. The rehabilitation research consortium of New York and New Jersey rehabilitation institutions reported a greater proportion of COVID-19 patients discharged to home compared with prepandemic data. Some institutions reported higher changes in functional scores during rehabilitation admission, compared with prepandemic data. CONCLUSIONS: The COVID-19 pandemic acutely affected patient care and overall institutional operations. The research consortium of New York and New Jersey rehabilitation institutions responded dynamically to bed expansions/contractions, staff deployment, and innovations that facilitated safe and effective patient care.

Effect of Comorbid Chronic Low Back Pain on Patient-Reported Outcome and Gait Parameters in Patients With Symptomatic Knee Osteoarthritis.

Knee osteoarthritis and chronic low back pain are common and often coexist. There are limited studies on the impact of coexisting musculoskeletal disorders on gait parameters and its association with self-assessed functional outcome. This study compared gait parameters, self-assessed functional outcome measurements, and quality-of-life scales between patients with knee osteoarthritis against those with coexisting knee osteoarthritis and chronic low back pain using gait analysis, Western Ontario and McMaster Osteoarthritis Index, and Short Form-36. Three hundred sixty-seven patients underwent gait analysis after the question-based functional outcome measurement. Pain, function, and quality of life were worse in the coexisting knee osteoarthritis and chronic low back pain group (n = 197) compared with the knee osteoarthritis only group (n = 170, P = 0.017, P = 0.004, P < 0.001, P = 0.004, respectively). The coexisting knee osteoarthritis and chronic low back pain group had significantly lower gait velocity and cadence than the knee osteoarthritis group (P = 0.028 and P = 0.003). The Western Ontario and McMaster Osteoarthritis Index Pain subscore was associated with gait velocity (P < 0.001) in the knee osteoarthritis group, whereas Short Form-36 physical composite was associated with gait velocity (P < 0.001) in the coexisting knee osteoarthritis and chronic low back pain group. Comorbid chronic low back pain in patients with knee osteoarthritis was associated with worse pain, function, quality of life, gait velocity, and cadence. Compared with the Western Ontario and McMaster Osteoarthritis Index, Short Form-36 may be a more suitable tool to track mobility outcome measure, such as gait velocity, in the management of the coexisting knee osteoarthritis and chronic low back pain.

Redefining Pathways into Acute Rehabilitation during the COVID-19 Crisis.

The coronavirus disease 2019 (COVID-19) pandemic has necessitated drastic changes across the spectrum of health care, all of which have occurred with unprecedented rapidity. The need to accommodate change on such a large scale has required ingenuity and decisive thinking. The field of physical medicine and rehabilitation has been faced with many of these challenges. Healthcare practitioners in New York City, the epicenter of the pandemic in the United States, were among the first to encounter many of these challenges. One of the largest lessons included learning how to streamline admissions and transfer process into an acute rehabilitation hospital as part of a concerted effort to make acute care hospital beds available as quickly as possible.

Suicide Reduction in Schizophrenia via Exercise (SUnRISE): study protocol for a multi-site, single-blind, randomized clinical trial of aerobic exercise for suicide risk reduction in individuals with schizophrenia.

BACKGROUND: Suicide risk among individuals with schizophrenia (SZ) is intractably high, with over 40% of individuals attempting to take their own lives during their lifetime and an estimated 5-10% completing suicide. At present, available pharmacological and psychotherapeutic treatments offer limited risk reduction benefits, and thus, there remains an urgent need to explore novel interventions that will ameliorate this risk. Aerobic exercise (AE) has been shown to improve a number of predictors of suicide risk (e.g., depressed mood, sleeping difficulties). As individuals with SZ display a highly sedentary lifestyle, AE may reduce suicide risk. METHODS: Employing a multi-site, single-blind, randomized clinical trial design, we will examine the impact of AE on risk for suicide and related variables in individuals with SZ. Participants will be randomized to one of two 12-week exercise interventions: AE or a stretching and toning (ST) control intervention. Primary outcome measures will include suicide risk (Columbia Suicide Severity Rating Scale, C-SSRS) and aerobic fitness (VO2max), along with additional measures of suicide risk, mood, emotion regulation, sleep, cognition, and physical activity, with assessments completed at baseline and after 6 and 12 weeks of interventions. DISCUSSION: It is hypothesized that AE will reduce suicide risk among individuals with SZ. This study may offer support for a more efficacious treatment method for this population in addition to the pre-existing pharmacological and psychotherapeutic treatment regimens. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03270098 . Registered on September 1, 2017.

Physiatry as a Leader for Postacute Care in Integrated Healthcare Systems.

Because health care is being moved to a higher level of accountability, there has been a focus on improving outcomes through improving postacute care. The issues of cost and readmissions to acute care settings are very important, but the focus on patient function has not been foremost. Because of the fact that most postacute care needs are based on functional limitations and that physiatrists are well versed in transitions of care, rehabilitation of patients back to community settings, team building, and leadership, it is appropriate for rehabilitation medicine to take a leadership role in the planning and development of postacute care services in the new integrated healthcare systems that are becoming prevalent in healthcare. This review discusses some of the issues in postacute care, the growth of the integrated health system model, and how there are opportunities and challenges for physiatric leadership to help develop these new models of care.

Improving Cognition via Exercise (ICE): Study Protocol for a Multi-Site, Parallel-Group, Single-Blind, Randomized Clinical Trial Examining the Efficacy of Aerobic Exercise to Improve Neurocognition, Daily Functioning, and Biomarkers of Cognitive Change in Individuals with Schizophrenia.

Individuals with schizophrenia (SZ) display cognitive deficits that have been identified as major determinants of poor functioning and disability, representing a serious public health concern and an important target for interventions. At present, available treatments offer only minimal to moderate benefits to ameliorate cognitive deficits. Thus, there remains an urgent need to identify novel interventions to improve cognition in people with SZ. Emerging evidence from animal and basic human research suggests aerobic exercise training (AE) has beneficial effects on cognition. Preliminary findings suggest that AE is efficacious in improving cognitive functioning in SZ, however the extant studies have been limited by small samples, a dearth of information on biologically-relevant covariates, and limited information on impact on daily functioning. Additionally, while AE-related cognitive benefits have been linked to Brain-Derived Neurotrophic Factor (BDNF) upregulation, this putative mechanism needs confirmation. The present report describes a study protocol designed to address these limitations-we review and summarize the current literature on treatment of cognitive deficits in SZ, state the rationale for employing AE to target these deficits, and describe the current protocol-a multi-site, single-blind, randomized clinical trial aiming to recruit 200 community-dwelling individuals with SZ. Participants are randomized to one of two 12-week interventions: AE using active-play video games (i.e., Xbox Kinect) and traditional cardiovascular exercise equipment or a stretching-and-toning (ST) control intervention. Participants undergo assessments of aerobic fitness, cognition, and daily functioning, as well as BDNF and other biomarkers of cognitive change, at baseline and after 6-and 12-weeks.

Sympathetic drive is modulated by central chemoreceptor activation.

To determine the effects of central chemoreceptor stimulation upon sympathetic modulation while minimizing baroreceptor influences, we performed a single-blind, counter-balanced, placebo-controlled trial of a modified hypercapnic/hyperoxic rebreathe protocol stimulus to activate the central chemoreflex. Muscle sympathetic nerve activity (MSNA), heart rate, blood pressure, and ventilation were recorded dynamically as subjects transitioned from a hypocapnia to hypercapnia state. The stages of data recording were defined as hyperventilation (HyV), pre-threshold (PreT) and post-threshold (PostT), with threshold being defined as the point of non-linear deviation in ventilation. The changes in MSNA (-4.2+/-52.4 arbitrary units (AU) vs. 245.0+/-84.0AU) and burst count (-0.1+/-0.7 bursts/segment vs. 2.5+/-1.7 bursts/segment) were significantly different between control and rebreathe for the HyV to PreT step. There was also a significant difference for PreT to PostT for total MSNA (3.9+/-65.4AU vs. 183.7+/-104.2AU). In a hypercapnic/hyperoxic state, the central chemoreceptors modulate sympathetic activity below the chemoreflex threshold independently of the baroreceptors, possibly contributing to basal autonomic/sympathetic tone. Central chemoreceptors also appear to play a significant role in sympathetic modulation after the threshold.