Fine-scale spatial and social patterns of SARS-CoV-2 transmission from identical pathogen sequences.

Pathogen genomics can provide insights into disease transmission patterns, but new methods are needed to handle modern large-scale pathogen genome datasets. Genetically proximal viruses indicate epidemiological linkage and are informative about transmission events. Here, we leverage pairs of identical sequences using 114,298 SARS-CoV-2 genomes collected via sentinel surveillance from March 2021 to December 2022 in Washington State, USA, with linked age and residence information to characterize fine-scale transmission. The location of pairs of identical sequences is highly consistent with expectations from mobility and social contact data. Outliers in the relationship between genetic and mobility data can be explained by SARS-CoV-2 transmission between postal codes with male prisons, consistent with transmission between prison facilities. Transmission patterns between age groups vary across spatial scales. Finally, we use the timing of sequence collection to understand the age groups driving transmission. This work improves our ability to characterize transmission from large pathogen genome datasets.

Relationships between body composition, anthropometrics, and standard lipid panels in a normative population.

Introduction: More than one third of adults in the United States (US) meet the clinical criteria for a diagnosis of metabolic syndrome, but often diagnosis is challenging due to healthcare access, costs and discomfort with the process and invasiveness associated with a standard medical examination. Less invasive and more accessible approaches to collecting biometric data may have utility in identifying individuals at risk of diagnoses, such as metabolic syndrome or dyslipidemia diagnoses. Body composition is one such source of biometric data that can be non-invasively acquired in a home or community setting that may provide insight into an individual's propensity for a metabolic syndrome diagnosis. Here we investigate possible associations between body composition, anthropometrics and lipid panels in a normative population. Methods: Healthy participants visited the Lab100 clinic location at a hospital setting in New York City and engaged in a wellness visit led by a nurse practitioner. Blood was analyzed at point-of-care using the Abbott Piccolo Xpress portable diagnostic analyzer (Abbott Laboratories, IL, USA) and produced direct measures of total cholesterol (TC), high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), very-low density lipoprotein (VLDL-C), and triglycerides (TG). Body composition and anthropometric data were collected using two separate pieces of equipment during the same visit (Fit3D and InBody570). Regression analysis was performed to evaluate associations between all variables, after adjusting for age, sex, race, AUDIT-C total score (alcohol use), and current smoking status. Results: Data from 199 participants were included in the analysis. After adjusting for variables, percentage body fat (%BF) and visceral fat levels were significantly associated with every laboratory lipid value, while waist-to-hip ratio also showed some significant associations. The strongest associations were detected between %BF and VLDL-C cholesterol levels (t = 4.53, p = 0.0001) and Triglyceride levels (t = 4.51, p = 0.0001). Discussion: This initial, exploratory analysis shows early feasibility in using body composition and anthropometric data, that can easily be acquired in community settings, to identify people with dyslipidemia in a normative population.

Health impacts reported in the Spinal Cord Injury COVID-19 Pandemic Experience Survey (SCI-CPES).

CONTEXT: In people with spinal cord injury (SCI), infections are a leading cause of death, and there is a high prevalence of diabetes mellitus, obesity, and hypertension, which are all comorbidities associated with worse outcomes after COVID-19 infection. OBJECTIVE: To characterize self-reported health impacts of COVID-19 on people with SCI related to exposure to virus, diagnosis, symptoms, complications of infection, and vaccination. METHODS: The Spinal Cord Injury COVID-19 Pandemic Experience Survey (SCI-CPES) study was administered to ask people with SCI about their health and other experiences during the COVID-19 pandemic. RESULTS: 223 community-living people with SCI (male = 71%; age = 52±15 years [mean±SD]; paraplegia = 55%) completed the SCI-CPES. Comorbidities first identified in the general population as associated with poor outcomes after COVID-19 infection were commonly reported in this SCI sample: hypertension (30%) and diabetes (13%). 23.5% of respondents reported a known infection exposure from someone who visited (13.5%) or lived in their home (10%). During the study, which included a timeframe when testing was either unavailable or scarce, 61% of respondents were tested for COVID-19; 14% tested or were presumed positive. Fever, fatigue, and chills were the most common symptoms reported. Of the 152 respondents surveyed after COVID-19 vaccines became available, 82% reported being vaccinated. Race and age were significantly associated with positive vaccination status: most (78%) individuals who were vaccinated identified as Non-Hispanic White and were older than those who reported being unvaccinated (57±14 vs. 43±13 years, mean±SD). CONCLUSIONS: Self-reported COVID-19 symptoms were relatively uncommon and not severe in this sample of people with SCI. Potential confounders and limitations include responder, recruitment and self-reporting biases and changing pandemic conditions. Future studies on this topic should query social distancing and other behavioral strategies. Large retrospective chart review studies may provide additional data on incidence and prevalence of COVID-19 infections, symptoms, and severities in the SCI population.

Spatiotemporal parameters from remote smartphone-based gait analysis are associated with lower extremity functional scale categories.

Objective: Self-report tools are recommended in research and clinical practice to capture individual perceptions regarding health status; however, only modest correlations are found with performance-based results. The Lower Extremity Functional Scale (LEFS) is one well-validated measure of impairment affecting physical activities that has been compared with objective tests. More recently, mobile gait assessment software can provide comprehensive motion tracking output from ecologically valid environments, but how this data relates to subjective scales is unknown. Therefore, the association between the LEFS and walking variables remotely collected by a smartphone was explored. Methods: Proprietary algorithms extracted spatiotemporal parameters detected by a standard integrated inertial measurement unit from 132 subjects enrolled in physical therapy for orthopedic or neurological rehabilitation. Users initiated ambulation recordings and completed questionnaires through the OneStep digital platform. Discrete categories were created based on LEFS score cut-offs and Analysis of Variance was applied to estimate the difference in gait metrics across functional groups (Low-Medium-High). Results: The main finding of this cross-sectional retrospective study is that remotely-collected biomechanical walking data are significantly associated with individuals' self-evaluated function as defined by LEFS categorization (n = 132) and many variables differ between groups. Velocity was found to have the strongest effect size. Discussion: When patients are classified according to subjective mobility level, there are significant differences in quantitative measures of ambulation analyzed with smartphone-based technology. Capturing real-time information about movement is important to obtain accurate impressions of how individuals perform in daily life while understanding the relationship between enacted activity and relevant clinical outcomes.

Development of the Spinal Cord Injury COVID-19 Pandemic Experience Survey (SCI-CPES).

CONTEXT: Early during the COVID-19 pandemic, rehabilitation providers received reports from people with spinal cord injury (SCI) of considerable disruptions in caregiver services, medical and nursing care, and access to equipment and supplies; concomitantly, the medical community raised concerns related to the elevated risk of acquiring the infection due to SCI-specific medical conditions. Due to the novel nature of the pandemic, few tools existed to systematically investigate the outcomes and needs of people with SCI during this emergency. OBJECTIVE: To develop a multidimensional assessment tool for surveying the experience of the COVID-19 pandemic on physical and psychological health, employment, caregiving services, medical supplies and equipment, and the delivery of medical care for people with SCI. METHODS: The Spinal Cord Injury COVID-19 Pandemic Experience Survey (SCI-CPES) study, conducted between July 2020 through August 2021, surveyed people with SCI about their experiences during the early COVID-19 pandemic. The SCI-CPES was developed by a SCI care and research consortium using an iterative process. RESULTS: Two hundred and twenty-three people completed the survey. Most respondents resided in the consortium catchment area. As the survey progressed, online informed consent became available allowing dissemination of the SCI-CPES nationally. CONCLUSIONS: The consortium rapidly implemented the capture of experiences with COVID-19 pandemic directly from people with SCI, including survey creation, institutional approvals, distribution, online e-consenting, and data collection. In the future, the SCI-CPES is adaptable for use in other types of emergencies and disasters.

Engagement in an mHealth-Guided Exercise Therapy Program Is Associated With Reductions in Chronic Musculoskeletal Pain.

CONTEXT: Chronic musculoskeletal pain costs the US $980 billion annually. Conservative treatments are the criterion standard, but scalable methods of treatment remain to be evaluated. OBJECTIVE: The aim of the study is to determine the effects of pain reduction and the perceived benefits of an mHealth exercise therapy program. DESIGN: This is a retrospective observational study on data from 3109 people (18-98, 49% female) with musculoskeletal pain in an mHealth exercise program. Presession pain was measured via 11-point numeric rating scale and nonstandardized single-item questions for work and quality of life; all were analyzed using mixed-effects models. RESULTS: By 11 sessions, there was an estimated a 2.09-point decrease in average numeric rating scale pain levels. There was an average percent increase of approximately 0.7 points for work life and quality of life ( tdf =6,632 = 12.06, P < 0.001). User engagement was high; 46% of participants were performing more than one session per day, and 88% were engaging within a week, indicating the feasibility of the deployment of an mHealth exercise app. CONCLUSIONS: An mHealth exercise program was associated with significant decrease in pain and increased perceived benefits in a large population. These findings serve as preliminary findings of the feasibility for mHealth exercise interventions as scalable tools to improve chronic musculoskeletal pain outcomes.

Treatments perceived to be helpful for neuropathic pain after traumatic spinal cord injury: A multicenter cross-sectional survey study.

DESIGN: Cross-sectional survey. OBJECTIVE: To evaluate the perceived helpfulness of pharmacological and non-pharmacological interventions and their combinations for neuropathic pain (NeuP) and subcategories of NeuP after spinal cord injury (SCI). SETTING: Six Spinal Cord Injury Model System Centers. METHODS: Three hundred ninety one individuals at least one year post traumatic SCI were enrolled. A telephone survey was conducted to determine the pharmacologic and non-pharmacologic treatments used in the last 12 months for each participant's three worst pains, whether these treatments were "helpful", and if currently used, each treatments' effectiveness. RESULTS: Two hundred twenty participants (56%) reported 354 distinct NeuPs. Pharmacological treatments rated helpful for NeuP were non-tramadol opioids (opioids were helpful for 86% of opioid treated NeuPs), cannabinoids (83%), and anti-epileptics (79%). Non-pharmacological treatments rated helpful for NeuP were massage (76%), body position adjustment (74%), and relaxation therapy (70%). Those who used both opioids and exercise reported greater NeuP treatment helpfulness compared to participants using opioids without exercise (P = 0.03). CONCLUSIONS: Opioids, cannabinoids, and massage were reported more commonly as helpful than treatments recommended as first-line therapies by current clinical practice guidelines (CPGs) for NeuP after SCI (antiepileptics and antidepressants). Individuals with SCI likely value the modulating effects of pharmacological and non-pharmacological treatments on the affective components of pain in addition to the sensory components of pain when appraising treatment helpfulness.

Orthostatic systemic and cerebral hemodynamics in newly injured patients with spinal cord injury.

BACKGROUND: Low blood pressure (BP) may lead to reduced cerebral blood flow velocity (CBFv) during an orthostatic challenge in newly injured patients with traumatic spinal cord injury (SCI), which, may relate to the neurological level of injury (NLI) as documented on the International Standards for the Neurologic Classification of SCI (ISNCSCI), or to evidence of cardiovascular autonomic impairment as determined by the International Standards to document remaining Autonomic Function after SCI (ISAFSCI). OBJECTIVE: To examine the influence of patient demographics, ISNCSCI and ISAFSCI scores on hemodynamic responses to a bedside sit-up test in newly injured patients with SCI. DESIGN: Cross-sectional, prospective analysis. METHODS: A modified sit-up test was conducted at the bedside with the hips at an angle between 45° and 90° and the legs horizontal, level with the hips. Heart rate, BP, and CBFv were recorded for 10 min in the supine and seated positions. RESULTS: Fifty-three newly injured patients (median 39.5 days post-injury) with traumatic SCI were enrolled. Overall, 28 (53%) patients met ISAFSCI criteria, and the number of criteria met (total score) was significantly related to orthostatic changes in CBFv. Change in SBP and change in CBFv were not significantly related, but NLI and total sensory score from the ISNCSCI were significant predictors of the change in CBFv. CONCLUSIONS: Total ISAFSCI score, NLI and sensory scores were positively associated with orthostatic changes in CBFv. Long term follow-up should be considered to determine the consequences of diminished CBFv on cognitive function and quality of life following SCI.

Treatments that are perceived to be helpful for non-neuropathic pain after traumatic spinal cord injury: a multicenter cross-sectional survey.

STUDY DESIGN: Cross-sectional survey. OBJECTIVES: The objective of the study was to identify the treatments that people with traumatic spinal cord injury (SCI) used for their non-neuropathic pains (nonNeuPs) and how they subjectively rated the helpfulness of those treatments. SETTING: Six centers from the Spinal Cord Injury Model Systems. METHODS: Three hundred ninety one individuals who were at least 1-year post-traumatic SCI were enrolled. A telephone survey was conducted for pharmacologic and non-pharmacologic treatments utilized in the last 12 months for each participant's three worst pains and the perceived helpfulness of each treatment for each pain. RESULTS: One hundred ninety (49%) participants reported at least one nonNeuP (Spinal Cord Injury Pain Instrument score < 2) in the previous 7 days. NSAIDs/aspirin, acetaminophen, opioids, and cannabinoids were the most commonly used and helpful pharmacologic treatments for overall nonNeuP locations (helpful in 77-89% of treated pains). Body position adjustment, passive exercise, massage, resistive exercise, and heat therapy were reported as the most commonly used non-pharmacological treatments for nonNeuPs. Heat therapy, aerobic exercise, massage, and body position adjustment were the most helpful non-pharmacological treatments for overall nonNeuP locations (helpful in 71-80% of treated pains). Perceived helpfulness of treatments varied by pain locations, which may be due to different mechanisms underlying pains in different locations. CONCLUSIONS: Results of the study may help guide clinicians in selecting pain-specific treatments for nonNeuPs. The self-reported helpfulness of heat therapy, exercise, and massage suggests a possible direction for clinical trials investigating these treatments of nonNeuP while limiting the side effects accompanying pharmacologic treatments.

The Effects of Early Mobilization on Patients Requiring Extended Mechanical Ventilation Across Multiple ICUs.

OBJECTIVES: 1) To successfully implement early mobilization of individuals with prolonged mechanical ventilation in multiple ICUs at a tertiary care hospital and 2) to reduce length of stay and improve quality of care to individuals in the ICUs. DESIGN: Comparative effectiveness cohort study based on a quality improvement project. SETTING: Five ICUs at a tertiary care hospital. PATIENTS: A total of 541 mechanically ventilated patients over a 2-year period (2014-2015): 280 and 261, respectively. Age ranged from 19 to 94 years (mean, 63.84; sd, 14.96). INTERVENTIONS: A hospital-based initiative spurred development of a multidisciplinary team, tasked with establishing early mobilization in ICUs. MEASUREMENTS AND MAIN RESULTS: Early mobilization in the ICUs was evaluated by the number of physical therapy consults, length of stay, individual treatment sessions utilizing functional outcomes, and follow-up visits. Implementation of an early mobilization protocol across all ICUs led to a significant increase in the number of physical therapy consults, a significant decrease in ICU and overall lengths of stay, significantly shorter days to implement physical therapy, and a significantly higher physical therapy follow-up rate. CONCLUSIONS: Mobilizing individuals in an intensive care setting decreases length of stay and hospital costs. With an interdisciplinary team to plan, implement, and evaluate stages of the program, a successful early mobilization program can be implemented across all ICUs simultaneously and affect change in patients who will require prolonged mechanical ventilation.

Exoskeletal-Assisted Walking During Acute Inpatient Rehabilitation Leads to Motor and Functional Improvement in Persons With Spinal Cord Injury: A Pilot Study.

OBJECTIVE: To explore the potential effects of incorporating exoskeletal-assisted walking (EAW) into spinal cord injury (SCI) acute inpatient rehabilitation (AIR) on facilitating functional and motor recovery when compared with standard of care AIR. DESIGN: A quasi-experimental design with a prospective intervention group (AIR with EAW) and a retrospective control group (AIR only). SETTING: SCI AIR facility. PARTICIPANTS: Ten acute inpatient participants with SCI who were eligible for locomotor training were recruited in the intervention group. Twenty inpatients with SCI were identified as matched controls by reviewing an AIR database, Uniform Data System for Medical Rehabilitation, by an individual blinded to the study. Both groups (N=30) were matched based on etiology, paraplegia/tetraplegia, completeness of injury, age, and sex. INTERVENTION: EAW incorporated into SCI AIR. MAIN OUTCOME MEASURES: FIM score, International Standards for Neurological Classification of Spinal Cord Injury Upper Extremity Motor Score and Lower Extremity Motor Scores (LEMS), and EAW session results, including adverse events, walking time, and steps. RESULTS: Changes from admission to discharge LEMS and FIM scores were significantly greater in the intervention group (LEMS change: 14.3±10.1; FIM change: 37.8±10.8) compared with the control group (LEMS change: 4.6±6.1; FIM change: 26.5±14.3; Mann-Whitney U tests: LEMS, P<.01 and FIM, P<.05). One adverse event (minor skin abrasion) occurred during 42 walking sessions. Participants on average achieved 31.5 minutes of up time and 18.2 minutes of walk time with 456 steps in one EAW session. CONCLUSIONS: Incorporation of EAW into standard of care AIR is possible. AIR with incorporated EAW has the potential to facilitate functional and motor recovery compared with AIR without EAW.

An interview based approach to the anorectal portion of the International Standards of Neurological Classification of Spinal Cord Injury Exam (I-A-ISNCSCI): a pilot study.

STUDY DESIGN: Prospective, single-blinded study. OBJECTIVE: To design and evaluate the use of an interview based version of the anorectal portion of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) exam in the acute inpatient rehabilitation (AIR) setting. SETTING: AIR unit. METHODS: Participants admitted to AIR underwent standard ISNCSCI exams (S-ISNCSCI) as part of routine inpatient care within 3 days of being administered an interview version of the anorectal portion of the ISNCSCI (I-A-ISNCSCI). Agreement between the anorectal portion of the S-ISNCSCI (S-A-ISNCSCI) and the I-A-ISNCSCI was evaluated. RESULTS: Forty of forty-five enrolled participants completed the assessments. Agreement between the I-A-ISNCSCI and S-A-ISNCSCI was substantial for anorectal sensation to light touch (k = 0.71, 95% CI 0.52-0.90, N = 36), pin prick (k = 0.68, 95% CI 0.48-0.87, N = 38), deep anal pressure (k = 0.77, 95% CI 0.53-1.00, N = 37), and completeness of injury based on combined sacral sensory criteria (k = 0.72, 95% CI 0.47-0.97, N = 40); and fair for voluntary anal contraction (k = 0.29, 95% CI -0.01 to 0.59, N = 36). Responses of "I don't know" were excluded from agreement analyses. CONCLUSIONS: This pilot study was a first step in developing interview based tools such as the I-A-ISNCSCI in an AIR setting providing convenient access to individuals with SCI and their direct feedback. The study design introduces potential recall bias and may not match true clinical situations such as remote follow-up of neurological changes for chronic patients. The use of interview based tools for assessing individuals with SCI remains worthy of further study.

Safety and feasibility of exoskeleton-assisted walking during acute/sub-acute SCI in an inpatient rehabilitation facility: A single-group preliminary study.

Context/objective: Information on the safety and feasibility of lower extremity powered exoskeletons for persons with acute/sub-acute spinal cord injury (SCI) is limited. Understanding the safety and feasibility of employing powered exoskeletons in acute/sub-acute (<6 months post injury) at a SCI acute inpatient rehabilitation (SCI-AIR) facility could guide clinical practice and provide a basis for larger clinical trials on efficacy and effectiveness. Design: Single group observational study. Setting: SCI-AIR. Participants: Participants (n = 12; age: 28-71 years; 58% AIS D; 58% male) with neurological levels of injuries ranging from C2 to L3. Interventions: Up to 90 min of exoskeleton-assisted locomotor training was provided up to three times per week during SCI-AIR. Outcome measures: Safety of device use during inpatient locomotor training was quantified as the number of adverse events (AE) per device exposure hour. Feasibility of device use was defined in terms of protocol compliance, intensity, and proficiency. Results: Concerning safety, symptomatic hypotension was the most common AE reported at 111-events/exoskeleton-hours. Protocol compliance had a mean (SD) of 54% (30%). For intensity, 77% of participants incorporated variable assistance into at least 1 walking session; 70% of participants' sessions were completed with a higher RPE than the physical therapist. In proficiency, 58% achieved at least minimal assistance when walking with the device. Conclusion: Exoskeleton training in SCI-AIR can be safe and feasible for newly injured individuals with SCI who have clinically defined ambulatory goals. Nonetheless, sufficient controls to minimize risks for AEs, such as hypotensive events, are required.

Pulse article: opioid prescription for pain after spinal cord damage (SCD), differences from recommended guidelines, and a proposed algorithm for the use of opioids for pain after SCD.

Study design: Online questionnaire of spinal cord injury (SCI) physicians. Objectives: The objective of this study is to characterize the approach to opioid prescription for persons with spinal cord damage (SCD). Setting: An international online questionnaire. Methods: A survey was posted online and circulated among international societies within the field of SCI medicine from August to November 2018. Results: One hundred and twenty-three physicians responded to the survey. Of these, 107 (92%) managed pain for persons with SCD. Most (82%) felt that opioid prescription was appropriate for uncontrolled acute pain, but fewer (67%) felt it was appropriate for chronic pain. Of those who felt opioids had a role in the treatment of neuropathic pain, 46% did not think there should be a specific upper limit of opioid dose. The majority (85%) would continue prescribing high doses (250 morphine milligram equivalent (MME) doses/day) if that dose were effective. Tramadol was the most common opioid prescribed first line. Conclusion: Most physicians who responded to this survey prescribe opioids for intractable pain after SCD. A significant proportion of respondents believed that there should not be a specific upper limit of opioid dose prescribed if the drug is tolerated; this does not align with current recommendations. Most physicians do not feel influenced in their prescribing habits by regulatory bodies. If physicians decide to taper an opioid that is being tolerated well, it is most commonly related to a fear of the patient developing an opioid-use disorder. The authors propose an algorithm that may help align practice patterns with current recommended practice guidelines.

Treatment of at-level spinal cord injury pain with botulinum toxin A.

Study design: Randomized, double-blinded, placebo-controlled, cross-over study. Objective: To explore whether botulinum toxin A (BoNTA) could be effective for treating at-level spinal cord injury (SCI) pain. Setting: Outpatient SCI clinic, New York, USA. Methods: Participants were randomized to receive subcutaneous injections of either placebo or BoNTA with follow-up (office visit, telephone, or e-mail) at 2, 4, 8, and 12 weeks to assess the magnitude of pain relief post injection. Crossover of participants was then performed. Those who received placebo received BoNTA, and vice versa, with follow-up at 2, 4, 8, and 12 weeks. Results: Eight participants completed at least one of the two crossover study arms. Four completed both arms. The median age of the eight participants was 45 years (range 32-61 years) and 75% were male. All had traumatic, T1-L3 level, complete SCI. Although our data did not meet statistical significance, we noted a higher proportion of participants reporting a marked change in average pain intensity from baseline to 8 and 12 weeks post-BoNTA vs. post-placebo (33% vs. 0%). At 2 and 4 weeks post-BoNTA, almost all participants reported some degree of reduced pain, while the same was not seen post-placebo (83% vs. 0%). Conclusion: The subcutaneous injection of BoNTA may be a feasible approach for the control of at-level SCI pain and is worthy of further study. Sponsorship: The onabotulinumtoxinA (BOTOX) used in this study was provided by Allergan (Irvine, CA).

The value of novel immuno-oncology treatments.

OBJECTIVES: To assess the value to society of improved survival from novel immuno-oncology (I-O) treatments. STUDY DESIGN: Case studies of ipilimumab for the treatment of advanced unresectable melanoma and nivolumab for advanced previously treated squamous non-small cell lung cancer (NSCLC). METHODS: Published data and survival analysis were used to estimate survival gains. We valued the gains using an economic model developed for application to discrete changes in life expectancy. We estimated aggregate utilization and value to society using cancer registry data and literature. We assessed the share of social value that flowed to the pharmaceutical manufacturer as sales revenue based on publicly available prices. RESULTS: For advanced melanoma, our analysis estimated an average real-world life expectancy (discounted at a 3% rate) of 32.4 months with ipilimumab versus 14.2 months with an existing standard of care. Treatment of advanced NSCLC with nivolumab generated a life expectancy of 28.1 months versus 14.3 months with an existing standard of care. Depending on model assumptions, the value of these survival gains ranged from $232,000 to $697,000 for a patient with melanoma and from $180,000 to $586,000 for one with NSCLC. Using a midpoint value to aggregate across treated patients over a 5-year window, the total value to society was estimated at $1.9 billion for ipilimumab in advanced melanoma and $1.7 billion for nivolumab in NSCLC. Less than 30% of the total value flowed to the pharmaceutical manufacturer in the form of profit. CONCLUSIONS: The novel I-O treatments studied here generate substantial survival gains and, thus, social value. Less than half of this value accrued to the pharmaceutical manufacturer as sales revenue.

Robotic Rehabilitation and Spinal Cord Injury: a Narrative Review.

Mobility after spinal cord injury (SCI) is among the top goals of recovery and improvement in quality of life. Those with tetraplegia rank hand function as the most important area of recovery in their lives, and those with paraplegia, walking. Without hand function, emphasis in rehabilitation is placed on accessing one's environment through technology. However, there is still much reliance on caretakers for many activities of daily living. For those with paraplegia, if incomplete, orthoses exist to augment walking function, but they require a significant amount of baseline strength and significant energy expenditure to use. Options for those with motor complete paraplegia have traditionally been limited to the wheelchair. While wheelchairs provide a modified level of independence, wheelchair users continue to face difficulties in access and mobility. In the past decade, research in SCI rehabilitation has expanded to include external motorized or robotic devices that initiate or augment movement. These robotic devices are used with 2 goals: to enhance recovery through repetitive, functional movement and increased neural plasticity and to act as a mobility aid beyond orthoses and wheelchairs. In addition, lower extremity exoskeletons have been shown to provide benefits to the secondary medical conditions after SCI such as pain, spasticity, decreased bone density, and neurogenic bowel. In this review, we discuss advances in robot-guided rehabilitation after SCI for the upper and lower extremities, as well as potential adjuncts to robotics.

Poorer outcomes among cancer patients diagnosed with Clostridium difficile infections in United States community hospitals.

BACKGROUND: Cancer predisposes patients to Clostridium difficile infection (CDI) due to health care exposures and medications that disrupt the gut microbiota or reduce immune response. Despite this association, the national rate of CDI among cancer patients is unknown. Furthermore, it is unclear how CDI affects clinical outcomes in cancer. The objective of this study was to describe CDI incidence and health outcomes nationally among cancer patients in the United States (U.S.). METHODS: Data for this study were obtained from the U.S. National Hospital Discharge Surveys from 2001 to 2010. Eligible patients included those at least 18 years old with a discharge diagnosis of cancer (ICD-9-CM codes 140-165.X, 170-176.X, 179-189.X, 190-209.XX). CDI was identified using ICD-9-CM code 008.45. Data weights were applied to sampled patients to provide national estimates. CDI incidence was calculated as CDI discharges per 1000 total cancer discharges. The in-hospital mortality rate and hospital length of stay (LOS) were compared between cancer patients with and without CDI using bivariable analyses. RESULTS: A total of 30,244,426 cancer discharges were included for analysis. The overall incidence of CDI was 8.6 per 1000 cancer discharges. CDI incidence increased over the study period, peaking in 2008 (17.2 per 1000 cancer discharges). Compared to patients without CDI, patients with CDI had significantly higher mortality (9.4% vs. 7.5%, p < 0.0001) and longer median LOS (9 days vs. 4 days, p < 0.0001). CONCLUSIONS: CDI incidence is increasing nationally among cancer patients admitted to U.S. community hospitals. CDI was associated with significantly increased mortality and hospital LOS.

Feasibility and Safety of a Powered Exoskeleton for Assisted Walking for Persons With Multiple Sclerosis: A Single-Group Preliminary Study.

OBJECTIVE: To examine the feasibility, safety, and secondary benefit potential of exoskeleton-assisted walking with one device for persons with multiple sclerosis (MS). DESIGN: Single-group longitudinal preliminary study with 8-week baseline, 8-week intervention, and 4-week follow-up. SETTING: Outpatient MS clinic, tertiary care hospital. PARTICIPANTS: Participants (N=13; age range, 38-62y) were mostly women with Expanded Disability Status Scale scores ranging from 5.5 to 7.0. INTERVENTION: Exoskeleton-assisted walk training. MAIN OUTCOME MEASURES: Primary outcomes were accessibility (enrollment/screen pass), tolerability (completion/dropout), learnability (time to event for standing, walking, and sitting with little or no assistance), acceptability (satisfaction on the device subscale of the Quebec User Evaluation of Satisfaction with Assistive Technology version 2), and safety (event rates standardized to person-time exposure in the powered exoskeleton). Secondary outcomes were walking without the device (timed 25-foot walk test and 6-minute walk test distance), spasticity (Modified Ashworth Scale), and health-related quality of life (Patient-Reported Outcomes Measurement and Information System pain interference and Quality of Life in Neurological Conditions fatigue, sleep disturbance, depression, and positive affect and well-being). RESULTS: The device was accessible to 11 and tolerated by 5 participants. Learnability was moderate, with 5 to 15 sessions required to walk with minimal assistance. Safety was good; the highest adverse event rate was for skin issues at 151 per 1000 hours' exposure. Acceptability ranged from not very satisfied to very satisfied. Participants who walked routinely improved qualitatively on sitting, standing, or walking posture. Two participants improved and 2 worsened on ≥1 quality of life domain. The pattern of spasticity scores may indicate potential benefit. CONCLUSIONS: The device appeared feasible and safe for about a third of our sample, for whom routine exoskeleton-assisted walking may offer secondary benefits.

Clostridium difficile infection health disparities by race among hospitalized adults in the United States, 2001 to 2010.

BACKGROUND: Recognition of health disparities in Clostridium difficile infection (CDI) is an initial step toward improved resource utilization and patient health. The purpose of this study was to identify health disparities by black vs. white race among hospitalized adults with CDI in the United States (U.S.) over 10 years. METHODS: This was a retrospective analysis of the U.S. National Hospital Discharge Surveys from 2001 to 2010. Eligible cases included adults with an ICD-9-CM code for CDI (008.45). Patients with missing race or "other race" were excluded. The primary outcome, CDI incidence, was calculated as CDI discharges per 1,000 total discharges. Data weights were used to determine national estimates. Secondary outcomes included in-hospital mortality, hospital length of stay (LOS), and severe CDI. Comparisons were made using bivariable analyses. Race was assessed as an independent risk factor for CDI outcomes using logistic regression or proportional hazards models. RESULTS: These data represent 1.7 million CDI discharges, where 90 % of patients were identified as white and 10 % black. Blacks differed from whites with respect to all baseline characteristics (p <0.0001). CDI incidence was significantly higher in whites compared to blacks (7.7/1,000 discharges vs. 4.9/1,000 discharges, p < 0.0001). Blacks had higher mortality (7.4 % vs. 7.2 %, p < 0.0001), LOS >7 days (57 % vs. 52 %, p < 0.0001), and severe CDI (24 % vs. 19 %, p < 0.0001). In multivariable analyses, black race was a positive predictor of mortality (OR 1.12, 95 % CI 1.09-1.15) and severe CDI (OR 1.09, 95 % CI 1.07-1.11), and negative predictor for hospital LOS (OR 0.93, 95 % CI 0.93-0.94). CONCLUSIONS: CDI incidence was higher for white patients; however, black race was independently associated with mortality and severe CDI.