Janice Weinberg

Yoga, Physical Therapy, or Education for Chronic Low Back Pain: A Randomized Noninferiority Trial

Low back pain is the leading cause of disability globally (1). Total annual back painrelated costs in the United States exceed

Hospital Variation in Utilization of Life-Sustaining Treatments among Patients with Do Not Resuscitate Orders

200 billion (2). Chronic low back pain (cLBP) affects approximately 10% of U.S. adults (3), but overall patient satisfaction with cLBP treatment is low (4). The impact of cLBP is greater in racial or ethnic minorities and in people of lower socioeconomic status (SES) (5). Physical therapy (PT), comprising individually tailored stretching and strengthening exercises, is the most common evidence-based, reimbursable, and nonpharmacologic physician referral for cLBP (6, 7). Clinical guidelines (8, 9), meta-analyses (10), and several large randomized controlled trials (1113) also support yoga, a practice including physical poses, breathing exercises, and meditation, as an effective cLBP treatment. To improve cLBP care, physicians, patients, and payers need to know how novel therapies like yoga compare with established treatments like PT. Noninferiority trials determine whether a new therapy is statistically as effective as an accepted treatment (14). This is particularly useful when the new therapy may have other potential benefits, such as lower cost. The U.S. Food and Drug Administration uses noninferiority as one criterion for approving new pharmaceuticals (15). Although no criteria have been established for when a new nonpharmacologic therapy should be integrated into mainstream clinical practice, demonstrating noninferiority to effective, reimbursed, and nonpharmacologic treatments is one reasonable requirement. Thus, we conducted a randomized controlled comparative effectiveness trial testing whether yoga was noninferior to PT in adults with cLBP. Methods Design Overview The study protocol (16) and treatment manuals (1720) were published previously. We conducted a 52-week, assessor-blinded randomized trial of yoga, PT, and education (a self-care book and newsletters) for adults with nonspecific cLBP. The study was advertised as a comparison of 3 credible cLBP treatments. All participants had access to usual medical care. The study consisted of a 12-week treatment phase and 40-week maintenance phase. The primary hypothesis was that yoga is noninferior to PT in the treatment phase for improving both back-related function and pain intensity. The secondary hypothesis was that both yoga and PT are superior to education for improving function and pain. The maintenance phase compared the effectiveness of different strategies for ongoing yoga and PT. Yoga participants who completed 1 or more yoga classes in the treatment phase were randomly assigned at 12 weeks to yoga drop-in classes or home practice. Physical therapy patients who completed 1 or more PT appointments in the treatment phase were randomly assigned to PT booster sessions or home practice. We hypothesized that at 52 weeks, yoga drop-in classes are superior to yoga home practice and PT booster sessions are superior to PT home practice. Participants were recruited from June 2012 to November 2013. Follow-up was completed in November 2014. The original research protocol and a summary of protocol changes are in Supplement 1. Supplement 1. Detailed Study Protocol Setting and Participants The study was done at a large academic safety-net hospital and 7 affiliated, federally qualified community health centers located in diverse neighborhoods. Staff doing data collection, entry, and analysis were masked to treatment assignment. The Boston University Institutional Review Board approved the study before data collection. We enrolled English-speaking adults aged 18 to 64 years who reported nonspecific low back pain lasting at least 12 weeks with an average pain intensity in the previous week of 4 or greater on an 11-point (0 to 10) numerical rating scale. Persons with specific causes of cLBP (for example, spinal stenosis) were excluded. Eligibility criteria are in Table 1 of Supplement 2. Recruitment strategies included clinician referrals, mailing letters to patients with cLBP who were identified through electronic health records, and distributing flyers in clinics and surrounding neighborhoods. Supplement 2. Data Supplement Randomization and Interventions After initial telephone screening, staff confirmed eligibility and obtained written informed consent during in-person meetings. Staff entered participants into StudyTRAX (ScienceTrax), a data management platform. StudyTRAX generated a randomization sequence using permuted block randomization with varying block sizes and a 2:2:1 ratio of yoga, PT, and education. After participants completed baseline surveys, unmasked staff informed them of their treatment assignments. Enrollment and randomization proceeded in 4 sequential cohorts of approximately 80 participants each. Yoga participants who attended at least 1 class in the treatment phase continued into the maintenance phase and were randomly assigned to weekly drop-in yoga classes or home practice only. Physical therapy participants with at least 1 PT visit in the treatment phase were randomly assigned to attend 5 booster sessions or home practice only during the maintenance phase. Education participants continued into the maintenance phase without additional randomization. A manualized yoga protocol (18) of 12 weekly 75-minute classes was adapted from previous studies in similar populations (21, 22) with input from expert yoga instructors, investigators, and former study participants (Table 2 of Supplement 2). Thirteen yoga instructors completed 8 hours of training and taught classes at 6 sites. Instructor assignments ensured a participantinstructor ratio of less than 5:1. Each class began with relaxation and meditation exercises, yoga breathing, and yoga philosophy. It continued with yoga poses and concluded with relaxation. Pose variations and aids (such as chair, strap, and blocks) accommodated various abilities. Thirty minutes of daily home practice, facilitated by a DVD, a manual, and take-home yoga supplies, was strongly encouraged. Participants recorded time spent practicing. Staff observed approximately 10% of classes to assess protocol fidelity by using a checklist. Maintenance phase classes were similarly structured except for a higher participantinstructor ratio (approximately 8:1). The manualized PT protocol (Figure 1 and Table 3 of Supplement 2) incorporated treatment-based classification (23, 24), graded exercise (25), and screening for fear-avoidance beliefs (26). Eight physical therapists delivered the intervention in 1 hospital-based and 2 community-based PT clinics. Physical therapists completed 8 hours of in-person training and Web-based modules (27). Participants were advised to attend fifteen 60-minute appointments over 12 weeks. Appointments included one-on-one work with the therapist and supervised aerobic exercise. All participants completed the Fear-Avoidance Beliefs Questionnaire (28). For PT participants with a high fear-avoidance score (29 on the work subscale), therapists provided The Back Book (29) and reinforced its psychologically informed principles to lower fear avoidance. Participants received written instructions and supplies for home practice and logged the number of exercises completed daily. Staff assessed protocol fidelity by reviewing therapists treatment flowsheets. Participants randomly assigned to booster sessions during the maintenance phase were advised to see the therapist at 4, 6, 8, 10, and 12 months. Education participants received The Back Pain Helpbook (30), which includes information on cLBP self-management, stretching, strengthening, and the role of emotions and fear avoidance. Previous cLBP trials (11, 12, 31) used this book as a credible control intervention. We provided a recommended reading schedule (Table 4 of Supplement 2). Every 3 weeks, participants received a 1- to 2-page newsletter (32), summarizing main points from assigned chapters, and a 5- to 10-minute check-in call from staff. In the maintenance phase, we made brief check-in calls every 6 weeks to encourage continued review of the book. Outcomes and Follow-up Coprimary outcomes were change from baseline to 12 weeks in scores on the modified Roland Morris Disability Questionnaire (RMDQ), a 23-point measure of back-related function with higher scores indicating worse function (33), and in pain (using an 11-point numerical rating scale for average intensity in the previous week, where 0 indicated no pain and 10 indicated worst pain possible) (34). Secondary outcomes included self-reported pain medication use in the previous week (yes or no), global improvement (7-point scale from extremely worsened to extremely improved), patient satisfaction with interventions (5-point scale from very dissatisfied to very satisfied) (35), and health-related quality of life (Short Form-36 Health Survey) (36). We collected data on work productivity, a secondary outcome, and will report them separately in a cost-effectiveness analysis. We also plan to report data on other exploratory measures collected (such as fear-avoidance beliefs, pain self-efficacy, depression, anxiety, and sleep) separately. Attendance at all yoga and PT sessions was recorded. Participants attending at least 9 yoga or 11 PT sessions (75% or 73% of sessions, respectively) were defined as adherent a priori. Education participants were asked how much of the book they had read. Those reporting having read at least 75% were defined as adherent a priori. After baseline data collection, study staff that was blinded to treatment assignment collected paper surveys completed at 6, 12, 26, 40, and 52 weeks. Adverse events were elicited directly from participants and in surveys. Participants received

Diagnostic Comparison of CT Scans and Colonoscopy for Immune-Related Colitis in Ipilimumab-Treated Advanced Melanoma Patients

100 gift cards after completing surveys at 12 and 52 weeks and

Active cocaine use does not increase the likelihood of hyperglycemic crisis

50 gift cards after the baseline questionnaire and surveys at 6, 26, and 40 weeks. Statistical Analysis The study was designed and powered to detect if yoga was noninferior to PT at 12 weeks for both primary outcomes. NBackgroundnYoga is effective for mild to moderate chronic low back pain (cLBP), but its comparative effectiveness with physical therapy (PT) is unknown. Moreover, little is known about yogas effectiveness in underserved patients with more severe functional disability and pain.nnnObjectivenTo determine whether yoga is noninferior to PT for cLBP.nnnDesignn12-week, single-blind, 3-group randomized noninferiority trial and subsequent 40-week maintenance phase. (ClinicalTrials.gov: NCT01343927).nnnSettingnAcademic safety-net hospital and 7 affiliated community health centers.nnnParticipantsn320 predominantly low-income, racially diverse adults with nonspecific cLBP.nnnInterventionnParticipants received 12 weekly yoga classes, 15 PT visits, or an educational book and newsletters. The maintenance phase compared yoga drop-in classes versus home practice and PT booster sessions versus home practice.nnnMeasurementsnPrimary outcomes were back-related function, measured by the Roland Morris Disability Questionnaire (RMDQ), and pain, measured by an 11-point scale, at 12 weeks. Prespecified noninferiority margins were 1.5 (RMDQ) and 1.0 (pain). Secondary outcomes included pain medication use, global improvement, satisfaction with intervention, and health-related quality of life.nnnResultsnOne-sided 95% lower confidence limits were 0.83 (RMDQ) and 0.97 (pain), demonstrating noninferiority of yoga to PT. However, yoga was not superior to education for either outcome. Yoga and PT were similar for most secondary outcomes. Yoga and PT participants were 21 and 22 percentage points less likely, respectively, than education participants to use pain medication at 12 weeks. Improvements in yoga and PT groups were maintained at 1 year with no differences between maintenance strategies. Frequency of adverse events, mostly mild self-limited joint and back pain, did not differ between the yoga and PT groups.nnnLimitationsnParticipants were not blinded to treatment assignment. The PT group had disproportionate loss to follow-up.nnnConclusionnA manualized yoga program for nonspecific cLBP was noninferior to PT for function and pain.nnnPrimary Funding SourcenNational Center for Complementary and Integrative Health of the National Institutes of Health.

Racial differences in colorectal cancer survival at a safety net hospital

OBJECTIVEnTo determine between-hospital variation in interventions provided to patients with do not resuscitate (DNR) orders.nnnDATA SOURCES/SETTINGnUnited States Agency of Healthcare Research and Quality, Healthcare Cost and Utilization Project, California State Inpatient Database.nnnSTUDY DESIGNnRetrospective cohort study including hospitalized patients aged 40 and older with potential indications for invasive treatments: in-hospital cardiac arrest (indication for CPR), acute respiratory failure (mechanical ventilation), acute renal failure (hemodialysis), septic shock (central venous catheterization), and palliative care. Hierarchical logistic regression to determine associations of hospital early DNR rates (DNR order placed within 24xa0hours of admission) with utilization of invasive interventions.nnnDATA COLLECTION/EXTRACTION METHODSnCalifornia State Inpatient Database, year 2011.nnnPRINCIPAL FINDINGSnPatients with DNR orders at high-DNR-rate hospitals were less likely to receive invasive mechanical ventilation for acute respiratory failure or hemodialysis for acute renal failure, but more likely to receive palliative care than DNR patients at low-DNR-rate hospitals. Patients without DNR orders experienced similar rates of invasive interventions regardless of hospital DNR rates.nnnCONCLUSIONSnHospitals vary widely in the scope of invasive or organ-supporting treatments provided to patients with DNR orders.

Antibody Response to Hepatitis B Virus Vaccine is Impaired in Patients With Inflammatory Bowel Disease on Infliximab Therapy

Checkpoint blockade is becoming more widespread, so the timely and accurate diagnosis of immune-related colitis is increasingly important. By comparing diagnoses with colonoscopy data, CT scans were a fast, accurate, and non invasive mode of diagnosing ipilimumab-induced immune-related colitis. Colitis can be a life-threatening toxicity for patients treated with immune checkpoint blockade antibodies. With the anticipated widespread use of these reagents, the timely and accurate diagnosis of immune-related colitis becomes increasingly important. To better understand the clinical presentation of colitis from ipilimumab and to assess the use of CT scans of the abdomen/pelvis as a diagnostic tool, we retrospectively analyzed patients with advanced melanoma who received ipilimumab at our institution. Ninety nine (33%) of 303 patients developed diarrhea during therapy, and 46 patients (15%) received corticosteroids for colitis. Of the patients with diarrhea, 48 (48%) underwent colonoscopy and 46 (46%) underwent both CT and colonoscopy. In the 34 patients (34%) with a CT and biopsy, CT was highly predictive of colitis on biopsy (positive predictive value 96%), and the absence of CT findings was predictive of a negative biopsy (negative likelihood ratio 0.2). In patients who had symptoms and CT evaluation, CT was highly predictive of the need for steroids to reach resolution of symptoms (positive predictive value 92%, positive likelihood ratio 7.3). We conclude that CT is a fast, reliable, and noninvasive mode of diagnosing colitis, whereas colonoscopy and biopsy may not be needed to establish that diagnosis. Cancer Immunol Res; 5(4); 286–91. ©2017 AACR.

The Impact of Clostridium difficile Infection on Future Outcomes of Solid Organ Transplant Recipients

Objective Hyperglycemic crisis encompasses a group of diabetes emergencies characterized by insulin deficiency with high morbidity and mortality. Cocaine use is increasingly prevalent in the United States and may be associated with increased risk of diabetic ketoacidosis. The objective was to determine if active cocaine use at hospital admission could be considered a risk factor for development of hyperglycemic crisis. Methods A retrospective case-control analysis was performed on 950 inpatients with hyperglycemia at an urban academic hospital. Patients admitted with non-emergent hyperglycemia were compared to patients who met criteria for diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), and hyperosmolar ketoacidosis (HK), based on the absence or presence of cocaine metabolites on urine toxicology screen. Outcomes included frequency of cocaine use in patients with DKA, HHS, HK, and non-emergent hyperglycemia; phenotypic characteristics of cocaine users vs. non-users with hyperglycemia; phenotypic characteristics of patients with hyperglycemic crisis vs. non-emergent hyperglycemia. Results 950 patients were admitted with hyperglycemia, 133 of which met criteria for hyperglycemic crisis. There was no significant difference in the frequency of cocaine use in individuals with non-emergent hyperglycemia compared to individuals with hyperglycemic crisis (16.9% vs. 17.2%, p = 0.90). 16.9% of patients with DKA, 16.4% of patients with HHS, and 6.4% of patients with HK were cocaine users. Conclusions We found no association between active cocaine use at the time of hospital admission and development of hyperglycemic crisis, when compared to non-emergent hyperglycemia. The role of routine screening for cocaine use in patients with hyperglycemic crisis is unclear.

A comparison of alcohol positive and alcohol negative trauma patients requiring an emergency laparotomy

BACKGROUNDnWhile racial disparity in colorectal cancer survival have previously been studied, whether this disparity exists in patients with metastatic colorectal cancer receiving care at safety net hospitals (and therefore of similar socioeconomic status) is poorly understood.nnnMETHODSnWe examined racial differences in survival in a cohort of patients with stage IV colorectal cancer treated at the largest safety net hospital in the New England region, which serves a population with a majority (65%) of non-Caucasian patients. Data was extracted from the hospitals electronic medical record. Survival differences among different racial and ethnic groups were examined graphically using Kaplan-Meier analysis. A univariate cox proportional hazards model and a multivariable adjusted model were generated.nnnRESULTSnBlack patients had significantly lower overall survival compared to White patients, with median overall survival of 1.9 years and 2.5 years respectively. In a multivariate analysis, Black race posed a significant hazard (HR 1.70, CI 1.01-2.90, p=0.0467) for death. Though response to therapy emerged as a strong predictor of survival (HR=0.4, CI=0.2-0.7, p=0.0021), it was comparable between Blacks and Whites.nnnCONCLUSIONSnDespite presumed equal access to healthcare and socioeconomic status within a safety-net hospital system, our results reinforce findings from previous studies showing lower colorectal cancer survival in Black patients, and also point to the importance of investigating other factors such as genetic and pathologic differences.

Positive and negative affect following marijuana use in naturalistic settings: An ecological momentary assessment study

BackgroundnStudies have demonstrated an association between anti-TNF/immunomodulator agents used in inflammatory bowel disease (IBD) and impaired hepatitis B virus (HBV) vaccine immunogenicity, but little data exist on whether specific medication types affect protective HBsAb titers. Our aim was to analyze this association.nnnMethodsnThis is a retrospective cohort study. Inclusion criteria: age ≥18, diagnosis of Crohns disease (CD) or ulcerative colitis (UC), previous HBV vaccination series and/or ≥1 positive HBsAb, and record of IBD therapy in 6 months before titer level. Patients were stratified based upon medication exposures: anti-TNF, immunomodulator, combination anti-TNF and immunomodulatory, and a reference arm. Titer levels following vaccination and specific medication types given in the 6 months before titer were recorded. Seroprotection was defined as HBsAb ≥10 IU/l and ≥100 IU/l.nnnResultsnThe study cohort (N = 391) was 70.8% white, 51.4% female and 64.2% had CD and 35.8% had UC. The mean age was 45.8 years. A significantly lower percentage of patients exposed to anti-TNF, immunomodulator or dual therapy had titers ≥10 (P < 0.01). Regarding specific medications, only patients exposed to infliximab (P < 0.01) were less likely to have titer levels ≥10, after controlling for other medication exposures, age at titer level, and interval time between vaccination/titer level. This was not found for patients exposed to adalimumab, methotrexate, 6-mercaptopurine, or azathioprine.nnnConclusionsnPatients exposed to infliximab were significantly less likely to have protective HBsAb titer levels following vaccination, a trend not seen in patients on adalimumab. Efforts to vaccinate IBD patients against HBV before use of immunomodulators and anti-TNFs, infliximab specifically, and screen periodically thereafter must be reinforced.

Yoga, Physical Therapy, or Education for Chronic Low Back Pain

OBJECTIVEClostridium difficile infection (CDI) is common in solid organ transplant (SOT) recipients, but few studies have examined long-term outcomes. We studied the impact of CDI after SOT on mortality and transplant organ complication-related hospitalizations (TOH).METHODSSOT recipients ≥18 years of age with at least 1 year of posttransplant data were analyzed using the MarketScan database for 2007-2014. Patients who died within one year of transplant were followed until death. Patients were grouped as early CDI (ie, first occurrence ≤90 days posttransplant), late CDI (ie, first occurrence >90 days posttransplant) and controls (ie, no CDI occurrence during follow-up). The risk of mortality or TOH after CDI was evaluated using Cox and logistic regressions, respectively.RESULTSOverall, 96 patients had early CDI, 97 patients had late CDI, and 5,913 patients were used as controls. The risk for death was significantly higher in the early CDI group than the control group (hazard ratio [HR],1.92; 95% confidence interval [CI], 1.12-3.29; P=.018); there was no significant difference between the late CDI group and the control group (HR, 0.86; 95% CI, 0.38-1.94; P=.717). Both the early CDI group (odds ratio [OR], 2.19; 95% CI, 1.45-3.31; P90 days posttransplant, both the early CDI group (n=89) and the late CDI group (n=97) had increased risk for death or TOH during follow-up than the control group (n=5,734).CONCLUSIONThough our study could not prove causality, both early and late CDI occurrence in SOT recipients were associated with worse future outcomes than for SOT recipients without CDI.Infect Control Hosp Epidemiol 2018;39:563-570.