Mortality with concurrent treatment with gabapentin and opioids among people with spine diagnoses in the U.S. Medicare population: a propensity-matched cohort study.

IMPORTANCE: Given the negative impact of opioid use on population health, prescriptions for alternative pain-relieving medications, including gabapentin, have increased. Concurrent gabapentin and opioid prescriptions are commonly reported in retrospective studies of opioid-related overdose deaths. OBJECTIVE: To determine whether people who filled gabapentin and opioid prescriptions concurrently ('gabapentin + opioids') had greater mortality than those who filled an active control medication (tricyclic antidepressants [TCAs] or duloxetine) and opioids concurrently ('TCAs/duloxetine + opioids'). We hypothesized that people treated with gabapentin + opioids would have higher mortality rates compared to people treated with TCAs/duloxetine + opioids. DESIGN: Propensity score-matched cohort study with an incident user, active control design. The median (maximum) follow-up was 45 (1093) days. SETTING: Population-based. PARTICIPANTS: Medicare beneficiaries with spine-related diagnoses 2017-2019. The primary analysis included those who concurrently (within 30 days) filled at least 1 incident gabapentin + at least 1 opioid or at least 1 incident TCA/duloxetine + at least 1 opioid. EXPOSURES: People treated with gabapentin + opioids (n=67,133) were matched on demographic and clinical factors in a 1:1 ratio to people treated with TCAs/duloxetine + opioids (n=67,133). MAIN OUTCOMES AND MEASURES: The primary outcome was mortality at any time. A secondary outcome was occurrence of a major medical complication at any time. RESULTS: Among 134,266 participants (median age 73.4 years; 66.7% female), 2360 died before the end of follow-up. No difference in mortality was observed between groups (adjusted hazard ratio (HR) and 95% confidence interval (CI) for gabapentin + opioids was 0.98 (0.90, 1.06); p=0.63). However, people treated with gabapentin + opioids were at slightly increased risk of a major medical complication (1.02 (1.00, 1.04); p=0.03) compared to those treated with TCAs/duloxetine + opioids. Results were similar in analyses (a) restricted to less than or = 30-day follow-up and (b) that required at least 2 fills of each prescription. CONCLUSIONS AND RELEVANCE: When treating pain in older adults taking opioids, the addition of gabapentin did not increase mortality risk relative to addition of TCAs or duloxetine. However, providers should be cognizant of a small increased risk of major medical complications among opioid users initiating gabapentin compared to those initiating TCAs or duloxetine.

Digital musculoskeletal program is associated with decreased joint replacement rates.

OBJECTIVES: To compare 12-month total knee arthroplasty (TKA) and total hip arthroplasty (THA) rates for digital musculoskeletal (MSK) program members vs patients who received traditional care for knee or hip osteoarthritis (OA). STUDY DESIGN: Retrospective, longitudinal study with propensity score-matched comparison group that used commercial medical claims data representing more than 100 million commercially insured lives. METHODS: Study participants with hip OA (M16.x) or knee OA (M17.x) International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes were identified in the medical claims database. Digital MSK program members were identified using record linkage tokens. The comparison group had hip- or knee-related physical therapy identified via ICD-10-CM and Current Procedural Terminology codes. Respectively in each knee and hip OA group, digital members were matched to control group patients with similar demographics, comorbidities, and baseline MSK-related medical care use. TKA and THA at 12 months post participation were compared. RESULTS: In the knee OA group, 739 of 56,634 control group patients were matched to 739 digital members. At 12 months, 3.79% of digital members and 14.21% of control group patients had TKA (difference, 10.42%; P < .001). In the hip OA group, 141 of 20,819 control group patients were matched to 141 digital members. At 12 months, 16.31% of digital members and 32.62% of control group patients had THA (difference, 16.31%; P = .001). CONCLUSIONS: These findings suggest that patients who participated in a digital MSK program to manage OA have lower rates of total joint arthroplasty in the 12 months after enrollment.

The cost of simplifying treatments for cystic fibrosis: Implications of the SIMPLIFY trial.

BACKGROUND: Dornase alfa and hypertonic saline are mucoactive therapies that can improve respiratory symptoms in people with cystic fibrosis (CF). A recent randomized control trial showed that participants with well-preserved pulmonary function taking elexacaftor + tezacaftor + ivacaftor (ETI) who discontinued dornase alfa or hypertonic saline for 6 weeks had no clinically meaningful decline in lung function. This may prompt discussions with care providers regarding ongoing use of these medications. OBJECTIVE: To compare the costs of outpatient medications between people taking ETI who continued or discontinued (1) dornase alfa or (2) hypertonic saline from 2 clinical trials and project cost differences in the US CF population if these 2 medications were used only intermittently for symptom relief instead of chronically. METHODS: The SIMPLIFY study was 2 parallel multicenter trials that randomized participants 1:1 to either continue or discontinue therapy. To estimate costs, we used data from the Merative MarketScan Databases to identify people with CF from 2020 to 2021. Our primary outcomes were differences in costs of outpatient prescription drugs among those who continued vs discontinued dornase alfa and, separately, hypertonic saline. We obtained adjusted differences in median costs. To estimate the annual cost savings if the population of people with CF taking ETI used these medications only intermittently, we multiplied the proportion of people in MarketScan with CF diagnoses who were taking each of these medications by the median cost savings per year and subtracted the cost of "rescue" use. RESULTS: A total of 392 participants from the dornase alfa trial and 273 from the hypertonic saline trial were included in analyses. The adjusted difference in median medication costs was not significant for the hypertonic saline trial, but we observed a significantly decreased 6-week cost of medications in the dornase alfa trial (adjusted median difference in costs between discontinue and continue of $5,860 (95% CI = $4,870-$6,850); P < 0.0001). We estimated that two-thirds of people with CF use ETI and dornase alfa in the United States; if they discontinued dornase alfa except for intermittent use, the resulting annual savings would be $1.21 billion. CONCLUSIONS: Although the costs of dornase alfa and hypertonic saline are smaller compared with ETI, reduction in use would lead to substantial prescription drug cost savings and reduce the treatment burden. However, individual benefits of these therapies should be considered, and decisions regarding changes in therapy remain an important discussion between people with CF and their providers. Study registration number: NCT04378153.

Frailty and Risk of Serious Infections in Patients With Rheumatoid Arthritis Treated With Biologic or Targeted-Synthetic Disease-Modifying Antirheumatic Drugs.

OBJECTIVE: It remains unknown whether frailty status portends an increased risk of adverse outcomes in patients with rheumatoid arthritis (RA) initiating biologic or targeted-synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs). The objective of our study was to evaluate the association between frailty and serious infections in a younger population of patients (<65 years old) with RA who initiated b/tsDMARDs. METHODS: Using MarketScan data, we identified new users of tumor necrosis factor inhibitors (TNFi), non-TNFi biologic DMARDs, or Janus kinase inhibitors (JAKi) between 2008 and 2019 among those with RA. Patients' baseline frailty risk score was calculated using a Claims-Based Frailty Index (≥0.2 defined as frail) 12 months prior to drug initiation. The primary outcome was time to serious infection; secondarily, we examined time-to-any infection and all-cause hospitalizations. We used Cox proportional hazards to estimate adjusted hazard ratios and 95% confidence intervals (95% CIs) and assessed the significance of interaction terms between frailty status and drug class. RESULTS: A total of 57,980 patients, mean (±SD) age 48.1 ± 10.1 were included; 48,139 (83%) started TNFi, 8,111 (14%) non-TNFi biologics, and 1,730 (3%) JAKi. Among these, 3,560 (6%) were categorized as frail. Frailty was associated with a 50% increased risk of serious infections (adjusted hazard ratio [95% CI] 1.5, 1.2-1.9) and 40% higher risk of inpatient admissions (1.4 [1.3-1.6]) compared with nonfrail patients among those who initiated TNFi. Frailty was also associated with a higher risk of any infection relative to nonfrail patients among those on TNFi (1.2 [1.1-1.3]) or non-TNFi (1.2 [1.0-1.4]) or JAKi (1.4 [1.0-2.0]). CONCLUSION: Frailty is an important predictor for the risk of adverse outcomes among patients with RA treated with biologic or targeted-synthetic DMARDs.

Characteristics associated with cystic fibrosis-related pulmonary exacerbation treatment location.

Previous studies indicate that hospital rather than home treatment of pulmonary exacerbations (PEx) in people with cystic fibrosis (CF) can improve outcomes. We evaluated characteristics of adult participants from the Standardized Treatment of Pulmonary Exacerbations (STOP2) trial with two separate comparisons: (1) those who were treated initially in hospital (N = 768) to those treated initially at home (N = 214) and (2) those treated only in hospital (N = 328) to those who were treated only at home or both at home and in hospital (N = 654). Participants who had Medicaid insurance, were treated for shorter duration, and traveled longer to reach treatment centers were more likely to have been treated initially in the hospital. Having Medicaid insurance, being treated for a shorter duration, and being male were associated with being treated only in the hospital. This analysis suggests decisions about the location of treatment are based on pragmatic factors rather than on clinical characteristics.

Opioid Initiation Within One Year After Starting a Digital Musculoskeletal (MSK) Program: An Observational, Longitudinal Study with Comparison Group.

Background: In-person, conservative care may decrease opioid use for chronic musculoskeletal (MSK) pain, but the impact of digitally delivered conservative care on opioid use is unknown. This study examines associations between a digital MSK program and opioid initiation and prescriptions among opioid naive adults with chronic MSK pain. Methods: This observational study used commercial medical and pharmacy claims data to compare digital MSK program members to matched physical therapy (PT) patients. Outcomes were any opioid prescriptions and opioid prescriptions per 100 participants within the 12-months after starting a digital MSK program. After propensity-score matching, we conducted multivariate regression models that controlled for demographic, comorbidity, and baseline MSK healthcare use. Results: The study included 4195 members and 4195 matched PT patients. For opioid initiation, 7.89% (95% Confidence Interval [CI]: 7.07%, 8.71%) of members had opioid prescriptions within 12 months after starting the digital MSK program versus 13.64% (95% CI: 12.60%, 14.67%) of matched PT patients (p < 0.001). Members had significantly fewer opioid prescriptions (16.73 per 100 participants; 95% CI: 14.11, 19.36) versus PT patients (22.36 per 100 participants; 95% CI: 19.99, 24.73). Members had lower odds (OR: 0.52, 95% CI: 0.45, 0.60) of initiating opioids and significantly fewer prescriptions per 100 participants (beta: -6.40, 95% CI: -9.88, -2.93) versus PT patients after controlling for available confounding factors. Conclusion: An MSK program that delivers conservative care digitally may be a promising approach for decreasing opioid initiation among individuals with chronic MSK pain given the limitations of the observational design and matching on only available covariates.

Exploring risk factors for persistent neurocognitive sequelae after hospitalization for COVID-19.

OBJECTIVE: In this study of patients hospitalized during acute SARS-CoV2 infection with 6-months of follow-up data, we identified risk factors associated with the development of neuro-PASC. METHODS: We conducted an exploratory, observational single-center cohort study of patients hospitalized for COVID-19 from November 2020 to March 2022. Our primary outcome was persistent neurocognitive symptoms, defined as fatigue, headache, loss of taste/smell, brain fog, confusion, concentration/memory/word finding difficulty, and/or change in speech present at 1-month and persisting for 6-months following acute SARS-CoV2 infection. Secondary outcomes included persistent impairment scores on PROMIS cognitive function and abilities scales. Multivariate logistic regression analyses identified potential risk factors for neuro-PASC. RESULTS: Of 89 participants, 60% reported persistent neurocognitive symptoms at 6-months; fatigue was the most prevalent, occurring in 53% of participants, followed by brain fog in 34% of participants. Lower self-reported socioeconomic status and increased pre-COVID-19 anxiety scores on the Hospital Anxiety and Depression Scale were associated with increased odds of developing persistent neurocognitive symptoms. Being female and of Hispanic descent were associated with increased odds of persistent cognitive function and ability impairment. INTERPRETATION: Sociodemographic factors and pre-COVID-19 anxiety symptoms may be important risk factors for neuro-PASC. These findings underscore the need to assess various sociodemographic factors in research on PASC. Our study also highlights premorbid mental health symptoms as a potential predictor of persistent neurocognitive symptoms following hospitalization with SARS-CoV2 infection.

Mortality among older adults with osteoporotic vertebral fracture.

We evaluated whether older adults who received kyphoplasty had reduced risk of mortality compared to those who did not. In unmatched analyses, those receiving kyphoplasty were at reduced risk of death but after matching on age and medical complications, patients who received kyphoplasty were at increased risk of death. PURPOSE: In previous observational studies, kyphoplasty for treatment of osteoporotic vertebral fractures has been associated with decreased mortality compared to conservative management. The purpose of this research was to determine whether older adults who received kyphoplasty had reduced risk of mortality compared to matched patients who did not. METHODS: Retrospective cohort study of US Medicare enrollees with osteoporotic vertebral fractures between 2017-2019 comparing patients who underwent kyphoplasty to those who did not. We identified 2 control groups a priori: 1) non-augmented patients who met inclusion criteria (group 1); 2) propensity-matched patients on demographic and clinical variables (group 2). We then identified additional control groups using matching for medical complications (group 3) and age + comorbidities (group 4). We calculated hazard ratios (HRs) and 95% confidence intervals (95% CIs) associated with mortality. RESULTS: A total of 235,317 patients (mean (± standard deviation) age 81.1 ± 8.3 years; 85.8% female) were analyzed. In the primary analyses, those who received kyphoplasty were at reduced risk of death compared to those who did not: adjusted HR (95% CI) in group 1 = 0.84 (0.82, 0.87); and in group 2 = 0.88 (0.85, 0.91). However, in post hoc analyses, patients who received kyphoplasty were at increased risk of death: adjusted HR (95% CI) in group 3 = 1.32 (1.25, 1.41) and 1.81 (1.58, 2.09) in group 4. CONCLUSION: An apparent benefit of kyphoplasty on mortality among patients with vertebral fractures was not present after rigorous propensity matching, illustrating the importance of comparing similar individuals when evaluating observational data.

Treatment With Opioids Is Not Associated With Poor Outcomes Among Older Adults With Lumbar Spinal Stenosis Receiving Epidural Injections.

STUDY DESIGN: Secondary analysis of a randomized controlled trial. OBJECTIVE: To assess how baseline treatment with opioids is associated with pain and function in older adults with lumbar spinal stenosis who receive epidural injections. SUMMARY OF BACKGROUND DATA: Data were obtained from the Lumbar Epidural Steroid injections for Spinal Stenosis trial, a double-blind, multisite, randomized controlled trial. METHODS: Baseline treatment with opioids was assessed from electronic medical record prescription pharmacy data or from health utilization records collected from patients. We calculated adjusted changes in back pain numerical rating scale, leg pain numerical rating scale, and back-related disability (Roland Morris Disability Questionnaire scores) from baseline to three weeks and to six weeks among patients treated and not treated with opioids at baseline using generalized linear regression. RESULTS: Baseline treatment with opioids was not significantly associated with back pain intensity (adjusted difference in means at three weeks of follow-up between patients treated with opioids at baseline versus not [±95% CI, 0.1 (-0.7, 0.7)], leg pain intensity [-0.2 (-0.9, 0.4)], or back-related function [-0.8 (-2.1, 0.4)]. We found similar results at six weeks of follow-up. CONCLUSIONS: Among older adults with lumbar spinal stenosis who are receiving epidural injections, those treated with opioids at baseline had similar outcomes to those who were not.

Predicting decompression surgery by applying multimodal deep learning to patients' structured and unstructured health data.

BACKGROUND: Low back pain (LBP) is a common condition made up of a variety of anatomic and clinical subtypes. Lumbar disc herniation (LDH) and lumbar spinal stenosis (LSS) are two subtypes highly associated with LBP. Patients with LDH/LSS are often started with non-surgical treatments and if those are not effective then go on to have decompression surgery. However, recommendation of surgery is complicated as the outcome may depend on the patient's health characteristics. We developed a deep learning (DL) model to predict decompression surgery for patients with LDH/LSS. MATERIALS AND METHOD: We used datasets of 8387 and 8620 patients from a prospective study that collected data from four healthcare systems to predict early (within 2 months) and late surgery (within 12 months after a 2 month gap), respectively. We developed a DL model to use patients' demographics, diagnosis and procedure codes, drug names, and diagnostic imaging reports to predict surgery. For each prediction task, we evaluated the model's performance using classical and generalizability evaluation. For classical evaluation, we split the data into training (80%) and testing (20%). For generalizability evaluation, we split the data based on the healthcare system. We used the area under the curve (AUC) to assess performance for each evaluation. We compared results to a benchmark model (i.e. LASSO logistic regression). RESULTS: For classical performance, the DL model outperformed the benchmark model for early surgery with an AUC of 0.725 compared to 0.597. For late surgery, the DL model outperformed the benchmark model with an AUC of 0.655 compared to 0.635. For generalizability performance, the DL model outperformed the benchmark model for early surgery. For late surgery, the benchmark model outperformed the DL model. CONCLUSIONS: For early surgery, the DL model was preferred for classical and generalizability evaluation. However, for late surgery, the benchmark and DL model had comparable performance. Depending on the prediction task, the balance of performance may shift between DL and a conventional ML method. As a result, thorough assessment is needed to quantify the value of DL, a relatively computationally expensive, time-consuming and less interpretable method.

Appendicular Lean Mass, Grip Strength, and the Incidence of Dementia Among Older Adults in the Health ABC Study.

BACKGROUND: Identification of novel risk factors for dementia in older adults could facilitate development of methods to identify patients most at risk and improve their cognitive outcomes. We aimed to determine whether lower appendicular lean mass (ALM), assessed by dual-energy x-ray absorptiometry (DXA), and lower grip strength are associated with a greater likelihood of incident dementia among older adults in the Health Aging and Body Composition Study (Health ABC). METHODS: Health ABC data from 1997 to 2008 were analyzed (n = 2 704). Baseline ALM to body mass index (BMI) ratio (ALMBMI) was assessed by DXA. Baseline grip strength was assessed by hand-held dynamometry. Incident dementia diagnosis was defined as either (i) dementia-related hospitalization plus a Modified Mini-Mental State Examination (3MS) score of ≤ 90; or (ii) record of prescription for anti-dementia medication; or (iii) decline of at least 1.5 SDs on the 3MS score compared to baseline. Cox proportional hazard models estimated associations of ALMBMI and grip strength with incident dementia over follow-up with and without adjusting for covariates, stratified by sex. RESULTS: Among older men, each standard deviation decrement in ALMBMI (adjusted hazard ratio [aHR]: 1.33; 95% confidence interval [CI]: 1.07, 1.65) or grip strength (aHR 1.22; 95% CI: 1.06, 1.41) was associated with increased likelihood of incident dementia. CONCLUSIONS: Lower ALMBMI and grip strength may be important risk factors for the development of dementia among older men. How these factors may belong to a causal pathway of dementia must be elucidated in future work.

Physical function and fatigue recovery at 6 months after hospitalization for COVID-19.

INTRODUCTION: There are an increasing number of individuals with long-term symptoms of coronavirus-19 disease (COVID-19); however, the prognosis for recovery of physical function and fatigue after COVID-19 is uncertain. OBJECTIVE: To report the changes in functional recovery between 1 and 6 months after hospitalization of adults hospitalized for COVID-19 and explore the baseline factors associated with physical function recovery. DESIGN: A prospective cohort study. SETTING: Tertiary care hospital. PARTICIPANTS: U.S. adult COVID-19 survivors. INTERVENTION: N/A. MAIN OUTCOME MEASURES: Telephone interviews assessed three outcome domains: basic and instrumental activities of daily living (ADLs) performance, fatigue, and general physical function (Health Assessment Questionnaire [HAQ]). RESULTS: The age of participants (n = 92) ranged from 22 to 95 years (54.3 ± 17.2). Across outcome domains, a majority (63%-67%) of participants developed new ADL impairment, fatigue, or worsening HAQ severity by 1 month. Of those, 50%-79% partially or fully recovered by 6 months, but 21%-50% did not recover at least partially. Fifteen to 30% developed new impairment between 1 and 6 months. For those without any improvement in ADL impairments at 6 months, lower socioeconomic status was significantly more common (p = .01) and age ≥ 65 (p = .06), trending toward being more common. CONCLUSION: In this cohort, a substantial proportion of the participants who developed new ADL impairment, worsening fatigue, or HAQ severity after hospitalization for COVID-19 did not recover at least partially by 6 months after discharge. Evaluating functional status 1 month after discharge may be important in understanding functional prognosis and recovery after hospitalization for COVID-19.

Estimating individualized treatment effects using a risk-modeling approach: an application to epidural steroid injections for lumbar spinal stenosis.

ABSTRACT: Conventional "1-variable-at-a-time" analyses to identify treatment effect modifiers are often underpowered and prone to false-positive results. This study used a "risk-modeling" approach guided by the Predictive Approaches to Treatment effect Heterogeneity (PATH) Statement framework: (1) developing and validating a multivariable model to estimate predicted future back-related functional limitations as measured by the Roland-Morris Disability Questionnaire (RMDQ) and (2) stratifying patients from a randomized controlled trial (RCT) of lumbar epidural steroid injections (LESIs) for the treatment of lumbar spinal stenosis into subgroups with different individualized treatment effects on RMDQ scores at the 3-week follow-up. Model development and validation were conducted in a cohort (n = 3259) randomly split into training and testing sets in a 4:1 ratio. The model was developed in the testing set using linear regression with least absolute shrinkage and selection regularization and 5-fold cross-validation. The model was then applied in the testing set and subsequently in patients receiving the control treatment in the RCT of LESI. R2 values in the training set, testing set, and RCT were 0.38, 0.32, and 0.34, respectively. There was statistically significant modification ( P = 0.03) of the LESI treatment effect according to predicted risk quartile, with clinically relevant LESI treatment effect point estimates in the 2 quartiles with greatest predicted risk (-3.7 and -3.3 RMDQ points) and no effect in the lowest 2 quartiles. A multivariable risk-modeling approach identified subgroups of patients with lumbar spinal stenosis with a clinically relevant treatment effect of LESI on back-related functional limitations.

Improving Power and Accuracy in Randomized Controlled Trials of Pain Treatments by Accounting for Concurrent Analgesic Use.

The 0 to 10 numeric rating scale of pain intensity is a standard outcome in randomized controlled trials (RCTs) of pain treatments. For individuals taking analgesics, there may be a disparity between "observed" pain intensity (pain intensity with concurrent analgesic use) and pain intensity without concurrent analgesic use (what the numeric rating scale would be had analgesics not been taken). Using a contemporary causal inference framework, we compare analytic methods that can potentially account for concurrent analgesic use, first in statistical simulations, and second in analyses of real (non-simulated) data from an RCT of lumbar epidural steroid injections. The default analytic method was ignoring analgesic use, which is the most common approach in pain RCTs. Compared to ignoring analgesic use and other analytic methods, simulations showed that a quantitative pain and analgesia composite outcome based on adding 1.5 points to pain intensity for those who were taking an analgesic (the QPAC1.5) optimized power and minimized bias. Analyses of real RCT data supported the results of the simulations, showing greater power with analysis of the QPAC1.5 as compared to ignoring analgesic use and most other methods examined. We propose alternative methods that should be considered in the analysis of pain RCTs. PERSPECTIVE: This article presents the conceptual framework behind a new quantitative pain and analgesia composite outcome, the QPAC1.5, and the results of statistical simulations and analyses of trial data supporting improvements in power and bias using the QPAC1.5. Methods of this type should be considered in the analysis of pain RCTs.

Long-term effectiveness of epidural steroid injections after new episodes of low back pain in older adults.

BACKGROUND: There is limited research on the long-term effectiveness of epidural steroid injections (ESI) in older adults despite the high prevalence of back and leg pain in this age group. We tested the hypotheses that older adults undergoing ESI, compared to patients not receiving ESI: (1) have worse pain, disability and quality of life ('outcomes') pre-ESI, (2) have improved outcomes after ESI and (3) have improved outcomes due to a specific ESI effect. METHODS: We prospectively studied patients ≥65 years old presenting to primary care with new episodes of back pain in three US healthcare systems (BOLD registry). Outcomes were leg and back pain intensity, disability and quality of life, assessed at baseline and 3-, 6-, 12- and 24-month follow-ups. We categorized participants as: (1) ESI within 6 months from the index visit (n = 295); (2) no ESI within 6 months (n = 4809); (3) no ESI within 6 months, propensity-score matched to group 1 (n = 483). We analysed the data using linear regression and Generalized Estimating Equations. RESULTS: Pain intensity, disability and quality of life at baseline were significantly worse at baseline in ESI patients (group 1) than in group 2. The improvement from baseline to 24 months in all outcomes was statistically significant for group 1. However, no statistically significant differences were observed between outcome trajectories for the propensity-score matched groups 1 and 3. CONCLUSIONS: Older adults treated with ESI have long-term improvement. However, the improvement is unlikely the result of a specific ESI effect. SIGNIFICANCE: In this large, two-year, prospective study in older adults with a new episode of low back pain, back pain, leg pain, disability and quality of life improved after epidural steroid injections; however, propensity-score matching revealed that the improvement was unlikely the result of a specific effect of the injections, indicating that epidural steroids are unlikely to provide long-term benefits in older adults with new episodes of back and leg pain.

Health care costs in a randomized trial of antimicrobial duration among cystic fibrosis patients with pulmonary exacerbations.

BACKGROUND: The purpose of these analyses was to determine whether overall costs were reduced in cystic fibrosis (CF) patients experiencing pulmonary exacerbation (PEx) who received shorter versus longer durations of treatment. METHODS: Among people with CF experiencing PEx, we calculated 30-day inpatient, outpatient, emergency room, and medication costs and summed these to derive total costs in 2020 USD. Using the Kaplan-Meier sample average (KMSA) method, we calculated adjusted costs and differences in costs within two pairs of randomized groups: early robust responders (ERR) randomized to receive treatment for 10 days (ERR-10 days) or 14 days (ERR-14 days), and non-early robust responders (NERR) randomized to receive treatment for 14 days (NERR-14 days) or 21 days (NERR-21 days). RESULTS: Patients in the shorter treatment duration groups had shorter lengths of stay per hospitalization (mean ± standard deviation (SD) for ERR-10 days: 7.9 ± 3.0 days per hospitalization compared to 10.1 ± 4.2 days in ERR-14 days; for NERR-14 days: 8.7 ± 4.9 days per hospitalization compared to 9.6 ± 6.5 days in NERR-21 days). We found statistically significantly lower adjusted mean costs (95% confidence interval) among those who were randomized to receive shorter treatment durations (ERR-10 days: $60,800 ($59,150 - $62,430) vs $74,420 ($72,610 - $76,450) in ERR-14 days; NERR-14 days: $66,690 ($65,960-$67,400) versus $74,830 ($73,980-$75,650) in NERR-21 days). CONCLUSIONS: Tied with earlier evidence that shorter treatment duration was not associated with worse clinical outcomes, our analyses indicate that treating with shorter antimicrobial durations can reduce costs without diminishing clinical outcomes.

Lean mass, grip strength, and hospital-associated disability among older adults in Health ABC.

INTRODUCTION: Older adults with cognitive impairment, including those with Alzheimer's disease and related dementias, are particularly at risk for hospitalization and hospital-associated disability. Understanding of key risk factors for hospital-associated disability is limited. Sarcopenia, age-related declines in muscle mass and strength, is common in older adults with cognitive impairment and may be an important risk factor for hospital-associated disability. METHODS: Using data from the Health ABC Study, we examined associations of pre-hospitalization appendicular lean mass (ALM) and grip strength with the development of a new activity of daily living (ADL) disability at the next annual assessment after hospitalization. RESULTS: Grip strength, but not ALM, was negatively associated with increased risk of hospital-associated ADL disability, and this association was greater among those with cognitive impairment compared to those without. DISCUSSION: Lower grip strength may be an important risk factor for hospital-associated ADL disability in older adults, particularly those with cognitive impairment.

Appendicular Lean Mass, Grip Strength, and the Development of Hospital-Associated Activities of Daily Living Disability Among Older Adults in the Health ABC Study.

BACKGROUND: Half of all physical disability, including activity of daily living (ADL) disability, among older adults occurs in the setting of hospitalization. This study examines whether appendicular lean mass (ALM) and grip strength, which are commonly included in various definitions of sarcopenia, are associated with the development of hospital-associated ADL disability in older adults in the Health ABC Study. METHODS: Individuals hospitalized during the first 5 years of follow-up (n = 1 724) were analyzed. ALM to body mass index (BMI) ratio (ALMBMI), by dual-energy x-ray absorptiometry (DXA), and grip strength, by hand-held dynamometery, were assessed annually. Development of new ADL disability was assessed at the time of the next annual assessment after hospitalization. Separate regression analyses modeled the association of prehospitalization ALMBMI or grip strength with death before the next scheduled annual assessment. Next, among those who survived to the next annual assessment, separate regression analyses modeled the association of ALMBMI or grip strength with development of ADL disability. RESULTS: Each standard deviation decrement in prehospitalization grip strength was associated with an adjusted 1.80 odds of new ADL disability at follow-up (95% CI: 1.18, 2.74). Low, compared with not low, grip strength (per FNIH definition) was associated with an adjusted 2.36 odds of ADL disability at follow-up (95% CI: 1.12, 4.97). ALM measures were not associated with the development of hospital-associated ADL disability. ALM and grip strength measures were not associated with death. CONCLUSIONS: Prehospitalization lower grip strength may be an important risk factor for ADL disability among older adult survivors of hospitalization.

Patient-reported functional outcomes 30 days after hospitalization for COVID-19.

BACKGROUND: Many coronavirus disease 2019 (COVID-19) survivors experience persistent symptoms, such as fatigue, dyspnea, and musculoskeletal pain. However, less is known about the impact of COVID-19 on longer term functional outcomes. OBJECTIVE: To evaluate patient-reported activity of daily living (ADL) function and fatigue symptoms 30 days after hospitalization for COVID-19. DESIGN: Cross-sectional study. SETTING: Tertiary care university hospital. PARTICIPANTS: Adults 18 years or older hospitalized for COVID-19 and survived to 30 days after discharge. METHODS: A standardized telephone questionnaire was administered 30 days after hospital discharge. MAIN OUTCOME MEASURES: Ability to perform basic and instrumental ADLs and fatigue symptoms severity (Patient-Reported Outcome Measurement Information System [PROMIS] Fatigue Short Form 7a) were assessed by self-report. RESULTS: Participants (n = 55) were 22-95 years old. Compared to pre-COVID hospitalization, 52% developed new difficulty and 6% new dependence with performing basic ADLs (bADLs), 48% developed new difficulty and 11% new dependence with instrumental ADLs (iADLs), and 69% experienced a clinically significant worsening in their fatigue symptom severity. The average fatigue symptom severity T-score before hospitalization was 44.2 ± 7.4 and after hospitalization was 54.5 ± 9.8. In exploratory multivariate analyses, each additional COVID symptom at presentation was associated with a predicted increase of 1.43 units (95% confidence interval [CI], 0.45-2.42) in the 30-day fatigue symptom severity T-score, each additional day of hospitalization was associated with an 1.2 times increased odds of worsening fatigue (95% CI, 0.98-1.5; p = .08), and each unit increase in baseline body mass index was associated with 0.8 times decreased odds of new bADL or iADL dependence at 30 days (95% CI, 0.65-0.99). CONCLUSIONS: New functional impairments are common at 30 days after discharge among survivors of hospitalization for COVID-19. Early rehabilitation, advance care planning, and referrals to appropriate therapies should be considered in postacute COVID-19 care to maximize patients' functional outcomes. However, ongoing research is still needed regarding management of these patients.

Health care costs related to home spirometry in the eICE randomized trial.

BACKGROUND: Home spirometry with regular symptom assessment is one strategy to track lung health to intervene early in episodes of pulmonary exacerbations (PE). In a multi-center randomized controlled trial home spirometry and symptom tracking demonstrated no significant differences regarding the primary clinical endpoint, FEV1, compared to usual care, but did identify differences in healthcare utilization. We used data from the Early Intervention in Cystic Fibrosis Exacerbation (eICE) study to evaluate whether home monitoring of PE is a cost-minimizing intervention in the context of this randomized trial. METHODS: We reviewed healthcare resource utilization of all 267 eICE participants, including outpatient visits, antibiotics and hospitalizations. Prices were identified in the IBM/Watson MarketScanⓇ Commercial Claims and Encounters Databases and averaged over the 2014-2017 period. Using total healthcare utilization costs, we generated summary statistics by intervention and protocol arm (total cost, mean cost, standard deviation). We performed Welch Two Sample t-tests to determine if total costs and cost by type of utilization differed significantly between groups. RESULTS: Outpatient visit costs were significantly higher by 13% in the Early Intervention (EI) than in the usual care (UC) arm ($3,345 vs. $2,966). We found no significant differences in outpatient antibiotic, hospitalization, or total health care costs between the arms. CONCLUSIONS: Within the context of the eICE trial, outpatient visits were significantly higher in those with experimental home spirometry care, but that did not translate into statistically significant differences of overall health care costs between the two arms.