Clinical Outcomes of Immune Checkpoint Inhibitors in Unique Cohorts Underrepresented in Clinical Trials.

Regulatory approval of immune checkpoint inhibitors (ICIs) was based on results of large, randomized clinical trials, resulting in limited outcomes data in patient cohorts typically underrepresented in such trials. The objective of this study was to evaluate the efficacy and safety of ICIs in these unique patient cohorts. This is a multicenter, retrospective analysis of real-world data at six academic and community clinics in the United States from 1 January 2011 to 1 April 2018. Patients were included if they had received at least one cycle of ICI treatment. Unique patient cohorts included age > 75 years, non-White race, positive smoking history, ECOG performance status (PS) ≥ 2, BMI ≥ 30 kg/m2, autoimmune diseases (AIDs), chronic viral infections (CVI), extensive prior lines of therapy (LOTs), or >three metastatic sites. Immune-related adverse events (irAEs), overall survival (OS), and time to treatment failure were evaluated in the entire cohort and in NSCLC patients treated with PD-(L)1 monotherapy. Outcomes and their association with unique patient cohorts were compared on univariate analysis and multivariate analysis to those without a particular characteristic in the entire NSCLC PD-(L)1 monotherapy cohorts. In total, 1453 patients were included: 56.5%-smokers, 30.4%-non-White, 22.8%-elderly, 20.8%-ECOG PS ≥ 2, 15.7%-history of AIDs, and 4.7%-history of CVI. The common ICIs were nivolumab (37.1%) and pembrolizumab (22.2%). Black patients, compared to White patients, experienced fewer irAEs (OR 0.54, p < 0.001). An ECOG PS of ≥2 (HR = 2.01, p < 0.001) and an increased number of previous LOTs were associated with poor OS (the median OS of 26.2 vs. 16.2 vs. 9.6 months for one vs. two vs. three prior LOTs, p < 0.001). The above results were confirmed in anti-PD-(L)1 monotherapy non-small cell lung cancer patients (n = 384). Overall, ICIs were safe and efficacious in these typically underrepresented patient cohorts. We noted ECOG PS ≥ 2 and an increased prior LOTs were associated with poor ICI efficacy, and Black patients, compared to White patients, experienced fewer irAEs.

The impact of immunosuppressive agents on immune checkpoint inhibitor efficacy in patients with advanced melanoma: A real-world, multicenter, retrospective study.

BACKGROUND: Immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) are often managed via immunosuppressive agents (ISAs); however, their impact on ICI efficacy is not well studied. The impact of the use of ISAs on ICI efficacy in patients with advanced melanoma was therefore investigated. METHODS: This is a real-world, multicenter, retrospective cohort study of patients with advanced melanoma who received ICIs (n = 370). Overall survival (OS) and time to treatment failure (TTF) from the time of ICI initiation were compared among patients in subgroups of interest by unadjusted and 12-week landmark sensitivity-adjusted analyses. The association of irAEs and their management with OS and TTF were evaluated using univariate and multivariable Cox proportional hazards regression models. RESULTS: Overall, irAEs of any grade and of grade ≥3 occurred in 57% and 23% of patients, respectively. Thirty-seven percent of patients received steroids, and 3% received other ISAs. Median OS was longest among patients receiving both (not reached [NR]), shorter among those receiving only systemic steroids (SSs) (84.2 months; 95% CI, 40.2 months to NR), and shortest among those who did not experience irAEs (10.3 months; 95% CI, 6-20.1 months) (p < .001). Longer OS was significantly associated with the occurrence of irAEs and the use of SSs with or without ISAs upon multivariable-adjusted analysis (p < .001). Similar results were noted with anti-programmed death 1 (PD-1) monotherapy and combination anti-PD-1 plus anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) therapy, and with 12-week landmark sensitivity analysis (p = .01). CONCLUSIONS: These findings in patients with melanoma who were treated with ICIs suggest that the use of SSs or ISAs for the management of irAEs is not associated with inferior disease outcomes, which supports the use of these agents when necessary.

Financial impact associated with implementation of the low back pain clinical practice guideline in outpatient physical therapist practice at a large academic medical center.

INTRODUCTION: Low back pain (LBP) is the top health condition requiring rehabilitation in the United States. The financial burden of managing LBP is also amongst the highest in the United States. Clinical practice guidelines (CPGs) provide management recommendations and have the potential to lower health costs. Limited evidence exists on the impact of CPG implementation on downstream medical costs. OBJECTIVE: To examine the impact of CPG implementation in physical therapist (PT) practice on direct and downstream costs for patients with LBP. METHODS: A retrospective observational study examined billing data from 270 patients with LBP who were treated at multiple sites within one large academic medical center by PTs who participated in a multifaceted CPG implementation program. Costs were analyzed for direct PT services, downstream medical services, and PT utilization from September 2017 to March 2018 (pre-implementation group) and compared with costs from June 2018 to December 2018 (post-implementation group). RESULTS: Direct PT costs were significantly lower post-implementation than pre-implementation mean: $2,863 USD (SD: $1,968) vs. $3,459 USD (SD: $2,838), p = .05, 95% CI [11, 1182]. All downstream costs were lower post-implementation with statistically significant lower costs found in downstream imaging: p = .04, 95% CI [32, 1,905]; pharmacy: p = .03, 95% CI [70, 1,217]; surgery: p = .03, 95% CI [446, 9,152], and "other": p = .02, 95% CI [627, 7,920]. CONCLUSION: Implementing the LBP CPG in outpatient PT practice can have a positive impact on lowering downstream costs and the potential to increase the value of PT services.

Dependence in prestroke mobility predicts adverse outcomes among patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Stroke survivors are commonly dependent in activities of daily living; however, the relation between prestroke mobility impairment and poststroke outcomes is poorly understood. The primary objective of this study was to evaluate the association between prestroke mobility impairment and 4 poststroke outcomes. The secondary objective was to evaluate the association between prestroke mobility impairment and a plan for physical therapy. METHODS: This was a secondary analysis of the National Stroke Project data, a retrospective cohort of Medicare beneficiaries who were hospitalized with an acute ischemic stroke (1998 to 2001). Logistic-regression modeling was used to examine the adjusted association between prestroke mobility impairment with patient outcomes and a plan for physical therapy. RESULTS: Among the 67,445 patients hospitalized with an ischemic stroke, 6% were dependent in prestroke mobility. Prestroke mobility dependence was independently associated with an increased odds of poststroke mobility impairment (odds ratio [OR]=9.9; 95% CI, 9.0 to 10.8); in-hospital mortality (OR=2.4; 95% CI, 2.2 to 2.7); discharge to a skilled nursing facility (OR=3.5; 95% CI, 3.2 to 3.8); and the combination of in-hospital death or discharge to a skilled nursing facility (OR=3.5; 95% CI, 3.3 to 3.8). Prestroke mobility dependence was independently associated with a decreased odds of having a plan for physical therapy (OR=0.79; 95% CI, 0.73 to 0.85). CONCLUSIONS: These data, obtained from a large, geographically diverse cohort from the United States, demonstrate a strong association between dependence in prestroke mobility and adverse outcomes among elderly stroke patients. Clinicians should screen patients for prestroke mobility impairment to identify patients at greatest risk for adverse events.

The effect of monochromatic infrared energy on transcutaneous oxygen measurements and protective sensation: results of a controlled, double-blind, randomized clinical study.

Monochromatic infrared energy has been reported to restore protective sensation by increasing circulation. A controlled, double-blind, quasi-experimental, randomized clinical study was conducted to 1) examine the effects of monochromatic infrared energy treatments on tissue perfusion, 2) determine the effects of a published monochromatic infrared energy neuropathy protocol on sensation on the feet of patients with diabetes and a loss of protective sensation; 3) examine monochromatic infrared energy's effect on pain; and 4) examine the relationship between transcutaneous oxygen levels and loss of protective sensation. The study was conducted at a wound and hyperbaric treatment center in Norwalk, Conn; 18 adults (12 men, six women; mean age 65 +/-13 years, range 39 to 86 years) with diabetes and loss of protective sensation were recruited using convenience sampling methods. All patients served as their own control. Pre- and post treatment tests assessed sensation, pain, and transcutaneous oxygen measurements on two sites per foot. Participants underwent a series of 30-minute monochromatic infrared energy treatments (one foot active treatment, one foot sham). Monochromatic infrared energy was delivered at the manufacturer pre-set level of energy of 1.5 J/cm(2)/min at a wavelength of 890 nm; sham units delivered no energy. Scores were analyzed using paired t-tests and Pearson's correlation coefficient. No significant differences were observed between active and sham treatments for transcutaneous oxygen values, pain, or sensation. Both active and sham monochromatic infrared energy-treated feet had significantly improved sensation when compared to pretest baseline scores (P <0.05). No statistical relationship was found between transcutaneous oxygen and sensation. This small study did not demonstrate any effects of monochromatic infrared energy treatment on transcutaneous oxygen measurements, pain, or sensation in adults with diabetes and loss of protective sensation.

Stress and compliance with a home exercise program among caregivers of children with disabilities.

PURPOSE: To determine the relationship between caregiver stress and compliance with home programs in caregivers of children with disabilities. METHODS: Sixty-six caregivers of children with disabilities responded to a mailed survey to determine their level of compliance with a prescribed home physical therapy program and the level of caregiver stress. Compliance was defined as the degree to which caregivers followed the prescribed frequency of the home program. RESULTS: Sixty-six percent of the caregivers reported some level of noncompliance with their home program. Linear regression analysis revealed a significant relationship between the caregivers' level of noncompliance with the home program and the level of stress that they reported. Correlation coefficients showed a significant relationship between family problems and noncompliance with home programs. As caregiver and family problems increased, noncompliance with home programs increased. CONCLUSIONS: Caregivers of children with disabilities experience stress that should be addressed by therapists to maximize compliance with home programs.