Improvements in Physical Function and Pain Interference and Changes in Mental Health Among Patients Seeking Musculoskeletal Care.

Importance: Among patients seeking care for musculoskeletal conditions, there is mixed evidence regarding whether traditional, structure-based care is associated with improvement in patients' mental health. Objective: To determine whether improvements in physical function and pain interference are associated with meaningful improvements in anxiety and depression symptoms among patients seeking musculoskeletal care. Design, Setting, and Participants: This cohort study included adult patients treated by an orthopedic department of a tertiary care US academic medical center from June 22, 2015, to February 9, 2022. Eligible participants presented between 4 and 6 times during the study period for 1 or more musculoskeletal conditions and completed Patient-Reported Outcomes Measurement Information System (PROMIS) measures as standard care at each visit. Exposure: PROMIS Physical Function and Pain Interference scores. Main Outcomes and Measures: Linear mixed effects models were used to determine whether improvements in PROMIS Anxiety and PROMIS Depression scores were associated with improved PROMIS Physical Function or Pain Interference scores after controlling for age, gender, race, and PROMIS Depression (for the anxiety model) or PROMIS Anxiety (for the depression model). Clinically meaningful improvement was defined as 3.0 points or more for PROMIS Anxiety and 3.2 points or more for PROMIS Depression. Results: Among 11 236 patients (mean [SD] age, 57 [16] years), 7218 (64.2%) were women; 120 (1.1%) were Asian, 1288 (11.5%) were Black, and 9706 (86.4%) were White. Improvements in physical function (ß = -0.14; 95% CI, -0.15 to -0.13; P < .001) and pain interference (ß = 0.26; 95% CI, 0.25 to 0.26; P < .001) were each associated with improved anxiety symptoms. To reach a clinically meaningful improvement in anxiety symptoms, an improvement of 21 PROMIS points or more (95% CI, 20-23 points) on Physical Function or 12 points or more (95% CI, 12-12 points) on Pain Interference would be required. Improvements in physical function (ß = -0.05; 95% CI, -0.06 to -0.04; P < .001) and pain interference (ß = 0.04; 95% CI, 0.04 to 0.05; P < .001) were not associated with meaningfully improved depression symptoms. Conclusions and Relevance: In this cohort study, substantial improvements in physical function and pain interference were required for association with any clinically meaningful improvement in anxiety symptoms, and were not associated with any meaningful improvement in depression symptoms. Patients seeking musculoskeletal care clinicians providing treatment cannot assume that addressing physical health will result in improved symptoms of depression or potentially even sufficiently improved symptoms of anxiety.

Relationships between improvement in physical function, pain interference, and mental health in musculoskeletal patients.

Importance: Among patients seeking care for musculoskeletal conditions, there is mixed evidence regarding whether traditional, structure-based care is associated with improvement in patients' mental health. Objective: To determine whether improvements in physical function and pain interference are associated with meaningful improvements in anxiety and depression symptoms among patients seeking musculoskeletal care. Design: Retrospective cohort study from June 22, 2015 to February 9, 2022. Setting: Orthopedic department of a tertiary care US academic medical center. Participants: Consecutive sample of adult patients who presented to the musculoskeletal clinic 4 to 6 times during the study period and completed Patient-Reported Outcomes Measurement Information System (PROMIS) measures as standard care at each visit. Exposure: PROMIS Physical Function and Pain Interference scores. Main Outcomes and Measures: Linear mixed effects models were used to determine whether: 1) PROMIS Anxiety and 2) PROMIS Depression scores improved as a function of improved PROMIS Physical Function or Pain Interference scores, after controlling for age, gender, race, and PROMIS Depression (for the Anxiety model) and PROMIS Anxiety (for the Depression model). Clinically meaningful improvement was defined as ≥3.0 points for PROMIS Anxiety and ≥3.2 points for PROMIS Depression. Results: Among 11,236 patients (mean [SD] age 57 [16] years), 9,706 (86%) were White, and 7,218 (64%) were women. Improvements in physical function (ß=-0.14 [95% CI -0.15- -0.13], p<0.001) and pain interference (ß=0.26 [0.25-0.26], p<0.001) were each associated with improved anxiety symptoms. To reach a clinically meaningful improvement in anxiety symptoms, an improvement of ≥21 [20-23] PROMIS points on Physical Function or ≥12 [12-12] points on Pain Interference would be required. Improvements in physical function (ß=-0.05 [- 0.06- -0.04], p<0.001) and pain interference (ß=0.04 [0.04-0.05], p<0.001) were not associated with meaningfully improved depression symptoms. Conclusions and Relevance: In this cohort study, substantial improvements in physical function and pain interference were required for association with any clinically meaningful improvement in anxiety symptoms and were not associated with any meaningful improvement in depression symptoms. Among patients seeking musculoskeletal care, musculoskeletal clinicians and patients cannot assume that addressing physical health will result in improved symptoms of depression or potentially even sufficiently improved symptoms of anxiety. Key Points: Question: Among patients seeking musculoskeletal care, are improvements in physical function and pain interference associated with meaningful changes in symptoms of anxiety and depression?Findings: In this large cohort study, improvement by ≥2.3 population-level standard deviations (SD) on PROMIS Physical Function or ≥1.2 SD on PROMIS Pain Interference were required for any association with meaningful improvement in anxiety symptoms. Improvements in physical function and pain interference were not associated with meaningfully improved depression symptoms.Meaning: Musculoskeletal clinicians and patients cannot assume that exclusively addressing the physical aspect of a musculoskeletal condition will improve symptoms of depression or potentially even anxiety.

Loss of Sirtuin 1 Alters the Secretome of Breast Cancer Cells by Impairing Lysosomal Integrity.

The NAD+-dependent deacetylase Sirtuin 1 (SIRT1) is down-regulated in triple-negative breast cancer. To determine the mechanistic basis by which reduced SIRT1 expression influences processes related to certain aggressive cancers, we examined the consequences of depleting breast cancer cells of SIRT1. We discovered that reducing SIRT1 levels decreased the expression of one particular subunit of the vacuolar-type H+ ATPase (V-ATPase), which is responsible for proper lysosomal acidification and protein degradation. This impairment in lysosomal function caused a reduction in the number of multi-vesicular bodies (MVBs) targeted for lysosomal degradation and resulted in larger MVBs prior to their fusing with the plasma membrane to release their contents. Collectively, these findings help explain how reduced SIRT1 expression, by disrupting lysosomal function and generating a secretome comprising exosomes with unique cargo and soluble hydrolases that degrade the extracellular matrix, can promote processes that increase breast-cancer-cell survival and invasion.