The M3 muscarinic acetylcholine receptor can signal through multiple G protein families.

The M3 muscarinic acetylcholine receptor (M3R) is a G protein coupled receptor (GPCR) that regulates important physiological processes including vascular tone, bronchoconstriction, and insulin secretion. It is expressed on a wide variety of cell types, including pancreatic beta, smooth muscle, neuronal, and immune cells. Agonist binding to the M3R is thought to initiate intracellular signaling events primarily through the heterotrimeric G protein Gq. However, reports differ on the ability of M3R to couple to other G proteins beyond Gq. Using members from the four primary G protein families (Gq, Gi, Gs, and G13) in radioligand binding, GTP turnover experiments, and cellular signaling assays including live cell G protein dissociation and second messenger assessment of cAMP and inositol trisphosphate, we show that other G protein families, particularly Gi and Gs, can also interact with the human M3R. We further show that these interactions are productive as assessed by amplification of classical second messenger signaling events. Our findings demonstrate that the M3R is more promiscuous with respect to G protein interactions than previously appreciated. Significance StatementThe study reveals that the human M3 muscarinic acetylcholine receptor (M3R), known for its pivotal roles in diverse physiological processes, not only activates intracellular signaling via Gq as previously known but also functionally interacts with other G protein families, such as Gi and Gs, expanding our understanding of its versatility in mediating cellular responses. These findings signify a broader and more complex regulatory network governed by M3R and have implications for therapeutic targeting.

Hospital Consumer Assessment of Healthcare Providers and Systems survey response rates are significantly affected by patient characteristics and postoperative outcomes for patients undergoing primary total knee arthroplasty.

INTRODUCTION: The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey measures patients' satisfaction of their hospital experience. A minority of discharged patients return the survey. Underlying bias among who ultimately returns the survey (non-response bias) after total knee arthroplasty (TKA) may affect results of the survey. Thus, the objective of the current study is to assess the relationship between patient characteristics and postoperative outcomes on HCAHPS survey nonresponse. METHODS: All adult patients at a single institution undergoing inpatient, elective, primary TKA between February 2013 and May 2020 were selected for analysis. Following discharge, all patients had been mailed the HCAHPS survey. The primary outcome analyzed in the current study is survey return. Patient characteristics, surgical variables, and 30-day postoperative outcomes were analyzed. Univariate and multivariate analyses were performed to identify factors independently associated with return of the HCAHPS survey. RESULTS: Of 4,804 TKA patients identified, 1,498 (31.22%) returned HCAHPS surveys. On multivariate regression analyses controlling for patient factors, patients who did not return the survey were more likely to have a higher American Society of Anesthesia score (ASA score of 4 or higher, OR = 2.37; P<0.001), and be partially or totally dependent (OR = 2.37; P = 0.037). Similarly, patients who did not return the survey were more likely to have had a readmission (OR = 1.94; P<0.001), be discharged to a place other than home (OR = 1.52; P<0.001), or stay in the hospital for longer than 3 days (OR = 1.43; P = 0.004). DISCUSSION: Following TKA, HCAHPS survey response rate was only 31.22% and completion of the survey was associated with several demographic and postoperative variables. These findings suggest that HCAHPS survey results capture a non-representative fraction of the true TKA patient population. This bias is necessary to consider when using HCAHPS survey results as a metric for quality of healthcare and federal reimbursement rates.

Patient Factors and Perioperative Outcomes Affect Hospital Consumer Assessment of Healthcare Providers and Systems Survey Response Rates After Primary Total Hip Replacement.

INTRODUCTION: The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey is a federally mandated survey that assesses patient satisfaction after hospitalization. It has been noted that a minority of patients actually return the survey. Potential bias in who does and does not respond to the survey (nonresponse bias) after total hip arthroplasty (THA) may affect the survey results. METHODS: All adult patients undergoing inpatient elective primary THA between February 2013 and May 2020 at a single institution were selected for retrospective analysis. After discharge, all had been mailed the HCAHPS survey, and the primary outcome for the current study was survey return. Patient characteristics and 30-day perioperative outcomes were assessed. Univariate and multivariate analyses were performed to determine correlations between the above variables and HCAHPS survey return status. RESULTS: Of 3,310 THA patients analyzed, 1,049 (31.69%) returned the HCAHPS surveys. On multivariate regression analyses, patients who did not return the survey were more likely to have a higher American Society of Anesthesia score (score of three or higher, odds ratio [OR] = 2.27; P < 0.001), be more functionally dependent (OR = 2.69; P = 0.005), or be Black/African American (OR = 3.40; P < 0.001). Similarly, patients who did not return the survey were more likely to have had any adverse event (OR = 1.80; P = 0.012), major adverse event (OR = 2.88; P = 0.007), readmission (OR = 2.13; P < 0.001), be discharged to a place other than home (OR = 1.71; P < 0.001), or stay in the hospital for longer than 3 days (OR = 1.89; P < 0.001). DISCUSSION: After THA, the HCAHPS survey response rate was only 31.69% and completion of the survey correlated with demographic and perioperative variables. These findings suggest that the HCAHPS survey results should be interpreted as a skewed sample of the true surgical patient population. Nonresponse bias is an important factor to consider when evaluating healthcare quality, patient satisfaction survey results, and their effects on federal hospital reimbursement rates.

Postoperative bracing practices after elective lumbar spine surgery: A questionnaire study of U.S. spine surgeons.

BACKGROUND: There is limited data available on the use of orthoses across varying elective spine surgeries. When previously studied in 2009, inconsistent lumbar postoperative bracing practices were reported. The present study aimed to provide a ten-year update regarding postoperative bracing practices after elective lumbar surgery among United States (U.S.) spine surgeons. METHODS: A questionnaire was distributed to attendees of the Lumbar Spine Research Society Annual Meeting (April 2019). The questionnaire collected demographic information, and asked surgeons to identify if they used orthoses postoperatively after ten elective lumbar surgeries. Information regarding type of brace, duration of use, and reason for bracing was also collected. Chi-square tests and one-way analysis of variance (ANOVA) were used for comparisons. RESULTS: Seventy-three of 88 U.S. attending surgeons completed the questionnaire (response rate: 83%). The majority of respondents were orthopaedic surgery-trained (78%), fellowship-trained (84%), and academic surgeons (73%). The majority of respondents (60%) did not use orthoses after any lumbar surgery. Among the surgeons who braced, the overall bracing frequency was 26%. This rate was significantly lower than that reported in the literature ten years earlier (p<0.0001). Respondents tended to use orthoses most often after stand-alone lateral interbody fusions (43%) (p<0.0001). The average bracing frequency after lumbar fusions (34%) was higher than the average bracing frequency after non-fusion surgeries (16%) (p<0.0001). The most frequently utilized brace was an off the shelf lumbar sacral orthosis (66%), and most surgeons braced patients to improve pain (42%). Of surgeons who braced, most commonly did so for 2-4 months (57%). CONCLUSION: Most surgeon respondents did not prescribe orthoses after varying elective lumbar surgeries, and the frequency overall was lower than a similar study conducted in 2009. There continues to be inconsistencies in postoperative bracing practices. In an era striving for evidence-based practices, this is an area needing more attention.

Geographic Variations and Trends in Primary and Revision Knee and Total Hip Arthroplasties in the United States.

BACKGROUND: Over 1 million joint arthroplasties are performed annually in the United States. Ideally, as devices and surgical techniques improve, the number of revision arthroplasties relative to primary arthroplasties should decrease. To our knowledge, this is the first study to evaluate state-by-state disparities in the ratio of revision to primary knee arthroplasty (unicompartmental and total) and total hip arthroplasty (THA). METHODS: The National Inpatient Sample was used to identify patients who had undergone primary or revision knee arthroplasty or primary or revision THA from 2001 to 2011. Demographic characteristics, surgical rates, and revision ratios (the number of revision procedures divided by the number of primary procedures) were determined for the United States as a whole and by state. RESULTS: During the study window, 47 states were sampled. For knee arthroplasty, 1,251,484 patients were identified: 91% underwent primary procedures and 9% underwent revision procedures. Compared with the primary knee arthroplasty cohort, the revision knee arthroplasty cohort had a younger mean age, had more male patients, and had more chronic conditions and longer hospitalizations (p < 0.001 for each). Over the years studied, the mean age of patients who had undergone primary knee arthroplasty decreased 1.8 years (p < 0.0001) and the mean age of those who had undergone revision knee arthroplasties decreased 2.4 years (p < 0.0001). The national revision ratio remained unchanged at around 0.1 (p = 0.8792). However, there was a 2.2-fold variation in revision ratio by state (revision ratio state range, 0.065 to 0.141). For THA, 614,638 patients were identified: 85% underwent primary procedures and 15% underwent revision procedures. Compared with the primary THA cohort, the revision THA cohort had an older mean age, had fewer male patients, and had more chronic conditions and longer hospitalizations (p < 0.001 for each). Over the years studied, the mean age of patients who had undergone primary THA decreased 1.5 years (p = 0.0016), whereas patients who had undergone revision had no significant age trend (p = 1.0000). Unlike for knee arthroplasty, the national THA revision ratio trended downward (0.24 evolved to 0.18, p = 0.0016), and there was a 2.1-fold variation in the revision ratio by state (revision ratio state range, 0.119 to 0.248). CONCLUSIONS: This study found significant variability in state-by-state revision ratios. It also found that the national revision ratio stayed relatively steady for knee arthroplasty but was decreasing for THA, and that patients who had undergone revision knee arthroplasty were getting younger, whereas patients who had undergone revision THA were not. These discrepancies suggest divergent histories for primary knee arthroplasty and THA and warrant further detailed evaluation. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Patient-related Factors and Perioperative Outcomes Are Associated with Self-Reported Hospital Rating after Spine Surgery.

BACKGROUND: Since 2013, the Centers for Medicare & Medicaid Services has tied a portion of hospitals' annual reimbursement to patients' responses to the Hospital Consumer Assessment and Healthcare Providers and Systems (HCAHPS) survey, which is given to a random sample of inpatients after discharge. The most general question in the HCAHPS survey asks patients to rate their overall hospital experience on a scale of 0 to 10, with a score of 9 or 10 considered high, or "top-box." Previous work has suggested that HCAHPS responses, which are meant to be an objective measure of the quality of care delivered, may vary based on numerous patient factors. However, few studies to date have identified factors associated with HCAHPS scores among patients undergoing spine surgery, and those that have are largely restricted to surgery of the lumbar spine. Consequently, patient and perioperative factors associated with HCAHPS scores among patients receiving surgery across the spine have not been well elucidated. QUESTIONS/PURPOSES: Among patients undergoing spine surgery, we asked if a "top-box" rating on the overall hospital experience question on the HCAHPS survey was associated with (1) patient-related factors present before admission; (2) surgical variables related to the procedure; and/or (3) 30-day perioperative outcomes. METHODS: Among 5517 patients undergoing spine surgery at a single academic institution from 2013 to 2017 and who were sent an HCAHPS survey, 27% (1480) returned the survey and answered the question related to overall hospital experience. A retrospective, comparative analysis was performed comparing patients who rated their overall hospital experience as "top-box" with those who did not. Patient demographics, comorbidities, surgical variables, and perioperative outcomes were compared between the groups. A multivariate logistic regression analysis was performed to determine patient demographics, comorbidities, and surgical variables associated with a top-box hospital rating. Additional multivariate logistic regression analyses controlling for these variables were performed to determine the association of any adverse event, major adverse events (such as myocardial infarction, pulmonary embolism), and minor adverse events (such as urinary tract infection, pneumonia); reoperation; readmission; and prolonged hospitalization with a top-box hospital rating. RESULTS: After controlling for potential confounding variables (including patient demographics), comorbidities that differed in incidence between patients who rated the hospital top-box and those who did not, and variables related to surgery, the patient factors associated with a top-box hospital rating were older age (compared with age ≤ 40 years; odds ratio 2.2, [95% confidence interval 1.4 to 3.4]; p = 0.001 for 41 to 60 years; OR 2.5 [95% CI 1.6 to 3.9]; p < 0.001 for 61 to 80 years; OR 2.1 [95% CI 1.1 to 4.1]; p = 0.036 for > 80 years), and being a man (OR 1.3 [95% CI 1.0 to 1.7]; p = 0.028). Further, a non-top-box hospital rating was associated with American Society of Anesthesiologists Class II (OR 0.5 [95% CI 0.3 to 0.9]; p = 0.024), Class III (OR 0.5 [95% CI 0.3 to 0.9]; p = 0.020), or Class IV (OR 0.2 [95% CI 0.1 to 0.5]; p = 0.003). The only surgical factor positively associated with a top-box hospital rating was cervical surgery (compared with lumbar surgery; OR 1.4 [95% CI 1.1 to 1.9]; p = 0.016), while nonelective surgery (OR 0.5 [95% CI 0.3 to 0.8]; p = 0.004) was associated with a non-top-box hospital rating. Controlling for the same set of variables, a non-top-box rating was associated with the occurrence of any adverse event (OR 0.5 [95% CI 0.3 to 0.7]; p < 0.001), readmission (OR 0.5 [95% CI 0.3 to 0.9]; p = 0.023), and prolonged hospital stay (OR, 0.6 [95% CI 0.4 to 0.8]; p = 0.004). CONCLUSIONS: Identifying patient factors present before surgery that are independently associated with HCAHPS scores underscores the survey's limited utility in accurately measuring the quality of care delivered to patients undergoing spine surgery. HCAHPS responses in the spine surgery population should be interpreted with caution and should consider the factors identified here. Given differing findings in the literature regarding the effect of adverse events on HCAHPS scores, future work should aim to further characterize this relationship. LEVEL OF EVIDENCE: Level III, therapeutic study.