Association of Surgical Treatment With Adverse Events and Mortality Among Medicare Beneficiaries With Proximal Humerus Fracture

Key Points Question Are higher rates of surgery for proximal humerus fracture associated with adverse events, mortality, and cost? Findings In this comparative effectiveness research study of 72 823 fee-for-service Medicare beneficiaries with a proximal humerus fracture in 2011, instrumental variable analysis showed that higher rates of surgery were significantly associated with increased costs, adverse event rates, and mortality risk at 1 year. These associations were even more striking for older patients, those with higher comorbidity burdens, and those with increased frailty. Meaning Orthopedic surgeons should be aware of the harms of extending the use of surgery to more clinically vulnerable patient subgroups.


Introduction
A meta-analysis 1 of existing randomized clinical trials suggests that the benefits and risks of surgery compared with conservative management vary, or are heterogeneous, across patients with proximal humerus fracture (PHF).The continued use of surgery over time suggests that surgeons have observed many patients improve after surgical treatment. 2,3In addition, lower surgery rates for more elderly patients with PHF suggest that surgeons recognize that the risks of surgery (eg, surgical complications, infections, and mortality) increase with patient complexity. 4][10][11][12][13] Can additional patients benefit from higher surgery rates, or would higher surgery rates put additional patients with PHF at unnecessary risk with little benefit?Substantial and persistent geographic variation in surgery rates for patients with PHF suggests that there is no consensus as to what the effective rate of surgery is. 2,31][12][13][14] Patients with PHF on the extensive margin are those who would be next to undergo surgery if surgery rates increased, or the first not to undergo surgery if surgery rates decreased.The objective of this study was to assess the outcome implications associated with higher surgery rates for Medicare patients with PHF.

Data and Sample
This was a retrospective comparative effectiveness research cohort study of all 130 959 Medicare beneficiaries in the United States with a PHF in 2011.This project was approved by the University of South Carolina institutional review board.A waiver of informed consent was granted because this

JAMA Network Open | Orthopedics
Surgical Treatment, Adverse Events, and Mortality Among Medicare Beneficiaries With Proximal Humerus Fracture study used deidentified Medicare data.This study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.
Individual patients with a radiography-confirmed diagnosis of PHF in 2011 were identified using Medicare Part B carrier, outpatient, and Medpar Part A inpatient claims.eTable 1 in the Supplement contains a full list of diagnosis codes used to identify patients with PHF.The index date of PHF was defined for each beneficiary as the first date of PHF in 2011.Full cohort inclusion criteria are described in more detail in our previous work 3 and in eTable 2 in the Supplement.Patients were required to survive the treatment period, which was the 60-day period following the index date of PHF.The full cohort of patients with PHF was stratified into subgroups to examine the differential outcomes of surgery on each subgroup of patients: aged less than 80 years vs 80 years or older, Charlson Comorbidity Index 22 score less than 2 vs 2 or higher, and Function-Related Indicators frailty score 23 less than 2 vs 2 or higher.

Treatment Measures
Patients undergoing 1 of 4 surgical procedures (reverse shoulder arthroplasty, hemiarthroplasty, open reduction internal fixation, and closed reduction internal fixation) during the 60 days following the index PHF diagnosis date were classified as surgically managed patients.Surgery claims were identified using Part B carrier, outpatient, and Medpar inpatient claims files.Patients not undergoing surgery during the 60-day treatment window were classified as conservatively managed patients.
Complete definitions of treatment variables are provided in eTable 3 in the Supplement.

Outcome Measures
The outcome period began on day 61 and ran through day 365 after the index fracture.Study outcomes included the occurrence of an adverse event, mortality, and shoulder-related, non-shoulder-related, and total health care costs from Medicare's perspective.In the year following the index fracture, any claim with at least 1 diagnosis of a surgical or medical complication was identified and defined as an adverse event.Adverse events were defined as medical and surgical complications typically associated with elderly adults or surgical repair of PHF and included infection, nerve injury, prosthetic complication, hematoma, avascular necrosis, adhesive capsulitis, shoulder instability or dislocation, pneumonia, cardiac dysrhythmias, congestive heart failure, and deep vein thrombosis or pulmonary embolism. 4

Covariates
The list of all patient demographic and clinical covariates specified in all estimation equations can be found in eTable 4 in the Supplement and in a previous publication. 3

Analytical Approach
5][26][27][28][29][30][31] Consequently, when treatment outcomes are heterogeneous across patients, estimates from these approaches can differ and reveal different information about the study population. 20,31Here we used instrumental variable estimators to assess our research question.The RAR estimators were provided for comparison.Table 1 summarizes the properties of these estimators when assessing the outcomes of surgery compared with conservative management.Instrumental variable estimators yield the average surgery effect for the subgroup of the patients whose surgery choices were sensitive to the instrumental variable used in the analysis, which is known as the local average treatment effect in the instrumental variable literature. 24,26To be unbiased, instrumental variable estimators assume that the distribution of potential outcomes under conservative management are the same for patients with different instrumental variable values. 24,26The RAR estimators yield estimates of the average surgery effect for the subgroup of the patients who chose surgery (eg, the average treatment effect on the treated). 10,17,30,32For the estimate of average treatment effect on the treated to be unbiased, RAR estimators assume that the distribution of potential outcomes under conservative management are the same for patients ultimately treated with either surgery or conservative management. 24,264][35][36][37][38][39][40][41][42][43][44] The use of local area practice style measures as an instrument enabled a direct estimate of the outcomes of higher surgery rates on study outcomes.We used quintiles of riskadjusted area surgery ratios (ASRs) across hospital referral regions (HRRs) as measures of local area practice styles.The ASRs were calculated for each HRR as the ratio of the number of patients with PHF in an HRR who underwent surgical treatment over the sum across these patients of their estimated probabilities of undergoing surgery.Estimated probabilities for each patient were produced from a logistic regression model of surgery choice as a function of measured covariates over the entire sample.Measured patient covariates in the model of surgery choice can be found in eTable 4 in the Supplement.The range of ASRs across all HRRs was divided into 5 quintiles, which became our instruments.More details on the construction of our instruments can be found in the eAppendix in the Supplement.Surgeons in HRRs with larger ASR values are theorized to have stronger beliefs as to the effectiveness of surgery compared with conservative management for patients with PHF.Patients in our sample were assigned the surgery rate and ASR value according to their residence HRR.Instrumental variable analysis was conducted using the procedure IVREG2 in Stata statistical software version 13.1 (StataCorp).All models controlled for patient demographic and clinical characteristics.We used RAR models to estimate the association between surgery and each study outcome after controlling for measured patient covariates associated with comorbidities and frailty.The RAR analysis was conducted using the Stata procedure REG.

Statistical Analysis
Descriptive statistics summarizing patient characteristics for surgery and conservative management groups were assessed by the 2-sample independent t test for continuous variables and Pearson χ 2 test for categorical data.The Cochrane-Armitage test was used to assess trends of patients grouped by ASR quintiles. 45,46A 2-sided P < .05 was considered statistically significant.F statistics testing whether instruments described a significant amount of variation in surgery rates were assessed for the sample population and subgroups according to age, comorbidities, and frailty.An F statistic greater than 10 is considered indicative of a strong instrument. 47SAS statistical software version 9.4 (SAS Institute) was used for building our analytic database, and Stata was used for statistical analyses.
Sensitivity analyses were conducted to assess the impact of cohort inclusion criteria and data extremes on the robustness of our findings and study conclusions.Data analysis was performed January through June 2019.

Sample Characteristics
The

Instrumental Variable Results
Table 4 shows instrumental variable estimates for the clinical outcomes.4 shows the mean percentage of patients undergoing surgery in each patient subgroup and the corresponding range in rates across the ASRs.Our instrumental variable surgery effect estimates directly stem from the variation in surgery rates within these ranges.In addition, the surgery rates in Table 4 for stratified subsets of our sample show that patients with PHF who were older, had higher comorbidity burdens, and greater frailty were less likely to undergo surgery (mean Instrumental variable estimates show that higher surgery rates for PHF were associated with higher adverse event rates and higher mortality in the full cohort and select patient subsets.These instrumental variable estimates show the absolute average effect of a 1-percentage point increase in surgery rates on study outcome rates.For example, the instrumental variable estimate for 1-year adverse event risk for the full cohort implies that a 1-percentage point increase in the surgery rate was associated with a 0.19-percentage point increase in the 1-year adverse event rates (β = 0.19; 95% CI, 0.09-0.27;P < .001).The instrumental variable estimate for 1-year mortality for the full cohort implies that a 1-percentage point increase in the surgery rate was associated with a 0.09percentage point increase in the 1-year mortality rates (β = 0.09; 95% CI, 0.04-0.15;P < .01).Furthermore, the adverse event and mortality risks associated with higher surgery rates were greatest in older patients and those with higher comorbidity burdens and frailty index scores.For example, the instrumental variable estimate for 1-year adverse event risk for the patients with higher comorbidity burdens (Charlson Comorbidity Index score Ն2) suggests that a 1-percentage point increase in surgery rates was associated with a 0.24-percentage point increase in the 1-year adverse event rates (β = 0.24; 95% CI, 0.11-0.36;P < .001)and a 0.15-percentage point increase in 1-year mortality rates (β = 0.15; 95% CI, 0.06-0.24;P < .01).Among the subset of patients with a Function-Related Indicator score of 2 or higher, a 1-percentage point increase in the surgery rate was associated with a 0.22-percentage point increase in the 1-year adverse event rate and a 0.11percentage point increase in the 1-year mortality rate.Among the subset of patients aged 80 years or older, a 1-percentage point increase in the surgery rate was associated with a 0.20-percentage point increase in the 1-year adverse event rate and a 0.11-percentage point increase in the 1-year mortality rate.
Table 5 shows instrumental variable estimates for cost outcomes.During the 60-day treatment period, shoulder-related (β = $5358), non-shoulder-related (β = $3555), and total (β = $8913) costs were higher in local areas with higher surgery rates in the full cohort and most subgroups.During the outcome period, higher surgery rates were associated with lower shoulder-related, non-shoulderrelated, and total costs for the full cohort and most patient subgroups, although most estimates did not reach significance.These results were especially pronounced in the more clinically vulnerable patient subgroups, which showed the greatest reductions in cost, although the estimates did not reach statistical significance.

Risk-Adjusted Results
Table 4 shows RAR estimates on clinical outcomes for the full sample and patient subgroups.In the full cohort and across all subgroups of patients with PHF, the probability of adverse events was higher for the surgically managed patients (a 1-percentage point increase in the surgery rate was associated with a 0.12-percentage point increase in the 1-year adverse event rate; β = 0.12; 95% CI, 0.11 to 0.13; P < .001).Across all subgroups, the risk-adjusted estimates suggest that surgery was associated with a decrease in the 1-year mortality rate compared with conservative management for the patients who underwent surgery.In the full cohort, a 1-percentage point increase in the surgery rate was associated with a 0.01-percentage point decrease in the 1-year mortality rate (β = −0.01;95% CI, −0.015 to −0.005; P < .001).
In Table 5, shoulder-related (β = $621), non-shoulder-related (β = $919), and total (β = $1541) costs were all higher among patients undergoing surgery compared with conservatively managed patients across all periods and subgroups.In the treatment period, surgical patients had total Medicare reimbursements that were a mean of $17 278 higher than those for conservatively managed patients, the majority of which was likely due to the surgical procedure.Shoulder-related, non-shoulder-related, and total costs were also higher for surgery recipients in the outcome period.
Sensitivity analyses were conducted to assess the impact of cohort inclusion criteria and data extremes on the robustness of our findings but did not yield materially different conclusions.

Discussion
Our analysis showed that higher rates of surgery were associated with increased 1-year mortality and adverse event rates.This finding suggests that surgery rates in 2011 for patients with PHF were higher than the effective rate and that a reduction in surgery rates could reduce mortality and adverse event rates for patients with PHF.This result is especially pronounced for older cohorts and those with higher comorbidity burdens and increased frailty.Similar to more well-studied fracture populations, such as patients with hip fracture, 49,50 patients with PHF are an especially frail population, and the surgery decision is associated with a series of events that can trigger poor outcomes, including death.Our instrumental variable estimates are unbiased if unmeasured patient differences between surgically and conservatively managed patients are unrelated to the instrument we selected.Consistent distributions in measured patient characteristics across patients grouped by our instrument in Table 3 support this assumption.
For comparison, we used risk-adjusted estimators to estimate the association between surgery and each study outcome by controlling for a series of measured baseline covariates.Risk-adjusted estimators provide estimates of the outcomes of surgery for the patients who undergo surgery.For risk-adjusted estimates to be unbiased, outcomes for surgical patients if they had not undergone surgery would have to be the same as those observed for the conservatively treated patients. 24,26sk-adjusted estimates suggested that surgical patients had lower risks of mortality after PHF.
However, we found meaningful differences in patient age, comorbidity burden, and frailty index between surgically and conservatively managed patients, which suggests that there are likely additional unmeasured differences between treatment groups that are partly responsible for the estimated treatment outcomes we observed.Given that patients with PHF undergoing surgery are younger, less frail, and have lower comorbidity burdens, it is likely that the estimates of reduced mortality from surgery are biased high as the result of unmeasured differences between the patients selected for surgery and conservative care.

Limitations
Our results should be viewed through the limitations of the study design.First, our adverse event and mortality instrumental variable estimates should be interpreted only within the surgery rate ranges we provided in Table 4.Because surgery outcomes are likely heterogeneous across patients with PHF, it is risky to generalize our estimates to surgery rates below or above these surgery rate ranges.

JAMA Network Open | Orthopedics
Surgical Treatment, Adverse Events, and Mortality Among Medicare Beneficiaries With Proximal Humerus Fracture Our study sample was from 2011, and surgery rates for PHF continue to change.The survival implications associated with surgery rate changes from different baseline rates should be evaluated.
Second, the International Classification of Diseases, Ninth Revision diagnosis codes available for this sample of Medicare data likely does not include information on many factors associated with patient survival, which are also associated with the choice of surgery, such as fracture complexity.Because, patients with complex fractures are more likely to undergo surgery, a portion of the mortality associated with surgery in our instrumental variable models will stem from differences in the distributions of fracture complexity across local areas.However, previous research 38 suggests that this bias risk is attenuated when large geographic areas such as the HRRs are used, as we did here.
However, future research using Medicare claims after 2015, which use International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnosis codes that reflect fracture complexity, is needed to validate this assumption.Third, and related to our second limitation, is the assumption that patients are similar across quintiles of our instrument.Our instrumental variable estimates are unbiased if unmeasured patient differences between surgically and conservatively managed patients are not associated with the instrument we selected.Although some minor differences in shoulder health were noted across instrument quintiles, mostly consistent distributions in measured patient characteristics across patients grouped by our instrument in Table 3 support our assumption that patients were similar across high and low surgery areas.
However, it must still be acknowledged that patient differences across areas, if they exist, could confound our findings.Fourth, we chose to exclude patients who did not survive the treatment period.Therefore, our results do not generalize to those patients who were very frail and not survive the 60 days following their fracture.

Conclusions
This study included a diverse, national sample of patients with PHF.We found wide treatment variation and sought to understand the implications associated with higher rates of surgery for patients with PHF on patient outcomes.[17][18][19][20] Our estimates provide evidence to suggest that current PHF surgery rates are higher than the effective surgery rate and that lowering surgery rates may be associated with lower 1-year mortality rates and adverse event risks.These results are especially pronounced for patients with PHF in highrisk patient subgroups.Because the choice of treatment can affect a number of measured and unmeasured variables, some of which could not be measured in this analysis, further analysis using patient-reported outcomes is warranted.
Mortality dates were obtained from the 2011 and 2012 Medicare Beneficiary summary files.The mortality variable was calculated during the 305-day period following the 60-day treatment window, which equaled 1 if the patient died during the period, and equaled 0 otherwise.Health care costs were summed across all Part A and Part B claims during 2 distinct outcome periods.The treatment window represented the 60-day period beginning on the day of the index fracture and ending 60 days thereafter (days 0-60).The outcome period began on day 61 and ran through day 365.Those claims with a diagnosis of 1 of 192 shoulder diagnoses were deemed a shoulder-related health care cost.All other claims without a shoulder diagnosis were categorized as non-shoulder-related costs.Total costs were a sum of shoulder-related and non-shoulder-related costs.All costs were from the perspective of the Medicare program and included payment amounts made by Medicare to health care professionals.

e
Total Part A and B payments made by Medicare for the beneficiary for the 365-day period after index proximal humerus fracture date.f Total Part A and B shoulder-related payments made by Medicare for the beneficiary for the 365-day period after index proximal humerus fracture date.g Total Part A and B non-shoulder-related payments made by Medicare for the beneficiary for the 365-day period after index proximal humerus fracture date.

Table 1 .
Assumptions Required and Treatment Effect Parameters Estimated for Risk-Adjusted Regression and Instrumental Variable Estimators Average effect of surgery compared with conservative management for the subgroup of patients whose surgery choices were sensitive to the instrumental variable specified (local average treatment effect) Distribution of potential outcomes under conservative management are the same for patients with different instrumental variable values

Table 3 .
Characteristics of Medicare Patients With Proximal Humerus Fracture in 2011 by Local Area Surgery Ratios a Cochrane-Armitage test was used to assess trends across area surgery ratio quintiles.b Beneficiary was fully dual-eligible for Medicare and Medicaid during the month of the index fracture.c Total Part A and B payments made by Medicare for the beneficiary for the 365 days before the index fracture date.d Adverse events include pneumonia, cardiac dysrhythmias, congestive heart failure, deep vein thrombosis or pulmonary embolism, infection, nerve injury, prosthetic complication, hematoma, avascular necrosis, adhesive capsulitis, and instability or dislocation.
Table 4 also shows the F statistic assessing the effects of our instrumental variable on surgery choice.Instruments with an F statistic less than 10 are considered weak and more susceptible to bias in the instrumental variable literature. 48All F statistics in this study are much greater than 10 (total cohort, 205.9; age <80 years, 98.9; age Ն80 years, 111.3;Charlson Comorbidity Index score <2, 95.2; Charlson Comorbidity Index

Table 4 .
Risk-Adjusted Regression and Instrumental Variable Estimates of the Association of Surgery With Adverse Events and Mortality for Medicare Patients With Proximal Humerus Fracture in 2011 and Stratified Subgroups b P < .001.c P < .01. d P < .05. e P < .10.

Table 5 .
Risk-Adjusted Regression and Instrumental Variable Estimates for the Association Between Surgery Utilization and Cost Outcomes for Medicare Patients With Proximal Humerus Fracture in 2011 and Stratified Subgroups b Outcome period is days 61 to 365.c Part A and B shoulder-related payments made by Medicare for the beneficiary.dPart A and B non-shoulder-related payments made by Medicare for the beneficiary.eTotal Part A and B shoulder-related and non-shoulder-related payments made by Medicare for the beneficiary.fP < .001.g P < .05. h P < .01. i P < .10.