Occupational tasks associated with shoulder pain and upper extremity disability: a cross-sectional study in the Johnston County Osteoarthritis Project.

BACKGROUND: Shoulder pain is a leading cause of disability. Occupations requiring high upper extremity demands may put workers at greater risk of shoulder injury and resulting pain. We examined associations of occupation with shoulder pain and upper extremity disability in the Johnston County Osteoarthritis Project. METHODS: Work industry and occupational tasks for the longest job held were collected from participants. At follow-up ranging from 4-10 years later, participants were asked about shoulder symptoms (pain, aching, or stiffness occurring most days of 1 month in the last year) and given a 9-item, modified Disabilities Arm Shoulder and Hand (DASH) questionnaire to categorize disability from 0-4 (none-worst). Logistic regression and cumulative logit regression models were used to estimate associations with prevalent shoulder symptoms and with worse disability category, respectively. Models were adjusted for cohort, age, sex, race, education and time to follow-up. Sex- and race-stratified associations were evaluated. RESULTS: Among 1560 included participants, mean age was 62 years (standard deviation ± 9 years); 32% were men, and 31% were Black. Compared to the managerial/professional industry, higher odds of both shoulder symptoms and worse upper extremity disability were seen for most industrial groups with physically demanding jobs, particularly the service industry. Work that often or always required lifting/moving > 10 lbs. was associated with higher odds of shoulder symptoms. Work that sometimes or always required heavy work while standing was associated with higher odds of shoulder symptoms, and this association was stronger among men and White workers. CONCLUSION: Physically demanding occupations were associated with increased occurrence of shoulder pain and disability. Mitigating specific physical work demands may reduce shoulder-related disability.

Environmental and genetic risk factors associated with total knee arthroplasty following cruciate ligament surgery.

Aims: The purpose of this study is to determine an individual's age-specific prevalence of total knee arthroplasty (TKA) after cruciate ligament surgery, and to identify clinical and genetic risk factors associated with undergoing TKA. Methods: This study was a retrospective case-control study using the UK Biobank to identify individuals reporting a history of cruciate ligament surgery. Data from verbal history and procedural codes recorded through the NHS were used to identify instances of TKA. Patient clinical and genetic data were used to identify risk factors for progression from cruciate ligament surgery to TKA. Individuals without a history of cruciate ligament reconstruction were used for comparison. Results: A total of 2,576 individuals with a history of cruciate ligament surgery were identified, with 290 (11.25%) undergoing TKA. In patients with prior cruciate ligament surgery, prevalence of TKA was 0.75% at age 45 years, 9.10% at age 65 years, and 20.43% at age 80 years. Patients with prior cruciate ligament surgery were 4.6 times more likely to have undergone TKA by age 55 years than individuals without prior cruciate ligament surgery. In the cruciate ligament surgery cohort, BMI > 30 kg/m2 (odds ratio (OR) 4.01 (95% confidence interval (CI) 2.74 to 5.87)), a job that always involved heavy manual or physical labour (OR 2.72 (95% CI 1.57 to 4.71)), or a job that always involved walking and standing (OR 2.58 (95% CI 1.58 to 4.20)) were associated with greater TKA odds. No single-nucleotide polymorphism (SNP) was associated with risk of TKA following cruciate ligament surgery. Conclusion: Patients with a history of prior cruciate ligament surgery have substantially higher risk of TKA and undergo arthroplasty at a relatively younger age than individuals without a history of prior cruciate ligament surgery. Physically demanding work and obesity were associated with higher odds of TKA after cruciate ligament surgery, but no SNP was associated with risk of TKA.

The Association of HIV Control and Immunosuppression With Risk of Non-AIDS-Defining Cancer Risk Among Patients on Antiretroviral Therapy.

BACKGROUND: People living with HIV (PWH) are experiencing an increased prevalence of non-AIDS-defining cancers (NADCs). Our study investigated the association of immunosuppression and HIV control with NADCs among PWH on antiretroviral therapy (ART) in the United States. METHODS: Among patients across 8 clinical cohorts on ART between 1996 and 2016, we assessed immune function and HIV control using 3 parameterizations of CD4 count and HIV-RNA viral load (VL): (1) CD4 or VL at ART initiation; (2) change in CD4 or VL after ART initiation; and (3) proportion of follow-up time at CD4 >500 cells/µL or VL <50 copies/mL. Cox models were used to ascertain the association of these measures with risk of a viral NADC or nonviral NADC. RESULTS: Among 29,568 patients on ART, there were 410 nonviral NADCs and 213 viral NADCs. PWH with a CD4 <200 cells/µL at ART initiation had an 80% elevated risk for developing a viral NADC. Each increase of 100 cells/µL in CD4 after ART initiation decreased risk by 14%. For viral and nonviral NADCs, 10% more follow-up time spent with a CD4 >500 cells/µL was associated with decreased risk [viral, adjusted hazard ratio (aHR): 0.82; 95% confidence intervals (CI): 0.78 to 0.86; nonviral, aHR: 0.88; 95% CI: 0.86 to 91], even after accounting for CD4 at ART initiation. When examining HIV control only, 10% more time with VL <50 copies/mL was significantly associated with decreased viral (aHR: 0.85; 95% CI: 0.82 to 0.89) and nonviral NADC risk (aHR: 0.88; 95% CI: 0.85 to 0.90). CONCLUSIONS: This study demonstrates that even for PWH on ART therapy, maintaining HIV control is associated with lower risk of both viral and nonviral NADCs.

Factors associated with genetic markers for rotator cuff disease in patients with atraumatic rotator cuff tears.

For atraumatic rotator cuff tears, genetics contributes to symptomatic tear risk and may influence rotator cuff healing after surgical repair. But little is known about how genetic factors influence rotator cuff tear patient characteristics at presentation. We collected saliva samples for genotyping from atraumatic rotator cuff tear patients. We examined nine single nucleotide polymorphisms (SNPs) associated with cuff tears in prior literature. We estimated associations of SNP dosage with (1) age at tear diagnosis, (2) bilateral atraumatic tear prevalence, and (3) tear size. Linear regression was used to estimate associations with diagnosis age adjusted for sex and principal components. Logistic regression and ordinal logistic regression were used to estimate associations with bilateral tear prevalence and tear size category, respectively, adjusting for age, sex, and principal components. Of 344 eligible patients, 336 provided sufficient samples for genotyping. Median age at tear diagnosis was 61, 22% (N = 74) had bilateral atraumatic tears, and 9% (N = 29) had massive tears. SNP rs13107325 in the SLC39A8 gene and rs11850957 in the STXBP6 gene were associated with younger diagnosis age even after accounting for multiple comparisons (rs13107325: -4 years, 95% CI = -6.5, -1.4; rs11850957: -2.7 years, 95% CI = -4.3, -1.1). No other significant associations were observed with diagnosis age, tear size, or bilateral tear prevalence. SLC39A8 encodes a Mn transporter. STXBP6 may play a role in inflammatory responses by altering phagocytosis and antigen presentation of monocytes and macrophages. Further research is needed to determine if genetic markers can be used alongside patient characteristics to aid in identifying optimal surgical repair candidates.

Failure of nonoperative care in adult symptomatic lumbar scoliosis: incidence, timing, and risk factors for conversion from nonoperative to operative treatment.

OBJECTIVE: The Adult Symptomatic Lumbar Scoliosis (ASLS) study is a prospective multicenter trial with randomized and observational cohorts comparing operative and nonoperative treatment for ASLS. The objective of the present study was to perform a post hoc analysis of the ASLS trial to examine factors related to failure of nonoperative treatment in ASLS. METHODS: Patients from the ASLS trial who initially received at least 6 months of nonoperative treatment were followed for up to 8 years after trial enrollment. Baseline patient-reported outcome measures (Scoliosis Research Society-22 [SRS-22] questionnaire and Oswestry Disability Index), radiographic data, and other clinical characteristics were compared between patients who did and did not convert to operative treatment during follow-up. The incidence of operative treatment was calculated and independent predictors of operative treatment were identified using multivariate regression. RESULTS: Of 135 nonoperative patients, 42 (31%) crossed over to operative treatment after 6 months and 93 (69%) received only nonoperative treatment. In the observational cohort, 23 (22%) of 106 nonoperative patients crossed over to surgery. In the randomized cohort, 19 (66%) of 29 patients randomized to nonoperative treatment crossed over to surgery. The most impactful factors associated with crossover from nonoperative to operative treatment were enrollment in the randomized cohort and baseline SRS-22 subscore < 3.0 at the 2-year follow-up, closer to 3.4 at 8 years. In addition, baseline lumbar lordosis (LL) < 50° was associated with crossover to operative treatment. Each 1-point decrease in baseline SRS-22 subscore was associated with a 233% higher risk of conversion to surgery (hazard ratio [HR] 2.33, 95% confidence interval [CI] 1.14-4.76, p = 0.0212). Each 10° decrease in LL was associated with a 24% increased risk of conversion to operative treatment (HR 1.24, 95% CI 1.03-1.49, p = 0.0232). Enrollment in the randomized cohort was associated with a 337% higher probability of proceeding with operative treatment (HR 3.37, 95% CI 1.54-7.35, p = 0.0024). CONCLUSIONS: Enrollment in the randomized cohort, a lower baseline SRS-22 subscore, and lower LL were associated with conversion from nonoperative treatment to surgery in patients (observational and randomized) who were initially managed nonoperatively in the ASLS trial.

Evaluation of Genetic and Nongenetic Risk Factors for Degenerative Cervical Myelopathy.

STUDY DESIGN: Cohort study. OBJECTIVE: We aimed to evaluate the associations of genetic and nongenetic factors with degenerative cervical myelopathy (DCM). SUMMARY OF BACKGROUND DATA: There is mounting evidence for an inherited predisposition for DCM, but uncertainty remains regarding specific genetic markers involved. Similarly, nongenetic factors are thought to play a role. MATERIALS AND METHODS: Using diagnosis codes from hospital records linked to the UK Biobank cohort, patients with cervical spondylosis were identified followed by the identification of a subset with DCM. Nongenetic variables evaluated included age, sex, race, Townsend deprivation index, body mass index, occupational demands, osteoporosis, and smoking. Genome-wide association analyses were conducted using logistic regression adjusted for age, sex, population principal components, and follow-up. RESULTS: A total of 851 DCM cases out of 2787 cervical spondylosis patients were identified. Several nongenetic factors were independently associated with DCM including age [odds ratio (OR)=1.11, 95% CI=1.01-1.21, P =0.024], male sex (OR=1.63, 95% CI=1.37-1.93, P <0.001), and relative socioeconomic deprivation (OR=1.03, 95% CI=1.00-1.06, P =0.030). Asian race was associated with lower DCM risk (OR=0.44, 95% CI=0.22-0.85, P =0.014). We did not identify genome-wide significant (≤5×10 -8 ) single-nucleotide polymorphisms (SNPs) associated with DCM. The strongest genome-wide signals were at SNP rs67256809 in the intergenic region of the genes LINC02582 and FBXO15 on chromosome 18 ( P =1.12×10 -7 ) and rs577081672 in the GTPBP1 gene on chromosome 22 ( P =2.9×10 -7 ). No SNPs reported in prior DCM studies were significant after adjusting for replication attempts. CONCLUSIONS: Increasing age, male sex, and relative socioeconomic deprivation were identified as independent risk factors for DCM, whereas Asian race was inversely associated. SNPs of potential interest were identified in GTPBP1 and an intergenic region on chromosome 18, but these associations did not reach genome-wide significance. Identification of genetic and nongenetic DCM susceptibility markers may guide understanding of DCM disease processes, inform risk, guide prevention and potentially inform surgical outcomes. LEVEL OF EVIDENCE: Prognostic level III.

Did the Physical and Mental Health of Orthopaedic Patients Change After the Onset of the COVID-19 Pandemic?

BACKGROUND: The 2019 novel coronavirus (COVID-19) pandemic has been associated with poor mental health outcomes and widened health disparities in the United States. Given the inter-relationship between psychosocial factors and functional outcomes in orthopaedic surgery, it is important that we understand whether patients presenting for musculoskeletal care during the pandemic were associated with worse physical and mental health than before the pandemic's onset. QUESTIONS/PURPOSES: (1) Did patients seen for an initial visit by an orthopaedic provider during the COVID-19 pandemic demonstrate worse physical function, pain interference, depression, and/or anxiety than patients seen before the pandemic, as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS) instrument? (2) During the COVID-19 pandemic, did patients living in areas with high levels of social deprivation demonstrate worse patterns of physical function, pain interference, depression, or anxiety on initial presentation to an orthopaedic provider than patients living in areas with low levels of social deprivation, compared with prepandemic PROMIS scores? METHODS: This was a retrospective, comparative study of new patient evaluations that occurred in the orthopaedic department at a large, urban tertiary care academic medical center. During the study period, PROMIS computer adaptive tests were routinely administered to patients at clinical visits. Between January 1, 2019, and December 31, 2019, we identified 26,989 new patients; we excluded 4% (1038 of 26,989) for being duplicates, 4% (1034 of 26,989) for having incomplete demographic data, 44% (11,925 of 26,989) for not having a nine-digit home ZIP Code recorded, and 5% (1332 of 26,989) for not completing all four PROMIS computer adaptive tests of interest. This left us with 11,660 patients in the "before COVID-19" cohort. Between January 1, 2021 and December 31, 2021, we identified 30,414 new patients; we excluded 5% (1554 of 30,414) for being duplicates, 4% (1142 of 30,414) for having incomplete demographic data, 41% (12,347 of 30,414) for not having a nine-digit home ZIP Code recorded, and 7% (2219 of 30,414) for not completing all four PROMIS computer adaptive tests of interest. This left us with 13,152 patients in the "during COVID-19" cohort. Nine-digit home ZIP Codes were used to determine patients' Area Deprivation Indexes, a neighborhood-level composite measure of social deprivation. To ensure that patients included in the study represented our overall patient population, we performed univariate analyses on available demographic and PROMIS data between patients included in the study and those excluded from the study, which revealed no differences (results not shown). In the before COVID-19 cohort, the mean age was 57 ± 16 years, 60% (7046 of 11,660) were women, 86% (10,079 of 11,660) were White non-Hispanic, and the mean national Area Deprivation Index percentile was 47 ± 25. In the during COVID-19 cohort, the mean age was 57 ± 16 years, 61% (8051 of 13,152) were women, 86% (11,333 of 13,152) were White non-Hispanic, and the mean national Area Deprivation Index percentile was 46 ± 25. The main outcome measures in this study were the PROMIS Physical Function ([PF], version 2.0), Pain Interference ([PI], version 1.1), Depression (version 1.0), and Anxiety (version 1.0). PROMIS scores follow a normal distribution with a mean t-score of 50 and a standard deviation of 10. Higher PROMIS PF scores indicate better self-reported physical capability, whereas higher PROMIS PI, Depression, and Anxiety scores indicate more difficulty managing pain, depression, and anxiety symptoms, respectively. Clinically meaningful differences in PROMIS scores between the cohorts were based on a minimum clinically important difference (MCID) threshold of 4 points. Multivariable linear regression models were created to determine whether presentation to an orthopaedic provider during the pandemic was associated with worse PROMIS scores than for patients who presented before the pandemic. Regression coefficients (ß) represent the estimated difference in PROMIS scores that would be expected for patients who presented during the pandemic compared with patients who presented before the pandemic, after adjusting for confounding variables. Regression coefficients were evaluated in the context of clinical importance and statistical significance. Regression coefficients equal to or greater than the MCID of 4 points were considered clinically important, whereas p values < 0.05 were considered statistically significant. RESULTS: We found no clinically important differences in baseline physical and mental health PROMIS scores between new patients who presented to an orthopaedic provider before the COVID-19 pandemic and those who presented during the COVID-19 pandemic (PROMIS PF: ß -0.2 [95% confidence interval -0.43 to 0.03]; p = 0.09; PROMIS PI: ß 0.06 [95% CI -0.13 to 0.25]; p = 0.57; PROMIS Depression: ß 0.09 [95% CI -0.14 to 0.33]; p = 0.44; PROMIS Anxiety: ß 0.58 [95% CI 0.33 to 0.84]; p < 0.001). Although patients from areas with high levels of social deprivation had worse PROMIS scores than patients from areas with low levels of social deprivation, patients from areas with high levels of social deprivation demonstrated no clinically important differences in PROMIS scores when groups before and during the pandemic were compared (PROMIS PF: ß -0.23 [95% CI -0.80 to 0.33]; p = 0.42; PROMIS PI: ß 0.18 [95% CI -0.31 to 0.67]; p = 0.47; PROMIS Depression: ß 0.42 [95% CI -0.26 to 1.09]; p = 0.23; PROMIS Anxiety: ß 0.84 [95% CI 0.16 to 1.52]; p = 0.02). CONCLUSION: Contrary to studies describing worse physical and mental health since the onset of the COVID-19 pandemic, we found no changes in the health status of orthopaedic patients on initial presentation to their provider. Although large-scale action to mitigate the effects of worsening physical or mental health of orthopaedic patients may not be needed at this time, orthopaedic providers should remain aware of the psychosocial needs of their patients and advocate on behalf of those who may benefit from intervention. Our study is limited in part to patients who had the self-agency to access specialty orthopaedic care, and therefore may underestimate the true changes in the physical or mental health status of all patients with musculoskeletal conditions. Future longitudinal studies evaluating the impact of specific COVID-19-related factors (for example, delays in medical care, social isolation, or financial loss) on orthopaedic outcomes may be helpful to prepare for future pandemics or natural disasters. LEVEL OF EVIDENCE: Level II, prognostic study.

Validation of Adult Spinal Deformity Surgical Outcome Prediction Tools in Adult Symptomatic Lumbar Scoliosis.

STUDY DESIGN: A post hoc analysis. OBJECTIVE: Advances in machine learning (ML) have led to tools offering individualized outcome predictions for adult spinal deformity (ASD). Our objective is to examine the properties of these ASD models in a cohort of adult symptomatic lumbar scoliosis (ASLS) patients. SUMMARY OF BACKGROUND DATA: ML algorithms produce patient-specific probabilities of outcomes, including major complication (MC), reoperation (RO), and readmission (RA) in ASD. External validation of these models is needed. METHODS: Thirty-nine predictive factors (12 demographic, 9 radiographic, 4 health-related quality of life, 14 surgical) were retrieved and entered into web-based prediction models for MC, unplanned RO, and hospital RA. Calculated probabilities were compared with actual event rates. Discrimination and calibration were analyzed using receiver operative characteristic area under the curve (where 0.5=chance, 1=perfect) and calibration curves (Brier scores, where 0.25=chance, 0=perfect). Ninety-five percent confidence intervals are reported. RESULTS: A total of 169 of 187 (90%) surgical patients completed 2-year follow up. The observed rate of MCs was 41.4% with model predictions ranging from 13% to 68% (mean: 38.7%). RO was 20.7% with model predictions ranging from 9% to 54% (mean: 30.1%). Hospital RA was 17.2% with model predictions ranging from 13% to 50% (mean: 28.5%). Model classification for all three outcome measures was better than chance for all [area under the curve=MC 0.6 (0.5-0.7), RA 0.6 (0.5-0.7), RO 0.6 (0.5-0.7)]. Calibration was better than chance for all, though best for RA and RO (Brier Score=MC 0.22, RA 0.16, RO 0.17). CONCLUSIONS: ASD prediction models for MC, RA, and RO performed better than chance in a cohort of adult lumbar scoliosis patients, though the homogeneity of ASLS affected calibration and accuracy. Optimization of models require samples with the breadth of outcomes (0%-100%), supporting the need for continued data collection as personalized prediction models may improve decision-making for the patient and surgeon alike.

Rod fractures in thoracolumbar fusions to the sacrum/pelvis for adult symptomatic lumbar scoliosis: long-term follow-up of a prospective, multicenter cohort of 160 patients.

OBJECTIVE: Previous reports of rod fracture (RF) in adult spinal deformity are limited by heterogeneous cohorts, low follow-up rates, and relatively short follow-up durations. Since the majority of RFs present > 2 years after surgery, true occurrence and revision rates remain unclear. The objectives of this study were to better understand the risk factors for RF and assess its occurrence and revision rates following primary thoracolumbar fusions to the sacrum/pelvis for adult symptomatic lumbar scoliosis (ASLS) in a prospective series with long-term follow-up. METHODS: Patient records were obtained from the Adult Symptomatic Lumbar Scoliosis-1 (ASLS-1) database, an NIH-sponsored multicenter, prospective study. Inclusion criteria were as follows: patients aged 40-80 years undergoing primary surgeries for ASLS (Cobb angle ≥ 30° and Oswestry Disability Index ≥ 20 or Scoliosis Research Society-22r ≤ 4.0 in pain, function, and/or self-image) with instrumented fusion of ≥ 7 levels that included the sacrum/pelvis. Patients with and without RF were compared to assess risk factors for RF and revision surgery. RESULTS: Inclusion criteria were met by 160 patients (median age 62 years, IQR 55.7-67.9 years). At a median follow-up of 5.1 years (IQR 3.8-6.6 years), there were 92 RFs in 62 patients (38.8%). The median time to RF was 3.0 years (IQR 1.9-4.54 years), and 73% occurred > 2 years following surgery. Based on Kaplan-Meier analyses, estimated RF rates at 2, 4, 5, and 8 years after surgery were 11%, 24%, 35%, and 49%, respectively. Baseline radiographic, clinical, and demographic characteristics were similar between patients with and without RF. In Cox regression models, greater postoperative pelvic tilt (HR 1.895, 95% CI 1.196-3.002, p = 0.0065) and greater estimated blood loss (HR 1.02, 95% CI 1.005-1.036, p = 0.0088) were associated with increased risk of RF. Thirty-eight patients (61% of all RFs) underwent revision surgery. Bilateral RF was predictive of revision surgery (HR 3.52, 95% CI 1.8-6.9, p = 0.0002), while patients with unilateral nondisplaced RFs were less likely to require revision (HR 0.39, 95% CI 0.18-0.84, p = 0.016). CONCLUSIONS: This study provides what is to the authors' knowledge the highest-quality data to date on RF rates following ASLS surgery. At a median follow-up of 5.1 years, 38.8% of patients had at least one RF. Estimated RF rates at 2, 4, 5, and 8 years after surgery were 11%, 24%, 35%, and 49%, respectively. Greater estimated blood loss and postoperative pelvic tilt were significant risk factors for RF. These findings emphasize the importance of long-term follow-up to realize the true prevalence and cumulative incidence of RF.

Occupational demands associated with rotator cuff disease surgery in the UK Biobank.

OBJECTIVES: Physically-demanding occupations may increase rotator cuff disease (RCD) risk and need for surgery. We linked a job-exposure matrix (JEM) to the UK Biobank cohort study to measure physical occupational exposures and estimate associations with RCD surgery. METHODS: Jobs and UK Standard Occupational Classification (SOC) codes were recorded during the UK Biobank verbal interview. Lifetime job histories were captured through a web-based survey. UK SOC codes were linked to a JEM based on the US O*NET database. O*NET-based scores [static strength, dynamic strength, general physical activities, handling/moving objects (range=1-7), time spent using hands, whole body vibration, and cramped/awkward positions (range=1-5)] were assigned to jobs. RCD surgeries were identified through linked national hospital inpatient records. Multivariable Cox regression was used to calculate hazard ratios (HR) as estimates of associations with RCD surgery. Among those with lifetime job histories, associations were estimated for duration of time with greatest exposure (top quartile of exposure). RESULTS: Of 277 808 people reporting jobs, 1997 (0.7%) had an inpatient RCD surgery. After adjusting for age, sex, race, education, area deprivation, and body mass index, all O*NET variables considered were associated with RCD surgery (HR per point increase range=1.10-1.45, all P<0.005). A total of 100 929 people reported lifetime job histories, in which greater exposures were significantly associated with RCD surgery after >10 years of work (eg, HR for 11-20 versus 0 years with static strength score ≥4 = 2.06, 95% confidence interval 1.39-3.04). CONCLUSIONS: Workplace physical demands are an important risk factor for RCD surgery, particularly for workers with more than a decade of exposure.

Proximal junctional failure in primary thoracolumbar fusion/fixation to the sacrum/pelvis for adult symptomatic lumbar scoliosis: long-term follow-up of a prospective multicenter cohort of 160 patients.

OBJECTIVE: Proximal junctional failure (PJF) is a severe form of proximal junctional kyphosis. Previous reports on PJF have been limited by heterogeneous cohorts and relatively short follow-ups. The authors' objectives herein were to identify risk factors for PJF and to assess its long-term incidence and revision rates in a homogeneous cohort. METHODS: The authors reviewed data from the Adult Symptomatic Lumbar Scoliosis 1 trial (ASLS-1), a National Institutes of Health-sponsored prospective multicenter study. Inclusion criteria were an age ≥ 40 years, ASLS (Cobb angle ≥ 30° and Oswestry Disability Index [ODI] ≥ 20 or Scoliosis Research Society revised 22-item questionnaire [SRS-22r] score ≤ 4.0 in pain, function, or self-image domains), and primary thoracolumbar fusion/fixation to the sacrum/pelvis of ≥ 7 levels. PJF was defined as a postoperative proximal junctional angle (PJA) change > 20°, fracture of the uppermost instrumented vertebra (UIV) or UIV+1 with > 20% vertebral height loss, spondylolisthesis of UIV/UIV+1 > 3 mm, or UIV screw dislodgment. RESULTS: One hundred sixty patients (141 women) were included in this analysis and had a median age of 62 years and a mean follow-up of 4.3 years (range 0.1-6.1 years). Forty-six patients (28.8%) had PJF at a median of 0.92 years (IQR 0.14, 1.23 years) following surgery. Based on Kaplan-Meier analyses, PJF rates at 1, 2, 3, and 4 years were 14.4%, 21.9%, 25.9%, and 27.4%, respectively. On univariate analysis, PJF was associated with greater age (p = 0.0316), greater body mass index (BMI; p = 0.0319), worse baseline patient-reported outcome measures (PROMs; ODI, SRS-22r, and SF-12 Physical Component Summary [PCS]; all p < 0.04), the use of posterior column osteotomies (PCOs; p = 0.0039), and greater postoperative thoracic kyphosis (TK; p = 0.0031) and PJA (p < 0.001). The use of UIV hooks was protective against PJF (p = 0.0340). On regression analysis (without postoperative measures), PJF was associated with greater BMI (HR 1.077, 95% CI 1.007-1.153, p = 0.0317), lower preoperative PJA (HR 0.607, 95% CI 0.407-0.906, p = 0.0146), and greater preoperative TK (HR 1.362, 95% CI 1.082-1.715, p = 0.0085). Patients with PJF had worse PROMs at the last follow-up (ODI, SRS-22r subscore and self-image, and SF-12 PCS; p < 0.04). Sixteen PJF patients (34.8%) underwent revision, and PJF recurred in 3 (18.8%). CONCLUSIONS: Among 160 primary ASLS patients with a median age of 62 years and predominant coronal deformity, the PJF rate was 28.8% at a mean 4.3-year follow-up, with a revision rate of 34.8%. On univariate analysis, PJF was associated with a greater age and BMI, worse baseline PROMs, the use of PCOs, and greater postoperative TK and PJA. The use of UIV hooks was protective against PJF. On multivariate analysis (without postoperative measures), a higher risk of PJF was associated with greater BMI and preoperative TK and lower preoperative PJA.

Occupational characteristics associated with SARS-CoV-2 infection in the UK Biobank during August-November 2020: a cohort study.

BACKGROUND: Occupational exposures may play a key role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection risk. We used a job-exposure matrix linked to the UK Biobank to measure occupational characteristics and estimate associations with a positive SARS-CoV-2 test. METHODS: People reporting job titles at their baseline interview in England who were < 65 years of age in 2020 were included. Healthcare workers were excluded because of differential access to testing. Jobs were linked to the US Occupational Information Network (O*NET) job exposure matrix. O*NET-based scores were examined for occupational physical proximity, exposure to diseases/infection, working outdoors exposed to weather, and working outdoors under cover (score range = 1-5). Jobs were classified as remote work using two algorithms. SARS-CoV-2 test results were evaluated between August 5th-November 10th, 2020, when the UK was released from lockdown. Cox regression was used to calculate adjusted hazard ratios (aHRs), accounting for age, sex, race, education, neighborhood deprivation, assessment center, household size, and income. RESULTS: We included 115,451 people with job titles, of whom 1746 tested positive for SARS-CoV-2. A one-point increase in physical proximity score was associated with 1.14 times higher risk of SARS-CoV-2 (95%CI = 1.05-1.24). A one-point increase in the exposure to diseases/infections score was associated with 1.09 times higher risk of SARS-CoV-2 (95%CI = 1.02-1.16). People reporting jobs that could not be done remotely had higher risk of SARS-CoV-2 regardless of the classification algorithm used (aHRs = 1.17 and 1.20). Outdoors work showed an association with SARS-CoV-2 (exposed to weather aHR = 1.06, 95%CI = 1.01-1.11; under cover aHR = 1.08, 95%CI = 1.00-1.17), but these associations were not significant after accounting for whether work could be done remotely. CONCLUSION: People in occupations that were not amenable to remote work, required closer physical proximity, and required more general exposure to diseases/infection had higher risk of a positive SARS-CoV-2 test. These findings provide additional evidence that coronavirus disease 2019 (COVID-19) is an occupational disease, even outside of the healthcare setting, and indicate that strategies for mitigating transmission in in-person work settings will remain important.

Patient-reported outcome measure clustering after surgery for adult symptomatic lumbar scoliosis.

OBJECTIVE: Adult symptomatic lumbar scoliosis (ASLS) is a widespread and debilitating subset of adult spinal deformity. Although many patients benefit from operative treatment, surgery entails substantial cost and risk for adverse events. Patient-reported outcome measures (PROMs) are patient-centered tools used to evaluate the appropriateness of surgery and to assist in the shared decision-making process. Framing realistic patient expectations should include the possible functional limitation to improvement inherent in surgical intervention, such as multilevel fusion to the sacrum. The authors' objective was to predict postoperative ASLS PROMs by using clustering analysis, generalized longitudinal regression models, percentile analysis, and clinical improvement analysis of preoperative health-related quality-of-life scores for use in surgical counseling. METHODS: Operative results from the combined ASLS cohorts were examined. PROM score clustering after surgery investigated limits of surgical improvement. Patients were categorized by baseline disability (mild, moderate, moderate to severe, or severe) according to preoperative Scoliosis Research Society (SRS)-22 and Oswestry Disability Index (ODI) scores. Responder analysis for patients achieving improvement meeting the minimum clinically important difference (MCID) and substantial clinical benefit (SCB) standards was performed using both fixed-threshold and patient-specific values (MCID = 30% of remaining scale, SCB = 50%). Best (top 5%), worst (bottom 5%), and median scores were calculated across disability categories. RESULTS: A total of 171/187 (91%) of patients with ASLS achieved 2-year follow-up. Patients rarely achieved a PROM ceiling for any measure, with 33%-43% of individuals clustering near 4.0 for SRS domains. Patients with severe baseline disability (< 2.0) SRS-pain and SRS-function scores were often left with moderate to severe disability (2.0-2.9), unlike patients with higher (≥ 3.0) initial PROM values. Patients with mild disability according to baseline SRS-function score were unlikely to improve. Crippling baseline ODI disability (> 60) commonly left patients with moderate disability (median ODI = 32). As baseline ODI disability increased, patients were more likely to achieve MCID and SCB (p < 0.001). Compared to fixed threshold values for MCID and SCB, patient-specific values were more sensitive to change for patients with minimal ODI baseline disability (p = 0.008) and less sensitive to change for patients with moderate to severe SRS subscore disability (p = 0.01). CONCLUSIONS: These findings suggest that ASLS surgeries have a limit to possible improvement, probably due to both baseline disability and the effects of surgery. The most disabled patients often had moderate to severe disability (SRS < 3, ODI > 30) at 2 years, emphasizing the importance of patient counseling and expectation management.

Tumor Necrosis Factor Inhibitors and the Risk of Cancer among Older Americans with Rheumatoid Arthritis.

BACKGROUND: TNF inhibitors (TNFi) effectively treat rheumatoid arthritis but may increase patient risk of some malignancies, particularly lymphomas or skin cancers. METHODS: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data to conduct a case-control study in patients with rheumatoid arthritis (2007-2015). Cases were individuals with a first cancer diagnosed in SEER registries (ages 66-99, 22 cancer sites, N = 10,263). Skin cancer cases [nonmelanoma skin cancer (NMSC, N = 501), basal cell carcinoma (BCC, N = 161), squamous cell carcinoma (SCC, N = 150)] and cancer-free controls (N = 30,475) were selected from Medicare beneficiaries residing in SEER areas. Cases and controls had prior Medicare claims-based evidence for rheumatoid arthritis, and TNFi exposure was ascertained from part B and part D claims. Logistic regression was used to estimate adjusted odds ratios (aOR). RESULTS: TNFi exposure was present in 16.2% of controls and 12.8% to 33.7% of cancer cases, varying by site. TNFi use was associated with increased risk of NMSC overall (aOR 1.32, 95% confidence interval 1.06-1.63), non-Hodgkin lymphoma (NHL) overall (1.28, 1.06-1.56) and, specifically, follicular lymphoma (2.63, 1.63-4.24). TNFi exposure was not associated with other SEER cancer sites, BCC or SCC specifically, or other common NHL subtypes. CONCLUSIONS: Among older adults with rheumatoid arthritis, TNFi exposure was associated with elevated risk of NMSC and NHL, driven specifically by follicular lymphoma. Exposure was not associated with increased risk for other cancer sites. IMPACT: Our results support a role for TNF in lymphomagenesis. Given the association with NMSC, patients initiating TNFi therapy may benefit from skin cancer screening and sun protection measures.

Orthopedic disease burden in adult patients with symptomatic lumbar scoliosis: results from a prospective multicenter study.

OBJECTIVE: Although the health impact of adult symptomatic lumbar scoliosis (ASLS) is substantial, these patients often have other orthopedic problems that have not been previously quantified. The objective of this study was to assess disease burden of other orthopedic conditions in patients with ASLS based on a retrospective review of a prospective multicenter cohort. METHODS: The ASLS-1 study is an NIH-sponsored prospective multicenter study designed to assess operative versus nonoperative treatment for ASLS. Patients were 40-80 years old with ASLS, defined as a lumbar coronal Cobb angle ≥ 30° and Oswestry Disability Index ≥ 20, or Scoliosis Research Society-22 questionnaire score ≤ 4.0 in pain, function, and/or self-image domains. Nonthoracolumbar orthopedic events, defined as fractures and other orthopedic conditions receiving surgical treatment, were assessed from enrollment to the 4-year follow-up. RESULTS: Two hundred eighty-six patients (mean age 60.3 years, 90% women) were enrolled, with 173 operative and 113 nonoperative patients, and 81% with 4-year follow-up data. At a mean (± SD) follow-up of 3.8 ± 0.9 years, 104 nonthoracolumbar orthopedic events were reported, affecting 69 patients (24.1%). The most common events were arthroplasty (n = 38), fracture (n = 25), joint ligament/cartilage repair (n = 13), and cervical decompression/fusion (n = 7). Based on the final adjusted model, patients with a nonthoracolumbar orthopedic event were older (HR 1.44 per decade, 95% CI 1.07-1.94), more likely to have a history of tobacco use (HR 1.63, 95% CI 1.00-2.66), and had worse baseline leg pain scores (HR 1.10, 95% CI 1.01-1.19). CONCLUSIONS: Patients with ASLS have high orthopedic disease burden, with almost 25% having a fracture or nonthoracolumbar orthopedic condition requiring surgical treatment during the mean 3.8 years following enrollment. Comparisons with previous studies suggest that the rate of total knee arthroplasty was considerably greater and the rates of total hip arthroplasty were at least as high in the ASLS-1 cohort compared with the similarly aged general US population. These conditions may further impact health-related quality of life and outcomes assessments of both nonoperative and operative treatment approaches in patients with ASLS.

Identification of a Novel Genetic Marker for Risk of Degenerative Rotator Cuff Disease Surgery in the UK Biobank.

BACKGROUND: While evidence indicates that familial predisposition influences the risk of developing degenerative rotator cuff disease (RCD), knowledge of specific genetic markers is limited. We conducted a genome-wide association study of RCD surgery using the UK Biobank, a prospective cohort of 500,000 people (40 to 69 years of age at enrollment) with genotype data. METHODS: Cases with surgery for degenerative RCD were identified using linked hospital records. The cases were defined as an International Classification of Diseases, Tenth Revision (ICD-10) code of M75.1 determined by a trauma/orthopaedic specialist and surgery consistent with RCD treatment. Cases were excluded if a diagnosis of traumatic injury had been made during the same hospital visit. For each case, up to 5 controls matched by age, sex, and follow-up time were chosen from the UK Biobank. Analyses were limited to European-ancestry individuals who were not third-degree or closer relations. We used logistic regression to test for genetic association of 674,405 typed and >10 million imputed markers, after adjusting for age, sex, population principal components, and follow-up. RESULTS: We identified 2,917 RCD surgery cases and 14,158 matched controls. We observed 1 genome-wide significant signal (p < 5 × 10-8) for a novel locus tagged by rs2237352 in the CREB5 gene on chromosome 7 (odds ratio [OR] = 1.17, 95% confidence interval [CI] = 1.11 to 1.24). The single-nucleotide polymorphism (SNP) rs2237352 was imputed with a high degree of confidence (info score = 0.9847) and is common, with a minor allele frequency of 47%. After expanding the control sample to include additional unmatched non-cases, rs2237352 and another SNP in the CREB5 gene, rs12700903, were genome-wide significant. We did not detect genome-wide significant signals at loci associated with RCD in previous studies. CONCLUSIONS: We identified a novel association between a variant in the CREB5 gene and RCD surgery. Validation of this finding in studies with imaging data to confirm diagnoses will be an important next step. CLINICAL RELEVANCE: Identification of genetic RCD susceptibility markers can guide understanding of biological processes in rotator cuff degeneration and help inform disease risk in the clinical setting. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Operative versus nonoperative treatment for adult symptomatic lumbar scoliosis at 5-year follow-up: durability of outcomes and impact of treatment-related serious adverse events.

OBJECTIVE: Although short-term adult symptomatic lumbar scoliosis (ASLS) studies favor operative over nonoperative treatment, longer outcomes are critical for assessment of treatment durability, especially for operative treatment, because the majority of implant failures and nonunions present between 2 and 5 years after surgery. The objectives of this study were to assess the durability of treatment outcomes for operative versus nonoperative treatment of ASLS, to report the rates and types of associated serious adverse events (SAEs), and to determine the potential impact of treatment-related SAEs on outcomes. METHODS: The ASLS-1 (Adult Symptomatic Lumbar Scoliosis-1) trial is an NIH-sponsored multicenter prospective study to assess operative versus nonoperative ASLS treatment. Patients were 40-80 years of age and had ASLS (Cobb angle ≥ 30° and Oswestry Disability Index [ODI] ≥ 20 or Scoliosis Research Society [SRS]-22 subscore ≤ 4.0 in the Pain, Function, and/or Self-Image domains). Patients receiving operative and nonoperative treatment were compared using as-treated analysis, and the impact of related SAEs was assessed. Primary outcome measures were ODI and SRS-22. RESULTS: The 286 patients with ASLS (107 with nonoperative treatment, 179 with operative treatment) had 2-year and 5-year follow-up rates of 90% (n = 256) and 74% (n = 211), respectively. At 5 years, compared with patients treated nonoperatively, those who underwent surgery had greater improvement in ODI (mean difference -15.2 [95% CI -18.7 to -11.7]) and SRS-22 subscore (mean difference 0.63 [95% CI 0.48-0.78]) (p < 0.001), with treatment effects (TEs) exceeding the minimum detectable measurement difference (MDMD) for ODI (7) and SRS-22 subscore (0.4). TEs at 5 years remained as favorable as 2-year TEs (ODI -13.9, SRS-22 0.52). For patients in the operative group, the incidence rates of treatment-related SAEs during the first 2 years and 2-5 years after surgery were 22.38 and 8.17 per 100 person-years, respectively. At 5 years, patients in the operative group who had 1 treatment-related SAE still had significantly greater improvement, with TEs (ODI -12.2, SRS-22 0.53; p < 0.001) exceeding the MDMD. Twelve patients who received surgery and who had 2 or more treatment-related SAEs had greater improvement than nonsurgically treated patients based on ODI (TE -8.34, p = 0.017) and SRS-22 (TE 0.32, p = 0.029), but the SRS-22 TE did not exceed the MDMD. CONCLUSIONS: The significantly greater improvement of operative versus nonoperative treatment for ASLS at 2 years was durably maintained at the 5-year follow-up. Patients in the operative cohort with a treatment-related SAE still had greater improvement than patients in the nonoperative cohort. These findings have important implications for patient counseling and future cost-effectiveness assessments.

Trends in rotator cuff repair rates and comorbidity burden among commercially insured patients younger than the age of 65 years, United States 2007-2016.

Background: Prior US studies have shown increasing rotator cuff repair rates through 2009. We hypothesize that rotator cuff repair rates are continuing to increase and the comorbidity profiles of patients are becoming more complex over time. Methods: We identified rotator cuff repairs in a large US cohort of people 18-64 years of age with ≥1 year of commercial insurance coverage. Repair rate trends across time were standardized by age, sex, and geographic region. Procedures were categorized as inpatient vs. outpatient and as arthroscopic vs. open. Prevalent comorbidities were defined as 1 inpatient diagnosis claim or 2 outpatient diagnosis claims during the year before rotator cuff repair. General population comorbidity prevalence was determined based on a random 5% sample of the commercially insured population and compared with patients with rotator cuff repair using standardized morbidity ratios. Results: From 2007 to 2016, 314,239 rotator cuff repairs were identified (165 repairs per 100,000 person-years). Rotator cuff repairs were performed more frequently in men, older people, and in the Midwest. Across time, cuff repair rates increased by 1.6% per year (95% confidence interval [CI] = +1.4%-1.7%) adjusting for demographics. The highest increases in repair rates were observed among patients aged 50-64 years (+2.0%, 95% CI = +1.8%-2.2%). Rotator cuff repairs were more frequently performed using an arthroscopic approach and in an outpatient setting in later calendar years. In 2016, 83% of rotator cuff repairs were arthroscopic procedures and 99% were performed as outpatient procedures. Comorbidity prevalence in rotator cuff repair patients increased across calendar time by 4.5% per year for hypertension (95% CI = +4.2%-4.7%), 2.3% per year for diabetes (+1.9%-2.7%), 0.9% per year for hypercholesterolemia (+0.3%-1.5%), 2.9% for congestive heart failure (+0.8%-4.9%), 4.2% for peripheral vascular disease (+2.4%-6.0%), and 4.2% for chronic pulmonary disease (+3.6%-4.8%). Comorbidity prevalence in repair patients was higher than prevalence in the general population, and prevalence relative to the general population was most heightened during later calendar years. For example, hypertension prevalence was 1.58 times higher in repair patients than the general population in 2007 (95% CI = 1.53-1.62), and 2.06 times higher in 2016 (95% CI = 2.02-2.11). Conclusion: Rotator cuff repair is becoming more frequent in the US commercially insured population, particularly in those 50-64 years of age. More rotator cuff repairs are being performed using an arthroscopic approach and in an outpatient setting. Over time, the comorbidity profile of patients undergoing rotator cuff repair is becoming more complex with greater prevalence of numerous conditions, including hypertension, peripheral vascular disease, and chronic pulmonary disease.

'Black Box' to 'Conversational' Machine Learning: Ondansetron Reduces Risk of Hospital-Acquired Venous Thromboembolism.

Machine learning, combined with a proliferation of electronic healthcare records (EHR), has the potential to transform medicine by identifying previously unknown interventions that reduce the risk of adverse outcomes. To realize this potential, machine learning must leave the conceptual 'black box' in complex domains to overcome several pitfalls, like the presence of confounding variables. These variables predict outcomes but are not causal, often yielding uninformative models. In this work, we envision a 'conversational' approach to design machine learning models, which couple modeling decisions to domain expertise. We demonstrate this approach via a retrospective cohort study to identify factors which affect the risk of hospital-acquired venous thromboembolism (HA-VTE). Using logistic regression for modeling, we have identified drugs that reduce the risk of HA-VTE. Our analysis reveals that ondansetron, an anti-nausea and anti-emetic medication, commonly used in treating side-effects of chemotherapy and post-general anesthesia period, substantially reduces the risk of HA-VTE when compared to aspirin (11% vs. 15% relative risk reduction or RRR, respectively). The low cost and low morbidity of ondansetron may justify further inquiry into its use as a preventative agent for HA-VTE. This case study highlights the importance of engaging domain expertise while applying machine learning in complex domains.

Differences in Functional Treadmill Tests in Patients With Adult Symptomatic Lumbar Scoliosis Treated Operatively and Nonoperatively.

STUDY DESIGN: Prospective longitudinal cohort. OBJECTIVES: The aim of this study was to determine whether functional treadmill testing (FTT) demonstrates differences between patients treated operatively and nonoperatively for adult symptomatic lumbar scoliosis (ASLS). SUMMARY OF BACKGROUND DATA: ASLS has become increasingly prevalent as the population ages. ASLS can be accompanied by neurogenic claudication, leading to difficulty walking. FTT may provide a functional tool to evaluate patients with ASLS. METHODS: One hundred and eighty-seven patients who underwent nonoperative (n = 88) or operative treatment (n = 99) of ASLS with complete baseline and 2-year post-treatment FTTs and concurrent patient-reported outcomes were identified. FTT parameters included maximum speed, time to onset of symptoms, distance ambulated, time ambulated, and Back and Leg pain severity before and after testing. RESULTS: At baseline, patients treated operatively reported worse post-FTT back pain (4.39 vs. 3.45, P = 0.032) than those treated nonoperatively, despite similar ODI, SRS-22 Pain and Activity domain scores. Mean time ambulated (+2.15 vs. -1.20 P = 0.001), pre-FTT back pain (+0.19 vs. -1.60, P < 0.000) and leg pain (+0.25 vs. -0.54, P = 0.024) improved in the operative group but deteriorated in the nonoperative group. On the 2-year follow-up FTT, both groups showed improvement in post-FTT back pain (-0.53 vs. -2.64, P < 0.000) and leg pain (-0.13 vs. -1.54, P = 0.001) severity but the improvement was statistically significantly greater in the operative compared to the nonoperative group. CONCLUSION: FTT results at baseline were worse in patients treated operatively than those treated non-operatively. FTT may be a useful adjunct to assess treatment outcomes in patients with ASLS and may help surgeons counsel patients regarding expectations 2 years after operative or nonoperative treatment for ASLS. At 2-year follow-up, time ambulated deteriorated in patients treated nonoperatively but improved in patients treated operatively. Although both groups showed improvement in post-FTT Back and Leg pain at 2 years, the improvement was greater in the operative compared to the nonoperative group. LEVEL OF EVIDENCE: 2.