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.

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.

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.

Incidence of hepatocellular carcinoma among older Americans attributable to hepatitis C and hepatitis B: 2001 through 2013.

BACKGROUND: In the United States, incidence and mortality rates of hepatocellular carcinoma (HCC) are increasing in older individuals. Chronic infection with hepatitis C virus (HCV) and hepatitis B virus (HBV) are important causes of HCC; however, the contribution of viral hepatitis to recent trends in HCC incidence among older Americans is unclear. METHODS: Data from the Surveillance, Epidemiology, and End Results-Medicare linkage (SEER-Medicare) for the years 2001 through 2013 were used to identify HCC cases among individuals aged ≥66 years and Medicare files were used to assess the HCV and HBV status of these HCC cases. Age-standardized incidence rates of HCV-attributable, HBV-attributable, and HCV/HBV-unrelated HCC were estimated overall and by age group, sex, and race/ethnicity. The authors also calculated annual percent changes (APCs) in HCC incidence. RESULTS: Between 2001 and 2013, a total of 15,300 HCC cases occurred in this population. Overall HCC rates increased 43% from 16.3 to 23.3 per 100,000 population (APC, 3.40% per year), whereas HCV-attributable HCC rates nearly doubled from 4.2 to 8.2 per 100,000 population (APC, 5.62% per year). HCC rates increased more slowly for HBV-attributable HCC (1.3 to 1.8 per 100,000 population; APC, 3.17% per year) and HCV/HBV-unrelated HCC (11.3 to 14.1 per 100,000 population; APC, 2.35% per year). The percentage of HCC cases with evidence of HCV infection increased from 25.7% in 2001 through 2004 to 32.3% in 2011 through 2013, whereas the percentage with HBV remained stable at 8%. In 2013, higher rates for both HCV-attributable and HBV-attributable HCC were noted among individuals aged 66 to 75 years, men, and individuals of Asian ancestry. CONCLUSIONS: Among Americans aged ≥66 years, HCC rates increased rapidly between 2001 and 2013. Although HCV-attributable cases contributed substantially to this increase, rates of HBV-attributable and HCV/HBV-unrelated HCC also rose during this period.

Risk of lung cancer in lung transplant recipients in the United States.

Lung transplant recipients have an increased risk of lung cancer that is poorly understood. Prior studies are largely descriptive and single-center, and have not examined risk factors or outcomes in this population. This registry-linkage study utilized matched transplant and cancer registry data from 17 US states/regions during 1987-2012. We used standardized incidence ratios (SIRs) to compare incidence with the general population, Poisson models to identify lung cancer risk factors, and Cox models to compare survival after diagnosis. Lung cancer risk was increased among lung recipients (SIR 4.8, 95% confidence interval [CI] 4.1-5.5). Those with single lung transplant had 13-fold (95% CI 11-15) increased risk in the native lung. Native lung cancer risk factors included age, prior smoking, time since transplant, and idiopathic pulmonary fibrosis. Compared with cases in the general population, lung cancers in recipients were more frequently localized stage (P = .02) and treated surgically (P = .05). However, recipients had higher all-cause (adjusted hazard ratio 1.90, 95% CI 1.52-2.37) and cancer-specific mortality (adjusted hazard ratio 1.67, 95% CI 1.28-2.18). In conclusion, lung cancer risk is increased after lung transplant, especially in the native lung of single lung recipients. Traditional risk factors are associated with lung cancer in these patients. Lung cancer survival is worse among lung recipients despite earlier diagnosis.

The Pattern of Acetabular Cartilage Wear Is Hip Morphology-dependent and Patient Demographic-dependent.

BACKGROUND: Acetabular cartilage damage has been described in patients with femoroacetabular impingement (FAI). However, most reports of articular cartilage damage in hip FAI have been focused on the acetabular cartilage and derived from single-center, retrospective studies of relatively small patient cohorts. Identifying patterns of articular cartilage wear is important in patient selection, treatment prognosis, and determining whether patterns of intraarticular cartilage wear are secondary to abnormal hip morphology. Using a multicenter, observational cohort, we sought to determine whether there was a specific pattern of cartilage wear across acetabular and femoral articular cartilage among patients with symptomatic FAI. QUESTIONS/PURPOSES: (1) Is there is a specific pattern of cartilage wear in the acetabulum and femoral head, assessed during hip arthroscopy, in cam FAI, pincer, and mixed-type hip pathologies? (2) Are there specific patterns of cartilage wear associated with duration of symptoms, age, and/or body mass index (BMI)? METHODS: A multicenter observational cohort and a hip preservation database from a senior author were used to identify 802 patients who underwent hip arthroscopy for the treatment of symptomatic FAI. The diagnosis of cam, pincer, or mixed-type FAI was determined by each treating surgeon at each institution using the minimum basic criteria of pain in the affected hip for a period of > 3 months, hip ROM, and radiographic findings. Acetabular and femoral head cartilage lesions were classified arthroscopically by location and severity for each group (cam, pincer, or mixed FAI). Cartilage wear was classified using the Beck classification and defined as cartilage lesions greater than Grade 1 (normal macroscopically sound cartilage). The assessment of cartilage wear was performed arthroscopically by experienced hip preservation surgeons who are a part of ANCHOR, a multicenter group that uses a longitudinally maintained database to investigate issues related to hip preservation surgery. Clinical characteristics, radiographic findings, and acetabular and femoral head damage by location and severity of wear were reported based on patient diagnoses of cam (n = 472), mixed (n = 290), and pincer (n = 40) FAI hip pathologies. Wald chi-square tests were used to test for differences in the presence of wear in each cartilage quadrant across hip pathologies, duration of symptoms, age, and BMI. One-way analysis of variance tests were used to test for differences in average grade of wear in each cartilage quadrant across hip pathologies, duration of symptoms, age, and BMI. A bivariate logistic regression model was used to identify factors independently associated with the presence of cartilage wear in the acetabulum and femoral head. Acetabular cartilage wear was present in 743 of 802 patients (93%) in the cohort. Femoral head cartilage wear was observed in only 130 (16%). RESULTS: We found significant associations between acetabular patterns of wear and FAI hip pathologies; specifically, we observed more frequent and severe debonding of acetabular cartilage in patients with symptomatic cam (93%, 1.7 ± 1.1 grade) and mixed (97%, 1.7 ± 1.2 grade) FAI compared with Pincer (75%, 1.5 ± 0.9 grade) FAI hip pathologies (p < 0.001). Superolateral peripheral cartilage lesions occurred more frequently and with greater severity in patients with cam (90% [416 of 472] prevalence, 3.1 ± 1.1 grade) and mixed (91% [260 of 290] prevalence, 3.1 ± 1.1 grade) FAI than in pincer (60% [24 of 40] prevalence, 2.2 ± 1.1 grade) FAI hip pathologies (p < 0.0001). Conversely, patients with pincer FAI most commonly demonstrated cartilage lesions with an even distribution at the anterior and superolateral acetabular rim: 64% (25 of 40) (mean grade 2.1 ± 1.0) and 60% (24 of 40) mean grade 2.2 ± 1.1, respectively. Age was associated with increased presence of wear in both the acetabulum (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.2-1.7; p = 0.005) and femoral head (OR, 1.08; 95% CI, 1.6-1.1; p < 0.001). BMI was associated with a greater presence of wear only in the femoral head (OR, 1.1; 95% CI, 1.2-1.1; p = 0.002). Specifically, compared with patients with a BMI < 30 kg/m, patients with a BMI ≥ 30 kg/m presented with more frequent and more severe lesions in the posterior peripheral acetabular rim (42% [47 of 117] versus 26% [171 of 677], p = 0.0006; grade 1.9 ± 1.3 versus grade 1.4 ± 0.9, p < 0.001), the anterolateral femoral head (22% [20 of 117] versus 9% [60 of 67], p = 0.006), and the anteromedial femoral head (15% [16 of 117] versus 6% [39 of 677], p = 0.002; grade 1.3 ± 0.8 versus grade 1.1 ± 0.6, p = 0.04). In general, we found that older patients (≥ 50 years old) presented with more frequent and more severe lesions in both the acetabulum and femoral head. We found no association between hip pathology and cartilage wear patterns in the examined femoral heads. CONCLUSIONS: Hip morphology affects the pattern of acetabular cartilage wear. More frequent and severe cartilage lesions were observed in patients with symptomatic FAI cam and mixed-type hip pathologies. Surgical attempts to restore normal anatomy to avoid FAI should be performed to potentially improve long-term joint homeostasis. Increasing age is an independent risk for cartilage wear in both the acetabulum and femoral head. Additionally, increased BMI is an independent risk factor for cartilage wear in the femoral head. In the future, prospective studies should provide further insight into the pathomechanics of early degenerative changes associated with hip FAI deformities. LEVEL OF EVIDENCE: Level III, prognostic study.

Cancer-Attributable Mortality Among People With Treated Human Immunodeficiency Virus Infection in North America.

BACKGROUND: Cancer remains an important cause of morbidity and mortality in people with human immunodeficiency virus (PWHIV) on effective antiretroviral therapy (ART). Estimates of cancer-attributable mortality can inform public health efforts. METHODS: We evaluated 46956 PWHIV receiving ART in North American HIV cohorts (1995-2009). Using information on incident cancers and deaths, we calculated population-attributable fractions (PAFs), estimating the proportion of deaths due to cancer. Calculations were based on proportional hazards models adjusted for age, sex, race, HIV risk group, calendar year, cohort, CD4 count, and viral load. RESULTS: There were 1997 incident cancers and 8956 deaths during 267145 person-years of follow-up, and 11.9% of decedents had a prior cancer. An estimated 9.8% of deaths were attributable to cancer (cancer-attributable mortality rate 327 per 100000 person-years). PAFs were 2.6% for AIDS-defining cancers (ADCs, including non-Hodgkin lymphoma, 2.0% of deaths) and 7.1% for non-AIDS-defining cancers (NADCs: lung cancer, 2.3%; liver cancer, 0.9%). PAFs for NADCs were higher in males and increased strongly with age, reaching 12.5% in PWHIV aged 55+ years. Mortality rates attributable to ADCs and NADCs were highest for PWHIV with CD4 counts <100 cells/mm3. PAFs for NADCs increased during 1995-2009, reaching 10.1% in 2006-2009. CONCLUSIONS: Approximately 10% of deaths in PWHIV prescribed ART during 1995-2009 were attributable to cancer, but this fraction increased over time. A large proportion of cancer-attributable deaths were associated with non-Hodgkin lymphoma, lung cancer, and liver cancer. Deaths due to NADCs will likely grow in importance as AIDS mortality declines and PWHIV age.

Contribution of solid organ transplant recipients to the pediatric non-hodgkin lymphoma burden in the United States.

BACKGROUND: Pediatric solid organ transplant recipients have a 100 to 200 times higher risk of non-Hodgkin lymphoma (NHL) than the general pediatric population. Consequently, transplant-related NHL may contribute considerably to the pediatric NHL burden in the United States. METHODS: A cohort study using a linkage between the US transplant registry and 16 cancer registries was conducted. Cancer incidence rates were calculated for people less than 20 years old in the transplant and general populations. Rates were applied to transplant registry and US census data to estimate pediatric NHL counts for transplant recipients and the general population. RESULTS: During 1990-2012, an estimated 22,270 NHLs were diagnosed in US children and adolescents; they included 628 cases diagnosed in transplant recipients. Thus, 2.82% of pediatric NHL diagnoses in the general population (95% confidence interval [CI], 2.45%-3.19%) occurred in transplant recipients. Among transplant recipients, the most common subtypes were diffuse large B-cell lymphoma (DLBCL; 64.5% of cases) and Burkitt lymphoma (BL; 8.6%). For DLBCL and BL, transplant recipients contributed 7.62% (95% CI, 6.35%-8.88%) and 0.87% (95% CI, 0.51%-1.23%) of diagnoses, respectively. The proportion of NHLs that occurred in transplant recipients was highest among children less than 5 years old (4.46%; 95% CI, 3.24%-5.69%) and in more recent calendar years (3.73% in 2010-2012; 95% CI, 2.07%-5.39%). DLBCL patterns were similar, with transplant recipients contributing 19.78% of cases among children less than 5 years old (95% CI, 12.89%-26.66%) and 11.4% of cases in 2010-2012 (95% CI, 5.54%-17.28%). CONCLUSIONS: Among children and adolescents, solid organ transplant recipients contribute a substantial fraction of NHL diagnoses, particularly DLBCL diagnoses. This fraction has increased over time. Prevention efforts targeted toward this group could reduce the overall pediatric NHL burden. Cancer 2017;123:4663-4671. © 2017 American Cancer Society.

Variation in Cancer Incidence among Patients with ESRD during Kidney Function and Nonfunction Intervals.

Among patients with ESRD, cancer risk is affected by kidney dysfunction and by immunosuppression after transplant. Assessing patterns across periods of dialysis and kidney transplantation may inform cancer etiology. We evaluated 202,195 kidney transplant candidates and recipients from a linkage between the Scientific Registry of Transplant Recipients and cancer registries, and compared incidence in kidney function intervals (time with a transplant) with incidence in nonfunction intervals (waitlist or time after transplant failure), adjusting for demographic factors. Incidence of infection-related and immune-related cancer was higher during kidney function intervals than during nonfunction intervals. Incidence was most elevated for Kaposi sarcoma (hazard ratio [HR], 9.1; 95% confidence interval (95% CI), 4.7 to 18), non-Hodgkin's lymphoma (HR, 3.2; 95% CI, 2.8 to 3.7), Hodgkin's lymphoma (HR, 3.0; 95% CI, 1.7 to 5.3), lip cancer (HR, 3.4; 95% CI, 2.0 to 6.0), and nonepithelial skin cancers (HR, 3.8; 95% CI, 2.5 to 5.8). Conversely, ESRD-related cancer incidence was lower during kidney function intervals (kidney cancer: HR, 0.8; 95% CI, 0.7 to 0.8 and thyroid cancer: HR, 0.7; 95% CI, 0.6 to 0.8). With each successive interval, incidence changed in alternating directions for non-Hodgkin's lymphoma, melanoma, and lung, pancreatic, and nonepithelial skin cancers (higher during function intervals), and kidney and thyroid cancers (higher during nonfunction intervals). For many cancers, incidence remained higher than in the general population across all intervals. These data indicate strong short-term effects of kidney dysfunction and immunosuppression on cancer incidence in patients with ESRD, suggesting a need for persistent cancer screening and prevention.

Trends in primary central nervous system lymphoma incidence and survival in the U.S.

It is suspected that primary central nervous system lymphoma (PCNSL) rates are increasing among immunocompetent people. We estimated PCNSL trends in incidence and survival among immunocompetent persons by excluding cases among human immunodeficiency virus (HIV)-infected persons and transplant recipients. PCNSL data were derived from 10 Surveillance, Epidemiology and End Results (SEER) cancer registries (1992-2011). HIV-infected cases had reported HIV infection or death due to HIV. Transplant recipient cases were estimated from the Transplant Cancer Match Study. We estimated PCNSL trends overall and among immunocompetent individuals, and survival by HIV status. A total of 4158 PCNSLs were diagnosed (36% HIV-infected; 0·9% transplant recipients). HIV prevalence in PCNSL cases declined from 64·1% (1992-1996) to 12·7% (2007-2011), while the prevalence of transplant recipients remained low. General population PCNSL rates were strongly influenced by immunosuppressed cases, particularly in 20-39 year-old men. Among immunocompetent people, PCNSL rates in men and women aged 65+ years increased significantly (1·7% and 1·6%/year), but remained stable in other age groups. Five-year survival was poor, particularly among HIV-infected cases (9·0%). Among HIV-uninfected cases, 5-year survival increased from 19·1% (1992-1994) to 30·1% (2004-2006). In summary, PCNSL rates have increased among immunocompetent elderly adults, but not in younger individuals. Survival remains poor for both HIV-infected and HIV-uninfected PCNSL patients.

Effects of maintenance immunosuppression with sirolimus after liver transplant for hepatocellular carcinoma.

For recipients of liver transplantations (LTs) for hepatocellular carcinoma (HCC), HCC recurrence after transplantation remains a major concern. Sirolimus (SRL), an immunosuppressant with anticarcinogenic properties, may reduce HCC recurrence and improve survival. In our study, the US Scientific Registry of Transplant Recipients was linked to pharmacy claims. For liver recipients transplanted for HCC, Cox regression was used to estimate associations of early SRL use with recurrence, cancer-specific mortality, and all-cause mortality, adjusting for recipient ethnicity, calendar year of transplant, total tumor volume, alpha-fetoprotein, transplant center size, use of interleukin 2 induction therapy, and allocated and calculated Model for End-Stage Liver Disease score. We performed stratified analyses among recipients who met Milan criteria, among those without renal failure, among those with deceased liver donors, by age at transplantation, and by tumor size. Among the 3936 included HCC LTs, 234 (6%) were SRL users. In total, there were 242 recurrences and 879 deaths, including 261 cancer-related deaths. All-cause mortality was similar in SRL users and nonusers (adjusted hazard ratio [aHR], 1.01; 95% CI, 0.73-1.39). HCC recurrence and cancer-specific mortality rates appeared lower in SRL users, but associations were not statistically significant (recurrence aHR, 0.86; 95% CI, 0.45-1.65; cancer-specific mortality aHR, 0.80; 95% CI, 0.43-1.50). Among recipients >55 years old, associations were suggestive of better outcomes for SRL users (all-cause mortality aHR, 0.62; 95% CI, 0.38-1.01; recurrence aHR, 0.52; 95% CI, 0.19-1.44; cancer-specific mortality aHR, 0.34; 95% CI, 0.11-1.09), whereas among recipients ≤55 years old, SRL users had worse outcomes (all-cause mortality aHR, 1.76; 95% CI, 1.12-2.75; recurrence aHR, 1.49; 95% CI, 0.62-3.61; cancer-specific mortality aHR, 1.54; 95% CI, 0.71-3.32). In conclusion, among HCC liver recipients overall, SRL did not appear beneficial in reducing all-cause mortality. However, there were suggestions of reductions in recurrence and cancer-specific mortality, and effects appeared to be modified by age at transplantation. Liver Transplantation 22 627-634 2016 AASLD.

Melanoma Outcomes in Transplant Recipients With Pretransplant Melanoma.

BACKGROUND: There are limited data on outcomes in transplant recipients with a history of pretransplant melanoma. OBJECTIVE: To determine whether pretransplant melanoma is associated with differences in survival or posttransplant melanoma risk. MATERIALS AND METHODS: We evaluated the outcomes of 185,039 US transplant recipients from the Transplant Cancer Match Study. We also evaluated the impact of transplantation on 141,441 patients with melanoma identified in cancer registries. RESULTS: There were 336 transplant recipients (0.18%) with pretransplant melanoma; they had increased risk of melanoma-specific mortality (hazard ratio [HR], 27; 95% confidence interval [CI], 11-64, p < .0001), overall mortality (HR, 1.3; 95% CI, 1.0-1.5, p = .02), and incident melanoma (HR, 5.4; 95% CI, 2.9-9.8, p < .0001) after transplant, compared with recipients without pretransplant melanoma. The 10-year absolute risk difference was 2.97% for melanoma-specific mortality, 3.68% for incident melanoma, and 14.32% for overall mortality. Among the 141,441 patients with melanoma in the general population, 68 (0.05%) subsequently received a transplant. Transplantation increased melanoma-specific mortality, but not significantly (HR, 1.7; 95% CI, 0.61-4.5, p = .32). CONCLUSION: Pretransplant melanoma is associated with increased melanoma-specific mortality, overall mortality, and incident melanoma after transplant. Nonetheless, the rarity of melanoma-related events supports the current practice for listing transplant candidates with a history of melanoma.

Lymphoma immune reconstitution inflammatory syndrome in the center for AIDS research network of integrated clinical systems cohort.

BACKGROUND: Lymphoma incidence is increased among human immunodeficiency virus (HIV)-infected individuals soon after antiretroviral therapy (ART), perhaps due to unmasking immune reconstitution inflammatory syndrome (IRIS). Clinical characteristics and survival for unmasking lymphoma IRIS have not been described. METHODS: We studied lymphoma patients in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) from 1996 until 2011. Unmasking lymphoma IRIS was defined as lymphoma within 6 months after ART accompanied by a ≥ 0.5 log10 copies/mL HIV RNA reduction. Differences in presentation and survival were examined between IRIS and non-IRIS cases. RESULTS: Of 482 lymphoma patients, 56 (12%) met criteria for unmasking lymphoma IRIS. Of these, 12 (21%) had Hodgkin lymphoma, 22 (39%) diffuse large B-cell lymphoma, 5 (9%) Burkitt lymphoma, 10 (18%) primary central nervous system lymphoma, and 7 (13%) other non-Hodgkin lymphoma. Median CD4 cell count at lymphoma diagnosis among IRIS cases was 173 cells/µL (interquartile range, 73-302), and 48% had suppressed HIV RNA <400 copies/mL. IRIS cases were similar overall to non-IRIS cases in histologic distribution and clinical characteristics, excepting more frequent hepatitis B and C (30% vs 19%, P = .05), and lower HIV RNA at lymphoma diagnosis resulting from the IRIS case definition. Overall survival at 5 years was similar between IRIS (49%; 95% confidence interval [CI], 37%-64%) and non-IRIS (44%; 95% CI, 39%-50%), although increased early mortality was suggested among IRIS cases. CONCLUSIONS: In a large HIV-associated lymphoma cohort, 12% of patients met a uniformly applied unmasking lymphoma IRIS case definition. Detailed studies of lymphoma IRIS might identify immunologic mechanisms of lymphoma control.

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.

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.

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.

Cost-effectiveness Improves for Operative vs Nonoperative Treatment of Adult Symptomatic Lumbar Scoliosis at Eight-Year Follow-up.

STUDY DESIGN: Secondary data analysis of the NIH sponsored study on Adult Symptomatic Lumbar Scoliosis (ASLS). OBJECTIVES: The purpose of this study is to perform a cost-effectiveness analysis comparing operative versus non-operative care for ASLS eight years after enrollment. SUMMARY OF BACKGROUND DATA: A prior cost-effectiveness analysis of the current cohort comparing operative to non-operative care at five years after enrollment showed and ICER of $44,033 in the As-Treated analysis and a ICER of $27,480 in the Intent-to-treat analysis. METHODS: Data was collected every three months for the first two years, then every six months for the remainder of the study. Data included use of non-operative modalities, medications and employment status. Costs for index and revision surgeries and non-operative modalities were determined using Medicare Allowable rates. Medication costs were determined using the RedBook and indirect costs were calculated based on reported employment status and income. Quality Adjusted Life Years (QALY) was determined using the SF6D. RESULTS: There were 101 cases in the Operative (Op) and 103 in the Non-operative (Non-Op) group with complete eight year data. Thirty-eight patients (37%) in the Non-Op group had surgery from 3 to 72 months after enrollment. An As-Treated analysis including only cases who never had surgery (N=65) or cases with complete eight-year post-operative data (N=101) showed that operative treatment was favored with an ICER of $20,569 per QALY gained which is within Willingness-to-Pay (WTP) thresholds. An Intent-to-Treat analysis demonstrated greater QALY gains and lower cost in the Op group (ICER = $-13,911). However, Intent-to-Treat analysis is influenced by Non-Op patients who crossed over to operative treatment at variable times during follow-up. CONCLUSION: Operative treatment was more cost-effective than non-operative treatment for ASLS at eight-year follow-up. The ICER continued to improve as compared to the five-year values ($20,569 vs. $44,033).

Incidence and timing of cancer in HIV-infected individuals following initiation of combination antiretroviral therapy.

BACKGROUND: Cancer is an important cause of morbidity and mortality in individuals infected with human immunodeficiency virus (HIV), but patterns of cancer incidence after combination antiretroviral therapy (ART) initiation remain poorly characterized. METHODS: We evaluated the incidence and timing of cancer diagnoses among patients initiating ART between 1996 and 2011 in a collaboration of 8 US clinical HIV cohorts. Poisson regression was used to estimate incidence rates. Cox regression was used to identify demographic and clinical characteristics associated with cancer incidence after ART initiation. RESULTS: At initiation of first combination ART among 11 485 patients, median year was 2004 (interquartile range [IQR], 2000-2007) and median CD4 count was 202 cells/mm(3) (IQR, 61-338). Incidence rates for Kaposi sarcoma (KS) and lymphomas were highest in the first 6 months after ART initiation (P < .001) and plateaued thereafter, while incidence rates for all other cancers combined increased from 416 to 615 cases per 100 000 person-years from 1 to 10 years after ART initiation (average 7% increase per year; 95% confidence interval, 2%-13%). Lower CD4 count at ART initiation was associated with greater risk of KS, lymphoma, and human papillomavirus-related cancer. Calendar year of ART initiation was not associated with cancer incidence. CONCLUSIONS: KS and lymphoma rates were highest immediately following ART initiation, particularly among patients with low CD4 cell counts, whereas other cancers increased with time on ART, likely reflecting increased cancer risk with aging. Our results underscore recommendations for earlier HIV diagnosis followed by prompt ART initiation along with ongoing aggressive cancer screening and prevention efforts throughout the course of HIV care.

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.

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.