Factors in Hand Surgery Access for Rheumatoid Arthritis Before vs After the Patient Protection and Affordable Care Act.

Importance: Rheumatoid arthritis (RA) has severe functional and economic consequences. The implications of the Patient Protection and Affordable Care Act (ACA) and demographic factors for access to surgical treatment are unclear. Objective: To investigate factors associated with time to RA hand surgery, surgical incidence, and cost after implementation of the ACA. Design, Setting, and Participants: This cross-sectional study used insurance data from the IBM MarketScan Research Databases from 2009 through 2020 to compare time to surgery, surgical incidence, and treatment cost for RA of the hand before and after ACA implementations. Included patients were 18 years or older with a new diagnosis for RA of the hand and at least 1 procedural code for arthroplasty, arthrodesis, tenolysis, tendon repair, or tendon transfer. Patients with coexisting inflammatory arthritis diagnoses were excluded. Demographic variables analyzed included patient sex, age at index date, residence within or outside a metropolitan statistical area (MSA; hereafter urban or nonurban), insurance and health plan type, Social Deprivation Index, Elixhauser Comorbidity Index score, and Rheumatic Disease Comorbidity Index. Data analysis occurred from October 2022 to April 2023. Exposures: Surgery for RA of the hand during the pre-ACA (before 2014) vs post-ACA (2014 or later) periods. Main Outcomes and Measures: Time to surgery, surgical incidence, and cost of treating RA in patients undergoing hand surgery for RA. Results: Among 3643 patients (mean [SD] age, 57.6 [12.3] years) who underwent hand surgery for RA, 3046 (83.6%) were women. Post-ACA passage, 595 (86.2%) patients who resided in urban areas had a significantly lower time to surgery than those who did not (-70.5 [95% CI, -112.6 to -28.3] days; P < .001). Among urban patients, the least socially disadvantaged patients experienced the greatest decrease in time to surgery after ACA but the change was not statistically significant. For all patients, greater social disadvantage (ie, a higher SDI score) was associated with a longer time to surgery in the post-ACA period; for example, compared with the least socially disadvantaged group (SDI decile, 0-10), patients in SDI decile 10 to 20 waited an additional 254.0 days (95% CI, 65.2 to 442.9 days; P = .009) before undergoing surgery. Compared with the pre-ACA period, the mean surgical incidence in the post-ACA period was 83.4% lower (162.3 vs 26.9 surgeries per 1000 person-years; P < .001), and surgical incidence was 86.3% lower in nonurban populations (27.2 vs 3.7 surgeries per 1000 person-years; P < .001) but only 82.8% lower in urban populations (135.1 vs 23.2 surgeries per 1000 person-years; P < .001). Per capita total costs of all treatment related to RA of the hand decreased in the post-ACA period but the change was not statistically significant. Insurer-paid costs were lower in the post-ACA period but the change was not statistically significant. Out-of-pocket expenses did not change. Conclusions and Relevance: Findings of this cross-sectional study suggest that after ACA passage, disparities exist in access to timely, cost-effective hand surgery for RA. Increased access to surgical hand specialists is needed for nonurban residents and those with greater social deprivation, along with insurance policy reforms to further decrease out-of-pocket spending for RA hand surgery.

[Self-perception of smoking cessation skills among Cardiology residents in Argentina]. / Autopercepción de las habilidades para la cesación del tabaquismo entre los residentes de cardiología en Argentina.

Objective: To evaluate the self-perception of cardiology residents in Argentina regarding their abilities to help their patients stop smoking, as well as their opinions about their knowledge and skills in this area. Materials and methods: A cross-sectional study was carried out using secondary data from a study carried out in five Latin American countries and Spain, focusing on the information provided by cardiology residents in Argentina. Discrete variables were expressed as median and interquartile range, and categorical variables were expressed as percentages, and were analyzed using the chi-square test or Fisher's exact test, depending on the relative frequency of the expected values. Results: 447 residents participated; 87.5% routinely provided brief advice to quit smoking, and 11.6% used validated questionnaires to assess the degree of addiction. Furthermore, 32.1% stated that they prescribed pharmacological treatment, but 53.1% were only familiar with a single drug. When asked about their self-perception of getting their patients to stop smoking, the median response was 5 (scale from 1 to 10); only 13.7% responded with a score of 8 or more. Conclusions: The present study suggests that cardiology residents in Argentina recognize the importance of carrying out smoking cessation interventions, but a high proportion of them do not feel qualified to do so.

Omics-Based Investigations of Breast Cancer.

Breast cancer (BC) is characterized by an extensive genotypic and phenotypic heterogeneity. In-depth investigations into the molecular bases of BC phenotypes, carcinogenesis, progression, and metastasis are necessary for accurate diagnoses, prognoses, and therapy assessments in predictive, precision, and personalized oncology. This review discusses both classic as well as several novel omics fields that are involved or should be used in modern BC investigations, which may be integrated as a holistic term, onco-breastomics. Rapid and recent advances in molecular profiling strategies and analytical techniques based on high-throughput sequencing and mass spectrometry (MS) development have generated large-scale multi-omics datasets, mainly emerging from the three "big omics", based on the central dogma of molecular biology: genomics, transcriptomics, and proteomics. Metabolomics-based approaches also reflect the dynamic response of BC cells to genetic modifications. Interactomics promotes a holistic view in BC research by constructing and characterizing protein-protein interaction (PPI) networks that provide a novel hypothesis for the pathophysiological processes involved in BC progression and subtyping. The emergence of new omics- and epiomics-based multidimensional approaches provide opportunities to gain insights into BC heterogeneity and its underlying mechanisms. The three main epiomics fields (epigenomics, epitranscriptomics, and epiproteomics) are focused on the epigenetic DNA changes, RNAs modifications, and posttranslational modifications (PTMs) affecting protein functions for an in-depth understanding of cancer cell proliferation, migration, and invasion. Novel omics fields, such as epichaperomics or epimetabolomics, could investigate the modifications in the interactome induced by stressors and provide PPI changes, as well as in metabolites, as drivers of BC-causing phenotypes. Over the last years, several proteomics-derived omics, such as matrisomics, exosomics, secretomics, kinomics, phosphoproteomics, or immunomics, provided valuable data for a deep understanding of dysregulated pathways in BC cells and their tumor microenvironment (TME) or tumor immune microenvironment (TIMW). Most of these omics datasets are still assessed individually using distinct approches and do not generate the desired and expected global-integrative knowledge with applications in clinical diagnostics. However, several hyphenated omics approaches, such as proteo-genomics, proteo-transcriptomics, and phosphoproteomics-exosomics are useful for the identification of putative BC biomarkers and therapeutic targets. To develop non-invasive diagnostic tests and to discover new biomarkers for BC, classic and novel omics-based strategies allow for significant advances in blood/plasma-based omics. Salivaomics, urinomics, and milkomics appear as integrative omics that may develop a high potential for early and non-invasive diagnoses in BC. Thus, the analysis of the tumor circulome is considered a novel frontier in liquid biopsy. Omics-based investigations have applications in BC modeling, as well as accurate BC classification and subtype characterization. The future in omics-based investigations of BC may be also focused on multi-omics single-cell analyses.

Multi-institutional Analysis of 505 Patients With Coronavirus Disease-2019 Supported With Extracorporeal Membrane Oxygenation: Predictors of Survival.

BACKGROUND: We reviewed our experience with 505 patients with confirmed coronavirus disease-2019 (COVID-19) supported with extracorporeal membrane oxygenation (ECMO) at 45 hospitals and estimated risk factors for mortality. METHODS: A multi-institutional database was created and used to assess all patients with COVID-19 who were supported with ECMO. A Bayesian mixed-effects logistic regression model was estimated to assess the effect on survival of multiple potential risk factors for mortality, including age at cannulation for ECMO as well as days between diagnosis of COVID-19 and intubation and days between intubation and cannulation for ECMO. RESULTS: Median time on ECMO was 18 days (interquartile range, 10-29 days). All 505 patients separated from ECMO: 194 patients (38.4%) survived and 311 patients (61.6%) died. Survival with venovenous ECMO was 184 of 466 patients (39.5%), and survival with venoarterial ECMO was 8 of 30 patients (26.7%). Survivors had lower median age (44 vs 51 years, P < .001) and shorter median time interval from diagnosis to intubation (7 vs 11 days, P = .001). Adjusting for several confounding factors, we estimated that an ECMO patient intubated on day 14 after the diagnosis of COVID-19 vs day 4 had a relative odds of survival of 0.65 (95% credible interval, 0.44-0.96; posterior probability of negative effect, 98.5%). Age was also negatively associated with survival: relative to a 38-year-old patient, we estimated that a 57-year-old patient had a relative odds of survival of 0.43 (95% credible interval, 0.30-0.61; posterior probability of negative effect, >99.99%). CONCLUSIONS: ECMO facilitates salvage and survival of select critically ill patients with COVID-19. Survivors tend to be younger and have shorter time from diagnosis to intubation. Survival of patients supported with only venovenous ECMO was 39.5%.

Patient-Reported Opioid Analgesic Use After Discharge from Surgical Procedures: A Systematic Review.

OBJECTIVE: This systematic review synthesizes evidence on patient-reported outpatient opioid analgesic use after surgery. METHODS: We searched PubMed (February 2019) and Web of Science and Embase (June 2019) for U.S. studies describing patient-reported outpatient opioid analgesic use. Two reviewers extracted data on opioid analgesic use, standardized the data on use , and performed independent quality appraisals based on the Cochrane Risk of Bias Tool and an adapted Newcastle-Ottawa scale. RESULTS: Ninety-six studies met the eligibility criteria; 56 had sufficient information to standardize use in oxycodone 5-mg tablets. Patient-reported opioid analgesic use varied widely by procedure type; knee and hip arthroplasty had the highest postoperative opioid use, and use after many procedures was reported as <5 tablets. In studies that examined excess tablets, 25-98% of the total tablets prescribed were reported to be excess, with most studies reporting that 50-70% of tablets went unused. Factors commonly associated with higher opioid analgesic use included preoperative opioid analgesic use, higher inpatient opioid analgesic use, higher postoperative pain scores, and chronic medical conditions, among others. Estimates also varied across studies because of heterogeneity in study design, including length of follow-up and inclusion/exclusion criteria. CONCLUSION: Self-reported postsurgery outpatient opioid analgesic use varies widely both across procedures and within a given procedure type. Contributors to within-procedure variation included patient characteristics, prior opioid use, intraoperative and perioperative factors, and differences in the timing of opioid use data collection. We provide recommendations to help minimize variation caused by study design factors and maximize interpretability of forthcoming studies for use in clinical guidelines and decision-making.

Reconnaissance of cumulative risk of pesticides and pharmaceuticals in Great Smoky Mountains National Park streams.

The United States (US) National Park Service (NPS) manages protected public lands to preserve biodiversity. Exposure to and effects of bioactive organic contaminants in NPS streams are challenges for resource managers. Recent assessment of pesticides and pharmaceuticals in protected-streams within the urbanized NPS Southeast Region (SER) indicated the importance of fluvial inflows from external sources as drivers of aquatic contaminant-mixture exposures. Great Smoky Mountains National Park (GRSM), lies within SER, has the highest biodiversity and annual visitation of NPS parks, but, in contrast to the previously studied systems, straddles a high-elevation hydrologic divide; this setting limits fluvial-inflows of contaminants but potentially increases visitation-driven contaminant deliveries. We leveraged the unique characteristics of GRSM to test further the importance of fluvial contaminant inflows as drivers of protected-stream exposures and to inform the relative importance of potential additional contaminant transport mechanisms, by comparing the estimated risks of 328 pesticides and pharmaceuticals in water at 16 GRSM stream locations to those estimated previously in SER streams. Extensive mixtures (31 compounds) were only observed in an atypical reach on the boundary of GRSM downstream of a wastewater discharge, while limited mixtures (2-5 compounds) were observed in one stream with elevated visitation pressure (recreational "tube floating"). The insecticide, imidacloprid, used to eradicate hemlock woolly adelgid, was detected in 8 (50%) streams. Infrequent exceedances of a cumulative ToxCast-based, exposure-activity ratio (ΣEAR) 0.001 screening-level of concern suggested limited risk to non-target, aquatic vertebrates, whereas exceedances of a cumulative benchmark-based, invertebrate toxicity quotient (ΣTQ) 0.1 screening level at 8 locations indicated generally high risk to invertebrates. The results are consistent with the importance of fluvial transport from extra-park sources as a driver of bioactive-contaminant mixture exposures in protected streams and illustrate the potential additional risks from visitation-driven and tactical-use-pesticides.

The association between maternal and paternal race and preterm birth.

BACKGROUND: Non-Hispanic black maternal race is a known risk factor for preterm birth. However, the contribution of paternal race is not as well established. OBJECTIVE: We sought to evaluate the risk of preterm birth among non-Hispanic black, non-Hispanic white, and mixed non-Hispanic black and non-Hispanic white dyads. STUDY DESIGN: This was a population-based cohort study of all live births in the United States from 2015 to 2017, using live birth records from the National Vital Statistics System. Singleton, nonanomalous infants whose live birth record included maternal and paternal self-reported race as either non-Hispanic white or non-Hispanic black were included. The primary outcome was preterm birth at <37 weeks' gestation; secondary outcomes included preterm birth at <34 and <28 weeks' gestation and delivery gestational age (as a continuous variable). Data were analyzed using chi-square, t test, analysis of variance, and logistic regression. A Kaplan-Meier survival curve was also generated. RESULTS: There were 11,809,599 live births during the study period; 4,008,622 births met the inclusion criteria. Of included births, 291,647 (7.3%) occurred at <37 weeks' gestation. Using the convention of maternal race first followed by paternal race, preterm birth at <37 weeks' gestation was most common among non-Hispanic black and non-Hispanic black dyads (n=70,987 [10.8%]), followed by non-Hispanic black and non-Hispanic white (n=3137 [9.5%]), non-Hispanic white and non-Hispanic black (n=9136 [8.3%]), and non-Hispanic white and non-Hispanic white dyads (n=209,387 [6.5%]; P<.001 for trend). Births at <34 weeks' (n=74,474) and <28 weeks' gestation (n=18,474) were also more common among non-Hispanic black and non-Hispanic black dyads. Specifically, 24,351 (3.7%) non-Hispanic black and non-Hispanic black, 1017 (3.1%) non-Hispanic black and non-Hispanic white, 2408 (2.2%) non-Hispanic white and non-Hispanic black, and 46,698 non-Hispanic white and non-Hispanic white dyads delivered at <34 weeks' gestation, and 7988 non-Hispanic black and non-Hispanic black (1.2%), 313 (1.0%) non-Hispanic black and non-Hispanic white, 584 (0.5%) non-Hispanic white and non-Hispanic black, and 9589 (0.3%) non-Hispanic white and non-Hispanic white dyads delivered at <28 weeks' gestation. Non-Hispanic white and non-Hispanic white dyads delivered at a mean 38.8± standard deviation of 1.7 weeks' gestation, although non-Hispanic white and non-Hispanic black, non-Hispanic black and non-Hispanic white, and non-Hispanic black and non-Hispanic black dyads delivered at 38.6±2.0, 38.5±2.3, and 38.3±2.4 weeks' gestation, respectively (P<.001). Adjusted odds ratios for the association between maternal or paternal race and preterm birth were highest for non-Hispanic black and non-Hispanic black dyads at each gestational age cutoff: adjusted odds ratio, 1.60 (95% confidence interval, 1.11-1.19) (<37 weeks' gestation); adjusted odds ratio, 2.47 (95% confidence interval, 2.41-2.53) (<34 weeks' gestation); and adjusted odds ratio, 4.22 (95% confidence interval, 4.04-4.41) (<28 weeks' gestation) compared with the non-Hispanic white referent group. Models adjusted for insurance status, chronic hypertension, tobacco use during pregnancy, history of previous preterm birth, and male fetus. In the Kaplan-Meier survival analysis, non-Hispanic black and non-Hispanic black dyads delivered the earliest across the range of delivery gestational ages compared with all other combinations of dyads. CONCLUSION: Non-Hispanic black paternal race is a risk factor for preterm birth and should be considered when evaluating maternal a priori risk of prematurity. Future research should investigate the mechanisms behind this finding, including determining the contribution of factors, such as racism, maternal and paternal genetics, and epigenetics to an individual's risk of preterm birth.

Temporary new implant spacers increase post-reimplantation total knee prosthesis survival after periprosthetic joint infection.

PURPOSE: Two-stage exchange arthroplasty is considered the gold standard for treatment of periprosthetic joint infection (PJI) following total knee arthroplasty (TKA). Antibiotic cement spacers can include cement-based spacers (CBS), new components (NEW), and autoclaved components (ACL). The factors that most influence post-reimplantation prosthesis (PRP) survival were determined. METHODS: A retrospective database review of patients undergoing two-stage exchange arthroplasty from 2008 to 2014 was performed. There were 85 patients, 25 patients and 30 patients in CBS, NEW and ACL groups, respectively. Patient, disease and surgical characteristics were collected and analyzed. Post-reimplantation prosthesis (PRP) survival was modeled using the Kaplan-Meier method. Cox proportional hazard modeling was then performed to identify risk factors associated with implant failure. RESULTS: Overall PRP survival was 82% in 140 unilateral TKAs. PRP survival between groups was 81%, 96% and 73% within the minimum 2-year follow-up period, respectively. There was a difference in median interval-to-reimplantation between groups (CBS, 72.0 days; NEW, 111.0 days; ACL, 84.0 days, p = 0.003). Adjusting for time-to-reimplantation, NEW spacers demonstrated greater PRP survival compared with ACL spacers (p = 0.044), and a trend towards greater survival compared with CBS spacers (p = 0.086). Excluding early failures (< 90 days), NEW spacers still demonstrated greater survival than ACL spacers (p = 0.046). Lower volume (≤ 10 within this series) surgeons tended to use more CBS spacers, while higher volume surgeons were comfortable with ACL spacers. CONCLUSIONS: There was greater PRP survival with NEW spacers. NEW spacers also demonstrated an increased inter-stage interval, likely because of increased comfort and motion. There were spacer choice differences between low- and high-volume surgeons. LEVEL OF EVIDENCE: III.

Precision medicine for pancreatic diseases.

PURPOSE OF REVIEW: We describe and contrast the strengths of precision medicine with Western medicine, and complex trait genetics with Mendelian genetics. Classic genetics focuses on highly penetrant pathogenic variants in a single gene believed to cause or confer a high risk for well-defined phenotypes. However, a minority of disorders have a single gene cause. Further, even individuals with identical Mendelian disease-associated genotypes may exhibit substantial phenotypic variability indicative of genetic and environmental modifiers. Still, most diseases are considered complex traits (or complex diseases). RECENT FINDINGS: New insights into the genetic underpinnings of complex traits provide opportunities for advances in diagnosis and management. Precision medicine provides the framework for integrating complex trait knowledge into clinical care through a sophisticated analysis pipeline. Multidimensional modeling of acquired diseases includes multiple genetic risks scattered over many genes and gene regulators that must be interpreted on the basis of functional evidence (e.g., genomics, transcriptomics) with structured models and expert systems; strengthened with machine learning and artificial intelligence. The choice of genotyping approaches (shotgun sequencing, single nucleotide polymorphism chips, targeted panels) is discussed. SUMMARY: The result of a good precision medicine tool is clinical-decision support and guidance to tackle complex disorders such as pancreatitis, diabetes, and pancreatic cancer oncogenesis.

Impact of hereditary pancreatitis on patients and their families.

Hereditary pancreatitis (HP), a highly penetrant (~80%) autosomal dominant disease associated with PRSS1 variants, causes acute pancreatitis in childhood and chronic pancreatitis by early adulthood. Other clinical features include pain, diabetes, and risk of pancreatic cancer. HP kindreds were prospectively recruited from 1995 to 2015. At enrollment, study participants completed medical and family history questionnaires, and provided samples for genotyping. Participants were recontacted between 2015 and 2017 and asked to complete a survey on concerns and experiences related to HP, PRSS1 testing, and genetic counseling. Data were analyzed with descriptive and thematic methods. Thirty-nine affected participants with HP and 21 unaffected family members completed the survey. Among unaffected family members, 'worry' and 'helplessness' were frequently described as the most difficult problem in their family because of HP, particularly with regard to pain. Three participants described the impact of drug addiction on their family. 'School or work limitations' was the leading financial concern, with 65.5% (36/55) rating it as 'moderately' or 'extremely important.' Unexpectedly, only 62% (21/34) of affected PRSS1 carriers believed the chance for a parent to pass HP to his or her children was 50%, whereas 18% (6/34) believed the chance was 100%. The impact of HP on individuals and families varied, which may reflect the highly unpredictable nature of HP severity and outcomes. Based on current and previously reported findings, an overview of important issues for genetic counselors to consider for counseling HP families is included.

Exposure and potential effects of pesticides and pharmaceuticals in protected streams of the US National park Service southeast region.

Globally, protected areas offer refugia for a broad range of taxa including threatened and endangered species. In the United States (US), the National Park Service (NPS) manages public lands to preserve biodiversity, but increasing park visitation and development of surrounding landscapes increase exposure to and effects from bioactive contaminants. The risk (exposure and hazard) to NPS protected-stream ecosystems within the highly urbanized southeast region (SER) from bioactive contaminants was assessed in five systems based on 334 pesticide and pharmaceutical analytes in water and 119 pesticides in sediment. Contaminant mixtures were common across all sampled systems, with approximately 24% of the unique analytes (80/334) detected at least once and 15% (49/334) detected in half of the surface-water samples. Pharmaceuticals were observed more frequently than pesticides, consistent with riparian buffers and concomitant spatial separation from non-point pesticide sources in four of the systems. To extrapolate exposure data to biological effects space, site-specific cumulative exposure-activity ratios (ΣEAR) were calculated for detected surface-water contaminants with available ToxCast data; common exceedances of a 0.001 ΣEAR effects-screening threshold raise concerns for molecular toxicity and possible, sub-lethal effects to non-target, aquatic vertebrates. The results illustrate the need for continued management of protected resources to reduce contaminant exposure and preserve habitat quality, including prioritization of conservation practices (riparian buffers) near stream corridors and increased engagement with upstream/up-gradient property owners and municipal wastewater facilities.

Increased expression of anion transporter SLC26A9 delays diabetes onset in cystic fibrosis.

Diabetes is a common complication of cystic fibrosis (CF) that affects approximately 20% of adolescents and 40%-50% of adults with CF. The age at onset of CF-related diabetes (CFRD) (marked by clinical diagnosis and treatment initiation) is an important measure of the disease process. DNA variants associated with age at onset of CFRD reside in and near SLC26A9. Deep sequencing of the SLC26A9 gene in 762 individuals with CF revealed that 2 common DNA haplotypes formed by the risk variants account for the association with diabetes. Single-cell RNA sequencing (scRNA-Seq) indicated that SLC26A9 is predominantly expressed in pancreatic ductal cells and frequently coexpressed with CF transmembrane conductance regulator (CFTR) along with transcription factors that have binding sites 5' of SLC26A9. These findings were replicated upon reanalysis of scRNA-Seq data from 4 independent studies. DNA fragments derived from the 5' region of SLC26A9-bearing variants from the low-risk haplotype generated 12%-20% higher levels of expression in PANC-1 and CFPAC-1 cells compared with the high- risk haplotype. Taken together, our findings indicate that an increase in SLC26A9 expression in ductal cells of the pancreas delays the age at onset of diabetes, suggesting a CFTR-agnostic treatment for a major complication of CF.

Association of Early Postoperative Pain Trajectories With Longer-term Pain Outcome After Primary Total Knee Arthroplasty.

Importance: Studies to date have not comprehensively examined pain experience after total knee arthroplasty (TKA). Discrete patterns of pain in this period might be associated with pain outcomes at 6 to 12 months after TKA. Objectives: To examine patterns of individual post-TKA pain trajectories and to assess their independent associations with longer-term pain outcome after TKA. Design, Setting, and Participants: This prospective cohort study combined data from a national US TKA cohort with ancillary pain severity data at 2 weeks and 8 weeks after the index TKA using a numeric rating scale. All participants received primary, unilateral TKA within the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement (FORCE-TJR) national network of community sites in 22 states or at the lead site (University of Massachusetts Medical School). Participants had a date of surgery between May 1, 2013, and December 1, 2014. The data analysis was performed between January 13, 2015, and July 5, 2016. Exposures: Pain trajectories in the postoperative period (8 weeks). Main Outcomes and Measures: Index knee pain at 6 months after TKA using the Knee Injury and Osteoarthritis Outcome Score (KOOS) pain scale. Group-based trajectory methods examined the presence of pain trajectories in the postoperative period (8 weeks) and assessed whether trajectories were independently associated with longer-term pain (6 months). Results: The cohort included 659 patients who underwent primary TKA with complete data at 4 points (preoperative, 2 weeks, 8 weeks, and 26 weeks). Their mean (SD) age was 67.1 (8.0) years, 64.5% (425 of 659) were female, the mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 30.77 (5.66), 94.5% (613 of 649) were white, and the mean (SD) preoperative 36-Item Short Form Health Survey physical component summary and mental component summary scores were 34.1 (8.2) and 53.8 (11.4), respectively. Two pain trajectory subgroups were identified at 8 weeks after TKA: patients who experienced fast pain relief in the first 8 weeks after TKA (fast pain responders, composing 72.4% [477 of 659] of the sample) and patients who did not (slow pain responders, composing 27.6% [182 of 659] of the sample). After adjusting for patient factors, the pain trajectory at 8 weeks after TKA was independently associated with the mean KOOS pain score at 6 months, with a between-trajectory difference of -11.3 (95% CI, -13.9 to -8.7). Conclusions and Relevance: The trajectory among slow pain responders at 8 weeks after surgery was independently associated with improved but greater persistent index knee pain at 6 months after TKA compared with that among fast pain responders. Early identification of patients with a trajectory of slow pain response at 8 weeks after TKA may offer an opportunity for interventions in the perioperative period to potentially improve the long-term pain outcomes after TKA.

A Qualitative Study of the Postoperative Pain Management Educational Needs of Total Joint Replacement Patients.

BACKGROUND: The majority of patients undergoing total joint replacement (TJR) experience surgical pain in the early postoperative period and managing pain can be challenging for orthopedic surgeons and their patients. AIMS: The objective of this study was to better understand the postoperative pain management education needs of elective total joint replacement patients. DESIGN: This study had a descriptive phenomenological, qualitative design using individual interviews. SETTINGS: Nine orthopedic surgeons offices in 8 states. PARTICIPANTS/SUBJECTS: Twenty-seven patients (mean age: 71 years; 74% female; 78% non-Hispanic white) completed the interview. METHODS: Patients were interviewed using open-ended questions, which included experiences with surgical pain after surgery and how it was managed, experiences with pain medicine, experience using non-medicine-related pain reduction methods, and suggestions for delivery of pain management information. RESULTS: Challenges identified for managing postoperative pain included loss of pain control and lack of information about prescribed opioids and nonopioid methods of managing pain. Facilitators included having a caregiver or family member in a health care field and previous experience managing postoperative pain. Participants believed that information about pain management would be helpful and should be delivered at multiple time points. CONCLUSIONS: With trends toward shorter hospital stays, as well as the growing opioid epidemic and the associated concerns regarding prescribing opioids, home-based pain management should be a priority. Interventions should include education about narcotic use and abuse as well as nonmedication approaches to pain management.

Childhood-Onset Eosinophilic Granulomatosis with Polyangiitis with a Vulvar Granuloma: A Case Report and Review of the Literature.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare multisystem necrotizing vasculitis associated with eosinophilia and extravascular granuloma and classically involving the upper and lower airways. There have only been a few reported cases of gynecologic involvement in EGPA. CASE: We present an 8-year-old girl diagnosed with EGPA with a vulvar granuloma in what is, to our knowledge, the first reported pediatric gynecologic manifestation of EGPA. Interestingly, the vulvar granuloma did not respond to initial immunosuppressant treatment with prednisone and methotrexate and required treatment regimen modification with mycophenolate mofetil resulting in granuloma resolution. SUMMARY AND CONCLUSION: EGPA in the pediatric population has a relatively high mortality rate compared with in the adult population thus it is important that vulvar granulomas associated with EGPA should be included in the differential diagnosis of a vulvar mass allowing for the prompt diagnosis and treatment of this potentially fatal disease in children.

Germline Variants and Risk for Pancreatic Cancer: A Systematic Review and Emerging Concepts.

Pancreatic cancer requires many genetic mutations. Combinations of underlying germline variants and environmental factors may increase the risk of cancer and accelerate the oncogenic process. We systematically reviewed, annotated, and classified previously reported pancreatic cancer-associated germline variants in established risk genes. Variants were scored using multiple criteria and binned by evidence for pathogenicity, then annotated with published functional studies and associated biological systems/pathways. Twenty-two previously identified pancreatic cancer risk genes and 337 germline variants were identified from 97 informative studies that met our inclusion criteria. Fifteen of these genes contained 66 variants predicted to be pathogenic (APC, ATM, BRCA1, BRCA2, CDKN2A, CFTR, CHEK2, MLH1, MSH2, NBN, PALB2, PALLD, PRSS1, SPINK1, TP53). Pancreatic cancer risk genes were organized into key biological mechanisms that promote pancreatic oncogenesis within an oncogenic model. Development of precision medicine approaches requires updated variant information within the framework of an oncogenic progression model. Complex risk modeling may improve interpretation of early biomarkers and guide pathway-specific treatment for pancreatic cancer in the future. Precision medicine is within reach.

Independent Heath Facility Meets Cancer Care Ontario and Canadian Association of Gastroenterology Guidelines for Endoscopic Procedure Wait Times While Meeting Quality Indicators: A Retrospective Review.

Background: Canadian independent health facilities (IHFs) have been implemented to reduce hospital endoscopy volume and expedite endoscopic evaluations for patients suspected to have underlying colorectal cancer. Methods: We conducted a retrospective review of a prospective database at a large-volume urban IHF. The primary outcomes were wait times, and the secondary outcomes were colonoscopy quality indicators and complication rates. Results: Median wait times from referral to colonoscopy met the recommendations set out by the Canadian Association of Gastroenterology and Cancer Care Ontario for all indications: chronic abdominal pain: 43 days; new onset change in bowel habits: 36 days; bright red rectal bleeding: 42 days; documented iron-deficiency anemia: 43 days; fecal occult blood test positive: 38 days; cancer likely based on imaging or physical exam: 23 days; chronic diarrhea and chronic constipation: 42 days; and screening colonoscopies: 55 days. Secondary outcomes of quality indicators and complication rates all met or exceeded the CCO and CAG recommendations. Conclusions: This IHF met the recommended wait times for all indications for colonoscopy while maintaining high procedural quality and safety. IHFs are one solution to help meet the increasing demand for colonoscopy in Ontario.

Hereditary Pancreatitis in the United States: Survival and Rates of Pancreatic Cancer.

OBJECTIVES: Hereditary pancreatitis (HP), an autosomal dominant disease typically caused by mutations in PRSS1, has a broad range of clinical characteristics and high cumulative risk of pancreatic cancer. We describe survival and pancreatic cancer risk in the largest HP cohort in the US. METHODS: HP probands and family members prospectively recruited from 1995 to 2013 completed medical and family history questionnaires, and provided blood for DNA testing. Overall survival (until 12/31/2015) was determined from the Social Security Death Index (SSDI), National Death Index (NDI), and family members. Cause of death was obtained from the NDI. RESULTS: 217 PRSS1 carriers (181 symptomatic) formed the study cohort. The most frequently detected mutations were p.R122H (83.9%) and p.N29I (11.5%). Thirty-seven PRSS1 carriers (30 symptomatic, 7 asymptomatic) were deceased at conclusion of the study (5 from pancreatic cancer). Median overall survival was 79.3 years (IQR 72.2-85.2). Risk of pancreatic cancer was significantly greater than age- and sex- matched SEER data (SIR 59, 95% CI 19-138), and cumulative risk was 7.2% (95% CI 0-15.4) at 70 years. DISCUSSION: We confirm prior observations on survival and pancreatic cancer SIR in PRSS1 subjects. Although risk of pancreatic cancer was significantly high in these patients, its cumulative risk was much lower than previous reports.