Citations

Abstract BACKGROUND Modern healthcare reforms focus on identifying and measuring the quality and value of care. Patient satisfaction is particularly important in the management of degenerative cervical radiculopathy (DCR) since it leads to significant neck pain and disability primarily affecting the patients’ quality of life. OBJECTIVE To determine the association of baseline and 12-mo Neck Disability Index (NDI) with patient satisfaction after elective surgery for DCR. METHODS The Quality Outcomes Database cervical module was queried for patients who underwent elective surgery for DCR. A multivariable proportional odds regression model was fitted with 12-mo satisfaction as the outcome. The covariates for this model included patients’ demographics, surgical characteristics, and baseline and 12-mo patient reported outcomes (PROs). Wald-statistics were calculated to determine the relative importance of each independent variable for 12-mo patient satisfaction. RESULTS The analysis included 2206 patients who underwent elective surgery for DCR. In multivariable analysis, after adjusting for baseline and surgery specific variables, the 12-mo NDI score showed the highest association with 12-mo satisfaction (Waldχ2-df = 99.17, 58.1% of total χ2). The level of satisfaction increases with decrease in 12-mo NDI score regardless of the baseline NDI score. CONCLUSION Our study identifies 12-mo NDI score as a very influential driver of 12-mo patient satisfaction after surgery for DCR. In addition, there are lesser contributions from other 12-mo PROs, baseline Numeric Rating Scale for arm pain and American Society of Anesthesiologists (ASA) grade. The baseline level of disability was found to be irrelevant to patients. They seemed to only value their current level of disability, compared to baseline, in rating satisfaction with surgical outcome.

Background: Periacetabular osteotomy (PAO) is the most common treatment for symptomatic acetabular dysplasia, or developmental dysplasia of the hip (DDH), in skeletally mature patients. The purpose of this multicenter cohort study was to delineate the long-term radiographic natural history of the dysplastic hip following PAO. Methods: We evaluated all patients undergoing PAO from 1996 to 2012 at 3 academic institutions in the United States. Inclusion criteria were PAO for DDH with a minimum 5-year radiographic follow-up. Exclusion criteria were PAO for isolated acetabular retroversion, neurogenic dysplasia, Legg-Calvé-Perthes disease, and prior hip surgery including osteotomies and arthroscopy. There were 288 patients, 83% of whom were women; the mean age and body mass index (BMI) were 29 years and 25 kg/m 2 , respectively. The mean clinical and radiographic follow-up was 9.2 years (range, 5.0 to 21.1 years). Every preoperative and postoperative hip radiograph was assessed to determine the degree of osteoarthritis according to the Tönnis classification. Survivorship was analyzed by multistate modeling, enabling assessment of progression through the Tönnis grades rather than just individual transitions as with Kaplan-Meier techniques. Results: At the time of final follow-up, 144 patients (50%) had progressed at least 1 Tönnis grade, with 42 patients (14.6%) undergoing total hip arthroplasty. The mean number of years spent in each Tönnis grade following PAO was 19 for Tönnis grade 1, 8 for Tönnis grade 2, and 4 for Tönnis grade 3. The probability of progression to total hip arthroplasty increased significantly on the basis of a higher initial Tönnis grade (p < 0.001). The most marked difference occurred between Tönnis grade 0 or 1 and Tönnis grade 2; for Tönnis grade 1, the probability of progression to total hip arthroplasty at 5 and 10 years was 2% and 11%, respectively, compared with 23% and 53%, respectively, for Tönnis grade 2. Conclusions: PAO effectively alters the natural history of DDH. Precise radiographic progression based on the Tönnis grade can now be used to ascribe prognosis for the native hip. Importantly, this investigation demonstrates a stark increase in progression to total hip arthroplasty within 10 years of PAO for patients with preoperative Tönnis grade-2 osteoarthritis compared with those with Tönnis grade-0 or 1 osteoarthritis. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Objective To compare the risk of mortality and morbidity between outborn and propensity score-matched inborn extremely preterm neonates. Setting Multiple neonatal intensive care units (NICU) across the USA. Patients Singleton neonates born at 22–29 weeks’ gestation with no major anomalies who were admitted to a NICU and discharged between 2000 and 2014. Outborn neonates were restricted to those who transferred into a NICU on the day of birth. Methods The association between inborn-outborn status and the time-to-event outcomes of in-hospital mortality and necrotising enterocolitis (NEC) were assessed using Cox proportional hazards regression. Logistic regression was used to assess the remaining secondary outcomes: retinopathy of prematurity requiring treatment (tROP), chronic lung disease (CLD), periventricular leucomalacia (PVL) and severe intraventricular haemorrhage (IVH). Since outborn status was not random, we used 1:1 propensity score matching to reduce the imbalance in illness severity. Results There were 59 942 neonates (7991 outborn) included in the study. Outborn neonates had poorer survival than inborns and higher rates of NEC, severe IVH, tROP and PVL. Inborn-outborn disparities in mortality were reduced over the study period. When analysing the matched cohort (6524 matched pairs), outborns were less likely to die in-hospital compared with inborns (HR 0.84, 95% CI 0.77 to 0.91). However, outborns experienced higher rates of NEC (HR 1.14, 95% CI 1.04 to 1.25), severe IVH (OR 1.52, 95% CI 1.38 to 1.68), tROP (OR 1.45, 95% CI 1.25 to 1.69) and CLD (OR 1.12, 95% CI 1.01 to 1.24). Conclusion Additional research is needed to understand the contributors to increased morbidity for outborn extremely preterm neonates and identify interventions that mitigate this risk.

Abstract Background: Different molecules within coffee may be pro-carcinogenic, while others may have anti-oxidant and anti-neoplastic effects. Hence, it can be hypothesized that coffee may have differing risk associations with specific colorectal cancer (CRC) subtypes. The aim of this study was to evaluate associations between coffee consumption and incident CRC overall, by anatomic subsite, and by molecularly defined tumor subtypes, in the population-based Iowa Women's Health Study (IWHS). Methods: IWHS participants, ages 55-69 years, provided dietary intake estimates using self-reported food frequency questionnaires at baseline (1986). From 35,216 women included the final analysis, 1298 developed CRC (673 with proximal CRC, 597 with distal CRC) through December 31, 2002 (end of the IWHS molecular epidemiology project study period). Archived, paraffin-embedded tissue specimens for 732 representative CRC cases were collected and analyzed to determine if coffee consumption (none or &lt;1 cup/month, &lt;1 cup/week, 1 cup/day, 2-3 cups/day and ≥4 cups/day) was associated with microsatellite instability (MSI-L/MSS or MSI-H), CpG island methylator phenotype (CIMP-negative or CIMP-positive), BRAF mutation status (BRAF-wildtype or BRAF-mutated), KRAS mutation status (KRAS-wildtype and KRAS-mutated), p53 protein expression level (p53 absent, low or high) and estrogen receptor β protein expression level (ERβ absent, low or high). Multivariable Cox regression models were fit to estimate relative risks (RR) and 95% confidence intervals (CI) with adjustment for age, smoking, alcohol use, diabetes, body mass index and waist-hip ratio, physical activity, estrogen use, dietary intake of fat, calcium, vitamin E, sucrose, red meat and methionine. P-values were not adjusted for multiple testing. Results: There was no significant difference in the risk of overall (RR, 1.05; 95% CI, 0.85-1.29; Ptrend=0.50), proximal (RR, 0.91; 95% CI, 0.68-1.21; Ptrend=0.57) or distal CRC (RR, 1.18; 95% CI, 0.86-1.64; Ptrend=0.19) in women who consumed ≥4 cups of coffee/day (caffeinated or decaffeinated), as compared to non-consumers. By CRC molecular subtypes for these same two exposure groups, women with ≥4 cups of coffee/day were more likely to develop ERβ-low CRC (RR, 2.98; 95% CI, 1.04-8.51; Ptrend=0.06), though no significant associations were observed for caffeinated or decaffeinated coffee specifically. In contrast, women who consumed ≥4 cups of decaffeinated coffee/day were less likely to develop MSI-L/MSS (RR, 0.57; 95% CI, 0.36-0.92; Ptrend=0.04) and BRAF-WT (RR, 0.69; 95% CI, 0.44-1.06; Ptrend=0.06) CRCs than non-consumers. Women who consumed ≥4 cups of caffeinated coffee/day were also less likely to develop p53-low CRCs (RR, 0.53; 95% CI, 0.24-1.15; Ptrend=0.02). Null associations were observed between decaffeinated coffee consumption and risk of CIMP-, KRAS- and p53- defined CRC subtypes, as well as between caffeinated coffee consumption and risk of MSI-, BRAF-, CIMP- or KRAS-defined CRC subtypes. Conclusion: In this prospective cohort study of older women, though coffee consumption was not associated with risk of overall or site-specific CRC, unique associations were observed with molecularly defined CRC subtypes, supporting a need for further investigation of the potential pro- and anti-carcinogenic effects of coffee constituents on biologic targets involved in colorectal carcinogenesis. Citation Format: Siddharth Singh, Robert Vierkant, Lori Tillmans, Alice Wang, Daniel Weisenberger, Peter Laird, Maki Inoue-Choi, Andrea Mariani, Charles Lynch, Kristin Anderson, Amy French, Robert Haile, Lisa Harnack, John Potter, Susan Slager, Thomas Smyrk, Stephen Thibodeau, James Cerhan, Paul Limburg. Coffee consumption and colorectal cancer risk by molecularly defined subtypes in a prospective cohort study of older women. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A44.

Humans are sexually dimorphic, with sex being the most persistent difference among humans over the course of our evolutionary history. Beyond the visible sex differences that can be considered true dimorphisms, there are also sex differences at the molecular and cellular scales. The role of these biological sex differences for human health, while being increasingly recognized, have long been underappreciated and underexplored. Frequently, these differences are only recognized in sex–specific diseases, such as genitourinary diseases and cancers. However, given the evidence for sex differences in the most basic aspects of human biology, including metabolism, cellular composition, and immune activity, these differences could have consequences for the etiology and pathophysiology of a majority of diseases. It is thus essential to consider the extent to which these differences may influence the various mechanisms underlying disease processes, response to treatment, and the maintenance of health in order to better improve patient outcomes. Here we review the evidence for a broad array of biological sex differences in humans and discuss how they may relate to observed sex differences in various diseases, with an emphasis on cancer, specifically glioblastoma. We further propose that mathematical approaches can be useful for exploring the extent to which sex differences affect disease outcomes and accounting for those in the development of therapeutic strategies.

AbstractPurposeThis report examines and evaluates pharmacogenomics as an emerging science as it relates to the Practice Advancement Initiative and its predecessor the Pharmacy Practice Model Initiative’s consensus statements for optimal pharmacy practice models.SummaryPharmacogenomics is one of many emerging sciences to impact medication management and delivery of patient care. Increasingly, biomarkers are included in drug labeling and can assist pharmacists with personalizing medicine to optimize patient therapies and avoid adverse effects. The 2011 ASHP Pharmacy Practice Model Summit generated a list of 147 consensus statements for optimal pharmacy practice. Of these, 1 statement explicitly describes adjustment of drug regimens based on genetic factors as an essential activity of pharmacist-provided drug regimens, and 9 other statements provide additional support for incorporation of this emerging science into all aspects of patient care provided by pharmacists. We describe 4 institutions that have made significant inroads to implementing pharmacogenomics, to provide a framework and serve as resources for other institutions initiating their own pharmacogenomics implementation journeys.ConclusionThrough prioritized efforts of the pharmacy profession and health care institutions, pharmacogenomics will be disseminated and implemented, and the goal of the Pharmacy Practice Model Initiative’s consensus statements of improving health care using patients’ genetic characteristics will be realized.

Purpose The purpose of this study was to examine the relationship between manifestations of racism in medical school and subsequent changes in graduating medical students’ intentions to practice in underserved or minority communities, compared with their attitudes and intentions at matriculation. Method The authors used repeated-measures data from a longitudinal study of 3,756 students at 49 U.S. medical schools that were collected from 2010 to 2014. They conducted generalized linear mixed models to estimate whether manifestations of racism in school curricula/policies, school culture/climate, or student attitudes/behaviors predicted first- to fourth-year changes in students’ intentions to practice in underserved communities or primarily with minority populations. Analyses were stratified by students’ practice intentions (no/undecided/yes) at matriculation. Results Students’ more negative explicit racial attitudes were associated with decreased intention to practice with underserved or minority populations at graduation. Service learning experiences and a curriculum focused on improving minority health were associated with increased intention to practice in underserved communities. A curriculum focused on minority health/disparities, students’ perceived skill at developing relationships with minority patients, the proportion of minority students at the school, and the perception of a tense interracial environment were all associated with increased intention to care for minority patients. Conclusions This study provides evidence that racism manifested at multiple levels in medical schools was associated with graduating students’ decisions to provide care in high-need communities. Strategies to identify and eliminate structural racism and its manifestations in medical school are needed.

Background: Two-stage exchange is the most common form of treatment of chronic infection following total hip arthroplasty (THA). We examined the prevalence of, and risk factors associated with, hip instability following 2-stage exchange as well as the fate of reimplanted hip prostheses that dislocated. Methods: Data on 515 2-stage exchange THAs performed between 2000 and 2014 at a single institution were retrospectively reviewed. Risk factors for instability as well as postoperative reoperations and revisions were analyzed. The impact of dislocation on these outcomes was evaluated as well. The mean age at the time of reimplantation was 65 years, and the mean duration of follow-up was 5 years (range, 2 to 15 years). Results: Dislocation occurred in 52 hips following reimplantation (cumulative probability = 8.9% at 1 year). There was a higher risk of instability in women (hazard ratio [HR] = 1.8, p = 0.038) and in those who had a history of dislocation prior to the 2-stage revision (HR = 5.1, p < 0.001). Younger age, body mass index, number of previous operations, spacer type, surgical approach, use of a constrained liner, femoral head diameter, and persistent or recurrent infection were not found to be significant risk factors. Patients with an absent or ununited greater trochanter or abductor deficiency also had a higher rate of dislocation (HR = 30, p < 0.001), as did patients who underwent reimplantation with a megaprosthesis (HR = 6.0, p < 0.001). The risk of additional reoperations (HR = 121, p < 0.001) and revision surgery (HR = 13, p < 0.001) was significantly higher in patients who experienced a dislocation after the 2-stage exchange. Conclusions: Dislocation after 2-stage exchange THA continues to be a major concern, with the 1-year cumulative probability found to be 9% in the present study. Female sex, a history of dislocation, an absent or ununited greater trochanter or abductor deficiency, and reimplantation with a megaprosthesis were identified as risk factors for dislocation. There is a remarkable 121-fold increase in the rate of reoperations and a 13-fold increase in the rate of revisions in hips that dislocated after 2-stage exchange THA. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.