Effect of Complementary Interventions to Redesign Care on Teamwork and Quality for Hospitalized Medical Patients : A Pragmatic Controlled Trial.

BACKGROUND: Multiple challenges impede interprofessional teamwork and the provision of high-quality care to hospitalized patients. OBJECTIVE: To evaluate the effect of interventions to redesign hospital care delivery on teamwork and patient outcomes. DESIGN: Pragmatic controlled trial. Hospitals selected 1 unit for implementation of interventions and a second to serve as a control. (ClinicalTrials.gov: NCT03745677). SETTING: Medical units at 4 U.S. hospitals. PARTICIPANTS: Health care professionals and hospitalized medical patients. INTERVENTION: Mentored implementation of unit-based physician teams, unit nurse-physician coleadership, enhanced interprofessional rounds, unit-level performance reports, and patient engagement activities. MEASUREMENTS: Primary outcomes were teamwork climate among health care professionals and adverse events experienced by patients. Secondary outcomes were length of stay (LOS), 30-day readmissions, and patient experience. Difference-in-differences (DID) analyses of patient outcomes compared intervention versus control units before and after implementation of interventions. RESULTS: Among 155 professionals who completed pre- and postintervention surveys, the median teamwork climate score was higher after than before the intervention only for nurses (n = 77) (median score, 88.0 [IQR, 77.0 to 91.0] vs. 80.0 [IQR, 70.0 to 89.0]; P = 0.022). Among 3773 patients, a greater percentage had at least 1 adverse event after compared with before the intervention on control units (change, 1.61 percentage points [95% CI, 0.01 to 3.22 percentage points]). A similar percentage of patients had at least 1 adverse event after compared with before the intervention on intervention units (change, 0.43 percentage point [CI, -1.25 to 2.12 percentage points]). A DID analysis of adverse events did not show a significant difference in change (adjusted DID, -0.92 percentage point [CI, -2.49 to 0.64 percentage point]; P = 0.25). Similarly, there were no differences in LOS, readmissions, or patient experience. LIMITATION: Adverse events occurred less frequently than anticipated, limiting statistical power. CONCLUSION: Despite improved teamwork climate among nurses, interventions to redesign care for hospitalized patients were not associated with improved patient outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Still haven't found what you're looking for: The sanctity of the search in filling pharmacy academic leadership roles.

INTRODUCTION: Professional pharmacy programs confront many changes that may lead to responsibility adjustments and position changes among leadership roles. Two distinct avenues for filling vacant or newly created roles with administrative responsibilities are the search process and the direct appointment. COMMENTARY: Of the two avenues for position recruitment, the search process is highly preferred. A search, whether national or internal, ensures a broader applicant pool, an opportunity for candidates to share their vision for the role, and protects notions of shared governance between faculty and administration. Direct appointments, though more expedient in the short-term, apply a harried approach to decision-making, circumvent consideration of the best candidates, and sever trust among faculty. IMPLICATIONS: Pharmacy academic leadership should preference the process of a proper and thorough search when faced with filling a vacant or newly created role. The temptation of the direct appointment, especially for roles with leadership responsibilities, should be avoided, as they are ultimately a deleterious shortcut.

Impact of a Co-curricular Poverty Simulation on Pharmacy Students' Socioeconomic and Patient Advocacy Attitudes and Beliefs.

Background: Pharmacists are well-positioned to assist patients facing poverty with financial and well-being resource navigation. Pharmacy educators must find avenues for students that foster awareness of applicable challenges encountered by economically disadvantaged patients. Objective: This study examines the impact of a poverty simulation on pharmacy students' socioeconomic and patient advocacy attitudes and beliefs. Methods: Third year professional pharmacy students participated in the Community Action Poverty Simulation (CAPS). Students were asked to voluntarily complete a survey prior to and following their participation. The survey was based upon a combination of 3 previously validated survey tools: Attitudes Toward Poverty (ATP) scale, Medical Student Attitudes Toward the Underserved (MSATU), and the Locus of Control Scale (LCS). Students also responded to open-ended questions postsimulation. Results: Forty of the 74 students completed both the presimulation and postsimulation surveys. Significant changes were seen in a matched sample analysis for 17 of 49 survey questions. Prominent differences (decreasing agreement) came from the statements: "An able-bodied person collecting welfare is ripping off the system" and "Welfare makes people lazy"; and increasing agreement that "I feel personally responsible for providing medical care to the needy." Open-ended survey responses reflected a greater understanding of time and effort needed to locate and navigate available resources, and challenges such as adhering to medication regimens due to inability to pay. Conclusion: A poverty simulation, such as CAPS, is an effective method to encourage pharmacy students to reflect on their future impact toward patients facing the challenges of poverty. The shift in students' attitudes and beliefs on various measures revealed that the simulation had an impact on altering perceptions for those with low socioeconomic status.

Depression Mediates the Relationships between Hallucinations, Delusions, and Social Isolation in First-Episode Psychosis.

Social isolation is common among individuals with schizophrenia spectrum and other psychotic disorders. Research indicates that social isolation relates to poorer mental health outcomes, depression, and negative symptoms, with less known about its relationship with positive symptoms. This study examined depression as a mediator in the relationships between positive symptoms (i.e., hallucinations and delusions) and social isolation among an early treatment phase sample in the United States. Data were obtained from the Recovery After an Initial Schizophrenia Episode project of the National Institute of Mental Health's Early Treatment Program. Participants (N = 404) included adults between ages 15 and 40 in a first episode of psychosis. Data were analyzed using structural equation modeling in Mplus (Version 8). The study showed that delusions (b = .095, SE = 0.04, p < .05) and hallucinations (b = .076, SE = 0.03, p < .01) were directly related to depression, and that both delusions (b = .129, SE = 0.06, p < .05) and depression (b = .254, SE = 0.09, p < .05) were directly related to social isolation. Findings of this study determined that depression functioned as a mediator in the relationships between positive symptoms and social isolation. Targeting psychosis symptomatology and depression in treatment, improving social skills and social support networks, and considering the role of stigma in social isolation are of great importance in the prevention of poorer mental health outcomes.

Psychometric evaluation of the Health Care Provider HIV/AIDS Stigma Scale (HPASS) using Rasch analysis.

INTRODUCTION: The role of pharmacists is crucial in the care of individuals with HIV/AIDS. However, stigma in health care settings can be a deterrent to providing appropriate care. This paper assessed psychometric properties and convergent validity of the Health Care Provider HIV/AIDS Stigma Scale (HPASS) among pharmacy students in the United States (US) using Rasch analysis. METHODS: Students enrolled in four US universities were administered the survey (N = 203). Rasch analysis was conducted for each HPASS subscale (Stereotyping, Discrimination, and Prejudice) to assess dimensionality, model data fit, item difficulty, individual stigma, distribution of items and persons across item-person map, and rating scale function. Convergent validity evidence was established by comparing Pearson's correlation coefficients between HPASS subscales and the AIDS Attitude Scale (AAS) Avoidance subscale. RESULTS: Two items in the Prejudice subscale were misfit and therefore removed. The 6-point rating scale did not perform satisfactorily for HPASS subscales. Item difficulty ranges were wide [Stereotyping (-5 to 0.8 logits), Discrimination (-6 to 1 logits), Prejudice (-5 to 0.4 logits)]. Items were biased towards measuring higher levels of stigma. Person separation index was satisfactory (Stereotyping = 2.2; Discrimination = 2.06; Prejudice = 2.17) as was person separation reliability (Stereotyping = 0.83; Discrimination = 0.81; Prejudice = 0.83). Convergent validity was established by showing significant correlations between HPASS subscales and AAS Avoidance (P < .001). CONCLUSIONS: Modifying or removing misfit items of HPASS and exploring alternate rating scales for HPASS subscales will help better assess HIV/AIDS related stigma among pharmacy students.

Teaching Spanish using the pharmacists' patient care process.

BACKGROUND AND PURPOSE: The Hispanic population of the United States now comprises the largest minority and is expected to increase. Student pharmacists must be prepared to care for this segment of the population. Efforts to learn medical Spanish will assist in these endeavors. EDUCATIONAL ACTIVITY AND SETTING: This paper describes the design and implementation of a novel course teaching Spanish for student pharmacists using the framework of the Pharmacists' Patient Care Process (PPCP). A two-credit hour elective course was developed to provide a focused course on practical Spanish used in the pharmaceutical care space. Lessons were framed with the various steps in the PPCP of collect, assess, plan, implement, and follow-up. FINDINGS: Interest in the course was high, with first through third professional year cohorts and varying Spanish experience represented. Student feedback from self-reflections and course evaluations revealed the course was helpful in increasing ability to work with patients of differing cultural backgrounds and in medical Spanish skill in pharmaceutical care. SUMMARY: Pharmacy programs can utilize the PPCP as an instructional method to increase offerings of medical Spanish in their curriculum with modest resource utilization.

When Human-Wildlife Conflict Turns Deadly: Comparing the Situational Factors That Drive Retaliatory Leopard Killings in South Africa.

Retaliatory killings caused by human-wildlife conflict have a significant impact on the survival of leopards. This study explores the reasons for retaliatory killings of leopards by interviewing community members in a small village in South Africa that experienced high incidences of human-leopard conflict. The semi-structured interviews focused on the reasons why retaliatory leopard killings occurred and how to best mitigate the situational factors that triggered these killings. Respondents cited four main problems that fueled these killings: the government's response to human-leopard conflict was slow and unwilling; this response involved inefficient methods; there were inadequate resources to respond to these killings; and there was a clear lack of laws or their application. Local stakeholders provided a range of innovative strategies to reduce human-leopard conflict and retaliatory killings. While all parties expressed different reasons why these solutions were or were not effective, their conclusions were often similar. The distrust that existed between the parties prevented them from recognizing or accepting their common ground. Based on existing human-wildlife conflict mitigation techniques and solutions identified by local stakeholders, this article explores how criminological techniques, including situational crime prevention, can help identify and frame effective interventions to reduce the number of illegal leopard killings driven by human-wildlife conflict.

Leveraging Expertise from Community Resources to Improve the Role of the Pharmacist in HIV Testing and Counseling.

The human immunodeficiency virus (HIV) epidemic continues to be a major global public health issue. Moreover, disparities continue to persist in HIV among racial and ethnic minority populations, with the highest rates of new diagnoses in Black/African American and Hispanic/Latino men who have sex with men in the United States. Pharmacists are one of the most accessible and trusted health care professionals. Therefore, it is imperative that student pharmacists are educated on culturally-competent HIV testing and risk behaviors counseling. This study describes the development of a partnership between a pharmacy school and a community-based organization to offer an HIV counseling and testing training program to help develop skills in delivering HIV testing services. The HIV counseling and testing training program contains learning modules that provide a wide array of in-depth information about HIV patient care in the community. The partnership allows for the enjoyment of a myriad of benefits for students, the pharmacy program, the community-based organization, and the public health of the community-at-large. Students feel more prepared and comfortable working with patients in discussing HIV transmission risk factors and test results as a result of this training. Such partnerships support the pharmacist's role in the public health arena. A successful and durable relationship between a community partner and a school of pharmacy is a feasible strategy for pharmacy progress in public health.

GPAs, PCATs, and Coupons: Wilting Quality in Pharmacy School Admissions and the Impact on Pharmacy Faculty.

INTRODUCTION: The number of available seats in US pharmacy schools has reached unprecedented numbers as applications are on the decline. A combination of forces signals that admissions to pharmacy school are becoming less selective. COMMENTARY: The conflict of balancing a need to fill the incoming class while maintaining selectivity is a growing problem in pharmacy education. Faculty may notice changes in the student quality and ultimately, program and graduate quality. Pressure from administration hinders faculty governance with negative consequences that impact faculty morale and the profession as a whole. Maintaining a firm position in the face of reduced applications is challenging but necessary if we are to protect the students we seek to support as faculty and stewards of the pharmacy profession. IMPLICATIONS: Faculty governance is at risk as pressure exists to admit less-prepared students into programs. Faculty must advocate for responsible leadership by initiating dialogue on admissions and selectivity. Furthermore, faculty mentorship programs need a new level of discussion that includes analysis and understanding of this paradigm in pharmacy academia.

Identifying opportunities for PharmD curricular reform by surveying oncology pharmacists about career preparedness and exposure.

INTRODUCTION: The primary objective of the study was to assess factors that predict pursuit of an oncology post-graduate year 2 (PGY-2) residency. Additional objectives included identifying the role of and exploring opportunities for PharmD curricula to increase student interest in the oncology field. METHODS: An anonymous 15-minute survey was developed and administered to oncology pharmacists and residents. Study participants were included if they were actively practicing as clinical pharmacists in an oncology setting in the US, maintained an active pharmacist license, and >18 years of age. Responses were analyzed using descriptive and inferential statistics. All results are reported in aggregate, with the exception of quotes obtained from open-ended responses. RESULTS: Eighty participants were included in analyses. After controlling for variance due to age, sex, race, years of practice, the number of oncology advanced pharmacy practice experiences (APPEs) correlated with pursuit of a PGY-2 residency in oncology (p = 0.047). Additionally, participants' perceived level of preparedness from didactic oncology training predicted pursuit of an oncology PGY-2 residency (p = 0.002). Emerging themes in pursuing oncology from open-ended items revealed that inclusion of supportive care in the didactic curriculum and having a family member or friend diagnosed with cancer were important factors. Additionally, participants' responses regarding PharmD curricula included recommendations to inform didactic and experiential education. CONCLUSIONS: The results support the need for reevaluation of oncology education in PharmD curricula. Further studies could explore specific aspects of didactic curriculum that impact the level of student preparedness, and which elements encourage a student pharmacist to seek further training in the oncology field.

Keratinocyte growth factor impairs human thymic recovery from lymphopenia.

BACKGROUND: The lymphocyte-depleting antibody alemtuzumab is a highly effective treatment of relapsing-remitting multiple sclerosis (RRMS); however 50% of patients develop novel autoimmunity post-treatment. Most at risk are individuals who reconstitute their T-cell pool by proliferating residual cells, rather than producing new T-cells in the thymus; raising the possibility that autoimmunity might be prevented by increasing thymopoiesis. Keratinocyte growth factor (palifermin) promotes thymopoiesis in non-human primates. METHODS: Following a dose-tolerability sub-study, individuals with RRMS (duration ≤10 years; expanded disability status scale ≤5·0; with ≥2 relapses in the previous 2 years) were randomised to placebo or 180mcg/kg/day palifermin, given for 3 days immediately prior to and after each cycle of alemtuzumab, with repeat doses at M1 and M3. The interim primary endpoint was naïve CD4+ T-cell count at M6. Exploratory endpoints included: number of recent thymic-emigrants (RTEs) and signal-joint T-cell receptor excision circles (sjTRECs)/mL of blood. The trial primary endpoint was incidence of autoimmunity at M30. FINDINGS: At M6, individuals receiving palifermin had fewer naïve CD4+T-cells (2.229x107/L vs. 7.733x107/L; p=0.007), RTEs (16% vs. 34%) and sjTRECs/mL (1100 vs. 3396), leading to protocol-defined termination of recruitment. No difference was observed in the rate of autoimmunity between the two groupsConclusion: In contrast to animal studies, palifermin reduced thymopoiesis in our patients. These results offer a note of caution to those using palifermin to promote thymopoiesis in other settings, particularly in the oncology/haematology setting where alemtuzumab is often used as part of the conditioning regime. TRIAL REGISTRATION: ClinicalTrials.gov NCT01712945Funding: MRC and Moulton Charitable Foundation.

Extracellular Lactate: A Novel Measure of T Cell Proliferation.

Following activation, T cells rapidly divide and acquire effector functions. This energetically demanding process depends upon the ability of T cells to undergo metabolic remodeling from oxidative phosphorylation to aerobic glycolysis, during which glucose is converted into lactate and released extracellularly. In this article, we demonstrate that extracellular lactate can be used to dynamically assess human T cell responses in vitro. Extracellular lactate levels strongly correlated with T cell proliferation, and measuring lactate compared favorably with traditional methods for determining T cell responses (i.e., [3H]thymidine incorporation and the use of cell proliferation dyes). Furthermore, we demonstrate the usefulness of measuring lactate as a read-out in conventional suppression assays and high-throughput peptide-screening assays. Extracellular lactate was stably produced over 7 d, and results were reproducibly performed over several freeze-thaw cycles. We conclude that the use of extracellular lactate measurements can be a sensitive, safe, stable, and easy-to-implement research tool for measuring T cell responses and cellular metabolic changes in vitro.

Skeletal Muscle Metabolic Dysfunction in Patients With Malignant Hyperthermia Susceptibility.

BACKGROUND: Malignant hyperthermia (MH), a pharmacogenetic disorder of skeletal muscle, presents with a potentially lethal hypermetabolic reaction to certain anesthetics. However, some MH-susceptible patients experience muscle weakness, fatigue, and exercise intolerance in the absence of anesthetic triggers. The objective of this exploratory study was to elucidate the pathophysiology of exercise intolerance in patients tested positive for MH with the caffeine-halothane contracture test. To this end, we used phosphorus magnetic resonance spectroscopy, blood oxygen level-dependent functional magnetic resonance imaging (MRI), and traditional exercise testing to compare skeletal muscle metabolism in MH-positive patients and healthy controls. METHODS: Skeletal muscle metabolism was assessed using phosphorus magnetic resonance spectroscopy and blood oxygen level-dependent functional MRI in 29 MH-positive patients and 20 healthy controls. Traditional measures of physical capacity were employed to measure aerobic capacity, anaerobic capacity, and muscle strength. RESULTS: During 30- and 60-second exercise, MH-positive patients had significantly lower ATP production via the oxidative pathway compared to healthy controls. MH-positive patients also had a longer recovery time with blood oxygen level-dependent functional MRI compared to healthy controls. Exercise testing revealed lower aerobic and anaerobic capacity in MH-positive patients compared to healthy controls. CONCLUSIONS: Results of this exploratory study suggest that MH-positive patients have impaired aerobic metabolism compared to healthy individuals. This could explain the exercise intolerance exhibited in MH-susceptible patient population.

Anterior Cervical Infection: Presentation and Incidence of an Uncommon Postoperative Complication.

STUDY DESIGN: Retrospective multi-institutional case series. OBJECTIVE: The anterior cervical discectomy and fusion (ACDF) affords the surgeon the flexibility to treat a variety of cervical pathologies, with the majority being for degenerative and traumatic indications. Limited data in the literature describe the presentation and true incidence of postoperative surgical site infections. METHODS: A retrospective multicenter case series study was conducted involving 21 high-volume surgical centers from the AOSpine North America Clinical Research Network, selected for their excellence in spine care and clinical research infrastructure and experience. Medical records for 17 625 patients who received cervical spine surgery (levels from C2 to C7) between January 1, 2005, and December 31, 2011, inclusive, were reviewed to identify the occurrence of 21 predefined treatment complications. Patients who underwent an ACDF were identified in the database and reviewed for the occurrence of postoperative anterior cervical infections. RESULTS: A total of 8887 patients were identified from a retrospective database analysis of 21 centers providing data for postoperative anterior cervical infections (17/21, 81% response rate). A total of 6 postoperative infections after ACDF were identified for a mean rate of 0.07% (range 0% to 0.39%). The mean age of patients identified was 57.5 (SD = 11.6, 66.7% female). The mean body mass index was 22.02. Of the total infections, half were smokers (n = 3). Two patients presented with myelopathy, and 3 patients presented with radiculopathic-type complaints. The mean length of stay was 4.7 days. All patients were treated aggressively with surgery for management of this complication, with improvement in all patients. There were no mortalities. CONCLUSION: The incidence of postoperative infection in ACDF is exceedingly low. The management has historically been urgent irrigation and debridement of the surgical site. However, due to the rarity of this occurrence, guidance for management is limited to retrospective series.

Esophageal Perforation Following Anterior Cervical Spine Surgery: Case Report and Review of the Literature.

STUDY DESIGN: Multicenter retrospective case series and review of the literature. OBJECTIVE: To determine the rate of esophageal perforations following anterior cervical spine surgery. METHODS: As part of an AOSpine series on rare complications, a retrospective cohort study was conducted among 21 high-volume surgical centers to identify esophageal perforations following anterior cervical spine surgery. Staff at each center abstracted data from patients' charts and created case report forms for each event identified. Case report forms were then sent to the AOSpine North America Clinical Research Network Methodological Core for data processing and analysis. RESULTS: The records of 9591 patients who underwent anterior cervical spine surgery were reviewed. Two (0.02%) were found to have esophageal perforations following anterior cervical spine surgery. Both cases were detected and treated in the acute postoperative period. One patient was successfully treated with primary repair and debridement. One patient underwent multiple debridement attempts and expired. CONCLUSIONS: Esophageal perforation following anterior cervical spine surgery is a relatively rare occurrence. Prompt recognition and treatment of these injuries is critical to minimizing morbidity and mortality.

C5 Palsy After Cervical Spine Surgery: A Multicenter Retrospective Review of 59 Cases.

STUDY DESIGN: A multicenter, retrospective review of C5 palsy after cervical spine surgery. OBJECTIVE: Postoperative C5 palsy is a known complication of cervical decompressive spinal surgery. The goal of this study was to review the incidence, patient characteristics, and outcome of C5 palsy in patients undergoing cervical spine surgery. METHODS: We conducted a multicenter, retrospective review of 13 946 patients across 21 centers who received cervical spine surgery (levels C2 to C7) between January 1, 2005, and December 31, 2011, inclusive. P values were calculated using 2-sample t test for continuous variables and χ2 tests or Fisher exact tests for categorical variables. RESULTS: Of the 13 946 cases reviewed, 59 patients experienced a postoperative C5 palsy. The incidence rate across the 21 sites ranged from 0% to 2.5%. At most recent follow-up, 32 patients reported complete resolution of symptoms (54.2%), 15 had symptoms resolve with residual effects (25.4%), 10 patients did not recover (17.0%), and 2 were lost to follow-up (3.4%). CONCLUSION: C5 palsy occurred in all surgical approaches and across a variety of diagnoses. The majority of patients had full recovery or recovery with residual effects. This study represents the largest series of North American patients reviewed to date.

The association among skeletal muscle phosphocreatine recovery, adiposity, and insulin resistance in children.

BACKGROUND: Obesity is associated with cardiometabolic disturbances, which may have significant implications for musculoskeletal health and exercise tolerance. OBJECTIVE: We sought to determine the association between muscle structure, function, and metabolism in adolescents across the weight spectrum. METHODS: This cross-sectional case-control study included overweight and obese participants (n = 24) 8-18 years of age with a body mass index (BMI) ≥ 85th percentile for age and gender, and non-obese participants (n = 24) with a BMI < 85th percentile. Body composition, physical activity, peak aerobic capacity, cardiometabolic blood markers and insulin resistance (measured by the homeostatic model assessment of insulin resistance, HOMA-IR), skeletal muscle mitochondrial oxidative capacity (via 31 Phosphorous-Magnetic Resonance Spectroscopy, 31 P-MRS, to assess phosphocreatine (PCr) recovery after exercise), and extramyocellular and intramyocellular lipid (IMCL) levels (via 1 Hydrogen-MRS) were assessed. Stepwise regression was performed to examine the factors associated with oxidative capacity. RESULTS: bese and overweight patients had similar age, height, and physical activity to non-obese controls, but obese and overweight participants exhibited higher insulin resistance. Obese and overweight participants had longer PCr recovery than non-obese controls following 5x30s of moderate-intensity exercise (51.2 ± 20.1 s vs. 23.9 ± 7.5 s, p = 0.004). In univariate correlation analysis, impaired PCr recovery was associated with a higher BMI z-score (rs = 0.51, p < 0.001), circulating triglycerides (rs = 0.41, p = 0.005), and HOMA-IR (rs = 0.46, p = 0.001). In stepwise multivariate regression analysis, impaired PCr recovery was associated with a higher BMI z-score (ß = 0.47, p = 0.002), but not insulin resistance (ß = 0.07, p = 0.07) or circulating triglycerides (ß = 0.16 p = 0.33). CONCLUSION: A slower phosphocreatine recovery following aerobic exercise is strongly associated with increasing adiposity. A slower metabolic recovery following aerobic exercise stress suggests that endurance exercise training in obese adolescents may be an optimal strategy to target exercise intolerance in this cohort.

Spinal Implant Density and Postoperative Lumbar Lordosis as Predictors for the Development of Proximal Junctional Kyphosis in Adult Spinal Deformity.

OBJECTIVE: To evaluate spinal implant density and proximal junctional kyphosis (PJK) in adult spinal deformity (ASD). METHODS: Consecutive patients with ASD receiving ≥5 level fusions were retrospectively analyzed between 2007 and 2010. INCLUSION CRITERIA: ASD, elective fusions, minimum 2-year follow-up. EXCLUSION CRITERIA: age <18 years, neuromuscular or congenital scoliosis, cervical or cervicothoracic fusions, nonelective conditions (infection, tumor, trauma). Instrumented fusions were classified by the Scoliosis Research Society-Schwab ASD classification. Statistical analysis consisted of descriptives (measures of central tendency, dispersion, frequencies), independent Student t tests, χ2, analysis of variance, and logistic regression to determine association of implant density [(number of screws + number of hooks)/surgical levels of fusion] and PJK. Mean and median follow-up was 2.8 and 2.7 years, respectively. RESULTS: Eighty-three patients (17 male, 66 female) with a mean age of 59.7 years (standard deviation, 10.3) were analyzed. Mean body mass index (BMI) was 29.5 kg/m2 (range, 18-56 kg/m2) with mean preoperative Oswestry Disability Index of 48.67 (range, 6-86) and mean preoperative sagittal vertical axis of 8.42. The mean levels fused were 9.95 where 54 surgeries had interbody fusion. PJK prevalence was 21.7%, and pseudoarthrosis was 19.3%. Mean postoperative Oswestry Disability Index was 27.4 (range, 0-74). Independent Student t tests showed that PJK was not significant for age, gender, BMI, rod type, mean postoperative sagittal vertical axis, or Scoliosis Research Society-Schwab ASD classification; but iliac fixation approached significance (P = 0.077). Implant density and postoperative lumbar lordosis (LL) were predictors for PJK (P = 0.018 and 0.045, respectively). Controlling for age, BMI, and gender, postoperative LL (not implant density) continued to show significance in multivariate logistic regression model. CONCLUSIONS: PJK, although influenced by a multitude of factors, may be statistically related to implant density and LL.

Increased THEMIS First Exon Usage in CD4+ T-Cells Is Associated with a Genotype that Is Protective against Multiple Sclerosis.

Multiple sclerosis is an autoimmune disease of the central nervous system. Genome wide association studies have identified over 100 common variants associated with multiple sclerosis, the majority of which implicate immunologically relevant genes, particularly those involved in T-cell development. SNP rs13204742 at the THEMIS/PTPRK locus is one such variant. Here, we have demonstrated mutually exclusive use of exon 1 and 2 amongst 16 novel THEMIS isoforms. We also show inverse correlation between THEMIS expression in human CD4+ T-cells and dosage of the multiple sclerosis risk allele at rs13204742, driven by reduced expression of exon 1- containing isoforms. In silico analysis suggests that this may be due to cell-specific, allele-dependent binding of the transcription factors FoxP3 and/or E47. Research exploring the functional implications of GWAS variants is important for gaining an understanding of disease pathogenesis, with the ultimate aim of identifying new therapeutic targets.