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Health care teams are most effective at addressing complex problems and improving health outcomes for underserved populations when team members bring diverse life experiences and perspectives to the effort. With rates of visual impairment expected to increase in the United States by 2050, especially among minority populations, diversification of the ophthalmology workforce will be critical in reducing disparities in access to and quality of vision health care. Currently, ophthalmology is less diverse with respect to race, ethnicity, and gender than graduating medical classes and other medical specialties, as well as the general US population. In addition, data on diversity in sexual orientation and gender identity, socioeconomic status, and disability are lacking in ophthalmology. The Minority Ophthalmology Mentoring and Rabb-Venable Excellence in Ophthalmology Programs are examples of initiatives to increase racial and ethnic diversity in the workforce and can serve as models for increasing other aspects of inclusiveness. Other strategies for improving vision health care for all Americans include continuing to support existing diversity programs and creating new ones; addressing unconscious and implicit bias in medical school, residency, and faculty selections; conducting holistic reviews of medical school and residency applications; diversifying selection committees and leadership; and encouraging faculty development of underrepresented groups.

Background Enhanced Recovery Pathways (ERP) have been shown to reduce racial disparities following surgery. The objective of this study is to determine whether ERP implementation mitigates racial disparities at a Veterans Affairs Hospital. Methods A retrospective cohort study was conducted using data obtained from the Veterans Affairs Surgical Quality Improvement Program. All patients undergoing elective colorectal surgery following ERP implementation were included. Current procedural terminology (CPT) codes were used to identify patients who underwent similar procedures prior to ERP implementation. Results Our study included 417 patients (314 pre-ERP vs. 103 ERP), 97.1% of which were male, with an average age of 62.32 (interquartile range (IQR): 25–90). ERP patients overall had a significantly shorter post-operative length of stay (pLOS) vs. pre-ERP patients (median 4 days (IQR: 3–6.5) vs. 6 days (IQR: 4–9) days (p Conclusions Racial disparities did not exist in patients undergoing elective surgery at a single VA Medical Center. Implementation of an ERP significantly reduced pLOS for black and white patients.

Background Combined liver-kidney transplantation (CLKT) improves survival for liver transplant recipients with renal dysfunction; however, the tenuous perioperative hemodynamic and metabolic milieu in high-acuity CLKT recipients increases delayed graft function and kidney allograft failure. We sought to analyze whether delayed KT through pumping would improve kidney outcomes following CLKT. Methods A retrospective analysis (University of California Los Angeles [n = 145], Houston Methodist Hospital [n = 79]) was performed in all adults receiving CLKT at 2 high-volume transplant centers from February 2004 to January 2017, and recipients were analyzed for patient and allograft survival as well as renal outcomes following CLKT. Results A total of 63 patients (28.1%) underwent delayed implantation of pumped kidneys during CLKT (dCLKT) and 161 patients (71.9%) received early implantation of nonpumped kidneys during CLKT (eCLKT). Most recipients were high-acuity with median biologic model of end-stage liver disease (MELD) score of, 35 for dCLKT and 34 for eCLKT (P = ns). Pretransplant, dCLKT had longer intensive care unit stay, were more often intubated, and had greater vasopressor use. Despite this, dCLKT exhibited improved 1-, 3-, and 5-year patient and kidney survival (P = 0.02) and decreased length of stay (P = 0.001), kidney allograft failure (P = 0.012), and dialysis duration (P = 0.031). This reduced kidney allograft futility (death or continued need for hemodialysis within 3 mo posttransplant) for dCLKT (6.3%) compared with eCLKT (19.9%) (P = 0.013). Conclusions Delayed implantation of pumped kidneys is associated with improved patient and renal allograft survival and decreased hospital length of stay despite longer kidney cold ischemia. These data should inform the ethical debate as to the futility of performing CLKT in high-acuity recipients.

Background: During adolescence, deselection from sport occurs during team try-outs when month of birth, stage of growth and maturation may influence selection. Aim: The purpose of this study was to identify differences in growth and maturity related factors between those selected and deselected in youth sports teams and identify short-term associations with continued participation. Subjects and methods: Eight hundred and seventy participants, aged 11–17 years, were recruited from six sports try-outs in Saskatchewan, Canada: baseball, basketball, football, hockey, soccer and volleyball. Two hundred and forty-four of the initial 870 (28%) returned for follow-up at 36 months. Chronological (years from birth), biological (years from age at peak height velocity (APHV)) and relative (month of birth as it relates to the selection band) ages were calculated from measures of date of birth, date of test, height, sitting height and weight. Parental heights were measured or recalled and participant’s adult height predicted. Reference standards were used to calculate z-scores. Sports participation was self-reported at try-outs and at 36-month follow-up. Results: There was an over-representation of players across all sports born in the first and second quartiles of the selection bands (p < 0.05), whether they were selected or deselected. z-scores for predicted adult height ranged from 0.1 (1.1) to 1.8 (1.2) and were significantly different between sports (p < 0.05). Height and APHV differences (p < 0.05) were found between selected and deselected male participants. In females only weight differed between selected and deselected female hockey players (p < 0.05); no further differences were found between selected and deselected female participants. Four per cent of deselected athletes exited sports participation and 68% of deselected athletes remained in the same sport at 36 months, compared with 84% of selected athletes who remained in the same sport. Conclusions: It was found that youth who attended sports team’s try-outs were more likely to be born early in the selection year, be tall for their age, and in some sports early maturers. The majority of both the selected and deselected participants continued to participate in sport 36 months after try-outs, with the majority continuing to participate in their try-out sport.

A better understanding of early brain changes that precede loss of independence in diseases like Alzheimer's disease (AD) is critical for development of disease-modifying therapies. Quantitative MRI, such as T2 relaxometry, can identify microstructural changes relevant to early stages of pathology. Recent evidence suggests heterogeneity of T2 may be a more informative MRI measure of early pathology than absolute T2. Here we test whether T2 markers of brain integrity precede the volume changes we know are present in established AD and whether such changes are most marked in medial temporal lobe (MTL) subfields known to be most affected early in AD. We show that T2 heterogeneity was greater in people with mild cognitive impairment (MCI; n = 49) compared to healthy older controls (n = 99) in all MTL subfields, but this increase was greatest in MTL cortices, and smallest in dentate gyrus. This reflects the spatio-temporal progression of neurodegeneration in AD. T2 heterogeneity in CA1-3 and entorhinal cortex and volume of entorhinal cortex showed some ability to predict cognitive decline, where absolute T2 could not, however further studies are required to verify this result. Increases in T2 heterogeneity in MTL cortices may reflect localised pathological change and may present as one of the earliest detectible brain changes prior to atrophy. Finally, we describe a mechanism by which memory, as measured by accuracy and reaction time on a paired associate learning task, deteriorates with age. Age-related memory deficits were explained in part by lower subfield volumes, which in turn were directly associated with greater T2 heterogeneity. We propose that tissue with high T2 heterogeneity represents extant tissue at risk of permanent damage but with the potential for therapeutic rescue. This has implications for early detection of neurodegenerative diseases and the study of brain-behaviour relationships.

In kidney transplantation, BK virus infection has historically resulted in high rates of graft dysfunction and graft loss. Unlike other opportunistic infections, no therapies have been shown to prevent BK. The purpose of the current study was to evaluate the safety and efficacy of ciprofloxacin for the prevention of BK viremia in kidney transplant recipients. Two hundred kidney transplant recipients were enrolled in a prospective, randomized, double-blind, placebo-controlled trial comparing a 3-month course of ciprofloxacin (n = 133) vs placebo (n = 67) for the prevention of BK viremia. The primary endpoint of BK viremia at month 6 posttransplant occurred in 25 (18.8%) patients in the ciprofloxacin group and 5 (7.5%) in the placebo group (P = .03). Higher rates of BK viremia (23.3% vs 11.9%; P = .06) and BK nephropathy (5.8% vs 1.5%; P = .26) remained at 12 months in the ciprofloxacin group. Ciprofloxacin use was associated with a significantly higher rate of fluoroquinolone-resistant gram-negative infections (83.3% vs 50%; P = .04). A 3-month course of ciprofloxacin was ineffective at preventing BK viremia in kidney transplant recipients and was associated with an increased risk of fluoroquinolone-resistant infections. Clinical trial registration number: NCT01789203.

An ideal model for decision making in cancer is shared decision-making (SDM). Primary facilitators in this model are information-seeking about treatment options and patient-physician trust. Previous studies have investigated the role of each of these parameters individually. However, little is known about their convergent role in treatment decision-making. Therefore, we explored perspectives of metastatic breast cancer (MBC) patients and healthcare professionals about the influence of health information-seeking and physician trust in the SDM process. Qualitative interviews with 20 MBC patients and 6 community oncologists, as well as 3 separate focus groups involving lay navigators, nurses, and academic oncologists, were conducted, recorded, and transcribed. Qualitative data analysis employed a content analysis approach, which included a constant comparative method to generate themes from the transcribed textual data. Five emergent themes were identified (1) physicians considered themselves as the patients' primary source of treatment information; (2) patients trusted their physician's treatment recommendations; (3) patients varied in their approach to seeking further health information regarding the discussed treatment options (e.g., internet websites, family and friends, support groups); (4) other healthcare professionals were cognizant of their fundamental role in facilitating further information-seeking; and (5) patient and physician discordant perspectives on shared decision making were present. Patient procurement of treatment information and the capacity to use it effectively in conjunction with patient trust in physicians play an important role in the shared decision-making process.

Background TruGraf v1 is a well-validated DNA microarray-based test that analyzes blood gene expression profiles as an indicator of immune status in kidney transplant recipients with stable renal function. Methods In this study, investigators assessed clinical utility of the TruGraf test in patient management. In a retrospective study, simultaneous blood tests and clinical assessments were performed in 192 patients at 7 transplant centers, and in a prospective observational study they were performed in 45 subjects at 5 transplant centers. Results When queried regarding whether or not the TruGraf test result impacted their decision regarding patient management, in 168 of 192 (87.5%) cases the investigator responded affirmatively. The prospective study indicated that TruGraf results supported physicians' decisions on patient management 87% (39/45) of the time, and in 93% of cases physicians indicated that they would use serial TruGraf testing in future patient management. A total of 21 of 39 (54%) reported results confirmed their decision that no intervention was needed, and 17 of 39 (44%) reported that results specifically informed them that a decision not to perform a surveillance biopsy was correct. Conclusions TruGraf is the first and only noninvasive test to be evaluated for clinical utility in determining rejection status of patients with stable renal function and shows promise of providing support for clinical decisions to avoid unnecessary surveillance biopsies with a high degree of confidence. TruGraf is an invaluable addition to the transplant physician's tool kit for managing patient health by avoiding painful and invasive biopsies, reducing health care costs, and enabling frequent assessment of patients with stable renal function to confirm immune quiescence.

TruGraf v1 is a laboratory-developed DNA microarray-based gene expression blood test to enable proactive noninvasive serial assessment of kidney transplant recipients with stable renal function. It has been previously validated in patients identified as Transplant eXcellence (TX: stable serum creatinine, normal biopsy results, indicative of immune quiescence), and not-TX (renal dysfunction and/or rejection on biopsy results). TruGraf v1 is intended for use in subjects with stable renal function to measure the immune status as an alternative to invasive, expensive, and risky surveillance biopsies. Materials and Methods In this study, simultaneous blood tests and clinical assessments were performed in 192 patients from 7 transplant centers to evaluate TruGraf v1. The molecular testing laboratory was blinded to renal function and biopsy results. Results Overall, TruGraf v1 accuracy (concordance between TruGraf v1 result and clinical and/or histologic assessment) was 74% (142/192), and a result of TX was accurate in 116 of 125 (93%). The negative predictive value for TruGraf v1 was 90%, with a sensitivity 74% and specificity of 73%. Results did not significantly differ in patients with a biopsy-confirmed diagnosis vs those without a biopsy. Conclusions TruGraf v1 can potentially support a clinical decision enabling unnecessary surveillance biopsies with high confidence, making it an invaluable addition to the transplant physician's tool kit for managing patients. TruGraf v1 testing can potentially avoid painful and risky invasive biopsies, reduce health care costs, and enable frequent assessment of patients with stable renal function to confirm the presence of immune quiescence in the peripheral blood.

Objective This case will illustrate the interdisciplinary management of an adolescent female patient with amelogenesis imperfecta (AI). It will contrast this approach and compare it to the previous "multidisciplinary" treatment rendered before the patient was referred for a second opinion. Clinical considerations The patient had a family history of AI affecting all of her permanent teeth. There were many impacted teeth. The majority of her family and relatives afflicted by this opted for dentures. The patient had undergone 2 years of treatment and was told that her "braces would be removed next week." Her new dentist was concerned because the case was not ready to restore. Conclusion He recommended referral to another orthodontist for a second opinion and formulation of an interdisciplinary treatment plan that would include a periodontist, endodontist, and restorative dentist. The patient's family accepted the second opinion referral and restarted treatment with an interdisciplinary team. The restorative dentist was the quarterback for this integrated and sequenced approach. The case was ultimately restored. A 35 year follow-up shows stability with a caries free, periodontally healthy, esthetic result.

The hippocampus and amygdala play an important role in the pathophysiology of posttraumatic stress disorder (PTSD). In fact, chronic PTSD has been consistently linked to reductions in hippocampal and amygdala volume. However, the acute impact posttraumatic stress has on the volume of these brain regions has received limited attention. Determining the acute impact posttraumatic stress has on brain volume may improve our understanding of the development of PTSD. Therefore, the present study recruited participants acutely (i.e., ∼1-month posttrauma) following trauma exposure and examined the relationship between brain volume (assessed at ∼1-month posttrauma) and posttraumatic stress symptoms (assessed at ∼1 and >3-months posttrauma) to determine whether brain volume was associated with acute posttraumatic stress symptom expression. Twenty-one trauma-exposed (TE) patients and 19 nontrauma-exposed (NTE) controls were recruited for the present study. Brain volume was assessed by structural magnetic resonance imaging completed during the ∼1-month assessment. Left hippocampal volumes were smaller in TE than NTE participants. Among TE participants, bilateral hippocampal volumes decreased as the number of days posttrauma increased. Further, bilateral hippocampal volumes varied negatively with the severity of posttraumatic stress symptoms at ∼1-month posttrauma. The present findings suggest that there is a progressive decrease in hippocampal volume acutely (e.g., within approximately 1 month) following trauma exposure, and demonstrates that acutely assessed hippocampal volumes vary with posttraumatic stress symptom expression. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

International audience; The purpose of this study was to examine the association between young players’ perception of mother’s and father’s responsiveness with their self-esteem, anxiety (i.e., worry), and thriving (i.e., positive affect, vitality, and life satisfaction). In total, 314 male British rugby players with a mean age of 16.23 years (SD = 0.26) completed the study in two phases: n = 124 (first dataset), and n = 192 (second dataset). Participants trained on average 3.14 times/week (SD = 0.94) and had been involved in rugby for an average of 8.21 years (SD = 2.89). Participants completed questionnaires measuring perceived parental responsiveness (PPR) for their mother and father, self-esteem, worry about sport performance, and thriving indicators (i.e., positive affect, vitality, and life satisfaction). The results consistently indicated that participants’ perceptions of their mother’s and father’s responsiveness positively related to thriving, and negatively related to their worry about sport performance, mediated by their self-esteem. Overall, the study highlights the need for parents to be provided with insights into the value of being responsive to their child and being encouraged to regularly talk with their child regarding their needs and desires, and seeking to understand how their child perceives the support they currently receive.

The purpose of this study was to explore the transitional experiences of British swimmers as they attempted to qualify for the Olympic Games and gain a place in the British Swimming World Class Performance Programme. An interpretive phenomenological analysis (IPA) approach was adopted (Smith JA. Psychol Health 1996;11:261-271). Six swimmers (aged 20-25 years), one of each of their parents, and four coaches completed interviews leading up to and following Olympic trials over an eight-month period. Audio recordings were transcribed verbatim and analyzed following the guidelines set out by Smith and Osborne (Smith JA, Osborn M. Qualitative psychology: A practical guide to research methods. London: Sage; 2003:51-80). Results indicated that athletes' transition experiences were characterized by a range of demands, which were categorized into five higher-order themes (a) Questioning "Am I good enough?"; (b) Managing and fulfilling expectations; (c) Operating within an environment that is working against them; (d) Lacking support and understanding of self and demands; and (e) Maintaining balance versus being an international swimmer. Overall, the results indicate that this attempted transition is complex, challenging, and unique and largely influenced by self-confidence. Addressing the individual factors impacting on athletes' self-confidence appears critical to enhancing swimmers' transitional experiences at the highest level.

Background Although secure messaging (SM) between patients and clinical team members is a recommended component of continuous care, uptake by patients remains relatively low. We designed a multicomponent Supported Adoption Program (SAP) to increase SM adoption among patients using the Veterans Health Administration (VHA) for primary care. Objective Our goals were to (1) conduct a multisite, randomized, encouragement design trial to test the effectiveness of an SAP designed to increase patient engagement with SM through VHA’s online patient portal (My HealtheVet [MHV]) and (2) evaluate the impact of the SAP and patient-level SM adoption on perceived provider autonomy support and communication. Patient-reported barriers to SM adoption were also assessed. Methods We randomized 1195 patients at 3 VHA facilities who had MHV portal accounts but had never used SM. Half were randomized to receive the SAP, and half served as controls receiving usual care. The SAP consisted of encouragement to adopt SM via mailed educational materials, proactive SM sent to patients, and telephone-based motivational interviews. We examined differences in SM adoption rates between SAP recipients and controls at 9 months and 21 months. Follow-up telephone surveys were conducted to assess perceived provider autonomy support and self-report of telephone communication with clinical teams. Results Patients randomized to the SAP had significantly higher rates of SM adoption than the control group (101/595, 17.0% vs 40/600, 6.7%; P Conclusions The multicomponent SAP was successful in increasing use of SM 10 percentage points above standard care; new SM adopters reported improved perceptions of provider autonomy support and less use of the telephone to communicate with their providers. Still, despite the encouragement and technical assistance provided through the SAP, adoption rates were lower than anticipated, reaching only 24% at 21 months (10% above controls). Common barriers to adoption such as limited perceived need for SM may be more challenging to address and require different interventions than barriers related to patient self-efficacy or technical difficulties. Trial Registration ClinicalTrials.gov NCT02665468; https://clinicaltrials.gov/ct2/show/NCT02665468

Background While many studies have tested the impact of a decision aid (DA) compared to not receiving any DA, far fewer have tested how different types of DAs affect key outcomes such as treatment choice, patient–provider communication, or decision process/satisfaction. This study tested the impact of a complex medical oriented DA compared to a more simplistic decision aid designed to encourage shared decision making in men with clinically localized prostate cancer. Methods 1028 men at 4 VA hospitals were recruited after a scheduled prostate biopsy. Participants completed baseline measures and were randomized to receive either a simple or complex DA. Participants were men with clinically localized cancer (N = 285) by biopsy and who completed a baseline survey. Survey measures: baseline (biopsy); immediately prior to seeing the physician for biopsy results (pre- encounter); one week following the physician visit (post-encounter). Outcome measures included treatment preference and treatment received, knowledge, preference for shared decision making, decision making process, and patients’ use and satisfaction with the DA. Results Participants who received the simple DA had greater interest in shared decision making after reading the DA (p = 0.03), found the DA more helpful (p’s Conclusions The simple DA led to increased desire for shared decision making and for less aggressive treatment. However, these differences disappeared following the physician visit, which appeared to change patients’ treatment preferences. Trial registration This trial was pre-registered prior to recruitment of participants.

PRéCIS:: This study addresses the paucity of literature examining glaucoma patients' distance from clinic on postoperative follow-up outcomes. Greater distance from clinic was associated with higher likelihood of loss to follow-up and missed appointments.To investigate the relationship of patient travel distance and interstate access to glaucoma surgery postoperative follow-up visit attendance.Retrospective longitudinal chart review of all noninstitutionalized adult glaucoma patients with initial trabeculectomies or drainage device implantations between April 4, 2014 and December 31, 2018. Patients were stratified into groups on the basis of straight-line distance from residence to University of North Carolina at Chapel Hill's Kittner Eye Center and distance from residence to interstate access. Corrective procedures, visual acuity, appointment cancellations, no-shows, and insurance data were recorded. Means were compared using 2-tailed Student t-test, Pearson χ, analysis of variance, and multivariate logistical regression determined odds ratios for loss to follow-up.In total, 199 patients met all inclusion criteria. Six-month postoperatively, patients50 miles from clinic had greater odds of loss to follow-up compared with patients25 miles (odds ratios, 3.47; 95% confidence interval, 1.24-4.12; P0.05). Patients50 miles from clinic had significantly more missed appointments than patients 25 to 50 miles away, and patients25 miles away (P=0.008). Patients20 miles from interstate access had greater loss to follow-up than those10 miles (t(150)=2.05; P0.05). Mean distance from clinic was 12.59 miles farther for patients lost to follow-up (t(197)=3.29; P0.01). Patients with Medicaid coverage had more missed appointments than those with Medicare plans (t(144)=-2.193; P0.05).Increased distance from clinic and interstate access are associated with increased missed appointments and loss to follow-up. Glaucoma specialists should consider these factors when choosing surgical interventions requiring frequent postoperative evaluations.

The novel coronavirus SARS-CoV-2 [coronavirus disease 2019 (COVID-19)] is a highly contagious and devastating virus that has currently infected over 2.5 million people worldwide and resulted in 177 641 deaths as of April 2020.1 Although most people diagnosed with COVID-19 exhibit mild-to-moderate symptoms, early reports from China described vulnerable patient populations, such as the elderly and those with chronic underlying medical conditions including the immunosuppressed, having more severe COVID-19-related illness compared to the general population.2,3 Solid organ transplant (SOT) recipients are one of the largest cohorts of immunosuppressed patients, yet little is known about their risk of contracting the virus, postinfection outcomes, and effect of immunosuppression on the clinical course of the disease. Unique challenges, such as immunosuppression management and interpretation of laboratory data, also exist. Current treatment strategies borrow upon prior experience from other pandemics, such as severe acute respiratory syndrome (SARS) and influenza A virus subtype.4 SARS-CoV-2 primarily affects the respiratory tract, progressing from pneumonia to acute respiratory distress syndrome in severe cases.5 In these cases, there is a recognized cytokine release syndrome (CRS) that when occurs results in multiorgan dysfunction and failure.6 The role of immunosuppression in mounting such inflammatory response is unclear. Inflammatory markers, such as C-reactive protein (CRP), lactate dehydrogenase (LDH), and D-dimer, may reflect disease progression and/or severity.7 Lymphopenia is reported as a common presentation among COVID-19 positive patients.8,9 Treatment options are limited. Antivirals such as hydroxychloroquine (HCQ) with or without azithromycin are widely used empiric options. Remdesivir, an RNA polymerase inhibitor, has shown in vitro activity against SARS-CoV-2 and is currently under phase 3 trial.10 Investigational agents to combat the cytokine response, such as tocilizumab, an interleukin 6 (IL-6) receptor inhibitor, are being studied. Although the exact role of immunosuppression on the progression of COVID-19 is unknown, early case reports of kidney transplant recipients suggest minimizing immunosuppression while continuing steroidal therapy.11 Evaluation of clinical symptoms, utility of biomarkers, and progression of disease are important to understand for optimizing the management in COVID-19 positive SOT recipients. The effect of COVID-19 on the heart, lung, liver, pancreas, and kidney transplant organ systems is not well described. Herein, we present our experience with 21 consecutive SOT recipients diagnosed with COVID-19 at the Houston Methodist J.C. Walter Transplant Center followed to April 22, 2020.

The purpose of the current study was twofold (a) to examine elite female athletes' experiences of their menstrual cycle, with a focus upon the impact on training and competition performance and (b) the openness of conversation pertaining to the menstrual cycle with coaching and support staff. Following receipt of institutional ethical approval, individual semi-structured interviews were conducted with 17 elite female athletes (25.5 ± 4.7 years) from multiple sports. Results revealed athletes' experiencing a natural menstrual cycle reported physical symptoms alongside mood disturbances and reduced motivation to train. The decision to actively control the menstrual cycle was often triggered by a desire to reduce the effect on competition, to lessen anxieties about making required weight or reduce distraction to manage during competition. Athletes indicated an openness to talk about the menstrual cycle to other females, however, there was variation in the comfort athletes experienced regarding talking to male coaches. Overall, the findings highlight the need to educate elite athletes and coaches on the menstrual cycle, considering it in the same light as other physiological functions in sport to improve health, well-being, and performance. Furthermore, providing education on how to construct positive conversations, equipping individuals with the correct terminology, and confidence to talk about the menstrual cycle will reduce some reservations identified through improved knowledge and understanding.

Highlights • Event-based prospective memory is impaired in people with mild cognitive impairment. • Prospective memory mirrors real-world behaviour. • Structural changes in the brain correlate with prospective memory scores. • Different aspects of prospective memory correlate with distinct brain networks. • Prospective memory might be a meaningful measure in clinical practice or research., Introduction : Prospective memory (PM) is a marker of independent living in Alzheimer's disease. PM requires cue identification (prospective component) and remembering what should happen in response to the cue (retrospective component). We assessed neuroanatomical basis and functional relevance of PM. Methods 84 older participants (53–94 years old, 58% male) with or without Mild Cognitive Impairment (MCI) performed PM tests, Activities of Daily Living (ADL) scale and had a structural MRI of the brain to estimate for cortical thickness and hippocampal subfield volumes. A General Linear Model cluster analysis was carried out using FreeSurfer to determine which cortical regions were correlated with PM scores. Results : Both components of PM are impaired in MCI (p

Background: Improving family caregiver preparation for surrogate decision making is a critical priority. Objective: Determine a parsimonious set of intrapersonal factors associated with family caregivers' confidence in making future medical decisions for their relatives with cancer. Methods: Cross-sectional mail survey. Family caregivers of Medicare beneficiaries with pancreatic, lung, brain, ovarian, head and neck, hematologic, and stage IV cancers from communities of eight U.S. cancer centers. Participants completed validated measures of their social and mental health, self-care behaviors, coping styles, and surrogate decision-making confidence. Using linear modeling, the Bayesian information criterion was used to identify factors associated with decision-making confidence. A bootstrap approach was used to conduct penalized inference on the selected model coefficients. Model fit validation was assessed with a random forest ensemble. Results: Caregivers (n = 294) were on average 65.5 years old, mostly female (72.8%), and care recipients' spouse/partner (60.2%). The parsimonious set of factors associated with low caregiver decision-making confidence included less engagement in spiritual growth self-care, more use of avoidant coping, low emotional social support, and younger care recipient age (in-sample R(2) = 0.22). These factors were also identified by a random forest approach. After overfitting adjustment (shrunken R(2) = 0.09), the strongest associations with low surrogate decision-making confidence were low spiritual growth self-care (adjusted standardized B = 0.17, p = 0.005) and high use of avoidant coping (adjusted standardized B = −0.12, p = 0.049). Discussion: Identifying strategies to enhance spiritual growth and reduce avoidant coping may be promising targets for interventions to improve family caregivers' confidence in future surrogate decision making.

Background Major depressive disorder (MDD) is associated with social cognitive deficits (e.g., poor affect recognition and impaired theory of mind). However, the contribution of social cognitive issues to psychosocial dysfunction in MDD (e.g., occupational functioning and interpersonal relationships) has not been investigated. The current study evaluated the relationship between specific social cognitive domains (e.g., prosody interpretation) and psychosocial dysfunction in subjects with lifetime MDD, as well as currently depressed, remitted, and healthy controls (HCs) subjects. Method Data were obtained from 213 participants in the Cognitive Function and mood study (CoFaMS), a cross-sectional study of mood, social cognition, cold cognition, and psychosocial functioning in mood disorders. Participants' (current MDD n = 42, remitted MDD n = 69, and HCs n = 102) social cognitive abilities were assessed using the Social Perception subtest of the Wechsler Adult Intelligence Scale, and psychosocial dysfunction was clinically evaluated with the Functioning Assessment Short Test (FAST). Results The results indicated that prosody interpretation, but not facial affect or meaning interpretation, was associated with psychosocial dysfunction in subjects with lifetime MDD, as well as remitted MDD subjects relative to HCs. In contrast, social cognition was not associated with functioning in participants with current MDD or in HCs. Conclusions These results suggest that the relationship between social cognition and psychosocial functioning differs between the acute and remitted stage of illness in MDD, and that prosody interpretation should be considered a treatment target in patients with residual psychosocial issues.

Background We investigated whether variation in post-acute care (PAC) services could be explained by surgeons discharging clinically similar patients to different PAC destinations, including home health (HH), skilled nursing facilities (SNF), and inpatient rehabilitation (IR). Methods We studied patients having colectomy, pancreatectomy or hepatectomy in the 2008–2011 Nationwide Inpatient Sample. We used propensity matching to determine: 1. Proportion of patients discharged to SNF/IR who could be matched to clinically similar patients discharged with HH. 2. Potential cost savings from greater use of HH. Results 30,843 patients were discharged with HH and 23,172 to SNF or IR. 14,163 (61%) SNF/IR patients could be matched to similar patients discharged with HH. Potential cost savings from increasing use of HH as an alternative to SNF/IR ranged from $2.5-$438 million annually. Conclusions There is considerable potential for reducing variation in PAC use and costs by better understanding how surgeons make decisions about PAC placement. Summary Many surgical patients discharged to inpatient rehabilitation or skilled nursing facilities have similar pre- and postoperative characteristics as individuals discharged home with home health. In order to reduce variation and deliver cost-effective care after discharge, it is important to understand how surgeons make decisions about post-acute care, and to develop processes to identify which type of post-acute care is best for each patient.

Background Cognitive dysfunction is a prevalent and disabling symptom of Major Depressive Disorder (MDD), and is often retained in the remitted stage of illness. Emerging evidence suggests that cognitive impairment may be associated with dysfunction in a number of psychosocial domains (e.g., workplace productivity, social relationships). The current study explored the relationship between cognition and psychosocial functioning in remitted MDD and in healthy controls. Methods Data were obtained from 182 participants of the Cognitive Function and Mood Study (CoFaM-S), a cross-sectional study of cognition, mood, and social cognition in mood disorders. Participants’ (Remitted MDD n = 72, Healthy n = 110) cognition was assessed with a battery of cognitive tests including the Repeatable Battery for the Assessment of Neuropsychological Function (RBANS) and other standard measures of cognition (e.g., The Tower of London task). Psychosocial functioning was clinically evaluated with the Functioning Assessment Short Test (FAST). Results The results indicated that executive functioning was the strongest independent predictor of functioning in remitted MDD patients, whereas various cognitive domains predicted psychosocial functioning in healthy individuals. Limitations Psychosocial functioning was measured with a clinical interview, and was therefore reliant on clinicians' judgement of impairment, as opposed to more objective measures of functioning. Conclusions These findings suggest that executive cognition plays an important role in functional recovery in remitted depression, and may be a crucial target in adjunctive treatment.

New treatments for chronic lymphocytic leukemia (CLL) with excellent response rates and varying toxicity profiles have emerged in recent years, creating an opportunity for a patient's personal preferences to contribute to treatment decisions. We conducted a prospective, quasi-experimental pre- and post-evaluation of a multilevel educational program and its impact on knowledge of CLL and shared decision-making (SDM). We educated patients, lay navigators, nurses/advanced practice providers (APPs), and physicians. Patients were evaluated for change in patient activation, distress, desired role in decision-making, perception of decision-making, satisfaction with oncologist explanation of treatment choice, and knowledge of CLL. Lay navigators, nurses/APPs, and physicians were evaluated for change in CLL knowledge and perception of decision-making. Forty-four patients, 33 lay navigators, 27 nurses/APPs, and 27 physicians participated in the educational program. We observed trends toward improved patient activation, with 68% before education versus 76% after education reporting a Patient Activation Measure (PAM) score of 3 or 4. The percentage of patients desiring and perceiving SDM trended upward from 47% to 67% and from 35% to 49%, respectively. The percentage of patients understanding that CLL is incurable increased from 80% to 90%, as did reporting awareness of signs of progression (64% to 76%). Patients' satisfaction with their oncologists' explanations of therapy increased significantly from 83% to 95% (p = .03). CLL knowledge increased after education for lay navigators (36% vs 63%) and nurses/APPs (35% vs 69%), and remained high for physicians (85% vs 87%). Nurses/APPs and physicians perceived at least some patient involvement in decision-making at baseline, whereas 12% of patients and 23% of lay navigators perceived that physicians made decisions independently. This project demonstrated trends toward improvements in patient engagement, prognostic awareness, knowledge of signs of progression, and SDM. These promising findings should be tested in larger samples. There remains an opportunity for further improvement in SDM.

The current research investigated whether learning spatial information from a map involves different modalities, which are managed by discrete components in working memory. In four experiments, participants studied a map either while performing a simultaneous interference task (high cognitive load) or without interference (low cognitive load). The modality of interference varied between experiments. Experiment 1 used a tapping task (visuospatial), Experiment 2 a backward counting task (verbal), Experiment 3 an articulatory suppression task (verbal) and Experiment 4 an n-back task (central executive). Spatial recall was assessed in two tests: directional judgements and map drawing. Cognitive load was found to affect spatial recall detrimentally regardless of interference modality. The findings suggest that when learning maps, people use a multimodal learning strategy, utilising resources from all components of working memory.

BACKGROUND Excessive weight (EW) gain is common after solid organ transplantation, but there is little information concerning obesity after pancreas transplantation. The study goal was to characterize EW gain after kidney-pancreas (KP) transplantation. METHODS This was a retrospective single-center review of 100 KP recipients transplanted between September 2007 and June 2015. RESULTS The median percent weight gain for all recipients at 1 year posttransplant was 10% (interquartile range, 2.7%-19.3%) of baseline weight. EW gain, defined as greater than or equal to a 19% 1-year increase in weight, included all recipients (n = 26) above the upper limit of interquartile range for weight gain at 1 year. In multivariate analysis, recipient age

The purpose of this study was to develop a grounded theory of the process of inspirational coach-leadership in sport. A Straussian grounded theory methodology was used. Semi-structured interviews and focus groups were conducted with athletes (n = 22) and coaches (n = 15). Data were analysed through a process of open and axial coding, and theoretical integration. Through the process of analysis, data were broken down into smaller units (concepts), relationships between concepts were identified, and a substantive grounded theory was developed. The grounded theory of inspirational coach-leadership was built around the core category of ‘athlete(s) inspired through changed awareness of their capabilities.’ The core category was underpinned by three categories: (a) Establishment of mutual trust and respect with athletes, whereby coaches need to establish trust with athletes in order to inspire athletes; (b) conditions under which inspiration has the potential to occur, which highlighted that athletes are inspired in situations where they are vulnerable or ignorant regarding their potential; and (c) coach acts to change athlete’s awareness of their capabilities, which denotes the specific behaviours coaches should display to inspire athletes in such conditions. The theory also highlights that a range of contextual factors relating to the coach, athletes, and performance-environment interact to impact upon the process. The theory predicts that consistency between coach behaviour and the conditions in which inspiration can occur will lead to athlete-inspiration, but only if the coach has established a foundation of trust and respect with the athlete.

OBJECTIVE The aim of this study was to examine the association of county-level food access, recreational opportunities, and natural amenities with participant engagement in a weight management program. METHODS In this cohort study, participants in the Veterans Health Administration MOVE! weight management program between October 1, 2007, and September 30, 2013, were observed for 12 months after enrollment. Engagement was measured as the number of program visits per year at 12 months. Cross-sectional analysis and spatial regression were used to examine county characteristics associated with greater participant engagement at 12 months. RESULTS A total of 321,624 participants in 2,708 counties were included. Greater engagement was associated with older age, female sex, white race, being married, and being retired. After accounting for similarities between nearby communities, engagement at 12 months was 3.1 visits higher for each additional farmers' market per 1,000 population (P = 0.01). Engagement was highest for participants living in counties with the most natural amenities (P

Apparent diffusion coefficient (ADC) of cerebral water, as measured by diffusion MRI, rapidly decreases in ischaemia highlighting a lesion in acute stroke patients. The MRI T(2) relaxation time changes in ischaemic brain such that T(2) in ADC lesions may be informative of the extent of tissue damage, potentially aiding in stratification for treatment. We have developed a novel user-unbiased method of determining the changes in T(2) in ADC lesions as a function of clinical symptom duration based on voxel-wise referencing to a contralateral brain volume. The spherical reference method calculates the most probable pre-ischaemic T(2) on a voxel-wise basis, making use of features of the contralateral hemisphere presumed to be largely unaffected. We studied whether T(2) changes in the two main cerebral tissue types, i.e. in grey matter (GM) and white matter (WM), would differ in stroke. Thirty-eight acute stroke patients were accrued within 9 hours of symptom onset and scanned at 3T for 3D T1-weighted, multi b-value diffusion and multi-echo spin echo MRI for tissue type segmentation, quantitative ADC and absolute T(2) images, respectively. T(2) changes measured by the spherical reference method were 1.94 ± 0.61, 1.50 ± 0.52 and 1.40 ± 0.54 ms/hour in the whole, GM and WM lesions, respectively. Thus, T(2) time courses were comparable between GM and WM independent of brain tissue type involved. We demonstrate that T(2) changes in ADC-delineated lesions can be quantified in the clinical setting in a user unbiased manner and that T(2) change correlated with symptom onset time, opening the possibility of using the approach as a tool to assess severity of tissue damage in the clinical setting.

ObjectivesThe objective of this study was to assess vitamin D status of US non-pregnant adults using a standardised assay across 15 mL/min/1.73 m2increments of kidney function, report the use of dietary supplements containing vitamin D and assess relationships between vitamin D and markers of bone resorption.DesignThis study is a cross-sectional evaluation.SettingThe study is from the US National Health and Nutrition Evaluation Survey in 2001–2012.ParticipantsThe participants were non-institutionalised, non-pregnant adults, age ≥20 years.Primary and secondary outcome measuresThe primary outcome measure was serum 25OHD evaluated using liquid chromatography-tandem mass spectroscopy traceable to international reference standards. Secondary outcome measures were use of dietary supplements containing vitamin D and the serum intact parathyroid hormone and bone-specific alkaline phosphatase in a subset of participants.ResultsThe median 25OHD concentration in 27 543 US non-pregnant adults was 25.7 ng/mL (range, 2.2–150.0 ng/mL). Vitamin D supplements were used by 38.0%; mean (SE)=757 (43) international units/day. The range of 25OHD concentration across groups, stratified by kidney function, was 23.0–28.1 ng/mL. The lowest concentration of 25OHD observed was in people with higher kidney function (23.0 ng/mL for estimated glomerular filtration rate >105 mL/min/1.73 m2). Only 24% of people not taking a dietary supplement had a 25OHD concentration >30 ng/mL. Serum intact parathyroid hormone inversely correlated with 25OHD within all kidney function groups. Bone-specific alkaline phosphatase was also negatively associated with 25OHD concentration.ConclusionsThese data indicate that 25OHD concentrations and supplement use may be suboptimal in a significant proportion of the population, across all kidney function levels. The response of bone resorption markers further suggests that 25OHD levels could be improved. Together, these data support a re-evaluation of the 25OHD concentration associated with health in adults.

INTRODUCTION: Treatment of vaso-occlusive episodes (VOE) are the most common reason for ED treatment of sickle cell disease (SCD). We 1) compared perceptions of the usability and ability to manage VOE pain between ED nurses and other ED provider types, ED sites, and VOE protocols (individualized versus weight-based), and 2) identified ED nurse and other provider protocol suggestions. METHODS: A secondary analysis of provider survey data collected immediately after caring for a patient enrolled in a randomized control trial comparing weight based vs. individualized opioid dosing for VOE. Research staff asked the ED nurse and other ED providers (nurse practitioners [NPs], physician assistants [PAs], residents and attending physicians) five questions related to the protocol’s ease of use and ability to manage pain. RESULTS: There were 236 surveys completed. Attending physicians (n=15), residents (n=88), PAs (n=21), and NPs (n=1) were more satisfied than nurses (n=111) with the clarity of the analgesic ordering (97.6% vs. 0%, p = 0.0001), and ability to manage the patient’s VOE pain (91% vs. 0%, p = 0.0001). When comparing both protocols with the usual ED strategy in their ED to manage VOE, more nurses than other ED providers perceived the study patients’ pain management protocol as better (100% vs. 35.2%, p = 0.0001).Other ED providers perceived the individualized versus weight-based protocol as better at managing pain than their usual ED strategy (70.3% vs. 59.5%, p = 0.04). CONCLUSION: The individualized protocol was perceived as better in managing VOE than the weight-based ED strategy. While physicians were satisfied with the clarity of the protocols, nurses were not. Improved protocol usability is required for widespread ED implementation.

Purpose: The current standard of care for patients with locally advanced prostate cancer is a combination of androgen deprivation and radiation therapy. Radiation is typically given with androgen suppression when testosterone levels are at their nadir. Recent reports have shown that androgen stimulation of androgen-deprived prostate cancer cells leads to formation of double-strand breaks (DSB). Here, we exploit this finding and investigate the extent and timing of androgen-induced DSBs and their effect on tumor growth following androgen stimulation in combination with ionizing radiation (IR). Experimental Design: Androgen-induced DNA damage was assessed by comet assays and γH2A.X foci formation. Effects of androgen stimulation and radiation were determined in vitro and in vivo with xenograft models. Results: We document that androgen treatment of androgen-deprived prostate cancer cell lines resulted in a dose- and time-dependent induction of widespread DSBs. Generation of these breaks was dependent on androgen receptor and topoisomerase II beta but not on cell-cycle progression. In vitro models demonstrated a synergistic interaction between IR and androgen stimulation when IR is given at a time point corresponding with high levels of androgen-induced DSB formation. Furthermore, in vivo studies showed a significant improvement in tumor growth delay when radiation was given shortly after androgen repletion in castrated mice. Conclusions: These results suggest a potential cooperative effect and improved tumor growth delay with androgen-induced DSBs and radiation with implications for improving the therapeutic index of prostate cancer radiation therapy. Clin Cancer Res; 22(13); 3310–9. ©2016 AACR. See related commentary by Chua and Bristow, p. 3124

Objective The objective of this study was to examine age-dependent changes in both T1-weighted and T2-weighted image contrasts and spin-echo T2 relaxation time in the human brain during healthy ageing. Methods A total of 37 participants between the ages of 49 and 87 years old were scanned with a 3 Tesla system, using T1-weighted, T2 weighted and quantitative spin-echo T2 imaging. Contrast between image intensities and T2 values was calculated for various regions, including between individual hippocampal subfields. Results The T1 contrast-to-noise (CNR) and gray:white signal intensity ratio (GWR) did not change in the hippocampus, but it declined in the cingulate cortex with age. In contrast, T2 CNR and GWR declined in both brain regions. T2 relaxation time was almost constant in gray matter and most (but not all) hippocampal subfields, but increased substantially in white matter, pointing to an age effect on water relaxation in white matter. Conclusions Changes in T1 and T2 MR characteristics influence the appearance of brain images in later life and should be considered in image analyses of aged subjects. It is speculated that alterations at the cell biology level, with concomitant alterations to the local magnetic environment, reduce dephasing and subsequently prolong spin-echo T2 through reduced diffusion effects in later life. Electronic supplementary material The online version of this article (doi:10.1007/s10334-016-0573-0) contains supplementary material, which is available to authorized users.

Background: The clinical and neurobiological underpinnings of transient nonmotor (TNM) psychiatric symptoms during the optimization of stimulation parameters in the course of subthalamic nucleus deep brain stimulation (STN-DBS) remain under intense investigation. Methods: Forty-nine patients with refractory Parkinson's disease underwent bilateral STN-DBS implants and were enrolled in a 24-week prospective, naturalistic follow-up study. Patients who exhibited TNM psychiatric manifestations during DBS parameter optimization were evaluated for potential associations with clinical outcome measures. Results: Twenty-nine TNM+ episodes were reported by 15 patients. No differences between TNM+ and TNM- groups were found in motor outcome. However, unlike the TNM- group, TNM+ patients did not report improvement in subsyndromal depression or quality of life. TNM+ episodes were more likely to emerge during bilateral monopolar stimulation of the medial STN. Conclusions: The occurrence of TNM psychiatric symptoms during optimization of stimulation parameters was associated with the persistence of subsyndromal depression and with lower quality of life ratings at 6 months. The neurobiological underpinnings of TNM symptoms are investigated yet remain difficult to explain.

A 64-year-old man who presented with photopsia was found to have elevated intraocular pressure in one eye and optic disc swelling in the other eye. He was initially diagnosed with neurocysticercosis and later metastatic lung adenocarcinoma. The purpose of this paper is to report a rare case of bilateral glare as the first sign of diffusely metastatic cancer and to raise clinical suspicion for systemic malignancy in the presence of multiple ocular manifestations.

Background: Patients with Major Depressive Disorder experience significantly reduced subjective Quality of Life (QOL), including impaired social and emotional functioning and greater fatigue and physical pain. Mounting evidence suggests that cognitive dysfunction (e.g., deficits in memory, executive function) contributes independently to the onset of reduced QOL, however the domain-specific nature of this relationship has not been investigated. The present study examined the relationship between specific cognitive domains (e.g., attention, spatial cognition) and specific deficits in mental and physical QOL in subjects with lifetime MDD, as well as acutely depressed, remitted and healthy participants. Methods: Data were obtained (N = 387) from the Cognitive Function and Mood Study (COFAMS), a cross-sectional study of emotional, functional and cognitive status in individuals with mood disorders. Participants' (acutely depressed n = 93, remitted n = 170, and healthy control n = 124) QOL was assessed with the 36-Item Short Form Health Survey (SF-36) and cognitive functioning was evaluated with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Colorado Assessment Tests (CATs) and the Psychology Experiment Building Language (PEBL). Results: Analyses revealed that poor immediate and delayed memory were associated with reduced mental QOL in individuals with lifetime MDD, acutely depressed, and healthy controls. In contrast, cognitive functioning was not associated with mental QOL in remitted patients. No cognitive domains were significantly related to physical QOL in any participant group. Conclusions: The result suggests that deficits in immediate and delayed memory may contribute to reduced mental QOL in acute MDD, whereas cognition does not appear to play a role in physical QOL. Memory should be considered important cognitive treatment targets for MDD patients suffering specifically from reduced mental QOL. Keywords: Quality of Life (QOL), Cognition, Major Depressive Disorder

OBJECTIVE: To investigate the effects of enhanced recovery after surgery (ERAS) on racial disparities in postoperative length of stay (pLOS) after colorectal surgery. BACKGROUND: Racial disparities in surgical outcomes exist. We hypothesized that ERAS would reduce disparities in pLOS between black and white patients. METHODS: Patients undergoing ERAS in 2015 were 1:1 matched by race/ethnicity, age, sex, and procedure to a pre-ERAS group from 2010 to 2014. After stratification by race/ethnicity, expected pLOS was calculated using the American College of Surgeons National Surgical Quality Improvement Project Risk Calculator. Primary outcome was the observed pLOS and observed-to-expected difference in pLOS. Secondary outcomes were National Surgical Quality Improvement Project postoperative complications including 30-day readmissions and mortality. Adjusted sensitivity analyses on pLOS were also performed. RESULTS: Of 420 patients (210 ERAS and 210 pre-ERAS) examined, 28.3% were black. Black and white patients were similar in age, body mass index, sex, American Anesthesia Association class, and minimally invasive approaches. Within the pre-ERAS group, black patients stayed a mean of 2.7 days longer than expected compared with white patients (P < 0.05). Overall, ERAS patients had a significantly shorter pLOS (5.7 vs 8 days) and observed-to-expected difference (−0.7 vs 1.4 days) compared with pre-ERAS patients (P < 0.01). In the ERAS group, disparities in pLOS were reduced with no differences in readmissions or mortality between black and white patients. On sensitivity analyses, race/ethnicity remained a significant predictor of pLOS among pre-ERAS patients, but not for ERAS patients. CONCLUSIONS: ERAS eliminated racial differences in pLOS between black and white patients undergoing colorectal surgery. Reduced pLOS occurred without increases in mortality, readmissions, and most postoperative complications. ERAS may provide a practical approach to reducing disparities in surgical outcomes.

OBJECTIVE To evaluate the extent to which cognitive measures in the recently developed THINC-integrated tool (THINC-it) are associated with global and domain specific psychosocial disability in patients with current and remitted major depressive disorder (MDD). METHODS Cross-sectional data (N = 127) were obtained from participants with current (n = 105) or remitted (n = 22) MDD who completed the THINC-it between July 2014 and June 2018. Major depressive disorder was diagnostically assessed with DSM-IV and DSM-5 criteria. The THINC-it includes 4 objective cognitive tests: the Spotter (ie, Choice Reaction Time), Symbol Check (ie, n-back), CodeBreaker (ie, Digit Symbol Substitution), and Trails (ie, Trail Making Test part B), as well as a measure of self-perceived cognitive deficits, the Perceived Deficits Questionnaire for Depression-5-item (PDQ-5-D). Psychosocial dysfunction was assessed with the Functioning Assessment Short Test. RESULTS The whole group analysis (ie, lifetime MDD) indicated that poor objective cognitive performance on the CodeBreaker (β = 0.346, P = .002) and Trails tasks (β = 0.232, P = .017) and greater self-reported cognitive deficits on the PDQ-5-D (β = 0.596, P < .001) were associated with more severe global psychosocial disability. In addition, performance on the CodeBreaker and Trails tasks showed dissociable relationships with specific psychosocial deficits (eg, occupational functioning, daily autonomy). The relationship between cognitive and psychosocial deficits was stronger in participants with current compared to remitted MDD. CONCLUSIONS Cognitive deficits identified by the THINC-it are associated with global and specific psychosocial deficits, highlighting the clinical value and utility of the THINC-it as a cognitive screening instrument in patients with MDD.

Posttraumatic stress disorder (PTSD) is associated with dysfunction of the neural circuitry that supports fear learning and memory processes. However, much of what is known about neural dysfunction in PTSD is based on research in chronic PTSD populations. Less is known about neural function that supports fear learning acutely following trauma exposure. Determining the acute effects of trauma exposure on brain function would provide new insight into the neural processes that mediate the cognitive-affective dysfunction associated with PTSD. Therefore, the present study investigated neural activity that supports fear learning and memory processes in recently Trauma-Exposed (TE) and Non-Trauma-Exposed (NTE) participants. Participants completed a Pavlovian fear conditioning procedure during functional magnetic resonance imaging (fMRI). During fMRI, participants' threat expectancy was continuously monitored. NTE participants showed greater threat expectancy during warning than safety cues, while no difference was observed in the TE group. This finding suggests TE participants overgeneralized the fear association to the safety cue. Further, only the TE group showed a negative relationship between fMRI signal responses within dorsomedial prefrontal cortex (PFC) and threat expectancy during safety cues. These results suggest the dorsomedial PFC mediates overgeneralization of learned fear as an acute result of trauma exposure. Finally, neural activity within the PFC and inferior parietal lobule showed a negative relationship with PTSD symptom severity assessed three months posttrauma. Thus, neural activity measured acutely following trauma exposure predicted future PTSD symptom severity. The present findings elucidate the acute effects of trauma exposure on cognitive-affective function and provide new insight into the neural mechanisms of PTSD.

Precision medicine promises to improve patient outcomes, but much is unknown about its adoption within health-care systems. A comprehensive implementation plan is needed to realize its benefits.We convened 80 stakeholders for agenda setting to inform precision medicine policy, delivery, and research. Conference proceedings were audio-recorded, transcribed, and thematically analyzed. We mapped themes representing opportunities, challenges, and implementation strategies to a logic model, and two implementation science frameworks provided context.The logic model components included inputs: precision medicine infrastructure (clinical, research, and information technology), big data (from data sources to analytics), and resources (e.g., workforce and funding); activities: precision medicine research, practice, and education; outputs: precision medicine diagnosis; outcomes: personal utility, clinical utility, and health-care utilization; and impacts: precision medicine value, equity and access, and economic indicators. Precision medicine implementation challenges include evidence gaps demonstrating precision medicine utility, an unprepared workforce, the need to improve precision medicine access and reduce variation, and uncertain impacts on health-care utilization. Opportunities include integrated health-care systems, partnerships, and data analytics to support clinical decisions. Examples of implementation strategies to promote precision medicine are: changing record systems, data warehousing techniques, centralized technical assistance, and engaging consumers.We developed a theory-based, context-specific logic model that can be used by health-care organizations to facilitate precision medicine implementation.

Social cognition is the ability to identify, perceive and interpret socially relevant information from the external world. It is an important adaptive trait, but is frequently affected in major depressive disorder by a mood-congruent interpretive bias. The present review examined the existing body of literature to determine (i) the impact social cognitive deficits in depression have on psychosocial functioning; and (ii) the utility of psychotropic, psychological and procedural interventions employed to target these deficits. A total of 107 studies met inclusion criteria for review. Social cognitive performance was found to adversely impact depressed patients' psychosocial functioning across the key domains of general cognitive functioning and quality of life. Secondly, many current therapies were found to have a normalising effect on the social cognitive abilities of subjects with major depressive disorder, both at a neural and functional level. In particular, certain anti-depressant medications corrected facial affect recognition deficits, while several psychotherapeutic approaches improved impairments in theory of mind and negative interpretive bias.

Background We compared short-term recovery for patients discharged to inpatient rehabilitation versus skilled nursing facilities after gastrointestinal surgery. Materials & methods We conducted a propensity-matched cohort study of 12,939 adults discharged to inpatient rehabilitation or skilled nursing facilities after colectomy, pancreatectomy or hepatectomy at hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program from 2011 to 2014. Primary outcomes were readmission and mortality rates 30 days after surgery. Results 9259 (72%) patients were discharged to skilled nursing facilities and 3680 (28%) to inpatient rehabilitation. Median age in both groups was 76 years and 82% of patients were white. There was no difference in 30-day readmission rates (16% for skilled nursing vs 16.8% for inpatient rehabilitation) but post-discharge mortality was higher for patients discharged to skilled nursing facilities (4.4%) compared to inpatient rehabilitation (1.6%, p Conclusions Increased utilization of inpatient rehabilitation services after gastrointestinal surgery may improve postoperative outcomes.

Background We sought to determine whether conversion from tacrolimus/mycophenolate mofetil (TAC-MMF) into tacrolimus/mTOR inhibitor (TAC-mTOR) immunosuppression would reduce the incidences of BK and CMV viremia after kidney/pancreas (KP) transplantation. Methods In this single-center review, the TAC-mTOR cohort (n = 39) was converted at 1 month post-transplant to an mTOR inhibitor and reduced-dose tacrolimus. Outcomes were compared to a cohort of KP recipients (n = 40) maintained on TAC-MMF. Results At 3 years post-transplant, KP survivals and incidences of kidney/pancreas rejection were equivalent between mTOR and MMF-treated cohorts. (P = ns). BK viremia-free survival was better for the mTOR vs MMF-treated group (P = .004). In multivariate analysis, MMF vs mTOR immunosuppression was an independent risk factor for BK viremia (hazard ratio 12.27, P = .02). Similarly, mTOR-treated recipients displayed better CMV infection-free survival compared to the MMF-treated cohort (P = .01). MMF vs mTOR immunosuppression (hazard ratio 18.77, P = .001) and older recipient age (hazard ratio 1.13 per year, P = .006) were independent risk factors for CMV viremia. Mean estimated GFR and HgbA1c levels were equivalent between groups at 1, 2, and 3 years post-transplantation. Conclusion Conversion from TAC/MMF into TAC/mTOR immunosuppression after KP transplantation reduced the incidences of BK and CMV viremia with an equivalent risk of acute rejection and similar renal/pancreas function.

OBJECTIVES: This study aimed to determine the effect on long-term survival of using optical coherence tomography (OCT) during percutaneous coronary intervention (PCI). BACKGROUND: Angiographic guidance for PCI has substantial limitations. The superior spatial resolution of OCT could translate into meaningful clinical benefits, although limited data exist to date about their effect on clinical endpoints. METHODS: This was a cohort study based on the Pan-London (United Kingdom) PCI registry, which includes 123,764 patients who underwent PCI in National Health Service hospitals in London between 2005 and 2015. Patients undergoing primary PCI or pressure wire use were excluded leaving 87,166 patients in the study. The primary endpoint was all-cause mortality at a median of 4.8 years. RESULTS: OCT was used in 1,149 (1.3%) patients, intravascular ultrasound (IVUS) was used in 10,971 (12.6%) patients, and angiography alone in the remaining 75,046 patients. Overall OCT rates increased over time (p < 0.0001), with variation in rates between centers (p = 0.002). The mean stent length was shortest in the angiography-guided group, longer in the IVUS-guided group, and longest in the OCT-guided group. OCT-guided procedures were associated with greater procedural success rates and reduced in-hospital MACE rates. A significant difference in mortality was observed between patients who underwent OCT-guided PCI (7.7%) compared with patients who underwent either IVUS-guided (12.2%) or angiography-guided (15.7%; p < 0.0001) PCI, with differences seen for both elective (p < 0.0001) and acute coronary syndrome subgroups (p = 0.0024). Overall this difference persisted after multivariate Cox analysis (hazard ratio [HR]: 0.48; 95% confidence interval [CI]: 0.26 to 0.81; p = 0.001) and propensity matching (hazard ratio: 0.39; 95% CI: 0.21 to 0.77; p = 0.0008; OCT vs. angiography-alone cohort), with no difference in matched OCT and IVUS cohorts (HR: 0.88; 95% CI: 0.61 to 1.38; p = 0.43). CONCLUSIONS: In this large observational study, OCT-guided PCI was associated with improved procedural outcomes, in-hospital events, and long-term survival compared with standard angiography-guided PCI.

The aim of this study was to compare endothelial cell loss and graft success 6 months after endothelial keratoplasty (EK) with paired donor corneas stored in Optisol GS and Life4°C solutions and their associated storage chambers.Donor pairs were stored, one in Optisol GS and the other in Life4°C, and prepared for Descemet stripping automated EK or Descemet membrane EK. Matched pairs of recipients with Fuchs dystrophy were randomized to 1 member of each donor pair. Clarity of recipient stroma, intraocular pressure, and complications were followed for 6 months. Central endothelial images of the donor cornea at screening and 3 and 6 months after EK were analyzed by a masked central reading center. Dual grading of endothelial cell density was performed using the center method. Differences in endothelial cell density and cell loss were examined by paired analysis.Thirty-two pairs were enrolled, and 27 were analyzed (5 had improper matching or loss to follow-up). Donor age was 59 ± 14 years, median death-to-surgery time was 4 days (range, 2-9 days), 6 recipient pairs had Descemet membrane EK, and 21 had Descemet stripping automated EK. Recipient age was comparable in the Optisol GS and Life4°C groups (70 vs. 68 years, respectively, P = 0.46). Six-month central endothelial cell loss did not differ significantly between the Life4°C and Optisol GS groups (18 ± 18% vs. 20 ± 20%, respectively, P = 0.55). All recipient corneas were clear at 6 months in both groups.Endothelial cell loss and graft success were comparable at 6 months for paired donor corneas stored in Optisol GS and Life4°C.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01657500.

Thalamic deep brain stimulation (DBS) is an FDA-approved neurosurgical treatment for medication-refractory essential tremor. Its therapeutic benefit is highly dependent upon stimulation frequency and voltage parameters. We investigated these stimulation parameter-dependent effects on neural network activation by performing functional magnetic resonance imaging (fMRI) during DBS of the ventral lateral (VL) thalamus and comparing the blood oxygenation level-dependent (BOLD) signals induced by multiple stimulation parameter combinations in a within-subjects study of swine. Low (10 Hz) and high (130 Hz) frequency stimulation was applied at 3, 5, and 7 volts in the VL thalamus of normal swine (n = 5). We found that stimulation frequency and voltage combinations differentially modulated brain network activity in the sensorimotor cortex, the basal ganglia, and the cerebellum in a parameter-dependent manner. Notably, in the motor cortex, high frequency stimulation generated a negative BOLD response, while low frequency stimulation increased the positive BOLD response. These frequency-dependent differential effects suggest that the VL thalamus is an exemplary target for investigating functional network connectivity associated with therapeutic DBS.

Incomplete hippocampal inversion (IHI) is an atypical anatomical pattern presented by the hippocampus. It is associated with several neuropathological conditions and is thought to be a factor of susceptibility to hippocampal sclerosis and loss of volume. The volume loss of hippocampus is an inevitable consequence of aging, and when accelerated it is commonly considered an imaging biomarker of Alzheimer's disease dementia.We have studied the relationship between IHI and hippocampal subfield volumes in a cohort of 60 healthy participants of 49-87 years of age. The presence and severity of IHI and hippocampal subfield volumes were quantified from T2 magnetic resonance (MR) images acquired at 3T.It was found that IHI presented in 23.3% of participants. Right unilateral IHI was rare (two cases, 3.3%) in comparison to left unilateral IHI (nine cases, 15%), with three (5%) of participants showing bilateral IHI. No significant relationships between the whole hippocampal volumes and IHI were observed. Instead, significant relationships between the volumes of the left and right cornu ammonis subfield-1 (CA1) and IHI scores were evident.The rates of IHI prevalence in the current cohort are similar to those previously reported in healthy cohorts. The IHI severity is related to hippocampal subfield volumes, most notably the CA1, which is a novel finding with potential implications in research on aging and dementia.

BACKGROUND: Quantitative T2 and diffusion MRI indices inform about tissue state and microstructure, both of which may be affected by pathology before tissue atrophy. PURPOSE: To evaluate the capability of both volumetric and quantitative MRI (qMRI) of the hippocampus and entorhinal cortex (EC) for classification of amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease dementia (ADD). STUDY TYPE: Retrospective cross-sectional study. POPULATION: Consecutive cohorts of healthy age-matched controls (n=62), aMCI patients (n=25) and ADD patients (n=14). FIELD STRENGTH AND SEQUENCE: 3T using T1-weighted imaging, T2-weighted imaging, T2 relaxometry and diffusion tensor imaging (DTI). ASSESSMENT: Montreal Cognitive Assessment (MoCA) and paired associate learning (PAL) tests for cognitive state. Hippocampal subfield volumes by the automated segmentation of hippocampal subfields system from structural brain images. T2 relaxation time and DTI indices quantified for hippocampal subfields. The fraction of voxels with high T2 values (>20 ms above subfield median) was calculated and regionalised for hippocampus and EC. STATISTICAL TESTS: Support vector machine (SVM) and receiver operating characteristic (ROC) analyses from cognitive and MRI data. RESULTS: Quantitative MRI classified aMCI and ADD with excellent sensitivity (79.0% and 94.5%, respectively) and specificity (85.6% and 86.1%, respectively), superior to volumes alone (70.0% and 84.5% for respective sensitivities; 82.2 and 91.1 for respective specificities) and similar to cognitive tests (61.7% and 87.5% for respective sensitivities; 88.2% and 90.7% for respective specificities). Regions of high T2 are dispersed throughout each hippocampal subfield in aMCI and ADD with higher concentration than controls, and was most pronounced in the EC. No other individual qMRI marker than EC volume can separate aMCI from ADD, however. DATA CONCLUSION: Quantitative MRI markers of hippocampal and entorhinal tissue states are sensitive and specific classifiers of aMCI and ADD. They may serve as markers of a neurodegenerative state preceding volume loss. KEYWORDS: T2 relaxometry, diffusion tensor imaging, hippocampus, mild cognitive impairment, Alzheimer’s disease dementia

Both recognition of familiar objects and pattern separation, a process that orthogonalises overlapping events, are critical for effective memory. Evidence is emerging that human pattern separation requires dentate gyrus. Dentate gyrus is intimately connected to CA3 where, in animals, an autoassociative network enables recall of complete memories to underpin object/event recognition. Despite huge motivation to treat age-related human memory disorders, interaction between human CA3 and dentate subfields is difficult to investigate due to small size and proximity. We tested the hypothesis that human dentate gyrus is critical for pattern separation, whereas, CA3 underpins identical object recognition. Using 3 T MR hippocampal subfield volumetry combined with a behavioural pattern separation task, we demonstrate that dentate gyrus volume predicts accuracy and response time during behavioural pattern separation whereas CA3 predicts performance in object recognition memory. Critically, human dentate gyrus volume decreases with age whereas CA3 volume is age-independent. Further, decreased dentate gyrus volume, and no other subfield volume, mediates adverse effects of aging on memory. Thus, we demonstrate distinct roles for CA3 and dentate gyrus in human memory and uncover the variegated effects of human ageing across hippocampal regions. Accurate pinpointing of focal memory-related deficits will allow future targeted treatment for memory loss.

MRI provides a sensitive and specific imaging tool to detect acute ischemic stroke by means of a reduced diffusion coefficient of brain water. In a rat model of ischemic stroke, differences in quantitative T1 and T2 MRI relaxation times (qT1 and qT2) between the ischemic lesion (delineated by low diffusion) and the contralateral non-ischemic hemisphere increase with time from stroke onset. The time dependency of MRI relaxation time differences is heuristically described by a linear function and thus provides a simple estimate of stroke onset time. Additionally, the volumes of abnormal qT1 and qT2 within the ischemic lesion increase linearly with time providing a complementary method for stroke timing.A (semi)automated computer routine based on the quantified diffusion coefficient is presented to delineate acute ischemic stroke tissue in rat ischemia. This routine also determines hemispheric differences in qT1 and qT2 relaxation times and the location and volume of abnormal qT1 and qT2 voxels within the lesion. Uncertainties associated with onset time estimates of qT1 and qT2 MRI data vary from ± 25 min to ± 47 min for the first 5 hours of stroke. The most accurate onset time estimates can be obtained by quantifying the volume of overlapping abnormal qT1 and qT2 lesion volumes, termed 'Voverlap' (± 25 min) or by quantifying hemispheric differences in qT2 relaxation times only (± 28 min). Overall, qT2 derived parameters outperform those from qT1. The current MRI protocol is tested in the hyperacute phase of a permanent focal ischemia model, which may not be applicable to transient focal brain ischemia.