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BACKGROUND: Uncertain prognosis presents a challenge for therapists in determining the most efficient course of rehabilitation treatment for individual patients. Cortical Sensorimotor network connectivity may have prognostic utility for upper extremity motor improvement because the integrity of the communication within the sensorimotor network forms the basis for neuroplasticity and recovery. OBJECTIVE: To investigate if pre-intervention sensorimotor connectivity predicts post-stroke upper extremity motor improvement following therapy. METHODS: Secondary analysis of a pilot triple-blind randomized controlled trial. Twelve chronic stroke survivors underwent 2-week task-practice therapy, while receiving vibratory stimulation for the treatment group and no stimulation for the control group. EEG connectivity was obtained pre-intervention. Motor improvement was quantified as change in the Box and Block Test from pre to post-therapy. The association between ipsilesional sensorimotor connectivity and motor improvement was examined using regression, controlling for group. For negative control, contralesional/interhemispheric connectivity and conventional predictors (initial clinical motor score, age, time post-stroke, lesion volume) were examined. RESULTS: Greater ipsilesional sensorimotor alpha connectivity was associated with greater upper extremity motor improvement following therapy for both groups (p

Subthreshold vibratory stimulation to the paretic wrist has been shown to prime the sensorimotor cortex and improve 2-week upper extremity (UE) therapy outcomes. The objective of this work was to determine feasibility, safety, and preliminary efficacy of the stimulation over a typical 6-week therapy duration. Four chronic stroke survivors received stimulation during 6-week therapy. Feasibility/safety/efficacy were assessed at baseline, posttherapy, and 1-month follow-up. For feasibility, all participants wore the device throughout therapy and perceived the stimulation comfortable/safe. Regarding safety, no serious/moderate intervention-related adverse events occurred. For efficacy, all participants improved in Wolf Motor Function Test and UE use in daily living based on accelerometry and stroke impact scale. Mean improvements at posttherapy/follow-up were greater than the minimal detectable change/clinically important difference and other trials with similar therapy without stimulation. In conclusion, the stimulation was feasible/safe for 6-week use. Preliminary efficacy encourages a larger trial to further evaluate the stimulation as a therapy adjunct.

Introduction: Thrombocytopenia (TCP) is a common finding in patients receiving continuous renal replacement therapy (CRRT). Objective: The purpose of this study was to assess the nature of TCP in patients receiving CRRT. Methods: This is a single-center case-control observational study of 795 patients involving over 166,950 h of delivered CRRT at Johns Hopkins Hospital. Concurrent TCP in patients receiving CRRT was defined as a decrease in platelet count of ≥50% any time within 72 h of initiation of CRRT with strict exclusion criteria. Results: There was a higher incidence of TCP in the cardiac intensive care unit (CICU) (22.5%) compared to medical ICU (MICU) (13.1%). Using logistic regression, the odds of developing concurrent TCP in patients receiving CRRT was 2.46 (95% CI 1.32–3.57, p < 0.05) times higher in the CICU compared with the MICU. There was no difference in the incidence of severe or profound TCP or timing of acute TCP between the CICU and MICU. Conclusion: Safe delivery of dialysis care in the ICU is paramount and creating awareness of potential risks such as concurrent TCP in patients receiving CRRT should be part of this care.

Transcranial direct current stimulation (tDCS) is reported to induce irritating skin sensations and occasional skin injuries, which limits the applied tDCS dose. Additionally, tDCS hardware safety profile prevents high current delivery when skin resistance is high.To test if decreasing skin resistance can enable high-dose tDCS delivery without increasing tDCS-related skin sensations or device hardware limits.We compared the effect of microdermabrasion and sonication on 2 mA direct current stimulation (DCS) through forearm skin for 2-3 min on 20 subjects. We also surveyed the subjects using a questionnaire throughout the procedure. We used a linear mixed-effects model for repeated-measures and multiple logistic regression, with adjustments for age, race, gender and visit.Microdermabrasion, with/out sonication, led to significant decrease in skin resistance (1.6 ± 0.1 kΩ or ∼32% decrease,Microdermabrasion (with/out sonication) resulted in reduced skin resistance without increase in perceived skin sensations with DCS. Higher current can be delivered with microdermabrasion-pre-treated skin without changing the device hardware while reducing, otherwise higher voltage required to deliver the same amount of current.

Objective Alterations in coagulation could mediate functional outcome in patients with hyperglycemia after acute ischemic stroke (AIS). We prospectively studied the effects of intensive versus standard glucose control on coagulation markers and their relationships to functional outcomes in patients with AIS. Approach The Insights on Selected Procoagulation Markers and Outcomes in Stroke Trial measured the coagulation biomarkers whole blood tissue factor procoagulant activity (TFPCA); plasma factors VII (FVII), VIIa (FVIIa), and VIII (FVIII); thrombin‐antithrombin (TAT) complex; D‐dimer; tissue factor pathway inhibitor, and plasminogen activator inhibitor‐1 (PAI‐1) antigen in patients enrolled in the Stroke Hyperglycemia Insulin Network Effort trial of intensive versus standard glucose control on functional outcome at 3 months after AIS. Changes in biomarkers over time (from baseline ≈12 hours after stroke onset) to 48 hours, and changes in biomarkers between treatment groups, functional outcomes, and their interaction were analyzed by two‐way analysis of variance. Results A total of 125 patients were included (57 in the intensive treatment group and 68 in the standard treatment group). The overall mean age was 66 years; 42% were women. Changes from baseline to 48 hours in coagulation markers were significantly different between treatment groups for TFPCA (P = 0.02) and PAI‐1 (P = .04) and FVIIa (P = .04). Increases in FVIIa and decreases in FVIII were associated with favorable functional outcomes (P = .04 and .04, respectively). In the intensive treatment group, reductions in TFPCA and FVIII and increases in FVIIa were greater in patients with favorable than unfavorable outcomes (P = .02, 0.002, 0.03, respectively). In the standard treatment group, changes in FVII were different by functional outcome (P = .006). Conclusions Intensive glucose control induced greater alterations in coagulation biomarkers than standard treatment, and these were associated with a favorable functional outcome at 3 months after AIS.

Background Atrial fibrillation (AF) is less common in African Americans (AA) than Caucasians (C) despite a higher prevalence of risk factors such as hypertension (HTN). Objective Test the hypothesis that differences in extracellular matrix (ECM) between AA and C in response to HTN might attenuate atrial enlargement and alter myocardial fibrosis. Methods ECM-related plasma biomarkers and echo data were collected from 326 C and 129 AA subjects with no history of AF, stratified by the presence of HTN, HTN with left ventricular hypertrophy (LVH), or HTN with LVH and heart failure with preserved ejection fraction (HFpEF). Results Left atrial size was significantly smaller and the extent of enlargement in the presence of HTN was less in AA despite similar ventricular relative wall thickness, echocardiographic measures of diastolic function, and 6 minute-walk-test. AA had significantly lower levels of collagen I telopeptide and higher levels of collagen I propeptide among all strata, suggesting unique collagen homeostasis. Matrix metalloproteinases (MMP) and tissue inhibitors of matrix metalloproteinase (TIMP) showed a distinctive response to HTN in AA, with significantly lower levels of MMP-2, MMP-3, and MMP-8 in AA with HTN and significantly lower levels of TIMP-1 and TIMP-3 in AA with HTN and AA with LVH. AA had significantly lower levels of NT-pro-BNP in all strata. Conclusion This cross-sectional study demonstrates a racial disparity in ECM blood biomarkers and atrial remodeling in response to HTN and in the development of LVH and HFpEF that may partly help explain the decreased risk of AF in AA.

Objective Develop a model to predict gastrostomy tube (GT) for feeding at discharge in infants born < 30 weeks’ (w) gestational age (GA). Study design A single-center retrospective study at academic NICU. Total of 391 (78 GT, 313 non-GT) infants < 30 w GA admitted in 2015–2018 split into test (15–16) and validation (17–18) cohorts. Classification and regression tree analysis was used to identify predictive factors for GT. Results Several factors were associated with GT requirements. Four factors included in the model were postmenstrual age (PMA) at first oral feeding, birth GA, high-frequency ventilation exposure, necrotizing enterocolitis stage II/III. Area under the receiver operator characteristic curve was 0.944 in the test cohort, 0.815 in the validation cohort. Implementation plan based on the model was developed. Conclusions We developed a predictive model to risk-stratify infants born < 30 w GA for failing full oral feeding. We hope implementation at 38 w PMA will result in earlier placement of needed GT and discharge.

BACKGROUND: Peripheral sensory stimulation augments post-stroke upper extremity rehabilitation outcomes. Most sensory stimulations interfere with natural hand tasks and the stimulation duration is limited. We developed TheraBracelet, low-level random-frequency vibration applied via a wristwatch, to enable stimulation during hand tasks and potentially extend stimulation durations. OBJECTIVE: To determine safety of prolonged exposure to TheraBracelet. METHODS: Single-site double-blind cross-over randomized controlled trial. Chronic stroke survivors were instructed to wear a device on the affected wrist for ≥8hr/day everyday for 2 months while coming to the laboratory weekly for evaluations, with a 2-week break between each month. The device applied vibration at 60% and 1% of the sensory threshold for the real and sham month, respectively. The order of the real and sham months was randomized/balanced. Adverse events (AEs) were assessed weekly, including worsening of hand sensation, dexterity, grip strength, pain, or spasticity and occurrence of skin irritation or swelling. Device-related AE rates were compared between the real and sham month. RESULTS: Twenty-five participants completed the study. Six participants (24%) experienced mild AEs involving worsened sensory scores that may be related to the intervention with reasonable possibility. Two experienced them in the real stimulation month only, 3 in the sham month only, and 1 in both months. Therefore, less participants experienced device-related AEs in the real than sham month. CONCLUSION: Daily stimulation using the device for a month is safe for chronic stroke survivors. Future studies examining the efficacy of pairing TheraBracelet with therapy for increasing neurorehabilitation outcomes is a logical next step.

Multi-arm multi-stage designs, in which multiple active treatments are compared to a control and accumulated information from interim data are used to add or remove arms from the trial, may reduce development costs and shorten the drug development timeline. As such, this adaptive update is a natural complement to Bayesian methodology in which the prior clinical belief is sequentially updated using the observed probability of success. Simulation is often required for planning clinical trials, to accommodate the complexity of the design, and to optimize key design characteristics. This paper addresses two key limiting factors in simulations, namely the computational burden and the time needed to obtain results. We first introduce a generic process for simulating Bayesian multi-arm multi-stage designs with binary endpoints. Then, to address the computational burden and time, we optimize the method for calculating the posterior probability and posterior predictive probability of success.

Background Peripheral sensory stimulation has been used in conjunction with upper extremity movement therapy to increase therapy-induced motor gains in patients with stroke. The limitation is that existing sensory stimulation methods typically interfere with natural hand tasks and thus are administered prior to therapy, requiring patients’ time commitment. To address this limitation, we developed TheraBracelet. This novel stimulation method provides subthreshold (ie, imperceptible) vibratory stimulation to the wrist and can be used during hand tasks/therapy without interfering with natural hand tasks. Objective The objective was to determine the feasibility of using TheraBracelet during therapy to augment motor recovery after stroke. Design The design was a triple-blinded pilot randomized controlled trial. Methods Twelve chronic stroke survivors were assigned to the treatment or control group. All participants completed 2-hour task practice therapy sessions thrice weekly for 2 weeks. Both groups wore a small vibrator on the paretic wrist, which was turned on to provide TheraBracelet stimulation for the treatment group and turned off for the control group to provide sham stimulation. Outcome measures (Box and Block Test [BBT] and Wolf Motor Function Test [WMFT]) were obtained at baseline, 6 days after therapy, and at follow-up 19 days after therapy. Results The intervention was feasible with no adverse events. The treatment group significantly improved their BBT scores after therapy and at follow-up compared with baseline, whereas the control group did not. For WMFT, the group × time interaction was short of achieving significance. Large effect sizes were obtained (BBT d = 1.43, WMFT d = 0.87). No indication of desensitization to TheraBracelet stimulation was observed. Limitations The limitation was a small sample size. Conclusions TheraBracelet could be a promising therapy adjuvant for upper extremity recovery after stroke.

Opioid Use Disorders (OUDs) and drug overdose deaths are increasing at alarmingly high rates in the United States. Stress and dysregulation in biologic stress response systems such as the hypothalamic-pituitary-adrenal axis and noradrenergic system appear to play an important role in the pathophysiology of substance use disorders and relapse to drug use, particularly for women. Alpha-2 adrenergic agonist medications effectively decrease noradrenergic activity and have demonstrated benefit in preventing relapse to substance use and decreasing stress-reactivity and craving in cocaine- and nicotine-dependent women, compared to men. Alpha-2 adrenergic agonists may help decrease stress reactivity in individuals with OUDs and prevent relapse to drug use, but gender differences have yet to be systematically explored. We describe the rationale, study design and methodology of a randomized, double-blind, placebo-controlled clinical trial examining gender differences in stress, craving and drug use among adult men and women with OUD taking methadone or buprenorphine and randomly assigned to an alpha-2 adrenergic agonist, lofexidine, compared to placebo. In addition, we describe methods for measuring daily stress, craving and drug use in participant's natural environment as well as participant's physiological (i.e., heart rate, cortisol) and psychological (i.e., stress, craving) response to laboratory social and drug cue stressors. Lastly, we detail methods adopted to sustain research activity while following guidelines for the COVID-19 pandemic. ClinicalTrials.gov Registration Number: NCT03718065.

Supplemental Digital Content is available in the text., Background: This study examines the feasibility and utility of integrating coronary computed tomography angiography and the HEART Pathway into a novel accelerated diagnostic protocol—called HEART-CT—and assesses its impact as an optional interactive decision support tool (smart form) in the electronic health record. Methods: This was a retrospective observational study performed in 2 adult emergency departments (ED) among patients evaluated for suspected acute coronary syndrome. Primary outcomes included the rate of discharge from the ED following HEART-CT Smart Form use, 30-day major adverse cardiac events (MACE), and ED length of stay (LOS). Hypothesis-generating outcomes included the rate of Smart Form use by ED providers and whether adhering to the HEART-CT recommendations was associated with improved outcomes. Results: The study included 672 subjects, 78.1% of whom were discharged from the ED. HEART-CT identified 76.7% of patients with increased risk HEAR scores as safe for discharge. No patients identified as low risk by HEART-CT had MACE within 30 days. Total mean ED LOS was 4.6 hours. ED providers used the HEART-CT smart form in 19.7% of eligible patients. ED providers who followed the HEART-CT recommendations had 3.41 times higher odds of ED discharging patients with increased risk HEAR scores than nonadherent providers (95% CI, 2.20-5.27). Conclusions: HEART-CT reclassified a large proportion of patients as safe for discharge, maintained a high sensitivity for detecting 30-day MACE, and had an acceptable ED LOS. Future studies should test the extent to which more automated clinical decision support improves provider adoption and clinical outcomes of HEART-CT.

ObjectiveThe Care-coordination Approach to Learning Lupus Self-Management (CALLS) study was designed to improve SLE disease self-management. This study aims to assess the benefits of the intervention compared with existing lupus care.MethodsParticipants were randomly assigned to participate in 12-weekly phone sessions with the patient navigator that included structured educational content, care coordination and patient-centred support services, or a usual care control condition. Validated measures of health literacy, self-efficacy, patient activation and disease activity were collected. We used least squares means and linear mixed-effects regression models for each outcome variable to assess the changes in outcome, from baseline to postintervention and to estimate the difference in these changes between the intervention and control group.ResultsThirty participants were enrolled and 14 were randomised to the treatment group. For perceived lupus self-efficacy, there was a significant increase in mean score for the intervention group, but not for the control group. With regard to disease activity, the experimental group experienced a slight decrease in mean flare score in the previous 3 months, whereas the control group experienced a slight increase, but this finding did not reach statistical significance. Trends were similar in self-reported global disease activity, but none of the findings were significant. Health literacy and patient activation measure scores remained largely unchanged throughout the study for the two groups.ConclusionThese findings suggest that the CALLS intervention may work to improve aspects of SLE disease self-management. Future research will be needed to validate these findings long-term.Trial registration numberNCT04400240.

Franck F Rahaghi,1 Richard Monk,2 Viswanathan Ramakrishnan,3 Tatsiana Beiko,2 Charlie Strange2 1Department of Pulmonary and Critical Care, Cleveland Clinic Florida, Weston, FL, USA; 2Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Medical University of South Carolina, Charleston, SC, USA; 3Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USACorrespondence: Franck F RahaghiDepartment of Pulmonary and Critical Care, Cleveland Clinic Florida, Weston, FL, USATel +1 954 659 5450Fax +1 954 6595451Email rahaghf@ccf.orgPurpose: The extent of the survival benefit of augmentation therapy for alpha-1 antitrypsin deficiency (AATD) in individuals with advanced COPD is difficult to define. We performed a retrospective analysis using all available data from the observational registry of individuals with severe deficiency of alpha-1 antitrypsin (AAT) conducted by the NHLBI investigators.Patients and Methods: Individuals (N=1129) with severe deficiency of AAT were evaluated for mortality using all data sources and stratified by 10% increments of baseline forced expiratory volume in 1 second (FEV1) percent predicted and by augmentation therapy status (ever receiving versus never receiving). Kaplan–Meier survival curves were constructed for each of the deciles comparing survival in treated vs non-treated groups. A multivariable model was performed to define the correlates of survival in individuals with FEV1 < 30% predicted.Results: Amongst all subjects, augmentation was associated with improved survival (p< 0.0001). Among the individuals ever receiving augmentation therapy, survival was better than for those not receiving augmentation at all 10% increments of FEV1% predicted from 10% to 60% (P values < 0.05 in all deciles). In subgroups of participants with hyperinflation defined as residual volume (RV)> 120% predicted and in subgroups of participants with reduced diffusing capacity for carbon monoxide (DLCO) < 70% predicted, there was significantly better survival for those ever receiving augmentation therapy than for those who never received augmentation (p< 0.001). A multivariable analysis showed that mortality benefit is influenced by age, DLCO % predicted, and augmentation therapy.Conclusion: There is a survival benefit from augmentation therapy in AATD between FEV1 values in the 10– 60% predicted range. Screening and treatment of AATD patients should therefore not be limited by the severity of illness as defined by FEV1.Keywords: alpha-1 antitrypsin deficiency, COPD, mortality, augmentation therapy, FEV1, survival

Background S-Nitrosoglutathione (GSNO) is a nitric oxide donor that has been investigated for neuroprotective and neuro-recovery effect. We aimed to conduct a systematic review on the published literatures using GSNO in both pre-clinical and clinical stroke studies. Methods We searched PubMed up to June 30, 2019, using the following keywords: S-Nitrosoglutathione, GSNO, stroke, cerebrovascular, carotid arteries, middle cerebral artery, and middle cerebral artery occlusion. Only studies published in the English language providing efficacy results of GSNO on ischemic stroke were included. Stroke Therapy Academic Industry Roundtable (STAIR) score was used to assess the quality of pre-clinical studies and PEDro score for clinical trials. A meta-analysis was conducted to compare the effect size. Results Of 39 articles identified, 10 (6 for pre-clinical and 4 for clinical studies) met the eligibility criteria and were included. The median STAIR score across the pre-clinical studies was 5.5 (range: 4–7), and the median PEDro score for the 4 clinical trials was 10 (ranged: 6 to 10). Among the 6 pre-clinical studies, GSNO reduced infarct size in 6 studies and improved neurological behavior scales in 5 studies compared to placebo. Inverse-variance weighted linear meta-analysis of standardized mean difference (Hedge's g) on 4 human studies revealed a big effect size (Hedge's g = −0.82, 95% CI: [−1.26, −0.38], P = .0003) favoring the GSNO group in term of reducing embolic signals. I2 value was 0 across the included clinical studies in the meta-analysis. Conclusions Pre-clinical studies showed positive benefit of GSNO in animal stroke models. The meta-analysis of clinical studies demonstrated that GSNO is effective in reducing embolic signals in patients with symptomatic internal carotid artery stenosis undergoing carotid endarterectomy or stenting. Further investigation of this molecule is warranted.

Despite advances in prevention and treatment, cigarette smoking remains a leading cause of preventable death in the United States. Although men and women are equally likely to attempt to quit smoking cigarettes, women are far less likely to achieve abstinence both during and following cessation treatment. Recent evidence suggests that ovarian hormone levels may play a role in successful abstinence attempts in women smokers. The primary goal of this exploratory prospective observational study was to estimate the association between within-participant levels of progesterone and estradiol with associated cigarettes smoked per day in adult women smokers (n = 104). The primary study outcome was self-reported cigarettes smoked per day (CPD) during a 2-week observational period collected using a daily smoking diary. Additionally, participants collected saliva daily, from which hormone levels (progesterone and estradiol) were derived. Higher within-participant progesterone levels were associated with a significant decrease in CPD (p = .008) whereas within-participant estradiol levels were unrelated to CPD (p = .25). Regression models indicated a single change in the trajectory of smoking behavior for both within-participant progesterone and estradiol. When progesterone values were below the change point, there was a significant inverse relationship between within-participant progesterone levels and smoking behavior (p = .025) whereas the relationship was attenuated for higher within-participant progesterone levels (p = .59). The effect of estradiol on smoking behavior was not significant when it was either below (p = .92) or above (p = .16) the change point. Higher within-participant levels of progesterone but not estradiol are associated with reduced CPD in nontreatment seeking women smokers.

Date Presented Accepted for AOTA INSPIRE 2021 but unable to be presented due to online event limitations. Uncertain poststroke prognosis makes it difficult for OTs to develop personalized treatments for their patients. This study evaluated electroencephalography (EEG) as a predictor of individual response to a rehabilitation program. Results demonstrate the potential for EEG to predict patients’ responsiveness to an upper extremity intervention. These findings may promote individualized treatment and encourage a larger follow-up study. Primary Author and Speaker: Amanda A. Vatinno Contributing Authors: Christian Schranz, Viswanathan Ramakrishnan, and Na Jin Seo

Patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) continue to have an unacceptably high mortality rate despite the progress achieved with pulmonary arterial vasodilator therapies.We sought to determine whether SSc-PAH is a clinically distinct pulmonary vascular disease phenotype when compared with idiopathic pulmonary arterial hypertension (IPAH) on the basis of progression of echocardiographic right ventricular (RV) dysfunction.Retrospective analysis of echocardiographic data in 13 patients with SSc-PAH and 11 patients with IPAH was used to delineate the progression of RV dysfunction during single or combination pulmonary arterial vasodilator therapy. All patients had right heart catheterization-confirmed pulmonary arterial hypertension as well as complete baseline (at the time of diagnosis) and follow-up (most recent) echocardiograms. We excluded patients with significant scleroderma-associated interstitial lung disease. Adjusting for time of follow-up and disease duration, we performed mixed model regression analyses comparing the changes between the two groups for different echocardiographic variables: tricuspid annular plane systolic excursion, tricuspid regurgitation jet velocity, right atrial area, and RV diameter.The mean ages for the SSc-PAH and IPAH groups were 60.8 and 48.2 years, respectively. The mean follow-up periods for the two groups were 3.8 and 1.95 years, respectively. Tricuspid annular plane systolic excursion did not improve in patients with SSc-PAH, whereas it increased in the patients with IPAH (-0.38 mm, P = 0.87; vs. +5.6 mm, P = 0.02). The other echocardiographic variables showed a trend toward worsening in the SSc-PAH group and improvement in the IPAH group.Our results indicate that, in patients with SSc-PAH, echocardiographic RV function does not improve over time compared with that of patients with IPAH, despite institution of pulmonary artery vasodilator therapies.

RATIONALE: Female cigarette smokers tend to show greater cessation failure compared to males. Variables that contribute to the maintenance of smoking, including stress and craving, may differentially impact male and female smokers. Novel pharmacotherapies, such as oxytocin, may attenuate stress reactivity and craving in smokers, but work in this area is limited. OBJECTIVES: This study assessed the influence of gender and oxytocin on stress reactivity, craving, and smoking in a randomized, placebo-controlled laboratory relapse paradigm. METHODS: Male and female adult cigarette smokers (ages 18–45) were enrolled (women oversampled 2:1) and completed a laboratory session, in which intranasal oxytocin or placebo was administered followed by a laboratory social stress task. The role of gender and oxytocin were assessed on measures of stress reactivity, cigarette craving, latency to smoke in a resistance task, subjective responses to smoking, and ad-libitum smoking. RESULTS: Participants (N=144) had a mean age of 31, were 63% female and 56% White. Following stress induction, female smokers evidenced greater subjective stress than males, though males demonstrated greater neuroendocrine reactivity and smoking intensity than females. No gender differences were demonstrated for craving. Oxytocin did not attenuate any aspect of stress reactivity, craving, smoking, or subjective responses to smoking compared to placebo. CONCLUSIONS: Gender differences in stress reactivity were shown in the hypothesized direction, but oxytocin appeared to exert little impact on subjective or behavioral metrics. Results highlight the complex relationship between gender, stress, and smoking, as well as the implications for oxytocin as a potential pharmacotherapy for smoking cessation.

OBJECTIVE: We sought to examine the impact of the Affordable Care Act on preventable hospitalizations and associated charges for patients living with systemic lupus erythematosus (SLE), before and after Medicaid expansion. METHODS: A retrospective, quasi-experimental study, using an Interrupted Time Series (ITS) research design, was used to analyze data from the Healthcare Cost and Utilization Project (HCUP) State Inpatient Databases (SID) for eight states. Lupus hospitalizations with a principal diagnosis of pre-determined ambulatory care sensitive (ACS) conditions were the unit of primary analysis. The primary outcome variable was access to care measured by preventable hospitalizations caused by an ACS condition. RESULTS: There were 204,150 lupus hospitalizations in the final analysis with the majority (53.5%) of lupus hospitalizations in states that did not expand Medicaid. In unadjusted analysis, Medicaid expansion states had significantly lower odds of having preventable lupus hospitalizations (OR 0.958); however, after adjusting for several covariates, Medicaid expansion states had increased odds of having preventable lupus hospitalizations (OR 1.302). Adjusted analysis showed that those with increased age, public insurance (Medicare or Medicaid), no health insurance, rural residence, or low income had significantly higher odds of having a preventable lupus hospitalization. States that expanded Medicaid had $523 significantly more charges than states that did not expand Medicaid. Older age and rural residence were associated with significantly higher charges. CONCLUSION: Our findings suggest that while Medicaid expansion increased health insurance coverage, it did not address other issues related to access to care that could reduce the number of preventable hospitalizations.

Background Systemic lupus erythematosus (SLE or lupus) is a chronic autoimmune disease that is associated with increased morbidity, mortality, healthcare costs and decreased quality of life. African Americans in the USA have three to four times greater prevalence of SLE, risk of developing SLE at an earlier age, and SLE-related disease activity, damage, and mortality compared with Caucasians, with the highest rates experienced by African American women. There is strong evidence that patient-level factors are associated with outcomes, which justifies targeting them with intervention. While evidence-based self-management interventions that incorporate both social support and health education have reduced pain, improved function, and delayed disability among patients with SLE, African Americans and women are still disproportionately impacted by SLE. Peer mentoring interventions are effective in other chronic conditions that disproportionately affect minorities, such as diabetes mellitus, HIV, and kidney disease, but there is currently no empirically tested peer mentoring intervention developed for patients with SLE. Preliminary data from our group suggest that peer mentoring improves self-management, reduces disease activity, and improves health-related quality of life (HRQOL) in African American women with SLE. Methods This study will test an innovative, manualized peer mentorship program designed to provide modeling and reinforcement by peers (mentors) to other African American women with SLE (mentees) to encourage them to engage in activities that promote disease self-management. Through a randomized, “mentored” or “support group” controlled design, we will assess the efficacy and mechanism(s) of this intervention in self-management, disease activity, and HRQOL. Discussion This is the first study to test peer mentorship as an alternative strategy to improve outcomes in African American women with SLE. This could result in a model for other programs that aim to improve disease self-management, disease activity, and HRQOL in African American women suffering from chronic illness. The peer mentoring approach is uniquely fitted to African Americans, and this intervention has the potential to lead to health improvements for African American women with SLE that have not been attainable with other interventions. This would significantly reduce disparities and have considerable public health impact. Trial registration ClinicalTrials.gov, NCT03734055. Registered on 27 November 2018. Electronic supplementary material The online version of this article (10.1186/s13063-019-3580-4) contains supplementary material, which is available to authorized users.

Peripheral sensory stimulation has been used as a method to stimulate the sensorimotor cortex, with applications in neurorehabilitation. To improve delivery modality and usability, a new stimulation method has been developed in which imperceptible random-frequency vibration is applied to the wrist concurrently during hand activity. The objective of this study was to investigate effects of this new sensory stimulation on the sensorimotor cortex. Healthy adults were studied. In a transcranial magnetic stimulation (TMS) study, resting motor threshold, short-interval intracortical inhibition, and intracortical facilitation for the abductor pollicis brevis muscle were compared between vibration on vs. off, while subjects were at rest. In an electroencephalogram (EEG) study, alpha and beta power during rest and event-related desynchronization (ERD) for hand grip were compared between vibration on vs. off. Results showed that vibration decreased EEG power and decreased TMS short-interval intracortical inhibition (i.e., disinhibition) compared with no vibration at rest. Grip-related ERD was also greater during vibration, compared to no vibration. In conclusion, subthreshold random-frequency wrist vibration affected the release of intracortical inhibition and both resting and grip-related sensorimotor cortical activity. Such effects may have implications in rehabilitation.

Current clinical classifications of chronic rhinosinusitis (CRS) have weak prognostic utility regarding treatment outcomes. Simplified discriminant analysis based on unsupervised clustering has identified novel phenotypic subgroups of CRS, but prognostic utility is unknown.We sought to determine whether discriminant analysis allows prognostication in patients choosing surgery versus continued medical management.A multi-institutional prospective study of patients with CRS in whom initial medical therapy failed who then self-selected continued medical management or surgical treatment was used to separate patients into 5 clusters based on a previously described discriminant analysis using total Sino-Nasal Outcome Test-22 (SNOT-22) score, age, and missed productivity. Patients completed the SNOT-22 at baseline and for 18 months of follow-up. Baseline demographic and objective measures included olfactory testing, computed tomography, and endoscopy scoring. SNOT-22 outcomes for surgical versus continued medical treatment were compared across clusters.Data were available on 690 patients. Baseline differences in demographics, comorbidities, objective disease measures, and patient-reported outcomes were similar to previous clustering reports. Three of 5 clusters identified by means of discriminant analysis had improved SNOT-22 outcomes with surgical intervention when compared with continued medical management (surgery was a mean of 21.2 points better across these 3 clusters at 6 months, P.05). These differences were sustained at 18 months of follow-up. Two of 5 clusters had similar outcomes when comparing surgery with continued medical management.A simplified discriminant analysis based on 3 common clinical variables is able to cluster patients and provide prognostic information regarding surgical treatment versus continued medical management in patients with CRS.

OBJECTIVES/GOALS: The objective of this study is to perform a systematic review and meta-analysis on the prognostic utility of electroencephalography (EEG) in stroke recovery. METHODS/STUDY POPULATION: A literature search was conducted using three electronic databases, including PubMed, Scopus, and CINAHL. Key search terms were “EEG,” “stroke,” and “rehabilitation”. Only peer-reviewed journal articles published in English that examined the relationship between EEG and a standardized clinical outcome measure(s) at a later time in stroke patients were included. Two independent raters completed data extraction and assessed methodological quality of the studies with the Downs and Black form. A linear meta-regression was performed across subsets of individual studies that utilized a common clinical outcome measure to determine the association between EEG and clinical outcome while adjusting for sample size and study quality. RESULTS/ANTICIPATED RESULTS: 56 papers met the inclusion criteria and were included in the systematic review. The prognostic value of EEG was evidenced at both the acute and chronic stages of stroke. The addition of EEG enhanced prognostic accuracy more than initial clinical assessment scores and/or lesion volume alone. In the meta-analysis, a subset of 10 papers that utilized the National Institutes of Health Stroke Scale (NIHSS) and a subset of 7 papers that utilized the Modified Rankin Scale (MRS) were included. Analysis demonstrated an association between EEG and the subsequent clinical outcome measures. DISCUSSION/SIGNIFICANCE OF IMPACT: Currently, prognosis is largely based on initial behavioral impairment level. However, post-stroke recovery outcomes are heterogeneous despite similar initial clinical presentations. Uncertain prognosis makes it difficult for clinicians to develop personalized treatment plans for patients. Improved prognosis for recovery may guide clinical management for stroke survivors by helping clinicians determine the maximally efficient course of treatment and care. This study suggests that prognostic accuracy may be enhanced using EEG.

Introduction Some evidence suggests that female smokers may show more context-dependent smoking and that males may show more stereotyped smoking (regardless of stress or cue exposure). The goal of this study was to characterize sex differences in response to stressful and smoking cues ecologically presented in daily life and variability in day-to-day smoking behavior. Methods Adult smokers (N = 177) provided ratings of mood and cigarette craving before and after stress and smoking cues were presented four times daily for 14 days via a mobile device. Linear mixed models tested whether (1) female smokers exhibited greater reactivity to stressful cues than male smokers; (2) pre-cue negative affect increased reactivity to smoking cues more in female smokers than male smokers; (3) across both sexes, greater reactivity to stressful and smoking cues correlated with greater quantity of smoking within a day; and (4) female smokers exhibited greater variability in cigarettes per day (CPD) relative to males. Results Relative to male smokers, female smokers reported greater negative affect, stress, and craving in response to stressful cues, but not smoking cues, after accounting for time since last cigarette and pre-cue responding. No sex differences in CPD or variability in CPD were detected. Days with higher subjective reactivity to cues were not associated with increased smoking, in either males or females. Conclusions Sex differences were observed in response to stress but not smoking cues in the natural environment of regular cigarette smokers. Further research is necessary to evaluate whether stress reactivity in female smokers is associated with reduced latency to smoke following stress exposure in daily life. Implications This study provides naturalistic evidence that female smokers may not be more reactive to smoking cues than males, but experience heightened stress and craving following stress exposure. There was no evidence to support the hypothesis that amount smoked per day varied more for females, relative to males, as a result of more context-driven smoking for females.

Objective To evaluate the Specific Test of Early Infant Motor Performance (STEP), a rapid screening test of preterm infants at risk for developmental delay. Study Design We prospectively studied 23 preterm infants’ performance on the STEP and the Test of Infant Motor Performance (TIMP) at term and 3 months, and on the Bayley-III at 12 months. We investigated the psychometric qualities of the STEP and determined STEP cutoff scores for low and high-performing infants. Results STEP scores at term and 3 months strongly correlate with 12-month Bayley-III gross motor and cognitive scaled scores, while TIMP scores did not. The STEP showed excellent reliability and required 6–10 min to administer. Conclusion STEP is a short, easy to administer, early developmental assessment with unique scoring that emphasizes qualitative and quantitative aspects of muscle tone in movements and predicts 12-month Bayley gross motor and cognitive scaled scores.

Objective: Evaluate brain metabolites, which reflect neuroinflammation, and relate to neurodevelopmental outcomes in healthy term neonates exposed to chorioamnionitis. Study Design: Thirty-one healthy term neonates with documented fetal inflammatory response after maternal chorioamnionitis underwent magnetic resonance spectroscopy (MRS), with voxels placed in basal ganglia (BG) and frontal white matter. Bayley III examinations were performed at 12 months of age. Result: Infants with below average outcomes did not show the same increase in NAA/Cho ratios postnatally as the group with normal outcomes. Decreased NAA/Cho and increased Lac/Cr in BG correlated with lower motor and cognitive composite scores, respectively, controlling for postnatal age. In males, increased lactate/NAA in BG were associated with lower motor scores. Funisitis severity was associated with decreased NAA/Cho and increased mI/NAA in males. Conclusion: In healthy term newborns with chorioamnionitis, MRS ratios shortly after birth may provide evidence of occult neuroinflammation, which may be associated with worse performance on 1-year neurodevelopmental tests.

Background Current clinical classifications of chronic rhinosinusitis (CRS) have been largely defined based upon preconceived notions of factors thought to be important, such as polyp or eosinophil status. Unfortunately, these classification systems have little correlation with symptom severity or treatment outcomes. Unsupervised clustering can be used to identify phenotypic subgroups of CRS patients, describe clinical differences in these clusters and define simple algorithms for classification. Methods A multi-institutional, prospective study of 382 patients with CRS who had failed initial medical therapy completed the Sino-Nasal Outcome Test (SNOT-22), Rhinosinusitis Disability Index (RSDI), Medical Outcomes Study Short Form-12 (SF-12), Pittsburgh Sleep Quality Index (PSQI), and Patient Health Questionnaire (PHQ-2). Objective measures of CRS severity included Brief Smell Identification Test (B-SIT), CT, and endoscopy scoring. All variables were reduced and unsupervised hierarchical clustering was performed. After clusters were defined, variations in medication usage were analyzed. Discriminant analysis was performed to develop a simplified, clinically useful algorithm for clustering. Results Clustering was largely determined by age, severity of patient reported outcome measures, depression, and fibromyalgia. CT and endoscopy varied somewhat among clusters. Traditional clinical measures, including polyp/atopic status, prior surgery, B-SIT and asthma, did not vary among clusters. A simplified algorithm based upon productivity loss, SNOT-22 score, and age predicted clustering with 89% accuracy. Medication usage among clusters did vary significantly. Conclusion A simplified algorithm based upon hierarchical clustering is able to classify CRS patients and predict medication usage. Further studies are warranted to determine if such clustering predicts treatment outcomes.

OBJECTIVE: To identify the vitamin D status to optimize calcium and bone health in preterm infants. STUDY DESIGN: Very low birth weight infants had measurement of 25-hydroxyvitamin D status and markers of calcium and bone health from birth to term age. Piecewise linear regression modeling was performed to identify a 25-hydroxyvitamin D threshold associated with stable parathyroid hormone concentration and bone mineralization. RESULTS: In a cohort of 89 infants at term age, femur BMC and density increased linearly with 25-hydroxyvitamin D status until reaching a threshold of 48 ng/mL and 46 ng/mL, respectively. Parathyroid hormone status decreased as vitamin D status increased until reaching a plateau at 25-hydroxyvitamin D of 42 ng/mL. CONCLUSION: Preterm infant vitamin D status was significantly associated with PTH status and femur mineralization with suggestion that achieving a specific 25-hydroxyvitamin concentration is associated with optimal calcium homeostasis and femur bone mineralization.

Historically, ordinal measures of functional outcome have been dichotomized for the primary analysis in acute stroke therapy trials. A number of alternative methods to analyze the ordinal scales have been proposed, with an emphasis on maintaining the ordinal structure as much as possible. In addition, despite the availability of longitudinal outcome data in many trials, the primary analysis consists of a single endpoint. Inclusion of information about the course of disease progression allows for a more complete understanding of the treatment effect. Multistate Markov modeling, which allows for the full ordinal scale to be analyzed longitudinally, is compared with previously suggested analytic techniques for the ordinal modified Rankin Scale (dichotomous-logistic regression; continuous-linear regression; ordinal- shift analysis, proportional odds model, partial proportional odds model, adjacent categories logit model; sliding dichotomy; utility weights; repeated measures). In addition, a multistate Markov model utilizing an estimate of the unobservable baseline outcome derived from principal component analysis is compared Each of the methods is used to re-analyze the National Institute of Neurological Diseases and Stroke tissue plasminogen activator study which showed a consistently significant effect of tissue plasminogen activator using a global test of four dichotomized outcomes in the analysis of the primary outcome at 90 days post-stroke in the primary analysis. All methods detected a statistically significant treatment effect except the multistate Markov model without predicted baseline (p = 0.053). This provides support for the use of the estimated baseline in the multistate Markov model since the treatment effect is able to be detected with its inclusion. Multistate Markov modeling allows for a more refined examination of treatment effect and describes the movement between modified Rankin Scale states over time which may provide more clinical insight into the treatment effect. Multistate Markov models are feasible and desirable in describing treatment effect in acute stroke therapy trials.

Purpose: This phase I study was conducted to determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) for the combination of bortezomib and alvocidib in patients with B-cell malignancies (multiple myeloma, indolent lymphoma, Waldenstrom macroglobulinemia, and mantle cell lymphoma). Experimental Design: Patients received bortezomib (intravenous push), followed by alvocidib (1-hour infusion), on days 1, 4, 8, and 11 of a 21-day treatment cycle. Patients experiencing responses or stable disease continued on treatment at the investigator's discretion. A standard 3+3 dose-escalation design was used to identify the MTD based on DLTs, and pharmacokinetic and pharmacodynamic studies were conducted. Results: A total of 44 patients were enrolled, with 39 patients assessed for response. The MTD was established as 1.3 mg/m2 for bortezomib and 40 mg/m2 for alvocidib. The most common hematologic toxicities included leukopenia, lymphopenia, neutropenia, and thrombocytopenia. The most common nonhematologic toxicities included diarrhea, fatigue, and sensory neuropathy. Three complete remissions (8%) and 10 partial remissions (26%) were observed for a total response rate of 33%. Pharmacokinetic findings with the current dosing regimen were consistent with the comparable literature and the hybrid dosing regimen. Pharmacodynamic study results did not correlate with clinical responses. Conclusions: The combination of bortezomib and alvocidib is tolerable, and an MTD has been established for this schedule. The regimen appears to be efficacious in patients with relapsed/refractory multiple myeloma or indolent non-Hodgkin lymphoma. As the nonhybrid regimen is less cumbersome than the previous hybrid dosing schedule regimen, the current schedule is recommended for successor studies. Clin Cancer Res; 20(22); 5652–62. ©2014 AACR.

Date Presented 04/05/19 Primary Author and Speaker: Turki Aljuhani Additional Authors and Speakers: Amanda Vatinno Contributing Authors: Alison Fluharty, Catilyn Taylor, Eli Schuster, V. Ramakrishnan, Patty Coker-Bolt, Na Jin Seo

Background The modified Rankin scale (mRS) is the most common functional outcome assessed in stroke trials. The proportional odds model is commonly used to analyze this ordinal outcome but it requires a restrictive assumption that a single odds ratio applies across the entire outcome scale. Aims The study aims to model the effect of tissue-type plasminogen activator on ordinal mRS, test model assumptions, and compare fits and predictive ability of the statistical models. Methods Several ordinal regression methods are presented and applied to a re-analysis of the 1995 NINDS tissue-type plasminogen activator study. Violations of the proportional odds assumption are demonstrated using graphs and statistical tests, and the partial proportional odds model is introduced and recommended as an alternative for the analysis of mRS. Results The partial proportional odds model relaxes the assumptions about treatment effect on the ordinal outcome scale and provides a better fit to the data than the commonly used proportional odds model (likelihood ratio test chi-square = 8·05, P = 0·005). It provides easily interpretable odds ratios and it is able to detect efficacy at the lower end and a lack of efficacy at the upper end of the mRS scale. Further, it provides lower prediction error than the proportional odds model (0·002 versus 0·005). Conclusion Assuming proportional odds when it does not hold can mask differential treatment effects at the upper end of the ordinal mRS scale and has implications for reduced power when studies are designed under this assumption.

Purpose Preclinical studies in human melanoma cell lines and murine xenograft tumor models suggest that the proteasome inhibitor bortezomib enhances the activity of the cytotoxic agent dacarbazine. We performed a phase I trial of bortezomib and dacarbazine in melanoma, soft tissue sarcoma, and amine precursor uptake and decarboxylation tumors. The primary objective was to identify recommended phase II doses for the combination. Experimental design Bortezomib and dacarbazine were both administered intravenously once weekly. All patients received prophylactic antiemetics. Dose escalation proceeded using a standard 3 + 3 design. Response was assessed according to NCI RECIST v1.0. Results Twenty eight patients were enrolled to six dose levels. Bortezomib 1.6 mg/m2 and dacarbazine 580 mg/m2 are the recommended phase II weekly doses. The combination was generally well tolerated. Among 15 patients with melanoma there was one durable complete response in a patient with an exon-11 cKIT mutation, and one partial response. Among 12 patients with soft tissue sarcoma there was one partial response. Conclusions Bortezomib 1.6 mg/m2 and dacarbazine 580 mg/m2 administered intravenously once weekly is well tolerated and has at least minimal activity in melanoma and soft tissue sarcoma.

OBJECTIVE To evaluate outcomes of robot-assisted sacrocolpopexy (RSCP) and sacrocervicopexy (RCSP). METHODS We conducted a prospective study of women undergoing RSCP or RCSP between June 2008 and January 2010. RESULTS A total of 85 cases (48 RSCP and 37 supracervical hysterectomy with concomitant RCSP) were performed: 33% (28/85) for stage II, 54% (46/85) for stage III, and 13% (11/85) for stage IV pelvic organ prolapse (POP). Six weeks postoperatively, 96% (80/83) had stage 0, 2.4% (2/83) had stage I, and 1.2% (1/83) had stage II POP (P < 0.001). Six months postoperatively, 77% (24/31) had stage 0, 6.5% (2/31) had stage I, and 16% (5/31) had stage II POP (P < 0.001). Mean surgical time, estimated blood loss, and length of hospital stay was 194 ± 54 minutes, 49 ± 48 cm, and 1.6 ± 0.72 days, respectively. There were 2 cases of mesh erosion (2.3%), both in the RSCP group. CONCLUSIONS RSCP and RCSP are effective, efficient, and safe procedures.

Objective: The purpose of this study was to identify risk factors associated with transfusion in women undergoing hysterectomy for benign disease. Methods: A retrospective chart review of women undergoing hysterectomy between June 2007 and July 2009 was conducted. Demographic data, pre- and postoperative hemoglobin (g/dL) values, surgical indication, estimated blood loss (EBL), route of hysterectomy, uterine weight, and perioperative complications were recorded from a departmental surgical database and electronic medical records. A logistic regression analysis was performed to identify independent risk factors for intra- and postoperative blood transfusion. Results: A total of 377 women were included. The overall rate of transfusion was 6.6%. On univariate analysis, the transfusion group had a significantly lower mean age (41.7 versus 44.8, p=0.03), lower pre- (9.28 versus 12.1, p

Purpose: A phase I study was conducted to determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) for the combination of bortezomib and alvocidib in patients with B-cell malignancies (multiple myeloma, indolent lymphoma, and mantle cell lymphoma). Experimental Design: Patients received bortezomib by intravenous push on days 1, 4, 8, and 11. Patients also received alvocidib on days 1 and 8 by 30-minute bolus infusion followed by a 4-hour continuous infusion. Treatment was on a 21-day cycle, with indefinite continuation for patients experiencing responses or stable disease. Dose escalation employed a standard 3 + 3 design until the MTD was identified on the basis of DLTs. Pharmacokinetic studies and pharmacodynamic studies were conducted. Results: Sixteen patients were treated. The MTD was established as 1.3 mg/m2 for bortezomib and 30 mg/m2 for alvocidib (both the 30-minute bolus and 4-hour infusions). Common hematologic toxicities included leukopenia, lymphopenia, neutropenia, and thrombocytopenia. Common nonhematologic toxicities included fatigue and febrile neutropenia. DLTs included fatigue, febrile neutropenia, and elevated aspartate aminotransferase (AST) levels. Two complete responses (CR; 12%) and five partial responses (PR; 31%) were observed at the MTD (overall response rate = 44%). Pharmacokinetic results were typical for alvocidib and pharmacodynamic studies yielded variable results. Conclusions: The combination of bortezomib and alvocidib is tolerable and an MTD has been established for the tested schedule. The regimen appears active in patients with relapsed and/or refractory multiple myeloma or non–Hodgkin's lymphoma, justifying phase II studies to determine the activity of this regimen more definitively. Clin Cancer Res; 17(10); 3388–97. ©2011 AACR.

Context. Chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting and persistent consequence of numerous classes of antineoplastic agents, affecting up to 30%e40% of patients. To date, there is no effective prevention or therapy. An evolving hypothesis for reducing CIPN pain involves direct nerve stimulation to reduce the pain impulse. Objectives. To evaluate the impact on CIPN associated with the MC5-A Calmare therapy device (Competitive Technologies, Inc. Fairfield, CT). Methods. The MC5-A Calmare therapy device is designed to generate a patient-specific cutaneous electrostimulation to reduce the abnormal pain intensity. Sixteen patients from one center received one-hour interventions daily over 10 working days. Results. Of 18 patients, 16 were evaluable. The mean age of the patients was 58.6 yearsdfour men and 14 womendand the duration of CIPN was three months to eight years. The most common drugs were taxanes, platinums, and bortezomib (Velcade, Millenium Pharmaceuticals, Cambridge MA). At the end of the study (Day 10), a 20% reduction in numeric pain scores was achieved in 15 of 16 patients. The pain score fell 59% from 5.81 � 1.11 before treatment to 2.38 � 1.82 at the end of 10 days (P < 0.0001 by paired t-test). A daily treatment benefit was seen with a strong statistically significant difference between the preand post-daily pain scores (P < 0.001). Four patients had their CIPN reduced to zero. A repeated-measures analysis using the scores from all 10 days confirmed these results. No toxicity was seen. Some responses have been durable without maintenance. Conclusions. Patient-specific cutaneous electrostimulation with the MC5-A Calmare device appears to dramatically reduce pain in refractory CIPN patients with no toxicity. Further studies are underway to define the benefit, mechanisms of action, and optimal schedule. J Pain Symptom Manage 2010;-:-e-. 2010 Published by Elsevier Inc on behalf of U.S. Cancer Pain Relief Committee.

Introduction Family history of prostate cancer is an established risk factor for prostate cancer. However, the relationship between family history of cancers other than prostate cancer and prostate cancer risk is inconclusive. This study sought to examine the association between family history of cancers and prostate cancer. Methods A case–control study was conducted in which cases and controls were randomly selected from a large urology clinic in Central Virginia. Cases were 600 histologically confirmed prostate cancer patients who were diagnosed between January 2000 and December 2005, and controls were 686 patients who visited the clinic during the same period and were diagnosed with urological illnesses other than cancers and prostate-related problems. Data on family history of cancers, lifestyle and demographic factors were collected through mail survey utilizing the method suggested by Dillman. Unconditional logistic regression analysis was used to estimate the odds ratios (OR) and the corresponding 95% confidence intervals (CI) after adjustment for potential confounding factors including body mass index (BMI), alcohol intake, physical activity, smoking, diet, history of vasectomy and sexually transmitted disease (STD), age, race, marital history, education, and income. Multiple comparisons adjustments were made using the Bonferroni adjustment. Results Men with a family history of any cancer in first-degree relatives including parents (OR = 2.42, 95% CI = 1.53–3.84) and parents only (OR = 1.90, 95% CI = 1.23– 2.94) were at increased risk of developing prostate cancer. Significant increased risk was also observed with family history of prostate cancer in first-degree relatives (OR = 2.68, 95% CI = 1.53–4.69) and parents only (OR = 3.26, 95% CI = 1.71–6.24). Even after adjustments for multiple comparisons, the significance persisted both in first-degree relatives (OR = 2.68, 95% CI = 1.16–6.21) and parents alone (OR = 3.26, 95% CI = 1.24– 8.63). Conclusion This study demonstrated an increased prostate cancer risk for men with a family history of any cancer or prostate cancer in first-degree relatives and parents alone. Health care providers need to be aware of the potential risk of family history of cancers on prostate cancer.

Purpose Many seriously ill patients with cancer do not discuss prognosis or advance directives (ADs), which may lead to inappropriate and/or unwanted aggressive care at the end of life. Ten years ago, patients with cancer said they would not like to discuss ADs with their oncologist but would be willing to discuss them with an admitting physician. We assessed whether this point of view still held. Patients and Methods Semi-structured interviews were conducted with 75 consecutively admitted patients with cancer in the cancer inpatient service. Results Of those enrolled, 41% (31 of 75) had an AD. Nearly all (87%, 65 of 75) thought it acceptable to discuss ADs with the admitting physician with whom they had no prior relationship, and 95% (62 of 65) thought that discussing AD issues was very or somewhat important. Only 7% (5 of 75) had discussed ADs with their oncologist, and only 23% (16 of 70) would like to discuss ADs with their oncologist. When specifically asked which physician they would choose, 48% (36 of 75) of patients would prefer their oncologist, and 35% (26 of 75) would prefer their primary care physician. Conclusion Fewer than half of seriously ill patients with cancer admitted to an oncology service have an AD. Only 23% (16 of 70) would like to discuss their ADs with their oncologist but nearly all supported a policy of discussing ADs with their admitting physician. However, fully 48% (36 of 75) actually preferred to discuss advance directives with their oncologist if AD discussion was necessary. We must educate patients on why communicating their ADs is beneficial and train primary care physicians, house staff, hospitalists, and oncologists to initiate these difficult discussions.

Introduction: The primary goal of stereotactic systems in deep brain stimulation (DBS) surgery is accurate delivery of a DBS lead to a target identified on imaging. Thus, it is critical to understand the accuracy of the stereotactic systems and the factors which may be associated with a decrease in accuracy. Methods: Ninety patients underwent microelectrode recording-guided placement of 139 DBS leads by a single surgeon using the Cosman-Roberts-Wells (CRW) frame (n = 70) or a frameless skull-mounted trajectory guide (Nexframe; n = 69). The final DBS location was identified on a postoperative CT fused to the preoperative CT and MRI scans. The difference between this final location and the expected location was calculated. Results: The vector error was 2.65 mm (standard error, 0.22) for the frame and 2.78 mm (standard error, 0.25) for the frameless methods (p = 0.69). There was a gradual decline in error for both systems over time, as the vector error of the last 20 implants was 1.99 for the CRW frame and 2.04 for the Nexframe (p = 0.86). Conclusions: This study shows that the CRW frame and Nexframe frameless systems have equivalent accuracy. Furthermore, the accuracy of both techniques improved over time, from 3 mm initially to 2 mm with current techniques.

SUMMARY Videotapes of ten children with ‘suspected’ cerebral palsy were used as stimuli to elicit physicians' decisions regarding referral for physical therapy. Respondents were 99 developmental or general pediatricians, orthopaedists, neurologists or physiatrists who were membes of the American Academy of Pediatrics or the American Academy of Cerebral Palsy. They rated their belief in the value of therapy; described their exprience, training and practices relating to management of cerebral palsy; and responded to cases with their assessment of severity, diagnosis and referral decision. The decision to refer was significantly related to perceived severity of the condition, diagnostic certainty, and beliefe in the efficacy of physical therapy. Referral rates did not vary with tendency to use physical therapy for other types of patients, nor with training, experience or self-rated expertise in cerebral palsy. RESUME Correlations sur les decisions des medecins de demander une reeducation kinesitherapique chez les enfants IMC Des enregistrements video de dix enfants avec suspicion d'IMC ont ete utilises pour provoquer les decisions de medecins concernant l'opportunite d'une reeducation kinesitherapique. Les personnes etudiees etaient 99 pediatres generaux ou specialises dans le devoloppement, chirurgiens orthopediques, neurologues ou psychiatres membres de l'Amcrican Academy of Pediatrics ou de l'American Academy of Cerebral Palsy. Iis evaluaient leur croyance dans l'interet de la reeducation. decrivaient leur experience, formation et pratique dans l'approche de l'IMC et jugeaient les cas en termes de gravite, de diagnostic et de decision de reeducation. Cette derniere decision etait liee a une perception de gravite, une certitude de diagnostique et une croyance dans l'efficacite de la reeducation. Les taux de decision ne variaient pas avec la tendance a faire appel a la reeducation pour d'autres types de patients, avec la formation, l'expeerience ou une auto-evaluation de competence en IMC. ZUSAMMENFASSUNG Grunde fur die arztliche Entscheidung, Kinder mil Cerebralparese zur Physiotherapie zu uberweisen Von 10 Kindern mit “Verdachf auf Cerebralparese wurden Videotapes benutzt, um arztliche Entscheidungen hinsichtlich einer Verordnung von Physiotherapie zu uberprufen. Die Ansprechpartner waren 99 Entwicklungs- oder Allgemeinpadiater, Orthopaden, Neurologen oder Naturhcilkundler, die Milglicdcr der American Academy of Pediatrics oder der American Academy of Cerebral Palsy waren. Sie begrundeten ihr Vertrauen in den Wert der Therapie; beschrieben ihre Erfahrung, Ausbildung und Praxis bei der Behandlung der Cerebralparese; und nahmen Sleliung zu Fallen durch Beurteilung des Schweregrades, der Diagnose und der Uberweisungsentscheidung. Die Entscheidung fur eine Uberweisung korrelierte signifikant mit dem Schweregrad der Erkrankung, der Sicherheit der Diagnose und dem Vertrauen auf den Erfolg der Physiotherapie. Die Uberweisungsraten anderten sich weder mit der Tendenz die physikalische Therapie fur andere Patientengruppen zu nutzen, noch mit der Ausbildung, Erfahrung oder Sachkenntnis fur Cerebralparese. RESUMEN Correlaciones de las decisiones de los medicos para enviar a fisioterapia a ninos con paralisis cerebral Las gravaciones de video de diez ninos ‘sospechosos’ de padecer paralisis cerebral fueron usados como estimulos para elicitar las decisiones de los medicos con respecto a enviarlos a sesiones de fisioterapia. Los que respondieron eran 99 pediatras generates o especialistas en el desarrollo, ortopedistas, neurologos o psiquiatras miembros de la Academia Americana de Pediatria o de la Academia Americana de Paralisis Cerebral. Valoraron su creencia en el valor de la terapia, describieron su experiencia, entrenamiento y practica, en relacion con el manejo de la paralisis cerebral y respondieron a los casos con su evaluacion sobre la gravedad, diagnostico y la decision de mandar al nino a fisioterapia. La decision del envio estaba significativamente relacionada a la evidente gravedad del caso, la certeza diagnostica y la creencia en la eficacia de la terpeutica fisica. El porcentaje de envios no variaba con la tendencia a utilizar la fisioterapia en otros tipos de pacientes, ni con el entrenamiento, experiencia y autovaloracion de la propia capacidad en el campo de la paralisis cerebral.

Background: To investigate the existence of a selection bias using a virtual radiotherapy dose-escalation trial. In dose-escalation trials, normal tissue constraints generally remain constant while the tumor dose is increased. Since tumor dose and normal tissue constraints are competing demands, a point will be reached at which the tumor dose cannot be increased without exceeding normal tissue constraints. Methods and Materials: In 9 patients with non–small-cell lung cancer, the tumor dose was escalated from 66 Gy to 78 Gy in 4-Gy dose levels using intensity-modulated radiotherapy planning, while the limiting normal tissue dose contraints remained constant. Dosimetric, radiobiologic, and other planning parameters were compared at the 66-Gy dose level for patients eligible for all dose levels and for those eligible only for lower dose levels. Results: Seven of 9 patients were eligible for all dose levels (Group E). Two of 9 patients ("ineligible" or Group I) qualified only for lower total doses (95% confidence interval, 0.075–0.6, significant). In Group E, mean planning target volumes were smaller (132 vs. 404 cm 3 , nonsignificant), monitor units per fraction were significantly lower (448 vs. 802, p = 0.0008), and the average composite score for plan quality was better than in Group I (0.012 vs. 0.068, nonsignificant). Average tumor-control probabilities were higher (0.33 vs. 0.23, nonsignificant), and normal tissue-complication probabilities were lower for Group E than for Group I. Conclusions: Patients eligible for higher dose levels had significantly superior estimated outcome parameters. A method to eliminate this source of error in the interpretation of dose-escalation trials is suggested.

The National Institutes of Health F series of training and fellowship grants provides graduate students with opportunities to demonstrate their potential as current and future researchers. Submitting a grant application provides excellent experience in the proposal writing, submission, and review processes, which is particularly important for graduate students pursuing academic careers. This article is intended to familiarize students with the grant application process and focuses on funding mechanisms available through the National Institutes of Health. We provide a detailed overview of the application process, including research proposal preparation and application submission. The review procedure is described, and we address the process for revising and resubmitting an application.

We report results of a randomized, double-blind, placebo-controlled, within-subject study (n = 8) to determine the ability of cocaethylene to modulate acute responses to cocaine and identify significant pharmacokinetic interactions between cocaine and cocaethylene. Stable plasma cocaethylene concentrations (0, 50, or 200 ng/ml) were maintained for 840 minutes. Cocaine (0, 0.25, or 0.5 mg/kg) was injected over 1 minute after 240 minutes of cocaethylene. Blood samples, subjective, and physiological measures were collected. No differences over baseline responses were observed following 240 minutes of a steady state cocaethylene infusion for cardiovascular or subjective responses. "Rush" duration following a cocaine challenge (0.5 mg/kg) declined when administered during the course of a 200 ng/mL cocaethylene infusion. (p = 0.01). No pharmacokinetic interaction occurred when cocaine was administered in conjunction with cocaethylene. Findings indicate that continuous 8-hour exposure to cocaethylene is safe, produces acute tolerance to itself, and reduces some behavioral effects of coadministered cocaine. Agonist substitution therapy may have potential as an alternative treatment for cocaine dependence.

Introduction Preclinical and human laboratory research suggests that (a) progesterone may decrease drug reward, craving, and smoking behavior, and (b) estradiol may enhance drug reward and smoking behavior. A modest majority of treatment research examining the relationship between menstrual cycle phase and outcomes suggests that the luteal menstrual phase, with its uniquely higher progesterone levels, is associated with better cessation outcomes. However, no studies to date have examined the effects of naturally occurring variation in progesterone and estradiol levels on medication-assisted smoking cessation. The present study sought to fill this notable gap in the treatment literature. Methods Weekly plasma progesterone and estradiol levels were obtained from nicotine-dependent female smokers enrolled in a 4-week cessation trial. Participants (N = 108) were randomized to receive a 4-week course of either varenicline (VAR) tablets and placebo patches or placebo tablets and nicotine patches. Plasma samples were obtained 1 week before their cessation attempt and weekly during medication administration. Abstinence was assessed weekly. Results Weekly hormone data replicated commonly observed menstrual cycle patterns of progesterone and estradiol levels. Importantly, increases in progesterone level were associated with a 23% increase in the odds for being abstinent within each week of treatment. This effect was driven primarily by nicotine patch-treated versus VAR-treated females. Conclusions This study was the first to identify an association between progesterone level (increasing) and abstinence outcomes in free-cycling women smokers who participated in a medication-based treatment. Furthermore, the potential benefits of progesterone may vary across different pharmacotherapies. Implications of these findings for smoking cessation intervention are discussed.