Microvascular changes in Down syndrome with Alzheimer's-type pathology: Insights into a potential vascular mechanism for Down syndrome and Alzheimer's disease.

INTRODUCTION: The mechanism triggering degeneration in Alzheimer's disease (AD) remains uncertain. Therapeutic failure following amyloid ß (Aß) removal casts doubt on amyloid neurotoxicity per se as the primary cause of AD. Impaired microvascular function has been suggested as an alternative etiology. People with Down syndrome (DS) develop Alzheimer's pathology, but whether microvascular impairment also occurs in DS (as in AD) is unknown. METHODS: We examined brain microvasculature in five DS subjects with AD-type histopathology, seven AD cases, and seven controls without AD-type pathology. We counted microvessels in five anatomic regions and assessed endothelial integrity by CD31 immunohistochemistry. RESULTS: Microvascular numbers and endothelial integrity were significantly diminished in DS brains compared with controls and were similar to AD brains. DISCUSSION: People with DS and trisomy 21 produce a large amount of Aß. If Alzheimer's pathology occurred in DS without microvascular loss or endothelial impairment, a direct neurotoxic Aß mechanism would be supported and microvascular impairment rejected. The observation of microvascular impairment in DS with Alzheimer's disease changes fails to reject the microvascular hypothesis and provides some support for this potential mechanism of injury.

The use of a kiosk-model bilingual self-triage system in the pediatric emergency department.

BACKGROUND: Streamlining the triage process is the key in improving emergency department (ED) workflow. Our objective was to determine if parents of pediatric ED patients in, low-literacy, inner-city hospital, who used the audio-assisted bilingual (English/Spanish) self-triage kiosk, were able to enter their child's medical history data using a touch screen panel with greater speed and accuracy than routine nurse-initiated triage. METHODS: Parent/child dyads visiting the pediatric ED for nonurgent conditions (February to April 2012) were randomized prospectively to self-triage kiosk group (n = 200) and standard nurse triage group (n = 200). Both groups underwent routine nurse-initiated triage that included verbal elicitation of basic medical history and manual entry into patients' electronic medical records. RESULTS: The kiosk user was a parent in 88.5% of the cases, a patient (range, 11-17 years) in 9.5% of the cases, and a proxy user (sibling or friend) in 2% of the cases. Language choice for kiosk use was equally distributed (English vs Spanish, 50.5% vs 49.5%). The mean (SD) time to enter medical history data by the kiosk group was significantly shorter than the standard nurse triage group (94.38 [38.61] vs 126.72 [62.61] seconds; P < 0.001). Significant inverse relationship was observed between parent education level and kiosk usage time (r = -0.26; P < 0.001). The mean inaccuracies were significantly lower for kiosk group (P < 0.05) in areas of medical, medication and immunization histories, and total discrepancy score. CONCLUSIONS: Kiosk triage enabled users to enter basic medical triage history data quickly and accurately in an ED setting with future potential for its wider use in improving ED workflow efficiency.

The amyloid hypothesis, time to move on: Amyloid is the downstream result, not cause, of Alzheimer's disease.

The "amyloid hypothesis" has dominated Alzheimer research for more than 20 years, and proposes that amyloid is the toxic cause of neural/synaptic damage and dementia. If correct, decreasing the formation or removing amyloid should be therapeutic. Despite discrepancies in the proposed mechanism, and failed clinical trials, amyloid continues to be considered the cause of a degenerative cascade. Alternative hypotheses must explain three features: (i) why amyloid toxicity is not the etiology of Alzheimer's disease (AD), (ii) what alternative mechanisms cause the degeneration and dementia of AD, and (iii) why increased amyloid accumulates in the brain in AD. We propose that AD, which occurs in elderly, already vulnerable brains, with multiple age-related changes, is precipitated by impaired microvascular function, resulting primarily from decreased Notch-related angiogenesis. With impaired microvasculature, a lack of vascular endothelial-derived trophic factors and decreased cerebral blood flow cause the atrophy of neural structures. Therapeutic strategies should focus on supporting normal angiogenesis.

2014 Report on the Milestones for the US National Plan to Address Alzheimer's Disease.

With increasing numbers of people with Alzheimer's and other dementias across the globe, many countries have developed national plans to deal with the resulting challenges. In the United States, the National Alzheimer's Project Act, signed into law in 2011, required the creation of such a plan with annual updates thereafter. Pursuant to this, the US Department of Health and Human Services (HHS) released the National Plan to Address Alzheimer's Disease in 2012, including an ambitious research goal of preventing and effectively treating Alzheimer's disease by 2025. To guide investments, activities, and the measurement of progress toward achieving this 2025 goal, in its first annual plan update (2013) HHS also incorporated into the plan a set of short, medium and long-term milestones. HHS further committed to updating these milestones on an ongoing basis to account for progress and setbacks, and emerging opportunities and obstacles. To assist HHS as it updates these milestones, the Alzheimer's Association convened a National Plan Milestone Workgroup consisting of scientific experts representing all areas of Alzheimer's and dementia research. The workgroup evaluated each milestone and made recommendations to ensure that they collectively constitute an adequate work plan for reaching the goal of preventing and effectively treating Alzheimer's by 2025. This report presents these Workgroup recommendations.

Evaluating the utility, reliability, and validity of a resident performance evaluation instrument.

OBJECTIVE: The primary goal of this project was to create and evaluate the utility, validity, and reliability of an instrument assessing resident performance during child and adolescent psychiatry (CAP) training. In three stages, the instrument was developed and evaluated for utility in assessing skills critical to CAP. Items on the Global Assessment Evaluation (GAE) were derived from the six core competencies identified by the American College of Graduate Medical Education (ACGME). Secondary goals included producing an instrument that could be used by other CAP training programs and describing a process that could be followed by training programs to create their own assessment instruments. METHODS: Faculty members developed a CAP resident performance evaluation instrument. In a three-stage process, faculty utilized the tool to evaluate residents during and after rotations. Statistical findings guided revisions to improve the utility and reliability of the instrument. For the final version of the GAE, intra-class correlation coefficients were calculated to assess inter-rater reliability, and Principal Components Analysis provided further insight into the dimensions of resident assessment. RESULTS: The final version of the GAE showed overall and construct validity by capturing significant differences among residents and matched faculty members' overall impressions of resident performance. Intra-class correlation coefficient values for the overall score (0.945) and individual scales showed good reliability. Resident performance was not correlated with rotation site or model of care. CONCLUSIONS: The GAE has proved a valuable instrument in tracking the progress, strengths, and weaknesses in resident performance over the course of training. Data from multiple evaluations over time provide useful information about resident performance in a way that one or few evaluations does not. This finding is consistent with the practice of semiannual reviews and the new Clinical Competency Committees, both of which are required by the ACGME.

Clinical outcomes of pediatric patients with acute abdominal pain and incidental findings of free intraperitoneal fluid on diagnostic imaging.

OBJECTIVES: The presence of free intraperitoneal fluid on diagnostic imaging (sonography or computed tomography [CT]) may indicate an acute inflammatory process in children with abdominal pain in a nontraumatic setting. Although clinical outcomes of pediatric trauma patients with free fluid on diagnostic examinations without evidence of solid-organ injury have been studied, similar studies in the absence of trauma are rare. Our objective was to study clinical outcomes of children with acute abdominal pain of nontraumatic etiology and free intraperitoneal fluid on diagnostic imaging (abdominal/pelvic sonography, CT, or both). METHODS: We conducted a retrospective review of medical records of children aged 0 to 18 years presenting to a pediatric emergency department with acute abdominal pain (nontraumatic) between April 2008 and March 2009. Patients with intraperitoneal free fluid on imaging were divided into 2 groups: group I, imaging suggestive of an intra-abdominal surgical condition such as appendicitis; and group II, no evidence of an acute surgical condition on imaging, including patients with equivocal studies. Computed tomograms and sonograms were reviewed by a board-certified radiologist, and the free fluid volume was quantitated. RESULTS: Of 1613 patients who underwent diagnostic imaging, 407 were eligible for the study; 134 (33%) had free fluid detected on diagnostic imaging. In patients with both sonography and CT, there was a significant correlation in the free fluid volume (r = 0.79; P < .0005). A significantly greater number of male patients with free fluid had a surgical condition identified on imaging (57.4% versus 25%; P < .001). Children with free fluid and an associated condition on imaging were more likely to have surgery (94.4% versus 6.3%; P < .001). CONCLUSIONS: We found clinical outcomes (surgical versus nonsurgical) to be most correlated with a surgical diagnosis on diagnostic imaging and not with the amount of fluid present.

Use of a silver-containing hydrofiber dressing for filling abscess cavity following incision and drainage in the emergency department: a randomized controlled trial.

OBJECTIVE: The objective of this study was to investigate whether the use of a silver-containing hydrofiber dressing to pack abscess cavity after incision and drainage (I & D) leads to faster wound healing and less pain. METHODS: Patients 18 years or older visiting the emergency department with cutaneous abscesses, requiring I & D, were randomly assigned to the intervention (Aquacel Ag; ConvaTec, Skillman, New Jersey) or standard care (iodoform) group between April 2008 and May 2009. Patients were followed up 48 to 72 hours and 10 to 14 days after the initial visit. Primary outcomes were the proportion of patients with greater than 30% reduction in surface area of abscess or cellulitis at first follow-up. RESULTS: Ninety-two patients were enrolled prospectively and randomly assigned to the Aquacel Ag or the iodoform groups; mean age was 38.0 (SD, 12.0) years; 49 patients were in the Aquacel Ag and 43 were in iodoform groups, respectively. There were no differences in demographic and clinical characteristics between groups. Logistic regression analysis showed that the intervention (Aquacel Ag) was independently associated with greater than 30% reduction in surface area of abscess (P = .002) but not in cellulitis at first follow-up. There was also significant decrease in pain intensity perceived by patients in the Aquacel Ag group based on the mean change in Facial Pain Scale scores between the initial visit and first follow-up. CONCLUSION: In patients with cutaneous abscesses, use of an antimicrobial hydrofiber ribbon dressing for packing was associated with faster wound healing and reduction in perceived pain in comparison with use of iodoform dressing.

Repeat operation for treatment of persistent pudendal nerve entrapment after pudendal neurolysis.

STUDY OBJECTIVES: To describe a new approach to transgluteal pudendal neurolysis and transposition and to review the outcome in 10 patients who underwent repeat operation because of persistent pudendal neuralgia after failing to improve after initial surgical decompression. DESIGN: Retrospective analysis (Canadian Task Force classification II-3). SETTING: Academic chronic pelvic pain practice at St. Joseph's Hospital and Medical Center in Phoenix, Arizona. PATIENTS: Women and men with persistent pudendal neuralgia after undergoing transgluteal pudendal neurolysis and transposition. INTERVENTION: Transgluteal decompression of the pudendal nerve was performed in all 10 patients. In brief, a transgluteal incision was made, and the pudendal nerve was identified via a nerve integrity monitoring system. Adhesiolysis was performed from the piriformis muscle to the distal Alcock canal using a Zeiss NC-4 surgical microscope. The nerve was then enclosed in NeuraWrap Nerve Protector and coated with activated platelet-rich plasma. An ON-Q PainBuster catheter was place along the nerve into the Alcock canal, and 0.5% bupivacaine was infused at 2 mL/hr. The sacrotuberous ligament was repaired using an Achilles or gracillis cadaver ligament. The overlying subcutaneous tissue and skin were then closed. MEASUREMENTS AND MAIN RESULTS: From June 2008 to March 2010, 10 consecutive patients (7 women and 3 men; age range, 29-81 years) underwent repeat operation with transgluteal decompression of the pudendal nerve. Neuropathic pain was unilateral (n = 8) or bilateral (n = 2), in the clitoris or penis (30%), vulva or scrotum (70%), perineum (40%), and rectum (50%). Of the 10 patients, 1 patient was lost to follow-up. Mean follow-up was 23 months. Eight of 9 patients reported global improvement, with 2 patients reporting complete resolution of symptoms. One patient reported no change. Pain, as measured using an 11-point numerical scale, improved from a mean of 7.2 to 4.0 (p = .02), with 5 patients reporting clinically significant improvement (change, ≥2). Comfortable sitting or maximum time that the patient was able to sit without exacerbation of pain improved in 8 patients, with a change in median time of 5 to 45 minutes (p = .008). Change in the ability to sit correlated well with patient-reported global improvement (correlation coefficient, 0.86). No patient experienced worsening of symptoms. CONCLUSION: Patients with persistent pudendal neuralgia after surgical decompression may benefit from repeat operation via our novel approach. Ability to sit correlates well with reported improvement due to surgery.

Cumulative effect of simvastatin, L-arginine, and tetrahydrobiopterin on cerebral blood flow and cognitive function in Alzheimer's disease.

BACKGROUND AND OBJECTIVES: Vascular disease is a known risk factor for Alzheimer's disease (AD). Endothelial dysfunction has been linked to reduced cerebral blood flow. Endothelial nitric oxide synthase pathway (eNOS) upregulation is known to support endothelial health. This single-center, proof-of-concept study tested whether the use of three medications known to augment the eNOS pathway activity improves cognition and cerebral blood flow (CBF). METHODS: Subjects with mild AD or mild cognitive impairment (MCI) were sequentially treated with the HMG-CoA reductase synthesis inhibitor simvastatin (weeks 0-16), L-arginine (weeks 4-16), and tetrahydrobiopterin (weeks 8-16). The primary outcome of interest was the change in CBF as measured by MRI from baseline to week 16. Secondary outcomes included standard assessments of cognition. RESULTS: A total of 11 subjects were deemed eligible and enrolled. One subject withdrew from the study after enrollment, leaving 10 subjects for data analysis. There was a significant increase in CBF from baseline to week 8 by ~13% in the limbic and ~15% in the cerebral cortex. Secondary outcomes indicated a modest but significant increase in the MMSE from baseline (24.2±3.2) to week 16 (26.0±2.7). Exploratory analysis indicated that subjects with cognitive improvement (reduction of the ADAS-cog 13) had a significant increase in their respective limbic and cortical CBF. CONCLUSIONS: Treatment of mild AD/MCI subjects with medications shown to augment the eNOS pathway was well tolerated and associated with modestly increased cerebral blood flow and cognitive improvement. TRIAL REGISTRATION: This study is registered in https://www. CLINICALTRIALS: gov ; registration identifier: NCT01439555; date of registration submitted to registry: 09/23/2011; date of first subject enrollment: 11/2011.

Pulmonary embolism at CT angiography: implications for appropriateness, cost, and radiation exposure in 2003 patients.

PURPOSE: To determine whether thromboembolic risk factor assessment could accurately indicate the pretest probability for pulmonary embolism (PE), and if so, computed tomographic (CT) angiography might be targeted more appropriately than in current usage, resulting in decreased costs and radiation exposure. MATERIALS AND METHODS: Institutional review board approval was obtained. Electronic medical records of 2003 patients who underwent CT angiography for possible PE during 1(1/2) years (July 2004 to February 2006) were reviewed retrospectively for thromboembolic risk factors. Risk factors that were assessed included immobilization, malignancy, hypercoagulable state, excess estrogen state, a history of venous thromboembolism, age, and sex. Logistic regressions were conducted to test the significance of each risk factor. RESULTS: Overall, CT angiograms were negative for PE in 1806 (90.16%) of 2003 patients. CT angiograms were positive for PE in 197 (9.84%) of 2003 patients; 6.36% were Emergency Department patients, and 13.46% were inpatients. Of the 197 patients with CT angiograms positive for PE, 192 (97.46%) had one or more risk factors, of which age of 65 years or older (69.04%) was the most common. Of the 1806 patients with CT angiograms negative for PE, 520 (28.79%) had no risk factors. The sensitivity and negative predictive value of risk factor assessment in all patients were 97.46% and 99.05%, respectively. All risk factors, except sex, were significant in the multivariate logistic regression (P < .031). CONCLUSION: In the setting of no risk factors, it is extraordinarily unlikely (0.95% chance) to have a CT angiogram positive for PE. This selectivity and triage step should help reduce current costs and radiation exposure to patients.

Is computed tomography a reliable diagnostic modality in detecting placental injuries in the setting of acute trauma?

OBJECTIVE: The objective of this study was to determine whether computed tomography (CT) is a reliable method of imaging to assess placental injury after acute trauma during pregnancy. STUDY DESIGN: This study was a retrospective review of digital CT images and electronically scanned charts of pregnant trauma patients identified from the hospital trauma registry list. RESULTS: Using delivery within 36 hours of trauma as the clinical marker for the occurrence of placental abruption, positive radiologic readings showed 86% sensitivity and 98% specificity. The overall accuracy was 96%. CONCLUSION: Given that defined patterns on CT can be identified and those can be correlated to actual abruption, CT may be a reliable method for evaluation of placental abruption after maternal trauma, especially in the face of abdominal trauma. Our results show that CT has both good sensitivity and specificity identifying abruption and should be considered for use in the management in the pregnant patient after trauma.

Ultrasound guidance for central venous catheter placement: results from the Central Line Emergency Access Registry Database.

BACKGROUND: Ultrasound guidance of central venous catheter (CVC) insertion improves success rates and reduces complications and is recommended by several professional and regulatory organizations. METHODS: This is a prospective observational study using data extracted from the Central Line Emergency Access Registry database, a multicenter online registry of CVC insertions from medical centers throughout the United States. We compared success rates with ultrasound and with the anatomic-landmark technique. RESULTS: A total of 1250 CVC placement attempts by emergency medicine residents during the study period were selected from the Central Line Emergency Access Registry database. Because a few attempts (n = 28) were made to place lines in either the left or right supraclavicular locations, data on these attempts were eliminated from the analysis. A total of 1222 CVC attempts from 5 institutions were analyzed. Successful placement on the first attempt occurred in 1161 (86%) cases and varied according to anatomic location. Ultrasound guidance was used in 478 (41%) of the initial attempts. The remainder of placements were presumably placed using the anatomic-landmark technique based on visible surface and palpatory subcutaneous structures. Overall successful placement rate did not vary according to the use of ultrasound guidance, nor did it vary at different anatomic sites. However, ultrasound was found to be significant for reducing the total number of punctures per attempt (P < .02, t = 2.30). CONCLUSIONS: Our study did not observe improved success with the use of ultrasound for CVC cannulation on the first attempt, but we did observe a reduced number of total punctures per attempt.

Transient tachypnea of the newborn: is labor prior to cesarean delivery protective?

Transient tachypnea of the newborn (TTN) is a common respiratory problem in newborns. This study aims to determine if cesarean delivery (CD) is a risk factor for TTN, and if labor prior to CD decreases this risk. A linked data set consisting of Arizona birth certificates (1994 to 1998) and infants enrolled in a high-risk perinatal program provided 800 TTN cases and 800 controls, stratified by year. The relationships of CD and labor to TTN were examined using logistic regression. CD was associated with an increased risk of TTN, whether it was accompanied by labor (odds ratio [OR] 2.68; 95% confidence interval [CI] 1.62 to 4.45) or not accompanied by labor (OR 2.88; 95% CI 2.01 to 4.13), even after adjusting for confounding variables. Labor did not affect the development of TTN, nor did it modify the association of CD with increased risk for TTN. CD is a risk factor for TTN. Labor prior to CD is not protective for TTN.

Knowledge and attitudes regarding preconception care in a predominantly low-income Mexican American population.

OBJECTIVE: The objective of the study was to determine knowledge and attitudes regarding preconception care in a low-income Mexican American population. STUDY DESIGN: This was a cross-sectional survey of 305 reproductive-age women at an urban public hospital. RESULTS: The sample was mostly Hispanic (88%) and pregnant (68%); 35% had not completed high school. Eighty-nine percent agreed that improving preconception health benefits pregnancy. Seventy-seven percent expressed some interest in preconception health care with the obstetrics gynecology office at the preferred location. The average knowledge of preconception care score was 76% (higher score more favorable). Areas of higher knowledge included the effects on pregnancy of folic acid; alcohol use; substance use; and verbal, physical, and sexual abuse; lower knowledge was found for the effects of cat litter and fish products. CONCLUSION: There was interest in preconception education and agreement that preconception health has a positive effect on pregnancy. Fewer respondents agreed that it had a good effect than a suburban sample in the same region (89% vs 98%).

Nulliparous term singleton vertex cesarean delivery rates: institutional and individual level predictors.

OBJECTIVE: This study was undertaken to determine individual and institutional level variables predictive of variations in nulliparous term singleton vertex cesarean delivery rates. STUDY DESIGN: Retrospective cohort study of 28,863 nulliparous term singleton vertex births at 40 Arizona hospitals. RESULTS: The average nulliparous term singleton vertex cesarean delivery rate was 22.0%, the lowest hospital rate was 10.3%, high, 34.2%. The following individual level variables increased the nulliparous term singleton vertex cesarean delivery rate in a multivariable model: increased mother's age, African American race, increased birthweight, labor induction, and the presence of medical conditions such as diabetes and hypertension. Of the institutional variables, after adjustment, the highest level of nursery or a higher percentage of government-paid births was associated with lower risks, whereas delivery at a hospital with the lowest level of care or with an obstetric and gynecology residency was associated with an increased risk of cesarean delivery. CONCLUSION: Substantial variations in nulliparous term singleton vertex cesarean delivery rates were seen in this comparative analysis of 40 hospitals.

The relationship of plasma glucose and glycosylated hemoglobin A1C levels among nondiabetic trauma patients.

OBJECTIVE: : Hyperglycemia (blood glucose >/=110 mg/dL) in trauma patients without a known history of diabetes mellitus (DM) is often attributed to the metabolic stress response of injury. We studied whether this hyperglycemia may actually indicate the presence of occult DM (ODM) as demonstrated by elevated glycosylated hemoglobin A1C (gHbA1C). METHODS: : After obtaining approval from the Institutional Review Board, a prospective, sequential case series study of nondiabetic adult patients presenting to an urban Level I trauma center from September 2006 to February 2007 was performed. In addition to basic demographics, all hyperglycemic patients had a measured gHbA1C. ODM was diagnosed when gHbA1C was >/=6%. RESULTS: : A total of 1,039 trauma patients were screened with 192 (18%) noted to be hyperglycemic. Of these 192 patients, 22% (n = 42) were found to have an elevated gHbA1C. Using logistic regression, being older (Odds ratio [OR] = 1.04; p < 0.004), having a higher body mass index (BMI) (OR = 1.12; p < 0.003), and being Native American (OR = 5.08; p < 0.017) were each identified as significant risk factors for elevated gHbA1C levels and the diagnosis of ODM. In contrast, the magnitude of observed hyperglycemia, gender, or other races were not shown to be significant risk factors for the presence of ODM. CONCLUSION: : Almost a quarter of nondiabetic trauma patients presenting with hyperglycemia were found to have elevated gHbA1C levels and ODM. Risk factors for ODM included advancing age and body mass index as well as being Native American. The hyperglycemia seen in trauma patients should not solely be attributed to the hormonal and metabolic response to injury; wider ODM screening for both acute management strategies and long-term health benefits is warranted.

A Randomized, Double-Blind Study of the Effects of a Sustained Release Formulation of Sodium Nitrite (SR-nitrite) on Patients with Diabetic Neuropathy.

BACKGROUND: Sodium nitrite has been reported to be effective in reducing chronic peripheral pain. OBJECTIVES: To evaluate the safety and efficacy of 40 and 80 mg, BID, of an oral sustained release formulation of sodium nitrite (SR-nitrite) in patients suffering from diabetic neuropathy, and to determine whether SR-nitrite would reduce the frequency of headaches reported previously by subjects receiving the same doses of an immediate release formulation. STUDY DESIGN: Phase II, single-center, randomized, double-blind, placebo controlled clinical trial. SETTING: The Ohio Pain Clinic and Kettering Medical Center. METHODS: Twenty-four patients were randomized to 40 mg or 80 mg SR-nitrite or placebo twice daily for 12 weeks. The primary objective was to determine whether headaches would be reduced using SR-nitrite. The primary efficacy endpoint was the mean difference in the change of the Neuropathic Pain Symptom Inventory (NPSI) pain score from baseline to that reported after 12 weeks of treatment. Secondary endpoints included changes from baseline for the Brief Pain Inventory (BPI) Scale, the RAND 36 questionnaire, Short Form McGill Questionnaire, daily patient reported score for neuropathic pain, changes in HbA1c, PulseOx and quantitative sensory testing. RESULTS: The number of subjects reporting adverse events and the number of adverse events did not change with dose. There were no reports of treatment-related headaches. Although no significant differences were identified in patient responses to the questionnaires, a trend was observed. In the NPSI assessment, patients in the 40 mg and 80 mg dose group reported a 12.7% and 22.0% reduction in pain, respectively, compared to an 8.4% reduction by patients in the placebo group. A trend was also observed with the BPI total severity score. However, the 40 mg dosing group reported the greatest reduction in pain using the McGill Pain index and via patient logs of daily pain scores, where the mean of pain scores reported by subjects in the 40 mg group dropped by day 41 and generally stayed lower than the mean of scores reported by subjects in either of the other two groups. Patients in the 80 mg SR-nitrite group had an improvement in both Nerve Sensory Conductance and Nerve Sensory Velocity. No changes were observed in HbA1c levels or PulseOx. LIMITATIONS: Small sample size. CONCLUSION: Sustained release sodium nitrite prevents the prevalent reports of headaches by patients treated with an immediate release formulation of sodium nitrite. In a previous study of patients with peripheral arterial disease (PAD), 40 mg BID treatment led to a statistically significant reduction in reported pain, similar trends were observed at the end of the trial period for most of the pain questionnaires used in the study. The 80 mg BID treatment had the more pronounced affect on bioactivity (quantitative sensory testing), which was similar to the PAD study, where this dose group had the greatest improvement in FMD {AU: spell out FMD}. The ability to alleviate pain with BID treatment of SR-nitrite offers promise for a new non-addictive, non-sedating treatment of chronic pain and warrants further study. KEY WORDS: Diabetes, diabetic neuropathy, neuropathic pain, peripheral neuropathy, sodium nitrite.

Assessment of inpatient psychiatric readmission risk among patients discharged on an antipsychotic polypharmacy regimen: A retrospective cohort study.

OBJECTIVE: Patients are frequently prescribed multiple antipsychotic medications, leading to higher healthcare costs and increased risk for side effects. The efficacy of multiple versus single antipsychotics to prevent acute relapse, measured by incidence of inpatient readmission, is investigated in Arizona, USA. METHOD: A retrospective chart review compared socio-demographic and clinical data from 1,010 patients discharged on a single and 377 discharged on multiple antipsychotic medications. Case management records were reviewed for readmission within one year of discharge. RESULTS: Younger age, diagnosis of Schizophrenia or Schizoaffective Disorder, prescription of mood stabilizer, shorter length of stay, and discharge to residential treatment or crisis recovery unit were associated with multiple antipsychotics at discharge. Readmission rates of the single (13.7%) versus multiple (15.9%) antipsychotic groups were not statistically different (p=0.286). Logistic regression analysis established that only age (younger) and the prescription of a mood stabilizer at discharge were significant predictors for increased risk for readmission (p=0.010 and p=0.049, respectively). A Cox survival analysis supported these findings. CONCLUSIONS: Concomitant antipsychotic polypharmacy at discharge did not reduce readmission risk over a one-year period. Given the increased risk of side effects and financial costs of polypharmacy, this study did not provide evidence to support this practice. Strikingly, only two variables predicted readmission risk, younger age and prescription of mood stabilizer. Although practitioners should follow practice guidelines more closely to prevent unnecessary exposure to potentially lethal side effects of antipsychotic polypharmacy, further studies are needed to better identify patients at high risk for readmission.

Novel ubiquitin neuropathology in frontotemporal dementia with valosin-containing protein gene mutations.

Frontotemporal dementia (FTD) with inclusion body myopathy and Paget disease of bone (IBMPFD) is a rare, autosomal-dominant disorder caused by mutations in the valosin-containing protein (VCP) gene, a member of the AAA-ATPase gene superfamily. The neuropathology associated with sporadic FTD is heterogeneous and includes tauopathies and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). However, there is limited information on the neuropathology in IBMPFD. We performed a detailed, systematic analysis of the neuropathologic changes in 8 patients with VCP mutations. A novel pattern of ubiquitin pathology was identified in IBMPFD that was distinct from sporadic and familial FTLD-U without VCP gene mutations. This was characterized by ubiquitin-positive neuronal intranuclear inclusions and dystrophic neurites. In contrast to FTLD-U, only rare intracytoplasmic inclusions were identified. The ubiquitin pathology was abundant in the neocortex, less robust in limbic and subcortical nuclei, and absent in the dentate gyrus. Only rare inclusions were detected with antibodies to VCP and there was no biochemical alteration in the VCP protein. VCP is associated with a variety of cellular activities, including regulation of the ubiquitin-proteasome system. Our findings are consistent with the hypothesis that the pathology associated with VCP gene mutations is the result of impairment of ubiquitin-based degradation pathways.

Utilization of the propensity score method: an exploratory comparison of proxy-completed to self-completed responses in the Medicare Health Outcomes Survey.

BACKGROUND: This research examined the use of the propensity score method to compare proxy-completed responses to self-completed responses in the first three baseline cohorts of the Medicare Health Outcomes Survey, administered in 1998, 1999, and 2000, respectively. A proxy is someone other than the respondent who completes the survey for the respondent. METHODS: The propensity score method of matched sampling was used to compare proxy and self-completed responses. A propensity score is a value that equals the estimated probability of a given individual belonging to a treatment group given the observed background characteristics of that individual. Proxy and self-completed responses were compared on demographics, the SF-36, chronic conditions, activities of daily living, and depression-screening questions. For each individual survey respondent, logistic regression was used to calculate the probability that this individual belonged to the proxy respondent group (propensity score). Pre and post adjustment comparisons were tested by calculating effect sizes. RESULTS: Differences between self and proxy-completed responses were substantially reduced with the use of the propensity score method. However, differences were still found in the SF-36, several demographics, several impaired activities of daily living, several chronic conditions, and one depression-screening question. CONCLUSION: The propensity score method helped to reduce differences between proxy-completed and self-completed survey responses, thereby providing an approximation to a randomized controlled experiment of proxy-completed versus self-completed survey responses.