Pharmacodynamics and effectiveness of topical nitroglycerin at lowering blood pressure during autonomic dysreflexia.

STUDY DESIGN: Secondary analysis of prospectively collected observational data assessing the safety of an autonomic dysreflexia (AD) management protocol. OBJECTIVES: To estimate the time to onset of action, time to full clinical effect (sustained systolic blood pressure (SBP) <160 mm Hg) and effectiveness of nitroglycerin ointment at lowering blood pressure for patients with spinal cord injuries experiencing AD. SETTING: US Veterans Affairs inpatient spinal cord injury (SCI) unit. METHODS: Episodes of AD recalcitrant to nonpharmacologic interventions that were given one to two inches of 2% topical nitroglycerin ointment were recorded. Pharmacodynamics as above and predictive characteristics (through a mixed multivariate logistic regression model) were calculated. RESULTS: A total of 260 episodes of pharmacologically managed AD were recorded in 56 individuals. Time to onset of action for nitroglycerin ointment was 9-11 min. Time to full clinical effect was 14-20 min. Topical nitroglycerin controlled SBP <160 mm Hg in 77.3% of pharmacologically treated AD episodes with the remainder requiring additional antihypertensive medications. A multivariate logistic regression model was unable to identify statistically significant factors to predict which patients would respond to nitroglycerin ointment (odds ratios 95% confidence intervals 0.29-4.93). The adverse event rate, entirely attributed to hypotension, was 3.6% with seven of the eight events resolving with close observation alone and one episode requiring normal saline. CONCLUSIONS: Nitroglycerin ointment has a rapid onset of action and time to full clinical effect with high efficacy and relatively low adverse event rate for patients with SCI experiencing AD.

Risk factors for community-associated multidrug-resistant Pseudomonas aeruginosa in veterans with spinal cord injury and disorder: a retrospective cohort study.

STUDY DESIGN: Retrospective cohort studyObjectives:To identify independent risk factors associated with community-associated multidrug-resistant Psedomonas aeruginosa (MDRPA) in a population of veterans with spinal cord injury and disorders (SCI/D). SETTING: A total of 127 Veterans Affairs healthcare facilities. METHODS: Laboratory results from 1 January 2012 to 31 December 2013 were collected, and MDRPA cultures were compared with non-MDRPA cultures. RESULTS: One thousand four hundred forty-one cultures were collected from Veterans with SCI/D, including 227 cultures with MDRPA isolates. Characteristics associated with an increased odds of MDRPA include age 50-64 (adjusted odds ratio (aOR)=1.80, 95% confidence interval (CI)=1.13-2.87), MDRPA culture in the past 365 days (aOR=9.12, 95% CI=5.88-14.15) and carbapenem exposure in the past 90 days (aOR=2.56, 95% CI=1.35-4.87). In contrast, paraplegia was associated with a 53% decreased odds of MDRPA compared with those with tetraplegia (aOR=0.47, 95% CI=0.32-0.69). CONCLUSIONS: Risk factors for community-associated MDRPA include prior history of MDRPA and exposure to carbapenems. Awareness of these factors is important for targeted prevention and treatment of MDRPA in patients with SCI/D.

Risk factors for osteoporotic fractures in persons with spinal cord injuries and disorders.

UNLABELLED: Clinical risk factors for fracture were explored among Veterans with a spinal cord injury. At the end of 11 years of follow-up, the absolute risk of fracture was approximately 20 %. Among the clinical and SCI-related factors explored, a prior history of fracture was strongly associated with incident fracture. INTRODUCTION: Few studies to date have comprehensively addressed clinical risk factors for fracture in persons with spinal cord injury (SCI). The purpose of this study was to identify risk factors for incident osteoporotic fractures in persons with a SCI that can be easily determined at the point of care. METHODS: The Veteran's Affairs Spinal Cord Dysfunction Registry, a national database of persons with a SCI, was used to examine clinical and SCI-related risk factors for fracture. Incident fractures were identified in a cohort of persons with chronic SCI, defined as SCI present for at least 2 years. Cox regression models were used to estimate the risk of incident fractures. RESULTS: There were 22,516 persons with chronic SCI included in the cohort with 3365 incident fractures. The mean observational follow-up time for the overall sample was 6.2 years (median 6.0, IQR 2.9-11.0). The mean observational follow-up time for the fracture group was 3.9 years (median 3.3, IQR 1.4-6.1) and 6.7 years (median 6.7, IQR 3.1-11.0) for the nonfracture group. By the end of the study, which included predominantly older Veterans with a SCI observed for a relatively short period of time, the absolute (i.e., cumulative hazard) for incident fractures was 0.17 (95%CI 0.14-0.21). In multivariable analysis, factors associated with an increased risk of fracture included White race, traumatic etiology of SCI, paraplegia, complete extent of SCI, longer duration of SCI, use of anticonvulsants and opioids, prevalent fractures, and higher Charlson Comorbidity Indices. Women aged 50 and older were also at higher risk of sustaining an incident fracture at any time during the 11-year follow-up period. CONCLUSIONS: There are multiple clinical and SCI-related risk factors which can be used to predict fracture in persons with a SCI. Clinicians should be particularly concerned about incident fracture risk in persons with a SCI who have had a previous fracture.

Development and validation of a computerized algorithm for International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI).

STUDY DESIGN: Validation study. OBJECTIVES: To describe the development and validation of a computerized application of the international standards for neurological classification of spinal cord injury (ISNCSCI). SETTING: Data from acute and rehabilitation care. METHODS: The Rick Hansen Institute-ISNCSCI Algorithm (RHI-ISNCSCI Algorithm) was developed based on the 2011 version of the ISNCSCI and the 2013 version of the worksheet. International experts developed the design and logic with a focus on usability and features to standardize the correct classification of challenging cases. A five-phased process was used to develop and validate the algorithm. Discrepancies between the clinician-derived and algorithm-calculated results were reconciled. RESULTS: Phase one of the validation used 48 cases to develop the logic. Phase three used these and 15 additional cases for further logic development to classify cases with 'Not testable' values. For logic testing in phases two and four, 351 and 1998 cases from the Rick Hansen SCI Registry (RHSCIR), respectively, were used. Of 23 and 286 discrepant cases identified in phases two and four, 2 and 6 cases resulted in changes to the algorithm. Cross-validation of the algorithm in phase five using 108 new RHSCIR cases did not identify the need for any further changes, as all discrepancies were due to clinician errors. The web-based application and the algorithm code are freely available at www.isncscialgorithm.com. CONCLUSION: The RHI-ISNCSCI Algorithm provides a standardized method to accurately derive the level and severity of SCI from the raw data of the ISNCSCI examination. The web interface assists in maximizing usability while minimizing the impact of human error in classifying SCI. SPONSORSHIP: This study is sponsored by the Rick Hansen Institute and supported by funding from Health Canada and Western Economic Diversification Canada.

Surgical compared with nonsurgical management of fractures in male veterans with chronic spinal cord injury.

STUDY DESIGN: Retrospective review of a clinical database. OBJECTIVES: To examine treatment modalities of incident appendicular fractures in men with chronic SCI and mortality outcomes by treatment modality. SETTING: United States Veterans Health Administration Healthcare System. METHODS: This was an observational study of 1979 incident fractures that occurred over 6 years among 12 162 male veterans with traumatic SCI of at least 2 years duration from the Veterans Health Administration (VA) Spinal Cord Dysfunction Registry. Treatment modalities were classified as surgical or nonsurgical treatment. Mortality outcomes at 1 year following the incident fracture were determined by treatment modality. RESULTS: A total of 1281 male veterans with 1979 incident fractures met inclusion criteria for the study. These fractures included 345 (17.4%) upper-extremity fractures and 1634 (82.6%) lower-extremity fractures. A minority of patients (9.4%) were treated with surgery. Amputations and disarticulations accounted for 19.7% of all surgeries (1.3% of all fractures), and the majority of these were done more than 6 weeks following the incident fracture. There were no significant differences in mortality among men with fractures treated surgically compared with those treated nonsurgically. CONCLUSIONS: Currently, the majority of appendicular fractures in male patients with chronic SCI are managed nonsurgically within the VA health-care system. There is no difference in mortality by type of treatment.

Morbidity following lower extremity fractures in men with spinal cord injury.

UNLABELLED: The Veterans Affairs Spinal Cord Dysfunction Registry from 2002 to 2007 was reviewed to determine whether men with spinal cord injury (SCI) and lower extremity fractures had an increased risk of complications compared to those without fractures. We determined that fractures are associated with significant consequences, particularly during the first month postfracture. INTRODUCTION: Despite increasing longevity, patients with SCI have a substantial number of illnesses and comorbid conditions. Lower extremity fractures are frequent events in these patients. However, whether these fractures are associated with any increased risk of complications in SCI is not certain. The purpose of this report was to determine the impact of lower extremity fractures on morbidities in men with SCI. METHODS: A population-based, nested, case-control (1,027 cases and 1,027 propensity-matched controls) of men enrolled in the Veterans Affairs Spinal Cord Dysfunction Registry from fiscal years 2002 to 2007 was reviewed to determine whether lower extremity fractures were associated with an increased risk for complications. RESULTS: In propensity score models matched for demographic (age, race) and SCI-related injury factors (level/completeness of SCI), Veterans Affairs-service connection status, and comorbidities, at 1 month following the fracture, there was an increased risk for respiratory infections, pressure ulcers, urinary tract infections, thromboembolic events, depression, and delirium (p ≤ 0.03 for all). Over 12 months, the only complication more common in fracture cases was pressure ulcers (p < 0.01), with an absolute difference of less than 2 % when compared to controls. There was no significant increased risk of cardiac arrhythmias at any time examined following fracture (≥0.12). CONCLUSIONS: Lower extremity fractures are associated with significant consequences in men with SCI during the first month postfracture, but they do not persist for a long term, except for pressure ulcers. Targeted interventions to prevent complications should be considered following lower extremity fractures in SCI, particularly in the first month following fracture.

Dysfunctional sleep in persons with spinal cord injuries and disorders.

STUDY DESIGN: Cross-sectional survey of veterans with spinal cord injuries and disorders (SCI/D). OBJECTIVES: To describe sleep dysfunction (independent of sleep apnea) in persons with traumatic and non-traumatic SCI/D, and to examine characteristics and health outcomes independently associated with sleep dysfunction unrelated to sleep apnea. SETTING: Seven Veterans Affairs SCI care facilities in the United States. METHODS: Mailed cross-sectional survey with follow-up calls completed by end of 2008. Bivariate analyses to compare measures outcomes in persons with SCI/D who were dysfunctional sleepers vs those who were not. Multivariate logistic regression used to identify variables independently associated with dysfunctional sleep in veterans with SCI/D. RESULTS: Overall, 49% of the sample had sleep dysfunction unrelated to sleep apnea. In this subgroup, bivariate analyses showed that a greater proportion of dysfunctional sleepers than non-dysfunctional sleepers were current smokers, had problems with drinking alcohol, hypertension, asthma, chronic obstructive pulmonary disease (COPD) and problematic weight gain. Variables independently associated with higher odds of dysfunctional sleep included white race, being a current smoker, problems with drinking alcohol, asthma, COPD and problematic weight gain. CONCLUSION: Consistent with epidemiological evidence for the general population, we found significant associations of sleep dysfunction with weight gain, smoking, alcohol misuse and select chronic conditions (COPD, asthma). Sustained sleep dysfunction may contribute to health deterioration and mortality, highlighting the need to address the high prevalence of sleep dysfunction (independent of sleep apnea) in persons with SCI/D. In particular, efforts aimed at modifying problematic weight gain, alcohol misuse and smoking are warranted in this cohort to improve sleep.

Bloodstream infections and setting of onset in persons with spinal cord injury and disorder.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: Health-care-associated (HCA) bloodstream infection (BSI) has been shown to be a distinct epidemiologic category in the general adult population, but few studies have examined specific patient populations. The objective of this study was to assess characteristics associated with BSI that occurred in the hospital (hospital-acquired, HA BSI), from health-care contact outside the hospital (HCA BSI) or in the community (community-acquired, CA BSI) in veterans with spinal cord injury and disorder (SCI&D). SETTING: Two United States Department of Veterans Affairs hospitals. METHODS: All patients with SCI&D with a positive blood culture admitted to study hospitals over a 7-year period (1 October 1997 to 30 September 2004). Demographics, medical characteristics and causative organisms were collected. RESULTS: Four hundred and thirteen episodes of BSI occurred in 226 patients, with a rate of 7.2 BSI episodes per 100 admissions: 267 (64.7%) were HA BSI, 110 (26.6%) were HCA BSI and 36 (8.7%) were CA BSI. Antibiotic resistance was more common in those with HA BSI (65.5%) compared with that in those with HCA (49.1%, P=0.001) and CA BSI (22.2%, P<0.0001). Methicillin resistance in Staphylococcus aureus was highly prevalent; HA BSI (84.5%), HCA BSI (60.6%) and CA BSI (33.3%). CONCLUSION: HCA BSI comprises one-quarter of all BSIs in hospitalized patients with SCI&D. Although those with HCA and CA BSI share similarities, several differences in medical characteristics and causal microorganism are noted. Treatment and management strategies for HCA and CA infections need to vary.

Gluconeogenesis, glucose handling, and structural changes in livers of the adult offspring of rats partially deprived of protein during pregnancy and lactation.

Maternal protein restriction is a model of fetal programming of adult glucose intolerance. Perfused livers of 48-h- starved adult offspring of rat dams fed 8% protein diets during pregnancy and lactation produced more glucose from 6 mM lactate than did control livers from rats whose dams were fed 20% protein. In control livers, a mean of 24% of the glucose formed from lactate in the periportal region of the lobule was taken up by the most distal perivenous cells; this distal perivenous uptake was greatly diminished in maternal low protein (MLP) livers, accounting for a major fraction of the increased glucose output of MLP livers. In control livers, the distal perivenous cells contained 40% of the total glucokinase of the liver; this perivenous concentration of glucokinase was greatly reduced in MLP livers. Intralobular distribution of phosphenolpyruvate carboxykinase was unaltered, though overall increased activity could have contributed to the elevated glucose output. Hepatic lobular volume in MLP livers was twice that in control livers, indicating that MLP livers had half the normal number of lobules. Fetal programming of adult glucose metabolism may operate partly through structural alterations and changes in glucokinase expression in the immediate perivenous region.

Proton NMR spectroscopic analysis of multiple acyl-CoA dehydrogenase deficiency--capacity of the choline oxidation pathway for methylation in vivo.

Proton NMR spectra of urine from subjects with multiple acyl-CoA dehydrogenase deficiency, caused by defects in either the electron transport flavoprotein or electron transport flavoprotein ubiquinone oxidoreductase, provide a characteristic and possibly diagnostic metabolite profile. The detection of dimethylglycine and sarcosine, intermediates in the oxidative degradation of choline, should discriminate between multiple acyl-CoA dehydrogenase deficiency and related disorders involving fatty acid oxidation. The excretion rates of betaine, dimethylglycine (and sarcosine) in these subjects give an estimate of the minimum rates of both choline oxidation and methyl group release from betaine and reveal that the latter is comparable with the calculated total body methyl requirement in the human infant even when choline intake is very low. Our results provide a new insight into the rates of in vivo methylation in early human development.

An investigation of argininosuccinic acid anhydrides in argininosuccinic acid lyase deficiency by 1H-NMR spectroscopy.

Argininosuccinate (ASA) is excreted in large amounts in the urine of patients with argininosuccinate lyase (EC 4.3.2.1) deficiency (ASLD). Previous workers have reported the presence of anhydrides of ASA in the urine of patients with this disorder. We have used 1H-NMR spectroscopy to investigate the presence of these compounds in untreated urine. Our results indicate that the anhydrides were absent from urine and are artifacts produced by the conditions prevailing in the methods of analysis previously used to investigate the urine from patients with ASLD. We have also attempted to reproduce the conditions that might promote the transition to the anhydrides in the urine from a patient with ASLD and in solutions of argininosuccinate. Resolution of ASA and the two anhydrides is possible and a spectrum of the urine from a patient with ASLD shows that the anhydrides are present at below 1% of the total ASA under normal physiological conditions.

Investigation of urea cycle enzyme disorders by 1H-NMR spectroscopy.

High resolution proton nuclear magnetic resonance spectroscopy (1H-NMR) has been used to study patients with inborn errors of the urea cycle to evaluate further the diagnostic potential of this technique. The 1H-NMR metabolic profile from the urine of patients with citrullinaemia and argininosuccinic aciduria consistently demonstrated the presence of the diagnostic metabolites citrulline, N-acetylcitrulline and argininosuccinate, respectively. The profile from the urine of patients with ornithine carbamoyl transferase deficiency, is potentially diagnostic, but orotate was only detected in samples from three out of four patients. The characteristic fingerprint that each of the metabolites produces is unlike that of any other we have seen, including analogues of the metabolites which are structurally very similar such as arginine, ornithine and aspartate. The level of excretion of the metabolites from the patients with citrullinaemia and argininosuccinic aciduria has been well within the range of NMR detection.

Physical and psychological predictors of exercise dosage in healthy adults.

PURPOSE: The purpose of this study was to examine the exercise dose-response issue in a sample of 121 regular exercisers categorized as relatively low, moderate, or high dosage physical activity participants. METHODS: Male and female students, faculty, and staff of a midwestern university, currently engaging in various exercise modalities at least two times per week, were assessed on a variety of factors hypothesized to impact one's degree of exercise involvement. RESULTS: ANOVA procedures indicated that low and high dosage groups differed significantly on the variables of age, exercise history, positive affect, and the locus of causality and stability attributional dimensions. Groups did not differ significantly in terms of body mass index, exercise efficacy, perceptions of either personal or external control over exercise behavior, or negative affective reactions to exercise behavior. CONCLUSIONS: Taken together, the findings of this study suggest that individuals who exercise at varying doses of physical activity may be differentiated by certain demographic, behavioral, physiological, and psychological variables.

Cerebral energy metabolism in isovaleric acidaemia.

A newborn infant with an acute metabolic encephalopathy caused by isovaleric acidaemia had severe impairment of cerebral energy metabolism. This was detected by phosphorus and proton magnetic resonance spectroscopy. After treatment she made excellent clinical recovery, her spectroscopic abnormalities resolved, and she was neurologically normal at the age of 1 year.

Neurologic recovery and neurologic decline after spinal cord injury.

Physicians caring for patients with spinal cord injury facilitate neurologic recovery by optimizing nutrition and general health, by coordinating active exercise and functional training to enhance the underlying synapse growth, reversal of muscle atrophy, and motor learning, and by controlling interfering spasticity. SCI physicians also must monitor for neurologic decline during initial rehabilitation and later in life, diagnose promptly and accurately such decline, and orchestrate the appropriate intervention.

Responses of retinal and visual pathway potentials of the guinea pig to nitrogen and helium at high pressure.

Electroretinographic, optic chiasm, and visual cortex potentials were monitored in the awake guinea pig as nitrogen pressures were raised to 16 ATA and held for 30 min. Pressurization to 90 ATA with helium in 10-ATA increments followed. We sought to (a) quantify the depressant effect of nitrogen on the retina as compared to the central visual pathway, and (b) to test for pressure reversibility. The electroretinogram was reduced approximately 15%, the chiasm potential by 15%, and the cortical response by 32% in 16 ATA nitrogen, and latent periods for the three signals increased an average of 5-8%. Helium at pressure did not restore the amplitude of the electroretinogram or optic chiasm response, but the visual cortex potential returned to control levels near 90 ATA total pressure. Reversal of the nitrogen-induced latency increases by helium was partially effective up to 40 ATA. Control latent periods were not reached. Further attenuation of the electroretinogram and chiasm response amplitudes, and increased latencies of all signals were observed at 50-90 ATA.

Purchasers look at physician hospital organizations.

Business leaders are finally seizing the opportunity to shape the future of this country's health care delivery system. One such system could be new, community-based alliances known as physician hospital organizations.

Seating pressures with conventional and dynamic wheelchair cushions in tetraplegia.

OBJECTIVE: To compare pressure relief from a dynamic wheelchair cushion to a tilt-in-space wheelchair with conventional cushions. STUDY DESIGN: Repeated measures analysis. SETTING AND SUBJECTS: Spinal cord injury unit; 16 tilt-in-space wheelchair users with motor-complete tetraplegia. MAIN OUTCOME MEASURES: Interface pressure at ischial tuberosities. RESULTS: Mean ischial pressure with subjects seated upright on the dynamic cushion during the low ischial pressure phase was lower than tilted pressure on the gel cushion, but it was not significantly different from tilted pressure on the dry-flotation cushion (dynamic/upright, 71 mm Hg; gel/tilted, 86 mm Hg; dry-flotation/tilted, 74 mm Hg; p<.05 dynamic vs. gel). Mean ischial pressure with subjects upright on the dynamic cushion during the high ischial pressure phase was significantly greater than the gel/upright and dry-flotation/upright conditions (dynamic/upright, 157 mm Hg; gel/upright, 128 mm Hg; dry-flotation/upright, 111 mm Hg; p<.001). CONCLUSION: The dynamic cushion produces similar pressure relief over the ischial tuberosities during the low pressure phase to a tilt-in-space wheelchair and conventional cushions. The dynamic cushion may be an alternative to a tilt-in-space wheelchair for some individuals.

Neurological worsening due to infection from renal stones in a multiple sclerosis patient.

Symptomatic bladder dysfunction occurs in the majority of patients with multiple sclerosis (MS). Although guidelines have been established for diagnosis and management of bladder dysfunction in these patients, they are sometimes overlooked in the primary care setting, leading to severe, life threatening complications. A 64-year-old male with a 31-year history of spastic quadriparetic MS and neurogenic bladder dysfunction managed with an indwelling catheter, presented to the hospital with worsening neurological function. He had developed increased weakness and cognitive impairment several weeks after being treated for a urinary tract infection (UTI). He had become unable to perform any activities of daily living or drive his power wheelchair. After an extensive work-up, he was found to have a large (14 x 18 x 30 cm) retroperitoneal abscess and multiple renal stones, including a large obstructing calculus in the collecting system near the ureteropelvic junction, and he underwent nephrectomy and abscess drainage. Of note, he had been found to have multiple renal stones and hydronephrosis on renal ultrasound 3 years earlier, but he had received no treatment. Following drainage of the abscess, his upper extremity neurological function returned to baseline, his cognitive status improved, and he regained the ability to perform activities of daily living. Patients with paralysis from MS, much like those with traumatic spinal cord injuries, are at grave risk of mortality and morbidity from undiagnosed and under-treated urinary complications. This case demonstrates that evaluation and appropriate treatment for complications of neurogenic bladder should be part of routine care for patients with MS. Current recommendations for evaluation and management of bladder dysfunction in patients with MS will be reviewed.

Clinician judgments of functional outcomes: how bias and perceived accuracy affect rating.

OBJECTIVE: To evaluate the accuracy of clinician judgments of patient function, the susceptibility of judges to bias, and the relation between a judge's degree of belief in his/her accuracy of classification to observed accuracy when using the FIM instrument. PARTICIPANTS: Fifty rehabilitation professionals. SETTING: 3 urban medical centers. DESIGN: Four randomized experiments among subjects to examine the effect of potentially biasing information on FIM ratings of patient vignettes. Participants answered 60 true/false questions regarding patient function and FIM score and indicated confidence in the accuracy of their answers. INTERVENTIONS: Manipulation of patient information. MAIN OUTCOME MEASURES: The standard FIM 7-point scale, observed proportion of correct responses to the 60 true/false questions, and a 6-category confidence scale for each of the 60 questions were used as dependent measures. RESULTS: FIM ratings assigned to others biased participants' FIM ratings of patient vignettes. Functional ability was overestimated when ratings in other domains were high and underestimated when they were low. Participants were overconfident in their ability to answer FIM questions accurately across all professional disciplines. CONCLUSION: Bias and poor judgment of level accuracy play a significant role in clinician ratings of patient functioning. Blind ratings and training in debiasing are potential solutions to the problem.