The effect of oxandrolone on the healing of chronic pressure ulcers in persons with spinal cord injury: a randomized trial.

BACKGROUND: Anabolic steroids have been reported to improve wound healing. OBJECTIVE: To determine whether oxandrolone increases the percentage of target pressure ulcers (TPUs) that heal compared with placebo and whether healed ulcers remain closed 8 weeks after treatment. DESIGN: Parallel-group, placebo-controlled, randomized trial conducted from 1 August 2005 to 30 November 2008. Patients, clinical care providers, study personnel, and statisticians were blinded to treatment assignment. (ClinicalTrials.gov: NCT00101361). SETTING: 16 inpatient spinal cord injury (SCI) services at Veterans Affairs medical centers. PATIENTS: 1900 prescreened, 779 screened, and 212 randomly assigned inpatients with SCI and stage III or IV TPUs. INTERVENTION: Oxandrolone, 20 mg/d (n = 108), or placebo (n = 104) until the TPU healed or 24 weeks. MEASUREMENTS: The primary outcome was healed TPUs. The secondary outcome was the percentage of TPUs that remained healed at 8-week follow-up. RESULTS: 24.1% (95% CI, 16.0% to 32.1%) of TPUs in oxandrolone recipients and 29.8% (CI, 21.0% to 38.6%) in placebo recipients healed (difference, -5.7 percentage points [CI, -17.5 to 6.8 percentage points]; P = 0.40). At 8-week follow-up, 16.7% (CI, 9.6% to 23.7%) of oxandrolone recipients and 15.4% (CI, 8.5% to 22.3%) of placebo recipients retained a healed TPU (difference, 1.3 percentage points [CI, -8.8 to 11.2 percentage points]; P = 0.70). No serious adverse events were related to oxandrolone. Liver enzyme levels were elevated in 32.4% (CI, 23.6% to 41.2%) of oxandrolone recipients and 2.9% (CI, 0.0% to 6.1%) of placebo recipients (P < 0.001). LIMITATIONS: Selection of severe wounds may have reduced treatment response. Approximately one third of patients did not complete the study in the treatment and placebo groups. The study was terminated after a futility analysis showed a low probability of detecting a significant difference between the groups. CONCLUSION: Oxandrolone showed no benefit over placebo for improving healing or the percentage of TPUs that remained closed after 8 weeks of treatment. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs.

A 24-hour feasibility study of intraurethral valved catheter for bladder management in males with spinal cord injury.

This feasibility study was conducted to evaluate design features of the novel intraurethral valved catheter, Surinate (Urovalve, Inc; Newark, New Jersey). The device extends from the bladder neck to just beyond the external sphincter and contains a valve that can be activated by an external magnet for bladder emptying. Five patients were recruited from the Edward Hines Jr Department of Veterans Affairs Hospital spinal cord injury population. We conducted cystometry and cystoscopy to evaluate the lower urinary tract. Then, the device was inserted for 24 hours with careful monitoring. The catheter was removed from the first patient because he developed autonomic dysreflexia during implantation. The next four patients used the catheter overnight and tolerated it well: one with independent use and two with increased abdominal pressure. Emptying time was 208 +/- 99 s, residual was 42 +/- 33 mL, and the first-stream flow rate was 1.8 +/- 0.7 mL/s. The safety tether was used in three patients because the extraction device did not work. Results showed effective implantation and stability of the device in the urethra. However, objectives for use and extraction were not met. This feasibility study provided important information that will help guide design improvements for the intraurethral valved catheter.

Colchicine treatment of alcoholic cirrhosis: a randomized, placebo-controlled clinical trial of patient survival.

BACKGROUND & AIMS: Colchicine improved survival and reversed cirrhosis in several small clinical trials. We compared the efficacy and safety of long-term colchicine, as compared with placebo, in patients with advanced alcoholic cirrhosis. METHODS: Five hundred forty-nine patients with advanced (Pugh B or C) alcoholic cirrhosis were randomized to receive either colchicine 0.6 mg twice per day (n = 274) or placebo (n = 275). Treatment lasted from 2 to 6 years. The primary outcome was all-cause mortality. Secondary outcomes were liver-related morbidity and mortality. Liver biopsy was requested prior to entry and after 24 months of treatment. RESULTS: Attendance at scheduled clinic visits and adherence with study medication were similar in colchicine and placebo groups. Alcohol intake was less than 1 drink per day in 69% of patients. In an intention-to-treat analysis, all-cause mortality was similar in colchicine (49%) and placebo (45%) patients (P = .371). Mortality attributed to liver disease was 32% in colchicine and 28% in placebo patients (P = .337). Fewer patients receiving colchicine developed hepatorenal syndrome. In 54 patients with repeat liver biopsies after 24 or more months of treatment, cirrhosis improved to septal fibrosis in 7 patients (3 colchicine, 4 placebo) and to portal fibrosis in 1 patient (colchicine). CONCLUSIONS: In patients with advanced alcoholic cirrhosis, colchicine does not reduce overall or liver-specific mortality. Liver histology improves to septal fibrosis in a minority of patients after 24 months of treatment, with similar rates of improvement in patients receiving placebo and colchicine. Colchicine is not recommended for patients with advanced alcoholic cirrhosis.

Controlling antimicrobial use and decreasing microbiological laboratory tests for urinary tract infections in spinal-cord-injury patients with chronic indwelling catheters.

PURPOSE: The effect of replacing the indwelling catheter of patients suspected of having a urinary tract infection (UTI) before collecting a urine sample on the number of organisms isolated in cultures and on drug and microbiology laboratory costs was studied. METHODS: Data were collected for all patients hospitalized in two spinal cord injury (SCI) units between October 2001 and March 2002 who had an indwelling catheter or suprapubic catheter and were suspected of having a UTI. Urine samples were obtained through a port of the indwelling catheter in one SCI unit, while the indwelling catheter was replaced immediately before each urine sample was obtained in the second SCI unit. Patient demographics, history of antimicrobial use, bacterial isolate sensitivity data, and current antimicrobial treatment were recorded. RESULTS: A total of 85 patients, 41 in the control group and 44 in the intervention group, were enrolled during the six-month study period. In the control and intervention groups, 93 and 79 organisms were isolated, respectively, with an average of 2 isolates per patient in the control group and 1 per patient in the intervention group. Patients in the control group had significantly more multidrug-resistant organisms in their urine, with 34 isolated from 26 patients (63%) (p < 0.001). Changing the indwelling catheter decreased antimicrobial and microbiology laboratory costs, resulting in a cost saving of $15.64 per patient. CONCLUSION: Replacement of the indwelling catheter before collecting a urine sample for culture and conducting susceptibility testing reduced the pathogens identified, the number of toxic antimicrobials prescribed to treat the infection, and the costs of antimicrobials and microbiology laboratory technician time.

Asthmatics with gastroesophageal reflux: long term results of a randomized trial of medical and surgical antireflux therapies.

OBJECTIVE: In short term studies, asthma symptoms and pulmonary function have been reported to improve during and after medical treatment or surgical correction of gastroesophageal reflux (GER). In this study, we aimed to determine whether prolonged treatment of GER altered the long term natural history of asthma in asthmatics with GER. METHODS: A total of 62 patients with both GER and asthma entered a randomized study of antireflux treatments for at least 2 yr: 24 controls (antacids as needed); 22 medical (ranitidine 150 mg t.i.d.); and 16 surgical (Nissen fundoplication). Asthma was defined as a previous diagnosis of asthma with discrete attacks of wheezing and 20% reversibility in airway disease. GER was defined as an abnormal ambulatory 24-h esophageal pH test and macroscopic or microscopic evidence of GER disease. Overall clinical status, asthma symptom scores, and pulmonary medication requirements were recorded monthly. Peak expiratory flow rates were recorded up to seven times per day for 1 wk of each month throughout the years. Pulmonary function, esophageal manometry, and endoscopy with biopsy were repeated yearly. RESULTS: The 62 patients were followed for up to 19.1 yr. In the surgical group, but not in the medical or control groups, there was an immediate and sustained reduction in acute nocturnal exacerbations of wheezing, coughing, and dyspnea. By the end of 2 yr, improvement, marked improvement, or cure in the overall asthma status occurred in 74.9% of the surgical group, 9.1% of the medical group and 4.2% of the control group, whereas the overall status worsened in 47.8% of the control group, 36.4% of the medical group, and 12.5% of the surgical group (p < 0.001, surgical vs medical and control). The mean asthma symptom score of the surgical group improved 43%, compared with less than 10% in the medical and control groups (p = 0.0009). As determined by changes in peak expiratory flow rates, there was no statistically significant difference in pulmonary function during the 2-yr period or during regularly scheduled follow-up. There was no difference in medication requirements among the groups. There was no difference between the groups in overall survival. CONCLUSION: In patients with both GER and asthma, antireflux surgery (but not medical therapy with ranitidine 150 mg t.i.d.) has minimal effect on pulmonary function, pulmonary medication requirements, or survival, but significantly improves asthma symptoms and overall clinical status.

Circadian variation in oxidative stress markers in healthy and type II diabetic men.

Seven clinically healthy, nondiabetic (ND) and four Type II diabetic (D) men were assessed for circadian rhythms in oxidative "stress markers." Blood samples were collected at 3h intervals for approximately 27 h beginning at 19:00h. Urine samples were collected every 3 h beginning with the 16:00h-19:00h sample. The dark (sleep) phase of the light-dark cycle extended from 22:30h to 06:30h, with brief awakening for sampling at 01:00h and 04:00h. Subjects were offered general hospital meals at 16:30h, 07:30h, and 13:30h (2400 cal in total/24h). Serum samples were analyzed for uric acid (UA) and nitrite (NO) concentrations, and urine samples were assayed for 8-hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA), and 8-isoprostane (ISP). Data were analyzed statistically both by the population multiple-components method and by the analysis of variance (ANOVA). The 24h mean level of UA and NO was greater in D than in ND subjects (424 vs. 338 micromol/L and 39.2 vs. 12.7 microM, respectively). A significant circadian rhythm in UA (p = 0.001) and NO (p = 0.048) was evident in ND but not in D (p = 0.214 and 0.065). A circadian rhythm (p = 0.004, amplitude = 8.6 pmol/kgbw/3h urine vol.) was also evident in urine 8-OHdG of ND but not of D. The 24h mean levels of ND and D were comparable (76.8 vs. 65.7 pmol/kgbw/3h urine vol.). No circadian rhythm by population multiple-components was evident in MDA and ISP levels of ND subjects, or in 8-OHdG, MDA, and ISP in D. However, a significant time-effect was demonstrated by ANOVA in all variables and groups. The 24h mean of MDA and ISP in D was significantly greater than in ND (214 vs. 119 nmol/3h urine vol. and 622 vs. 465 ng/3h urine vol.). The peak concentrations of the three oxidative "stress markers" in urine, like those of serum NO, occurred early in the evening in both groups of men. This observation suggests a correlation between increased oxidative damage and increased rate of anabolic-catabolic events as evidenced by similarities in the timing of peak NO production and in parameters relevant to metabolic functions.

A database of self-reported secondary medical problems among VA spinal cord injury patients: its role in clinical care and management.

An interactive data management (IDM) system for the Spinal Cord Injury (SCI) Service was developed to collect self-reported patient data related to secondary medical complications and to provide feedback to the SCI rehabilitation team. The long-term objective is to improve clinical care through a process of staff review of current rehabilitation programs in the areas of prevalence, prevention, and management. Based on data from the first 99 SCI patients visiting the clinic and hospital after the installation of the IDM system, SCI patients reported high rates of current problems with spasticity (53 percent), pain (44 percent), and pressure ulcers (38 percent). Respiratory (12 percent) and bowel (14 percent) problems were less common current problems. The SCI staff questioned the reportedly high spasticity rates. They thought that the patients' answers might have indicated simply the occurrence of spasticity, rather than the more important issue of severe spasticity that interferes with daily activities. The staff suggested several additional spasticity questions to add to the study. In other areas, only a small percentage of patients wanted to talk with a therapist about prevention of pressure ulcers. Patients who had urinary problems consistently reported five urinary signs (e.g., cloudy urine). The clinical staff found these data informative and stated that they should continue to be collected.

Treatment of Spasticity in Spinal Cord Injury with Dronabinol, a Tetrahydrocannabinol Derivative.

Spinal-cord-injured patients and the medical literature have increasingly reported anecdotes regarding tetrahydrocannabinol (THC)-induced spasmolysis. These reports motivated this trial of dronabinol, a THC derivative, for the treatment of spasticity in the spinal-cord-injured population. Five made quadriplegic patients were given oral dronabinol in escalating doses from 5 mg BID to 20 mg TID in addition to their current, but ineffective, spasmolytic regime. The pendulum drop test was used to quantify spasticity (stiffness) in the knees. The Weschler Memory Scale (WMS), Profile of Mood States (POMS), and personal interviews were administered by the clinical psychologist to evaluate any changes in the subjects' cognition and/or emotional states. Spasticity was markedly improved in two of the five subjects, unchanged in a third, fluctuated in a fourth and made progressively worse in a fifth. The WMS revealed improvement in memory skills of two subjects and no change in the other. Psychological interviews and the POMS indicated decreased vigor in all subject, but otherwise demonstrated highly individualized emotional changes as indicated by increases and/or decreases in the dysphoric mood scales.