Controlled clinical trials in cystic fibrosis--are we doing better?

We have previously reported the time trends, design and interventions in randomised controlled trials (RCTs) in cystic fibrosis (CF) from 1961 through 1997 [Cheng K, Smyth RL, Motley J, O'Hea U, Ashby D, Randomised controlled trials in cystic fibrosis (1966-1997) categorized by time, design, and intervention. Pediatr Pulmonol 2000, 29:1-7.]. We maintain an ongoing register of all RCTs and controlled clinical trials (CCTs) in CF and have noted that in the five years since 1997 there has been a 48% increase in published trials. We aimed to assess whether this increase has been associated with an improvement in design quality. All RCTs and CCTs from 1961-2002 were assessed. Two epochs were then compared, 1961-1997 and 1998-2002. For each trial we recorded the design, participant numbers and the intervention studied. 261 trials in 1998-2002 were compared with 544 trials in 1961-1997. Comparing the two epochs a similar proportion of trials were parallel, double-blind and placebo controlled; also the median number of participants was similar. In the later epoch 25% of trials were multicentre, compared with 11% previously. Whilst this recent increase in clinical trials in CF is welcome, this has not been associated with improvements in quality. The trend for an increasing proportion of trials to be multicentre is encouraging. There are however, still deficiencies in the design of clinical trials in CF.     

2,3-Butanedione monoxime protects mice against the convulsant effect of picrotoxin by facilitating GABA-activated currents

While adult mice receiving picrotoxin (PTX) alone responded with clonic and tonic-clonic seizures, this response was greatly suppressed for mice simultaneously injected with 2,3-butanedione monoxime (BDM). For example, 60% and 10% of the mice convulsed when injected (i.p.) with 3.0 mg/kg PTX alone or PTX plus 205 mg/kg of BDM, respectively. In contrast, a non-oxime analogue of BDM, 2,3-butanedione (BTD), did not have this anticonvulsant effect. In order to explore the basis for the anticonvulsant effect of BDM, we recorded GABA-activated currents (I_GABA) of frontal cortical as well as ventromedial hypothalamic neurons before, during and after exposure to this oxime. BDM had a biphasic effect on concentrations (100 μM-40 mM) decreased and lower concentrations (0.01 μM–0.001 μM) potentiatedI_GABA; these effects of BDM reversed upon washout of the oxime. In contrast, BTD had no effect onI_GABA. Finally, when 0.001 μM BDM, 10–30 μM PTX and GABA were co-applied the inhibitory effect of the toxin onI_GABA was markedly suppressed. These data suggest that the anticonvulsant effect of oximes involves facilitation of the inhibitory action of GABA.     

Drug and alcohol treatment services effective for methamphetamine abuse.

BACKGROUND: Methamphetamine abuse has become a major public health problem as demonstrated by increases in the number of emergency room visits, substance abuse treatment episodes, and arrests attributable to methamphetamine manufacture and abuse. We examine the effectiveness of conventional substance abuse treatment in the recovery of individuals seeking voluntary treatment for methamphetamine abuse. METHODS: At the request of the Iowa Department of Public Health, the Iowa Consortium for Substance Abuse Research and Evaluation contacted clients who had been admitted to voluntary treatment for methamphetamine abuse. Staff from the Consortium asked subjects to volunteer for follow-up interviews at designated intervals following admission. Agency staff conducted interviews based on the Mini International Neuropsychiatric Interview (MINI) at admission and at designated intervals and reported results to the Consortium for analysis. RESULTS: Subjects were predominantly Caucasian and over one half were female with an average age of 30 years. The criminal justice system was a primary referral source. Reported psychiatric symptoms dropped substantially in the first 60 days following admission and appeared to remain low at 6 and 12 months. Most clients reported abstinence and employment and denied arrests at the 6-month interview. Outcomes were not correlated with psychiatric symptoms. CONCLUSIONS: Psychiatric symptoms improved over time with usual substance abuse treatment. There was no evidence that referral by the court system or symptoms of antisocial personality disorder affected outcome. Conventional treatment resulted in sobriety, employment, and fewer arrests at 6 and 12 months following treatment.     

Fluoroscopic percutaneous lumbar zygapophyseal joint cyst rupture: a clinical outcome study

Background contextLumbar zygapophyseal joint (Z-joint) synovial cysts can cause low back pain (LBP), spinal stenosis, and lower extremity radiculopathy. In the literature, there are several minimally invasive techniques described with mixed results. Typical recommended treatment is surgical resection of the cyst. Currently, there is little information available concerning the efficacy and outcome with treatment of Z-joint synovial cyst by percutaneous, fluoroscopic, contrast-enhanced distention, and rupture.PurposeTo evaluate the therapeutic value and safety of Z-joint cyst rupture in symptomatic patients.Study design/settingRetrospective cohort study in an academic outpatient physiatric spine practice.Patient sampleThirty-two patients with moderate-to-severe LBP and leg pain (18 women and 14 men with an age range of 46–86 y; mean age, 66 y) with an average preprocedure symptom duration of 5 months. The patient's clinical symptoms correlated with magnetic resonance imaging studies documenting the presence of a synovial cyst at the corresponding level and side of symptoms. Patients had at least 6 months follow-up (range, 6–24).Outcome measuresNumerical Pain Rating Scale, Roland-Morris Disability Questionnaire, North American Spine Society four-point patient satisfaction survey, recurrence of synovial cyst requiring repeat rupture, and need for surgical intervention.MethodsPatients with symptomatic lumbar Z-joint synovial cyst were identified and their charts were reviewed. Patients included in the study either had symptomatic lumbar LBP or LBP with associated lower extremity radiculopathy. All patients in the study had magnetic resonance imaging's documenting Z-joint synovial cyst that corresponded with the patients' clinical symptoms. All patients received fluoroscopically guided, contrast-enhanced, percutaneous facet cyst distention and rupture followed by an intra-articular facet joint injection of 1 cc kenalog and 1 cc of 1% lidocaine. Seventeen of the patients also received a transforaminal epidural steroid injection just before facet cyst rupture. Telephone follow-up was conducted on all patients.ResultsExcellent long-term (average follow-up 1 y; range, 6–24 mo) pain relief was achieved in 23 (72%) of 32 patients undergoing facet cyst rupture. Twelve patients (37.5%) had synovial cyst recurrence and 11 chose to undergo repeat rupture, which resulted in 5 patients (45%) obtaining complete relief of symptoms and 6 patients (55%) requiring surgical intervention for cyst removal. Fisher exact test demonstrated that all patients who did not have a cyst recurrence were a success and obtained complete relief of symptoms (p<.0002). Patients who underwent a repeat rupture had a 50% chance of a successful outcome. There was no statistical significance between a successful outcome and level of facet cyst rupture, the presence of spondylolisthesis, sex, age, or having a transforaminal epidural steroid injection at the time of the procedure. Wilcoxon signed-rank test demonstrated that the difference in Numerical Pain Rating Scale and Roland-Morris Disability Questionnaire scores before and after the procedure was statistically significant (p<.0001). No complications were reported.ConclusionsFluoroscopic percutaneous Z-joint cyst rupture appears to be a safe and effective minimally invasive treatment option. This procedure should be considered before surgical intervention.