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External ventricular drains (EVD) are crucial for the emergency management of hydrocephalus and raised intracranial pressure. Infection is the most morbid and costly cause of EVD malfunction and can cost up to $50,000 US to treat per case. In 2007, Canberra Hospital changed EVD management protocols requiring set-up of EVD transducer systems in theatre, cessation of prophylactic antibiotics after 24hours, cerebrospinal fluid (CSF) samples second or third daily and discontinuation of elective EVD changes. The current study aimed to retrospectively audit EVD inserted between 2006 and 2010 in order to determine the impact of these changes. There was a non-significant downward trend in infection rates from 20.93% to 11.50% (p=0.343) after the protocol changes. Patient age (OR=1.032, p=0.064, confidence interval (CI): 0.998-1.067) and sex (OR=1.405, p=0.595, CI: 0.401-4.917) were not significantly associated with infection. However, multiple drains were associated with a significant increase in infections rates (OR=21.96, p=0.001, CI: 6.103-79.023) and systemic perioperative antibiotic prophylaxis was associated with decreased rates of infections (OR=0.269, p=0.044, CI: 0.075-0.964). Our study showed a non-significant downwards trend in infections with introduction of changes to hospital protocol and illustrated some risk factors for infection in the Australian setting.

The molecular basis for alternative lengthening of telomeres (ALT), a prognostic marker for glioma patients, remains unknown. We examined TP53 status in relation to telomere maintenance mechanism (TMM) in 108 patients with glioblastoma multiforme and two patients with anaplastic astrocytoma from New Zealand and United Kingdom. Tumor samples were analyzed with respect to telomerase activity, telomere length, and ALT-associated promyelocytic leukemia nuclear bodies to determine their TMM. TP53 mutation was analyzed by direct sequencing of coding exons 2 to 11. We found an association between TP53 mutation and ALT mechanism and between wild-type TP53 and telomerase and absence of a known TMM (P < 0.0001). We suggest that TP53 deficiency plays a permissive role in the activation of ALT. (Cancer Res 2006; 66(13): 6473-6)

A modified Stroop protocol was administered to a sample of 80 dependent drug users (62 males, 18 females) prior to beginning a time-limited outpatient treatment study combining pharmacotherapy and cognitive-behavioral coping skills therapy for cocaine, marijuana, or heroin dependence. Results indicated that cocaine-dependent participants responded more slowly than marijuana-dependent participants to all stimulus words. Cocaine words yielded slower reaction times than neutral words across all treatment groups. The heroin- and cocaine-dependent groups' overall performance did not differ. There was no treatment group by drug word interaction. For cocaine-dependent participants, Stroop performance in the presence of cocaine stimuli was associated with worse treatment outcome. In conclusion, Stroop performance may have prognostic utility among drug-dependent patients in a cognitive-behavioral coping skills intervention and may highlight the mechanisms associated with changing substance use in this treatment modality.

The aim of this study was to test the hypothesis that desipramine would be an effective treatment in cocaine abusers with current depressive disorders.This was a randomized, 12-week, double-blind, 'placebo-controlled trial of outpatients (N = 111) meeting DSM-III-R criteria for cocaine dependence and major depression or dysthymia (by SCID interview). Participants were treated with desipramine, up to 300 mg per day, or matching placebo. All patients received weekly individual manual-guided relapse prevention therapy. Weekly outcome measures included the Clinical Global Impression Scale, self-reported cocaine use and craving, urine toxicology, and the Hamilton Depression Scale (biweekly). Summary measures of mood and cocaine use outcome were compared between treatment groups with chi2- or t-tests. Dichotomous summary measures of depression response and cocaine response were the primary outcomes. Mixed effect models were also fit to explore the relationship of cocaine use to mood improvement and treatment over weeks in the trial.Desipramine was associated with a higher rate of depression response (51%, 28/55) than placebo (32%, 18/56) (p0.05), but treatment groups did not differ in rate of cocaine response. Depression improvement was associated with improvement in cocaine use. Desipramine was associated with more dropouts due to side effects and medical adverse events, while placebo was associated with more dropouts due to psychiatric worsening.Desipramine was an effective treatment for depression among cocaine-dependent patients. Improvement in mood was associated with improvement in cocaine abuse, but a direct effect of medication on cocaine outcome was not clearly established and rates of sustained abstinence were low. Future research should examine newer antidepressant medications with more benign side effect profiles and combinations of behavioral and pharmacological treatments to maximize effects on cocaine use.

This study examined the characteristics of gay men attending circuit parties and their drug use. In particular, the role of methylenediomethamphetamine (MDMA, "ecstasy") was considered in relation to other drug use and sexual behavior. A one-page survey was distributed to 173 men attending a circuit party. Respondents were generally gay men, Caucasian, employed, and well-educated. Twenty-five percent self-identified as HIV-positive. Eighty-six percent reported using at least one substance on the day of the party; polydrug use was frequent. The most common substances were MDMA, ketamine, and methamphetamine. MDMA use was highly associated with ketamine, methamphetamine, and cocaine use. MDMA use was also associated with significantly more receptive anal intercourse. Circuit parties are settings of increased drug use and associated high-risk sexual behavior. A better understanding of these issues is needed to develop interventions aimed at reducing drug use and sexual risk taking among gay men who attend circuit parties.

There is a noticeable lack of targeted treatment options for marijuana dependence, in particular pharmacologic approaches. This is the first study evaluating a targeted pharmacologic approach for marijuana dependence. The goals of the study were to determine if such patients would seek pharmacologic treatment, whether these patients could be retained in treatment using a design previously developed for cocaine-dependent patients, and especially whether divalproex sodium showed promise as a treatment agent for marijuana dependence. We found that marijuana-dependent patients will seek treatment, and such patients can be adequately maintained in a pharmacologic trial. Regardless of treatment group, patients reported a significant reduction in their frequency and amount of marijuana use as well as a reduction in irritability. Given the lack of proven effective treatments for marijuana dependence, pharmacotherapies should be sought. The design of a preliminary clinical trial should include a psychosocial/behavioral intervention emphasizing motivation and medication compliance and a placebo control group.

Object. Pseudotumor cerebri, or benign intracranial hypertension, is a condition of raised intracranial pressure in the absence of a mass lesion or cerebral edema. It is characterized by headache and visual deterioration that may culminate in blindness. Pseudotumor cerebri is caused by venous sinus obstruction in an unknown percentage of cases. The purpose of this study was to investigate the role of cerebral venous sinus disease in pseudotumor cerebri and the potential of endoluminal venous sinus stent placement as a new treatment. Methods. Nine consecutive patients in whom diagnoses of pseudotumor cerebri had been made underwent examination with direct retrograde cerebral venography (DRCV) and manometry to characterize the morphological features and venous pressures in their cerebral venous sinuses. The cerebrospinal fluid (CSF) pressure was measured simultaneously in two patients. If patients had an amenable lesion they were treated using an endoluminal venous sinus stent. Five patients demonstrated morphological obstruction of the venous transverse sinuses (TSs). All lesions were associated with a distinct pressure gradient and raised proximal venous sinus pressures. Four patients underwent stent insertion in the venous sinuses and reported that their headaches improved immediately after the procedure and remained so at 6 months. Vision was improved in three patients, whereas it remained poor in one despite normalized CSF pressures. Conclusions. Patients with pseudotumor cerebri should be evaluated with DRCV and manometry because venous TS obstruction is probably more common than is currently appreciated. In patients with a lesion of the venous sinuses, treatment with an endoluminal venous sinus stent is a viable alternative for amenable lesions.

A small, controlled study was conducted to assess whether pergolide mesylate has clinical promise as a treatment for cocaine abuse prior to embarking on a larger, randomized, double-blind, controlled trial. Fourteen individuals were placed on placebo for 2 weeks, followed by a 24-week single-blind study in which they were placed on pergolide for 12 weeks, followed by placebo for 12 weeks. Another 14 patients received single-blind placebo for two weeks and then were randomized into a 24-week double-blind, placebo-controlled, multiple baseline design. Initially, patients enrolled in the study were placed on risperidone (n = 9) or placebo (n = 5). During the first 12 weeks, retention was worse for those receiving pergolide compared to risperidone or placebo. Neither risperidone nor pergolide were more efficacious in reducing cocaine use than placebo. Although earlier open studies found pergolide to show promise as a treatment for cocaine abuse, this study did not support these earlier findings. Comparing an agent to both an active control and placebo group may better predict whether a promising new agent will have clinical utility compared to the standard open trial.

The treatment and research of dissociative disorders, particularly dissociative identity disorder (DID), are hampered by professional skepticism and diagnostic uncertainties. Almost always associated with severe and sustained childhood trauma, its chief manifestations are at least two distinct and separate identities which have an independent manner of existing in the world. It is also associated with a high degree of psychiatric comorbidity. Among the most frequent diagnoses found in patients with DID are substance use and dependence. For a variety of reasons there has been little dialogue among the disciplines that study patients with trauma and those that study and treat substance abuse. Clinicians dealing with a primarily substance-abusing population are likely to encounter but not recognize these patients. The authors present several representative cases illustrative of features of patients with DID. The epidemiology, phenomenology and presentation of DID, as well as its relation to posttraumatic stress disorder are discussed. Little systematic investigation exists on the treatment of DID in general, and substance abuse in DID in particular. The authors draw upon the existing literature, and their experience to discuss treatment strategies aimed at treating patients with both diagnoses. Ignoring either diagnosis is likely to be detrimental to patients; both disorders and their coexistence need to be addressed.

Spirituality is a neglected area of study and research in the treatment of addictions. The role of spirituality in the treatment of the dually diagnosed has received particularly scant attention. One hundred and one patients on an in-patient dual-diagnosis unit, as well as the 31 members of the nursing staff who treat them were surveyed. Patients and staff were questioned about their spiritual beliefs and what was the role of spirituality in the patients' recovery from addiction. Staff were questioned about their own spirituality and what they think the patients' level of spirituality is. In addition the staff were asked what they think the patients' view of spiritually is. Results indicate that the patients and staff are equally spiritually oriented. The patients view spirituality as essential to their recovery and value spiritual programming in their treatment more than some concrete items. The nursing staff underestimated both the patients' level of spirituality and this importance placed on spiritual issues. The authors suggest that more attention should be given by staff to spirituality in the treatment of this population.

This study tested the hypothesis that the antidepressant venlafaxine would be an effective treatment for cocaine abusers with concurrent depressive disorders.This was a randomized, 12-week, double-blind, placebo-controlled trial of outpatients (N = 130) meeting DSM-IIIR criteria for cocaine dependence and major depression or dysthymia (by SCID interview). Participants were treated with venlafaxine, up to 300 mg/day versus placebo. All patients received weekly individual manual-guided relapse prevention therapy. Weekly outcome measures included Clinical Global Impression Scale (CGI), self-reported cocaine use, urine toxicology and the Hamilton Depression Scale (Ham-D).Mood response, defined as a 50% reduction in the Ham-D between randomization and end of study, was 41% (26/64) on venlafaxine, and 33% (22/66) on placebo (p = .39). Measures of depression (Ham-D and CGI) improved more rapidly on venlafaxine than placebo, but these differences disappeared by weeks 6-8. Cocaine outcomes did not differ between treatment groups, and the proportion of patients achieving three or more consecutive weeks of urine-confirmed abstinence was low (venlafaxine: 16%; placebo: 15%). Reduction in cocaine use was associated with mood response.Overall, venlafaxine was not superior to placebo on either mood or cocaine use outcomes. Mood improvement was associated with improvement in cocaine use. However, placebo mood response was only moderate, and the proportion of patients achieving sustained abstinence was low. This suggests that the subgroup of cocaine-dependent patients with depressive disorders is relatively treatment resistant, and that further research is needed to improve outcomes for these patients.

The present study investigated the efficacy of nefazodone and bupropion-sustained release for treating cannabis dependence. A double-blind, placebo-controlled, piggy back design was employed to assess if nefazodone and bupropion-sustained release increased the probability of abstinence from cannabis and reduced the severity of cannabis dependence and cannabis withdrawal symptoms during a 13-week outpatient treatment program. One-hundred and six participants (Mean = 32 years; females n = 25) were randomized to one of three medication conditions (nefazodone, bupropion-sustained release, or placebo) and participated in a weekly, individually based coping skills therapy program. Results indicated an increased probability of achieving abstinence over the course of treatment and a decrease in the severity of cannabis dependence and the withdrawal symptom of irritability. There were no significant effects demonstrated for nefazodone and bupropion-sustained release on cannabis use or cannabis withdrawal symptoms. The results indicate nefazodone and bupropion-sustained release may have limited efficacy in treating cannabis dependence.

Occasionally, large benign intracranial tumours which have existed for many years present as a relatively acute problem. The mechanisms underlying the sudden change are sometimes unclear but infarction of the benign tumour, subsequent cerebral oedema and an increase in intracranial pressure have been reported. The authors describe such a case of focal infarction in a meningioma with a precise chronology of the clinical, radiological and pathologic findings.

There are few published studies assessing the efficacy of pharmacologic treatments for attention-deficit hyperactivity disorder (ADHD) among substance abusers seeking treatment. Eleven patients who met DSM-IV diagnostic criteria for cocaine dependence and adult ADHD were entered into a 12-week single-blind trial of divided daily doses of bupropion (BPR). All patients received weekly individual standardized relapse prevention therapy. Treatment compliance and retention were good. Patients reported significant reductions in attention difficulties, hyperactivity and impulsivity. Self-reported cocaine use, cocaine craving, and cocaine positive toxicologies, also decreased significantly. In a previously published trial, 12 patients who met similar diagnostic criteria for adult ADHD and cocaine dependence were entered into a 12-week trial of divided daily doses of sustained-release methylphenidate (MPH). Improvements observed on BPR were similar to, and did not differ from those previously observed with MPH. These preliminary data suggest that BPR may be as effective as sustained-release MPH, when combined with relapse prevention therapy, for cocaine abusers with adult ADHD. However, a future study directly comparing BPR to MPH in a double-blind placebo-controlled trial is needed.

There appears to be a link between depression and cocaine that is both complex and elusive. The purpose of this study was to examine the effect of venlafaxine, a broad spectrum antidepressant, in the treatment of 13 patients who were diagnosed with cocaine dependence and comorbid major depressive disorder (MDD).The majority of the patients in the study were part of a larger double-blind trial using desipramine. This subgroup consisted of people who had failed to respond to desipramine or could not tolerate its side effects. Thirteen patients were enrolled, 10 men and 3 women. Of the patients, 11 completed the 12-week study. All of the patients had a Hamilton Depression (HAM-D) score greater than 14 at baseline, and each had used at least $20 worth of cocaine per week in the 4 weeks prior to entering the study. In addition, all of the patients received weekly relapse prevention therapy throughout the study. The median dose of venlafaxine was 150 mg/day.The 11 patients who completed the study had significant reductions in mood symptoms by the end of the study. The average total HAM-D score at baseline was 18.0 +/- 3.2; at Week 2, it was 1.9 +/- 0.94; and at the end of the study, it was 1.4 +/- 1.8. The majority of patients reported reductions of cocaine use short of abstinence. All subjects reported a greater than 75% reduction in cocaine use compared to baseline. There were no serious side effects.The results of this small study indicate that venlafaxine may be a safe, well-tolerated, rapidly acting, and effective treatment for patients with a dual diagnosis of depression and cocaine dependence.

This study compares the views on spirituality of dually diagnosed patients (diagnosed with both substance abuse and general psychiatric disorders) and medical students in order to investigate their respective orientations toward spirituality and their views of the importance of spirituality in the treatment of addiction. We administered a modified version of Feagin's "Orientation to Life and God Scale" to assess religious and spiritual orientation in both the patients and students. A second series of items was developed and administered in order to compare the patients' and students' perceptions of the relative importance of a religious and spiritual orientation in substance abuse treatment. A third series of items was also given to compare the nature of religious and health-related services on the inpatient unit that patients and students most wanted to see improved. We found that the medical students responsible for treating substance abuse are significantly less religiously and spirituality oriented than the patients they treat, and that the students do not indicate that spirituality is an important component in the care of these patients. It may be clinically relevant to train medical students in the potential importance of spirituality in addiction treatment so that they can incorporate spirituality into the treatment of addictions.

To the Editor.— Erythropoietic protoporphyria (EPP) is an inherited disorder of heme synthesis due to a defect in the enzyme activity of ferrochelatase, which results in the accumulation of free protporphyrin IX in erythrocytes and plasma, and is associated with cutaneous photosensitivity to UV light (around 400 nm). It is one of the two most common porphyrias, rivaling porphyria cutanea tarda in prevalence. Treatment of the cutaneous symptoms of EPP entail avoidance of sunlight and wearing of protective clothing. Beta carotene, used systemically in doses that produce clinical carotenodermia (recommended serum carotene levels above 400 μg/dL), affords most patients limited photoprotection. It has long been recognized that erythrocyte protoporphyrinis significantly increased in lead toxicity and some anemias without cutaneous photosensitivity. 1 In these cases, protoporphyrin is mainly bound to zinc in the form of zinc protoheme, whereas, in EPP, the accumulated protoporphyrin is metal free. The affinity of zinc for protoporphyrin, and the reduction in erythrocyte photohemolysis that results from cheletion of free protoporphyrin, has been previously demonstrated. 2