Systematic review of prospective studies investigating “remission” from amphetamine,cannabis, cocaine or opioid dependence

Aims

To review and summarize existing prospective studies reporting on remission from dependence upon amphetamines, cannabis, cocaine or opioids.

Methods

Systematic searches of the peer-reviewed literature were conducted to identify prospective studies reporting on remission from amphetamines, cannabis, cocaine or opioid dependence. Searches were limited to publication between 1990 and 2009. Reference lists of review articles and important studies were searched to identify additional studies. Remission was defined as no longer meeting diagnostic criteria for drug dependence or abstinence from drug use; follow-up periods of at least three years were investigated. The remission rate was estimated for each drug type, allowing pooling across studies with varying follow-up times.

Results

There were few studies examining the course of psychostimulant dependence that met inclusion criteria (one for amphetamines and four for cocaine). There were ten studies of opioid and three for cannabis dependence. Definitions of remission varied and most did not clearly assess remission from dependence. Amphetamine dependence had the highest remission rate (0.4477; 95%CI 0.3991, 0.4945), followed by opioid (0.2235; 95%CI 0.2091, 0.2408) and cocaine dependence (0.1366; 95%CI 0.1244, 0.1498). Conservative estimates of remission rates followed the same pattern with cannabis dependence (0.1734; 95%CI 0.1430, 0.2078) followed by amphetamine (0.1637; 95%CI 0.1475, 0.1797), opioid (0.0917; 95%CI 0.0842, 0.0979) and cocaine dependence (0.0532; 95%CI 0.0502, 0.0597).

Conclusions

The limited prospective evidence suggests that “remission” from dependence may occur relatively frequently but rates may differ across drugs. There is very little research on remission from drug dependence; definitions used are often imprecise and inconsistent across studies and there remains considerable uncertainty about the longitudinal course of dependence upon these most commonly used illicit drugs.     

CDH1-related hereditary diffuse gastric cancer syndrome: clinical variations and implications for counseling

CDH1 mutation carriers have a strongly increased risk of developing gastric cancer (GC) and lobular breast cancer (LBC). Clinical data of GC cases and surgical and histological data of prophylactic gastrectomies and mastectomies of all 10 Dutch CDH1 mutation families were collected. In vitro functional assays were performed to analyze the nature of the newly found missense mutation c.1748T>G (p.Leu583Arg). Ten different CDH1 mutations were found. Functional assays gave strong arguments for the pathogenic nature of the p.Leu583Arg mutation. The pedigrees comprised 36 GC cases (mean age 40 years, range 20-72 years) and one LBC case. Twenty-nine/37 carriers alive, aged 18-61 years, underwent prophylactic gastrectomy. Invasive GC-foci and premalignant abnormalities were detected in 2 and 25 patients, respectively. In four patients GC/signetring cell (SRC) foci were diagnosed at preoperative gastroscopy. Long-standing presence of SRCs without progression to invasive carcinoma was shown in two others. Multifocal LBC/LCIS was found in the two prophylactic mastectomy specimens. Clefts of lip and/or palate (CL/P) were reported in seven individuals from three families. The age at onset and aggressiveness of GC is highly variable, which has to be included in counseling on planning prophylactic gastrectomies. The incidence of LBC is expected to increase and prophylactic mastectomy needs to be considered. The relationship between CL/P and CDH1 needs further study to inform future parents from hereditary diffuse gastric cancer (HDGC) families adequately.     

Cognitive behavioural therapy for depression, panic disorder and generalized anxiety disorder: a meta-regression of factors that may predict outcome

OBJECTIVE: To determine which factors impact on the efficacy of cognitive behavioural therapy (CBT) for depression and anxiety. Factors considered include those related to clinical practice: disorder, treatment type, duration and intensity of treatment, mode of therapy, type and training of therapist and severity of patients. Factors related to the conduct of the trial were also considered, including: year of study, country of study, type of control group, language, number of patients and percentage of dropouts from the trial. METHOD: We used the technique of meta-analysis to determine an overall effect size (standardized mean difference calculated using Hedges' g) and meta-regression to determine the factors that impact on this effect size. We included randomized controlled trials with a wait list, pill placebo or attention/psychological placebo control group. Study participants had to be 18 years or older and all have diagnosed depression, panic disorder (with or without agoraphobia) or generalized anxiety disorder (GAD). Outcomes of interest included symptom, functioning and health-related quality of life measures, reported as continuous variables at post-treatment. RESULTS: Cognitive behavioural therapy for depression, panic disorder and GAD had an effect size of 0.68 (95% CI=0.51-0.84, n=33 studies, 52 comparisons). The heterogeneity in the effect sizes was fully explained by treatment, duration of therapy, inclusion of severe patients in the trial, year of study, country of study, control group, language and number of dropouts from the control group. Disorder was not a significant predictor of the effect size. CONCLUSIONS: Cognitive behavioural therapy is significantly less effective for severe patients and trials that compared CBT to a wait-list control group found significantly larger effect sizes than those comparing CBT to an attention placebo, but not to a pill placebo. Further research is needed to determine whether CBT is effective when provided by others than psychologists and whether it is effective for non-English-speaking patient groups.     

Large induction of type III deiodinase expression after partial hepatectomy in the regenerating mouse and rat liver

The deiodinase types 1 (D1) and 2 (D2) catalyze the activation of T4 to T3, whereas type 3 deiodinase (D3) catalyzes the inactivation of T3 and T4. D3 plays a key role in controlling thyroid hormone bioavailability. It is highly expressed during fetal development, but also in other processes with increased cell proliferation, e.g. in vascular tumors. Because tissue regeneration is dependent on cellular proliferation and is associated with activation of fetal genes, we evaluated deiodinase activities and mRNA expression in rat and mouse liver, as well as the local and systemic thyroid hormone status after partial hepatectomy (PH). We observed that in rats, D3 activity was increased 10-fold at 20 h and 3-fold at 48 h after PH; D3 mRNA expression was increased 3-fold at 20 h. The increase in D3 expression was associated with maximum 2- to 3-fold decreases of serum and liver T3 and T4 levels at 20 to 24 h after PH. In mice, D3 activity was increased 5-fold at 12 h, 8-fold at 24 h, 40-fold at 36 h, 15-fold at 48 h, and 7-fold at 72 h after PH. In correlation with this, D3 mRNA was highest (6-fold increase), and serum T3 and T4 were lowest at 36 h. Furthermore, as a measure for cell proliferation, 5-bromo-2'-deoxyuridine incorporation peaked at 20-24 h after PH in rats and at 36 h in mice. No significant effect on D1 activity or mRNA expression was found after PH. D2 activity was always undetectable. In conclusion, we found a large induction of hepatic D3 expression after PH that was correlated with an increased cellular proliferation and decreased serum and liver T3 and T4 levels. Our data suggest that D3 is important in the modulation of thyroid hormone levels in the regenerating liver, in which a decrease in cellular T3 permits an increase in proliferation.     

The effects of Guillain-Barré syndrome on the close relatives of patients during the first year

OBJECTIVE: To study the impact of Guillain-Barré Syndrome (GBS) on the psychosocial functioning of the closest relative and on family functioning during the first year after GBS. METHOD: At 1 (=T1), 3 (=T3), 6 (=T6), and 12 months (=T12) after the onset of GBS, relatives of patients received the General Health Questionnaire (GHQ28) and the Family Assessment Device (FAD). Sixty-three relatives returned the GHQ28 at all four designated intervals. At T1 the relatives also received a questionnaire that contained questions on the impact on their daily life. The answers to these questions yielded a Daily Living Impact index. From the 110 relatives, 86 returned this questionnaire. RESULTS: 72% of the 86 relatives reported one or more problems in daily living. At T1 the scores of the GHQ subscales ranged from normal to mildly disturbed. The relatives showed significant improvement in their somatic complaints and anxiety during the first half year. Social dysfunction remained somewhat less than normal, severe depression was not found. At T1 and T3 the scores of the GHQ28 and some subscales differed significantly depending on the severity of the functional status of the patient, but not at T6 and T12. Relatives of patients with severe residua at 1 month score worse on the GHQ28 and most subscales at 6 months. The FAD was normal at all moments measured. CONCLUSIONS: Psychological morbidity of close relatives is significantly higher in the first months after the onset of GBS. The patient's condition has an important impact on the psychosocial functioning of close relatives. Therefore, a family approach is recommended to neurologist and other medical personnel during the first period of the disease. Also patient support groups may play a beneficial role for the relatives of GBS patients.     

Successful intra-arterial thrombolysis beyond the accepted 6-hour time window in two young patients

Two young women with ischemic stroke successfully underwent intra-arterial thrombolysis (IAT) 10 and 11 h, respectively after stroke onset. A 23-year-old (case 1) and a 22-year-old woman (case 2) who developed severe neurological deficits (NIHSS 20 and 13, respectively) were presented to our hospital 9 h after onset of the symptoms. In case 1 a CT angiography (CTA) revealed an occlusion of the left middle cerebral artery (MCA) and in case 2 CTA showed a large embolus at the left carotid bifurcation, almost entirely occluding the internal carotid artery. We decided to apply IAT beyond the generally accepted 6-hour time window. Case 1 was treated with 2 mg rtPA administered locally in the occluded MCA followed by 70 mg rtPA (1 mg/min) and case 2 was treated with 100,000 IU urokinase in the left common carotid artery followed by 200,000 IU during 2 h and 10 mg abciximab. In case 1 IAT resulted in complete recanalisation of the MCA within 3 h and complete resolution of symptoms in the following six weeks. In case 2 IAT resulted in an initial 50% reduction of the thrombus. After nine days CTA showed complete lysis and the patient had completely recovered. Both patients suffered from Anti-Phospholipid-Syndrome. The results show that IAT may be beneficial to young patients with a severe stroke, even beyond the 6-hour time window.     

Altered cingulate sub-region activation accounts for task-related dissociation in ERN amplitude as a function of obsessive-compulsive symptoms

Larger error-related negativities (ERNs) have been consistently found in obsessive-compulsive disorder (OCD) patients, and are thought to reflect the activities of a hyperactive cortico-striatal circuit during action monitoring. We previously observed that obsessive-compulsive (OC) symptomatic students (non-patients) have larger ERNs during errors in a response competition task, yet smaller ERNs in a reinforcement learning task. The finding of a task-specific dissociation suggests that distinct yet partially overlapping medio-frontal systems underlie the ERN in different tasks, and that OC symptoms are associated with functional differences in these systems. Here, we used EEG source localization to identify why OC symptoms are associated with hyperactive ERNs to errors yet hypoactive ERNs when selecting maladaptive actions. At rest, OC symptomatology predicted greater activity in rostral anterior cingulate cortex (rACC) and lower activity in dorsal anterior cingulate cortex (dACC). When compared to a group with low OC symptom scores, the high OC group had greater rACC reactivity during errors in the response competition task and less deactivation of dACC activity during errors in the reinforcement learning task. The degree of activation in these areas correlated with ERN amplitudes during both tasks in the high OC group, but not in the low group. Interactive anterior cingulate cortex (ACC) systems associated avoidance of maladaptive actions were intact in the high OC group, but were related to poorer performance on a third task: probabilistic reversal learning. These novel findings link both tonic and phasic activities in the ACC to action monitoring alterations, including dissociation in performance deficits, in OC symptomatic participants.