Do individuals with a severe mental illness experience greater alcohol and drug-related problems? A test of the supersensitivity hypothesis

The supersensitivity hypothesis posits that individuals with a severe mental illness (i.e., schizophrenia and bipolar disorder; SMI) are more likely to be diagnosed with a substance abuse as opposed to a substance dependence diagnosis, and experience greater negative consequences associated with substance use at lower levels of consumption, as compared with non-SMI substance abusers. This is the first known study to test this hypothesis with a control group of non-SMI substance abusing individuals. Forty-two individuals with only a substance use disorder (SUD-only) and 53 dually diagnosed individuals (DD) were compared on measures of substance use, alcohol and drug dependence, negative consequences, substance use outcome expectancies, and motivation for change. A third group of SMI-only individuals (i.e., no SUD; n=35) were also recruited and all three groups were compared on psychological symptoms. Substance use, negative consequences, substance use outcome expectancies, motivation for change, and severity of alcohol and drug dependence were not found to differ significantly between the DD and SUD-only groups. However, the DD group had significantly greater levels of psychological symptoms, as compared with the SMI-only and SUD-only groups. Overall, this study does not provide support for the supersensitivity hypothesis.     

Readiness for mental health treatment and for changing alcohol use in patients with comorbid psychiatric and alcohol disorders: Are they congruent?

Patients with comorbid psychiatric and alcohol disorders may be ready to change one problem but not the other. This study compared 132 dually diagnosed patients' readiness for mental health treatment to their readiness to change alcohol use. The patients completed a measure of readiness to change alcohol use [the University of Rhode Island Change Assessment Scale-Alcohol (URICA-A)] and the new Readiness for Mental Health Treatment measure. Confirmatory factor analysis (CFA) reveals that the measures have similar factor structures, but correlation and cluster analyses suggest that separate levels of patient motivation exist for mental health treatment and changing alcohol use. The newly developed mental health treatment measure will help clinicians tailor interventions to their patients' needs.     

Incidence and risk of severe infections associated with aflibercept in cancer patients: a systematic review and meta‐analysis

Aims

Aflibercept is an engineered humanized vascular endothelial growth factor (VEGF)‐targeted agent. Severe infections are serious adverse event associated with aflibercept. However, the contribution of aflibercept to infection is still unknown. We thus conducted this meta‐analysis to investigate the overall incidence and risk of developing severe infections in cancer patients treated with aflibercept.

Methods

Electronic databases including PubMed, Embase and abstracts presented at American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) meeting were searched. Eligible studies were phase II and III prospective clinical trials of aflibercept in cancer patients with toxicity profile on infections. Summary incidences, relative risk (RR), odds ratio (OR) and 95% confidence intervals (95% CIs) were calculated by using either random effects or fixed effect models according to the heterogeneity of included studies.

Results

A total of 4310 patients with a variety of solid tumours from 10 prospective clinical trials were included in the meta‐analysis. The incidence of high grade infections associated with aflibercept was 7.3% (95% CI 4.3, 12.0%), with a mortality of 2.2% (95% CI 1.5, 3.1%). In addition, patients treated with aflibercept had a significantly increased risk of developing high grade (RR 1.87, 95% CI 1.52, 2.30; P < 0.001) and fatal (OR 2.16, 95% CI 1.14, 4.11; P = 0.018) infections. No evidence of publication bias was observed. Furthermore, the risk of infections with aflibercept was substantially higher than bevacizumab.

Conclusions

Aflibercept is associated with a significant increased risk of developing severe infections in patients with solid tumours. Frequent clinical monitoring and appropriate management for infections should be emphasized during aflibercept treatment.     

Use of lamotrigine to augment clozapine in patients with resistant schizophrenia and comorbid alcohol dependence: a potent anti-craving effect?

Comorbid alcohol dependence is common in patients with schizophrenia and is associated with a variety of serious adverse consequences. Although case reports exist concerning the positive impact of lamotrigine addition on clozapine treatment in resistant schizophrenia, a review of the literature fails to document any evidence regarding a combination of the two in the treatment of patients with schizophrenia and comorbid alcohol dependence. In the present study, we present three cases in which patients with resistant schizophrenia and comorbid alcohol use disorder were given lamotrigine to augment clozapine. Our findings suggest that clozapine plus lamotrigine may be helpful in reducing alcohol consumption and craving among patients with schizophrenia and comorbid alcohol dependence.     

Does managing the consumption of people with severe alcohol dependence reduce harm? A comparison of participants in six Canadian managed alcohol programs with locally recruited controls

Introduction and Aims

Managed alcohol programs (MAP) are intended for people with severe alcohol‐related problems and unstable housing. We investigated whether MAP participation was associated with changes in drinking patterns and related harms.

Design and Methods

One hundred and seventy‐five MAP participants from five Canadian cities (Hamilton, Ottawa, Toronto, Thunder Bay and Vancouver) and 189 same‐city controls were assessed for alcohol consumption, health, safety and harm outcomes. Length of stay in a MAP was investigated as a predictor of drinking patterns, non‐beverage alcohol consumption and related harms. Statistical controls were included for housing stability, age, gender, ethnic background and city of residence. Negative binomial regression and logistic regression models were used.

Results

Recently admitted MAP participants (≤2 months) and controls were both high consumers of alcohol, predominantly male, of similar ethnic background, similarly represented across the five cities and equally alcohol dependent (mean Severity of Alcohol Dependence Questionnaire = 29.7 and 31.4). After controlling for ethnicity, age, sex, city and housing stability, long‐term MAP residents (>2 months) drank significantly more days (+5.5) but 7.1 standard drinks fewer per drinking day than did controls over the last 30 days. Long‐term MAP residents reported significantly fewer alcohol‐related harms in the domains of health, safety, social, legal and withdrawal.

Discussion and Conclusions

Participation in a MAP was associated with more frequent drinking at lower quantities per day. Participation was associated with reduced alcohol‐related harms over the past 30 days. Future analyses will examine outcomes longitudinally through follow‐up interviews, police and health care records.

     

High‐ and low‐dose Mazindol for cocaine dependence in methadone‐maintained patients: A preliminary evaluation

We conducted a preliminary investigation comparing high‐dose mazindol (8 mg/day), low dose mazindol (1 mg/day), and placebo for cocaine abstinence initiation in a 12‐week, double‐blind, randomized clinical trial enrolling 17 cocaine‐dependent, methadone‐maintained patients. Outcome data did not support a difference between the two dose levels on percentage positive urine screens positive for cocaine (1 mg mazindol=68%, 8 mg mazindol=75%, placebo=91%). Doses of mazindol greater than 8 mg may be needed for a cocaine blocking effect, although potential pressor effects may be a limiting factor.     

Does gender contribute to heterogeneity in criteria for cannabis abuse and dependence? Results from the national epidemiological survey on alcohol and related conditions

Previous research has noted that a unidimensional latent construct underlies criteria for cannabis abuse and dependence. However, no study to date has explored whether gender contributes to heterogeneity in the latent abuse and dependence construct and furthermore, whether after accounting for differences in the mean scores of abuse and dependence across genders, there is any evidence for heterogeneity in the individual abuse and dependence criteria. The present study utilizes data on criteria for cannabis abuse and dependence from a large, nationally representative sample (National Epidemiological Survey on Alcohol and Related Conditions) of 8172 lifetime cannabis users to investigate whether gender contributes to heterogeneity in the underlying construct of cannabis abuse and dependence, and in each individual criterion as well. Analyses, all of which were conducted in MPlus, included factor analysis, as well as MIMIC and multiple-group models for an examination of dimensionality and gender heterogeneity, respectively. Results favor a unidimensional construct for cannabis abuse/dependence, as seen in prior research. We also identify two abuse (legal and hazard) and two dependence (quit and problems) criteria, which show significant gender heterogeneity with the abuse criteria exhibiting higher thresholds in women and the dependence criteria in men. We conclude that the criteria that serve as indicators of DSM-IV cannabis abuse and dependence do not function identically in men and women and that certain criteria (e.g. hazardous use) require further refinement.     

Sulfur mustard exposure and mental health in survivors of Iran–Iraq war with severe lung injuries

To evaluate mental health status of the survivors with sulfur mustard (SM) induced severe lung injury (n?=?291), Iranian standardized symptom checklist 90-revised (SCL90-R) questionnaire was used. The global severity index (GSI) was compared with the cutoff point of Iranian general population (0.4). About (32.9%, n?=?96) had a positive history of previous psychiatric problems. Additional war-related injuries was observed in (89.4%, n?=?261). The mean GSI (1.74?±?0.74) significantly was higher compared to standardized Iranian cutoff point (p?p?相似文献   

Alcohol‐related mortality in Europe: A tentative analysis from the EU project “alcohol consumption and alcohol problems among women in European countries”

Mortality data were collected for eight of the nine study countries in the BIOMED‐II concerted action “Alcohol Consumption and Alcohol Problems among Women in European Countries”;: Finland, France, Germany, Italy, The Netherlands, the United Kingdom (Scotland), Sweden, and Switzerland. An analysis of mortality that is limited to causes of death that are fully attributable to alcohol (DAA) results in a large underestimation of alcohol‐related mortality (ARM) rates in all study countries and especially among females. These estimates can be improved by including an analysis of selected causes of death that are indirectly attributable to alcohol. This produces geographic and time‐trend variability of ARM rates that are more congruent with alcohol drinking levels and trends. From this study, it is evident that when German data are analyzed separately for the former German Democratic Republic (GDR) and the former Federal Republic of Germany (FRG), two distinct ARM patterns result. The authors underline methodologic limits of this study and recommend procedures for a more reliable calculation of European ARM estimates.     

Are substance use, abuse and dependence associated with study participation? Predictors of offspring nonparticipation in a twin-family study

OBJECTIVE: Although epidemiologic studies have reported that problem drinking is associated with nonresponse to surveys, it is unclear whether parents' alcoholism is associated with nonresponse in their offspring. This question is particularly important to family studies of alcoholism. In the current study we constructed a model of offspring nonparticipation in a twin-family design and computed weights to recapture the distribution of offspring alcohol abuse and dependence. METHOD: In 1999, the first wave of a longitudinal study of offspring of alcoholic twins was conducted via telephone interview with members of the Vietnam Era Twin Registry. The target offspring sample consisted of 2,096 male and female children, of whom 1,270 were successfully interviewed. Offspring response status was classified as participation, refusal or unavailable/no consent. Stepwise logistic regression models were used to identify variables that were significantly associated with one or both types of offspring nonparticipation. A multinomial logit procedure with backward deletion was then used to build a model of the three levels of child response. RESULTS: Paternal alcoholism was not significantly associated with offspring nonresponse, although offspring nonparticipation because of not being located, or being deceased, disabled or unavailable was associated with current paternal smoking, paternal divorce and paternal marital status (after adjustment for other predictor variables). CONCLUSIONS: The most important conclusion to be drawn from current results is that the alcohol abuse and dependence history of fathers should not bias analyses in family studies of alcoholism when data are collected via telephone interview. Study limitations and directions for future research are discussed.     

Population pharmacokinetics of edoxaban in patients with symptomatic deep‐vein thrombosis and/or pulmonary embolism—the Hokusai‐VTE phase 3 study

AimsThis study characterized the population pharmacokinetics of edoxaban in patients with symptomatic deep‐vein thrombosis and/or pulmonary embolism in the Hokusai‐VTE phase 3 study. The impact of the protocol‐specified 50% dose reductions applied to patients with body weight ≤ 60 kg, creatinine clearance (CL_cr) of 30 to 50 ml min^–1 or concomitant P‐glycoprotein inhibitor on edoxaban exposure was assessed using simulations.MethodsThe sparse data from Hokusai‐VTE, 9531 concentrations collected from 3707 patients, were pooled with data from 13 phase 1 studies. In the analysis, the covariate relationships used for dose reductions were estimated and differences between healthy subjects and patients as well as additional covariate effects of age, race and gender were explored based on statistical and clinical significance.ResultsA linear two‐compartment model with first order absorption preceded by a lag time best described the data. Allometrically scaled body weight was included on disposition parameters. Apparent clearance was parameterized as non‐renal and renal. The latter increased non‐linearly with increasing CL_cr. Compared with healthy volunteers, inter‐compartmental clearance and the CL_cr covariate effect were different in patients (+64.6% and +274%). Asian patients had a 22.6% increased apparent central volume of distribution. The effect of co‐administration of P‐glycoprotein inhibitors seen in phase 1 could not be confirmed in the phase 3 data. Model‐based simulations revealed lower exposure in dose‐reduced compared with non‐dose‐reduced patients.ConclusionsThe adopted dose‐reduction strategy resulted in reduced exposure compared with non‐dose‐reduced, thereby overcompensating for covariate effects. The clinical impact of these differences on safety and efficacy remains to be evaluated.     

“About last night”: The social ecology of sexual behavior relative to alcohol use among adolescents and young adults in substance abuse treatment

Data were collected in face-to-face interviews from 120 substance-abusing adolescents and young adults (87 men, 33 women; Mage=17.2 years old) recruited from residential and nonresidential treatment facilities in South Florida. Participants described two recent sexual events, one with and one without concurrent alcohol use. Participants described social aspects of these sexual events, actual and intended behaviors, and their feelings about sex in the two alcohol-use contexts. High levels of discrete, risky behaviors occurred in both contexts. Event analysis produced only limited evidence suggesting a higher level of risk in the alcohol-use context. Participants reported less positive feelings about sex when alcohol was used.     

Decreased drinking in adults with co-occurring cannabis and alcohol use disorders in a treatment trial for marijuana dependence: Evidence of a secondary benefit?

The purpose of the present study was to investigate whether cannabis dependent users who met criteria for a secondary diagnosis of alcohol use disorder (AUD) would increase their use of alcohol in response to decreasing their use of marijuana in a behavioral treatment trial for cannabis use disorder (CUD). This phenomenon is commonly known as “substance substitution.” Participants were randomly assigned to one of four 9-session treatment conditions with cannabis and alcohol use measured at baseline, posttreatment, and at 4 follow-ups through 14 months. Of those enrolled (n = 198), 27 (13.6%) also met criteria for AUD. Linear mixed models were used to analyze alcohol use over time with cannabis use and time as predictors. Findings demonstrated that there were no associations between declines in cannabis use and changes in alcohol consumption in the full sample. However, among those with CUD who also had AUD, declines in cannabis use significantly predicted concurrent declines in alcohol use (p < .05). This study did not find evidence of substance substitution among individuals receiving treatment for CUD. Contrary to expectations, the results indicated that individuals with AUD were more likely to decrease, rather than increase, their alcohol use when they reduced their marijuana use. Treatment for CUD in this study appeared to result in improvements in substance use generally, at least for those with comorbid AUD.     

rhBNP therapy can improve clinical outcomes and reduce in‐hospital mortality compared with dobutamine in heart failure patients: a meta‐analysis

Aims

A meta‐analysis was performed to compare the therapeutic outcomes in patients treated for heart failure (HF) with recombinant human brain natriuretic peptide (rhBNP) and dobutamine.

Methods

PubMed, Embase and the Chinese Biomedical Database were exhaustively searched to identify studies relevant to this meta‐analysis. Eight cohort studies were found suitable for inclusion. Data regarding trial validity, methodological processes and clinical outcomes were extracted.

Results

Patients treated with rhBNP showed statistically significant reduction of in‐hospital mortality and re‐admission rates compared with the dobutamine treated patient group (both P < 0.05). Further, the rhBNP treated patient group showed higher survival outcomes, compared with dobutamine treated patients, when the post‐treatment follow‐up period was longer than 6 months (P < 0.05). Stratified analysis based on ethnicity showed a dramatic decrease of in‐hospital mortality among mixed race HF patients receiving rhBNP treatment (P < 0.05), but such decreases were not statistically significant in Asian and Caucasian populations (both P > 0.05). On the other hand, re‐admission rates were significantly lower in rhBNP treated Caucasian and mixed race populations (both P < 0.05). Notably, in rhBNP treated group, dose levels of 0.015 and 0.03 incrementally lowered the re‐admission rates, displaying dose effect, and the re‐admission rates at both rhBNP doses were significantly lower than the dobutamine treated group (both P < 0.05).

Conclusions

Our meta‐analysis results suggested that rhBNP therapy is associated with lower in‐hospital mortality and re‐admission rates in HF patients compared to the dobutamine regimen. Nevertheless, large scale prospective, randomized trials are necessary to confirm these findings.