A DNA Methylation Signature of Addiction in T Cells and Its Reversal With DHEA Intervention.

Previous studies in animal models of cocaine craving have delineated broad changes in DNA methylation profiles in the nucleus accumbens. A crucial factor for progress in behavioral and mental health epigenetics is the discovery of epigenetic markers in peripheral tissues. Several studies in primates and humans have associated differences in behavioral phenotypes with changes in DNA methylation in T cells and brain. Herein, we present a pilot study (n = 27) showing that the T cell DNA methylation profile differentiates persons with a substance use disorder from controls. Intervention with dehydroepiandrosterone (DHEA), previously shown to have a long-term therapeutic effect on human addicts herein resulted in reversal of DNA methylation changes in genes related to pathways associated with the addictive state.

Changes in consumption of opioid analgesics in Israel 2009 to 2016: An update focusing on oxycodone and fentanyl formulations.

PURPOSE: The purpose of the study is to assess opioid (morphine, methadone, oxycodone, pethidine, and fentanyl) consumption in Israel during 2009 to 2016 and identify recent trends. METHODS: Data for all treatment settings, private and public, for the years 2009 to 2016, were extracted from the Israel Ministry of Health's Pharmaceutical Administration database. The data were used to calculate defined daily doses (DDD) per 1000 inhabitants per day, of the various drugs. RESULTS: Consumption of the 5 opioids increased by 68%, from 3.40 DDD/1000 inhabitants/day in 2009 to 5.72 DDD/1000 inhabitants/day in 2016. This trend resulted mostly from increases in oxycodone consumption from 0.50 DDD/1000 inhabitants/day to 2.03 DDD/1000 inhabitants/day (namely, 4-fold) and in fentanyl consumption, from 1.09 DDD/1000 inhabitants/day to 2.33 DDD/1000 inhabitants/day (about 2-fold). The use of the 3 remaining opioids decreased substantially as follows: pethidine from 0.03 DDD/1000/day in 2009 to 0.007 DDD/1000 inhabitants/day in 2016 (-67%), methadone from 1.61 DDD/1000 inhabitants/day to 1.20 DDD/1000 inhabitants/day (-25%), and morphine from 0.17 DDD/1000 inhabitants/day to 0.15 DDD/1000 inhabitants/day (-12%). An increasing trend was also observed in the use of oxycodone/naloxone (Targin) and oxycodone/acetaminophen (Percocet) combinations, while a decrease was observed in the use of pure oxycodone formulations. CONCLUSIONS: The increase in opioid consumption persisted throughout the years 2009 to 2016. This has been associated with substantial changes in the patterns of prescribing opioids, characterized by increases in oxycodone and fentanyl prescriptions and decreases in morphine, methadone, and pethidine prescriptions. A national program aiming to ensure safe use of opioids in the treatment of chronic pain is warranted.

No apparent association between bipolar disorder and cancer in a large epidemiological study of outpatients in a managed care population.

An association between bipolar disorder (BD) and cancer risk has been reported. The purpose of this study was to investigate this association through linkage analysis of a national HMO database and a national cancer registry. All members of the Leumit Health Services (LHS) HMO of Israel from 2000 to 2012 were included. Members with a recorded diagnosis of BD and a record of at least one written or dispensed prescription for pharmacotherapy for treatment of BD were classified as patients with BD. We linked the LHS population with the Israel National Cancer Registry database to capture all cases of cancer reported. Standardized incidence ratios (SIRs) for cancer in the BD population as compared with non-BD LHS members were calculated. A total of 870 323 LHS members were included in the analysis; 3304 of whom met the criteria for inclusion in the BD arm. We identified 24 515 and 110 cancer cases among members without BD and with BD, respectively. Persons with BD were no more likely than other HMO members to be diagnosed with cancer during the follow-up period [SIR, males=0.91, 95% confidence interval (CI): 0.66-1.22; SIR, females=1.15, 95% CI: 0.89-1.47]. Sensitivity analysis using different criteria for positive BD classification (lithium treatment alone or registered physician diagnosis) had no effect on the estimate of cancer risk. A nonstatistically significant association between breast cancer and BD among women was observed (SIR=1.24, 95% CI: 0.79-1.86). These findings do not corroborate previously reported associations between BD and elevated cancer risk.

Trends in the use of antipsychotics in the Israeli inpatient population, 2004-2013.

BACKGROUND: Although serious mental illneses are treated with both typical and atypical antipsychotic grugs, trends in their use in psychiatric inpatient population in Israel are unrecognized. The aim of this study was to detect trends in the use of typical and atypical antipsychotic drugs in the Israeli inpatient psychiatric population throughout the last decade. METHODS: Data regarding allocation of typical and atypical antipsychotics, over the period 2004 to 2013, were extracted from the electronic records of SAREL, Israel's largest private supplier of drugs to healthcare and medical facilities. The data were converted to defined daily doses (DDD) per 1000 inpatients per day. RESULTS: Usage of the ten atypical antipsychotic agents allocated through Israel's national health care system increased by 73 %, from 128.09 DDD/1000 inpatients/day in 2004 to 221.69 DDD/1000 inpatients/day in 2013. This rise from 2004 to 2013 was largely due to a 1.6-fold increase in the administration of olanzapine (48.31 to 79.57 DDD/1000 inpatients/day), a 4.4-fold increase of quetiapine (9.74 to 43.04 DDD/1000 inpatients/day) and 3.7-fold increase of amisulpride (5.54 to 20.38 DDD/1000 inpatients/day). At the same period, the total utilization of 12 main typical antipsychotics decreased by 15.5 %, from 148.67 DDD/1000 inpatients/day in 2004 to 125.57 DDD/1000 inpatients/day in 2013. Over the entire period, total DDDs of both classes of antipsychotics (typical and atypical) increased by 38 %. CONCLUSIONS: Similar to trends in the treatment of psychiatric outpatients in other countries, there was a substantial increase in the administration of atypical antipsychotic drugs to the Israeli psychiatric inpatient population across the study period. A decrease in the use of typical antipsychotics (substitution), polypharmacy, administration for more indications (supplementation) and the use of larger doses of antipsychotics may account, in part, for this increase. The findings have implications for mental health policy in the context of the Mental Health Care System Reform. Systematic studies on appropriate dosing of antipsychotics and augmentation strategies are warranted.

Effect of dehydroepiandrosterone add-on therapy on mood, decision making and subsequent relapse of polydrug users.

A major problem in the treatment of addiction is predicting and preventing relapse following a rehabilitation program. Recently, in preclinical rodent studies dehydroepiandrosterone (DHEA) was found to markedly improve the resistance to drug reuse. In a double-blind, placebo-controlled study, we examined the effect of DHEA on relapse rates in adult polydrug users taking part in a detoxification program enriched with intensive psychosocial interventions and aftercare. During treatment, participants (79 percent males, mean age 28) consumed DHEA (100 mg/day) or placebo daily for at least 30 days. Of the 121 initial volunteers, 64 participated for at least 1 month. While in treatment, DHEA reduced negative affect on the Positive and Negative Affect Scale (F = 4.25, P = 0.04). Furthermore, in a 16-month follow-up, we found that reuse rates in the DHEA condition were about a third compared with placebo (12 versus 38 percent; χ(2) = 5.03, P = 0.02). DHEA treatment also resulted in an increase in DHEA sulfate (DHEA-S) 1 month following treatment, and the level of DHEA-S predicted relapse in the follow-up assessment.

Dental Health and the Type of Antipsychotic Treatment in Inpatients with Schizophrenia.

AIM: This study examined the association between dental conditions in hospitalized patients with ICD-10 schizophrenia and type of antipsychotic treatment. Based on the literature suggesting that atypical antipsychotics are thought to be more tolerable than typical antipsychotics, we hypothesized that hospitalized patients with schizophrenia treated with atypicals would have better dental health than those treated with typicals alone or with a combination of both (combined group). METHODS: A representative sample of 348 patients (69% males), aged 51.4 (SD=14.5, range 31-58) years, was assessed on the standardized criteria of the Decayed, Missing and Filled Teeth (DMFT) index and component scores. Data on medication were extracted from patients' electronic medical records. RESULTS: Patients treated with typicals had significantly higher DMFT index scores than those who received atypicals (23.5±9.9 vs. 19.0±10.5; p < 0.05), and higher Missing (20.2±11.6 vs. 13.5±11.2; p < 0.01) and lower Filled (1.0±2.4 vs. 2.1±3.9; p < 0.05) teeth component scores. No between-group differences in Decayed component scores were found (2.3±3.4 and 3.4±5.0, respectively; p > 0.05). The combined treatment group was situated in between the typicals and atypicals groups on all measures. CONCLUSIONS: The results suggest that patients with schizophrenia maintained on atypicals have better dental health than patients treated with typicals or with a combination of both. From an oral health perspective, monotherapy with atypicals is superior to both typical and atypical/typical treatments. Although the choice between typical and atypical antipsychotic agents is based mainly on clinical psychiatric efficacy, the benefit of atypicals with regard to dental health should be taken into consideration in clinician's decision making.

Validation of the HCR-20 Scale for Assessing Risk of Violent Behavior in Israeli Psychiatric Inpatients.

BACKGROUND: Assessment of risk of violent behavior in forensic psychiatric practice is a complex and responsible clinical task and the use of a valid instrument can make the expert's work more effective. The Historical Clinical and Risk Management scale 20 (HCR-20) is a widely accepted measure of the risk of violence, sexual and criminal behavior. The aim of this study was to validate the HCR-20 in Israeli psychiatric inpatient settings. METHOD: In a prospective design, data were collected on 150 male patients aged 15-65, diagnosed with ICD-10 schizophrenia, who were hospitalized in three wards: an acute psychiatric ward (n=50), a high security ward (n=50), and an open ward (n=50). The HCR-20, as the predictor measure, and the Positive and Negative Syndrome Scale, as a concurrent measure, werecompleted at baseline, and the Violence Assessment Scale, as the outcome measure, was completed at 6-, 12- and 18-month follow-up points. RESULTS: Internal consistency reliability was good for the total HCR-20 scale, satisfactory for the H-subscale, but low for the C- and R-subscales. Concurrent validity was good for the C-subscale, and discriminative validity was reasonable for the C- and H-subscales. The total scale as well as the Historical and Clinical subscales predicted the risk of physical as well as physical/sexual violent behavior at both 6- and 18-month follow-up points. CONCLUSIONS: Appropriate psychometric properties of the HCR-20 suggest that it can serve as a useful measure of the risk of violent behavior in psychiatric settings in Israel. Further research is necessary to confirm norms and cut-off scores, using a larger representative sample.

Associations between attachment and psychopathology dimensions in a large sample of patients with psychosis.

Attachment theory is a powerful theoretical framework that complements and extents current models psychosis. We tested the hypothesis that attachment anxiety and avoidance are differentially associated with the severity of positive, negative and general psychopathology symptoms in patients with a diagnosis of psychosis. Five hundred patients with DSM-IV or ICD-10 diagnoses of psychotic disorders (schizophrenia, schizoaffective or non-affective psychosis) from independent samples from Netherlands, United Kingdom and Israel completed the Relationship Questionnaire. Psychopathology was assessed with the Positive and Negative Syndromes Scale. We used both categorical and dimensional approach to attachment data, which were analyzed using ANOVA with post-hoc tests, Pearson's correlations and multiple regression analysis. The conservative level of statistical significance was established (p < 0.001) to control for multiple testing. After adjustment for possible confounders, attachment anxiety predicted severity of positive symptoms as well as affective symptoms. Both attachment anxiety and avoidance were associated with severity of hallucinations and persecution Contrary to predictions, attachment avoidance was not associated with overall scores for negative symptoms, although there was some evidence of relatively weaker association between avoidance and social and emotional withdrawal.

Validation of the Hebrew and Arabic Versions of the Outcome Questionnaire (OQ-45).

BACKGROUND: Measuring the progress of mental health treatment aids in assessment and monitoring of psychotherapeutic outcomes. The OQ-45 is a widely accepted measure of such outcomes. The aim of this study was to validate the Hebrew and Arabic versions of the OQ-45. METHOD: Data were collected from three samples: non patient university students (n=189), university mental health clinic patients (n=37), and outpatient mental health clinic patients (n=135). Subjects completed the OQ-45 as well as the BSI and PHQ-9 questionnaires. RESULTS: Test-retest and internal reliability, and concurrent and discriminative validity of both OQ-45 versions were satisfactory. Sensitivity of the Hebrew and Arabic versions was 0.70 and 0.80, respectively, and the specificity was 0.69and 0.93, respectively. Sensitivity-to-change was noted only for the Symptom Distress (SD) subscale. LIMITATIONS: Sensitivity-to-change was not demonstrated for the total OQ-45, possibly due to a too-short follow-up period. CONCLUSIONS: Adequate psychometric properties of the Hebrew and Arabic OQ-45 suggest that they can serve as useful measures of mental health treatment in Israel.Further research is necessary to confirm norms, cut-off scores and sensitivity-to-change using a larger representative population and diverse types of treatment over a longer period of time.

Trends in dual diagnosis of severe mental illness and substance use disorders, 1996-2010, Israel.

OBJECTIVES: (1) To examine the trends in the incidence of dual diagnosis (DD) of severe mental illness and substance-related disorders among inpatients in Israel, and (2) the demographic and clinical correlates of DD patients. METHOD: Using data from the National Psychiatric Case Register, we identified 56,774 inpatients aged 15-64 whose first psychiatric hospitalization occurred between 1996 and 2010. We compared the characteristics of inpatients having DD with drugs, alcohol or drug/alcohol abuse with those with mental disorder only. RESULTS: Over the period, DD with drugs decreased from 8.2% in 1996 to 6% in 2010; DD with alcohol increased from 3% to 4% and DD with drugs/alcohol from 2% to 4%. DD with drugs was highest, whereas DD with alcohol was lowest for the youngest age- group in 1996 but increased to the same as other age-groups in 2006-2010. Male gender, a previous suicide attempt, compulsory hospitalizations and marital status were positive predictors for all DD. Immigrant status was a positive predictor of DD with alcohol, but the opposite for DD with drugs; being Jewish and psychotic diagnosis was a positive predictor of DD with drugs, but negative for DD with alcohol. CONCLUSIONS: Over the study period, DD with drugs has decreased among young patients, although it is still higher than among older groups. However, DD with alcohol or drugs/alcohol has increased in the younger group. The clinical-demographic profile of DD patients was similar to that from the relevant literature, except for immigrant status that was negatively associated with DD with drugs.

Baclofen as add-on to standard psychosocial treatment for alcohol dependence: a randomized, double-blind, placebo-controlled trial with 1 year follow-up.

BACKGROUND: Limited clinical trials and case-reports yielded conflicting results regarding the efficacy of baclofen (a GABAB agonist) in the treatment of alcohol dependence. The aim of this study was to test the efficacy and tolerability of baclofen in alcohol dependent patients in Israel. METHODS: The study was a double-blind, placebo-controlled, randomized trial comparing 50mg/day of baclofen to placebo over 12 weeks, in addition to a standard psychosocial intervention program, with 26-week and 52-week follow-up observations. The percentages of heavy drinking days and abstinent days were the primary outcome measures, and craving, distress and depression levels; self-efficacy; social support from different sources; and health-related quality of life (HRQL) were secondary outcomes. Tolerability was also examined. RESULTS: Sixty-four patients were randomized; 62% completed the 12-week trial and 37% completed the 52-week follow-up. No between group differences were found in the percentages of heavy drinking and abstinent days. A significant reduction in levels of distress, depression and craving and improved HRQL occurred for both arms, whereas self-efficacy and social support remained unchanged in both groups. No adverse events were observed. CONCLUSIONS: Unlike previous positive trials in Italy, and similarly to a negative trial in the USA, we found no evidence of superiority of baclofen over placebo in the treatment of alcohol dependence. However, the high placebo response undermines the validity of this conclusion. Therefore, more placebo-controlled trials are needed to either verify or discard a possible clinical efficacy of baclofen for alcohol dependence.

The Israel Survey of Mental Health among Adolescents: prevalence of attention-deficit/hyperactivity disorder, comorbidity, methylphenidate use, and help-seeking patterns.

BACKGROUND: The prevalence of ADHD is controversial, with many feeling that this disorder is over- or under-diagnosed. OBJECTIVES: To study the prevalence of attention-deficit/hyperactivity disorder (ADHD) and its association with sociodemographic characteristics, comorbid mental disorders, medical services, and methylphenidate use in the Israeli adolescent population. METHODS: The Israel Survey of Mental Health among Adolescents was conducted in a representative national sample of 14-17 year olds and their mothers. The Development and Well-Being Assessment was administered to identify DSM-IV diagnoses of ADHD and comorbid mental and learning disorders, and the results were verified by senior child psychiatrists. Respondents were also asked about their use of medical services and psychotropic drug intake in the past 12 months. RESULTS: Three percent of the adolescents met the DSM-IV criteria for ADHD. ADHD was significantly associated with gender (higher prevalence in boys than girls), ethnicity (higher prevalence in Jews than Arabs/Druze), referral to a medical professional, and maternal help-seeking for the emotional or behavioral problems of the adolescent. Medication was prescribed to 2.9% of adolescents: 34.6% with a diagnosis of ADHD had not been prescribed methylphenidate in the past year, and 34.6% of the medicated subjects did not have a diagnosis of ADHD. None of the Arab/Druze adolescents was receiving stimulants compared to 3.7% of the Jewish adolescents. CONCLUSIONS: Despite advances in public awareness of mental disorders in youth, a substantial proportion of older Israeli adolescents, especially from minority groups, are under-diagnosed or untreated. At the same time, many, especially from the Jewish majority, are over-diagnosed and potentially over-treated. Ethnic disparities in rates of mental health care highlight the urgent need to identify and overcome barriers to the recognition and treatment of these conditions.

Trends in attention deficit hyperactivity disorder drugs consumption, Israel, 2005-2012.

PURPOSE: The aim of this study was to describe trends in attention deficit hyperactivity disorder (ADHD) drugs consumption in Israel (Ritalin, Concerta, Daytrana, Vyvanse, Focalin, and Adderall) over the 8 years, 2005-2012, and to explore explanations for changes in amounts and patterns of the utilization. METHODS: Data for the period from 2005 to 2012 were extracted from the database maintained by the Israel Ministry of Health's Pharmaceutical Administration. The data were converted into a defined daily dose (DDD) per 1000 inhabitants per day. RESULTS: Consumption of all ADHD drugs covered by Israel's national health care system doubled over the study period, from 4.02 DDD/1000 inhabitants/day in 2005 to 9.92 DDD/1000 inhabitants/day in 2012. This rise was largely due to a fivefold increase in Concerta consumption (from 0.46 DDD/1000 inhabitants/day in 2005 to 2.28 DDD/1000 inhabitants/day in 2012) and a threefold increase in Ritalin consumption (from 1.43 DDD/1000 inhabitants/day in 2005 to 4.84 DDD/1000 inhabitants/day in 2012). Adderall (amphetamine mixed salts) consumption rose by 30% for the same period. A substantial trend was noted for increased utilization of high-dose formulations together with proportional decline in low-dose consumption. In the same period, cost of the medications has been reduced an average by 20-25%. CONCLUSIONS: There has been a drastic rise in ADHD drugs consumption in Israel over 2005-2012. This has been associated with substantial reduction in cost and changes in the pattern of prescribing that characterized by increased prescription of high-dose long-acting preparations of ADHD drugs and decreased prescription of their low-dose, short-acting formulations.

The CANSAS self-report for screening of needs in outpatients with schizophrenia and schizoaffective disorders.

The importance of needs assessment for service development has been widely recognized. In this study we examined the agreement between the Camberwell Assessment of Need Short Appraisal Schedule self-report version (CANSAS-P) and the Camberwell Assessment of Need interview-based scale in 100 outpatients with schizophrenia and schizoaffective disorders. We found equivalent number of met, unmet, and no needs for most of the domains of the two instruments. Both intraclass correlations and Kappa reliability coefficients were high for most need domains. The high agreement between the two instruments suggests that the CANSAS-P can be used as a screening tool to detect unmet needs in both clinical routine practice and research surveys in mental health outpatient settings.

Interpersonal distances, coping strategies and psychopathology in patients with depression and schizophrenia.

AIM: To explore (1) intergroup differences in comfortable interpersonal distances (CIDs) and the use of coping strategies; (2) the association of these parameters with individual symptomatology; and (3) the interplay between CIDs and coping styles in patients with depression and schizophrenia. METHODS: The parameters of interest were assessed by means of standardized questionnaires: CID and Coping Inventory for Stressful Situations. Psychopathology was evaluated with the Beck Depression Inventory and Positive and Negative Syndromes Scale. ANOVA, Pearson's correlations and multiple regression analyses were used to examine relationships among the variables. RESULTS: Compared with controls, depressed patients were more distanced from family members, significant others and self-images, whereas patients with schizophrenia were less distanced from neutral and threat-related stimuli. Distancing from self-images was mostly associated with depression severity in depressed patients, whereas distancing from hostile and threat-related stimuli with the severity of psychotic and affective symptoms in patients with schizophrenia. Both patient groups used more emotion-oriented than task-oriented and avoidance-oriented coping strategies. Self-distancing among patients with schizophrenia was positively associated with the use of the social diversion coping, implying social support seeking. CONCLUSION: Patients with depression and schizophrenia use different maladaptive emotion - regulation strategies to cope with their symptoms and related distress. Training in stress management might provide these patients with skills for more effective emotion regulation.

Contribution of attachment insecurity to health-related quality of life in depressed patients.

AIM: To examine the individual contributions of insecure attachment styles and depression symptom severity to health-related quality of life (HRQoL) in patients diagnosed with adjustment disorder (AJD) with depressed mood. METHODS: Participants were 67 patients diagnosed with International Classification of Diseases, Tenth edition AJD with depressed mood, who completed standardised self-report questionnaires measuring study variables. Mean scores and SDs were computed for the outcome and predictor measures. Pearson correlations among the measures were computed. The study hypotheses were tested using analysis of variance (ANOVA) and multiple regression analyses. All analyses were performed using the SPSS-17 software package (SPSS Inc., Chicago, IL, United States). RESULTS: ANOVA showed a significant main effect of the insecure attachment styles on depression symptom severity and life satisfaction scores. The results suggest that depressive symptoms were more severe (F = 4.13, df = 2.67, P < 0.05) and life satisfaction was poorer (F = 5.69, df = 2.67, P < 0.01) in both anxious-ambivalently and avoidantly attached patients compared with their securely attached counterparts, whereas the two insecure groups did not significantly differ by these variables. The anxious/ambivalent attachment style and depression symptom severity significantly contributed to HRQoL, accounting for 21.4% and 29.7% of the total variance, respectively [R(2) = 0.79; Adjusted R(2) = 0.77; F (5, 67) = 33.68, P < 0.0001], even after controlling for gender, marital and employment status confounders. CONCLUSION: The results show that the anxious/ambivalent attachment style together with depression symptom severity substantially and independently predict the HRQoL outcome in AJD with depressed mood.

Attachment styles and affect regulation among outpatients with schizophrenia: relationships to symptomatology and emotional distress.

OBJECTIVES: Using the model of activation and dynamics of the attachment system (Shaver & Mikulincer, 2002) and dynamic stress-vulnerability models of psychosis (Ingmar & Luxton, 2005) as the analytical frameworks, the authors tested the hypothesis that the insecure attachment styles are differentially associated with the severity of psychopathological symptoms and emotional distress among outpatients with International Classification of Diseases, Tenth edition (ICD-10) diagnosis of schizophrenia. METHODS: Attachment styles were identified using the Relationship Questionnaire (Bartholomew & Horowitz, 1991) among 100 outpatients with an ICD-10 schizophrenia diagnosis. Current symptom severity was measured by the Positive and Negative Syndromes Scale (Kay, Fiszbein, & Opler, 1987) and emotional distress by the General Health Questionnaire (Goldberg & Williams, 1988). Univariate and multivariate analyses were performed to test the hypotheses. RESULTS: The preoccupied and fearful-avoidant attachment patterns were associated with higher scores of psychotic (delusions, suspiciousness/persecution, and hallucinatory behaviour) and affective (anxiety, tension, guilt feeling, and depression) symptoms, whereas the dismissing-avoidant style was associated with only anxiety. All the insecure attachment styles were associated with elevated emotional distress. CONCLUSIONS: The findings support the hypothesis of a predisposing role of the preoccupied and fearful-avoidant styles in psychotic symptom formation and call for cognitive interpersonal interventions geared to reduce symptom and emotional distress severity.

Mortality and causes of death among users of methadone maintenance treatment in Israel, 1999-2008.

OBJECTIVES: To determine all-cause and specific-causes mortality, in the years 1999-2008, among opioid-dependent users treated at methadone maintenance treatment (MMT) clinics in Israel and to compare the obtained results with data from relevant studies worldwide. METHOD: The records of patients treated at MMT units were linked to the nationwide database of causes of death. Information about the Israeli general population from the Central Bureau of Statistics was used for comparison to match sex and age to the cohort under study. Crude mortality rates (CMRs) per 100 persons per year (PY) and standardized mortality ratios (SMRs) with 95% confidence intervals (CIs) were calculated. RESULTS: The overall CMR for MMT users was 1.49/100 PY (CI 1.40-1.59) and was not associated with gender, age at entering MMT, ethnicity, and immigrant status. The leading causes of mortality were sudden/undefined death (0.31/100 PY, CI 0.26-0.35), overdose (0.22/100 PY, CI 0.17-0.27), and cancer (0.15/100 PY, CI 0.12-0.18). The MMT users were 12.2 times more likely to die from all causes than people from the general population. Overall, our estimates were comparable with the figures pooled from relevant studies. CONCLUSIONS: The results suggest that the excess mortality of MMT users is associated with an increased morbidity, which alone or in combination with service-related risks, lead to worse outcomes.

Ten-year quality of life outcomes among patients with schizophrenia and schizoaffective disorder II. Predictive value of psychosocial factors.

PURPOSE: To identify psychosocial predictors of change in health-related quality of life among patients with schizophrenia (SZ) and schizoaffective (SA) disorders over a 10-year period. METHODS: In a naturalistic longitudinal design, 108 patients with SZ/SA disorders completed a comprehensive rating scale battery including self-reported quality of life, emotional distress symptoms, coping styles, sense of self-efficacy, and social support, as well as observer-rated psychopathology, medication side effects, and general functioning at 2 time points, baseline and 10 years later. RESULTS: Regression models revealed that reduction in self-reported symptoms of depression, sensitivity or anxiety along with increase in self-efficacy, social support, and emotion-oriented coping scores predicted improvement in domain-specific perceived quality of life. Adjustment of the psychosocial models for the effects of disorder-related factors (psychopathology, functioning, and medication side effects) confirmed the above findings and amplified their statistical power. CONCLUSIONS: In the long-term course of severe mental disorders (SZ/SA), changes in the psychosocial factors are stronger predictors of subjective quality of life outcome than disorder-related changes. The findings enable better understanding of the combined effects of psychopathology and psychosocial factors on quality of life outcome over a 10-year period.

Differences in the consumption rates and regulatory barriers to the accessibility of strong opioid analgesics in Israel and St. Petersburg.

OBJECTIVE: To compare trends in opioid consumption in Israel and St. Petersburg/Russia (morphine, oxycodone, pethidine, fentanyl, methadone, buprenorphine, trimeperidine, and papaveretum) over the period 2000-2008, and to describe the regulatory barriers to their accessibility as an exploratory variable for between-country differences. METHODS: Data were drawn from the databases maintained by the Israel Ministry of Health's Pharmaceutical Administration and the St. Petersburg Central Pharmaceutical Reserve. The data were converted into a defined daily dose (DDD)/1,000 inhabitants/day. Regulation was evaluated according to the WHO guidelines for the assessment of national opioid regulation. RESULTS: The opioid consumption rates in Israel were substantially higher than those in St. Petersburg. The excess in DDD/1,000 inhabitants/day was for fentanyl +0.287 in 2000 and +1.206 in 2008, for morphine +0.245 in 2000 and +0.122 in 2008, and for pethidine/trimeperidine +0.035 in 2000 and +0.007 in 2008. Oxycodone consumption increased in Israel from 0.31 DDD/1,000 inhabitants/day in 2000 to 0.46 DDD/1,000 inhabitants/day in 2008, whereas this analgesic is not available in St. Petersburg. Methadone and buprenorphine consumption rose in Israel, whereas these drugs are not available in Russia. Conversely, omnopon consumption decreased in St. Petersburg from 0.0206 DDD/1,000 inhabitants/day in 2000 to 0.00304 DDD/1,000 inhabitants/day in 2008, whereas the compound is not available in Israel. St. Petersburg differs from Israel with less opioid formulary availability and greater regulatory restrictions. CONCLUSION: The results suggest that strong opioid analgesics consumption rates in St. Petersburg yield those in Israel, and that the between-countries differences in opioid formularies availability and legal and regulatory barriers to opioids accessibility are responsible for the consumption discrepancies.