An exploratory study of the prevalence and adverse associations of in-school traditional bullying and cyberbullying among adolescents in Connecticut.

Bullying, traditional or cyber, among adolescents, is a public health concern. In this study, we explored frequencies and correlates of different forms of bullying among Connecticut high-school students. Youth Risk Behavior Survey data from 2019 from Connecticut adolescents (N = 1814) were used. χ2 tests and survey-weighted logistic regressions examined relationships between bullying subgroups (in-school traditional bullying (ISTB) only, cyberbullying only, and both) and mental concerns, risk behaviors, academic performance, physical health, and receipt of social support, with the logistic regressions adjusted for demographics. The past-12-month frequency of having experienced only cyberbullying was 5.6%, only ISTB was 9.1%, and both forms was 8.7%. Between-group differences were observed by bullying status in terms of sex and race/ethnicity. In adjusted models, bullying status was associated with suicide attempts, suicidal ideation, self-harm, depression/dysphoria, mental health, use of alcohol, marijuana, injection drugs, tobacco, and e-vapor, gambling, driving under influence of alcohol, high-risk sexual behavior, physical fights, weapon-carrying, injuries/threats at school, feeling unsafe at school, dating violence, obesity, poor general health, insecure housing, less perceived family support, and poor academic performance. People experiencing both types of bullying were typically more likely to report adverse measures. High-school students commonly report bullying. The findings that both forms (traditional and cyber) were more robustly linked to negative experiences highlight the need for examining further relationships between types and patterns of bullying and mental health and functioning. Better understanding may help improve preventive anti-bullying interventions.

Alcohol use, alcohol use disorder and heavy episodic drinking in the Eastern Mediterranean region: A systematic review.

BACKGROUND AND AMS: Despite the evident public health impact, the extent and patterns of alcohol use in the Eastern Mediterranean countries remain understudied. The latest estimation for the last 12-month use of alcohol in the region was 2.9% in 2016 by the World Health Organization. We reviewed the main indicators for alcohol consumption in the region since 2010. METHODS: We systematically searched on-line databases until September 2023, together with other global and regional sources for studies on the adult general population (aged ≥ 15 years) and young general populations (aged < 18 years) and studies on the treatment-seeking individuals with substance use in Eastern Mediterranean countries. Studies were included from 22 countries: Afghanistan, Bahrain, Djibouti, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Pakistan, Palestine, Qatar, Saudi Arabia, Somalia, Sudan, Syria, Tunisia, United Arab Emirates and Yemen. RESULTS: A total of 148 were included (n = 95 on the prevalence of alcohol use, n = 46 on the prevalence of alcohol use disorder, regular use and heavy episodic drinking, n = 35 on alcohol use pattern among people who use substances and one report on alcohol per capita consumption, n = 29 had data for more than one category). The pooled prevalence of the last 12-month alcohol use in the adult general population was 9.5% [95% confidence interval (CI) = 6.4-13.7] among males, 2.8% (95% CI = 1.3-5.5\) among females and 6.2% (95% CI = 3.9-9.6) in both sexes in the region, with notable subregional variations. Data on the prevalence of alcohol use disorder and heavy drinking were limited to several countries, with heterogeneous indicators. The pooled estimate of alcohol as the primary substance of use among treatment-seeking people who used substances was 16.9% (95% CI = 8.8-26.9). CONCLUSIONS: More than 30 million adults in the Eastern Mediterranean region used alcohol in the last 12 months, with a prevalence of 6.2%. This is far fewer than the global estimate of 43% of the population aged 15 years and above, but is approximately two times more than the previous estimate (2.9%), reported by the World Health Organization in 2016, which might show an increasing trend.

A Six-Year Follow-up of People Who Use Cannabis in Iran - A Case Series.

Background: Frequent cannabis use is associated with adverse health-related outcomes. This study followed up individuals who used cannabis to assess their use and adverse event status. Methods: The eligible individuals, recruited in the Iranian Mental Health Survey (IranMHS), were contacted via telephone calls six years after the index interview. The frequency of cannabis use and the occurrence of selected adverse events were recorded. The baseline status was extracted from the index survey. If any individual was inaccessible, his/her vital status was assessed. Findings: Of the 50 eligible individuals (all male), two had died. Moreover, from among 25 reached participants, 19 reported abstinence from cannabis in the past year, and 18 reported at least one adverse event in the past six years. Violence and imprisonment were the most common events reported. Conclusion: Six years after the index interview, most of the participants abstained from cannabis. Besides, adverse events were common, emphasizing the need for further investigations on larger samples of cannabis users.

Risk of incident cardiovascular diseases at national and subnational levels in Iran from 2000 to 2016 and projection through 2030: Insights from Iran STEPS surveys.

BACKGROUND: Cardiovascular Disease (CVD) is the leading cause of death in developing countries. CVD risk stratification guides the health policy to make evidence-based decisions. AIM: To provide current picture and future trend of CVD risk in the adult Iranian population. METHODS: Nationally representative datasets of 2005, 2006, 2007, 2008, 2009, 2011, and 2016 STEPwise approach to non-communicable diseases risk factor surveillance (STEPS) studies were used to generate the 10-year and 30-year risks of CVD based on Framingham, Globorisk, and World Health Organization (WHO) risk estimation models. Trend of CVD risk was calculated from 2000 until 2016 and projected to 2030. RESULTS: In 2016, based on Framingham model, 14.0% of the Iranian, aged 30 to 74, were at great risk (≥20%) of CVD in the next 10 years (8.0% among females, 20.7% among males). Among those aged 25 to 59, 12.7% had ≥45% risk of CVD in the coming 30 years (9.2% among females, 16.6 among males). In 2016, CVD risk was higher among urban area inhabitants. Age-standardized Framingham 10-year CVD risk will increase 32.2% and 19%, from 2000 to 2030, in females and males, respectively. Eastern provinces had the lowest and northern provinces had the greatest risk. CONCLUSIONS: This study projected that CVD risk has increased from 2000 to 2016 in Iran. Without further risk factor modification, this trend will continue until 2030. We have identified populations at higher risks of CVD to guide future intervention.

Prevalence of injecting drug use and HIV, hepatitis B, and hepatitis C in people who inject drugs in the Eastern Mediterranean region: a systematic review and meta-analysis.

BACKGROUND: Considerable disease burden is attributed to injecting drug use (IDU). This regional systematic review and meta-analysis aimed to assess the prevalence of IDU and the characteristics of people who inject drugs in the 22 countries of the WHO Eastern Mediterranean region. METHODS: We conducted a systematic review and meta-analysis on the prevalence of IDU, estimation of the population size of people who inject drugs, the characteristics of people who inject drugs, commonly injected drugs, the prevalence of HIV, hepatitis C virus, and hepatitis B virus in people who inject drugs, and opioid agonist treatment and needle and syringe programme services. We searched PubMed, Web of Science, Scopus, Embase, and the Index Medicus for the Eastern Mediterranean Region for documents published between Jan 1, 2010, and April 17, 2022, with no language restrictions. We also searched government reports, civil society information, and UN websites and databases for grey literature published between Jan 1, 2010, and April 17, 2022. Documents were eligible if they reported or estimated an indicator of interest, or reported enough data to permit calculation of the indicator. We extracted data from the eligible documents and calculated national and regional estimates. FINDINGS: We identified 38 283 documents and included 201 documents in the systematic review. A total of 115 documents were included for the four outcomes for which meta-analyses were performed. The number of people who inject drugs was estimated as 864 597 (95% CI 641 909-1 205 255), amounting to a prevalence of 20·0 per 10 000 adults (95% CI 14·9-27·9) in the region. Among people who inject drugs, the prevalence of HIV was estimated as 19·22% (95% CI 12·86-26·36), hepatitis C virus as 44·82% (29·32-61·16), and hepatitis B virus as 2·66% (0·84-7·26). Countries varied greatly regarding the variables of interest and the availability of relevant data. Nine countries provided needle and syringe programme services and seven countries provided opioid agonist treatment services, mostly with very low, low, or unclear coverage. INTERPRETATION: The prevalence of IDU in the Eastern Mediterranean region is lower than the global mean, particularly among women. The HIV infection rate is higher than the global mean, and the hepatitis C virus infection rate is lower than the global mean. Harm-reduction services are underdeveloped. Data collection on IDU and provision of services need improvement in the region. FUNDING: World Health Organization. TRANSLATIONS: For the Arabic, Farsi and French translations of the abstract see Supplementary Materials section.

Drug use, drug use disorders, and treatment services in the Eastern Mediterranean region: a systematic review.

Drug use is an increasing global public health concern. We reviewed the prevalence and patterns of drug use, drug use disorders, and the extent of treatment services in 21 countries and one territory in the Eastern Mediterranean region from 2010 to 2022. Online databases were systematically searched on April 17, 2022, along with other sources for grey literature. The extracted data were analysed and used for synthesis at the country, subregional, and regional levels. The prevalence of drug use is higher in the Eastern Mediterranean region than global estimates, with cannabis, opium, khat, and tramadol among the main drugs used in the region. Data on the prevalence of drug use disorders were scarce and heterogeneous. Treatment facilities for drug use disorders are available in most countries, but opioid agonist treatment exists in only seven countries. There is a need to expand evidence-based and cost-effective care. Limited data exist, especially regarding drug use disorders, treatment coverage, and drug use among women and young people.

Loneliness in the presence of others: A mixed-method study of social networks of caregivers of patients with severe mental disorders.

BACKGROUND: One in four families has at least one member with a mental disorder and families are the main caregivers in most patients in low and middle-income countries. Caregivers experience disruption in their routine lives, increased responsibilities, increased need for support, and changes in their network. The role of personal support networks in the health and burden of the caregivers is complex and depends on the context, cultural and socioeconomical variables. In this study, we aimed to investigate the personal support network of caregivers of patients with severe mental illness in Iran. METHODS: By using a mixed-methods design, we focused on the structure and composition of caregiver networks, as well as self-perceived caregiver support. RESULTS: We found that the support network of caregivers was mostly composed of immediate family members whom themselves were selectively chosen as a result of the multidimensional process of interaction between stigma, availability, and the perceived needs of caregivers. The participants mentioned economic and instrumental supports more frequently than emotional support, probably reflecting their unmet basic needs. Advocacy for providing formal systemic supports to caregivers, as well as interventions that expand caregivers personal support network is recommended. CONCLUSIONS: Most participants of the study were relatively isolated and had a small network of support, mostly composed of immediate family members. Stigma was a serious source of family distress for caregivers and a limiting factor in social relationships.

Mortality and negative outcomes of opioid use and opioid use disorder: a 6-year follow-up study.

BACKGROUND AND AIMS: There is a paucity of data on outcomes of opioid use disorder (OUD) from low- and middle-income countries. We aimed to investigate the mortality as well as negative social and health outcomes in a 6-year follow-up study of a cohort of individuals with opioid use, including those with OUD, in Iran. DESIGN AND SETTING: Participants with opioid use initially interviewed in late 2011 in the Iranian National Mental Health Survey (IranMHS)-a household survey of 15-64-year-old population-were followed-up in early 2018. PARTICIPANTS: All respondents (n = 236) who had reported use of any opioids at least five times during the 12-month period prior to the index interview were included in the study. MEASUREMENTS: Composite International Diagnostic Interview (CIDI) version 2.1 was used for assessment of opioid use and OUD at baseline. Vital status in the follow-up was ascertained through contact with participants/informants, primarily via telephone calls and also through the death registration systems. Weighted incidence rates of negative consequences of opioid use (e.g. incarceration, suicide attempts, violent behavior) were estimated for those who were interviewed. FINDINGS: Seven (3.3%) of the 236 participants with opioid use including four (3.1%) of the 136 with OUD had died by the time of the follow-up interview, resulting in death rates of 0.49 [95% confidence interval (CI) = 0.21-1.38] and 0.53 (95% CI = 0.16-2.62) per 100 person-years, respectively. Overall, 35.0% of participants with opioid use and 44.0% of those with OUD among the 145 individuals interviewed at follow-up experienced non-fatal serious adverse outcomes. CONCLUSIONS: In Iran, opioid use and opioid use disorder are associated with increased mortality and other adverse outcomes.

Comparison of self-reported substance use with biological testing among treatment-seeking patients with opioid use disorder.

BACKGROUND: Several factors may influence the validity of self-report. In this study, we aimed to assess the validity of self-reported drug use compared to urine testing among treatment-seeking patients with opioid use disorder (OUD). METHODS: This cross-sectional study recruited 293 patients with OUD, referred to the Iranian National Center for Addiction Studies (INCAS) clinic, from November 2015 to June 2017. The study compared self-reported opioid use in the past 72 h with the results of urinalysis, using immunoassay technique. We estimated sensitivity, negative predictive value, percent agreement, positive percent agreement, and Cohen's kappa statistics for those with OUD. RESULTS: The sensitivity of self-reported opioid use was 85.9%. Percent agreement, positive percent agreement, and Cohen's Kappa statistics between self-reported opioid use and urine testing for morphine in the first month were 88.5%, 78.1%, and 77.0, respectively. Multilevel logistic regression showed that longer treatment duration (OR = 1.21, 95%CI: 1.07-1.37, p-value = 0.002) was significantly associated with the agreement of self-reported opioid use with urine testing. CONCLUSION: Self-report can be used as a reliable method for monitoring treatment adherence combined with random urine tests.

HIV prevalence among non-injecting people who use drugs and related factors in Iran: A systematic review and meta-analysis.

ISSUES: This systematic review aimed to provide an updated estimate on the prevalence of human immunodeficiency virus (HIV) infection among non-injecting people who use drugs (PWUD) and the various subgroups and the odds of HIV infection in the injecting compared to non-injecting PWUD. APPROACH: A comprehensive search of international, regional and national databases was performed from January 2005 to May 2020. We conducted backward citation tracking of the included studies and contacted experts for unpublished studies. Studies providing HIV prevalence among non-injecting PWUD were included. Data were also drawn from a previous systematic review, covering 10 years from 1998 to 2007, and was added to the new database. The HIV prevalence was pooled for non-injecting PWUD and other subgroups using the random-effects model. KEY FINDINGS: Seventeen studies with a total sample of 9912 non-injecting PWUD were found. The prevalence of HIV infection was 1.9% (95% confidence interval 0.9, 3.1) for 2007 and afterward (nine studies). It was not significantly different from the estimate for the years before 2007 (0.5%; 95% confidence interval 0.0, 2.0; eight studies). No significant difference was found among gender subgroups. The overall estimate of odds of HIV infection among injecting PWUD was 5.7 (95% confidence interval 3.2, 10.0) times higher than non-injecting PWUD. IMPLICATIONS AND CONCLUSIONS: The HIV prevalence among the non-injecting PWUD was higher than the general population in Iran. Targeting non-injection PWUD by preventive measures such as harm reduction, drug and psychoeducation, and surveillance seem to be crucial in reducing HIV prevalence in this group.

Public health risks associated with methadone in Iran: A systematic review and meta-analysis.

BACKGROUND: There has been a marked growth in methadone maintenance treatment (MMT) in Iran in the past two decades with positive health outcomes. We conducted a systematic review of studies on the prevalence of non-prescribed methadone use, methadone use disorder, and methadone-related poisoning and mortality in Iran. METHODS: We searched International and Iranian databases up to May 2020 and contacted relevant experts. The pooled proportions were estimated through random-effects model. Methadone-related adverse outcomes were evaluated over time. RESULTS: Sixty-five studies were included. The pooled estimates of non-prescribed methadone use in the last 12-month were 2.7% (95%CI: 0.9-5.4) and 0.1% (95%CI: 0.03-0.2) in the male and female general population, respectively. Among people who use drugs, 8.4% reported daily non-prescribed use in 2018. Four heterogeneous studies in drug treatment centers reported the existence of treatment-seeking for methadone use disorder. Methadone was responsible for 10.4% (95%CI: 4.5-18.3) of cases of acute poisoning in adults and 16.0% (95%CI: 9.3-24.1) in children. Methadone was reported as a cause of death in 53.5% of substance-related deaths referred to the Legal Medicine Organization while being the only cause in 35.8% of all cases. CONCLUSION: Non-prescribed use of methadone in the general population is much less than opiates and some other available prescription opioids, like tramadol. However, notwithstanding the large and successful MMT program in Iran, increasing trends in methadone-related poisoning and deaths pose serious public health concerns. There is an urgent need to explore these fatal and non-fatal poisoning cases and implement policies to curb the harms associated with methadone use.

The immune system and autism spectrum disorder: association and therapeutic challenges.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, affecting communication and behavior. Historically, ASD had been described as a purely psychiatric disorder with genetic factors playing the most critical role. Recently, a growing body of literature has been emphasizing the importance of environmental and immunological factors in its pathogenesis, with the autoimmune process attracting the most attention. This study provides a review of the autoimmune involvement in the pathogenesis of ASD. The\r\nmicrobiome, the representative of the innate immune system in the central nervous system (CNS), plays a critical role in triggering inflammation. Besides, a bidirectional communicational pathway between the CNS and the intestine called the gut­brain­axis is linked to the development of ASD. Moreover, the higher plasma level of pro­inflammatory cytokines in ASD patients and the higher prevalence of autoimmune disorders in the first­degree family members of affected persons are other clues of the immune system involvement in\r\nthe pathogenesis of ASD. Furthermore, some anti­inflammatory drugs, including resveratrol and palmitoylethanolamide have shown promising effects by relieving the manifestations of ASD. Although considerable advances have been made in elucidating the role of autoimmunity in the ASD pathogenesis, further studies with stronger methodologies are needed to apply the knowledge to the definitive treatment of ASD.

Evidence for an increase in cannabis use in Iran - A systematic review and trend analysis.

BACKGROUND AND AIMS: Cannabis is the most widely used illicit substance globally. In this systematic review, we examined the prevalence and trends of cannabis use and cannabis use disorder in Iran. METHODS: We searched International and Iranian databases up to March 2021. Pooled prevalence of use among sex subgroups of the general population, university and high school students, combined youth groups, and high-risk groups was estimated through random-effects model. Trends of various use indicators and national seizures were examined. RESULTS: Ninety studies were included. The prevalence estimates of last 12-month cannabis use were 1.3% (95%CI: 0.1-3.6) and 0.2% (95%CI: 0.1-0.3) among the male and female Iranian general population, respectively. The prevalence of cannabis use disorder among general population in national studies rose from 0% in 2001 to 0.5% in 2011. In the 2016-2020 period, the pooled prevalence estimates of last 12-month cannabis use were 4.9% (95% CI: 3.4-6.7) and 0.3% (95% CI: 0.0-1.3) among males and females of "combined youth groups", respectively. The linear trend of last 12-month cannabis use among males of "combined youth groups" and among female university students increased significantly from 2000 to 2020. CONCLUSIONS: Prevalence of cannabis use in Iran is low compared to many countries. However, there is strong evidence of an increase in cannabis use among the youth and some evidence for an increase in cannabis use disorder.

Buprenorphine abuse and health risks in Iran: A systematic review.

INTRODUCTION: Buprenorphine maintenance treatment (BMT) is widely used in Iran, and its use is growing continuously. We reviewed studies on buprenorphine use, non-prescribed use, use disorder and treatment-seeking for it, buprenorphine-associated poisoning, and mortality in Iran in the current systematic review. METHODS: An Iranian database (Scientific Information Database; SID) and three International electronic databases (PubMed, Scopus, and Web of Science) were searched for publications up to August 2020 for the relevant data. Opportunistic methods (Contact with experts and backward citation tracking) were also used for this purpose. Identified records were screened for eligibility criteria, and data of included studies were extracted. For context, the trend of BMT in the country was also examined. RESULTS: Ten studies were found on the prevalence of non-prescribed buprenorphine use, seven were on the regular use and use disorder, and two studies on buprenorphine poisoning. The last 12-month prevalence of non-prescribed use was lower than 0.5 % in the general population, university, and high school students. The indicator was 2.5 % among persons who use drugs in a 2018 national study. The proportion of buprenorphine poisoning was 4.9 % among all illicit substance poisoning cases admitted to a hospital. The proportion of buprenorphine poisoning cases among all acute pediatric drug poisoning cases increased from 1.2 % to 2.5 % in a 3-year study. CONCLUSION: Despite the expansion of BMT in Iran in the last decade, the adverse health consequences associated with buprenorphine are infrequent, when compared to other opioids used in Iran, suggesting the safety of BMT for future expansion.

Autism spectrum disorders and natural killer cells: a review on pathogenesis and treatment.

Introduction: Autism spectrum disorder (ASD), as a wide spectrum of neurodevelopmental disorders, is characterized by early-onset impairments in social-communication, repetitive behaviors, and restrictive interests.Areas covered: Although still unknown, there are some pieces of evidence suggesting altered immune function in the etiology of ASD. This review aims to summarize studies linking Natural Killer (NK) cells to ASD by searching through databases like MEDLINE and Scopus up to October 2020. NK cells play important roles in the innate immune system and immune regulation. As parts of the immune system, they interact with the neural system as well. Immune dysregulations such as autoimmunity and improper immune responses to both internal and external stimulations, especially in early developmental stages of the brain, may induce neurodevelopmental disorders. NK cells' dysfunction in children with ASD as well as their parents have been highlighted in many studies.Expert opinion: Changes in the frequency, gene expressions, cytotoxicity features, and receptors of NK cells are reported in children with ASD. Immune therapy for children with ASD with immune abnormality has shown promising results. However, further studies are needed to elucidate the exact role of NK cells in the pathogenesis of ASD providing future treatment options for these children.

Hepatitis B virus infection among people who use drugs in Iran: a systematic review, meta-analysis, and trend analysis.

BACKGROUND: People who use drugs (PWUD) are considered as one of the main at-risk populations for Hepatitis B virus (HBV) infection. We conducted a systematic review on the prevalence of HBV infection among PWUD in Iran. METHODS: Consistent with PRISMA guideline, international (Medline, Web of Science, Scopus, and Embase) and national (Scientific Information Database) databases were searched using a comprehensive search strategy up to September 2019. The retrieved records were reviewed, and experts were contacted for unpublished studies. Studies on Iranian PWUD reporting HBV surface Antigen (HBsAg) prevalence among people who inject drugs (PWID) and non-injecting PWUD were included. HBsAg prevalence was pooled for PWID and non-injecting PWUD and for other subgroups using random-effects model meta-analysis. The trend of HBV prevalence over time was investigated using meta-regression analysis. RESULTS: Overall, 35 studies reported data on HBV infection among PWID (33 studies) and non-injecting PWUD (11 studies). The pooled prevalence of HBsAg among PWID was 4.8% (95% CI 3.7-6.2). The only risk factor significantly associated with the odds of positive HBsAg in PWID was the previous history of imprisonment (OR 1.72, 95% CI 1.29-2.30, p value = 0.000). The pooled estimate of HBsAg among non-injecting PWUD was 2.9% (95% CI 2.5-3.2). Time trend analyses showed significant decrease in HBV prevalence among PWID reaching from 8.2% (95% CI 3.9-16.5) in 2004-2006 to 3.1% (95% CI 2.3-4.1) in 2016 and later (b = -0.07; p value = 0.05). No significant trend was detected for non-injecting PWUD. CONCLUSION: The prevalence of HBV infection among non-injecting PWUD and even PWID was not considerably higher than the Iranian general population. This might be the result of extensive harm reduction interventions in Iran. However, it seems that there are subgroups of PWID, who do not adequately benefit from existing harm reduction interventions. Future programs should more specifically target these high-risk groups.

Tramadol use and public health consequences in Iran: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Misuse of tramadol, an opioid prescription analgesic, is known as a public health challenge globally. We aimed to systematically review studies on the prevalence of non-prescribed use, regular tramadol use and dependence, tramadol-induced poisoning and mortality in Iran. METHODS: Consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, international (Medline, Scopus, Web of Science) and Persian (SID) databases were systematically searched up to June 2019. Other relevant data were collected through personal contacts and review of reference lists. Pooled estimates of prevalence of tramadol use in subgroups of males and females, percentage of tramadol poisoning among admitted poisoning cases, tramadol-associated seizures and mortality among tramadol poisonings and percentage of tramadol as a cause of death among fatal drug-poisoning records were estimated through a random-effects model. RESULTS: A total of 84 records were included. Pooled estimates of last 12-month use of tramadol in the Iranian general population were 4.9% [95% confidence interval (CI) = 4.1-5.9] and 0.8% (95% CI = 0.2-1.8) among males and females, respectively. The estimates for last 12-month use among Iranian male and female university students were 4.8% (95% CI = 1.9-8.9) and 0.7% (95% CI = 0.3-1.1), respectively. Six heterogeneous reports indicated the existence of regular use of tramadol and dependence in Iran. Sixty-two studies provided data on tramadol-induced poisoning, seizures and mortality. The pooled estimate of the percentage of tramadol poisoning among all drug-poisoning patients was 13.1% (95% CI = 5.7-22.9). The overall estimates of seizures and mortality among tramadol-poisoning patients were 34.6% (95% CI = 29.6-39.8) and 0.7% (95% CI = 0.0-1.9), respectively. The pooled percentage of tramadol-related fatalities among drug-poisoned cases was 5.7% (95% CI = 0.5-15.4). CONCLUSION: Despite control policies, tramadol use is as prevalent as the use of illicit opioids in Iran. Numerous cases of tramadol abuse, dependence, poisonings, seizures and hundreds of tramadol-related deaths have been reported in recent years.

Microstructural Changes in Patients With Parkinson's Disease Comorbid With REM Sleep Behaviour Disorder and Depressive Symptoms.

The diagnosis of Parkinson's disease (PD) is currently anchored on clinical motor symptoms, which appear more than 20 years after initiation of the neurotoxicity. Extra-nigral involvement in the onset of PD with probable nonmotor manifestations before the development of motor signs, lead us to the preclinical (asymptomatic) or prodromal stages of the disease (various nonmotor or subtle motor signs). REM sleep behavior disorder (RBD) and depression are established prodromal clinical markers of PD and predict worse motor and cognitive outcomes. Nevertheless, taken by themselves, these markers are not yet claimed to be practical in identifying high-risk individuals. Combining promising markers may be helpful in a reliable diagnosis of early PD. Therefore, we aimed to detect neural correlates of RBD and depression in 93 treatment-naïve and non-demented early PD by means of diffusion MRI connectometry. Comparing four groups of PD patients with or without comorbid RBD and/or depressive symptoms with each other and with 31 healthy controls, we found that these two non-motor symptoms are associated with lower connectivity in several white matter tracts including the cerebellar peduncles, corpus callosum and long association fibers such as cingulum, fornix, and inferior longitudinal fasciculus. For the first time, we were able to detect the involvement of short association fibers (U-fibers) in PD neurodegenerative process. Longitudinal studies on larger sample groups are needed to further investigate the reported associations.