Transgenerational epigenetics in substance abuse: exploring the inheritable DNA methylation underlying the agressive behaviour and altered stress response. / Professor Dr Teh Lay Kek, Professor Dr Mohd Zaki Salleh and Dr. Richard Muhammad Johari James

Addiction is defined as a chronic, relapsing disease that is characterized by (1) compulsive behaviour to seek and take drug, (2) loss of control due to limited intake (3) emergence of negative emotional states (e.g., dysphoria, anxiety, irritability) when access to the drug is prevented (Koob and Le Moal, 1997). Addictive behaviours include a complex variety of symptoms, including loss of control over its use, compulsive use, continued use despite negative consequences, and drug cravings. Of the 20.5 million Americans 12 or older that had a substance use disorder in 2015, 2 million had a substance use disorder involving prescription pain relievers and 591,000 had a substance use disorder involving heroin (Center for Behavioral Health Statistics and Quality, 2016). It is estimated that 23% of individuals who use heroin develop opioid addiction (National Institute on Drug Abuse, 2014; Centers for Disease Control and Prevention, 2016). It is also a chronic relapsing disorder characterized by cycles of escalating drug exposure, intermittent episodes of withdrawal with or without maintained abstinence, and acute or chronic relapse to drug use. Heroin and morphine are more widely used than any other illicit opioids with 13,852 users in Malaysia alone. The profile of drug users detected in 2015 recorded that 97.97% of the addicts are male (Statistics of Drug Users in Malaysia, 2015). Psychiatric comorbidity is commonly found among individuals with addictive disorders. The addicted patients often suffer from anxiety disorders. Hodgson and colleagues (2016) has confirmed the shared genetic underpinnings of addiction and anxiety. Genomic loci that involved in the etiology of the comorbid disorders were found to be heritable. However, a phenotypical study on this inheritance was not yet studied. The association between heroin use and crime has been widely documented. Researchers have consistently found that a large proportion of the heroin-dependent population regularly engage in criminal activity (Inciardi and Chambers, 1972; Voss and Stephens, 1973). Kokkevi et al. (1993), for example, reported that 79% of a small community of heroin-dependent individuals had been arrested and 60% had been convicted for a criminal offence. Recurrent cycles of heroin use and abstinence are thought to cause neurobiological changes in brain regions associated with reward, motivation, stress, learning and executive function (Jentsch and Taylor 1999; Koob and Le Moal 2008; Kreek et al. 2009a,b; Le Merrer et al. 2009; Winstanley et al. 2010). Such changes are thought to persist across extended drug-free periods to alter an individual's response to drug re-exposure and contribute to subsequent escalation of drug use (i.e., relapse-like behaviour) (Dalley et al. 2005)

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research