Review of deaths related to taking ecstasy, England and Wales, 1997-2000

Original article can be found at: http://www.bmj.com/archive/--Copyright BMJ Publishing Group Ltd DOI : 10.1136/bmj.326.7380.80Peer reviewe

Novel Psychoactive Substances: : the pharmacology of stimulants and hallucinogens

This is an Accepted Manuscript of an article published by Taylor & Francis in Expert Review of Clinical Pharmacology, on March 2016, available online at doi: : http://www.tandfonline.com/doi/full/10.1586/17512433.2016.1167597.There are increasing levels of concern relating to the rapidly evolving novel psychoactive substances/NPS and web markets’ scenarios. The paper aims at providing an overview of the clinical pharmacological issues related to some of the most popular NPS categories, e.g. stimulants and hallucinogens. NPS intake is typically associated with the imbalance of a complex range of neurotransmitter pathways/receptors, namely: dopamine; cannabinoid/CB1; and 5-HT2A. The intake is almost invariably undetectable with standard screening tests. Hence, it may frequently occur that the acute management of NPS misusers will need to focus on decreasing levels of both self/outward-directed aggression and agitation. Benzodiazepines may be considered as first line treatment. Alternatively, propofol and/or antipsychotics can be administered. Focus will be as well on treatment of possible rhabdomyolysis and hyperthermia. Indeed, future studies should inform better tailored management/treatment strategies.Peer reviewedFinal Accepted Versio

Primary care physician practices in the diagnosis, treatment and management of men with chronic prostatitis/chronic pelvic pain syndrome.

To describe practice patterns of primary care physicians (PCPs) for the diagnosis, treatment and management of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), we surveyed 556 PCPs in Boston, Chicago, and Los Angeles (RR=52%). Only 62% reported ever seeing a patient like the one described in the vignette. In all, 16% were 'not at all' familiar with CP/CPPS, and 48% were 'not at all' familiar with the National Institutes of Health classification scheme. PCPs reported practice patterns regarding CP/CPPS, which are not supported by evidence. Although studies suggest that CP/CPPS is common, many PCPs reported little or no familiarity, important knowledge deficits and limited experience in managing men with this syndrome

The Politics of Service Delivery Reform

This article identifies the leaders, the supporters and the resisters of public service reform. It adopts a principal–agent framework, comparing reality with an ‘ideal’ situation in which citizens are the principals over political policy-makers as their agents, and policy-makers are the principals over public service officials as their agents. Reform in most developing countries is complicated by an additional set of external actors — international financial institutions and donors. In practice, international agencies and core government officials usually act as the ‘principals’ in the determination of reforms. The analysis identifies the interests involved in reform, indicating how the balance between them is affected by institutional and sectoral factors. Organizational reforms, particularly in the social sectors, present greater difficulties than first generation economic policy reforms

Teleintervention's effects on breastfeeding in low-income women in high income countries: a systematic review and meta-analysis.

BACKGROUND: Many mothers in high-income countries (HIC) do not breastfeed to the World Health Organisation's recommendation of two years. This is particularly true for low-income women (LIW). They often face additional socio-structural barriers that encourage early discontinuation and are inadequately supported by current healthcare interventions. Teleinterventions are flexible and widely used following the global pandemic and increase maternal autonomy over intervention delivery. They show promise in improving other maternal conditions in LIW, including postpartum depression. Teleinterventions can increase breastfeeding rates in the wider maternal population, however their efficacy for this underserved population has not yet been systematically assessed. This meta-analysis aimed to identify if teleinterventions increase 'exclusive' or 'any' breastfeeding by LIW in HIC at 1-, 3-4, and 6-months postpartum. METHODS: We searched five online databases for randomised controlled trials assessing breastfeeding teleinterventions for LIW in HIC. Risk ratios (RR) were used to calculate the average effect of teleinterventions on 'any' and 'exclusive' breastfeeding at at 1-, 3-4, and 6-months postpartum using random effects meta-analysis. Study bias was assessed using the Revised Cochrane risk-of-bias tool for randomised trials (RoB2), and outcome quality was evaluated against GRADE criteria. RESULTS: Nine studies met inclusion criteria: six providing telephone calls, two text messages and one an online support group. All the studies were conducted in the United States, with small sample sizes and a high risk of bias. Pooled results indicate teleinterventions modestly increase 'any' and 'exclusive' breastfeeding at all time points, with a statistically significant increase in 'exclusive' breastfeeding after 3-4 months (RR 1.12, 95% CI [1.00,1.25]). At 3-4 months teleinterventions providing peer support were more effective than educational teleinterventions at promoting any and exclusive breastfeeding. Evidence for all outcomes were rated 'low' or 'very low' quality using the GRADE tool, mainly due to high attrition and low power. CONCLUSIONS: Despite insufficient high-quality research into breastfeeding teleinterventions for LIW, our results suggest teleinterventions may improve exclusive and any breastfeeding. Given breastfeeding is particularly low in LIW population from HIC, our findings are promising and require further exploration by larger, methodologically sound trials in other HIC

FAK acts as a suppressor of RTK-MAP kinase signalling in Drosophila melanogaster epithelia and human cancer cells

Receptor Tyrosine Kinases (RTKs) and Focal Adhesion Kinase (FAK) regulate multiple signalling pathways, including mitogen-activated protein (MAP) kinase pathway. FAK interacts with several RTKs but little is known about how FAK regulates their downstream signalling. Here we investigated how FAK regulates signalling resulting from the overexpression of the RTKs RET and EGFR. FAK suppressed RTKs signalling in Drosophila melanogaster epithelia by impairing MAPK pathway. This regulation was also observed in MDA-MB-231 human breast cancer cells, suggesting it is a conserved phenomenon in humans. Mechanistically, FAK reduced receptor recycling into the plasma membrane, which resulted in lower MAPK activation. Conversely, increasing the membrane pool of the receptor increased MAPK pathway signalling. FAK is widely considered as a therapeutic target in cancer biology; however, it also has tumour suppressor properties in some contexts. Therefore, the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours

An exploratory study of information sources and key findings on UK cocaine-related deaths.

Cocaine-related deaths have increased since the early 1990s in Europe, including the UK. Being multi-factorial, they are difficult to define, detect and record. The European Monitoring Centre for Drugs and Drug Addiction commissioned research to: describe trends reported to Special Mortality Registries and General Mortality Registers; provide demographic and drug-use characteristic information of cases; and establish how deaths are identified and classified. A questionnaire was developed and piloted amongst all European Monitoring Centre for Drugs and Drug Addiction Focal Point experts/Special Mortality Registries: 19 (63%) responded; nine countries provided aggregated data. UK General Mortality Registers use cause of death and toxicology to identify cocaine-related deaths. Categorisation is based on International Classification of Diseases codes. Special Mortality Registries use toxicology, autopsy, evidence and cause of death. The cocaine metabolites commonly screened for are: benzoylecgonine, ecgonine methyl ester, cocaethylene and ecgonine. The 2000s saw a generally accelerating upward trend in cases, followed by a decline in 2009. The UK recorded 2700-2900 deaths during 1998-2012. UK Special Mortality Registry data (2005-2009) indicate: 25-44 year-olds account for 74% of deaths; mean age=34 (range 15-81) years; 84% male. Cocaine overdoses account for two-thirds of cases; cocaine alone being mentioned/implicated in 23% in the UK. Opioids are involved in most (58%) cocaine overdose cases

Novel psychoactive substances: the pharmacology of stimulants and hallucinogens

There are increasing levels of concern relating to the rapidly evolving novel psychoactive substances/NPS and web markets' scenarios. The paper aims at providing an overview of the clinical pharmacological issues related to some of the most popular NPS categories, e.g. stimulants and hallucinogens. NPS intake is typically associated with the imbalance of a complex range of neurotransmitter pathways/receptors, namely: dopamine; cannabinoid/CB1; and 5-HT2A. The intake is almost invariably undetectable with standard screening tests. Hence, it may frequently occur that the acute management of NPS misusers will need to focus on decreasing levels of both self/outward-directed aggression and agitation. Benzodiazepines may be considered as first line treatment. Alternatively, propofol and/or antipsychotics can be administered. Focus will be as well on treatment of possible rhabdomyolysis and hyperthermia. Indeed, future studies should inform better tailored management/treatment strategies

Modelling the impact of improving screening and treatment of chronic hepatitis C virus infection on future hepatocellular carcinoma rates and liver-related mortality.

BACKGROUND: The societal, clinical and economic burden imposed by the complications of chronic hepatitis C virus (HCV) infection - including cirrhosis and hepatocellular carcinoma (HCC) - is expected to increase over the coming decades. However, new therapies may improve sustained virological response (SVR) rates and shorten treatment duration. This study aimed to estimate the future burden of HCV-related disease in England if current management strategies remain the same and the impact of increasing diagnosis and treatment of HCV as new therapies become available. METHODS: A previously published model was adapted for England using published literature and government reports, and validated through an iterative process of three meetings of HCV experts. The impact of increasing diagnosis and treatment of HCV as new therapies become available was modelled and compared to the base-case scenario of continuing current management strategies. To assess the 'best case' clinical benefit of new therapies, the number of patients treated was increased by a total of 115% by 2018. RESULTS: In the base-case scenario, total viraemic (HCV RNA-positive) cases of HCV in England will decrease from 144,000 in 2013 to 76,300 in 2030. However, due to the slow progression of chronic HCV, the number of individuals with cirrhosis, decompensated cirrhosis and HCC will continue to increase over this period. The model suggests that the 'best case' substantially reduces HCV-related hepatic disease and HCV-related liver mortality by 2020 compared to the base-case scenario. The number of HCV-related HCC cases would decrease 50% by 2020 and the number progressing from infection to decompensated cirrhosis would decline by 65%. Therefore, compared to projections of current practices, increasing treatment numbers by 115% by 2018 would reduce HCV-related mortality by 50% by 2020. CONCLUSIONS: This analysis suggests that with current treatment practices the number of patients developing HCV-related cirrhosis, decompensated cirrhosis and HCC will increase substantially, with HCV-related liver deaths likely to double by 2030. However, increasing diagnosis and treatment rates could optimise the reduction in the burden of disease produced by the new therapies, potentially halving HCV-related liver mortality and HCV-related HCC by 2020

Commentary on: Attafi IM, Albeishy MY, Oraiby ME, Khardali IA, Shaikhain GA, Fageeh MM. Postmortem Distribution of Cathinone and Cathine in Human Biological Specimens in a Case of Death Associated wit

The interpretation of post-mortem human tissue toxicology levels may be affected by the sampling site chosen. It is important to bear this in mind when looking at the psychoactive constituents of khat (Catha edulis Forsk) that have been consumed and have contributed to or caused death.The post-mortem levels of cathine, cathinone and norephedrine/ norpseudoephedrine are very rarely reported, thereby making it impossible for toxicologists, pathologists and others investigating khat-related fatalities to decide if a level is toxic or fatal. This paper presents all the published data that exists to help start documenting this neglected area. Such information should be collected and reported on a systematic basis to facilitate correct interpretations in the future