Crime and Violence among MDMA Users in the United States

The question of whether MDMA use is associated with increased crime and violence has not been adequately explored especially in nationally representative samples. This study used data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) to assess the association between MDMA use and violent and non-violent antisocial behavior while controlling for sociodemographic variables, lifetime psychiatric, alcohol and drug use disorders, and family history of antisocial behavior. MDMA users, both male and female, were involved in a number of crimes in acts of violence including drunk driving, shoplifting, theft, intimate partner violence, and fighting. Notably, female MDMA users were more antisocial than male non-MDMA users. Although adjusting the results for numerous confounds attenuated the relationships, MDMA users were still at significantly greater odds of engaging in violent and nonviolent crime than non-MDMA users. Although MDMA has been considered a facilitator of empathy and closeness, the current study suggests a dark side as MDMA is associated with a broad array of crimes and transgressions. Additional tests of the MDMA-crime link are needed to properly inform policy.     

Quality target negotiation in health care: evidence from the English NHS

We examine how public sector third-party purchasers and hospitals negotiate quality targets when a fixed proportion of hospital revenue is required to be linked to quality. We develop a bargaining model linking the number of quality targets to purchaser and hospital characteristics. Using data extracted from 153 contracts for acute hospital services in England in 2010/2011, we find that the number of quality targets is associated with the purchaser’s population health and its budget, the hospital type, whether the purchaser delegated negotiation to an agency, and the quality targets imposed by the supervising regional health authority.     

Use of retail data in the assessment of natural experiments: the case of Reducing the Strength,an intervention to reduce alcohol availability

BackgroundRetailers routinely collect data about people's purchasing behaviours and access to consumer products associated with health and wellbeing. Here we discuss how retail data can be used in public health research and consider potential strengths and limitations to such research. To illustrate the discussion we refer to an evaluation of an intervention called Reducing the Strength, whereby off-licence shops and supermarkets voluntarily stopped selling inexpensive superstrength (≥6·5% alcohol by volume) beers and ciders.MethodsMonthly data from a large retail chain (East of England Co-operative Society) were obtained for three UK counties (141 stores). In one county the intervention started 12 months earlier than the others, allowing for a pre–post study design with a delayed implementation comparator. Difference-in-differences analysis of unit alcohol sales controlled for socioenvironmental confounders and shop-level characteristics including shop size, parking facilities, cash machines, opening hours, and other factors.FindingsThe retail data detailed shop-level characteristics and sales data such as prices, quantities, product brands, alcohol content, sales, and factors affecting sales. The wide geographical coverage, shop-level data, including data for potential confounding factors, and frequent timepoints made the retail data well-suited for a quasi-experimental evaluation capitalising on temporal and spatial variations in intervention exposure. Limitations of this study include a lack of longitudinal data for individual customers, and shops that are not covered by the data. Qualitative interviews with shop workers and customers, and triangulation using alternative data sources can help to address limitations. Alternative sources of retail data such as private sector consultants who specialise in collecting shop-level and sales data for a range of companies might also address some limitations; however, there are potential barriers of expense, accessibility, and coverage associated with the use of such consultants.InterpretationIncreasingly, researchers recognise the potential of retail data for evaluating interventions affecting social determinants of health and inequalities, such as local access to alcohol. However, shop-level data have frequently proved difficult for researchers to obtain. By obtaining such data we have been able to assess, using a quasi-experimental design, the effects of removing strong, cheap beers and ciders from shops. We have also been able to explore in more detail how to optimise the strengths and address some limitations of the data in ways that could potentially assist others planning to use this important data source in their research.FundingThe study is funded as part of the School of Public Health Research by NHS National Institute of Health Research. AJ, SA, and JW contributed as employees of Public Health Suffolk, Suffolk County Council.     

The effect of information technology on hospital performance

While healthcare entities have integrated various forms of health information technology (HIT) into their systems due to claims of increased quality and decreased costs, as well as various incentives, there is little available information about which applications of HIT are actually the most beneficial and efficient. In this study, we aim to assist administrators in understanding the characteristics of top performing hospitals. We utilized data from the Health Information and Management Systems Society and the Center for Medicare and Medicaid to assess 1039 hospitals. Inputs considered were full time equivalents, hospital size, and technology inputs. Technology inputs included personal health records (PHR), electronic medical records (EMRs), computerized physician order entry systems (CPOEs), and electronic access to diagnostic results. Output variables were measures of quality, hospital readmission and mortality rate. The analysis was conducted in a two-stage methodology: Data Envelopment Analysis (DEA) and Automatic Interaction Detector Analysis (AID), decision tree regression (DTreg). Overall, we found that electronic access to diagnostic results systems was the most influential technological characteristics; however organizational characteristics were more important than technological inputs. Hospitals that had the highest levels of quality indicated no excess in the use of technology input, averaging one use of a technology component. This study indicates that prudent consideration of organizational characteristics and technology is needed before investing in innovative programs.     

The heritability of level and rate-of-change in cognitive functioning in Danish twins aged 70 years and older

To investigate heritable influences on overall level and rate-of-change in cognitive ability, biometric growth models were fit to cognitive data from nearly 1000 Danish twins age 70 years and older. Twins are participants in the ongoing Longitudinal Study of Aging Danish Twins, a cohort-sequential study of twins assessed every 2 years for up to four waves. Cognitive ability was assessed by five brief cognitive tasks: a fluency measure, forward and backward digit span, and immediate and delayed list recall. Model-fitting results indicated that although the overall level of cognitive functioning was highly heritable (h(2) = .76, 95% confidence interval of .68 to .82), the rate of linear change was not (h(2) = .06, 95% confidence interval of .00 to .57). These findings suggest that the search for specific genes might reasonably focus on average level of cognitive performance, whereas specific environmental influences might account for cognitive change.     

Ovariectomy Enhances Acetylcholinesterase Activity But Does Not Alter Ganglioside Content in Cerebral Cortex of Female Adult Rats

In the present work we investigated the effect of ovariectomy on acetylcholinesterase (AChE) activity and ganglioside content in cerebral cortex of female rats. We also studied the activity of butyrylcholinesterase (BuChE) in serum of these animals. Adult Wistar rats were divided into three groups: (1) naive females (control), (2) sham-operated females and (3) castrated females (ovariectomy). Thirty days after ovariectomy, rats were sacrificed by decapitation without anaesthesia. Blood was collected and the serum used for BuChE determination. Cerebral cortex was homogenized to determine AChE activity and extracted with chlorophorm:methanol for ganglioside evaluation. Results showed that rats subjected to ovariectomy presented a significant increase of AChE activity, but did not change the content and the profile of gangliosides in cerebral cortex when compared to sham or naive rats. BuChE activity was decreased in serum of rats ovariectomized. Our findings suggest that the alteration in the activity of brain AChE, as well as serum BuChE activity caused by ovariectomy may contribute to the impaired cognition and/or other neurological dysfunction found in post-menopausal women.     

Müllerian inhibiting substance blocks the protein kinase A-induced expression of cytochrome p450 17alpha-hydroxylase/C(17-20) lyase mRNA in a mouse Leydig cell line independent of cAMP responsive element binding protein phosphorylation

Müllerian inhibiting substance (MIS) is produced by fetal Sertoli cells and causes regression of the Müllerian duct in male fetuses shortly after commitment of the bipotential embryonic gonad to testes differentiation. MIS is also produced by the Sertoli cells and granulosa cells of the adult gonads where it plays an important role in regulating steroidogenesis. We have previously shown that MIS can dramatically reduce testosterone synthesis in Leydig cells by inhibiting the expression of cytochrome P450 17alpha-hydroxylase/C(17-20) lyase (Cyp17) mRNA in vitro and in vivo. To characterize the signal transduction pathway used by MIS to control expression of endogenous Cyp17 in a mouse Leydig cell line, we demonstrate that MIS inhibits both LH- and cAMP-induced expression of Cyp17 at concentrations as low as 3.5 nM and for as long as 18 h. The induction of steroidogenic acute regulatory protein (StAR) mRNA by cAMP, however, was slightly increased by addition of MIS. Protein kinase A (PKA) inhibition with H-89 blocked Cyp17 mRNA induction, suggesting that MIS interferes with the PKA signal transduction pathway. Inhibition of Cyp17 induction was not seen with added U0126, and wortmannin inhibited the induction incompletely. In addition, phosphorylation of the cAMP responsive element binding protein (CREB) was not detected following 50 micro M cAMP exposure, a concentration sufficient for Cyp17 mRNA induction. Moreover, CREB phosphorylation, which was observed with addition of 500 micro M cAMP, was not inhibited by coincubation with MIS. Taken together, these results suggest that cAMP induces expression of Cyp17 by a PKA-mediated mechanism and that this induction, which is inhibited by MIS signal transduction, does not require CREB activity, and is distinct from that used to induce steroidogenic acute regulatory protein expression.     

Treatment of hot flashes with transdermal estradiol administration

A randomized prospective double blind study was performed to assess the ability of a transdermal therapeutic system (TTS) delivering estradiol (E2) to suppress hot flashes (HFs) in symptomatic postmenopausal women. Patients were given placebo or E2 in four doses for a 20-day period, and serum gonadotropin and estrogen levels and the occurrences of HFs were measured. Administration of placebo had no measurable effect on either estrogen or gonadotropin levels or the occurrence of HFs. A dose-response relationship was found between the rate of E2 administered and the circulating level of E2, with 25, 50, 100, and 200 micrograms/24 h dosages raising the mean E2 concentrations from mean baseline levels of 5-8 pg/ml to 18, 38, 73, and 100 pg/ml, respectively. Estrone levels also increased with TTS application, but to a lesser extent than did E2 levels. Dose-response reductions of FSH and LH with increasing amounts of E2 administration occurred, but gonadotropin levels were not lowered in any of the patients into the ranges found in premenopausal women. TTS application significantly suppressed the occurrence of HFs at the 50 micrograms/24 h dosage and higher. A significant negative correlation (r = 0.6045; P less than 0.001) between E2 levels and the rates of occurrence of HFs was found during hormone administration. Based on this regression, 50% and 100% reductions of HFs should occur at 61 and 122 pg/ml E2. These data indicate that the transdermal delivery of E2 with these systems significantly reduced the occurrence of HFs and allowed definition of the therapeutic range of hormone replacement in terms of lost ovarian function, as reflected by circulating E2 levels.     

Anticoagulant Reversal in Gastrointestinal Bleeding: Review of Treatment Guidelines

Background

Patients receiving anticoagulant therapies, such as vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs), commonly experience gastrointestinal (GI) bleeding as a complication and may require anticoagulant reversal prior to endoscopic treatment. Anticoagulant reversal agents include prothrombin complex concentrates (PCCs; including 3 or 4 coagulation factors), plasma, vitamin K, and target-specific DOAC reversal agents (e.g., idarucizumab and andexanet alfa).

Aim

To review current US, as well as international, guidelines for anticoagulant reversal agents in patients on VKAs or DOACs presenting with GI bleeding prior to endoscopy, guideline-based management of coagulation defects, timing of endoscopy, and recommendations for resumption of anticoagulant therapy following hemostasis. Supporting clinical data were also reviewed.

Methods

This is a narrative review, based on PubMed and Internet searches reporting GI guidelines and supporting clinical data.

Results

GI-specific guidelines state that use of reversal agents should be considered in patients with life-threatening GI bleeding. For VKA patients presenting with an international normalized ratio >?2.5, guidelines recommend PCCs (specifically 4F-PCC), as they may exhibit greater efficacy/safety compared with fresh frozen plasma in reversal of VKA-associated GI bleeding. For DOAC patients, most guidelines recommend targeted specific reversal agents in the setting of GI bleeding; however, PCCs (primarily 4F-PCC) are often listed as another option. Resumption of anticoagulant therapy following cessation of GI bleeding is also recommended to reduce risks of future thromboembolic complications.

Conclusions

The utility of anticoagulant reversal agents in GI bleeding is recognized in guidelines; however, such agents should be reserved for use in truly life-threatening scenarios.