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Stimulants are considered the first-line treatment for Attention Deficit Hyperactivity Disorder (ADHD) in the US and they are used in other indications. Stimulants are also diverted for non-medical purposes. Ethnic and regional differences in ADHD diagnosis and in stimulant use have been identified in earlier research. The objectives of this report were to examine the pharmacoepidemiological pattern of these controlled substances over the past decade and to conduct a regional analysis. Data (drug weights) reported to the US Drug Enforcement Administration's Automation of Reports and Consolidated Orders System for four stimulants (amphetamine, methylphenidate, lisdexamfetamine, and methamphetamine) were obtained from 2006 to 2016 for Unites States/Territories. Correlations between state level use (mg/person) and Hispanic population were completed. Amphetamine use increased 2.5 fold from 2006 to 2016 (7.9 to 20.0 tons). Methylphenidate use, at 16.5 tons in 2006, peaked in 2012 (19.4 tons) and subsequently showed a modest decline (18.6 tons in 2016). The consumption per municipality significantly increased 7.6% for amphetamine and 5.5% for lisdexamfetamine but decreased 2.7% for methylphenidate (all p < .0005) from 2015 to 2016. Pronounced regional differences were also observed. Lisdexamfetamine use in 2016 was over thirty-fold higher in the Southern US (43.8 mg/person) versus the Territories (1.4 mg/person). Amphetamine use was about one-third lower in the West (48.1 mg/person) relative to the Northeastern (75.4 mg/person, p < .05) or the Midwestern (69.9 mg/person, p ≤ .005) states. States with larger Hispanic populations had significantly lower methylphenidate (r(49) = -0.63), lisdexamfetamine (B, r(49) = -0.49), and amphetamine (r(49) = -0.43) use. Total stimulant usage doubled in the last decade. There were dynamic changes but also regional disparities in the use of stimulant medications. Future research is needed to better understand the reasons for the sizable regional and ethnic variations in use of these controlled substances.

Previous preclinical research has shown that extracorporeal devices can be used to enhance the delivery and distribution of systemically administered anticancer drugs, resulting in increased intratumoural concentrations. We aimed to assess the safety and feasibility of targeted release and enhanced delivery of doxorubicin to solid tumours from thermosensitive liposomes triggered by mild hyperthermia, induced non-invasively by focused ultrasound. We did an open-label, single-centre, phase 1 trial in a single UK hospital. Adult patients (aged ≥18 years) with unresectable and non-ablatable primary or secondary liver tumours of any histological subtype were considered for the study. Patients received a single intravenous infusion (50 mg/m2) of lyso-thermosensitive liposomal doxorubicin (LTLD), followed by extracorporeal focused ultrasound exposure of a single target liver tumour. The trial had two parts: in part I, patients had a real-time thermometry device implanted intratumourally, whereas patients in part II proceeded without thermometry and we used a patient-specific model to predict optimal exposure parameters. We assessed tumour biopsies obtained before and after focused ultrasound exposure for doxorubicin concentration and distribution. The primary endpoint was at least a doubling of total intratumoural doxorubicin concentration in at least half of the patients treated, on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT02181075, and is now closed to recruitment. Between March 13, 2015, and March 27, 2017, ten patients were enrolled in the study (six patients in part I and four in part II), and received a dose of LTLD followed by focused ultrasound exposure. The treatment resulted in an average increase of 3·7 times in intratumoural biopsy doxorubicin concentrations, from an estimate of 2·34 μg/g (SD 0·93) immediately after drug infusion to 8·56 μg/g (5·69) after focused ultrasound. Increases of two to ten times were observed in seven (70%) of ten patients, satisfying the primary endpoint. Serious adverse events registered were expected grade 4 transient neutropenia in five patients and prolonged hospital stay due to unexpected grade 1 confusion in one patient. Grade 3–4 adverse events recorded were neutropenia (grade 3 in one patient and grade 4 in five patients), and grade 3 anaemia in one patient. No treatment-related deaths occurred. The combined treatment of LTLD and non-invasive focused ultrasound hyperthermia in this study seemed to be clinically feasible, safe, and able to enhance intratumoural drug delivery, providing targeted chemo-ablative response in human liver tumours that were refractory to standard chemotherapy. Oxford Biomedical Research Centre, National Institute for Health Research.

The US mainland is experiencing an epidemic of opioid overdoses. Unfortunately, the US Territories (Guam, Puerto Rico, and the Virgin Islands) have often been overlooked in opioid pharmacoepidemiology research. This study examined common prescription opioids over the last decade. The United States Drug Enforcement Administration's Automation of Reports and Consolidated Orders System (ARCOS) was used to report on ten medical opioids: buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, oxycodone, and oxymorphone, by weight from 2006 to 2017. Florida and Hawaii were selected as comparison areas. Puerto Rico had the greatest Territorial oral morphine mg equivalent (MME) per capita (421.5) which was significantly higher ( < .005) than the Virgin Islands (139.2) and Guam (118.9) but significantly lower than that of Hawaii (794.6) or Florida (1,509.8). Methadone was the largest opioid by MMEs in 2017 in most municipalities, accounting for 41.1% of the total in the Virgin Islands, 37.9% in Florida, 36.6% in Hawaii but 80.8% in Puerto Rico. Puerto Rico and Florida showed pronounced differences in the distribution patterns by pharmacies, hospitals, and narcotic treatment programs for opioids. Continued monitoring of the US Territories is needed to provide a balance between appropriate access to these important agents for cancer related and acute pain while also minimizing diversion and avoiding the opioid epidemic which has adversely impacted the US mainland.

The US is experiencing an epidemic of opioid overdoses which may be at least partially due to an over-reliance on opioid analgesics in the treatment of chronic non-cancer pain and subsequent escalation to heroin or illicit fentanyl. As Texas was reported to be among the lowest in the US for opioid use and misuse, further examination of this state is warranted. This study was conducted to quantify prescription opioid use in Texas. Data was obtained from the publicly available US Drug Enforcement Administration's Automation of Reports and Consolidated Orders System (ARCOS) which monitors controlled substances transactions from manufacture to commercial distribution. Data for 2006-2017 from Texas for ten prescription opioids including eight primarily used to relieve pain (codeine, fentanyl, hydrocodone, hydromorphone, meperidine, morphine, oxycodone, oxymorphone) and two (buprenorphine and methadone) for the treatment of an Opioid Use Disorder (OUD) were examined. The change in morphine mg equivalent (MME) of all opioids (+23.3%) was only slightly greater than the state's population gains (21.1%). Opioids used to treat an OUD showed pronounced gains (+90.8%) which were four-fold faster than population growth. Analysis of individual agents revealed pronounced elevations in codeine (+387.5%), hydromorphone (+106.7%), and oxycodone (+43.6%) and a reduction in meperidine (-80.3%) in 2017 relative to 2006. Methadone in 2017 accounted for a greater portion (39.5%) of the total MME than hydrocodone, oxycodone, morphine, hydromorphone, oxymorphone, and meperidine, combined. There were differences between urban and rural areas in the changes in hydrocodone and buprenorphine. Collectively, these findings indicate that continued vigilance is needed in Texas to appropriately treat pain and an OUD while minimizing the potential for prescription opioid diversion and misuse. Texas may lead the US in a return to pre-opioid epidemic prescription levels.

There have been dynamic changes in prescription opioid use in the US but the state level policy factors contributing to these are incompletely understood. We examined the association between the legalization of recreational marijuana and prescription opioid distribution in Colorado. Utah and Maryland, two states that had not legalized recreational marijuana, were selected for comparison. Prescription data reported to the Drug Enforcement Administration for nine opioids used for pain (e.g., fentanyl, morphine, hydrocodone, hydromorphone, oxycodone, oxymorphone) and two primarily for opioid use disorder (OUD, methadone and buprenorphine) from 2007 to 2017 were evaluated. Analysis of the interval pre (2007–2012) versus post (2013–2017) marijuana legalization revealed statistically significant decreases for Colorado (P < 0.05) and Maryland (P < 0.01), but not Utah, for pain medications. There was a larger reduction from 2012 to 2017 in Colorado (–31.5%) than the other states (–14.2% to –23.5%). Colorado had a significantly greater decrease in codeine and oxymorphone than the comparison states. The most prevalent opioids by morphine equivalents were oxycodone and methadone. Due to rapid and pronounced changes in prescription opioid distribution over the past decade, additional study with more states is needed to determine whether cannabis policy was associated with reductions in opioids used for chronic pain.

ObjectivesThe Maine Diversion Alert Program grants healthcare providers access to law enforcement data on drug charges. The objectives of this report were to analyse variations in drug charges by demographics and examine recent trends in arrests, prescriptions of controlled substances and overdoses.DesignObservational.SettingArrests, controlled prescription medication distribution and overdoses in Maine.ParticipantsDrug arrestees (n=1272) and decedents (n=2432).Primary outcome measuresArrestees were analysed by sex and age. Substances involved in arrests were reported by schedule (I–V or non-controlled prescription) and into opioids, stimulants or other classes. Controlled substances reported to the Drug Enforcement Administration (2007–2017) were evaluated. Drug-induced deaths (2007–2017) reported to the medical examiner were examined by the substance(s) identified.ResultsMales were more commonly arrested for stimulants and schedule II substances. More than two-thirds of arrests involved individuals under the age of 40. Individuals age >60 were elevated for oxycodone arrests. Over three-fifths (63.38%) of arrests involved schedule II–IV substances. Opioids accounted for almost half (44.6%) of arrests followed by stimulants (32.5%) and sedatives (9.1%). Arrests involving buprenorphine exceeded those for oxycodone, hydrocodone, methadone, tramadol and morphine, combined. Prescriptions for hydrocodone (−56.0%) and oxycodone (−46.9%) declined while buprenorphine increased (+58.1%) between 2012 and 2017. Deaths from 2007 to 2017 tripled. Acetylfentanyl and furanylfentanyl were the most common fentanyl analogues identified.ConclusionsAlthough the overall profile of those arrested for drug crimes in 2017 involve males, age <40 and heroin, exceptions (oxycodone for older adults) were observed. Most prescription opioids are decreasing while deaths involving opioids continue to increase in Maine.

Online medical reference websites are utilized by health care providers to enhance their education and decision making. However, these resources may not adequately reveal pharmaceutical-author interactions and their potential conflicts of interest (CoIs). This investigation: (1) evaluates the correspondence of two well-utilized CoI databases: the Centers for Medicare and Medicaid Services Open Payments (CMSOP) and ProPublica’s Dollars for Docs (PDD) and (2) quantifies CoIs among authors of a publicly available point of care clinical support website which is used to inform evidence-based medicine decisions. Two data sources were used: the hundred most common drugs and the top fifty causes of death. These topics were entered into a freely available database. The authors (N = 139) were then input into CMSOP and PDD and compensation and number of payments were determined for 2013–2015. The subset of highly compensated authors that also reported “Nothing to disclose” were further examined. There was a high degree of similarity between CMSOP and PDD for compensation (R 2  ≥ 0.998) and payment number (R 2  ≥ 0.992). The amount received was 1.4% higher in CMSOP ($4,059,194) than in PDD ($4,002,891). The articles where the authors had received the greatest compensation were in neurology (Parkinson’s Disease = $1,810,032), oncology (Acute Lymphoblastic Leukemia = $616,727), and endocrinology (Type I Diabetes = $377,388). Two authors reporting “Nothing to disclose” received appreciable and potentially relevant compensation. CMSOP and PDD produced almost identical results. CoIs were common among authors but self-reporting may be an inadequate reporting mechanism. Recommendations are offered for improving the CoI transparency of pharmaceutical-author interactions in point-of-care electronic resources.

Cross-sectional imaging plays an ever-increasing role in the management of the acutely ill patient. There is 24/7 demand for radiologists at all levels of training to interpret complex scans, and alongside this an increased expectation that the requesting physician should be able to recognise important cross-sectional anatomy and pathology in order to expedite patient management. Emergency Cross-sectional Radiology addresses both these expectations. Part I demystifies cross-sectional imaging techniques. Part II describes a wide range of emergency conditions in an easy-to-read bullet point format. High quality images reinforce the findings, making this an invaluable rapid reference in everyday clinical practice. Emergency Cross-sectional Radiology is a practical aide-memoire for emergency medicine physicians, surgeons, acute care physicians and radiologists in everyday reporting or emergency on-call environments.

Goodman and Gilman’s The Pharmacological Basis of Therapeutics (GGPBT) has been a cornerstone in the education of pharmacists, physicians, and pharmacologists for decades. The objectives of this study were to describe and evaluate the 13th edition of GGPBT on bases including: (1) author characteristics; (2) recency of citations; (3) conflict of interest (CoI) disclosure; (4) expert evaluation of chapters. Contributors’ (N = 115) sex, professional degrees, and presence of undisclosed potential CoI—as reported by the Center for Medicare and Medicaid’s Open Payments (2013–2017)—were examined. The year of publication of citations was extracted relative to Katzung’s Basic and Clinical Pharmacology (KatBCP), and DiPiro’s Pharmacotherapy: A Pathophysiologic Approach (DiPPAPA). Content experts provided thorough chapter reviews. The percent of GGPBT contributors that were female (20.9%) was equivalent to those in KatBCP (17.0%). Citations in GGPBT (11.5 ± 0.2 years) were significantly older than those in KatBCP (10.4 ± 0.2) and DiPPAPA (9.1 ± 0.1, p < 0.0001). Contributors to GGPBT received USD 3 million in undisclosed remuneration (Maximum author = USD 743,718). In contrast, DiPPAPA made CoI information available. Reviewers noted several strengths but also some areas for improvement. GGPBT will continue to be an important component of the biomedical curriculum. Areas of improvement include a more diverse authorship, improved conflict of interest transparency, and a greater inclusion of more recent citations.

Stimulants are considered the first-line treatment for Attention Deficit Hyperactivity Disorder (ADHD) in the US and they are used in other indications. Stimulants are also diverted for non-medical purposes. Ethnic and regional differences in ADHD diagnosis and in stimulant use have been identified in earlier research. The objectives of this report were to examine the pharmacoepidemiological pattern of these controlled substances over the past decade and to conduct a regional analysis. Data (drug weights) reported to the US Drug Enforcement Administration's Automation of Reports and Consolidated Orders System for four stimulants (amphetamine, methylphenidate, lisdexamfetamine, and methamphetamine) were obtained from 2006 to 2016 for Unites States/Territories. Correlations between state level use (mg/person) and Hispanic population were completed. Amphetamine use increased 2.5 fold from 2006 to 2016 (7.9 to 20.0 tons). Methylphenidate use, at 16.5 tons in 2006, peaked in 2012 (19.4 tons) and subsequently showed a modest decline (18.6 tons in 2016). The consumption per municipality significantly increased 7.6% for amphetamine and 5.5% for lisdexamfetamine but decreased 2.7% for methylphenidate (all p < .0005) from 2015 to 2016. Pronounced regional differences were also observed. Lisdexamfetamine use in 2016 was over thirty-fold higher in the Southern US (43.8 mg/person) versus the Territories (1.4 mg/person). Amphetamine use was about one-third lower in the West (48.1 mg/person) relative to the Northeastern (75.4 mg/person, p < .05) or the Midwestern (69.9 mg/person, p [less than or equal to] .005) states. States with larger Hispanic populations had significantly lower methylphenidate (r(49) = -0.63), lisdexamfetamine (B, r(49) = -0.49), and amphetamine (r(49) = -0.43) use. Total stimulant usage doubled in the last decade. There were dynamic changes but also regional disparities in the use of stimulant medications. Future research is needed to better understand the reasons for the sizable regional and ethnic variations in use of these controlled substances.