Fentanyl analog trends in Washington D.C. observed in needle-exchange syringes.

Fentanyl has played a significant role in the opioid crisis, proving to be a persistent problem due to its analgesic effects and addictive nature. Consequently, fentanyl analogs have been identified as a rising threat in the illicit drug market, contributing to thousands of both fatal and nonfatal overdoses in the United States. A profile of the fentanyl and fentanyl analogs present in Washington D.C. was developed by analyzing syringe extracts obtained from needle-exchange programs in the city. Gas chromatography-mass spectrometry (GC-MS) with selected ion monitoring (SIM) acquisition provided a targeted analysis scheme to detect trace amounts of nine compounds: acetyl fentanyl, para-fluorofentanyl, fentanyl, methoxyacetyl fentanyl, meta-chlorofentanyl, carfentanil, valeryl fentanyl, beta-hydroxythiofentanyl, and furanyl fentanyl. In total, 332 syringe extracts were analyzed. The detected analytes and their percent prevalences were fentanyl (72.29 %), acetyl fentanyl (11.44 %), para-fluorofentanyl (6.63 %), and furanyl fentanyl (3.61 %). Tandem use was detected with combinations of fentanyl with acetyl fentanyl (12.08 %), fentanyl with para-fluorofentanyl (7.08 %), fentanyl with furanyl fentanyl (4.58 %), and fentanyl with acetyl fentanyl and para-fluorofentanyl (2.08 %). The identities of the analogs present, their relative potencies, and tandem use trends provides valuable information, especially for medical personnel who respond to opioid-related overdoses and deaths. Based on the fentanyl analog trends and tandem use of these compounds revealed in this study, it is recommended that Congress passes the permanent classification of fentanyl analogs as Schedule I drugs.

Analysis of drug residue in needle-exchange syringes in Washington, D.C.

For the first time in Washington, D.C., an analysis of drug residue from used needle-exchange syringes has been performed. This analysis is part of a larger initiative to understand the District of Columbia's illicit drug supply and its intravenous (IV) user's consumption trends as our nation faces the opioid epidemic. The goal of this study is to develop a more comprehensive monitoring program that provides real-time analysis necessary for public health organizations, in addition to providing initial observations of drugs detected. A total of 1187 syringes were analyzed over a period of nine months. Of these, 732 syringes (61.7%) were confirmed to contain a controlled dangerous substance (CDS). Fentanyl was detected in 490 syringes, the most observed CDS in all syringes analyzed. Heroin was the second most detected CDS, observed in 192 syringes. The third most detected CDS was cocaine, which was observed in 132 syringes, followed by the fourth most detected CDS, methamphetamine, observed in 82 syringes. Novel findings of this study include the first reported detections of methamphetamine, synthetic cathinones, and synthetic cannabinoids in used syringes in D.C. Ninety-seven syringes that contained no CDS contained a non-controlled substance of interest, such as diphenhydramine, xylazine, and etizolam. One limitation of this study is that this method cannot determine whether mixtures present in syringes stem from mixtures present prior to injection, back-to-back usage, or sharing of needles. This preliminary study illustrates the strength of surveillance to monitor drug trends and can be used to detect emerging novel dangerous substances in the future.

Commentary: considerations for using the 'Trials within Cohorts' design in a clinical trial of an investigational medicinal product.

BACKGROUND: The 'trials within cohorts' (TwiC) design is a pragmatic approach to randomised trials in which trial participants are randomly selected from an existing cohort. The design has multiple potential benefits, including the option of conducting multiple trials within the same cohort. MAIN TEXT: To date, the TwiC design methodology been used in numerous clinical settings but has never been applied to a clinical trial of an investigational medicinal product (CTIMP). We have recently secured the necessary approvals to undertake the first CTIMP using the TwiC design. In this paper, we describe some of the considerations and modifications required to ensure such a trial is compliant with Good Clinical Practice and international clinical trials regulations. We advocate using a two-stage consent process and using the consent stages to explicitly differentiate between trial participants and cohort participants who are providing control data. This distinction ensured compliance but had consequences with respect to costings, recruitment and the trial assessment schedule. CONCLUSION: We have demonstrated that it is possible to secure ethical and regulatory approval for a CTIMP TwiC. By including certain considerations at the trial design stage, we believe this pragmatic and efficient methodology could be utilised in other CTIMPs in future.

Comparisons of Esophageal Function Tests between Chinese and British Patients with Gastroesophageal Reflux Disease.

Objective. To investigate the esophageal function tests in British and Chinese patients with gastroesophageal reflux disease (GERD). Methods. Patients with GERD were selected from the functional gut clinic, London, and digestive department, Beijing Chao-Yang Hospital, after taking the examinations of High-resolution Manometry and Impedance (HRiM) and 24-hour Multi-Channel Intraluminal Impedance and pH Recording (MII/pH) between 2013 and 2014. Chinese healthy volunteers who undertook HRiM were also selected as control group. Results. Fifty-nine British and 82 Chinese patients with GERD and 62 Chinese healthy volunteers were entered. Values for British patients, Chinese patients, and healthy volunteers were as follows: Lower esophageal sphincter pressure (LESP) 16.0 ± 8.6, 16.5 ± 10.0, and 26.4 ± 10.9 mmHg, peristalsis (normal/small break/large break) 24/12/23, 44/10/28, and 57/1/4, total bolus transit time (TBTT) 7.3 ± 1.3, 7.6 ± 1.2, and 6.9 ± 0.9 s, and complete bolus transit rate (CBTR) 66.7 ± 37.8, 61.7 ± 36.4, and 90.3 ± 14.0%, respectively. Stepwise linear regression analysis showed that age, gender, and ethnicity did not have significant effect on LESP, TBTT, esophageal peristalsis, and CBTR in patients with GERD. Conclusions. British and Chinese patients with GERD presented similar values of LESP, TBTT, and impaired esophageal peristalsis and CBTR.

Safety and efficacy of Gammaplex® in idiopathic thrombocytopenic purpura (ClinicalTrials.gov--NCT00504075).

BACKGROUND AND OBJECTIVES: This multicentre, open-label study investigated the safety and efficacy of Gammaplex, a 5% Intravenous Immunoglobulin (IVIg), in patients with idiopathic (immune) thrombocytopenic purpura (ITP). MATERIALS AND METHODS: Patients were between the ages of 6 and 70 years; had ITP for at least six months and had a platelet count ≤ 20 × 10(9)/L. Eligible patients were dosed with 1 g/kg of Gammaplex on two consecutive days, followed by assessment of safety and efficacy on Days 3, 5, 9, 14, 21, 32 and 90. Response was defined as the increase in platelet count to a threshold of ≥ 50 × 10(9)/L on or before Day 9 after the first dose of Gammaplex. RESULTS: All 35 patients received at least one infusion of Gammaplex. Twenty-nine (83%) patients responded to Gammaplex, similar to the historical control, with a 95% lower one-sided confidence interval of 68.9%. Median duration of response was 10.0 days, with an overall reduction in bleeding episodes. Gammaplex provided supranormal concentrations of total IgG; mean peak concentration (Cmax) of 45.3 g/L (4.53 g/dL), with a mean half-life of 28.5 days. Fifteen patients reported 63 Adverse Drug Reactions (ADRs); the most common were headache (10 patients), vomiting (6 patients) and pyrexia (5 patients). Five of these ADRs were considered serious, one patient had three concurrent Serious Adverse Events (SAEs); these were vomiting, dehydration and headache. Two other patients each had one SAE (headache). There were no unexpected Adverse Events (AEs) or thromboembolic episodes and no significant changes in vital signs, biochemical, haematological and virology results. CONCLUSION: Gammaplex achieved a very high concentration of serum IgG but was well-tolerated and effective in the treatment of ITP with a similar degree of efficacy to the pre-determined historical control group and the pre-set statistical criteria. TRIAL REGISTRATION: ClinicalTrials.gov NCT00504075 Clinical Trials Registry India 000016.

Producing highly charged ions without solvent using laserspray ionization: a total solvent-free analysis approach at atmospheric pressure.

First examples of highly charged ions in mass spectrometry (MS) produced from the solid state without using solvent during either sample preparation or mass measurement are reported. Matrix material, matrix/analyte homogenization time and frequency, atmospheric pressure (AP) to vacuum inlet temperature, and mass analyzer ion trap conditions are factors that influence the abundance of the highly charged ions created by laserspray ionization (LSI). LSI, like matrix-assisted laser desorption/ionization (MALDI), uses laser ablation of a matrix/analyte mixture from a surface to produce ions. Preparing the matrix/analyte sample without the use of solvent provides the ability to perform total solvent-free analysis (TSA) consisting of solvent-free ionization and solvent-free gas-phase separation using ion mobility spectrometry (IMS) MS. Peptides and small proteins such as non-ß-amyloid components of Alzheimer's disease and bovine insulin are examples in which LSI and TSA were combined to produce multiply charged ions, similar to electrospray ionization, but without the use of solvent. Advantages using solvent-free LSI and IMS-MS include simplicity, rapid data acquisition, reduction of sample complexity, and the potential for an enhanced effective dynamic range. This is achieved by more inclusive ionization and improved separation of mixture components as a result of multiple charging.