PRAgmatic Clinical Trial Design of Integrative MediCinE (PRACTICE): A Focus Group Series and Systematic Review on Trials of Diabetes and Kidney Disease

Background: Pragmatic trials inform clinical decision with better generalizability and can bridge different streams of medicine. This study collated the expectations regarding pragmatic trial design of integrative medicine (IM) for diabetes and kidney diseases among patients and physicians. Dissonance between users' perspective and existing pragmatic trial design was identified. The association between risk of bias and pragmatism of study design was assessed.Method: A 10-group semi-structured focus group interview series [21 patients, 14 conventional medicine (ConM) and 15 Chinese medicine (CM) physicians] were purposively sampled from private and public clinics in Hong Kong. Perspectives were qualitatively analyzed by constant comparative method. A systematic search of four databases was performed to identify existing IM pragmatic clinical trials in diabetes or kidney disease. Primary outcomes were the pragmatism, risk of bias, and rationale of the study design. Risk of bias and pragmatism were assessed based on Cochrane risk-of-bias tool and PRECIS-2, respectively. The correlation between risk of bias and pragmatism was assessed by regression models with sensitivity analyses.Results: The subtheme on the motivation to seek IM service was analyzed, covering the perceived limitation of ConM effect, perceived benefits of IM service, and assessment of IM effectiveness. Patients expected IM service to retard disease progression, stabilize concomitant drug dosage, and reduce potential side effects associated with ConM. In the systematic review, 25 studies from six countries were included covering CM, Korean medicine, Ayurvedic medicine, and western herbal medicine. Existing study designs did not include a detailed assessment of concomitant drug change and adverse events. Majority of studies either recruited a non-representative proportion of patients as traditional, complementary, and integrative medicine (TCIM) diagnosis was used as inclusion criteria, or not reflecting the real-world practice of TCIM by completely dropping TCIM diagnosis in the trial design. Consultation follow-up frequency is the least pragmatic domain. Increase in pragmatism did not associate with a higher risk of bias.Conclusion: Existing IM pragmatic trial design does not match the patients' expectation in the analysis of incident concomitant drug change and adverse events. A two-layer design incorporating TCIM diagnosis as a stratification factor maximizes the generalizability of evidence and real-world translation of both ConM and TCIM.

Psychedelic drug use and schizotypy in young adults

Despite recently resurrected scientific interest in classical psychedelics, few studies have focused on potential harms associated with abuse of these substances. In particular, the link between psychedelic use and psychotic symptoms has been debated while no conclusive evidence has been presented. Here, we studied an adult population (n = 1032) with a special focus on young (18–35 years) and healthy individuals (n = 701) to evaluate the association of psychedelic drug use with schizotypy and evidence integration impairment typically observed in psychosis-spectrum disorders. Experimental behavioural testing was performed in a subsample of the subjects (n = 39). We observed higher schizotypy scores in psychedelic users in the total sample. However, the effect size was notably small and only marginally significant when considering young and healthy subjects (Cohen’s d = 0.13). Controlling for concomitant drug use, none of our analyses found significant associations between psychedelic use and schizotypal traits. Results from experimental testing showed that total exposure to psychedelics (frequency and temporal proximity of use) was associated with better evidence integration (Cohen’s d = 0.13) and a higher sensitivity of fear responses (Cohen’s d = 1.05) to the effects instructed knowledge in a reversal aversive learning task modelled computationally with skin conductance response and pupillometry. This effect was present even when controlling for demographics and concomitant drug use. On a group level, however, only difference in sensitivity of fear responses to instructed knowledge reached statistical significance. Taken together, our findings suggest that psychedelic drug use is only weakly associated with psychosis-like symptoms, which, in turn, is to a large extent explained by psychiatric comorbidities and use of other psychoactive substances. Our results also suggest that psychedelics may have an effect on flexibility of evidence integration and aversive learning processes, that may be linked to recently suggested therapeutic effects of psychedelic drugs in non-psychotic psychiatric populations.

A STUDY AIMED TO INCREASE THE KNOWLEDGE ABOUT THE FIXED DOSE COMBINATIONS (FDC'S) AND IRRATIONAL FDC'S AVIALABLE IN INDIA.

Fixed dose combinations(FDC's) is a combination of 2 or more than 2 drugs in a single dosage formulations, it should not be confused with concomitant drug therapy which refers to taking 2 or more than 2 drugs separately. Fixed dose combinations may be rational or irrational. In India there are more FDC's than single drugs and majority of those FDC's are irrational. Many of these irrational FDC's are widely prescribed. The WHO essential medicine list incorporates only 23 FDC's while as the National list of essential medicines(NLEM) of 2011 has only 12 FDC's.

Contextual culpability: How drinking and social context impact sentencing of violence

The controversial effect of intoxication on sentencing outcomes has received renewed attention with a series of new empirical studies. However, these studies have relied on survey data that conflate alcohol and drug intoxication and miss pertinent contextual features of the offence. This article explores how alcohol intoxication, and its social context, impact sentence outcomes for violent offences. To do so, the probability of custodial sentence severity is modelled using multilevel Cox regression using data from online sentence transcripts. Findings contribute insights into how punishment is shaped by not only the presence of alcohol intoxication in offending but also in which contexts by highlighting the significant punitive effects of reference to concomitant drug use, the defendant drinking together with the victim and if the offence occurred in a private setting. This helps clarify complex considerations taken into account by sentencers when processing cases and the need for clearer guidance.

1287. Pharmacokinetics, Safety, and Tolerability of Nacubactam after Single Coadministration with β-Lactams in Japanese Healthy Subjects

Background A single administration of nacubactam (NAC) with concomitant β-lactams in Japanese healthy subjects was conducted to assess pharmacokinetics (PK), safety, and tolerability of NAC in coadministration with cefepime (FEP), aztreonam (ATM), meropenem (MEM), or piperacillin (PIP). Methods The administration period included Period I, Period II, and Period III where NAC alone, concomitant drug alone, NAC and concomitant drug were administered by 1hour-IV infusion in each period. The dose of each drug tested was 2 g of NAC, FEP, ATM, MEM and 4 g of PIP and 8 subjects were administered in each cohort (32 subjects in total). Results Plasma NAC concentrations and NAC urinary excretion rate after coadministration with each concomitant drug were similar to those of administration of NAC alone. The PK parameter of NAC showed the similar value both after administration of NAC alone and after concomitant administration with each concomitant drug. Based on these findings, it was confirmed that coadministration of NAC with FEP, ATM, MEM or PIP did not affect the PK of NAC. Plasma concentrations and urinary excretion rate of FEP, ATM, MEM or PIP after coadministration of each concomitant drug with NAC were similar to those of administration of each concomitant drug alone. The PK parameter of each β-lactam tested showed the similar value both after administration of β-lactam alone and after concomitant administration with NAC. Based on these finding, it was confirmed that coadministration of each concomitant drug with NAC did not affect the PK of FEP, ATM, MEM and PIP. As for the safety, there was no serious adverse event, all of TEAEs reported were mild in severity and judged to be “not related”. Conclusion It was confirmed that single coadministration of NAC with FEP, ATM, MEM, or PIP did not affect the both PKs of NAC and β-lactams, and was safe and well-tolerated in Japanese healthy subjects. Disclosures Masayo Asano, BS, Meiji Seika Pharma Co., Ltd. (Employee) Hiroki Sato, BS, Meiji Seika Pharma Co., Ltd. (Employee) Jun Morita, PhD, Meiji Seika Pharma Co., Ltd. (Employee) Kazuya Ishiwata, MS, Meiji Seika Pharma Co., Ltd. (Employee) Kenichiro Kondo, PhD, Meiji Seika Pharma Co., Ltd. (Employee)