Comparison of induction and recovery characteristics of Propofol and Sevoflurane in daycare adult tonsillectomies

Background: Type2 diabetes mellitus (T2DM) is a highly inheritable disease. Transcription factor 7- like 2 (TCF7L2) gene regulates the expression of glucagon-like peptide 1 (GLP-1) in L cells of small intestine. GLP1 plays a critical role in blood glucose homeostasis by stimulating postprandial insulin secretion and increasing insulin sensitivity. Aim of the study: TCF7L2 gene variants may affect the susceptibility to Type 2 diabetes by altering GLP-1 levels. Materials and methods: This case-control study was conducted with 90 newly diagnosed patients with Type2 diabetes mellitus as cases and 90 age and sex-matched healthy volunteers as controls. TCF7L2 rs7903146 genotyping was done and we also estimated Fasting and postprandial GLP -1 level, Fasting and Postprandial insulin level and calculated HOMA-IR in both cases and controls. Results: Out study showed that T+ genotype, lower fasting GLP-1 level and lower postprandial GLP1 levels were more observed among cases as compared to controls. Low mean GLP 1 activity, high Mean HOMA-IR, low postprandial insulin, low percentage rise in insulin were observed among T+ genotype than among T- genotypic individuals. Conclusion: Hence, the study concludes that T+ genotype causes a decrease in GLP-1 levels, which in turn by decreasing postprandial insulin levels and by increasing insulin resistance increases the risk of Type2 diabetes.

Phase I Dose-Finding Study of OPB-111077, a Novel STAT3 Inhibitor, in Patients with Advanced Hepatocellular Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The signal transducer and activator of transcription 3 (STAT3) signaling pathway might be a promising therapeutic target for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This study was a multicenter, open-label, non-comparative, dose escalating phase I study of OPB-111077, an oral STAT3 inhibitor, in patients with advanced HCC who failed on sorafenib. Continuous dosing (daily administration, 50 to 400 mg) and intermittent dosing (4-days on/3-days off administration: 300 to 900 mg) regimens were evaluated and the dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and recommended dose (RD) were the primary endpoints. RESULTS: A total of 33 patients (19 for continuous dosing and 14 for intermittent dosing) were enrolled. One patient experienced a DLT with grade 3 dizziness, but the MTD was identified in neither the continuous nor the intermittent dosing cohorts. The RDs were determined to be 250 mg for the continuous dosing regimen and 600 mg for the intermittent dosing regimen. There was no treatment-related death; five patients (15.2%) had grade 3-4 toxicities including thrombocytopenia (6%), fatigue (3%), and dizziness (3%). No patients achieved complete or partial responses and the median progression-free survival was 1.4 months (95% confidence interval, 0.8 to 2.8). CONCLUSION: OPB-111077 was well tolerated in patients with advanced HCC after sorafenib failure, but only showed limited preliminary efficacy outcomes. Further investigation of the role of the STAT3 signaling pathway in HCC and the development of biomarkers for STAT3 inhibitors are warranted.

Comparison of pharmacokinetic characteristics of two Tegoprazan (CJ-12420) formulations in healthy male subjects

Proton-pump inhibitors (PPIs) are effectively used to treat acid-related diseases, including gastroesophageal reflux disease (GERD); however, many unmet medical needs still exist. As a new treatment option, potassium-competitive acid blockers (P-CABs), such as tegoprazan, have been developed. This study was performed to compare the pharmacokinetics (PKs) between two formulations (test and reference drugs) of tegoprazan 100 mg tablets. A randomized, single oral dose, two-treatment, two-period, two-sequence study was conducted with 12 healthy subjects. Each subject received the test drug or reference drug in the first period and the alternative treatment in the second period. For PK evaluation, blood samples were collected up to 48 hours post-dose in each period. The plasma concentrations of tegoprazan and its active metabolite (M1) were measured by liquid chromatography-tandem mass spectrometry. PK parameters, including maximum plasma concentration (C(max)) and area under the concentration-time curve from zero to the last measurable time (AUC(last)), were estimated using a non-compartmental method. The plasma concentration-time profiles of the two formulations were comparable. The geometric mean ratios [90% confidence intervals (CIs)] of the test drug to the reference drug for C(max) and AUC(last) were 0.98 (0.85–1.12) and 1.03 (0.93–1.13), respectively. The corresponding values of M1 were 0.99 (0.89–1.11) and 1.01 (0.93–1.09), respectively. The two formulations of tegoprazan exhibited comparable PK profiles, fulfilling the regulatory criteria for bioequivalence.

Broader Transparency on Risk-benefit Assessment of the Bial Trial in France.

On 11 January 2016, a Phase I trial of an experimental fatty acid amide hydrolase inhibitor for pain developed by Bial-Portela was halted after six healthy volunteers were admitted to the University of Rennes Hospital in France. One volunteer died and four suffered severe neurological injuries. It is a dreadful reminder of the Tenegero trial that also hospitalized six volunteers in 2006. Three major similarities were observed between the Tegenero and Bial trials. The first similarity is related to the dosing interval protocol. There is a lack of information about whether the multiple-dose regimen included adequate time intervals between individuals receiving the drug. The second similarity is on the dosing calculation that was based on the ‘no adverse effect level’ (NOAEL). The third similarity is observed in terms of how there was no prior publication of preclinical findings in the public domain before the start of both trials. There have been calls for the full release of the Investigation Medicinal Product Dossier and the Investigator’s Brochure, as these data are critical to maximize patient safety in the future and should outweigh considerations of commercial confidentiality. Likewise, it is necessary for the Brest Regional Ethics Committee to release its documents, which captured the risk-benefit assessment in approving the Bial trial, for external scrutiny.

Effect of Stimulus Waveform of Biphasic Current Pulse on Retinal Ganglion Cell Responses in Retinal Degeneration (rd1) mice

A retinal prosthesis is being developed for the restoration of vision in patients with retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Determining optimal electrical stimulation parameters for the prosthesis is one of the most important elements for the development of a viable retinal prosthesis. Here, we investigated the effects of different charge-balanced biphasic pulses with regard to their effectiveness in evoking retinal ganglion cell (RGC) responses. Retinal degeneration (rd1) mice were used (n=17). From the ex-vivo retinal preparation, retinal patches were placed ganglion cell layer down onto an 8x8 multielectrode array (MEA) and RGC responses were recorded while applying electrical stimuli. For asymmetric pulses, 1st phase of the pulse is the same with symmetric pulse but the amplitude of 2nd phase of the pulse is less than 10 microA and charge balanced condition is satisfied by lengthening the duration of the pulse. For intensities (or duration) modulation, duration (or amplitude) of the pulse was fixed to 500 micros (30 microA), changing the intensities (or duration) from 2 to 60 microA (60 to 1000 micros). RGCs were classified as response-positive when PSTH showed multiple (3~4) peaks within 400 ms post stimulus and the number of spikes was at least 30% more than that for the immediate pre-stimulus 400 ms period. RGC responses were well modulated both with anodic and cathodic phase-1st biphasic pulses. Cathodic phase-1st pulses produced significantly better modulation of RGC activity than anodic phase-1st pulses regardless of symmetry of the pulse.

A Phase I Study of Oral Paclitaxel with a Novel P-Glycoprotein Inhibitor, HM30181A, in Patients with Advanced Solid Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study is to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, and recommended phase II dose of an oral drug composed of paclitaxel and HM30181A, which is an inhibitor of P-glycoprotein, in patients with advanced cancers. MATERIALS AND METHODS: Patients with advanced solid tumors received standard therapy were given the study drug at escalating doses, using a 3+3 design. The study drug was orally administered on days 1, 8, and 15, with a 28-day cycle of administration. The dose of paclitaxel was escalated from 60 to 420 mg/m2, and the dose of HM30181A was escalated from 30-210 mg/m2. RESULTS: A total of twenty-four patients were enrolled. Only one patient experienced a dose-limiting toxicity-a grade 3 neutropenia that persisted for more than 2 weeks, at 240 mg/m2 of paclitaxel. MTD was not reached. The maximum plasma concentration was obtained at a dose level of 300 mg/m2 and the area under the curve of plasma concentration-time from 0 to the most recent plasma concentration measurement of paclitaxel was reached at a dose level of 420 mg/m2. The absorption of paclitaxel tends to be limited at doses that exceed 300 mg/m2. The effective plasma concentration of paclitaxel was achieved at a dose of 120 mg/m2. Responses of 23 patients were evaluated; 8 (34.8%) had stable disease and 15 (65.2%) had progressive disease. CONCLUSION: The study drug appears to be well tolerated, and the effective plasma concentration of paclitaxel was achieved. The recommended phase II dose for oral paclitaxel is 300 mg/m2.

Hahnemann and the methodology of pathogenetic trials in healthy volunteers: a reappraisal / Hahnemann e a metodologia de ensaios patogenéticos em voluntários saudáveis: uma reavaliação / Hahnemann y la metodología de ensayos patogenéticos en voluntarios sanos: una reevaluación

This article assesses the guidelines and protocols that Hahnemann developed for homeopathic pathogenetic trials (HPTs) - often referred to as proving - and reappraise them in the light of more recent knowledge and protocols for clinical trials involving human subjects. Innovative features and methods introduced by Hahnemann and aimed at reducing bias are noted. A number of features which are now known to lead to bias in trials and which may be included in the reporting of symptoms are discussed in relation to HPTs. These features include: absence of control groups, absence of random allocation, absence of blinding, the inclusion of trivial and pre-existing symptoms, the inclusion of well-known acquaintances as trial participants, and the lack of definition of the healthy state. Advice from experts and papers published in recent decades related to the design of HPTs are discussed. The importance of developing methods to screen participants in HPTs for susceptibility to the tested medicine is discussed. The absence of trials meeting high quality standards in their design is highlighted. The article concludes with a plea for researchers to show the same desire for rigour and innovation that Hahnemann did in the development of HPTs, whilst fully recognising the requirements and protocols necessary for any trial of medicines on human beings, so that, as Hahnemann wanted, only reliable symptoms from HPTs will be admitted in the materia medica and clinical practice.

Este artigo discute as orientações e protocolos desenvolvidos por Hahnemann, para a realização de ensaios homeopáticos patogenésicos e reavalia-os com base no conhecimento e protocolos atuais, usados em pesquisas clínicas envolvendo humanos. Técnicas e métodos inovadores foram introduzidos por Hahnemann objetivando a redução de viéses estatísticos. Alguns aspectos metodológicos que podem induzir viéses em ensaios patogenésicos e que podem levar a inclusão incorreta de sintomas são discutidos. Dentre vários, podemos citar: ausência de grupo controle, ausência de randomização, ausência de protocolo cego, inclusão de sintomas triviais e pré-existentes, inclusão de conhecidos como participantes no estudo e a falta de definição do estado saudável. Recomendações de especialistas e de trabalhos publicados recentemente, relacionados aos ensaios patogenésicos são discutidos. A importância do desenvolvimento de métodos capazes de identificar a susceptibilidade dos participantes, aos medicamentos testados, é discutida. A ausência de ensaios desenhados com alto padrão metodológico é destacada. Este artigo termina com um apelo para que pesquisadores mantenham o mesmo desejo pela inovação e rigor metodológico, como Hahnemann, no desenvolvimento dos ensaios patogenésicos, não obstante atendendo plenamente os protocolos e requerimentos necessários para qualquer ensaio de medicamentos, com humanos, de forma que, como Hahnemann queria, somente sintomas confiáveis possam ser admitidos na matéria medica e na prática clínica.

Este artículo reevalúa las orientaciones y protocolos que Hahnemann formuló para los ensayos patogenéticos homeopáticos (HPTs) a la luz de conocimientos y protocolos recientes para la investigación en seres humanos. Son mencionados algunos aspectos y métodos innovadores formulados por Hahnemann, en particular aquellos destinados a reducir sesgos. Un número de aspectos actualmente conocidos que llevan a sesgos en ensayos y que pueden aparecer en el reporte de síntomas son discutidos en el contexto de los HPTs. Entre estos aspectos se menciona: ausencia de grupos-controle, ausencia de distribución aleatoria, falta de cegamiento, inclusión de síntomas triviales y pre-existentes, inclusión de personas conocidas como participantes del estudio y la falta de definición del concepto de estado de salud. Se discute la opinión de expertos así como la literatura especializada publicada en las últimas décadas sobre el diseño de HPTs. También es abordad la importancia de formular métodos para seleccionar participantes en HPTs en función de su susceptibilidad a la droga estudiada. Es resaltada la falta de estudios de alta calidad metodológica. O artículo concluye con una convocatoria para que los investigadores utilicen el mismo rigor e espíritu innovador que Hahnemann en el desarrollo de HPTs, y que al mismo tiempo reconozcan plenamente los requisitos y protocolos necesarios en cualquier ensayo de drogas en seres humanos de modo a cumplir el desiderátum de Hahnemann: admitir solamente síntomas confiables en la materia médica y la práctica clínica.

The Effect of Phase 1 Cardiac Rehabilitation Nursing Care on Knowledge, Anxiety and Self-Care Behavior in Patients with Acute Myocardial Infarction / 성인간호학회지

The purpose of this study was to identify the effects of phase 1 cardiac rehabilitation nursing care on cardiac rehabilitation knowledge, anxiety, and self-care behavior in patients with acture myocardial infarction. The study design was composed of a nonequivalent control group non-synchronized design and a non-equivalent control group post-test design. The subjects of the study consisted of thirty-four acute myocardial infarction patients hospitalized at a university hospital in Taegu between February 16, 1998 and May 12, 1998. the 34 research subjects were assigned to experimental( 17 patients ) and control( 17 patients ) groups. The phase 1 cardiac rehabilitation nursing care was composed of cardiac rehabilitation education taken from a rehabilitation manual and booklet, and participating in a progressive exercise program. After discharge, a phone interview was conducted in order to encourage the self-care behavior. The modified Knowledge Scale developed by Rahe et al.(1975) and translated into Korean by Hwang(1986), and the modified Self-Care Scale of exercise and diet based on Hickey et al.(1992), were used for data collection. Analysis of data was done by use of Chi-square test, t-test, Repeated measure ANOVA, Simple Main Effect, and Time contrast. The results of this study are as follows : 1. The first hypothesis, "The experimental group which received the phase 1 cardiac rehabilitation nursing care will have a higher level of knowledge than the control group", was supported(F=24.07, p=.000). 3. The third hypothesis, "The experimental group which received the phase 1 cardiac rehabilitation nursing care will have higher self-care behavior scores than the control group", was supported( t=-15.49, p=.000 ). From the above results, it can be concluded that phase 1 cardiac rehabilitation nursing care is an effective nursing intervention knowledge, reducing anxiety, and improving self-care behavior in patients with acute myocardial infarction.