Impossibility to eliminate observer effect in the assessment of adherence in clinical trials.

PURPOSE: To utilize the Travoprost Dosing Aid (DA) in the assessment of patient medication adherence, while also determining whether or not altering the functionality of the DA in three randomized subject groups can reduce observer effect. METHODS: Forty-five subjects were randomized into three groups: two with monitored DAs and one without monitoring. One group of subjects was given a DA that both monitored drop usage and had visual and audible alarms, while the other monitored group included subjects given a DA that had no alarms but continued to monitor drop usage. The third group was given a DA that had no alarm reminders or dose usage monitoring. Subjects were informed that some monitors would not be functional, in an attempt to reduce observer effect, or the effect of being monitored on subject behavior and adherence. A six-item questionnaire was also utilized to assess how the subjects felt about their adherence and DA use. RESULTS: The overall adherence rates were found to be 78% in the fully functional group (95% confidence interval: 70-88) and 76% in the no alarms group (95% confidence interval: 65-89). No association was seen between questionnaire response and medication adherence. The patients in the DA group without alarms had a significantly higher odds ratio of medication adherence if they reported on the questionnaire that using the DA did affect how much they used their drops. CONCLUSION: Though the use of DA was expected to reveal different rates of adherence depending on the functionality of the DA between groups, patients with a nonfunctioning DA did not have a significant difference in medication adherence compared to those given a fully functional DA. This supports that an observer effect was not reduced despite these interventions, and that the subjects adhered to taking their medications as if they had a functioning DA and were being monitored

‘The smell of death and the smell of life’: authenticity, anxiety and perceptions of death at Varanasi’s cremation grounds

This paper contributes to an understanding of existential authenticity and existential anxiety in tourism studies through an investigation of tourists' perceptions of death, the Self, and "others" at the Hindu cremation grounds in Varanasi, India. Encounters with death at dark tourism sites serve as reminders of one's own mortality affecting one's attitude towards death, perception of self, and even challenging one's personal values. Existentialists assert that anxiety is a condition of existential authenticity, and therefore moments of the existentially authentic experience are not always pleasurable. This paper argues that confrontation with death, as exemplified by the Aghori rituals and the cremation grounds in Varanasi, offers tourists an opportunity to examine the inevitability that life will end and to engage with this existential predicament and anxiety in an embodied sense, thereby pushing some of them towards life changes in the pursuit of existential authenticity

Dosing and safety profile of aficamten in symptomatic obstructive hypertrophic cardiomyopathy: results from from SEQUOIA‐HCM

Background: Aficamten, a novel cardiac myosin inhibitor, reversibly reduces cardiac hypercontractility in obstructive hypertrophic cardiomyopathy. We present a prespecified analysis of the pharmacokinetics, pharmacodynamics, and safety of aficamten in SEQUOIA‐HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM). Methods and Results: A total of 282 patients with obstructive hypertrophic cardiomyopathy were randomized 1:1 to daily aficamten (5–20 mg) or placebo between February 1, 2022, and May 15, 2023. Aficamten dosing targeted the lowest effective dose for achieving site‐interpreted Valsalva left ventricular outflow tract gradient <30 mm Hg with left ventricular ejection fraction (LVEF) ≥50%. End points were evaluated during titration (day 1 to week 8), maintenance (weeks 8–24), and washout (weeks 24–28), and included major adverse cardiac events, new‐onset atrial fibrillation, implantable cardioverter‐defibrillator discharges, LVEF <50%, and treatment‐emergent adverse events. At week 8, 3.6%, 12.9%, 35%, and 48.6% of patients achieved 5‐, 10‐, 15‐, and 20‐mg doses, respectively. Baseline characteristics were similar across groups. Aficamten concentration increased by dose and remained stable during maintenance. During the treatment period, LVEF decreased by −0.9% (95% CI, −1.3 to −0.6) per 100 ng/mL aficamten exposure. Seven (4.9%) patients taking aficamten underwent per‐protocol dose reduction for site‐interpreted LVEF <50%. There were no treatment interruptions or heart failure worsening for LVEF <50%. No major adverse cardiovascular events were associated with aficamten, and treatment‐emergent adverse events were similar between treatment groups, including atrial fibrillation. Conclusions: A site‐based dosing algorithm targeting the lowest effective aficamten dose reduced left ventricular outflow tract gradient with a favorable safety profile throughout SEQUOIA‐HCM

Compliance to tobacco-free guidelines (Cigarettes and Other Tobacco Products Act) in medical institute of North India

Background: The study aimed to investigate the compliance to prohibition of smoking (under Section 4 of Cigarettes and Other Tobacco Products Act [COTPA]) and other provisions under COTPA in a medical college situated in Chandigarh, the first smoke-free city of the country. Methods: It was a cross-sectional survey conducted at 57 sites within the medical institute. The data were collected using the structured compliance monitoring tool based on the COTPA guidelines. Results: “No active smoking” was seen at 75% of sites and there was display of signage at 28% of sites. There was the absence of cigarette butts, used matchsticks, gutkha wrappers, etc., in corners which are the secondary indicators of smoking at 70% of all sites surveyed. Conclusion: The study highlights the various loop holes in successful enforcement of COTPA. The study highlights the need to sensitize the administration on COTPA implementation with the development of well-established coordinating systems, wide publicity, and empowering reporting officers to compound offence and impound fine

Determination of paroxetine in blood and urine using micellar liquid chromatography with electrochemical detection

Paroxetine is a potent selective serotonin reuptake inhibitor used for the treatment of depression and related mood disorders. A micellar liquid chromatographic method was developed for the determination of paroxetine in serum and urine. Detection of paroxetine was carried out using a C18 column and a mobile phase of 0.15 M sodium dodecyl sulfate, 6% 1-pentanol at pH 3 (buffer salt 0.01 M NaH2PO4) running under isocratic mode at 1.0 mL/min and electrochemical detection at 0.8 V. The analyte was eluted without interferences in 0.9999; 0.5-5 mg/mL range), accuracy (88-97.5%, recovery), repeatability (RSD < 0.54%), intermediate precision (RSD < 0.54%), limit of detection and quantification (0.001 and 0.005 mg/mL, respectively) and robustness (RSD < 3.63%). Developed method was successfully applied to real blood and urine samples as well as in spiked serum and urine samples. The developed method was specific, rapid, precise, reliable, accurate, inexpensive and then suitable for routine analysis of paroxetine in monitorized samples

Synthesis and cytotoxic evaluation of substituted 3-(3′-indolyl-/3′-pyridyl)-isoxazolidines and bis-indoles

AbstractRegio- and stereoselective 1,3-dipolar cycloadditions of C-(3-indolyl)-N-phenylnitrone (10) were carried out with different mono-substituted, disubstituted and cyclic dipolarophiles under mono-mode microwave irradiation to obtain substituted 3-(indol-3′-yl)-N-phenyl-isoxazolidines (16–22). Reactions of nitrone (10) with allenic esters under similar conditions afforded, via a domino process, bis-indole derivatives (23a–c) along with compounds 24 and 25. Similarly, reactions of C-(3-pyridyl)-N-phenylnitrone (26) with mono-substituted, disubstituted and cyclic dipolarophiles were carried out in refluxing dry toluene to obtain substituted 3-(3′-pyridyl)-N-phenylisoxazolidines (27–34). Some of the compounds (16f, 18b, 23a, 23c, 27c and 29f) display significant cytotoxicity against a number of human cancer cell lines