The impact of different data handling strategies in exploratory and confirmatory factor analysis of diary measures: an evaluation using simulated and real-world asthma nighttime symptoms diary data.

BACKGROUND: Daily diaries are an important modality for patient-reported outcome assessment. They typically comprise multiple questions, so understanding their underlying structure is key to appropriate analysis and interpretation. Structural evaluation of such measures poses challenges due to the high volume of repeated measurements. Potential strategies include selecting a single day, averaging item-level observations over time, or using all data while accounting for its multilevel structure. METHOD: The above strategies were evaluated in a simulated dataset via exploratory and confirmatory factor modelling by comparing their impact on various estimates (i.e., inter-item correlations, factor loadings, model fit). Each strategy was additionally explored using real-world data from an observational study (the Asthma Nighttime Symptoms Diary). RESULTS: Both single day and item average strategies resulted in biased factor loadings. The former displayed lower overall bias (single day: 0.064; item average: 0.121) and mean square error (single day: 0.007; item average: 0.016) but greater frequency of incorrect factor number identification compared with the latter (single day: 46.4%; item average: 0%). Increased estimated inter-item correlations were apparent in the item-average method. Non-trivial between- and within-person variance highlighted the utility of a multilevel approach. However, convergence issues and Heywood cases were more common under the multilevel approach (90.2% and 100.0%, respectively). CONCLUSIONS: Our findings suggest that a multilevel approach can enhance our insight when evaluating the structural properties of daily diary data; however, implementation challenges still remain. Our work offers guidance on the impact of data handling decisions in diary assessment.

Investigating the role of endogenous opioids and KATP channels in glycerol-induced acute renal failure.

The present study was designed to investigate the possible role of endogenous opioids and K(ATP) channels in glycerol-induced acute renal failure (ARF) in rats. The rats were subjected to rhabdomyolytic ARF by single intramuscular injection of hypertonic glycerol (50% v/v; 8 mL/kg), and the animals were sacrificed after 24 h of glycerol injection. The plasma creatinine, blood urea nitrogen, creatinine clearance, and histopathological studies were performed to assess the degree of renal injury. Naltrexone (2.5, 5.0 and 10.0 mg/kg s.c.), glibenclamide (5.0 and 10.0 mg/kg i.p.), and minoxidil (25 and 50 mg/kg) were employed to explore the role of endogenous opioids and K(ATP) channels in rhabdomyolysis-induced ARF. Pretreatment with naltrexone and glibenclamide attenuated hypertonic glycerol-induced renal dysfunction in a dose-dependent manner, suggesting the role of endogenous opioids and K(ATP) channels in the pathogenesis of myoglobuniric renal failure. However, the simultaneous pretreatment with naltrexone (10 mg/kg s.c.) and glibenclamide (10 mg/kg i.p.) did not enhance the reno-protective effects of individual drugs, suggesting that release of endogenous opioids and opening of K(ATP) channels constitute a single pathway in acute renal injury triggered by hypertonic glycerol-induced rhabdomyolysis. Furthermore, administration of minoxidil abolished the attenuating effects of naltrexone in glycerol-induced renal failure, suggesting that opening of K(ATP) channels is downstream to opioid receptor activation. It is concluded that hypertonic glycerol-induced rhabdomyolysis may involve release of endogenous opioids that in turn modulate K(ATP) channels to contribute in the pathogenesis of ARF.

Extending pharmacological spectrum of opioids beyond analgesia: multifunctional aspects in different pathophysiological states.

Opioids are well known to exert potent central analgesic actions. In recent years, the numerous studies have unfolded the critical role of opioids in the pathophysiology of various diseases as well as in biological phenomenon of therapeutic interest. The endogenous ligands of opioid receptors are derived from three independent genes and their appropriate processing yields the major representative opioid peptides beta-endorphin, met-enkephalin, leu-enkephalin and dynorphin, respectively. These peptides and their derivatives exhibit different affinity and selectivity for the mu-, delta- and kappa-receptors located on the central and the peripheral neurons, neuroendocrine, immune, and mucosal cells and on many other organ systems. The present review article highlights the role of these peptides in central nervous system disorders such as depression, anxiety, epilepsy, and stress; gastrointestinal disorders such as diarrhea, postoperative ileus, ulceration, and irritable bowel syndrome; immune system and related inflammatory disorders such as osteoarthritis and rheumatoid arthritis; and others including respiratory, alcoholism and obesity/binge eating. Furthermore, the key role of opioids in different forms of pre- and post-conditioning including ischemic and pharmacological along with in remote preconditioning has also been described.