A randomized controlled trial of CBT-I and PAP for obstructive sleep apnea and comorbid insomnia : main outcomes from the MATRICS study

Study Objectives -- To investigate treatment models using cognitive behavioral therapy for insomnia (CBT-I) and positive airway pressure (PAP) for people with obstructive sleep apnea (OSA) and comorbid insomnia. Methods -- 121 adults with OSA and comorbid insomnia were randomized to receive CBT-I followed by PAP, CBT-I concurrent with PAP, or PAP only. PAP was delivered following standard clinical procedures for in-lab titration and home setup and CBT-I was delivered in four individual sessions. The primary outcome measure was PAP adherence across the first 90 days, with regular PAP use (≥4 h on ≥70% of nights during a 30-day period) serving as the clinical endpoint. The secondary outcome measures were the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) with good sleeper (PSQI 7) serving as the clinical endpoints. Results -- No significant differences were found between the concomitant treatment arms and PAP only on PAP adherence measures, including the percentage of participants who met the clinical endpoint. Compared to PAP alone, the concomitant treatment arms reported a significantly greater reduction from baseline on the ISI (p = .0009) and had a greater percentage of participants who were good sleepers (p = .044) and remitters (p = .008). No significant differences were found between the sequential and concurrent treatment models on any outcome measure. Conclusions -- The findings from this study indicate that combining CBT-I with PAP is superior to PAP alone on insomnia outcomes but does not significantly improve adherence to PAP

Use of ring-expanded diamino- and diamidocarbene ligands in copper catalyzed azide-alkyne "click" reactions

The two-coordinate ring-expanded N-heterocyclic carbene copper­(I) complexes [Cu­(RE-NHC)₂]⁺ (RE-NHC = 6-Mes, 7-<i>o</i>-Tol, 7-Mes) have been prepared and shown to be effective catalysts under neat conditions for the 1,3-dipolar cycloaddition of alkynes and azides. In contrast, the cationic diamidocarbene analogue [Cu­(6-MesDAC)₂]⁺ and the neutral species [(6-MesDAC)­CuCl]₂ and [(6-MesDAC)₂(CuCl)₃] show good activity when the catalysis is performed on water

Luotonin-a based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells

A series of novel quinazolinone hybrids were synthesized by employing click chemistry and evaluated for anti-proliferative activities against MCF-7, HeLa and K562 cell lines. Among these cell lines, HeLa cells were found to respond effectively to these quinazolinone hybrids with IC<SUB>50</SUB> values ranging from 5.94 to 16.45 &#x03BC;M. Some of the hybrids (4q, 4r, 4e, 4k, 4t, 4w) with promising anti-cancer activity were further investigated for their effects on the cell cycle distribution. FACS analysis revealed the G1 cell cycle arrest nature of these hybrids. Further to assess the senescence inducing ability of these compounds, a senescence associated β-gal assay was performed. The senescence inducing nature of these compounds was supported by the effect of hybrid (4q) on p16 promoter activity, the marker for senescence. Moreover, cells treated with most effective compound (4q) show up-regulation of p53, p21 and down-regulation of HDAC-1, HDAC-2, HDAC-5 and EZH2 mRNA levels. Docking results suggest that, the triazole nitrogen showed Zn<SUP>+2</SUP> mediated interactions with the histidine residue of HDACs

Cyclic Guanidines as Efficient Organocatalysts for the Synthesis of Polyurethanes

A systematic survey of basic/nucleophilic organocatalysts for the polyaddition in bulk of polyols, PEG-600, and PTMO-650, to isophorone diisocyanate (IPDI) has been performed. Guanidines were shown to be very efficient catalysts for the urethane linkage formation. Bicyclic penta-alkylated guanidines such as MTBD led to polyurethane molecular weight and dispersity that are in the range of those observed with tin-based catalysts such as DBTDL. Tetra-alkylated guanidine such as TBD was shown to be a weaker catalyst as compared to pentaalkylated guanidines, as a result of its high reactivity toward isocyanate, resulting in the formation of a less nucleophilic urea. Although the mechanism has not yet been firmly established, these experiments suggest that a nucleophilic-catalysis mechanism, involving the attack of one of the nitrogen of the guanidine onto the unsaturated system of the isocyanate, should not be totally ruled out with such strong Bronsted base catalysts

A randomized controlled trial of cognitive behavioral therapy for insomnia and PAP for obstructive sleep apnea and comorbid insomnia: effects on nocturnal sleep and daytime performance

This study examines the impact of cognitive behavioral therapy for insomnia (CBT-I) and positive airway pressure (PAP) therapy for comorbid insomnia and sleep apnea on nocturnal sleep and daytime functioning. A partial factorial design was used to examine treatment pathways with CBT-I and PAP and the relative benefits of each treatment. One hundred eighteen individuals with comorbid insomnia and sleep apnea were randomized to receive CBT-I followed by PAP, self-monitoring followed by CBT-I concurrent with PAP, or self-monitoring followed by PAP only. Participants were assessed at baseline, PAP titration, and 30 and 90 days after PAP initiation. Outcome measures included sleep diary- and actigraphy-measured sleep, Flinders Fatigue Scale, Epworth Sleepiness Scale, Functional Outcome of Sleep Questionnaire, and cognitive emotional measures. A main effect of time was found on diary-measured sleep parameters (decreased sleep onset latency and wake after sleep onset; increased total sleep time and sleep efficiency) and actigraphy-measured sleep parameters (decreased wake after sleep onset; increased sleep efficiency) and daytime functioning (reduced Epworth Sleepiness Scale, Flinders Fatigue Scale; increased Functional Outcome of Sleep Questionnaire) across all arms (all < .05). Significant interactions and planned contrast comparisons revealed that CBT-I was superior to PAP and self-monitoring on reducing diary-measured sleep onset latency and wake after sleep onset and increasing sleep efficiency, as well as improving Functional Outcome of Sleep Questionnaire and Flinders Fatigue Scale compared to self-monitoring. Improvements in sleep and daytime functioning were found with PAP alone or concomitant with CBT-I. However, more rapid effects were observed on self-reported sleep and daytime performance when receiving CBT-I regardless of when it was initiated. Therefore, concomitant treatment appears to be a favorable approach to accelerate treatment outcomes. Registry: ClinicalTrials.gov; Name: Multidisciplinary Approach to the Treatment of Insomnia and Comorbid Sleep Apnea (MATRICS); URL: https://clinicaltrials.gov/ct2/show/NCT01785303; Identifier: NCT01785303. Tu AY, Crawford MR, Dawson SC, et al. A randomized controlled trial of cognitive behavioral therapy for insomnia and PAP for obstructive sleep apnea and comorbid insomnia: effects on nocturnal sleep and daytime performance. . 2022;18(3):789-800

A randomized controlled trial of CBT-I and PAP for obstructive sleep apnea and comorbid insomnia : effects on nocturnal sleep and daytime performance

This study examines the impact of cognitive-behavioral therapy for insomnia (CBT-I) and positive airway pressure (PAP) therapy for comorbid insomnia and sleep apnea (COMISA) on nocturnal sleep and daytime functioning. A partial factorial design was used to examine treatment pathways with CBT-I and PAP and the relative benefits of each treatment. 118 individuals with COMISA were randomized to receive CBT-I followed by PAP, self-monitoring followed by CBT-I concurrent with PAP, or self-monitoring followed by PAP only. Participants were assessed at baseline, PAP titration, and 30- and 90-days after PAP initiation. Outcome measures included sleep diary- and actigraphy-measured sleep, Flinders Fatigue Scale(FFS), Epworth Sleepiness Scale(ESS), Functional Outcome of Sleep Questionnaire(FOSQ), and cognitive-emotional measures. A main effect of time was found on diary-measured sleep parameter (decreased sleep onset latency[SOL] and wake after sleep onset[WASO]; increased total sleep time[TST] and sleep efficiency[SE]) and actigraphy-measured sleep parameter (decreased WASO; increased SE) and daytime functioning (reduced ESS, FFS; increased FOSQ) across all arms (all p< 0.05). Significant interactions and planned contrast comparisons revealed that CBT-I was superior to PAP and self-monitoring on reducing diary-measured SOL and WASO and increasing SE; as well as improving FOSQ and FFS compared to self-monitoring. Improvements in sleep and daytime functioning were found with PAP alone or concomitant with CBT-I. However, more rapid effects were observed on subjective sleep and daytime performance when receiving CBT-I regardless of when it was initiated. Therefore, concomitant treatment appears to be a favorable approach to accelerate treatment outcomes. Registry: ClinicalTtrials.gov; Identifier: NCT01785303