Comorbidity of chronic insomnia with medical problems

STUDY OBJECTIVES: Determine the comorbidity of insomnia with medical problems. DESIGN: Cross-sectional and retrospective. PARTICIPANTS: Community-based population of 772 men and women, aged 20 to 98 years old. MEASUREMENTS: Self-report measures of sleep, health, depression, and anxiety. RESULTS: People with chronic insomnia reported more of the following than did people without insomnia: heart disease (21.9% vs 9.5%), high blood pressure (43.1% vs 18.7%), neurologic disease (7.3% vs 1.2%), breathing problems (24.8% vs 5.7%), urinary problems (19.7% vs 9.5%), chronic pain (50.4% vs 18.2%), and gastrointestinal problems (33.6% vs 9.2%). Conversely, people with the following medical problems reported more chronic insomnia than did those without those medical problems: heart disease (44.1% vs 22.8%), cancer (41.4% vs 24.6%), high blood pressure (44.0% vs 19.3%), neurologic disease (66.7% vs 24.3%), breathing problems (59.6% vs 21.4%), urinary problems (41.5% vs 23.3%), chronic pain (48.6% vs 17.2%), and gastrointestinal problems (55.4% vs 20.0%). When all medical problems were considered together, only patients with high blood pressure, breathing problems, urinary problems, chronic pain, and gastrointestinal problems continued to have statistically higher levels of insomnia than those without these medical disorders. CONCLUSION: This study demonstrates significant overlap between insomnia and multiple medical problems. Some research has shown it is possible to treat insomnia that is comorbid with select psychiatric (depression) and medical (eg, pain and cancer) disorders, which in turn increases the quality of life and functioning of these patients. The efficacy of treating insomnia in many of the above comorbid disorders has not been tested, indicating a need for future treatment research.     

Analgesia for major laparoscopic abdominal surgery: a randomised feasibility trial using intrathecal morphine

Effective pain control enhances patient recovery after surgery. Laparoscopic techniques for major abdominal surgery are increasingly utilised to reduce surgical trauma. Intrathecal morphine is an attractive analgesic option that is gaining popularity. However, limited evidence guides its use in the setting of laparoscopic surgery. In addition, enhanced recovery after surgery pathways advocate opioid-sparing techniques. We conducted a feasibility trial to compare intrathecal morphine with non-neuraxial analgesia in laparoscopic or laparoscopic-assisted major abdominal surgery to inform the design of a future large clinical trial. This multicentre, double-blind, randomised controlled trial was conducted at two tertiary hospitals in Australia. Fifty-one patients were randomly allocated to receive either intrathecal morphine (intervention group) or a sham subcutaneous injection of normal saline in the lumbar area (control group) immediately before the induction of general anaesthesia. Co-primary outcomes were patient recruitment and successful adherence to treatment allocation as per the study protocol. The primary endpoints of feasibility and protocol adherence were met with a 46% recruitment rate (51 of 110 eligible patients) and 96% protocol adherence. There was only one patient with failed access to the intrathecal space. For secondary endpoints, fewer patients in the intrathecal morphine group required opioids in the post-anaesthesia care unit, their postoperative pain scores at rest were lower across the four time-points measured (p = 0.007), but not dynamic pain scores (p = 0.061), and pruritus was more common following intrathecal morphine (p = 0.007). Total oral morphine equivalents until postoperative day 3 were less in the intrathecal morphine group (median (95%CI) difference 82 (−13 to 168) mg), but this reduction was not statistically significant (p = 0.10). These findings support conducting a definitive clinical trial.     

Impact of a risk-stratified thromboprophylaxis protocol on the incidence of postoperative venous thromboembolism and bleeding

Efforts to reduce postoperative venous thromboembolism are challenging due to heterogeneity in thromboprophylaxis practice. As a result, a ‘one-size-fits-all’ approach that accounts for surgery-specific risk, but fails to account for patient-level variation, is often adopted by healthcare networks. Updated clinical practice guidelines have advocated an individualised risk-stratified approach that balances the risk:benefit ratio associated with thromboprophylaxis; however, there are limited data confirming effectiveness of these recommendations on the incidence of postoperative venous thromboembolism and bleeding. We developed the surgical-thrombo-embolism-prevention protocol, a novel risk-stratified algorithm that classified patients into low-, intermediate-, and high-risk profiles according to surgical procedure and patient baseline medical risk. Expert-endorsed risk-specific thromboprophylaxis strategies were then applied. A staged quality improvement program was developed to implement the protocol. We postulated that compliance with the protocol would reduce postoperative venous thromboembolism rates without increasing the incidence of postoperative bleeding. Between June 2013 and March 2018, we evaluated the efficacy, safety and sustainability of this risk-stratified approach in 24,953 surgical admissions at a dedicated cancer centre. By final implementation, program compliance was 91%. Postoperative venous thromboembolism rates reduced from 3.1 per 1000 surgical admissions to 0.6 per 1000 surgical admissions (relative risk reduction 79%; p < 0.005). Postoperative bleeding rates also declined from 10.0 per 1000 surgical admissions to 6.3 per 1000 surgical admissions (relative risk reduction 37%; p = 0.02). Sustained improvement was evident more than 3 years after implementation. Implementation of the surgical-thrombo-embolism-prevention protocol significantly reduced the incidence of postoperative venous thromboembolism supporting its validation at other institutions.     

A randomised controlled trial comparing deep neuromuscular blockade reversed with sugammadex with moderate neuromuscular block reversed with neostigmine

Deep neuromuscular block aims to improve operative conditions during laparoscopic surgery with a lower intra-abdominal pressure. Studies are conflicting on whether meaningful improvements in quality of recovery occur beyond emergence, and whether lower intra-abdominal pressure is achieved. In this pragmatic randomised trial with 1:1 allocation, adults undergoing elective laparoscopic surgery were allocated to moderate neuromuscular block reversed with neostigmine, or deep neuromuscular block reversed with sugammadex. Allocation was revealed to the anaesthetist only. Primary outcome was cognitive recovery of the Postoperative Quality of Recovery Scale, 7 days after surgery. Secondary outcomes included recovery in other domains of the Postoperative Quality of Recovery Scale at 15 min and 40 min; days 1, 3, 7, 14; and 1 and 3 months after surgery. Chi-square test was used for the primary outcome, and generalised linear mixed model for recovery over time between groups. Of 350 participants randomised, 140 (deep) and 144 (moderate) were analysed for the primary outcome. There was no difference in the Postoperative Quality of Recovery Scale cognitive domain at day 7 (deep 92.9% vs. moderate 91.8%, OR 1.164; 95%CI 0.486–2.788, p = 0.826), or at any other time-point. No significant difference was observed for physiological, emotive, activities of daily living, nociception, or overall recovery. Length of stay in the recovery area (mean (SD) deep 108 (58) vs. moderate 109 (57) min, p = 0.78) and hospital (1.8 (1.9) vs. 2.6 (3.5) days, p = 0.019) was not different. Intra-abdominal pressure and surgical operating conditions were not different between groups. Deep neuromuscular block did not improve quality of recovery compared with moderate neuromuscular block in operative laparoscopic surgery over a 1-h duration.     

O-2050 facilitates noradrenaline release and increases the CB1 receptor inverse agonistic effect of rimonabant in the guinea pig hippocampus

The cannabinoid CB₁ receptors on the noradrenergic neurons in guinea pig hippocampal slices show an endogenous endocannabinoid tone. This conclusion is based on rimonabant, the facilitatory effect of which on noradrenaline release might be due to its inverse CB₁ receptor agonism and/or the interruption of a tonic inhibition elicited by endocannabinoids. To examine the latter mechanism, a neutral antagonist would be suitable. Therefore, we studied whether O-2050 is a neutral CB₁ receptor antagonist in the guinea pig hippocampus and whether it mimics the facilitatory effect of rimonabant. CB₁ receptor affinity of O-2050 was quantified in cerebrocortical membranes, using ³H-rimonabant binding. Its CB₁ receptor potency and effect on ³H-noradrenaline release were determined in superfused hippocampal slices. Its intrinsic activity at CB₁ receptors was studied in hippocampal membranes, using ³⁵S-GTPγS binding. Endocannabinoid levels in hippocampus were determined by liquid chromatography-multiple reaction monitoring. O-2050 was about ten times less potent than rimonabant in its CB₁ receptor affinity, potency and facilitatory effect on noradrenaline release. Although not affecting ³⁵S-GTPγS binding by itself, O-2050 shifted the concentration-response curve of a CB₁ receptor agonist to the right but that of rimonabant to the left. Levels of anandamide and 2-arachidonoyl glycerol in guinea pig hippocampus closely resembled those in mouse hippocampus. In conclusion, our results with O-2050 confirm that the CB₁ receptors on noradrenergic neurons of the guinea pig hippocampus show an endogenous tone. To differentiate between the two mechanisms leading to an endogenous tone, O-2050 is not superior to rimonabant since O-2050 may increase the inverse agonistic effect of endocannabinoids.     

Prevalence of Linda Virus Neutralizing Antibodies in the Austrian Pig Population

A novel pestivirus species, termed Lateral-shaking Inducing Neuro-Degenerative Agent virus (LindaV), was discovered in a piglet-producing farm in Austria in 2015 related to severe congenital tremor cases. Since the initial outbreak LindaV has not been found anywhere else. In this study, we determined the seroprevalence of LindaV infections in the domestic pig population of Austria. A fluorophore labeled infectious cDNA clone of LindaV (mCherry-LindaV) was generated and used in serum virus neutralization (SVN) assays for the detection of LindaV specific neutralizing antibodies in porcine serum samples. In total, 637 sera from sows and gilts from five federal states of Austria, collected between the years 2015 and 2020, were analyzed. We identified a single serum showing a high neutralizing antibody titer, that originated from a farm (Farm S2) in the proximity of the initially affected farm. The analysis of 57 additional sera from Farm S2 revealed a wider spread of LindaV in this pig herd. Furthermore, a second LindaV strain originating from this farm could be isolated in cell culture and was further characterized at the genetic level. Possible transmission routes and virus reservoir hosts of this emerging porcine virus need to be addressed in future studies.     

Tunable Pseudo-Piezoelectric Effect in Doped Calcium Titanate for Bone Tissue Engineering

CaTiO₃ is a promising candidate as a pseudo-piezoelectric scaffold material for bone implantation. In this study, pure and magnesium/iron doped CaTiO₃ are synthesized by sol-gel method and spark plasma sintering. Energy dispersive X-ray mapping confirm the homogenous distribution of doping elements in sintered samples. High-energy X-ray diffraction investigations reveal that doping of nanostructured CaTiO₃ increased the strain and defects in the structure of CaTiO₃ compared to the pure one. This led to a stronger pseudo-piezoelectric effect in the doped samples. The charge produced in magnesium doped CaTiO₃ due to the direct piezoelectric effect is (2.9 ± 0.1) pC which was larger than the one produced in pure CaTiO₃ (2.1 ± 0.3) pC, whereas the maximum charge was generated by iron doped CaTiO₃ with (3.6 ± 0.2) pC. Therefore, the pseudo-piezoelectric behavior can be tuned by doping. This tuning of pseudo-piezoelectric response provides the possibility to systematically study the bone response using different piezoelectric strengths and possibly adjust for bone tissue engineering.     

Permeability measurements with closed vesicles from rat liver nuclear envelopes.

Closed nuclear envelope ghosts in the physiological orientation were prepared from rat liver and nuclei as previously described. Here we report transport measurements of various proteins and ribonucleic acids across the envelope of these vesicles. Histones were accumulated rapidly in the ghosts, in contrast to other, nonnuclear, proteins. Triton X-100 removal of the external nuclear membrane from loaded vesicles, as well as comparative studies with open vesicles, excluded the effects of external adsorption. The exchange rate of histones across the nuclear envelope is strongly depressed in the presence of GTP and GDP. The vesicles contain the translocation mechanism for poly(A)-containing RNA. The translocation of poly(A), messenger RNA, and ribosomal RNA was investigated after entrapment of these nucleic acids during the preparation of vesicles. Our data show that the complete export of only poly(A)-containing RNA from the vesicles is enhanced in the presence of 2 mM ATP. This RNA, as well as poly(A), is transported unidirectionally.