How effective are Z-drug hypnotics for treatment of adult insomnia? Meta-analysis of data submitted to the Food and Drug Administration

The Problem: Z-drugs are the most commonly prescribed hypnotics worldwide. They are widely prescribed because general practitioners and patients believe that they are effective and superior to older hypnotics. Previous meta-analyses of Z-drugs suffer from publication or reporting bias and did not adequately examine study heterogeneity. We wanted to investigate the effectiveness of Z-drugs in adults using a data source that was less likely to be affected by publication bias. The approach: We examined clinical trials of currently approved Z-drugs submitted to the Food and Drug Administration (FDA) since pharmaceutical companies are required to provide information on all sponsored trials, whether published or not, when applying for new drug approvals. We included randomized double blind placebo controlled trials and excluded studies with a crossover design, those including healthy patients with normal sleep or single night studies with induced insomnia. We analysed drug efficacy as change score from baseline to posttest for drug and placebo groups, and the difference of both change scores for available outcomes. Weighted raw and standardized mean differences with their confidence intervals (CIs) under random-effects assumptions were calculated for polysomnographic (PSG) and subjective outcomes: wake after sleep onset, sleep latency, number of awakenings, total sleep time, sleep efficiency, subjective sleep quality, and morning sleepiness score. We performed weighted regression moderator analysis to explain heterogeneity of drug effects. Findings: We included 16 studies comprising 4973 subjects from different countries, varying drug dosages, treatment lengths and study years. Z-drugs showed significant but small improvements (reductions) only in PSG (d+ = -0.36, 95% CI = -0.57 to -0.16) and subjective sleep latency (d+ = -0.33, 95% CI = -0.62 to -0.041) compared with placebo. Analyses of weighted mean raw differences indicated that drugs decreased sleep latency by only 22 minutes (95% CI = -33 TO -11) with no evidence of change in other measures. Moderator analyses indicated that sleep latency was more likely to be reduced with larger drug doses, studies published earlier, including higher proportions of younger or women patients, and of longer treatment duration. Consequences: This study of FDA data shows that, despite being commonly prescribed, Z-drugs have limited benefit with small reductions in subjective and PSG sleep latency especially with larger dosages, but no improvement in other sleep measures compared to placebo. Placebo effects were moderate for sleep latency. Doctors and patients need to be aware of the relative benefits as well as harms of hypnotic drugs when deciding to use them in preference to psychological treatments

Advancements of combustion technologies in the ammonia-fuelled engines

The worldwide decarbonisation movement has turned ammonia into one of the attractive alternative fuel for power generation. This paper reviews the progress of ammonia combustion technologies in spark ignition engine, compression ignition engine, and gas turbine. Relevant publications from prominent academic journals were acquired from credible scholarly databases and analysed. Ammonia dissociation and separate hydrogen supply were typically employed to deliver hydrogen to enhance ammonia reaction in the spark ignition engine. To achieve satisfactory engine performances with thermal efficiency of around 30%, a hydrogen mass fraction of roughly 10% is required for the ammonia/hydrogen engine. Engine parameters optimisation may be needed to increase hydrogen mass fraction further. Aqueous ammonia elevates heat release rate of full load compression ignition engine by almost 10%. However, prolonged ignition delay could potentially lead to higher engine noise levels. Multiple fuel injection optimisation is seemingly a more promising solution for improving ammonia compression ignition engine performances. In recent years, partial premixed combustion has gained considerable interest in hydrogen/ammonia gas turbine combustion research. This is mainly due to its ability to operate at equivalence ratio as low as 0.4, and in the slight fuel-rich regime. For operation at equivalence ratio 1.05, the nitric oxide concentration was decreased by a factor of approximately 5.9 when compared with that of stoichiometric condition. In all, ammonia offers a practical opportunity for sustainable power generation via internal combustion engines and gas turbine. Ground-breaking combustion technologies are crucial to boost the adoption of ammonia in these engines

H2-rich syngas strategy to reduce NOx and CO emissions and improve stability limits under premixed swirl combustion mode

The combustion performance of H2-rich model syngas was investigated by using a premixed swirl flame combustor. Syngas consisting mainly of H2 and CO was blended with components such as CH4 and CO2 in a mixing chamber prior to combustion at atmospheric condition. The global flame appearance and emissions performance were examined for high (H2/CO = 3) and moderate (H2/CO = 1.2) H2-rich syngases. Results showed that higher H2 fractions in the syngases produce lower NOx emissions per kWh basis across all equivalence ratios tested. CO emissions are equivalence ratio dependent and are less affected by the H2 fraction in the syngas. Increasing CO2 diluent ratios result in the decrease of NOx, particularly for moderate H2-rich syngases. In contrast, syngas without CO shows an increase of NOx with increasing CO2 for fuel-lean mixtures. Addition of CO2 increases the lean blowout limit of all syngases. Higher fraction of H2 produces lower lean blowout limits due to the characteristics of high diffusivity of hydrogen molecules and high flame speed that assist in the stabilisation of the flame under flame-lean conditions. The range of blowout limits for moderate and high H2-rich and pure hydrogen syngases under diluent ratios up to 25% were within the range of ϕ = 0.12–0.15

Tracheal rupture after endotracheal intubation - A report of three cases -

Tracheal rupture is a rare but serious complication that occurs after endotracheal intubation. It usually presents as a linear lesion in the membranous wall of the trachea, and is more prevalent in women and patients older than 50 years. The clinical manifestations of tracheal injury include subcutaneous emphysema and respiratory distress. We report the cases of three female patients of old age presenting tracheal rupture after endotracheal intubation. Two cases received surgical repair without complication and one recovered uneventfully after conservative management. We presume that the tracheal injuries were caused by over-inflation of cuff and sudden movement of the tube by positional change. Therefore, we recommend cuff pressure monitoring during general anesthesia and minimized movement of the head and neck at positional change

Visualisation and performance evaluation of biodiesel/methane co-combustion in a swirl-stabilised gas turbine combustor

While dual fuel firing of power generation combustion systems can improve the fuel flexibility of such systems, several studies on compression ignition engines have also shown a positive impact on NOX and PM emissions. Previous multiphase fuel combustion studies for combustion turbines are limited, thus the present study addresses that gap by fuelling a model swirl stabilised gas turbine combustor with a blend of waste cooking oil-derived biodiesel and methane. Methane was increasingly injected into swirling combustion air flow while simultaneously reducing the biodiesel spray flowrate across a pressure atomiser, thus maintaining an overall equivalence ratio of 0.7 while delivering a thermal power output of 15 kW in all cases, except for flame stability range trials. Direct flame imaging, CH* and C2* chemiluminescence imaging, post combustion emissions as well as stability performance of the flames were evaluated. NOX emissions were found to decrease by 29% and unburnt hydrocarbons increased by 10% as the fraction of methane in fuel mix increased to 30%. Further, flame images suggest increased wrinkling and perturbing of the flame front as gas fraction of the biodiesel/methane flame increases. However, the temporal variation of integral intensity of CH* and C2* species chemiluminescence point to at least an 8% improvement in flame stability when 30% of flame heat output is supplied by methane compared to neat biodiesel burn. Also, it was found that flame stability limits reduce as methane partly replaces biodiesel in the flame

Muscular Apoptosis but Not Oxidative Stress Increases with Old Age in a Long-Lived Diver, the Weddell Seal

Seals experience repeated bouts of ischemia–reperfusion while diving, potentially exposing their tissues to increased oxidant generation and thus oxidative damage and accelerated aging. We contrasted markers of oxidative damage with antioxidant profiles across age and sex for propulsive (longissismus dorsi) and maneuvering (pectoralis) muscles of Weddell seals to determine whether previously observed morphological senescence is associated with oxidative stress. In longissismus dorsi, old (age 17–26 years) seals exhibited a nearly 2-fold increase in apoptosis over young (age 9–16 years) seals. There was no evidence of age-associated changes in lipid peroxidation or enzymatic antioxidant profiles. In pectoralis, 4-hydroxynonenal-Lys (4-HNE-Lys) levels increased 1.5-fold in old versus young seals, but lipid hydroperoxide levels and apoptotic index did not vary with age. Glutathione peroxidase activity was 1.5-fold higher in pectoralis of old versus young animals, but no other antioxidants changed with age in this muscle. With respect to sex, no differences in lipid hydroperoxides or apoptosis were observed in either muscle. Males had higher HSP70 expression (1.4-fold) and glutathione peroxidase activity (1.3-fold) than females in longissismus dorsi, although glutathione reductase activity was 1.4-fold higher in females. No antioxidants varied with sex in pectoralis. These results show that apoptosis is not associated with oxidative stress in aged Weddell seal muscles. Additionally, the data suggest that adult seals utilize sex-specific antioxidant strategies in longissismus dorsi but not pectoralis to protect skeletal muscles from oxidative damage

Oxygenated sunflower biodiesel: spectroscopic and emissions quantification under reacting swirl spray conditions

The spray combustion characteristics of sunflower (Helianthus annuus) biodiesel/methyl esters (SFME) and 50% SFME/diesel blend and diesel were investigated via a liquid swirl flame burner. The swirl flame was established at atmospheric condition by using a combined twin-fluid atomiser-swirler configuration at varied atomising air-to-liquid ratios (ALR) of 2.0–2.5. Diesel flame showed a sooty flame brush downstream of the main reaction zone, as opposed to the biodiesel flame which showed a non-sooty, bluish flame core. Biodiesel flame exhibited a more intense flame spectra with higher OH* radicals as compared to diesel. Higher preheating main swirl air temperature led to higher NO emission, while CO correspondingly decreased. Sunflower-derived biodiesel generally exhibited slightly higher NO and CO levels than diesel when compared at the same power output, mostly due to higher flame temperature and fuel chemistry effect. By increasing ALR, a significant reduction of NO and CO for both fuel types were concurrently achieved, presenting a strategy to control emissions and atomise biodiesel with higher viscosity under swirl combustion mode