Difference In Onset Time Research Articles

Antifungal Drugs and Drug-Induced Liver Injury: A Real-World Study Leveraging the FDA Adverse Event Reporting System Database.

Aims: We aimed to estimate the risk of drug-induced liver injury (DILI) from various antifungal treatments with azoles and echinocandins causing in real-world practice. Methods: We performed disproportionality and Bayesian analyses based on data from the first quarter in 2004 to the third quarter in 2021 in the Food and Drug Administration Adverse Event Reporting System to characterize the signal differences of antifungal drugs-related DILI. We also compared the onset time and mortality differences of different antifungal agents. Results: A total of 2943 antifungal drugs-related DILI were identified. Affected patients tended to be aged >45 years (51.38%), with more males than females (49.03% vs. 38.09%). Antifungal drug-induced liver injury is most commonly reported with voriconazole (32.45%), fluconazole (19.37%), and itraconazole (14.51%). Almost all antifungal drugs were shown to be associated with DILI under disproportionality and Bayesian analyses. The intraclass analysis of correlation between different antifungal agents and DILI showed the following ranking: caspofungin (ROR = 6.12; 95%CI: 5.36–6.98) > anidulafungin (5.15; 3.69–7.18) > itraconazole (5.06; 4.58–5.60) > voriconazole (4.58; 4.29–4.90) > micafungin (4.53; 3.89–5.27) > posaconazole (3.99; 3.47–4.59) > fluconazole (3.19; 2.93–3.47) > ketoconazole (2.28; 1.96–2.64). The onset time of DILI was significantly different among different antifungal drugs (p < 0.0001), and anidulafungin result in the highest mortality rate (50.00%), while ketoconazole has the lowest mortality rate (9.60%). Conclusion: Based on the Food and Drug Administration Adverse Event Reporting System database, antifungal drugs are significantly associated with DILI, and itraconazole and voriconazole had the greatest risk of liver injury. Due to indication bias, more clinical studies are needed to confirm the safety of echinocandins.

ADDITION OF DEXMEDETOMIDINETO LIGNOCAINE FOR INTRAVENOUS REGIONAL ANESTHESIA IN UPPER EXTREMITY ORTHOPAEDIC SURGERIES

Objective: The objective of this study was to determine the duration of onset and regression time of sensory and motor blocks, the quality of anesthesia, and post-operative analgesia by the addition of dexmedetomidine to local anesthetic solution in intravenous regional anesthesia (IVRA) in upper extremity orthopedic surgeries. Methods: This is a prospective, randomized, and double blind clinical trial. Ninety American Society of Anaesthesiologists Grade I and II patients of either gender between 18 and 60 years of age scheduled for elective upper extremity orthopedic surgeries lasting for &lt;90 min were included in the study. Patients were randomly allocated to two Groups A and B of 45 each. Group A received 3 mg/kg preservative free lignocaine alone and Group B received 3 mg/kg preservative free lignocaine with dexmedetomidine, 0.5 μg/kg in IVRA. Result: Onset time of sensory blockade in Group A and B was 5.6±0.93 min and 3.9±0.63 min, respectively. Onset time of motor blockade in Group A and Group B was 15.01±4.53 min and 10.74±3.64 min, respectively. The difference in onset time of sensory and motor blockade between the two groups was statistically significant (p&lt;0.05). Sensory blockade recovery time after release of tourniquet was 6.9±0.53 min in Group A and 29.21±5.23 min in Group B. Motor blockade recovery time was 4.35±0.76 min for Group A and 12.32±7.23 min for Group B. The difference in sensory and motor blockade recovery time between the two groups was statistically significant (p&lt;0.05). Conclusion: Dexmedetomidine on addition to lignocaine for IVRA provided rapid onset of sensory and motor blockade, prolonged duration of sensory and motor blockade, and reduced tourniquet pain.

Consecutive Days of Racing Does Not Affect Sleep in Professional Road Cyclists.

Professional road cycling races are physiologically demanding, involving successive days of racing over 1 to 3 weeks of competition. Anecdotal evidence indicates that cyclists' sleep duration either increases or deteriorates during these competitions. However, sleep duration in professional cyclists during stage races has not been assessed. This study examined the amount/quality of sleep obtained by 14 professional cyclists competing in the Australian Tour Down Under. Sleep was assessed using wrist activity monitors and self-report sleep diaries on the night prior to start of the race and on each night during the race. The impact of each day of the race on sleep onset, sleep offset, time in bed, sleep duration, and wake duration was assessed using separate linear mixed effects models. During the race, cyclists obtained an average of 6.8 (0.9)hours of sleep between 23:30 and 07:27hours and spent 13.9% (4.7%) of time in bed awake. Minor differences in sleep onset (P = .023) and offset times (P ≤.001) were observed during the week of racing, but these did not affect the amount of sleep obtained by cyclists. Interestingly, the 3 best finishers in the general classification obtained more sleep than the 3 worst finishers (7.2 [0.3] vs 6.7 [0.3]h; P = .049). Contrary to anecdotal reports, the amount of sleep obtained by cyclists did not change over the course of the 1-week race and was just below the recommended target of 7 to 9hours for adults.

Age-related changes in protective arm reaction kinematics, kinetics, and neuromuscular activation during evoked forward falls.

Fall related injuries in older adults are a major healthcare concern. During a fall, the hands and arms play an important role in minimizing trauma from ground impact. Although older adults are able to orient the hands and arms into a protective orientation after falling and prior to ground impact, an inability to avoid increased body impact occurs with age. Previous investigations have generally studied rapid arm movements in the pre-impact phase or absorbing energy in the post-impact phase. There are no known studies that have directly examined both the pre-impact and post-impact phase in sequence in a forward fall. The aim of this study was to identify age-related biomechanical and neuromuscular changes in evoked arm reactions in response to forward falls that may increase fall injury risk. Fourteen younger and 15 older adults participated. Falls were simulated while standing with torso and legs restrained via a moving pendulum system from 4 different initial lean angles. While there was not a significant age-related difference in the amount of energy absorbed post-impact (p=0.68), older adults exhibited an 11% smaller maximum vertical ground reaction force when normalized to body weight (p=0.031), and 8 degrees less elbow extension at impact (p=0.045). A significant interaction between age and initial lean angle (p=0.024), indicated that older adults required 54%, 54%, 41%, and 57% greater elbow angular displacement after impact at the low, medium, medium-high, and high initial lean angles compared to younger adults. These results suggested older adults may be at greater risk of increased body impact due to increased elbow flexion angular displacement after impact when the hands and arms are able to contact the ground first. Both groups exhibited robust modulation to the initial lean angle with no observed age-related differences in the initial onset timing or amplitude of muscle activation levels. There were no significant age-related differences in the EMG timing, amplitude or co-activation of muscle activation preceding impact or following impact indicating comparable neuromotor response patterns between older and younger adults. These results suggest that aging changes in muscular elements may be more implicated in the observed differences than changes in neuromuscular capacity. Future work is needed to test the efficacy of different modalities (e.g. instruction, strength, power, perturbation training, fall landing techniques) aimed at reducing fall injury risk.

A Comparison Between the Adductor Pollicis Muscle Using TOF-Watch SX and the Abductor Digiti Minimi Muscle Using TetraGraph in Rocuronium-Induced Neuromuscular Block: A Prospective Observational Study

The commonly used acceleromyography (AMG)-based neuromuscular monitor TOF-Watch SX is no longer manufactured. Recently, a new portable electromyography (EMG)-based neuromuscular monitor TetraGraph was introduced in clinical anesthesia. The aim of the study was to compare the responses obtained simultaneously from the abductor digiti minimi (ADM) muscle with TetraGraph and the adductor pollicis (AP) muscle with TOF-Watch SX during rocuronium-induced neuromuscular block. Patients undergoing orthopedic surgery with general anesthesia were enrolled in this prospective, observational study. During total intravenous general anesthesia, train-of-four (TOF) responses following 0.9-mg·kg -1 rocuronium administration were monitored at the AP muscle with TOF-Watch SX and the ADM muscle with TetraGraph on the opposite arms. Sugammadex 2 mg·kg -1 was administered when both devices showed TOF counts (TOFCs) = 2. The primary outcome was time from rocuronium administration to first appearance of posttetanic count (PTC) response (first PTC). The secondary outcomes were baseline TOF ratios (TOFRs), onset time, time to first reappearance of TOFC = 1 (time to TOFC1), time to first reappearance of TOFC = 2 (time to TOFC2), and time from sugammadex administration to TOFR ≥0.9 with TetraGraph or to normalized TOFR ≥0.9 with TOF-Watch SX (recovery time). We used paired t test and Wilcoxon signed-rank test to analyze parametric and nonparametric data, respectively. P <.05 defined statistical significance. A total of 20 patients were analyzed. The baseline TOFRs were significantly higher with TOF-Watch SX than with TetraGraph (105 [96-110] vs 100 [98-101]; P = .0002). The time to first PTC (minutes) (31.7 ± 9.6 vs 41.1 ± 12.3; P < .001), time to TOFC1 (minutes) (48.0 ± 12.7 vs 58.8 ± 19.2; P < .001), time to TOFC2 (minutes) (56.2 ± 15.7 vs 74.2 ± 23.7; P < .001), and recovery time (seconds) (61.5 [32-148] vs 75.5 [94-102]); P = .043) were significantly faster with TOF-Watch SX than with TetraGraph. There were no significant differences in onset time. TOF-Watch SX overestimated recovery from rocuronium-induced neuromuscular block compared with TetraGraph.

Clinical Evaluation of Analgesic Efficacy and Safety of IV Nalbuphine versus IV Butorphanol in Patients Undergoing Tympanoplasty: A Randomised Clinical Study

Introduction: Middle Ear Surgeries (MESs) are generally performed using local anaesthesia under sedation. Butorphanol and nalbuphine both are well-known synthetic opioid with agonist-antagonist characteristics. However, no reports present a direct comparison of the analgesic efficacy of these two drugs. Aim: To evaluate analgesic efficacy of intravenous butorphanol versus intravenous nalbuphine during Monitored Anaesthesia Care (MAC) in patients undergoing tympanoplasty. Materials and Methods: This randomised clinical trial was conducted at the Department of Anaesthesiology, School of Medicine, D.Y. Patil Deemed to be University, Mumbai, Maharashtra India, from March 2018 to March 2021. Total 112 adult patients, undergoing tympanoplasty, were randomly allocated into two groups. Group N received 0.2 mg/kg nalbuphine intravenous (i.v.) and group B received i.v. 0.02 mg/ kg butorphanol. The patients were then evaluated for analgesic efficacy, sedation, blood pressure, Mean Arterial Pressure (MAP), Heart Rate (HR), Respiratory Rate (RR), blood oxygen levels (SpO2 ), Visual Analogue Scale (VAS) Score, need for intraoperative rescue sedation/analgesia, duration of action and side-effects. Results: A significant difference was observed in the patients’ responses to needle prick, where only 8 (13.3%) subjects gave a vocal response in group N versus 22 (36.6%) in group B. A significant difference in the mean time of onset of pain amongst both the group was recorded (3.16±1.38 hrs in group N and 2.63±1.19 hrs in group B). A significant difference was also recorded in the mean VAS at 15th (p-value=0.012) and 30th min (p-value= 0.017). Only 7 patients (11.6%) from group N, and 12 patients (20%) from group B required rescue agent (0.5 mcg/kg/ hour dexmedetomidine injection and 75 mg diclofenac sodium injection intravenous). Conclusion: Both 0.2 mg/kg nalbuphine and 0.2 mg/kg butorphanolprovide satisfactory results in terms of analgesic efficacy, sedation, hemodynamic and respiratory parameters, albeit, nalbuphine can be coined to be superior in terms of response to pin prick and duration of action.

Dexmedetomidine in combination with ketamine for pediatric procedural sedation or premedication: A meta-analysis.

To evaluate effectiveness of combinational use of dexmedetomidine and ketamine (DEX-KET) for pediatric procedural sedation or premedication. Relevant studies were identified after a literature search in electronic databases and study selection was based on precise eligibility criteria. Meta-analyses of mean differences were performed to examine differences in sedation onset and recovery times between DEX-KET and comparators. Changes from baseline in heart rate (HR), respiratory rate, oxygen saturation, and mean arterial pressure (MAP), were pooled. Meta-analyses of proportions were performed to estimate incidence of adverse events. 15 studies (1087 patients) were included. Onset of sedation was significantly shorter in DEX-KET than in DEX group. HR declined in DEX-KET group from start (-3.5 beats per minute (BPM) [95% CI: -5.1, -1.9]) through midpoint (-7.2 BPM [95% CI: -12.1, -2.3]) and at end of sedation (-8.7 BPM [95% CI: -13.1, -4.4]). Decrease in HR after DEX administration at start was -11.6 BPM [95% CI: -16.0, -7.1] and remained consistent afterward. There was no change in MAP during DEX-KET sedation. However, after DEX administration, MAP decreased by -6.9 [95% CI: -10.4, -3.3] at start, -7.8 [95% CI: -11.4, -4.2] at middle, and by -6.6 [95% CI: -14.4, 1.1] at end of sedation. Incidence of hypotension was 3% [95% CI: 0, 9] in DEX-KET, 7% [95% CI: 2, 14] in DEX, and 0% [95% CI: 0, 2] in KET groups. Incidence of bradycardia was 2% [95% CI: 0, 6] with DEX-KET and 12% [95% CI: 5, 20] with DEX. Incidence of oxygen desaturation was 3% [95% CI: 0, 8] in DEX-KET, 2% [95% CI: 0, 6] in DEX, 12% [95% CI: 5, 20] in KET, and 13% [95% CI: 6, 21] in PROP-KET groups. MIDA-KET sedation had 13% [95% CI: 4, 25] incidence of tachycardia. DEX-KET for pediatric sedation results in better sedation outcomes than DEX or KET by shortening onset of sedation and recovery while maintaining hemodynamic and respiratory stability with low incidence of adverse events. DEX sedation was associated with higher incidence of bradycardia. Higher incidence of oxygen desaturation was observed with KET and PROP-KET whereas MIDA-KET was associated with higher incidence of tachycardia.

Aneurysm and Artery Dissection Following the Use of Vascular Endothelial Growth Factor Inhibitor: A Real-World Analysis Using a Spontaneous Reporting System.

BackgroundPharmacological inhibition of angiogenesis via the vascular endothelial growth factor pathway is an important therapeutic target that prevents tumor growth and the formation of metastases. Although vascular endothelial growth factor inhibitor (VPI) is well understood as a well‐defined safety profile, few real‐world studies are comparing the incidence, clinical features, and prognosis of the aneurysm and artery dissection.Methods and ResultsTo evaluate and compare the links between different VPIs and aneurysm and artery dissection, we identified 634 reports with VPIs in the US Food and Drug Administration Adverse Event Reporting System database ranging between January 2004 to March 2020. We used the reporting odds ratio for the association between the use of VPIs and aneurysm and artery dissection. The reporting odds ratio (3.68, 95%, 2.18‒6.23) shows that ramucirumab has a stronger correlation than other VPIs. The results show a significant difference in onset time (P<0.001). The median time to aneurysm and artery dissection was 79.5 (interquartile interval, 19.0–273.5) days after VPI administration. The results also show that VPI‐associated aneurysm and artery dissection was reported more often in men (n=336, 59.68% versus n=227, 40.32%), and there were more cases in patients aged between 45 to 74 years than those <45 years (n=312, 68.12% versus n=18, 3.93%); patients aged ≥75 years accounted for 27.95% (n=128). Finally, the suspected drugs generally led to 19.98% deaths and 29.81% hospitalizations.ConclusionsWe identified signals for aneurysm and artery dissection following various VPIs in real‐world practice via the Food and Drug Administration Adverse Event Reporting System, which represents the first step for continued pharmacovigilance investigation.

OR68. The impact of coronavirus disease 2019 pandemic on acute coronary syndrome hospitalizations, treatments, and outcomes: a dual-center observational study

Background and AimsSince March 2020, transmission of coronavirus disease 2019 (COVID-19) in Indonesia have led to substantial decline in non-COVID-19 hospitalizations and healthcare services. We ought to determine the impact of COVID-19 pandemic on acute coronary syndrome (ACS) hospitalizations, treatments, and outcomes.Methods and ResultsWe conducted a dual-center observational study in Bogor City General Hospital and Kediri General Hospital, Indonesia. We included all ACS patients between January-June 2020. Subjects were divided into two groups: pandemic period (admitted in March-June 2020) and pre-pandemic period (admitted in January-February 2020). 279 subjects were involved (107 pandemic vs 172 pre-pandemic). Monthly average ACS admissions reduced by 68.6% during pandemic period compared to pre-pandemic period. Proportion of STEMI subjects was significantly higher during pandemic compared to pre-pandemic (56.1% vs 38.4%; p = 0.004). Proportion of Killip 3-4 subjects was also significantly higher during pandemic compared to pre-pandemic (26.2% vs 14.5%; p = 0.016). However, reperfusion therapy (PCI or fibrinolytic) proportion for STEMI subjects was significantly lower during pandemic compared to pre-pandemic (16.7% vs 31.8%; p = 0.049), although there was no significant difference in onset time of ACS symptoms before hospitalization (p = 0.793). In-hospital mortality rate was significantly higher during pandemic compared to pre-pandemic (15.9% vs 8.1%; p = 0.045).ConclusionThere was a significant decline in ACS hospitalizations, increased proportion of STEMI and KILLIP 3-4 patients, and higher in-hospital mortality rate in the pandemic period compared to pre-pandemic period. Paradoxically, reperfusion therapy proportion in STEMI patients has reduced significantly during pandemic period.

Grapevine Rpv3-, Rpv10- and Rpv12-mediated defense responses against Plasmopara viticola and the impact of their deployment on fungicide use in viticulture

BackgroundThe high susceptibility of European grapevine cultivars (Vitis vinifera) to downy mildew (Plasmopara viticola) leads to the intensive use of fungicides in viticulture. To reduce this input, breeding programs have introgressed resistance loci from wild Vitis species into V. vinifera, resulting in new fungus-resistant grapevine cultivars (FRC). However, little is known about how these different resistance loci confer resistance and what the potential reduction in fungicide applications are likely to be if these FRCs are deployed. To ensure a durable and sustainable resistance management and breeding, detailed knowledge about the different defense mechanisms mediated by the respective Rpv (Resistance to P. viticola) resistance loci is essential.ResultsA comparison of the resistance mechanisms mediated by the Rpv3–1, Rpv10 and/or Rpv12-loci revealed an early onset of programmed cell death (PCD) at 8 hours post infection (hpi) in Rpv12-cultivars and 12 hpi in Rpv10-cultivars, whereas cell death was delayed in Rpv3-cultivars and was not observed until 28 hpi. These temporal differences correlated with an increase in the trans-resveratrol level and the formation of hydrogen peroxide shortly before onset of PCD. The differences in timing of onset of Rpv-loci specific defense reactions following downy mildew infection could be responsible for the observed differences in hyphal growth, sporulation and cultivar-specific susceptibility to this pathogen in the vineyard. Hereby, Rpv3- and Rpv12/Rpv3-cultivars showed a potential for a significant reduction of fungicide applications, depending on the annual P. viticola infection pressure and the Rpv-loci. Furthermore, we report on the discovery of a new P. viticola isolate that is able to overcome both Rpv3- and Rpv12-mediated resistance.ConclusionThis study reveals that differences in the timing of the defense reaction mediated by the Rpv3-, Rpv10- and Rpv12-loci, result in different degrees of natural resistance to downy mildew in field. Vineyard trials demonstrate that Rpv12/Rpv3- and Rpv3-cultivars are a powerful tool to reduce the dependence of grape production on fungicide applications. Furthermore, this study indicates the importance of sustainable breeding and plant protection strategies based on resistant grapevine cultivars to reduce the risk of new P. viticola isolates that are able to overcome the respective resistance mechanism.

A Novel Etomidate Analog EL-0052 Retains Potent Hypnotic Effect and Stable Hemodynamics without Suppressing Adrenocortical Function.

Etomidate is a potent and rapidly acting anesthetic with high therapeutic index (TI) and superior hemodynamic stability. However, side effect of suppressing adrenocortical function limits its clinical use. To overcome this side effect, we designed a novel etomidate analog, EL-0052, aiming to retain beneficial properties of etomidate and avoid its disadvantage of suppressing adrenocortical steroid synthesis. Results exhibited that EL-0052 enhanced GABAA receptors currents with a concentration for EC50 of 0.98 ± 0.02 μM, which was about three times more potent than etomidate (3.07 ± 1.67 μM). Similar to hypnotic potency of etomidate, EL-0052 exhibited loss of righting reflex with ED50s of 1.02 (0.93-1.20) mg/kg in rats and 0.5 (0.45-0.56) mg/kg in dogs. The TI of EL-0052 in rats was 28, which was higher than 22 of etomidate. There was no significant difference in hypnotic onset time, recovery time, and walking time between EL-0052 and etomidate in rats. Both of them had minor effects on mean arterial pressure in dogs. EL-0052 had no significant effect on adrenocortical function in dogs even at a high dose (4.3 × ED50), whereas etomidate significantly inhibited corticosteroid secretion. The inhibition of cortisol synthesis assay showed that EL-0052 had a weak inhibition on cortisol biosynthesis in human H259 cells with an IC50 of 1050 ± 100 nM, which was 2.09 ± 0.27 nM for etomidate. EL-0052 retains the favorable properties of etomidate, including potent hypnotic effect, rapid onset and recovery, stable hemodynamics, and high therapeutic index without suppression of adrenocortical function. SIGNIFICANCE STATEMENT: The novel etomidate analog EL-0052 retains the favorable properties of etomidate without suppressing adrenocortical function and provides a new strategy to optimize the structure of etomidate.

모어청자에 의한 일본어 어두 폐쇄음의 지각*

It is known that the voicing contrast for Japanese word-initial stops is primarily realized as differences in the voice onset time (VOT). However, recent studies have reported that voiced stops are more often produced with a positive VOT than with a negative VOT among the younger generation nationwide. It is also known that post-stop F0 is associated with the stop contrast, but the degree of F0 use differs from region to region. This study explores whether the difference in post-stop F0 functions as a perceptual cue to the stop contrast along with VOT. Fifty-five college students who are native listeners from four different regions participated in two or three perception tests. The results show that VOT is a primary cue to the voiced-voiceless distinction of word-initial stops, but that the effect of post-stop F0 on the stop contrast is marginal. The post-stop F0 is involved in perception only when VOT is ambiguous, such that a sound with high F0 is more often perceived as a voiceless stop, but not vice versa. The results of this study indicate that the acoustic parameters associated with the stop contrast are not the same in production and perception, and suggest that other factors such as context, which is not an acoustic characteristic, may also be involved in the stop contrast.

Sleeping through COVID-19: a longitudinal comparison of 2019 and 2020 infant auto-videosomnography metrics.

With the outbreak of the COVID-19 pandemic, pediatric experts called attention to the potential adverse effects of living restrictions (e.g., lockdown) on child well-being, but at the same time- acknowledged their possible benefits. To date, only few data-driven reports have been published on child sleep during COVID-19, and all have been based on parent- or self-reports. This study used auto-videosomnography to capture the effects of COVID-19 stay-at-home orders imposed in the USA on objectively measured infant sleep. Auto-videosomnography metrics of infants assessed nightly between January and May 2020 were compared with metrics of an equivalent infant cohort, assessed in the corresponding 2019 period. A total of 610 infants (50.7% girls) aged 6-18 months (M = 11.8, SD = 3.6) were included, with 71,472 analyzed nights. Multilevel models were applied to assess differences between 2019 and 2020 infant sleep pre- and during-lockdown. Whereas infant cohorts were equivalent in demographic and January-March/April sleep characteristics, during the 2020 lockdown infants had longer nighttime sleep durations (Mdifference = 11.0 min, p = .01), later morning rise times (Mdifference = 9.5 min, p = .008), and later out-of-crib times (Mdifference = 12.3 min, p < .0001), compared to the equivalent 2019 period. In addition, weekday-weekend differences in sleep onset and midpoint times were diminished during 2020 home-confinement compared to the equivalent 2019 period (2019: Mdifference = 5.5 min, p < .0001; Mdifference = 4.5 min, p < .0001; 2020: Mdifference = 2.3 min, p = .01; Mdifference = 3.1 min, p < .0001, respectively). Notwithstanding the negative implications of COVID-19 living restrictions in other domains, our findings indicate that there might be a silver lining-in promoting longer and more consistent infant sleep. These benefits should be considered in determining policy for the current and future pandemics.

The effect of COVID-19 lockdowns on sleep time perception: Comparing actigraphy and sleep diary measures

COVID-19 has become a long-term problem, and global pandemic conditions may persist for years. Researchers are providing mounting evidence of relationships between COVID-19 lockdowns and sleep problems. However, few studies have investigated the impact of home isolation on sleep time perception, especially in comparable social isolation situations with similar pressures. Subjective sleep time perception parameters were derived from sleep diaries. Objective parameters were derived from actigraphy. Subjective and objective data were obtained between February 17 and February 27, 2020 from 70 adult participants subject to COVID-19 related lockdown provisions in China. We divided participants into a home stayers (HS) group (subject to full stay-at home orders) and an area-restricted workers (ARW) group (permitted to work at their nearby workplaces). The HS group demonstrated significantly delayed actigraphy-defined sleep onset time compared to self-reported sleep onset time; this effect was absent in the ARW group. Between-group differences in actigraphy-defined sleep onset time and significant between-group differences for actigraphy-defined and self-reported wake-up time were observed. HS group participants also presented significantly delayed actigraphy-defined wake-up time compared with self-reported wake-up time. No significant effect was found on total sleep time perception. Moreover, sleep/wake time misperception were found to be associated with daylight exposure and physical activity levels respectively. To the extent they are generalizable, these results suggest that lockdown restrictions can affect sleep onset and wake-up time perception but not total sleep time perception. Public health policy should consider such effects in the present pandemic situation and in future emergent public health situations.

Pericardial Toxicities Associated With Immune Checkpoint Inhibitors: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS) Database.

Introdution: Immune checkpoint inhibitors (ICIs) have significantly improved clinical outcomes for a wide range of cancers but can also lead to serious or fatal immune-related adverse events (irAEs). Although ICI-related pericardial toxicities have been reported, the clinical features are not well characterized in real-world studies. Objective: To characterize the main features of ICI-related pericardial toxicities and identify factors associated with death. Methods: Data from January 1, 2011 to March 31, 2020 in the FDA Adverse Event Reporting System database were retrieved for disproportionality analysis. We used the reporting odds ratio and the information component (IC) to evaluate the association between ICIs and pericardial adverse events. Clinical characteristics of patients with ICI-associated pericardial toxicities were collected and compared between fatal and non-fatal groups. The time to onset following different ICI regimens was further investigated. Results: We identified a total of 705 ICI-associated pericardial toxicities which appeared to influence more men (53.90%) than women (36.03%), with a median age of 63 (interquartile range [IQR] 54–69) years. Patients with lung cancer accounted for the largest proportion (55.6%). ICI therapies were detected with pharmacovigilance signals of pericardial toxicities, corresponding to IC025 = 2.11 and ROR 4.87 [4.51–5.25]. Nevertheless, there was a lack of association between anti-CTLA-4 and pericardial toxicities. There was no difference in onset time among all ICI regimens. However, TTO of fatal cases (25 days (interquartile range [IQR] 6–70)) occurred statistically earlier than non-fatal cases (42 days (IQR 12–114), p = 0.003). Conclusion: ICI monotherapy (PD-1/PD-L1 therapy) and combination therapy can lead to pericardial toxicities that can result in serious outcomes and tend to occur early. Early recognition and management of ICI-related pericardial disorders should attract clinical attention. The findings require further clinical surveillance for the quantification.

The Effects of Cigarette Smoking on Steroidal Muscular Relaxants and Antibiotics Used: A Prospective Cohort Study.

Background: The impact of cigarette smoking on perianesthesia management is not clear elucidated. This paper studies the impact of long-term cigarette smoking on the dose-response of rocuronium and vecuronium used under general anesthesia and the type of antibiotics used after surgery. Methods: We enrolled 240 participants from a teaching hospital in China in which finally enrolled in 221 participants. 106 participants have a history of long-term cigarette use and 115 participants without a history of smoking. All participants received general anesthesia for various surgeries, and rocuronium was used as the muscular relaxant. The primary outcome was the effective onset time of rocuronium after adjusting for its dose. The secondary outcomes included a recovery index and the time of muscle recovery changing from 25 to 75%. Results: There was no measurable difference in the muscle relaxant onset time, duration of effectiveness, 75% recovery, recovery index, dose of opiates, anesthetics during surgery, or complication rate between smokers or non-smokers. However, the results showed a significant difference in antibiotic use between smokers and non-smokers (chi-squared = 13.695, p < 0.001), and a significant difference in the type of antibiotics used (chi-squared = 21.465, p = 0.003). Smokers had a significantly higher rate of cefathiamidine use. Conclusion: Smoking cigarettes had no effect on muscle relaxants used under general anesthesia, but patients who had a history of smoking were more likely to receive antibiotics after surgery. Clinical Trial Registration: http://www.chictr.org.cn/index.aspx, identifier ChiCTR-OIC-16009157.

Discovering distorted repeating patterns in polyphonic music through longest increasing subsequences

We study the problem of identifying repetitions under transposition and time-warp invariances in polyphonic symbolic music. Using a novel onset-time-pair representation, we reduce the repeating pattern discovery problem to instances of the classical problem of finding the longest increasing subsequences. The resulting algorithm works in time where n is the number of notes in a musical work. We also study windowed variants of the problem where onset-time differences between notes are restricted, and show that they can also be solved in time using the algorithm.

Characteristics of diplopia in a pediatric population

To evaluate the characteristics of diplopia in children at a single tertiary eye care center. The medical records of patients with diplopia onset at age 18 years or younger presenting during the period 2015-2018 were reviewed retrospectively. Demographic information, clinical characteristics, diagnoses, treatment, and outcome data were collected. The exact χ2 test was used to compare groups and select post hoc analyses were performed using the Fisher exact or exact χ2 tests. A total of 244 patients (average age, 12.2 years at presentation) were included. The most common clinical diagnoses were nonparalytic strabismus (49.2%), trauma (9.4%), and cranial nerve palsies (9%). There was no statistically significant difference in median age of diplopia onset in those with nonparalytic strabismus, cranial nerve palsies, and vision- or life-threatening conditions. There was a statistically significant difference in timing of onset of diplopia at presentation in vision- or life-threatening conditions compared to nonparalytic strabismus (P < 0.0001) and cranial nerve palsies (P = 0.01) and for neurologic symptoms in vision- or life- threatening conditions compared to nonparalytic strabismus (P = 0.032) and cranial nerve palsies (P = 0.0051). In patients with more than one neurologic symptom, the majority (58.3%) had a vision- or life-threatening condition. Initial interventions included observation (28.7%), prisms (18.4%), updating refractive correction (14.3%), and strabismus surgery (11.1%). In patients with follow-up data, 5.3% had resolution of diplopia prior to their clinic visit, and 46.6% had resolution after initial intervention. In our study cohort, most children who presented with diplopia had nonemergent conditions. In those with life-threatening conditions, diplopia tended to have an acute onset and associated neurologic signs and visual symptoms.

English

BACKGROUND Shivering is commonly encountered complication following spinal anaesthesia leading to discomfort and interference with monitoring during caesarean section. There is no definite aetiology for this and hence no definite treatment is available. Hence, we wanted to study effect of temperature variation of spinal inject on post spinal shivering during caesarean section. METHODS This prospective randomized double-blind study was conducted on 80 parturients posted for elective caesarean section allocated to two groups of 40 each receiving 2.0 mL of 0.5 % hyperbaric bupivacaine with temperature of 220 C (group I) or 370 C (group II) intrathecally at L3 - L4 interspace. Onset of shivering, its severity and incidence were noted. Data was analysed using various tests and P-value &lt; 0.05 was considered as significant and P-value &lt; 0.01 was considered highly significant. RESULTS Demographic characters, surgical parameters as well as onset time of sensory blockade, maximum sensory blockade, time to achieve maximum sensory and motor blockade were comparable in the two groups. Shivering was present in 57.5 % of patients in group I and 32.5 % in group II and this difference was statistically significant. Overall, shivering percentage was 45 % although difference in mean onset time was not significant in the two groups. Grades of shivering were comparable in both groups. CONCLUSIONS Warm solutions used intrathecally can reduce incidence of shivering following spinal anaesthesia in caesarean section although it doesn’t influence intensity of shivering. KEY WORDS Neuraxial Anaesthesia, Temperature Variation, Post Spinal Shivering

A Randomised Controlled Study of Two Different Doses of Bupivacaine in Ultrasound Guided Axillary Brachial Plexus Block

Introduction: The use of Ultrasound (USG) for needle precision aids in reduction of local anaesthetic volume needed for peripheral nerve blockade. Conventional dosages of 30 to 40 mL of local anaesthetic mixture have been used in peripheral nerve blockades but using a lesser volume will reduce the incidence of local anaesthesia associated systemic toxicity. Aim: To assess the efficacy of two different doses 20 mL and 25 mL of Bupivacaine in USG guided axillary plexus block. Materials and Methods: Sixty patients requiring forearm and hand surgeries were randomised into two groups. Group A received low volume (20 mL of 0.375% bupivacaine) and group B received intermediate volume (25 mL of 0.375% bupivacaine). The quality of anaesthesia in regards to sensory and motor blockade, duration of analgesia, haemodynamic variability and complications were evaluated. Successful block was defined by Vester Anderson’s criteria. Duration of analgesia was measured using Visual Analogue Scale (VAS). Statistical comparison of all continuous variables were assessed utilising Student’s t-test and Mann-Whitney U-test as applicable. Results: No significant difference in onset times were observed as far as sensory and motor blockade was concerned between the two groups A and B with p-values of 0.69 and 0.40, respectively. Group B had significantly longer duration of block in comparison with Group A (p&lt;0.001). Two patients in group A and one patient in Group B required supplemental analgesia with fentanyl boluses. Haemodynamics were stable and no complications were seen in both the groups. Conclusion: Lower volume of Bupivacaine is convincingly prudent for regional blockade under USG guidance than suggested in literature.