Hydroxychloroquine-azithromycin,doubase C,and QTc prolongation in congolese patients with COVID-19:Myth or reality?

BACKGROUND QTc interval prolongation with an increased risk of torsade de pointes(Tsd)has been described in coronavirus disease 2019(COVID-19)patients treated with hydroxychloroquine(HCQ)and azithromycin(AZI)in Western countries.In the DR Congo,few studies have evaluated the safety of this association or proposed new molecules.AIM To determine the incidence of QTc prolongation and Tsd in COVID-19 patients treated with HCQ-AZIs vs doubase C(new molecule).METHODS In present randomized clinical trial,we have included patients with mild or moderate COVID-19 treated with either HCQ-AZI or doubase C.Electrocardiogram(ECG)changes on day 14 of randomization were determined based on pretreatment tracing.Prolonged QTc was defined as≥500 ms on day 14 or an increase of≥80 ms compared to pretreatment tracing.Patients with cardiac disease,those undergoing other treatments likely to prolong QTc,and those with disturbed ECG tracings were excluded from the study.RESULTS The study included 258 patients(mean age 41±15 years;52%men;3.4%diabetics,11.1%hypertensive).Mild and moderate COVID-19 were found in 93.5%and 6.5%of patients,respectively.At baseline,all patients had normal sinus rhythm,a mean heart rate 78±13/min,mean PR space 170±28 ms,mean QRS 76±13 ms,and mean QTc 405±30 ms.No complaints suggesting cardiac involvement were reported during or after treatment.Only four patients(1.5%)experienced QTc interval prolongation beyond 500 ms.Similarly,only five patients(1.9%)had an increase in the QTc interval of more than 80 ms.QTc prolongation was more significant in younger patients,those with high viral load at baseline,and those receiving HCQ-AZI(P<0.05).None of the patients developed Tsd.CONCLUSION QTc prolongation without Tsd was observed at a lower frequency in patients treated with HCQ-AZI vs doubase C.The absence of comorbidities and concurrent use of other products that are likely to cause arrhythmia may explain our results.

超对称Bullough-Dodd模型的prolongation分析

在扭曲仿射代数 A(2 )2 上建立了超对称的 Bullough-Dodd模型 .Prolongation方法的研究表明 ,该模型承认一个 Lax pair,从 Lax意义上证明该模型可积 .另外 ,当该超对称模型的所有费米量为零时 ,该系统就定义了一个新奇的由单标量玻色场指数相互作用构成的可积模型 .这个发现还打破了长久以来的一种认识 :只有 sinh-Gordon和标准Bullough-Dodd模型是 Liouville模型 .

Prolongation structure for nonlinear integrable couplings of a KdV soliton hierarchy

In this paper, a new nonlinear integrable coupling system of the soliton hierarchy is presented. Prom the Lax pairs, the coupled KdV equations are constructed successfully. Based on the prolongation method of Wahlquist and Estabrook, we study the prolongation structure of the nonlinear integrable couplings of the KdV equation.

Prolongation structure of the variable coefficient KdV equation

The prolongation structure methodologies of Wahlquist-Estabrook [Wahlquist H D and Estabrook F B 1975 J. Math. Phys. 16 1] for nonlinear differential equations are applied to a variable-coefficient KdV equation. Based on the obtained prolongation structure, a Lie algebra with five parameters is constructed. Under certain conditions, a Lie algebra representation and three kinds of Lax pairs for the variable coefficient KdV equation are derived.

THE PROLONGATION STRUCTURES AND NONLOCAL SYMMETRIES FOR MODIFIED BOUSSINESQ SYSTEM

The Wahlquist-Estabrook （WE） prolongation structures of modified Boussi-nesq （MB） system are studied from the coverings point of view. The realizations and classifications of one-dimensional coverings of this system are obtained completely. More-over the sufficient and necessary conditions for a vector field to be a nonlocal symmetry of this system are also demonstrated in the WE prolongation structures.

Fermionic Covariant Prolongation Structure for a Super Nonlinear Evolution Equation in 2+1 Dimensions

The integrability of a （2＋1）-dimensional super nonlinear evolution equation is analyzed in the framework of the fermionie covariant prolongation structure theory. We construct the prolongation structure of the multidimen- sional super integrable equation and investigate its Lax representation. Furthermore, the Backlund transformation is presented and we derive a solution to the super integrable equation.

Use of Human Embryonic Stem Cell-Derived Cardiomyocyte Clusters to Assess Potential for Chronic Treatment with Compounds to Cause QT Prolongation

Drug-induced QT prolongation is a serious clinical issue in developing novel drug candidates and marketing drugs. A major cause of QT prolongation is direct inhibition of human ether-à-go-go-related gene (hERG) channels. Reduction in repolarization-related channel expression levels on plasma membranes is another mechanism that induces QT prolongation. Recently, we established a system for assessing the risk of QT prolongation by using human embryonic stem cell-derived cardiomyocyte clusters (hES-CMCs) in which the field potential duration (FPD) or corrected FPD (FPDc) was measured as an indicator of drug-induced QT interval prolongation. Here, we examined whether this system was able to detect FPDc prolongation caused by pentamidine or probucol, both of which can induce QT prolongation after long-term treatment. hES-CMCs were treated with pentamidine or probucol, and the FPDc of the same clusters was measured 10 min, 4 h, and 24 h after the start of treatment. Concentration-dependent FPDc prolongation was observed at 24 h, but not at 10 min, with pentamidine or probucol treatment. These results suggest that the hES-CMC-based assessment system can be used to detect both acute (at 10 min) and delayed (at 24 h) QT prolongation risk on the same platform by simple alteration of the extended culture period.

Antipsychotic Medication and Risk of QTc Prolongation: Focus on Multiple Medication and Role of Cytochrome P450 Isoforms

Objective: To identify the effects of antipsychotics on QTc prolongation in light of age, gender, antipsychotic combination pattern, antipsychotic doses and cytochrome P450 (CYP) mediation, using large database describing the antipsychotic treatment of patients with schizophrenia in Japan. Methods: Using database of 4176 patients with schizophrenia discharged between April 2004 and March 2005 and receiving outpatient treatment from 526 psychiatric hospitals in Japan. Of the patients, 1437 were included for the analysis. These patients were classified into three groups according to the antipsychotic CPZ-equivalent doses that they received (low, 1 - 299 mg;middle, 300 - 999 mg;and high, ≥1000 mg). QTc intervals ≥ 440 msec were considered prolonged. We reviewed all the package inserts of the antipsychotics used from the website of Pharmaceuticals and Medical Devices Agency. Results: The mean QTc interval of the total patient group was 410.4 ± 23.3 msec. The females had significantly higher QTc values than the males (414.5 ± 24.0 vs. 406.8 ± 22.2 msec, respectively;p 0.05). Logistic regression analysis revealed that female gender (odds ratio [OR] = 1.83;95% CI: 1.28 - 2.56), CYP3A4-metabolized drugs (OR 1.56;95% CI: 1.05 - 2.30) were associated with an increased risk of QTc prolongation. Conclusion: The co-prescription of CYP3A4-mediated antipsychotic drugs should be carefully considered in females due to potential risk of QTc prolongation. Further studies of the cardiovascular safety of antipsychotics are warranted in patients receiving multiple medications.

Covariant Prolongation Structure, Conservation Laws and Soliton Solutions of the Gross-Pitaevskii Equation in the Bose-Einstein Condensate

In this paper, we investigate the Gross-Pitaevskii (GP) equation which describes the propagation of an electron plasma wave packet with a large wavelength and small amplitude in a medium with a parabolic density and constant interactional damping by the Covariant Prolongation Structure Theory. As a result, we obtain general forms of Lax-Pair representations. In addition, some hidden structural symmetries that govern the dynamics of the GP equation such as SL(2,R), SL(2,C), Virasoro algebra, SU(1,1) and SU(2) are unearthed. Using the Riccati form of the linear eigenvalue problem, infinite number of conservation laws of the GP equation is explicitly constructed and the exact analytical soliton solutions are obtained by employing the simple and straightforward Hirota’s bilinear method.

The Prolongation Structures for the System of the Reaction-Diffusion Type

Equations of the reaction-diffusion type are very well known and have been extensively studied in many research areas. In this paper, the prolongation structures for the system of the reaction-diffusion type are investigated from theory of coverings. The realizations and the classifications of the one-dimensional coverings of the system are researched. And the corresponding conservation law of the one-dimensional Abelian coverings is concluded, which is closely connected with the symmetry of the system by Noether theorem.

Effect of natural prolongation with geological features on maritime delimitation

The United Nations Convention on the Law of the Sea entitled the coastal States to naturally extend the continental shelf, which has caused more drastic disputes of maritime delimitation. This paper devotes to clarifying the significant concept of natural prolongation through an effect method combing the legal principles and technical analysis. Firstly, the classic samples with respect of the development of geological features are traced. Based on these samples, the classification with a model is proposed in order to affirm the concept＇s significance under certain geomorphologic situations. Lastly, scientific analysis is used to present two potential prolongation situations and emphasize that all the technical analysis on maritime delimitation should be complied with international law and protect the common interest of all the mankind.

Comparison of QT Correction Methods in the Pediatric Population of a Community Hospital: A Retrospective Study

Objective:Accurate measurement of QT interval,the ventricular action potential from depolarization to repolarization,is important for the early detection of Long QT syndrome.The most effective QT correction(QTc)formula has yet to be determined in the pediatric population,although it has intrinsically greater extremes in heart rate(HR)and is more susceptible to errors in measurement.The authors of this study compare six dif-ferent QTc methods(Bazett,Fridericia,Framingham,Hodges,Rautaharju,and a computer algorithm utilizing the Bazett formula)for consistency against variations in HR and RR interval.Methods:Descriptive Retrospective Study.We included participants from a pediatric cardiology practice of a community hospital who had an ECG performed in 2017.All participants were healthy patients with no past medical history and no regular med-ications.Results:ECGs from 95 participants from one month to 21 years of age(mean 9.7 years)were included with a mean HR of 91 beats per minute(bpm).The two-sample paired t-test or Wilcoxon signed-rank test assessed for any difference between QTc methods.A statistically significant difference was observed between every combination of two QTc formulae.The Spearman’s rank correlation analysis explored the QTc/HR and QTc/RR relationships for each formula.Fridericia method was most independent of HR and RR with the lowest absolute value of correlation coefficients.Bazett and Computer had moderate correlations,while Framingham and Rautaharju exhibited strong correlations.Correlations were positive for Bazett and Computer,reflecting results from prior studies demonstrating an over-correction of Bazett at higher HRs.In the linear QTc/HR regression analysis,Bazett had the slope closest to zero,although Computer,Hodges,and Fridericia had comparable values.Alternatively,Fridericia had the linear QTc/RR regression coefficient closest to zero.The Bland-Altman method assessed for bias and the limits of agreement between correction formulae.Bazett and Computer exhibited good agreement with minimal bias along with Framingham and Rautaharju.To account for a possible skewed distri-bution of QT,all the above analyses were also performed excluding the top and bottom 2%of data as sorted by heart rate ranges(N=90).Results from this data set were consistent with those derived from all participants(N=95).Conclusions:Overall,the Fridericia correction method provided the best rate correction in our pedia-tric study cohort.

Recovering from prolonged cardiac arrest induced by electric shock:A case report

BACKGROUND Cardiac arrest(CA)induced by electric shock is a rare occurrence,particularly in cases of prolonged CA.Currently,there is limited literature on similar incidents,and we present a relevant case report.CASE SUMMARY A 27-year-old Asian male man,experiencing respiratory CA due to electric shock,was successfully restored to sinus rhythm after 50 min of cardiopulmonary resuscitation and 8 electrical defibrillation sessions.In the subsequent stages,the patient received multiple organ function protection measures,leading to a successful recovery and eventual discharge from the hospital.CONCLUSION Prolonging resuscitation time can enhance the chances of survival for patients,this study provide valuable insights into the management of electric shock-induced CA.

Brain protective effect of dexmedetomidine vs propofol for sedation during prolonged mechanical ventilation in non-brain injured patients

BACKGROUND Dexmedetomidine and propofol are two sedatives used for long-term sedation.It remains unclear whether dexmedetomidine provides superior cerebral protection for patients undergoing long-term mechanical ventilation.AIM To compare the neuroprotective effects of dexmedetomidine and propofol for sedation during prolonged mechanical ventilation in patients without brain injury.METHODS Patients who underwent mechanical ventilation for>72 h were randomly assigned to receive sedation with dexmedetomidine or propofol.The Richmond Agitation and Sedation Scale(RASS)was used to evaluate sedation effects,with a target range of-3 to 0.The primary outcomes were serum levels of S100-βand neuron-specific enolase(NSE)every 24 h.The secondary outcomes were remifentanil dosage,the proportion of patients requiring rescue sedation,and the time and frequency of RASS scores within the target range.RESULTS A total of 52 and 63 patients were allocated to the dexmedetomidine group and propofol group,respectively.Baseline data were comparable between groups.No significant differences were identified between groups within the median duration of study drug infusion[52.0(IQR:36.0-73.5)h vs 53.0(IQR:37.0-72.0)h,P=0.958],the median dose of remifentanil[4.5(IQR:4.0-5.0)μg/kg/h vs 4.6(IQR:4.0-5.0)μg/kg/h,P=0.395],the median percentage of time in the target RASS range without rescue sedation[85.6%(IQR:65.8%-96.6%)vs 86.7%(IQR:72.3%-95.3),P=0.592],and the median frequency within the target RASS range without rescue sedation[72.2%(60.8%-91.7%)vs 73.3%(60.0%-100.0%),P=0.880].The proportion of patients in the dexmedetomidine group who required rescue sedation was higher than in the propofol group with statistical significance(69.2%vs 50.8%,P=0.045).Serum S100-βand NSE levels in the propofol group were higher than in the dexmedetomidine group with statistical significance during the first six and five days of mechanical ventilation,respectively(all P<0.05).CONCLUSION Dexmedetomidine demonstrated stronger protective effects on the brain compared to propofol for long-term mechanical ventilation in patients without brain injury.

Intensive care unit-acquired weakness–preventive,and therapeutic aspects;future directions and special focus on lung transplantation

In this editorial,comments are made on an interesting article in the recent issue of the World Journal of Clinical Cases by Wang and Long.The authors describe the use of neural network model to identify risk factors for the development of intensive care unit(ICU)-acquired weakness.This condition has now become common with an increasing number of patients treated in ICUs and continues to be a source of morbidity and mortality.Despite identification of certain risk factors and corrective measures thereof,lacunae still exist in our understanding of this clinical entity.Numerous possible pathogenetic mechanisms at a molecular level have been described and these continue to be increasing.The amount of retrievable data for analysis from the ICU patients for study can be huge and enormous.Machine learning techniques to identify patterns in vast amounts of data are well known and may well provide pointers to bridge the knowledge gap in this condition.This editorial discusses the current knowledge of the condition including pathogenesis,diagnosis,risk factors,preventive measures,and therapy.Furthermore,it looks specifically at ICU acquired weakness in recipients of lung transplantation,because–unlike other solid organ transplants-muscular strength plays a vital role in the preservation and survival of the transplanted lung.Lungs differ from other solid organ transplants in that the proper function of the allograft is dependent on muscle function.Muscular weakness especially diaphragmatic weakness may lead to prolonged ventilation which has deleterious effects on the transplanted lung–ranging from ventilator associated pneumonia to bronchial anastomotic complications due to prolonged positive pressure on the anastomosis.

Prevalence and Factors Associated with Diabetes among City Hall Workers, Bohicon, Benin

Introduction: Living and working conditions are increasingly conducive to a sedentary lifestyle. Many administrative workers are exposed daily to long hours of work in a prolonged sitting position, which can favour the onset of diabetes. The aim of the study was to determine the prevalence and factors associated with diabetes among workers at a town hall in Benin in 2019. Methods: This was a descriptive cross-sectional study conducted from December 2018 to January 2019. Exhaustive recruitment was carried out. Data were collected during a face-to-face interview, using a standardized questionnaire including socio-professional factors, behavioral factors, anthropometric measurements, and blood glucose. Frequencies were calculated. Frequencies were compared using the chi-square and Fisher tests. The significance threshold was 5%. Results: A total of 85 workers were included. Their mean age was 41.55 ± 9.82 years, with a sex ratio of 6.1. = The prevalence of diabetes was estimated at 8.2% [95% CI: 3.38 - 16.23%] and 3 of the workers knew they had diabetes. A family history of diabetes was associated with diabetes (p = 0.032). Occupationally, 10.77% of permanent employees had diabetes, compared with 0.0% of non-permanent employees;12.50% of employees with at least 10 years’ seniority had diabetes, compared with 7.25% of those with less seniority;19.05% of employees who spent at least 6 hours a day sitting at work had diabetes, compared with 4.69% of those who spent less time sitting. Conclusion: Preventing chronic disease in the workplace is part of promoting workers’ health, and must take into account occupational factors such as prolonged sitting.

The Prolongation Structure of a Coupled Kdv Equation

The new coupled KdV equation proposed by Ohta and Hirota, in which the phase shift depends on the mutual positions of solitons at the initial time, is investigated in the framework of prolongation structure theory. Its Lax representation is constructed.

Preoperative Fasting of More Than 14 Hours Increases the Risk of Time-to-Death after Cardiothoracic Surgery in Children:A Retrospective Cohort Study

Background:Prolonged preoperative fasting can cause hypoglycemia,hyperglycemia,and intravascular volume depletion in children.We aimed to examine whether prolonged preoperative fasting is associated with in-hospital mortality and other morbidities in pediatric cardiothoracic surgery.Methods:This retrospective cohort study included children aged 0–3 years who underwent cardiac surgery between July 2014 and October 2020.The patient demographic data,surgery-related and anesthesia-related factors,and postoperative outcomes,including hypoglycemia,hyperglycemia,sepsis,length of intensive care unit stay,and in-hospital mortality,were recorded.The main exposure and outcome variables were prolonged fasting and time-to-death after surgery,respectively.The associations between prolonged fasting and perioperative death were analyzed using multivariate Cox regression analysis.Results:In total,402 patients were recruited.The incidence of perioperative mortality was 21%(85/402).The proportion of perioperative deaths was significantly higher in the prolonged fasting group than that in the normal fasting group.The proportion of postoperative bacteremia and hypoglycemia was significantly higher in the very prolonged fasting group than that in the prolonged fasting group.After adjusting for preoperative conditions and anesthesia-and surgery-related factors,preoperative prolonged fasting>14.4 h was significantly associated with time-to-death(HR[95%CI]:2.2[1.2,3.9],p=0.036).The 30-day survival rates of fasting time>14.4 h,9.25–14.4 h,and<9.25 h were 0.67(0.55,0.81),0.79(0.72,0.87),and 0.85(0.79,0.91),respectively.Conclusions:Preoperative fasting of more than 14.4 h was associated with a two-fold increase in the hazard rate of time-to-death in children who underwent cardiac surgery.

Gemcitabine-induced peripheral vascular disease and prolonged response in a patient with metastatic pancreatic adenocarcinoma:A case report

BACKGROUND Gemcitabine is an antimetabolite used in the treatment of pancreatic cancer.One of the side effects of gemcitabine is vascular toxicity.Here,we report the case of a patient treated with gemcitabine who had peripheral vascular disease concomi-tant with a prolonged antitumor response.CASE SUMMARY A 75-year-old man was diagnosed with locally recurrent pancreatic cancer.Partial response was achieved after 9 mo of gemcitabine.At the same time,the patient reported peripheral vascular disease without necrosis.Chemotherapy was suspended,and after one month the Positron Emission Tomography(PET)scan showed locoregional tumor recurrence.Gemcitabine was resumed and partial response was obtained,but peripheral vascular disease occurred.CONCLUSION Our results suggest that the appearance of peripheral vascular disease may be related to a prolonged response to gemcitabine.

A Preliminary Study of Medical Books on Health Care for the Elderly and Prolonging Life in the Early 20th Century

The present research of Chinese medical history lack detailed discussions on Chinese medicine philology of the elderly and the various sorting of related literature of physiology and diseases both at home and abroad.Based on previous literature,the article aims to introduce the publishing trend of medical books on health cultivation and prolonging life on since modern times,generally describe its significance,and initially analyze the contents related to health cultivation for the elderly.The article finds out that after the scientific concepts were imported into China in large quantities from the beginning of the 20th century,the past superstitions rose again.The sciences of nutrition,bacteriology,and physiology in such books had all verified that the road to immortality was possible.The concept of longevity at the time emphasized a concept that could be controlled by science.With the advancement of scientific research and health concepts,people believed that they could eventually achieve immortality.It was obvious that people were filled with optimism about science at that time,thus gradually subverting the definition of the elderly.