Lengthening Of Interval Research Articles

Cardiac electrical and functional activity following an outdoor cold-water swimming event

AimsParticipation in outdoor cold-water swimming (OCWS) events combines endurance exercise and cold exposure. Concerns have emerged about the potential risk of acute adverse cardiac events during OCWS, particularly during endurance events. We analysed the effect of prolonged OCWS on cardiac function in trained athletes. MethodsThe swimming event consisted of laps over a 1000-m course, for up to 6 h, in water at 15 °C. Twenty participants (11 males, 47.3 ± 8.6 years old) were included. Core temperature (Tcore) was monitored using an ingestible temperature sensor during and up to 1 h after the swim. Body composition, blood pressure, electrocardiogram (ECG), and transthoracic echocardiography were assessed 1 day before the event and within the first hour upon completion of the swim. ResultsMean body mass index was 27.1 ± 5.1 kg/m2 and fat mass was 25.2 ± 9.1 %. Mean duration of swimming was 214 ± 115 min. Minimum Tcore was 35.6 ± 1.3 °C. A significant lengthening of the QT interval corrected (QTc) for heart rate was observed post-exercise (437.7 ± 27.7 vs. 457.2 ± 35.9 ms, p = 0.012), with 5 participants exhibiting post-exercise QTc >500ms. OCWS did not alter the biventricular systolic function and left ventricular relaxation. No correlation was observed between ΔQTc and ΔTcore. ConclusionOCWS seemed to acutely delay post-exercise cardiac repolarization without alteration of cardiac function in a healthy trained population. Additional investigations would be warranted to explore the clinical implications of QT lengthening and its relationship with autonomic nervous system regulation during OCWS.

Drug-induced increase in dispersion of ventricular repolarization in patients with heart failure with preserved ejection fraction

BackgroundHeart failure (HF) with preserved ejection fraction (HFpEF) is associated with enhanced response to drug-induced QT interval lengthening. We determined the influence of HFpEF on drug-induced lengthening of dispersion of repolarization, a measure of proarrhythmic risk. MethodsWe administered intravenous ibutilide 0.003 mg/kg to 10 patients with HFpEF and 10 age- and sex-matched controls without HF. Twelve‑lead electrocardiograms were obtained prior to ibutilide and serially for 8 h post-ibutilide. Tpeak-Tend, a measure of dispersion of ventricular repolarization, and heart rate-corrected J-Tpeak (J-Tpeakc), representing early repolarization, were measured by an investigator blinded to study groups. ResultsBaseline (pre-ibutilide) Tpeak-Tend and J-Tpeakc were not significantly different in the HFpEF and control groups. Maximum Tpeak-Tend was longer in the HFpEF group than in the control group (85 ± 10 vs 73 ± 8 ms, p = 0.01). Additionally, % change from baseline in Tpeak-Tend was greater in the HFpEF group [median (IQR) 17 (11) vs 8 (3)%, p = 0.003]. The area under the effect curve from 0 to 8 hours following ibutilide (including the 10-minute infusion) (AUEC0-8.17) for Tpeak-Tend was also larger in the HFpEF group (600 ± 42 vs. 543 ± 49 ms•hr, p = 0.03). Maximum J-Tpeakc, % change from baseline in J-Tpeakc and AUEC0-8.17 for J-Tpeakc in the two groups were not significantly different. ConclusionHFpEF is associated with enhanced response to drug-induced increases in dispersion of repolarization.

Impact of COVID-19 on a real-world treat-and-extend regimen with aflibercept for neovascular age-related macular degeneration

ObjectiveTo assess the effect of the COVID-19 pandemic on injection intervals among patients treated for neovascular age-related macular degeneration. DesignRetrospective cohort study. ParticipantsPatients treated at a single practice using a treat-and-extend regimen with intravitreal aflibercept between December 2018 and April 2021. MethodsThe primary outcome was the change in injection intervals. Secondary outcomes included differences in best-recorded visual acuity (BRVA) and central subfield thickness (CST). Associations were evaluated with linear mixed-effects modelling. ResultsThis study included 1839 injections from 185 eyes (141 patients). The median (interquartile range) injection intervals in the pre-COVID-19 and COVID-19 periods were 60 (42–70) and 70 (49–90) days, respectively. The pandemic was associated with a mean injection interval lengthening of 7.2 days (P < 0.001), a decrease in BRVA of 3.1 Early Treatment Diabetic Retinopathy Study letters (P < 0.001), and a reduction in CST of 14.7 μm (P = 0.003). The presence of exudative intraretinal fluid was associated with a reduction in treatment intervals of 11.1 days (P < 0.001), a reduction in BRVA of 1.9 Early Treatment Diabetic Retinopathy Study letters (P < 0.001), and an increase in CST of 52.4 μm (P < 0.001). The presence of subretinal fluid was associated with a reduction in treatment intervals of 8.5 days (P < 0.001) and an increase in CST of 21.6 μm (P < 0.001). ConclusionsThis real-world study estimated that the severe acute respiratory syndrome coronavirus 2 pandemic resulted in an injection extension of 7.2 days with associated decreases in BRVA and CST that are unlikely clinically significant on a population basis. This builds on evidence suggesting that long-term vascular endothelial growth factor suppression can facilitate meaningful interval extensions while maintaining visual acuity.

A PARTICULAR CASE OF CARDIAC ARREST

Abstract 88–year–old man with arterial hypertension, cognitive impairment, carrier of dual–chamber PM due to sinus node disease. Diagnosis of congenital long QT syndrome (LQT1) approximately 20 years ago during family screening (syncopal episodes in his son positive for LQT1), no history of syncope or major arrhythmias. In home therapy with mirtazapine and norvasc. He arrived in our cardiac intensive care unit for ACC on torsade de pointes trated with two cycles of CPR and 1 DC shock at 200 Joules with ROSC. On arrival ECG evidence of electrically induced ventricular rhythm, QTc 850 msec. On echocardiogram akinesia of the mid–basal segments of all the LV walls (takotsubo–like) with EF 25–30%. On coronary angiography non critical multivessel coronary disease. At laboratory tests increase of WBC, PCR and PCT, slight plateau movement of troponin, normal electrolytes. The patient underwent a chest CT scan with evidence of an inflammatory focus for which antibiotic therapy was started. Congenital long QT syndrome (LQTS) is an inherited condition characterized by prolongation of the QT interval (more than 450 ms in men and 460 ms in women), associated with repolarization abnormalities. There are three main forms transmitted via AD: LQT1, LQT2 and LQT3. The most common variant is LQT1 caused by a loss of function mutation in the KCNQ1 gene which causes a reduction in the outgoing potassium current during phase 3 of the action potential. In these patients, episodes of syncope caused by torsade de pointes, major arrhythmias and sudden cardiac death are frequent. Patients with LQTS should avoid taking drugs that can prolong the QT interval such as some antipsychotics, antidepressants (like mirtazapina that can cause QT prolongation, torsade de pointes, ventricular tachycardia and sudden cardiac death if administered at high doses or in patients with predisposing factors), antibiotics. Furthermore, there are various factors that can influence the QT prolongation: electrolyte alterations, physical stress, cerebrovascular events. The use of mirtazapine for a long period in association with takotsubo syndrome (probably triggered by underlying pneumonia) in a patient with LQTS, may have resulted in massive lengthening of the QT interval causing torsade de pointes and therefore ACC. During the hospitalization, mirtazapine was suspended and nadolol was introduced with a progressive reduction of the QT segment. No new arrhythmic events were recorded.

Analytical model of meshing stiffness, load sharing, and transmission error for internal spur gears with profile modification

The influence of the teeth geometry on the load distribution, transmission error, and meshing stiffness of internal spur gears is very similar to that of external gears. Therefore, the formulation of the models for strength and dynamic calculations for internal and external gears is also similar. However, the internal gears have usually greater values of the contact ratio, frequently above 1.8, even 1.9. In these cases, the lengthening of the contact interval due to the elastic deflections of the teeth may result in an effective contact ratio greater than 2, with the subsequent changes in the load sharing and transmission error. These changes are not properly described by the theoretical models for high contact ratio spur gears. In this paper, a model of load sharing, quasi-static transmission error, and time-varying meshing stiffness for internal spur gears with profile modification is presented, which has been applied to low contact ratio internal gears which, due to the transmitted load, become high contact ratio internal gears. The influence of the variations of the transmitted load on the load capacity is also studied.

Swimming and acoustic calling behavior attributed to Bryde’s whales in the central North Pacific

A unique acoustic call type was identified and attributed to Bryde’s whales in the central North Pacific in 2015, but little is known about the distribution, calling behavior, or swimming behavior of Bryde’s whales in the region. Acoustic detections attributed to Bryde’s whales were used to localize and track individual whales on the U.S. Pacific Missile Range Facility (PMRF) in Kaua‘i, Hawai‘i. This study included 150 acoustically derived tracks from recordings spanning the years 2011–2022 with recording effort in nearly every month. Bryde’s whale movement was examined relative to calendar year, day of year, hour of day, wind speed, and acoustic calling rate. Hidden Markov models were used to identify two kinematic states (slower, less directional movement and faster, more directional movement). The findings indicate that Bryde’s whales were more likely to travel in a faster and more directional state during the daytime than at night and between May and August when compared to other times of year. The along-track acoustic cue rate was examined for 118 tracks, and the findings indicate a possible lengthening of the median inter-call interval over the duration of the study period. These results are an important first step in understanding more about behavior in Bryde’s whales, a relatively under-studied species.

Ефективність і безпечність безперервного внутрішньовенного введення лідокаїну як компонента інтраопераційного знеболювання та післяопераційної інтенсивної терапії при обширних резекціях печінки

Purpose - to improve the effectiveness and determine the safety of intraoperative analgesia and postoperative intensive care for extensive liver resections with intravenous lidocaine compared with traditional analgesia and the use of epidural anesthesia. Materials and methods. 108 patients of 18 years of age and older who underwent extensive liver resection were examined and analyzed. The studied patients were stratified into three groups, depending on the choice of intra- and postoperative analgesia: the Group I (22 patients) - intravenous lidocaine administration + traditional intra- and postoperative analgesia, the Group II (73 patients) - epidural anesthesia (EDA) in the thoracic spine + traditional intra - and postoperative analgesia, the Group III (13 patients) - control, which used only traditional intra- and postoperative analgesia. Probability of differences was assessed using Student’s t-test, non-parametric Mann-Whitney U-test, Pearson’s χ2 test. Results. The blood lidocaine concentration in 2 hours after surgery was higher in the Group II (2.37±1.08 μg/ml) compared to the Group I (1.84±1.16 μg/ml). The values for 14 hours after the intervention did not differ (2.62±2.56 μg/ml - in the Group I, 2.85±1.25 μg/ml - in the Group II). In some cases, the local anesthetic content exceeded the toxic level without corresponding clinical symptoms. Intravenous lidocaine administration led to a decrease pain intensity within 4 days after surgery by almost 1.5 times, epidural administration - by 1.5-2 times compared to the standard analgesia, and was also accompanied by a lengthening of the time interval until the first injection of narcotic analgesics from 86.968.2 min to 394.3666.5 and 553.252.8.5 min, respectively. Changing the route of local anesthetic administration from epidural to intravenous led to decrease intraoperative volume of infusion therapy from 9.4±2.5 ml/kg/h to 7.4±1.3 ml/kg/h, as well as to reduction of the norepinephrine dose to eliminate hypotension by 1.3 times. Lidocaine administration attenuated the intensity of the systemic inflammatory response syndrome, which was manifested by a reduction in the concentration of IL-1, IL-4, IL-10 compared to multicomponent analgesia without a statistical difference with the epidural route of lidocaine administration. Conclusions. The use of lidocaine as an adjuvant in traditional intra- and postoperative analgesia for extensive liver resection reduces pain intensity and the degree of systemic inflammatory response syndrome. Changing the method of using lidocaine from epidural to intravenous leads to more stable intraoperative blood circulation, reduction the volume of infusion therapy and the need for sympathomimetic support without increasing blood concentration, and in the proposed method is an attractive alternative to epidural analgesia. The research was carried out in accordance with the principles of the Declaration of Helsinki. The study protocol was approved by the Local Ethics Committee of the institution mentioned in the work. Informed consent of the patients was obtained for the research. No conflict of interests was declared by the authors.

Особенности реакции сердечно-сосудистой системы организма человека на погружение в холодную воду

Winter swimming implies extreme cold stress, which can cause respiratory disorders, arrhythmias, and elevated blood pressure even in generally healthy people. Pre-training examinations for athletes practicing winter swimming should include additional criteria evaluating reaction of the cardiovascular system (CVS) to cold water. This study aimed to determine the risk of pathological abnormalities in the examined individuals exhibiting different CVS reactions to immersion in cold water. We assessed reactivity of CVS with the help of a cold-hypoxic test (CHT), following a previously developed algorithm. The subjects of the analysis were CVS reactions to CHT and physical data collected after swimming in cold water. The study involved 255 female and 205 male participants, all of them almost healthy, aged 18–25 years. They participated in testing in a laboratory setting. Poly-Spektr-8/E cardiograph was used to record ECGs, and GraphPad Prism 8 package for Windows 10 for statistical analysis. Findings: in highly reactive and reactive participants, CHT causes lengthening of the PQ interval, with its value in the initial state (IS) equal to 158 ± 7.2, and with CHT — 178 ± 9.1 (p &lt; 0.01); in subjects of he paradoxical type, CHT, against the background of higher pulse, triggered increase of QTc, which in the IS was 405 ± 7.1, with CHT — 420 ± 7.5 (p &lt; 0.05). As for blood pressure, on average, CHT made it grow, SBD by 17.4 ± 4.3 mmHg, DBP by 12.9 ± 3.1 mmHg (p &lt; 0.05). Swimmers adapted to cold, when swimming in cold water, had QTc above normal in 50% of cases: e.g., if IS of QTc was 434 ± 24 s, after swimming it increased to 492 ± 25 s. After a 200 m swim at t = 1.5–2 °C, the average blood pressure in the group, compared to IS, increased, with SBD growing by 16.9 ± 3.1 mmHg, and DBP — by 12.3 ± 2.3 mmHg (p &lt; 0.05). Having analyzed the data, we conclude that CHT can be the basis of additional criteria extending examinations for athletes seeking admittance to cold water swimming.

Hepatorenal and renocardial syndrome in young patients with acute glomerulonephritis

In this paper we discuss classical types of acute glomerulonephritis in young adults, when the intake of paracetamol and diclofenac led to a dysfunctional and organic liver injury, at the same time it negatively affected the course of acute glomerulonephritis. To study the characteristics of the development of acute reno-cardial syndrome (ARCS) Goal: Assessment of cause and effect relations of renal, hearts and liver injuries in young adults in acute post-streptococcal glomerulonephritis (APSG). With acute nephritic syndrome (ANS) complicated by acute kidney injury (AKI) and without it, to identify the role of the etiological factor on the course of APSG. Methods and Material: 220 male patients with APSG with ANS aged 18-20 were examined. The patients were divided into 2 groups based on the functional state of kidneys. The first group included 140 patients with APSG without ANS, the second group included 80 patients with AKI. Results: Out 66 patients had subclinical liver injury, which resulted from the effect of antipyretic hepatotoxic drugs taken in the initial stage of the disease. Due to the toxic and immunological liver injury, levels of transaminases increase, and albumin levels decrease. These changes occur along with the development of APSG and are correlated with some laboratory values. Impairment of cardiovascular function was observed in all 220 patients. ECG and Echocardiography studies conducted during the cardiac asthma attacks occurred as a decrease of voltage, broadening of the P wave, lengthening of the PQ interval, broadening of the QRS complex, dilatations of the right and left atrium. The severity of clinical manifestations of AKI and ARCS correlates with the degree of macrohematuria, GFR decrease, complement C3 fraction, monocyte. Conclusion. In APSG liver injury has a toxicoallergic character. Frequency of liver injury depends on specific features of a particular organism, it does not depend on the dose of the taken drug. In case of any type of acute glomerulonephritis it is necessary to assess the functional state of liver and after the treatment of the main disease hepatologist follow-up of patients is recommended. Thus in the development of acute reno-cardial syndrome (ARCS) the degree of manifestation of hypervolemia with hypertension, as a result of active immune inflammation of the glomerular apparatus with the development of AKI, plays the main role in the development of ARCS with APSG.. As a rule ARCS in case of APSG with ANS in young adults has a successful outcome.

Effect of mandibular advancement splint therapy on cardiac autonomic function in obstructive sleep apnoea.

This study aimed to evaluate the effect of mandibular advancement splint (MAS) therapy on cardiac autonomic function in patients with obstructive sleep apnoea (OSA) using heart rate variability (HRV) analysis. Electrocardiograms (ECG) derived from polysomnograms (PSG) of three prospective studies were used to study HRV of patients with OSA before and after MAS treatment. HRV parameters were averaged across the entire ECG signal during N2 sleep using 2-min epochs shifted by 30s. Paired t-tests were used to compare PSG and HRV measures before and after treatment, and the percent change in HRV measures was regressed on the percent change in apnoea-hypopnea index (AHI). In 101 patients with OSA, 72% were Caucasian, 54% men, the mean age was 56±11 years, BMI 29.8±5.3 kg/m2, and treatment duration was 4.0±3.2 months. After MAS therapy, there was a significant reduction in OSA severity (AHI, - 18 ± 16 events per hour, p < 0.001) and trends towards increased low-frequency to high-frequency ratio, low-frequency power, and reduced high-frequency power (LF:HF, - 0.4 ± 1.5, p = 0.01; LF, - 3 ± 16 nu, p = 0.02, HF, 3.5 ± 13.7 nu, p = 0.01). Change in NN intervals correlated with the change in AHI (β(SE) = - 2.21 (0.01), t = - 2.85, p = 0.005). No significant changes were observed in the time-domain HRV markers with MAS treatment. The study findings suggestthat successful MAS treatment correlates with changes in HRV, specifically the lengthening of NN intervals, a marker for improved cardiac autonomic adaptability.

Lung Cancer Screening in Asia: An Expert Consensus Report

IntroductionThe incidence and mortality of lung cancer are highest in Asia compared with Europe and USA, with the incidence and mortality rates being 34.4 and 28.1 per 100,000 respectively in East Asia. Diagnosing lung cancer at early stages makes the disease amenable to curative treatment and reduces mortality. In some areas in Asia, limited availability of robust diagnostic tools and treatment modalities, along with variations in specific health care investment and policies, make it necessary to have a more specific approach for screening, early detection, diagnosis, and treatment of patients with lung cancer in Asia compared with the West. MethodA group of 19 advisors across different specialties from 11 Asian countries, met on a virtual Steering Committee meeting, to discuss and recommend the most affordable and accessible lung cancer screening modalities and their implementation, for the Asian population. ResultsSignificant risk factors identified for lung cancer in smokers in Asia include age 50 to 75 years and smoking history of more than or equal to 20 pack-years. Family history is the most common risk factor for nonsmokers. Low-dose computed tomography screening is recommended once a year for patients with screening-detected abnormality and persistent exposure to risk factors. However, for high-risk heavy smokers and nonsmokers with risk factors, reassessment scans are recommended at an initial interval of 6 to 12 months with subsequent lengthening of reassessment intervals, and it should be stopped in patients more than 80 years of age or are unable or unwilling to undergo curative treatment. ConclusionsAsian countries face several challenges in implementing low-dose computed tomography screening, such as economic limitations, lack of efforts for early detection, and lack of specific government programs. Various strategies are suggested to overcome these challenges in Asia.

Effect of oral clonidine premedication on PR interval in patients undergoing rhinoplasty and functional endoscopic sinus surgery (FESS)

Background &amp; Objective: Clonidine, an alpha-2-agonist, plays a pivotal role in mitigating the sympathetic response during general anesthesia, thereby enhancing intraoperative hemodynamic stability. Despite its recognized benefits, reports of adverse cardiopulmonary effects have surfaced. This study investigates the impact of oral clonidine administered as premedication on patients undergoing rhinoplasty or Functional Endoscopic Sinus Surgery (FESS), with a focus on assessing alterations in the PR interval observed in postoperative electrocardiograms (ECG).&#x0D; Methodology: A Randomized Clinical Trial (RCT) comprised fifty patients scheduled for rhinoplasty or FESS under general anesthesia. Each participant underwent a standard 12-lead ECG, followed by the administration of 300 µg oral clonidine 30 min prior to entering the operating room. Anesthesia induction adhered to a uniform protocol for all subjects. Comprehensive ECG monitoring throughout the surgical procedure and recovery period facilitated the recording of any observed changes. Six hours post-clonidine administration, a second standard 12-lead ECG was obtained and juxtaposed with the initial recording.&#x0D; Results: Analysis revealed a lengthening of the PR interval in 23 (46%) of the cases. Within this cohort, 21 instances exhibited a prolongation falling within the normal range (0.12-0.2 sec), while the remaining two cases displayed abnormal prolongation (&gt; 0.2 sec) (P &lt; 0.001).&#x0D; Conclusion: This investigation suggests that premedication with oral clonidine, in the patients undergoing rhinoplasty or functional endoscopic sinus surgery, has the potential to extend the PR interval.&#x0D; Key words: Clonidine; PR interval; Rhinoplasty; Functional Endoscopic Sinus Surgery&#x0D; Citation: Saeed R, Qazi ZUS, Shah SMA, Bukhari S, Kanwal R, Kakepotto IA. Effect of oral clonidine premedication on PR interval in patients undergoing rhinoplasty and functional endoscopic sinus surgery (FESS). Anaesth. pain intensive care 2023;27(6):731−736; DOI: 10.35975/apic.v27i6.2343&#x0D; Received: August 24, 2023; Revised: November 03, 2023; Accepted: November 22, 2023

Sodium bicarbonate reverts electrophysiologic cardiotoxicity of ropivacaine faster than lipid emulsions in a porcine model.

Ropivacaine has been described as a safer local anaesthetic (LA); however, serious cardiotoxic accidents have been reported. Intravenous-lipid-emulsion (ILE) therapy during LA intoxication seems to act as an antidote. Sodium bicarbonate is the standard treatment for sodium channel blocker drug toxicity. We compared both antidotes on the reversion of electrophysiologic toxicity induced by ropivacaine. Ropivacaine 5mg kg-1 was administered in 24 pigs, and 3min later, the animals received ILE: 1.5ml kg-1 + 0.25 ml kg-1 min-1 (ILE group); sodium bicarbonate: 2mEq kg-1 + 1mEq kg-1 h-1 (NaHCO3 group); saline solution (CTL group). Electrophysiological parameters were evaluated for 30 min. The area under the curve (AUC) for the first 5 or 30 min was compared between groups. Ropivacaine induced a lengthening of the PR interval by 17% (P= 0.0001), His-ventricle-interval by 58% (P= 0.001), sinus QRS complex by 56% (P= 0.0001), paced QRS at 150 bpm by 257% (P= 0.0001), and at 120 bpm by 143% (P= 0.0001) in all groups. At 5min after treatment, sinus QRS in the NaHCO3 group was shorter than that in the CTL group (AUCQRS5 , P= 0.003) or ILE group (AUCQRS5 , P= 0.045). During the first minute, seven of the animals in the NaHCO3 group vs. two in the ILE or 0 in the CTL group recovered more than 30% of the sinus QRS previously lengthened by ropivacaine (P= 0.003). Sodium bicarbonate reversed the electrophysiological toxicity of ropivacaine faster than ILE and control groups.

Symptomatic Bradycardia in a Young Adult After Camping.

Scenario: An 18-year-old man with no significant medical history arrived at the emergency department via ambulance after a sudden syncopal episode of unknown cause. He had just returned from camping a few days prior. At the time of the episode, the patient was performing chores and his mother found him down and disoriented. En route to the hospital, emergency medical services reported a heart rate of 48/min and a blood pressure of 72/33 mm Hg; he was treated with a 500-mL saline bolus. During examination, he recalled the event and stated that he had felt dizzy so he had lain down. At this time, he reported no shortness of breath, chest pain, nausea, vomiting, changes in vision or hearing, or headache. Vital signs upon his arrival at the emergency department were recorded as heart rate 67/min, blood pressure 97/64 mm Hg, body temperature 38 °C (100.7 °F), respiratory rate 18/min, and oxygen saturation (via pulse oximetry) 98% on room air. A 12-lead electrocardiogram (ECG) was obtained after a bradycardic telemetry alarm. The rhythm strip of the 12-lead ECG is shown here.Mobitz II second-degree atrioventricular block at a heart rate of 60/min with bundle branch block (BBB) and a prolonged QTc interval.Atrioventricular (AV) block occurs when the electrical impulses traveling from the sinoatrial (SA) node through the AV node are impaired. The physiological reason for AV blocks is that gap junctions, protein channels that transfer electrical impulses between cells, are scarce in and around the AV node. The scarcity of gap junctions delays electrical conduction to allow the atria enough time to empty blood into the ventricles, but when this delay becomes excessive, it can cause symptoms. There are 3 types of AV block: first-degree AV block implies slowed conduction; second-degree AV block implies partial conduction from the SA node through the AV node; and third-degree AV block implies complete block of conduction from the SA node through the AV node. The rhythm above has a regularly irregular pattern with partial conduction exhibited by every third P wave lacking an associated QRS complex, consistent with second-degree AV block.Second-degree AV blocks are subdivided into Mobitz type I (Wenckebach) and Mobitz type II. Mobitz type I is characterized as progressive lengthening of the conduction time through the AV node until an electrical impulse is completely blocked, appearing on the ECG as progressive lengthening of the PR interval until a P wave appears without an associated QRS complex. Mobitz type I is typically caused by drugs, electrolyte imbalances, or myocarditis. In contrast, Mobitz type II is characterized as a consistent conduction time through the AV node, and a blocked electrical impulse typically in a predictable pattern (every second beat, third beat, etc). On the ECG, Mobitz type II is characterized as a fixed PR interval with a P wave that appears without an associated QRS complex. Mobitz type II is typically caused by idiopathic fibrosis of the conduction system, inflammatory conditions such as rheumatic fever and Lyme disease, and infiltrative myocardial disease.On this strip, the PR interval is fixed at 162 ms and every third P wave is blocked, which is consistent with second-degree AV block (Mobitz II). A BBB (evidenced by the prolonged QRS duration of 138 ms) and a prolonged corrected QT interval (480 ms) also are apparent. The BBB is presumably a left BBB, owing to the broad, monophasic R wave in lead V5.This young adult with no significant medical history had a new onset of unexplained second-degree AV block (Mobitz II), a left BBB, and a prolonged QTc, all of which were confirmed on the 12-lead ECG. Given his recent camping trip, Lyme disease was suspected and later confirmed. Lyme disease is caused by a spirochete (Borrelia burgdorferi), which can infect the myocardium and induce an inflammatory reponse of the transmural and conductive tissues. Notably, AV blocks are the most common cardiac manifestation of Lyme disease; 98% of adults with cardiac manifestations of Lyme disease will develop first-degree AV block, and up to 50% of those patients may transition to a third-degree AV block.In this case, the problem did not advance beyond second-degree AV block (Mobitz II) and the arrhythmia was intermittent. From a nursing standpoint, important actions include preparing for temporary pacing and diligent cardiac monitoring. In this case, the heart block resolved after treatment with antibiotics.

A large genome-wide association study of QT interval length utilizing electronic health records.

QT interval length is an important risk factor for adverse cardiovascular outcomes; however, the genetic architecture of QT interval remains incompletely understood. We conducted a genome-wide association study of 76,995 ancestrally diverse Kaiser Permanente Northern California members enrolled in the Genetic Epidemiology Research on Adult Health and Aging cohort using 448,517 longitudinal QT interval measurements, uncovering 9 novel variants, most replicating in 40,537 individuals in the UK Biobank and Population Architecture using Genomics and Epidemiology studies. A meta-analysis of all 3 cohorts (n = 117,532) uncovered an additional 19 novel variants. Conditional analysis identified 15 additional variants, 3 of which were novel. Little, if any, difference was seen when adjusting for putative QT interval lengthening medications genome-wide. Using multiple measurements in Genetic Epidemiology Research on Adult Health and Aging increased variance explained by 163%, and we show that the ≈6 measurements in Genetic Epidemiology Research on Adult Health and Aging was equivalent to a 2.4× increase in sample size of a design with a single measurement. The array heritability was estimated at ≈17%, approximately half of our estimate of 36% from family correlations. Heritability enrichment was estimated highest and most significant in cardiovascular tissue (enrichment 7.2, 95% CI = 5.7-8.7, P = 2.1e-10), and many of the novel variants included expression quantitative trait loci in heart and other relevant tissues. Comparing our results to other cardiac function traits, it appears that QT interval has a multifactorial genetic etiology.

Antipsychotic drugs and QT interval prolongation

Prolongation of myocardial repolarization, i.e. lengthening of the QTc interval on surface electrocardiogram (ECG), with increased risk of cardiac arrhythmias, has been recognized as a side effect of many drugs. Most first and second generation antipsychotic drugs can cause dose-related prolongation of QTc, although there are important differences in the potency of individual agents. ECGs in 46 patients suffering from schizophrenic disorder and treated with different antipsychotic drugs one week after the admission to the psychiatric hospital were analyzed in this prospective observational study. Hearth rate, QT interval and QTc interval were assessed. The average daily dose of prescribed antipsychotic drugs was calculated. Average QTc interval was 417 msec, only 3 out of 46 (6,5%) patients had QTc over 450 msec and only one patient (2,2%) had QTc over 500 msec. No differences in QTc interval between patients who were treated either with first or second generation antipsychotic drug or with combination of both were found. Female participants had significantly longer OTc interval than male participants (p &lt; 0,05). Results raise the question of the clinical relevance of a single ECG for diagnostics of cardiac complications in schizophrenia patients and suggest the need to conduct ECG monitoring in patients with high risk for cardiac complications during antipsychotic treatment.

Congenital Long QT Syndrome: A Review of Genetic and Pathophysiologic Etiologies, Phenotypic Subtypes, and Clinical Management.

Congenital Long QT Syndrome (CLQTS) is the most common inherited arrhythmia. The QT interval, which marks the duration of ventricular depolarization and repolarization in the myocardium, can be prolonged due to mutations in genes coding for the ion channel proteins that govern the cardiac action potential. The lengthening of the QT interval can lead to a wide range of clinical symptoms, including seizures, torsades de pointes, and fatal arrhythmias. There is a growing body of evidence that has revealed the genetic mutations responsible for the pathophysiology of CLQTS, and this has led to hypotheses regarding unique triggers and clinical features associated with specific gene mutations. Epidemiologic evidence has revealed a 1-year mortality rate of approximately 20% in untreated CLQTS patients, and a <1% of 1-year mortality rate in treated patients, underscoring the importance of timely diagnosis and effective clinical management. There are many phenotypic syndromes that constitute CLQTS, including but not limited to, Jervell and Lange-Nielsen syndrome, Romano and Ward syndrome, Andersen-Tawil syndrome, and Timothy syndrome. In this review, we aim to (1) summarize the genetic, epidemiologic, and pathophysiological basis of CLQTS and (2) outline the unique features of the phenotypic subtypes and their clinical management.

De-Escalation of Anti-Tumor Necrosis Factor Alpha Agents and Reduction in Adverse Effects: A Systematic Review.

Background: The long-term use of anti-TNF-α agents can lead to adverse effects, such as infections and immune-mediated cutaneous reactions. Whether de-escalation by dose reduction or interval lengthening reduces these adverse effects is uncertain. This systematic review aims to compare the incidence of infections and skin manifestations after anti-TNF-α dose de-escalation with standard dosing. Methods: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception to 14 January 2022. Randomized controlled trials (RCTs) and observational studies comparing anti-TNF-α de-escalation strategies with standard dosing among patients with inflammatory conditions, that report on infections, skin manifestations, or both, were included. The risk of bias was assessed with the revised Cochrane risk-of bias tool (RCTs) or the Newcastle–Ottawa scale (non-RCTs). Results: Fourteen RCTs and six observational studies (or 2706 patients) were included. Eight RCTs had low risk of bias or some concerns. Four non-RCTs were of good methodological quality. The studies described patients with axial spondyloarthritis (8 studies, 780 patients), rheumatoid arthritis (7 studies, 1458 patients), psoriasis (3 studies, 332 patients), or inflammatory bowel disease (2 studies, 136 patients). De-escalation strategies included interval lengthening (12 studies, 1317 patients), dose reduction (6 studies, 1130 patients), or both (2 studies, 259 patients). Overall, the occurrence of infections and skin manifestations did not differ between standard treatment and de-escalation. The disappearance of infections or skin manifestations after de-escalation was only reported in two studies. The majority of studies focused on etanercept and adalimumab. Heterogeneity in reporting of infections and skin manifestations precluded meta-analysis. Conclusion: We found that anti-TNF-α de-escalation does not reduce infections or skin reactions. A de-escalation strategy should not be recommended for the sole purpose of reducing drug-related adverse effects. The meticulous documentation of adverse effects is recommended to further address this question. Registration: PROSPERO CRD42021252977.

The influence of non-steroidal anti-inflammatory drugs with different mechanisms of action on the course of stress reaction, the functional state of kidneys, liver, and heart on the model of acute general cooling

Inhibitors of the arachidonic acid cascade have significant potential as the agents for the prevention of severe cold injuries. The results of the previous studies have demonstrated the pronounced frigoprotective properties of certain non-steroidal anti-inflammatory drugs, primarily diclofenac sodium, etoricoxib, darbufelone mesylate, under the conditions of acute general cooling.&#x0D; The aim of the study: to investigate the effect of non-steroidal anti-inflammatory drugs with various mechanisms of action on the course of the stress reaction, the functional state of the kidneys, liver, and heart using the model of acute general cooling.&#x0D; Materials and Methods: The experiment was carried out using 35 outbreed male rats weighing 256±5 g. The studied drugs were administered intragastrically 30 minutes before cold injury modelling: diclofenac sodium at a dose of 7 mg/kg, etoricoxib at a dose of 5 mg/kg, darbufelone mesylate at a dose of 20 mg/kg. Acute general cooling was induced by exposure at –18 °C for 2 hours. The efficacy of the studied drugs was evaluated by the values as follows: the body temperature (measured rectally), the course of a stress reaction according to the criteria of “the stress triad”, the functional state of the kidney and liver according to the changes in the blood serum biochemical parameters, the functional state of the heart according to the electrocardiogram.&#x0D; Results: It was found that etoricoxib and darbufelone mesylate, and especially diclofenac sodium, demonstrate frigoprotective properties, reducing the severity of hypothermia, have stress-protective activity and a beneficial effect on the functional state of the kidneys. All investigated non-steroidal anti-inflammatory drugs prevent a decrease in myocardial contractility (by the effect on the systolic index) and lengthening of the QT interval caused by acute cold injury. Diclofenac sodium, unlike etoricoxib and darbufelone mesylate, does not enhance the effect of acute general cooling on intraventricular conduction. Under acute exposure to cold, no significant changes in the functional state of the liver were observed, including the groups receiving the nonsteroidal anti-inflammatory medicines.&#x0D; Conclusions: The prophylactic administration of the arachidonic acid cascade inhibitors, especially the non-selective COX-2 inhibitor diclofenac sodium, reduces the severity of the stress response, contributes to the maintenance of the renal and cardiac function. There are no significant changes in the functional state of the liver under conditions of the experiment

Birth Spacing and Fertility in the Presence of Son Preference and Sex-Selective Abortions: India's Experience Over Four Decades.

Since the advent of prenatal sex-determination technologies in the mid-1980s, India has experienced an increasingly male-biased sex ratio at birth, presumably from sex-selective abortions. Abortions lengthen birth intervals, but we know little about how birth spacing has changed or the effects of these changes. I show that, although the overall length of birth intervals increased from 1970 to the mid-2010s, well-educated women with no sons had the most substantial lengthening, as well as the most male-biased sex ratios. Furthermore, most of these changes took place immediately after the introduction of prenatal sex-determination technologies. Consequently, some women without sons now have longer birth intervals than those with sons, reversing India's traditional spacing pattern. Women with low education continue short birth spacing when they have no sons, with only limited evidence of male-biased sex ratios. Because of the rapid lengthening of birth intervals, period fertility rates substantially overestimated how fast cohort fertility fell. Moreover, predicted cohort fertility is still 10%-20% above the period fertility rate. If the lengthening of birth intervals arises from repeated abortions, the associated short pregnancy spacing may counteract any positive effects of longer birth spacing. There is, however, no evidence of this effect on infant mortality. Judging from sex ratios, sex-selective abortion use is not declining.