Drug-induced QT prolongation and torsades de pointes: evaluation of a QT nomogram

BACKGROUND: Although QT prolongation is associated with increased risk of torsade de pointes (TdP), the precise relationship is not well defined. AIM: To evaluate the performance of a QT nomogram in assessing the risk of TdP from QT-RR combinations. DESIGN: Systematic review. METHODS: We systematically searched MEDLINE/EMBASE for cases of drug-induced TdP. Controls were patients taking non-cardiotoxic drugs in overdose. Inclusion criteria were definite TdP, normal ECG before or after the event, association with a drug/toxin and QT-RR measurements available. The upper bound of a QT-RR cloud diagram developed from human preclinical studies was converted into a QT nomogram [QT vs. heart rate (HR)]. QT-HR combinations for TdP cases and controls were plotted with the QT nomogram, and curves corresponding to a QTc = 440 ms and QTc = 500 ms for comparison (Bazett's correction). RESULTS: We identified 129 cases of TdP. TdP cases occurred at lower HR values with longer QT intervals, with most cases occurring at HR 30-90 bpm. Controls were more evenly distributed, with HR 40-160 bpm. The sensitivity and specificity of the QT nomogram were 96.9% (95%CI 93.9-99.9) and 98.7% (95%CI 96.8-100), respectively. For Bazett QTc = 440 ms, sensitivity and specificity were 98.5% (95%CI 96.3-100) and 66.7% (95%CI 58.6-74.7), respectively, whereas for Bazett QTc =500 ms they were 93.8% (95%CI 89.6-98.0) and 97.2% (95%CI 94.3-100), respectively. DISCUSSION: The QT nomogram is a clinically relevant risk assessment tool that accurately predicts arrhythmogenic risk for drug-induced QT prolongation. Further prospective evaluation of the nomogram is needed.     

Assessing risk of a prolonged QT interval–a survey of emergency physicians

Background

Although QT prolongation is associated with an increased risk of torsades de pointes (TdP), it is unclear how clinicians determine risk in individual patients with prolonged QT.

Aims

To investigate physicians’ interpretation of electrocardiogram (ECG) values in patients with a prolonged QT in reference to risk of TdP.

Methods

A survey was sent to Australasian emergency physicians (EPs) to investigate interpretation of ECG data in risk assessment for TdP. The survey contained three sections: demographic information, questions on heart rate correction and six sets of ECG data which the clinician ranked from low to high risk. Risk analysis for ECG values was performed by producing histograms of the distribution of responses for each of the six sets of ECG parameters. These distributions were compared to predicted distributions based on Bazett’s corrected QT>500 ms and the QT nomogram. The QT nomogram is a recently developed method for assessing whether QT-HR pairs are associated with increased risk of TdP by plotting them to determine if they are above an at risk line—the nomogram.

Results

Of 720 surveys sent out, 249 were returned (35%). A heart rate correction was used by 90% of respondents and the median “at risk” QTc judged by EPs was 450 ms [interquartile range (IQR): 440–500 ms]. Respondents were divided as to whether bradycardia increased the risk of TdP, with equal numbers responding “no change” and “more caution”. In four of the six sets of ECG parameters, EPs had a similar risk distribution to that predicted by Bazett. For one point predicted to be high risk by the QT nomogram, there was a uniform (undecided) risk distribution by EPs.

Conclusions

EPs mainly relied on Bazett’s correction as their method of TdP risk assessment, which may be problematic for bradycardic patients.     

Torsades de pointes episode in a woman with high-grade fever and inflammatory activation: A case report

BACKGROUNDQT interval prolongation can induce torsades de pointes (TdP), a potentially fatal ventricular arrhythmia. Recently, an increasing number of non-cardiac drugs have been found to cause QT prolongation and/or TdP onset. Moreover, recent findings have demonstrated the key roles of systemic inflammatory activation and fever in promoting long-QT syndrome (LQTS) and TdP development.CASE SUMMARYA 30-year-old woman was admitted with a moderate to high-grade episodic fever for two weeks. The patient was administered with multiple antibiotics after hospitalization but still had repeating fever and markedly elevated C-reactive protein. Once after a high fever, the patient suddenly lost consciousness, and electrocardiogram (ECG) showed transient TdP onset after frequent premature ventricular contraction. The patient recovered sinus rhythm and consciousness spontaneously, and post-TdP ECG revealed a prolonged QTc interval of 560 ms. The patient’s clinical manifestations and unresponsiveness to the antibiotics led to the final diagnosis of adult-onset Still’s disease (AOSD). There was no evidence of cardiac involvement. After the AOSD diagnosis, discontinuation of antibiotics and immediate initiation of intravenous dexamethasone administration resulted in the normal temperature and QTc interval. The genetic analysis identified that the patient and her father had heterozygous mutations in KCNH2 (c.1370C>T) and AKAP9 (c.7725A>C). During the 2-year follow-up period, the patient had no recurrence of any arrhythmia and maintained normal QTc interval.CONCLUSIONThis case study highlights the risk of systemic inflammatory activation and antibiotic-induced TdP/LQTS onset. Genetic analysis should be considered to identify individuals at high risk of developing TdP.     

Clinical characteristics of patients with drug-induced QT interval prolongation and torsade de pointes: identification of risk factors

The present study aimed to investigate the causative medications and underlying risk factors that predispose to drug-induced QT interval prolongation. Twenty-one patients with drug-induced long QT (90% females, mean age 64.3 ± 14.1 years) were included in the study. Transthoracic echocardiography as well as continuous or ambulatory 48-h electrocardiographic monitoring was carried out in all patients during their hospitalization. The mean corrected QT (QTc) interval was 542 ± 56.8 ms. Known cardiac agents (mainly class III antiarrhythmics) were implicated in 13/21 (62%), antipsychotics in 8/21 (38%), and antibiotics in 5/21 patients (24%). Potential drug-interactions through inhibition of cytochrome P450 isoenzymes were considered responsible in 5/21 cases (24%). The underlying cardiovascular diseases included hypertension (57%) with left ventricular hypertrophy (29%), paroxysmal atrial tachyarrhytmias (48%), heart failure (14%), valvular heart disease (10%), and coronary artery disease (5%). Torsade de pointes (TdP) was recorded in 6/21 of patients, and cardiac arrest necessitating resuscitation occurred in five of them. A significant correlation was observed between administration of cardiac agents and TdP events (P < 0.05). TdP and cardiac arrest events were both associated with a QTc interval >510 ms (P < 0.05). Advanced age (>60 years), female gender, hypertension and paroxysmal atrial tachyarrhytmias were the most common identifiable pre-existing factors for drug-induced long QT in our patient cohort. Marked QTc interval prolongation should be considered of prognostic significance for TdP and cardiac arrest events.     

Difference in QT Interval Measurement on Ambulatory ECG Compared with Standard ECG

Measurement of the QT interval on standard ECG has diagnostic importance in the congenital long QT syndrome, in pharmacological therapy of arrhythmias, as well as in ischemic heart disease. It has been suggested that QT prolongation on ambulatory ECG (Holter) may have similar importance. To assess agreement between methods, QT interval measurement on standard ECG was compared to that on Holter. Simultaneously obtained ECG and Holter tracings (25 mm/s) of the same complexes in leads V₁ and V₅ were studied in 14 patients (age range 4–36 years). ECG pairs (n = 100, 49 V₁ and 51 V₅) were compared over a range of QT interval from 300–620 ms, as determined with the use of calipers by two observers blinded to pairing relationship. Correlation between methods was high for both observers (observer 1: r[V₁] = 0.872, r[V₅] = 0.973; observer 2: r[V₁] = 0.972, r[V₅] = 0.988), and interobserver variability was small (> 85% of measurements within 20 ms). As compared to ECG, Holter underestimated QT interval in V₁ mean difference (QT [Holter]—QT [ECG]) observer 1 (-23 ms, P < 0.001), observer 2 (-7 ms, P < 0.05), and overestimated QT in V5, mean difference observer 1 (+ 13 ms, P < 0.001), observer 2 (+13 ms, P < 0.001). However, individual variation between methods was wide, as expressed by the difference between individual measurements (95% confidence interval [V₁]: observer 1 [-99 to +53 ms] observer 2 [-47 to +33 ms]; [V₅]: observer 1 [-33 to +59 ms] observer 2 [-17 to +43 ms]). Furthermore, when using the QTA (interval from onset of Q wave to apex of T wave) similar variability was observed. In the assessment of QT interval, potential sources of error of this magnitude could limit the clinical utility of ambulatory monitoring in detecting prolongation of the QT interval for diagnostic purposes.     

Effects of Celecoxib on the QTc Interval: A Thorough QT/QTc Study

PurposeCelecoxib is a selective cyclooxygenase-2 inhibitor widely used in patients with osteoarthritis and rheumatoid arthritis. Recently, nonclinical data on the inhibition of human ether-à-go-go–related gene potassium channels by celecoxib were reported, but there is no compelling evidence for this finding in humans. The aim of this study was to assess the potential effects of celecoxib on cardiac repolarization by conducting a thorough QT study, which was designed in compliance with the related guidelines.MethodsThis randomized, open-label, positive- and negative-controlled, crossover clinical study was conducted in healthy male and female subjects. Each subject received, in 1 of 4 randomly assigned sequences, all of the following 3 interventions: celecoxib 400 mg once daily for 6 days; a single dose of moxifloxacin 400 mg, which served as a positive control to assess the assay sensitivity; and water without any drug, which served as a negative control. Serial 12-lead ECG and blood samples for pharmacokinetic analysis were collected periodically over 24 h. Individually RR-corrected QT intervals (QTcI) and Fridericia method–corrected QT intervals (QTcF) were calculated and evaluated.FindingsTwenty-eight subjects were allocated to 1 of the 4 intervention sequences. The largest time-matched mean effects of celecoxib on the QTcI and QTcF were <5 ms, and the upper bounds of the 1-sided 95% CIs of those values did not exceed 10 ms. Moreover, none of the subjects had an absolute QTcI value of >450 ms or a change from baseline in QTcI of >60 ms after multiple administrations of celecoxib. The QTcI did not show a positive correlation with celecoxib concentrations in the range up to ~2700 μg/L. The overall effects of moxifloxacin on the QTcI and QTcF were enough to establish assay sensitivity. No serious adverse events were reported, with a total of 11 AEs reported in 8 subjects.ImplicationsCelecoxib caused no clinically relevant increase in the QT/QTc interval at the maximum dose level used in current practice settings. ClinicalTrials.gov identifier: NCT03822520.     

High prevalence of the risk factors for QT interval prolongation and associated drug–drug interactions in coronary care units

Objectives: Patients admitted in coronary care units are susceptible to QT interval prolongation due to numerous risk factors. The purpose of this study was to identify the prevalence of risk factors for QT interval prolongation; QT prolonging medications; drug–drug interactions; their predictors; and torsades de pointes risks of drugs.

Methods: After obtaining approval, this cross-sectional study was carried out during one-year period in coronary care units of two major tertiary care hospitals of Khyber Pakhtunkhwa, Pakistan. The Arizona Center for Education and Research on Therapeutics QT drugs lists and Micromedex DrugReax® were used to identify the QT prolonging medications and QT prolonging drug–drug interactions.

Results: Total 649 patients were included in this study. The most frequent QT prolonging risk factors included use of ≥ 1 QT prolonging drugs (74.9%) and myocardial infarction (61.3%). Total 181 patients were presented with 361 QT prolonging drug–drug interactions. There was significant association of the occurrence of QT prolonging drug–drug interactions with female gender (p = 0.01), 9–10 prescribed medications (p = 0.001), and > 10 prescribed medications (p < 0.001).

Conclusions: The majority of patients presented with multiple risk factors for QT prolongation in coronary care units which may precipitate lethal outcomes.     

Factors predictive of alcohol consumption among senior high school students in Phayao province,Thailand

Abstract

Objectives: To identify factors predictive of alcohol consumption among senior high school students in Phayao province, Thailand, where there is a high prevalence of alcohol consumption among adolescents.

Methods: A cross-sectional study in which 317 grade 11 senior high school students participated in a survey during June 2012. Data were collected by face-to-face interviews. Chi-square and multivariate logistic regression were used to determine the factors predictive of alcohol consumption among the subjects.

Results: Over two-thirds of the students (66.9%) had consumed alcohol in their lifetime, 58.7% in the previous year and 17.4% in the previous month. Following univariate analysis, seven factors – gender, age, GPA, allowance, first age of drinking, peer drinking and alcohol knowledge were identified as being significantly associated with drinking (p?<?0.05). Multivariate analysis revealed four factors to be predictive of alcohol among high school students: peer drinking (OR?=?3.59, 95%CI?=?1.99–6.44), alcohol knowledge (OR?=?2.64, 95%CI?=?1.47–4.72), GPA?≥?2.5 (OR?=?0.32, 95%CI?=?0.16–0.64) and allowance (OR?=?0.15, 95%CI?=?0.04–0.58).

Conclusion: Peer drinking was the strongest predictor of adolescent alcohol consumption, while alcohol knowledge had negative correlation with alcohol consumption. Hence, peer influence and appropriate alcohol knowledge should be considered as key areas in attempts to reduce alcohol consumption among senior high school students.     

多普勒超声心动描记术检测胎儿机械性QT间期

目的 探讨多普勒超声心动描记术在测量胎儿机械性QT间期中的应用价值。 方法 对胎儿心脏无异常的早孕期、中孕期和晚孕期孕妇各100名行胎儿多普勒超声心动描记术检查。记录左心室流入道及流出道血流频谱,测量机械性QT间期,即自二尖瓣舒张期A峰结束至下一个舒张期E峰开始的时间,同时测量胎儿心率。 结果 胎儿机械性QT间期和心率呈正态分布,早孕、中孕和晚孕组胎儿机械性QT间期均值的95%可信区间分别为225.25~231.21 ms、241.21~248.79 ms和253.23~259.45 ms;不同孕期组间胎儿机械性QT间期和心率的差异均有统计学意义(P均<0.01);胎儿机械性QT间期与孕周呈正相关(r=0.499,P<0.01),胎儿心率与孕周呈负相关(r=-0.628,P<0.01)。 结论 应用多普勒超声心动描记术检测胎儿机械性QT间期简便易行,图像清晰且重复性好,可为临床诊断胎儿心律失常提供重要依据。     

Disproportionality analysis of buprenorphine transdermal system and cardiac arrhythmia using FDA and WHO postmarketing reporting system data

Objective: Positive-controlled clinical studies have shown a dose dependent effect of buprenorphine transdermal system on QTc interval prolongation. This study provides assessment of the buprenorphine transdermal system and cardiac arrhythmia using US FDA and WHO postmarketing reporting databases.

Methods: Disproportionality analysis of spontaneously reported adverse events to assess whether the reporting rate of cardiac arrhythmia events was disproportionately elevated relative to expected rates of reporting in both FDA and WHO databases. Cardiac arrhythmia events were identified using the standardized Medical Dictionary for Regulatory Activities query for torsade de pointes and/or QT prolongation (TdP/QTP). The threshold for a signal of disproportionate adverse event reporting was defined as the lower 90% confidence limit ≥ 2 of the Empiric Bayes geometric mean in FDA database and as the lower 95% confidence limit of the Informational Component >0 in WHO database.

Results: There were 124 (<1%) and 77 (2%) cardiac arrhythmia event cases associated with buprenorphine transdermal as compared to 3206 (12%) and 2913 (14%) involving methadone in the FDA and WHO databases, respectively. In the FDA database methadone was associated with a signal of disproportionate reporting for TdP/QTP (EB05 3.26); however, buprenorphine transdermal was not (EB05 0.33). In the WHO database methadone was associated with a signal of disproportionate reporting for TdP/QTP (IC025 2.66); however, buprenorphine transdermal was not (IC025 ?0.88). Similar trends were observed in sensitivity analyses by age, gender, and specific terms related to ventricular arrhythmia.

Conclusions: The signal identified in the transdermal buprenorphine thorough QTc study, which led to a dose limitation in its US label, does not translate into a signal of increased risk for cardiac arrhythmia in real world use, as assessed by this method of analyzing post-market surveillance data.     

Electrocardiographic and Clinical Predictors of Torsades de Pointes Induced by Almokalant Infusion in Patients with Chronic Atrial Fibrillation or Flutter: A Prospective Study

The aim of this study was to identify predictors of torsades de pointes (TdP) in patients with atrial fibrillation (AF) or flutter exposed to the Class III antiarrhythmic drug almokalant. TdP can be caused by drugs that prolong myocardial repolarization. One hundred patients received almokalant infusion during AF (infusion 1) and 62 of the patients during sinus rhythm (SR) on the following day (infusion 2). Thirty-two patients converted to SR. Six patients developed TdP. During AF, T wave alternans was more common prior to infusion (baseline) in patients developing TdP (50% vs 4%, P < 0.01). After 30 minutes of infusion 1, the TdP patients exhibited a longer QT interval (493 ± 114 vs 443 ± 54 ms [mean ± SD], P < 0.01), a larger precordial QT dispersion (50 ± 74 vs 27 ± 26 ms, P < 0.05), and a lower T wave amplitude (0.12 ± 0.22 vs 0.24 ± 0.16 mV. P < 0.01). After 30 minutes of infusion 2, they exhibited a longer QT interval (672 ± 26 vs 489 ± 74 ms, P < 0.001), a larger QT dispersion in precordial (82 ± 7 vs 54 ± 52 ms, P < 0.01) and extremity leads (163 ± 0 vs 40 ± 34 ms, P < 0.001), and T wave alternans was more common (100% vs 0%, P < 0.001). Risk factors for development of TdP were at baseline: female gender, ventricular extrasystoles, and treatment with diuretics; and, after 30 minutes of infusion: sequential bilateral bundle branch block, ventricular extrasystoles in bigeminy, and a biphasic T wave. Patients developing TdP exhibited early during almokalant infusion a pronounced QT prolongation, increased QT dispersion, and marked morphological T wave changes.     

High prevalence of four long QT syndrome founder mutations in the Finnish population

Aims. Long QT syndrome (LQTS) is an inherited arrhythmia disorder with an estimated prevalence of 0.01%–0.05%. In Finland, four founder mutations constitute up to 70% of the known genetic spectrum of LQTS. In the present survey, we sought to estimate the actual prevalence of the founder mutations and to determine their effect sizes in the general Finnish population.

Methods and results. We genotyped 6334 subjects aged≥30 years from a population cohort (Health 2000 study) for the four Finnish founder mutations using Sequenom MALDI-TOF mass spectrometry. The electrocardiogram (ECG) parameters were measured from digital 12-lead ECGs, and QT intervals were adjusted for age, sex, and heart rate using linear regression. A total of 27 individuals carried one of the founder mutations resulting in their collective prevalence estimate of 0.4% (95% CI 0.3%–0.6%). The KCNQ1 G589D mutation (n=8) was associated with a 50 ms (SE 7.0) prolongation of the adjusted QT interval (P=9.0×10^?13). The KCNH2 R176W variant (n=16) resulted in a 22 ms (SE 4.7) longer adjusted QT interval (P=2.1×10^?6).

Conclusion. In Finland 1 individual out of 250 carries a LQTS founder mutation, which is the highest documented prevalence of LQTS mutations that lead to a marked QT prolongation.     

Approach to Evaluating QT Prolongation of Quetiapine Fumarate in Late Stage of Clinical Development Using Concentration-QTc Modeling and Simulation in Japanese Patients With Bipolar Disorder

PurposeQuetiapine has been reported to prolong the QT interval, and has been used as a positive control in thorough QT studies. The objective of the present study was to evaluate, in the late stages of clinical development, the QT-prolongation effects of the extended-release (XR) formulation of quetiapine at the approved dose in Japanese patients with bipolar disorder, using concentration–QT modeling and simulation.MethodsPlasma concentrations of quetiapine and 4 of its metabolites (M1, M2, M4, and M5), and the QT interval corrected using the Fridericia formula (QTcF), were used for the concentration–QT analysis. Data from intensive electrocardiogram monitoring at predose and at 4, 6, 10, and 24 h after the administration of the last dose were pooled from a Phase I trial (6949-CL-0006) and from sparse sampling in late-stage clinical trials (6949-CL-0005, -0021, −0022, and −0023) in Japanese patients (N = 505). The upper limit of 1-sided 95% confidence interval (CI) of the changes from baseline in QTcF (ΔQTcF) at the geometric mean Cmax of a therapeutic dose of 300 mg once daily was predicted using a linear mixed-effects model, with the intercept as a random effect specifying a subject effect.FindingsFor quetiapine and M2, but not M1, M4, or M5, positive slopes were observed between ΔQTcF and concentration. The predicted upper limits of the 1-sided 95% CIs did not exceed the regulatory threshold of 10 msec. Therefore, QTc prolongation is unlikely to be clinically relevant at the approved dose of quetiapine XR.ImplicationsIn this pooled data analysis of the QT-prolongation effects of the quetiapine XR, positive relationships between ΔQTcF and quetiapine and M2 concentrations were observed. However, the predicted upper limits of the 1-sided 95% CIs did not exceed 10 msec. Therefore, QTc prolongation is unlikely to be clinically relevant at the approved dose. ClinicalTrials.gov identifiers: NCT01725282, NCT01919008, NCT01725308, NCT01737268, and NCT02362412.     

The ability of preoperative factors to predict patient-reported disability following surgery for rotator cuff pathology

Purpose: Minimal research has examined the prognostic ability of shoulder examination data or psychosocial factors in predicting patient-reported disability following surgery for rotator cuff pathology. The purpose of this study was to examine these factors for prognostic value in order to help clinicians and patients understand preoperative factors that impact disability following surgery.

Methods: Sixty-two patients scheduled for subacromial decompression with or without supraspinatus repair were recruited. Six-month follow-up data were available for 46 patients. Patient characteristics, history of the condition, shoulder impairments, psychosocial factors, and patient-reported disability questionnaires were collected preoperatively. Six months following surgery, the Western Ontario Rotator Cuff Index (WORC) and global rating of change dichotomized subjects into responders versus nonresponders. Logistic regression quantified prognostic ability and created the most parsimonious model to predict outcome.

Results: Being on modified job duty (OR?=?.17, 95%CI: 0.03–0.94), and having a worker’s compensation claim (OR?=?0.08, 95%CI: 0.01–0.74) decreased probability of a positive outcome, while surgery on the dominant shoulder (OR?=?11.96, 95%CI: 2.91–49.18) increased probability. From the examination, only impaired internal rotation strength was a significant univariate predictor. The Fear-avoidance Beliefs Questionnaire (FABQ) score (OR?=?0.95, 95%CI: 0.91–0.98) and the FABQ_work subscale (OR?=?0.92, 95%CI: 0.87–0.97) were univariate predictors. In the final model, surgery on the dominant shoulder (OR?=?8.9, 95%CI 1.75–45.7) and FABQ_work subscale score?≤25 (OR?=?15.3, 95%CI 2.3–101.9) remained significant.

Discussion: Surgery on the dominant arm resulted in greater improvement in patient-reported disability, thereby increasing the odds of a successful surgery. The predictive ability of the FABQ_work subscale highlights the potential impact of psychosocial factors on patient-reported disability.

• Implications for Rehabilitation

• Impairment-based shoulder measurements were not strong predictors of patient-reported outcome.

• Having high fear-avoidance behavior scores on the FABQ, especially the work subscale, resulted in a much lower chance of responding well to rotator cuff surgery as measured by self-reported disability.

• Having surgery on the dominant shoulder, as compared to the nondominant side, resulted in larger improvements in disability levels.

     

QT Interval in Children with Sensory Neural Hearing Loss

EL HABBAL, M.H., et al. : QT Interval in Children with Sensory Neural Hearing Loss. Long QT syndrome was first described in children with congenital sensory neural hearing loss (SNHL). The deafness was attributed to abnormalities in potassium ion channels of the inner ear. Similar channels are present in the heart and its dysfunction causes long QT syndrome. Whether congenital SNHL is associated with prolonged QT is unknown. This study examined 52 patients (median age 8.35 years, range 0.21–17.42 years) with SNHL and compared them to 63 healthy children (median age 10.2 years; range 0.67–19 years). An observer, who was blinded from the presence or absence of SNHL, measured QT, QTc intervals and dispersions from a standard 12‐lead electrocardiogram. To assess the cardiac autonomic enervation, power spectral analysis of heart rate variability was determined using a 24‐hour ambulatory heart rate monitor and was expressed as high (HF) to low frequency (LF) ratio. Left ventricular size and functions were evaluated by using two‐dimensional echocardiography. The medians (and ranges) of QT intervals were 340 ms (230–420 ms) in patients and 320 ms (240–386 ms) in the control group (P < 0.01 ). The QTc was longer in patients with SNHL (median 417 ms, range 384–490 ms) than in controls (median 388 ms, range 325–432 ms, P < 0.001 ). QT dispersions in SNHL were higher (median .038 ms, range 00–11 ms) than controls (median 27 ms, range 00–52 ms, P < 0.001 ). T wave inversion (n = 16 ) and alternans (n = 3 ) occurred in patients with SNHL. Heart rates were similar in both groups. Some deaf patients (n = 8 ) had dizzy episodes with a QTc > 440 ms. The HF:LF ratio was 1.32 (0.516–2.33) in deaf patients and 1.428 (0.67–2.3) in the control group (P > 0.1 ). Left ventricular size and functions were similar and normal in deaf patients and controls. In children, congenital SNHL is associated with a prolonged QT interval.     

Comorbidity burden conditions the prognostic performance of D-dimer in elderly patients with acute pulmonary embolism

Introduction

The prognostic accuracy of D-dimer for risk assessment in acute Pulmonary Embolism (APE) patients may be hampered by comorbidities. We investigated the impact of comorbidity burden (CB) by using the Charlson Comorbidity Index (CCI), on the prognostic ability of D-dimer to predict 30 and 90-day mortality in hemodynamically stable elderly patients with APE.

Prehospital sepsis alert notification decreases time to initiation of CMS sepsis core measures

Objective

To determine if prehospital identification of sepsis will affect time to Centers for Medicare and Medicaid services (CMS) sepsis core measures and improve clinical outcomes.

Relationship Between QT Interval Duration and Electrical Induction of Ventricular Tachycardia

The relation of inducible ventricular tachycardia (VT) to QT interval duration of ventricular paced rhythm has not been evaluated. To clarify this relation we measured corrected QT interval duration (QT_C) during sinus rhythm and QT interval duration during ventricular paced rhythm (QT-V) in patients with coronary artery disease without (non-VT group = group B) and with inducible VT (VT group = group A). Duration of QT-V was greater in the VT group (n = 20) compared with non-VT group (n = 20) during ventricular pacing at cycle lengths of 600 ms (424 ± 26 vs 396 ± 19 ms, P < 0.01), of 500 ms (407 ± 20 vs 383 ± 21 ms, P < 0.01), and of 400 ms (390 ± 21 vs 362 ± 17 ms, P < 0.001). During sinus rhythm the mean values of QT_C were similar in both groups (408 ± 25 vs 413 ± 20 ms, NSJ. During ventricular stimulation the percentage of patients with values of QT-V exceeding 380 ms was 35% in non-VT group and 95% in VT group (P <0.01) at cycle length of 500 ms and 5% versus 60%, respectively, (P < 0.01), at cycle length of 400 ms. Thus, a trend toward longer QT values of ventricular paced rhythm exists in patients with inducible VT.     

The effect of whole-body vibration therapy on bone metabolism,motor function,and anthropometric parameters in women with postmenopausal osteoporosis

Purpose: To review the research literature on the effectiveness of whole-body vibration (WBV) therapy in women with postmenopausal osteoporosis.

Methods: A systematic review was conducted by two independent reviewers. Mean differences (MDs), standardized mean differences (SMDs), and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed with the I² test. The Cochrane risk of bias tool was used to assess the methodological quality of the selected studies.

Results: Nine randomized controlled trials involving 625 patients met the inclusion criteria. No significant improvement was found in bone mineral density (BMD) (SMD?=??0.06, 95%CI=??0.22–0.11, p?=?0.50); bone turnover markers (MD?=??0.25, 95%CI=??0.54–0.03, p?=?0.08); anthropometric parameters, including muscle mass, fat mass, body mass index (BMI), and weight (SMD?=?0.02, 95%CI=??0.16–0.21, p?=?0.81); or maximal isotonic knee extensor strength (SMD?=?0.16, 95%CI=??0.63–0.95, p?=?0.69). However, maximal isometric knee extensor strength improved (SMD?=?0.71, 95%CI?=?0.34–1.08, p?=?0.0002).

Conclusions: WBV is beneficial for enhancing maximal isometric knee extensor strength, but it has no overall treatment effect on BMD, bone turnover markers, anthropometric parameters, or maximal isotonic knee extensor strength in women with postmenopausal osteoporosis.

• Implication of rehabilitation

• Osteoporosis is the leading underlying cause of fractures in postmenopausal women, whole body vibration (WBV) has received much attention as a potential intervention for the management of osteoporosis in recent years.

• Whole body vibration is beneficial for enhancing maximal isometric knee extensor strength in women with postmenopausal osteoporosis.

• Whole body vibration has no overall treatment effect on bone mineral density, bone turnover markers, anthropometric parameters and maximal isotonic knee extensor strength in women with postmenopausal osteoporosis.