Low-dose l-isoproterenol versus salbutamol in hospitalized pediatric patients with severe acute exacerbation of asthma: A double-blind,randomized controlled trial

BackgroundAlthough the guidelines in most countries do not recommend continuous inhalation of l-isoproterenol to treat pediatric patients with acute severe exacerbation of asthma, lower dose of l-isoproterenol has been widely used in Japan. To determine whether the efficacy of low-dose l-isoproterenol was superior to that of salbutamol, we conducted a double-blind, randomized controlled trial.MethodsHospitalized patients aged 1–17 years were eligible if they had severe asthma exacerbation defined by the modified pulmonary index score (MPIS). Patients were randomly assigned (1:1) to receive inhalation of l-isoproterenol (10 μg/kg/h) or salbutamol (500 μg/kg/h) for 12 hours via a large-volume nebulizer with oxygen. The primary outcome was the change in MPIS from baseline to 3 hours after starting inhalation. Trial registration number UMIN000001991.ResultsFrom December 2009 to October 2013, 83 patients (42 in the l-isoproterenol group and 41 in the salbutamol group) were enrolled into the study. Of these, one patient in the l-isoproterenol group did not receive the study drug and was excluded from the analysis. Compared with salbutamol, l-isoproterenol reduced MPIS more rapidly. Mean (SD) changes in MPIS at 3 hours were −2.9 (2.5) in the l-isoproterenol group and −0.9 (2.3) in the salbutamol group (difference −2.0, 95% confidence interval −3.1 to −0.9; P < 0.001). Adverse events occurred in 1 (2%) and 11 (27%) patients in the l-isoproterenol and salbutamol groups, respectively (P = 0.003). Hypokalemia and tachycardia occurred only in the salbutamol group.ConclusionsLow-dose l-isoproterenol has a more rapid effect with fewer adverse events than salbutamol.     

The Role of the Medical Expert in the Retrospective Assessment of Testamentary Capacity

Objectives:Physicians and other mental health experts are increasingly called on to assist the courts with the determination of testamentary capacity. We aim to improve the understanding of the retrospective assessment of testamentary capacity for medical experts in order to provide more useful reports for the court’s determinations and to provide a methodology for the retrospective assessment of testamentary capacity.Method:Medical experts with experience in the retrospective assessment of testamentary capacity collaborated with lawyers who practice estate litigation. The medical literature on the assessment of testamentary capacity was reviewed and integrated. The medical experts provided a clinical perspective, while the lawyers ensured that the case law and legal perspective were integrated into this review.Results:The focus and limitations of the medical expert are outlined including the need to be objective, nonpartisan, and fair. For the benefit of the court, the medical expert should describe the nature and severity of relevant medical, psychiatric, and cognitive disorders, and how they may impact on the specific criteria for testamentary capacity as defined by the leading case of Banks v Goodfellow. Medical experts should opine only on the issue of vulnerability to influence and defer to the court to determine the facts of the case regarding any influence that may have been exerted.Conclusions:Although the ultimate determination of testamentary capacity is a legal one, medical experts can help the court achieve the most informed legal decision by providing relevant information on clinical issues that may impact the criteria for testamentary capacity.     

Utility of QT interval corrected by Rautaharju method to predict drug-induced torsade de pointes

Introduction: New QT correction formulae derived from large populations are available such as Rautaharju’s [QTcRTH?=?QT * (120?+?HR)/180] and Dmitrienko’s [QTcDMT?=?QT/RR^0.413]. These formulae were derived from 57,595 and 13,039 cases, respectively. Recently, a study has shown that they did not experience errors across a wide range of heart rates compared to others.

Objectives: (1) To determine the best cut-off value of QTcRTH and QTcDMT as a predictor of torsade de pointes (TdP) and (2) to compare the sensitivity and specificity using the cut-off value of QTcRTH with those of the QTcBazett (QTcBZT), QTcFridericia (QTcFRD), and QT nomogram.

Methods: Data were derived from two data sets. All cases aged over 18 years with an exposure to QT-prolonging drugs. Group-1, all cases developed TdP. Data in Group-1 were obtained from systematic review of reported cases from Medline since its establishment until 10 December 2015. Group-2 is composed of those who overdosed on QT prolonging drugs but did not develop TdP. This data set was previously extracted from a chart review of three medical centers from January 2008 to December 2010. Data from both groups were used to calculate QTcRTH and QTcDMT. The cut-off values from QTcRTH and QTcDMT that provided the best sensitivity and specificity to predict TdP were then selected. The same method was applied to find those values from QTcBZT, QTcFRD, and QT nomogram. The receiver operating characteristic curve (ROC) was applied where appropriate.

Results: Group-1, 230 cases of drug-induced TdP were included from the systematic review of Medline. Group-2 (control group), which did not develop TdP, consisted of 292 cases. After applying all of the correction methods to the two datasets, the best cut-off values that provided the best accuracy (Ac) with the best sensitivity (Sn) and specificity (Sp) for each formula were as follows: QTcRTH at 477 milliseconds (ms), Ac?=?89.08%, Sn?=?91.30% (95%CI?=?86.89–94.61), Sp?=?87.33%(95%CI?=?82.96–90.92); QTcDMT at 475?ms, Ac?=?88.31%, Sn?=91.30% (95%CI?=?86.89–94.61), Sp?=?85.96%(95%CI?=?81.44–89.73); QTcBZT at 490?ms, Ac?=?86.97%, Sn?=?88.26% (95%CI?=?83.38–92.12), Sp?=?85.96% (95%CI?=?81.44–89.73); QTcFRD at 473?ms, Ac?=?88.89%, Sn?=?89.13% (95%CI?=?84.37–92.84), Sp =88.70% (95%CI?=?84.50–92.09). We found a significant difference (p-value?=?0.0020) between area under the ROC of the QTcRTH (0.9433) and QTcBZT (0.9225) but not QTcFRD (0.9338). The Ac, Sn, and Sp of the QT nomogram were 89.08%, 91.30% (95%CI?=?86.89–94.61), and 87.33% (95%CI?=?82.96–90.92), respectively, and they were all equal to those of QTcRTH.

Conclusion: Rautaharju method not only produced minimal errors for QT interval correction but also at QTcRTH 477?ms, it could predict TdP as accurately as QT nomogram and was better than the QTcBZT.     

Motor unit number index (MUNIX) in the quantitative assessment of severity and surgical outcome in cervical spondylotic amyotrophy

ObjectiveTo assess the feasibility of motor unit number index (MUNIX) in the quantitative assessment of the cervical spondylotic amyotrophy (CSA).MethodsMUNIX was recorded bilaterally on the abductor pollicis brevis, abductor digiti minimi, biceps brachii and middle deltoid in 41 normal controls and 47 patients with CSA (distal-type to proximal-type ratio: 25 to 22). Additionally, patients were assessed on handgrip strength (HGS), the disabilities of arm, shoulder and hand (DASH) and Medical Research Council (MRC) scales. These examinations were re-evaluated approximately 18 months after surgery in 37 of these CSA patients.ResultsMUNIX values were noticeably lower in the mainly affected muscles of CSA patients than those in controls (P < 0.05), and 49.0% (51/104) of the tested muscles with abnormal MUNIX measurements showed normal muscle strength. Significant correlations between MUNIX measurements and both DASH and MRC scores were observed in both CSA patient groups (P < 0.05). Postoperative longitudinal follow-up analysis identified significant increase in motor unit number in both CSA patient groups within approximately 18 months (P < 0.05), with or without improved measures of motor function.ConclusionsA significant reduction in MUNIX values related to motor impairment was observed in CSA patients, even in the subclinical stage. Compared to measures of motor function, the MUNIX measurements in the patients with CSA improved more noticeably after surgical intervention.SignificanceMUNIX may serve as an available supplementary test to quantitatively evaluate the motor dysfunction in CSA and to track its progression, that is complementary to conventional electromyography.     

Development of a Simulation-Based Mastery Learning Curriculum for Breaking Bad News

Introduction

Physician communication impacts patient outcomes. However, communication skills, especially around difficult conversations, remain suboptimal, and there is no clear way to determine the validity of entrustment decisions. The aims of this study were to 1) describe the development of a simulation-based mastery learning (SBML) curriculum for breaking bad news (BBN) conversation skills and 2) set a defensible minimum passing standard (MPS) to ensure uniform skill acquisition among learners.