Multiple clinical profiles of families with the short QT syndrome.

Aims: Short QT syndrome (SQTS) is a rare cardiac channelopathy characterized by a shortened corrected QT (QTc)-interval that can lead to ventricular arrhythmias and sudden cardiac death. The aim of this study was to investigate the clinical phenotypes and long-term outcomes of three families harbouring genetic mutations associated with the SQTS. Methods and results: Clinical data included medical history, physical examination, 12-lead ECG, 24-h Holter-ECG, and transthoracic echocardiography from three index patients and their first-degree relatives. Next generation clinical exome sequencing and genetic cascade screening were performed in index patients and their relatives, respectively. Two index patients experienced malignant ventricular arrhythmias and one patient suffered from arrhythmogenic syncope during a median follow-up period of 8 years. They all had genetic mutations associated with the SQTS. Two mutations were found in the KCNH2 gene, and one in the CACNA2D gene. One patient had an additional SCN10A variant. Alive and mutation-positive family members had short QTc-intervals, but no further phenotypic manifestations. None of the mutation-negative family members had an abnormal ECG or any symptoms. In all patients with shortened QTc-intervals, the QTc-interval had a low long-term variability and QTc shortening always remained detectable by 12-lead ECG. Conclusion: This study shows the variety of phenotypic manifestations in different families with SQTS. It further emphasizes the importance of a 12-lead ECG for early diagnosis, and the utility of next generation sequencing for the identification of mutations associated with the SQTS.

The development and validation of a health-related quality of life questionnaire for pre-school children with a chronic heart disease.

PURPOSE: Heart diseases are often associated with residual injuries, persisting functional restrictions, and long-term sequelae for psychosocial development. Currently, there are no disease-specific instruments to assess the health-related quality of life (HrQoL) of pre-school children. The aims of this study were to develop a parent proxy instrument to measure the HrQoL of children aged 3-7 years with a heart disease and to confirm its validity and reliability. METHODS: Items from the Preschool Pediatric Cardiac Quality of Life Inventory (P-PCQLI) were generated through focus groups of caregivers. In a pilot study, comprehensibility and feasibility were tested. Five subdimensions were defined theoretically. Psychometric properties were analysed within a multicentre study with 167 parental caregivers. RESULTS: The final 52-item instrument contains a total score covering five moderately inter-correlated dimensions. The total score of the questionnaire showed a very high internal consistency (Cronbachs' α = 0.95). Test-retest correlation was at r tt = 0.96. External validity was indicated by higher correlations (r = 0.24-0.68) with a generic paediatric quality of life questionnaire (KINDL) compared to the Strengths and Difficulties Questionnaire (r = 0.17 to 0.59). Low P-PCQLI total scores were significantly associated with inpatient as opposed to outpatient treatment (t = 6.04, p < .001), with at least moderate disease severity ((t = 5.05, p < .001) NYHA classification) and with poorer prognosis (t = 5.53, p < .001) as estimated by the physician. CONCLUSIONS: The P-PCQLI is reliable and valid for pre-school children with a heart disease. It could be used as a screening instrument in routine care, and for evaluation of HrQoL outcomes in clinical trials and intervention research.

Dental student suturing skills: a multicentre trial of a checklist-based assessment.

BACKGROUND: The assessment of clinical skills is essential to determine whether an undergraduate is competent to perform the tasks outlined in the curriculum. Such assessments in dentistry have historically not been subjected to large scale validity and reliability testing due the relatively small student numbers at each institute. The aims of this study were to test the validity and reliability of a standardised, checklist-based, suturing objective structured clinical examination (OSCE) and then to perform a multicentre trial to determine its performance over a large cohort of students. MATERIALS AND METHODS: A total of seven UK schools agreed to take part in the trial. To test the validity and reliability of the checklist, the examiner at each institution reviewed and scored video footage of 10 students performing the assessment. Each institution then carried out the assessment providing a checklist score and a global score for each of their own students. RESULTS: The assessment was well received by the staff, with acceptable inter-examiner variability. In total, 496 students completed the suturing OSCE with a success rate of 81% with a variation between schools of between 66% and 96%. A significant correlation was found between the checklist score and the global score (r = 0.361, P = 0.000). No one item on the checklist was found to be a determinant factor in the outcome of the OSCE. CONCLUSIONS: This checklist-based assessment of suturing skills was found to have face and content validity. Its reliability was promising, but merits further investigation. There may be an argument for the standardisation of the assessment of this core surgical skill throughout several UK-based dental schools.

Use of induction therapy in pediatric heart transplant recipients in Switzerland - Analysis of the Swiss national database.

BACKGROUND: Data on individualized immunosuppressive protocols for the pediatric heart recipients are missing in Europe. To contribute to this very small but specialized field, we describe the use of induction therapy (IT) in pediatric heart transplant patients in Switzerland and the retrospective outcomes. METHOD: This is a retrospective national database analysis of children <19 years of age at time of heart transplantation (HT) from 05/2008-01/2018. Use of IT or no IT, use of steroids, calculated panel reactive antibodies (cPRA) and outcomes (Mortality, post-transplant lymphoproliferative disease (PTLD), rejection rates) were studied within a mean follow-up period of 2.9 years (0.2-8.1 years). RESULTS: All 32 patients (12♂, 20♀), median age at HT of 6.4 years (24 days - 18 years) received IT using either polyclonal antibodies (ATG; 72%) or interleukin-2 receptor antagonist (anti-IL-2R mAb; 28%). Length of treatment was median of 4 (1-63) days. At time of HT all patients received steroids, while at discharge 32% and one year after HT 19%. Kaplan-Meier analysis of survival revealed a one-year survival of 86%. Three out of 7 patients with elevated cPRA (43%) died. Median time to first treated rejection was 19.4 months (±60.5 SD) without significant difference if treated with anti-IL-2R mAb or ATG (p:0.5). No development of PTLD, chronic renal failure needing ongoing renal replacement therapy or diabetes mellitus were recorded. DISCUSSION: This is the first report of the national practice use of IT within Switzerland. It reveals a high use of IT, no development of PTLD and a low use of steroids at one-year post HT.

Electrocardiographic changes during continuous intravenous application of bupivacaine in neonatal pigs.

BACKGROUND: It is controversial as to whether T-wave elevation is caused by local anaesthetics, epinephrine, or their combination. It has been shown that T-elevation after intravascular injection of a small bupivacaine test dose is caused by epinephrine and not by bupivacaine. The aim of this study was to investigate ECG changes with higher doses of i.v. bupivacaine. METHODS: Thirty neonatal pigs were anaesthetized with sevoflurane and their tracheas intubated and artificially ventilated. Under steady-state conditions, bupivacaine was continuously infused (flow rate 3.2 ml kg(-1) min(-1)) by a syringe infusion pump through a central venous catheter. Group 1 received bupivacaine 0.125%, Group 2 bupivacaine 0.5%. The ECG was continuously printed and subsequently analysed for alterations in heart rate, ventricular de- and repolarization, and arrhythmias at 1.25, 2.5, and 5 mg kg(-1) bupivacaine infused. RESULTS: Sinus rhythm persisted in all pigs. Heart rate decreased progressively in both groups, but this was significantly more pronounced in Group 1. T-wave elevation occurred in 40% and 0% (Groups 1 and 2) at 1.25 mg kg(-1), in 80% and 0% at 2.5 mg kg(-1), and in 93% and 80% at 5 mg kg(-1) bupivacaine infused. There were significant differences between the two groups at 1.25 and 2.5 mg kg(-1) infused. CONCLUSIONS: Higher doses of i.v. infused bupivacaine can cause T-elevation. With slower injection technique, T-elevation can already be detected at lower bupivacaine doses administered.

A generic consensus assessment of undergraduate competence in forceps exodontia in the United Kingdom.

UNLABELLED: The assessment of competence in clinical skills has become more frequent in published healthcare curricula and syllabuses recently. There are agreed mechanisms for the assessment of competence in the post-graduate environment, but no consensus within the undergraduate curriculum. This paper seeks to develop an agreed generic checklist for the assessment of competence in forceps exodontia. MATERIALS AND METHODS: A modified Delphi process was undertaken with representatives from all UK dental schools (n = 13) to develop a generic checklist for the assessment of competence in forceps exodontia. A content analysis of the assessments employed by each school was used to help discussion and inform the Delphi process. RESULTS: Seven schools currently employ a summative assessment of competence in forceps exodontia, with the majority employing a structured clinical objective test (n = 6). From the seven assessments, there were a total of 29 putative items and 10 putative domains identified for a generic checklist. These were reduced to five domains and 19 items through the content analysis and Delphi process, and a generic overarching checklist was created. CONCLUSION: Using this generic checklist, it may now be possible to pool data inter-institution to perform more powerful analyses on how our students obtain, or fail to obtain competence in forceps exodontia.

Catheter ablation in ASymptomatic PEDiatric patients with ventricular preexcitation: results from the multicenter "CASPED" study.

BACKGROUND: As there are limited data about the clinical practice of catheter ablation in asymptomatic children and adolescents with ventricular preexcitation on ECG, we performed the multicenter "CASPED" (Catheter ablation in ASymptomatic PEDiatric patients with Ventricular Preexcitation) study. METHODS AND RESULTS: In 182 consecutive children and adolescents aged between 8 and 18 years (mean age 12.9 ± 2.6 years; 65% male) with asymptomatic ventricular preexcitation, a total of 196 accessory pathways (APs) were targeted. APs were right sided (62%) or left sided (38%). The most common right-sided AP location was the posteroseptal region (38%). Ablation was performed using radiofrequency (RF) energy (93%), cryoablation (4%) or both (3%). Mean procedure time was 137.6 ± 62.0 min with a mean fluoroscopy time of 15.6 ± 13.8 min. A 3D mapping or catheter localization system was used in 32% of patients. Catheter ablation was acutely successful in 166/182 patients (91.2%). Mortality was 0% and there were no major periprocedural complications. AP recurrence was observed in 14/166 patients (8.4%) during a mean follow-up time of 19.7 ± 8.5 months. A second ablation attempt was performed in 20 patients and was successful in 16/20 patients (80%). Overall, long-term success rate was 92.3%. CONCLUSION: In this retrospective multicenter study, the outcome of catheter ablation for asymptomatic preexcitation in children and adolescents irrespective of antegrade AP conduction properties is summarized. The complication rate was low and success rate was high, the latter mainly depending on pathway location. The promising results of the study may have future impact on the ongoing risk-benefit discussion regarding catheter ablation in the setting of asymptomatic preexcitation in children and adolescents.

Cardiac output measurement in children: comparison of Aesculon cardiac output monitor and thermodilution.

BACKGROUND: We compared cardiac output (CO) measurements by the non-invasive electrical velocimetry (Aesculon) monitor with the pulmonary artery catheter (PAC) thermodilution method in children. METHODS: CO values using the Aesculon monitor and PAC thermodilution were simultaneously recorded during cardiac catheterization in children. Measurements were performed under general anaesthesia. To compare, three consecutive measurements for each patient within 3 min were obtained. The means of the three values were compared using simple regression and Bland-Altman analysis. Data were presented as mean (sd). A mean percentage of <30% was defined to indicate clinical useful reliability of the Aesculon monitor. RESULTS: A total of 50 patients with a median (range) age of 7.5 (0.5-16.5) yr were enrolled in the study. Mean CO values were 3.7 (1.5) litre min(-1) (PAC thermodilution) and 3.1 (1.7) litre min(-1) (Aesculon) monitor). Analysis for CO measurement showed a good correlation between the two methods (r=0.894; P<0.0001). The bias between the two methods was 0.66 litre min(-1) with a precision of 1.49 litre min(-1). The mean percentage error for CO measurements was 48.9% for the Aesculon monitor when compared with PAC thermodilution. CONCLUSIONS: Electrical velocimetry using the Aesculon monitor did not provide reliable CO values when compared with PAC thermodilution. Whether the Aesculon monitor can be used as a CO trend monitor has to be assessed by further investigations in patients with changing haemodynamics.

Regional cerebral oxygenation by NIRS does not correlate with central or jugular venous oxygen saturation during interventional catheterisation in children.

PURPOSE: To evaluate whether regional cerebral oxygenation (rSO(2)) by near-infrared spectroscopy correlates with central venous (SvO(2)) or internal jugular (SjO(2)) oxygen saturation, and whether changes over time (Delta) in rSO(2) (DeltarSO(2)) predict changes in SvO(2) (DeltaSvO(2)) and SjO(2) (DeltaSjO(2)). METHODS: The rSO(2) values were measured using the INVOS 5100 cerebral oximeter in children undergoing interventional cardiac catheterization and were compared with the oxygen saturation of analysed central venous and internal jugular blood samples. Changes over time (Delta) were calculated as the difference between the values before and after catheter intervention for rSO(2).(DeltarSO(2)), SvO(2).(DeltaSvO(2)) and SjO(2).(DeltaSjO(2)). Simple regression and Bland-Altman analysis were performed. Data are presented as median (range). RESULTS: Sixty patients aged 4.3 (0.2-16.0) years were investigated. A closer correlation was found between rSO(2) and SvO(2) (r=0.728, P<0.0001) than between rSO(2) and SjO(2) (r=0.665, P<0.0001). The bias between rSO(2) and SvO(2).(SjO(2)) was 0.17% (-0.60%), with limits of agreement from -15.5% to 15. 9% (-18.6-17.4%). The sensitivity/specificity for DeltarSO(2) to indicate a fall in SvO(2) or in SjO(2) was 70.3%/65.2% and 68.6%/60.0%, respectively. CONCLUSION: Neither absolute values nor changes in rSO(2) using the INVOS 5100 allowed reliable estimation of SvO(2) or SjO(2) and their trends.

Comparison of cardiac output measurement using the CardioQP oesophageal Doppler with cardiac output measurement using thermodilution technique in children during heart catheterisation.

The minimally invasive CardioQP oesophageal Doppler probe estimates cardiac output by measuring blood flow velocity in the descending aorta. Individual variables to enter are patient's age, weight and height. We measured cardiac output simultaneously with CardioQP and pulmonary artery catheter thermodilution techniques during heart catheterisation in 40 paediatric patients with congenital heart defects. Median [range] age was 8.2 years [0.5-16.7 years], cardiac output values measured by thermodilution and CardioQP were 3.6 l.min(-1) [1.2-7.1 l.min(-1)] and 3.0 l.min(-1) [0.7-6.7 l.min(-1)], respectively. These values showed only moderate correlation (r = 0.809; p < 0.0001). Bias and precision were 0.66 l.min(-1) and 1.79 l.min(-1) (95% limits of agreement: -1.13 to +2.45 l.min(-1)). Based on our preliminary experience, cardiac output values measured by CardioQP in children do not reliably represent cardiac output values compared with the thermodilution technique. We suggest measurement of individual aortic diameter to improve performance of the CardioQP.

Anaesthesia recovery quality after racemic ketamine or S-ketamine administration to male cats undergoing neutering surgery.

Postoperative anaesthesia recovery and analgesia qualities were compared in cats anaesthetised with racemic ketamine (RS-ket) or S-ketamine (S-ket) undergoing orchiectomy. Twenty client-owned male cats received medetomidine (0.03 mg/kg) and S-ket (6 mg/kg; n = 10) or RS-ket (10 mg/kg; n = 10), all intramuscularly. After routine orchiectomy, animals received atipamezole (0.15 mg/kg) intramuscularly. Thirty and 60 min after atipamezole administration, one observer unaware of the treatment identity evaluated analgesia using a visual analogue scale (VAS) and, by means of four points scales, sedation, unprovoked behaviour and behavioural reactions to external stimuli. Cats with a VAS > or = 15 mm were to receive butorphanol. Times to sternal and standing positions were recorded. After 60 min, cats were given carprofen (4 mg/kg) subcutaneously. Anaesthesia with S-ket, at 60% of the RS-ket dose, provided faster recoveries. At 60 min, undisturbed cats in S-ket group had a trend towards fewer behavioural changes. Cats in RS-ket group were more sedate at 30 min and responded with a lower intensity to external stimulation. Immediate postoperative analgesia was considered adequate for both groups and no cat required butorphanol administration.

Meeting and greeting in the clinical setting - are we doing what patients want?

Objective To determine how patients want to be greeted by clinicians on a first encounter in the clinical setting.Setting A UK dental teaching hospital in 2015/16.Materials and methods Data was collected prospectively via 450 patient questionnaires. The results were stratified by generational cohort and compared to assess if there was an association between patient preferences and the generational theory.Results Patients preferred to be greeted informally by their first name and didn't mind how the clinician introduced themselves or preferred them to use their first name also. Patients showed a preference to shake hands with their clinician, particularly in older generational cohorts. The majority of patients believed that it was helpful to know the training grade of the clinician providing treatment but didn't understand what the different grades meant. Patients believed that explaining the different training grades and using colour-coded uniforms would be useful.Conclusions Consideration should be given to addressing patients informally by their first name and shaking hands at a first encounter. Clinicians should routinely disclose their training grade when introducing themselves and consideration should be given to providing patients with an explanation of the different training grades and using colour-coded uniforms to avoid confusion.

Pharmacokinetics of ametantrone acetate (NSC-287513).

Ametantrone is the second anthracene derivative to enter clinical trials. The pharmacokinetic parameters for ametantrone acetate (CI-881) were characterized in six patients concurrently with the phase I clinical trial. Biological samples were assayed by a specific and sensitive high-performance liquid chromatography procedure. Plasma levels of ametantrone declined in a triexponential fashion, with a mean terminal half-life (t 1/2 gamma) of 25 h. The estimated mean total-body plasma clearance was 25.9 +/- 14.7 1 h-1 m-2. The steady-state volume of distribution (Vdss) was large, averaging 568 +/- 630 l/m2. Excretion of unchanged ametantrone in the urine over 48 h averaged 5.7% of the total dose, indicating that there is another major route of elimination.

Melatonin therapy of advanced human malignant melanoma.

We undertook a study to investigate the therapeutic potential of orally administered melatonin in patients with advanced melanoma. Forty-two patients received melatonin in doses ranging from 5 mg/m2/day to 700 mg/m2/day in four divided doses. Two were excluded from analysis. After a median follow-up of 5 weeks, six patients had partial responses, six additional patients had stable disease. Sites of response included the central nervous system, subcutaneous tissue and lung. The median response duration was 33 weeks for the partial responders. There was a suggestion of a dose-response relationship. The toxicity encountered was minimal and consisted primarily of fatigue in 17 of 40 patients. Melatonin also appeared to reduce basal levels of follicle-stimulating hormone (FSH). No significant changes were encountered in serum levels of luteinizing hormone (LH) or thyroid stimulating hormone (TSH). We conclude that further study of melatonin as a potentially useful agent in metastatic melanoma is warranted.

Serum melatonin levels in melanoma patients after repeated oral administration.

The goal of this study was to determine the effect of oral melatonin in divided doses on plasma melatonin levels in patients with metastatic melanoma. Hourly blood samples were obtained from five patients for 24 h prior to melatonin administration and for 24 h during oral administration of melatonin, 50 mg every 4 h. In two of the five patients, the expected nocturnal plasma melatonin peak was observed. Oral melatonin was well absorbed. Plasma melatonin levels exhibited six peaks and troughs, were two to four-fold higher during peaks than troughs, and remained more than 25 times higher than peak pretreatment melatonin levels, even during troughs. Divided oral doses of melatonin were well tolerated and maintained plasma melatonin levels 25-80 times higher than endogenous peak values.

A test material for tissue characterisation and system calibration in MRI.

A tissue-equivalent test material for MRI has been produced from a polysaccharide gel, agarose, containing gadolinium chloride chelated to EDTA. By varying the amounts of each constituent, the T1 and T2 of the material can be varied independently. As a result, the entire range of in vivo tissue relaxation times can be covered. Through the mathematical modelling of the 1H relaxation theories for both the gel and chelated paramagnetic ion, it has been possible to create a material with relaxation properties and behaviour predictable as functions of both the Larmor frequency and temperature. The similarity of the material to in vivo tissues, in terms of its biological and physical NMR characteristics, makes it an excellent tissue-equivalent substance, in addition to being an accurate calibration standard for routine MRI.

Temporal parameters and patterns of the foot roll over during walking: normative data for healthy adults.

Temporal parameters of the gait cycle and foot roll over in 105 healthy adults (75 women and 30 men aged 16 to 63 years) were collected using foot switches. The subjects walked unobserved at their preferred pace and velocity in a hallway 19 m long and 2.8 m wide. After correction for height, a significant gender influence remained on stance parameters and stride duration. For these adults, age had an effect on the forward tilt of the foot and the double support time only. Differences due to side related only to foot patterning and not stride, stance and swing times. Asymmetry coefficient for temporal parameters of gait cycle and foot roll over revealed the greatest asymmetry in metatarsal head and great toe latency and support. These reference data are considered valid in a laboratory using sensors and signal processing comparable to ours.

An education programme for people with cancer.

Evidence suggests that cancer patients want support, information and to be involved in treatment decisions. A course designed in the USA aims to help cancer patients learn more about the disease and become an informed part of the therapeutic team. The introduction of a similar course at one UK centre suggested that it is an effective way of informing and supporting people.

A chemical burn from a garlic poultice applied to the face to treat toothache: a case report.

This case report is of a significant chemical burn to the face resulting from the use of an external garlic poultice for toothache. The patient used internet search engines to seek a toothache remedy and did not identify any reports of this complication. This report aims to inform all dentists of the risks of raw garlic application to the skin and also to ensure that in the future any patient using the internet for a toothache remedy will be made aware of the potential risk and how to avoid it.

Cardiac disease in children and young adults with various lysosomal storage diseases: Comparison of echocardiographic and ECG changes among clinical groups.

BACKGROUND: Lysosomal storage disease (LSD) is a rare inherited disease group. Consecutively there are few data on cardiac changes in mucopolysaccharidosis (MPS), Anderson Fabry disease (AFD), and other LSD (oLSD) including Pompe disease (PD) and Danon disease (DD), I-cell disease ICD and mucolipidosis III (ML III). METHODS: Between 1994 and 2011, we identified 39 patients with LSD: 25 with MPS, 8 with AFD, and 6 with oLSD including PD (1), ML III (2), DD (1), and ICD (2) at our institution fulfilling the inclusion criteria of at least one echocardiogram and ECG. RESULTS: Median age was 11.4 years (range: 2-27), 22 were females (56%). Normal echocardiograms were present in 12 patients (31%): 4 with MPS (16%), 7 AFD (88%), and 1 oLSD (17%). Valvular heart disease was present in 23 patients (59%) occurring more often in MPS (76%) and oLSD (67%) than in AFD (0%) (p < 0.001). The most common ECG abnormality was a short PR interval in 10 of 35 patients (29%) occurring in all LSD groups. Median follow-up was 5.8 (0.2-22.2) years showing diminished 5-year survival compared to an age-matched group. However, no patient died due to a cardiac cause and no cardiovascular intervention was necessary. CONCLUSION: Echocardiographically detectable cardiovascular involvement in children with LSD is mostly confined to MPS and oLSD. Valve thickening in echo and a short PR interval in the ECG are the most frequent abnormalities. Routine repeat assessment is recommended in LSD. However, significant cardiac disease necessitating cardiac intervention is rare during a short follow-up.