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1.
bioRxiv ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38979132

ABSTRACT

Nicotinamide adenine dinucleotide (NAD) is essential for many enzymatic reactions, including those involved in energy metabolism, DNA repair and the activity of sirtuins, a family of defensive deacylases. During aging, levels of NAD + can decrease by up to 50% in some tissues, the repletion of which provides a range of health benefits in both mice and humans. Whether or not the NAD + precursor nicotinamide mononucleotide (NMN) extends lifespan in mammals is not known. Here we investigate the effect of long-term administration of NMN on the health, cancer burden, frailty and lifespan of male and female mice. Without increasing tumor counts or severity in any tissue, NMN treatment of males and females increased activity, maintained more youthful gene expression patterns, and reduced overall frailty. Reduced frailty with NMN treatment was associated with increases in levels of Anerotruncus colihominis, a gut bacterium associated with lower inflammation in mice and increased longevity in humans. NMN slowed the accumulation of adipose tissue later in life and improved metabolic health in male but not female mice, while in females but not males, NMN increased median lifespan by 8.5%, possible due to sex-specific effects of NMN on NAD + metabolism. Together, these data show that chronic NMN treatment delays frailty, alters the microbiome, improves male metabolic health, and increases female mouse lifespan, without increasing cancer burden. These results highlight the potential of NAD + boosters for treating age-related conditions and the importance of using both sexes for interventional lifespan studies.

2.
Laryngoscope ; 134(7): 3377-3383, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38214415

ABSTRACT

BACKGROUND: Pediatric tracheostomy decannulation protocols vary among institutions and may include toleration of Passy Muir Valve (PMV), microlaryngoscopy and bronchoscopy (MLB) findings, and polysomnography evaluation. Transtracheal pressure (TTP) is an objective measurement utilized to evaluate PMV toleration. We aimed to investigate the role of TTP in decannulation candidates and compare TTP measurements with polysomnography and MLB findings. METHODS: A retrospective cohort study of children who underwent TTP measurement during PMV trial between December 2012 and November 2022. RESULTS: A total of 79 patients underwent TTP measurement and MLB evaluation; of these, 16 (20.3%) patients had a capped polysomnography. Twenty-eight (35.4%) patients had TTPs ≤10 cm H2O, and 51 (64.6%) patients had TTPs >10 cm H2O. The most common indication for tracheostomy was upper airway obstruction (n = 41, 51.9%), followed by a need for mechanical ventilation (n = 24, 30.4%). Twenty-five (31.6%) patients were decannulated. Patients with TTPs ≤10 cm H2O had a mean Apnea-Hypopnea Index of 0.17 ± 0.26/h compared with 6.93 ± 7.67/h in those with TTPs >10 cm H2O, p = 0.0365. Patients with TTPs >10 cm H2O were found to have a significantly higher occurrence of airway obstruction (96.1% vs. 46.4%, p < 0.0001) and multilevel airway obstruction (70.6% vs. 21.4%, p < 0.0001) on MLB. Neither TTP measured at time of PMV assessment nor capped polysomnography was associated with successful decannulation. CONCLUSIONS: TTP measurements at time of PMV evaluation are associated with polysomnography and MLB findings. One-time PMV measurements were not indicative of decannulation success. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3377-3383, 2024.


Subject(s)
Device Removal , Polysomnography , Pressure , Tracheostomy , Humans , Retrospective Studies , Male , Female , Child, Preschool , Child , Infant , Bronchoscopy/methods , Laryngoscopy/methods , Airway Obstruction/diagnosis , Airway Obstruction/therapy , Airway Obstruction/physiopathology , Respiration, Artificial/methods
3.
Am J Speech Lang Pathol ; 32(6): 2792-2801, 2023 11 06.
Article in English | MEDLINE | ID: mdl-37682537

ABSTRACT

PURPOSE: Infants with perceived feeding problems are frequently referred for assessment of their feeding abilities. However, little is known regarding how healthy nondysphagic infants perform on commonly used assessments, making determination of impairment difficult. The aim of this investigation was to elucidate the characteristics of healthy term infant feeding performance using three commonly employed clinical assessments: Neonatal Eating Assessment Tool-Mixed (NeoEat-Mixed), Oral Feeding Scale, and Early Feeding Skills (EFS). METHOD: In this prospective case-control study, we recruited 30 infants without feeding impairments to undergo video-monitored bottle feeds under their normal feeding conditions. Caregiver perception of infant feeding was evaluated using the NeoEat-Mixed. Milk ingestion was monitored real time using the Oral Feeding Scale for rate of milk transfer and modified proficiency as characterized by the total volume consumed out of the total volume the caregiver provided. Videos were analyzed by two speech pathologists using the EFS assessment. Descriptive statistics were used to characterize performance. RESULTS: Participants underwent feeding monitoring at an average chronological age of 4 ± 2 months. Caregivers primarily reported normal, nonconcerning feeding patterns across all of the NeoEAT-Mixed outcomes. Infants consumed milk at an average rate of transfer of 7 ± 3 ml/min, a modified proficiency of 50 ± 21%, and achieved the highest OFS score of 4 (93%, n = 28). The majority of infants scored the best EFS score (mature-3) as it related to the absence of color changes during the feed (97%, n = 29), although commonly scored in the worst EFS score (immature-1) in their presentation of one or more compelling stress cues (63%, n = 19). CONCLUSION: Establishing healthy term infant normative values for commonly used feeding assessments is critical in accurately distinguishing infants with feeding impairments from those with normal developmental variants.


Subject(s)
Bottle Feeding , Feeding Behavior , Infant, Newborn , Infant , Humans , Case-Control Studies
4.
Heart Rhythm O2 ; 4(4): 225-231, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37124556

ABSTRACT

Background: Pacing-induced cardiomyopathy (PICM) is an important cause of heart failure in patients with a right ventricular pacing burden. Recent evidence suggests that an upgrade to cardiac resynchronization therapy (CRT) may confer benefit in PICM. Objective: To assess the extent and identify predictors of improvement following upgrade to CRT in patients with PICM. Methods: We retrospectively analyzed 43 patients undergoing CRT upgrade for PICM over the 10-year period of 2011 to 2021 at our center. All patients with PICM who underwent device upgrade from a dual- or single-chamber ventricular pacemaker to CRT were included. PICM was defined as a decrease of ≥10% in left ventricular ejection fraction (LVEF), resulting in an LVEF <50% among patients with ≥20% Right ventricular pacing burden without an alternative cause for cardiomyopathy. Results: LVEF significantly improved from 28.7% preupgrade to 44.3% post-CRT upgrade (P < .01). Of 37 patients with severe LV dysfunction, 34 (91.9%) improved to an LVEF >35% and 13 (35.1%) improved to an LVEF >50%. The LV end-diastolic diameter decreased from 5.9 cm preupgrade to 5.4 cm postupgrade (P < .01). Using linear regression, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use was associated with significant LVEF improvement (+7.21%, P = .05). We observed a low rate of complications, and 1 in 4 CRT upgrades required venoplasty (n = 10 of 43, 23.3%). Conclusion: We provide further evidence for the benefit of CRT upgrade in the management of patients with PICM.

5.
J Interv Card Electrophysiol ; 66(6): 1455-1464, 2023 Sep.
Article in English | MEDLINE | ID: mdl-36525168

ABSTRACT

BACKGROUND: Adverse structural and electrical remodeling underlie persistent atrial fibrillation (PersAF). Restoration of sinus rhythm (SR) prior to ablation in PersAF may improve the underlying substrate, thus improving arrhythmia outcomes. The aim of this study was to evaluate if the presence of SR at time of ablation is associated with improved long-term arrhythmia outcomes of a limited catheter ablation (CA) strategy in PersAF. METHODS: Patients with PersAF undergoing pulmonary vein isolation at our institution from 2014-2018 were included. We compared patients who presented for ablation in SR (by cardioversion and/or antiarrhythmic drugs [AADs]) to those who presented in AF. Primary outcome of interest was freedom from atrial arrhythmias (AAs) on or off AADs at 1 year after single ablation. Secondary outcomes included freedom from AAs on or off AADs overall, freedom from AAs off AADs at 1 year, and time to recurrent AF. RESULTS: Five hundred seventeen patients were included (322 presented in AF, 195 SR). The primary outcome was higher in those who presented for CA in SR as compared to AF (85.6% vs. 77.0%, p = 0.017). Freedom from AAs off AAD at 12 months was also higher in those presenting in SR (59.0% vs. 44.4%; p = 0.001) and time to recurrent AF was longer (p = 0.008). Presence of SR at CA was independently associated with the primary outcome at 12 months (OR 1.77; 95% CI 1.08-2.90) and overall (OR 1.89; 95% CI 1.26-2.82). CONCLUSIONS: Presence of SR at time of ablation is associated with improved long-term arrhythmia outcomes of limited CA in PersAF.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Humans , Pulmonary Veins/surgery , Treatment Outcome , Anti-Arrhythmia Agents/therapeutic use , Time Factors , Catheter Ablation/adverse effects , Recurrence
6.
Heart Rhythm ; 19(10): 1620-1628, 2022 10.
Article in English | MEDLINE | ID: mdl-35276321

ABSTRACT

BACKGROUND: The right ventricle (RV) is uncommonly implicated in postinfarction ventricular tachycardia (VT). The prevalence and features of the RV substrate participating in postinfarction VT are undefined. OBJECTIVES: The purpose of this study was to characterize critical right ventricular substrate (CRVS) involvement in patients with postinfarction VT. METHODS: We retrospectively reviewed 1279 patients with postinfarction VT undergoing catheter ablation at our center from January 2000 through May 2020. Cases with CRVS defined by conclusive demonstration of participation in VT with activation, entrainment, and/or pacemapping during sinus rhythm were identified. RESULTS: CRVS was identified in 27 of 1279 patients (2.1%): age 65 ± 13 years, 96% male, median left ventricular (LV) ejection fraction 25%, and 93% with left bundle branch block (LBBB) morphology VT. CRVS was identified by RV activation and/or entrainment mapping (n = 19) or by the presence of low-voltage abnormal electrograms with excellent pacemap for the targeted VT and noninducibility after ablation (n = 8). VT termination during RV ablation occurred in 15 patients. After median follow-up of 20 months (interquartile range 9-53 months) and median of 2 procedures (interquartile range 1-3), 22 of 27 patients (80%) had no VT recurrence and 11 (41%) died. CONCLUSION: The RV contains critical substrate elements of postinfarction VT in at least 2.1% of cases. RV mapping should be considered in cases in which LV mapping fails to demonstrate adequate targets, particularly in patients with LBBB morphology VT.


Subject(s)
Catheter Ablation , Tachycardia, Ventricular , Aged , Bundle-Branch Block , Female , Heart Ventricles , Humans , Male , Middle Aged , Retrospective Studies , Tachycardia, Ventricular/epidemiology , Tachycardia, Ventricular/etiology , Tachycardia, Ventricular/surgery , Treatment Outcome
7.
Psychopharmacology (Berl) ; 239(7): 2317-2329, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35348804

ABSTRACT

RATIONALE: A significant obstacle to an improved understanding of pathological dissociative and psychosis-like states is the lack of readily implemented pharmacological models of these experiences. Ketamine has dissociative and psychotomimetic effects but can be difficult to use outside of medical and clinical-research facilities. Alternatively, nitrous oxide (N2O) - like ketamine, a dissociative anaesthetic and NMDAR antagonist - has numerous properties that make it an attractive alternative for modelling dissociation and psychosis. However, development and testing of such pharmacological models relies on well-characterized measurement instruments. OBJECTIVES: To examine the factor structures of the Clinician Administered Dissociative States Scale (CADSS) and Psychotomimetic States Inventory (PSI) administered during N2O inhalation in healthy volunteers. METHODS: Secondary analyses of data pooled from three previous N2O studies with healthy volunteers. RESULTS: Effect sizes for N2O-induced dissociation and psychotomimesis were comparable to effects reported in experimental studies with sub-anaesthetic ketamine in healthy volunteers. Although, like ketamine, a three-factor representation of N2O-induced dissociation was confirmed, and a more parsimonious two-factor model might be more appropriate. Bayesian exploratory factor analysis suggested that N2O-induced psychosis-like symptoms were adequately represented by two negative and two positive symptom factors. Hierarchical cluster analysis indicated minimal item overlap between the CADSS and PSI. CONCLUSION: N2O and ketamine produce psychometrically similar dissociative states, although parallels in their psychosis-like effects remain to be determined. The CADSS and PSI tap largely non-overlapping experiences under N2O and we propose the use of both measures (or similar instruments) to comprehensively assess anomalous subjective states produced by dissociative NMDAR antagonists.


Subject(s)
Ketamine , Psychotic Disorders , Anesthetics, Dissociative , Bayes Theorem , Dissociative Disorders/chemically induced , Dissociative Disorders/diagnosis , Humans , Nitrous Oxide/adverse effects , Receptors, N-Methyl-D-Aspartate
8.
Heart Rhythm ; 19(2): 187-194, 2022 02.
Article in English | MEDLINE | ID: mdl-34601127

ABSTRACT

BACKGROUND: Ventricular tachycardia (VT) substrate in left ventricular (LV) nonischemic cardiomyopathy (NICM) consists of fibrosis with surviving myocardium. OBJECTIVE: The purpose of this study was to determine whether, in patients with LV NICM and sustained VT, reduced QRS amplitude and QRSf during sinus rhythm can identify the presence and location of abnormal septal (S-NICM) and/or free-wall (FW-NICM) VT substrate. METHODS: We compared patients with NICM and VT (group 1) with electroanatomic mapping septal (S-NICM; n = 21) or free-wall (FW-NICM; n = 20) VT substrate to a 38-patient reference cohort (group 2) with cardiac magnetic resonance imaging (cMRI) and NICM but no VT referred for primary prevention implantable cardioverter-defibrillator (26 [68.4%] with late gadolinium enhancement). RESULTS: Group 1 had lower QRS amplitude in leads II (0.60 ± 0.22 vs 0.86 ± 0.35, P <.001), aVR (0.60 ± 0.24 vs 0.75 ± 0.31, P = .002), aVF (0.48 ± 0.20 vs 0.70 ± 0.28, P <.001), and V2 (1.09 ± 0.52 vs 1.38 ± 0.55, P = .001) than group 2. QRS <0.55 mV in lead aVF identified VT and accompanying substrate with sensitivity 70% and specificity 71%. Most group 1 and group 2 patients had 12-lead ECG QRS fractionation (QRSf) in ≥2 contiguous leads (78% vs 63.2%, P = .14). Sensitivity and specificity for ≥2 QRSf leads identifying respective regional electroanatomic or cMRI abnormalities were 76% and 50% for inferior, 44% and 87% for lateral, and 21% and 89% for anterior leads. CONCLUSION: In LV NICM, low frontal plane QRS (<0.55 mV in aVF) is associated with VT substrate. Although multilead QRS fractionation is associated with the presence and location of VT substrate, it is frequently identified in patients without VT with cMRI abnormalities.


Subject(s)
Cardiomyopathies/diagnostic imaging , Cardiomyopathies/physiopathology , Magnetic Resonance Imaging, Cine , Tachycardia, Ventricular/diagnostic imaging , Tachycardia, Ventricular/physiopathology , Contrast Media , Electrocardiography , Epicardial Mapping , Female , Fibrosis , Humans , Male , Middle Aged , Prospective Studies
9.
Circ Arrhythm Electrophysiol ; 14(12): e010279, 2021 12.
Article in English | MEDLINE | ID: mdl-34847692

ABSTRACT

BACKGROUND: The substrate for ventricular tachycardia (VT) in left ventricular (LV) nonischemic cardiomyopathy may be epicardial. We assessed the prevalence, location, endocardial electrograms, and VT ablation outcomes in LV nonischemic cardiomyopathy with isolated epicardial substrate. METHODS: Forty-seven of 531 (9%) patients with LV nonischemic cardiomyopathy and VT demonstrated normal endocardial (>1.5 mV)/abnormal epicardial bipolar low-voltage area (LVA, <1.0 mV and signal abnormality). Abnormal endocardial unipolar LVA (≤8.3 mV) and endocardial bipolar split electrograms and predictors of ablation success were assessed. RESULTS: Epicardial bipolar LVA (27.3 cm2 [interquartile range, 15.8-50.0]) localized to basal (40), mid (8), and apical (3) LV with basal inferolateral LV most common (28/47, 60%). Of 44 endocardial maps available, 40 (91%) had endocardial unipolar LVA (24.5 cm2 [interquartile range, 9.4-68.5]) and 29 (67%) had characteristic normal amplitude endocardial split electrograms opposite the epicardial LVA. At mean of 34 months, the VT-free survival was 55% after one and 72% after multiple procedures. Greater endocardial unipolar LVA than epicardial bipolar LVA (hazard ratio, 10.66 [CI, 2.63-43.12], P=0.001) and number of inducible VTs (hazard ratio, 1.96 [CI, 1.27-3.00], P=0.002) were associated with VT recurrence. CONCLUSIONS: In patients with LV nonischemic cardiomyopathy and VT, the substrate may be confined to epicardial and commonly basal inferolateral. LV endocardial unipolar LVA and normal amplitude bipolar split electrograms identify epicardial LVA. Ablation targeting epicardial VT and substrate achieves good long-term VT-free survival. Greater endocardial unipolar than epicardial bipolar LVA and more inducible VTs predict VT recurrence.


Subject(s)
Cardiomyopathies/physiopathology , Catheter Ablation , Pericardium/surgery , Tachycardia, Ventricular/surgery , Adult , Cardiomyopathies/diagnostic imaging , Cardiomyopathies/epidemiology , Catheter Ablation/adverse effects , Electrophysiologic Techniques, Cardiac , Female , Fibrosis , Humans , Magnetic Resonance Imaging, Cine , Male , Middle Aged , Myocardium/pathology , Pennsylvania/epidemiology , Pericardium/diagnostic imaging , Pericardium/physiopathology , Predictive Value of Tests , Prevalence , Progression-Free Survival , Recurrence , Retrospective Studies , Risk Assessment , Risk Factors , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/epidemiology , Tachycardia, Ventricular/physiopathology , Time Factors
10.
Pacing Clin Electrophysiol ; 44(11): 1949-1951, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34346519

ABSTRACT

Left ventricular assist devices (LVAD) produce electromagnetic interference (EMI) which can have implications when patients require cardiac implantable electronic devices. Leadless pacemakers have been successfully implanted in patients with Heartmate 2 and Heartmate 3 LVADs without evidence of EMI or device-to-device interaction. Here we report a case of a Heartmate 3 LVAD and Micra VR transcatheter pacing system interaction requiring device repositioning.


Subject(s)
Atrioventricular Block/therapy , Heart-Assist Devices/adverse effects , Pacemaker, Artificial/adverse effects , Aged , Device Removal , Fluoroscopy , Humans , Male , Prosthesis Design , Telemetry
12.
Dis Markers ; 2021: 5511267, 2021.
Article in English | MEDLINE | ID: mdl-34257744

ABSTRACT

BACKGROUND: The burden and persistence of atrial fibrillation (AF) have been associated with the presence and extent of left atrial (LA) fibrosis. Recent reports have implicated an association between the extent of LA fibrosis and the outcome of pulmonary vein isolation (PVI). We aimed to analyse the value of an automated scar quantification method in the prediction of success following PVI. METHODS: One hundred and nine consecutive patients undergoing PVI for paroxysmal or persistent AF were included in our observational study with a 2-year follow-up. Prior to PVI, patients underwent high-definition LA electroanatomical mapping, and scar burden was quantified by automated software (Voltage Histogram Analysis, CARTO 3, Biosense Webster), then classified into 4 subgroups (Dublin Classes I-IV). Recurrence rates were analysed on and off antiarrhythmic drug therapy (AAD), respectively. RESULTS: The overall success rate was 74% and 67% off AAD at 1- and 2-year follow-up, respectively. Patients with Dublin Class IV had significantly lower success rates (p = 0.008, off AAD). Dublin Class IV (OR = 2.27, p = 0.022, off AAD) and the presence of arrhythmia in the blanking period (OR = 3.28, p = 0.001, off AAD) were the only significant predictors of recurrence. The use of AAD did not affect these results. CONCLUSIONS: We propose a classification of low voltage areas based on automated quantification by software during 3D mapping prior to PVI. Patients with high burden of low voltage areas (>31% of <0.5 mV, Dublin Class IV) have a higher risk of recurrence following PVI. Information gathered during electroanatomical mapping may have important prognostic value.


Subject(s)
Atrial Fibrillation/surgery , Catheter Ablation , Clinical Decision Rules , Heart Atria/pathology , Adult , Aged , Aged, 80 and over , Atrial Fibrillation/diagnosis , Atrial Fibrillation/pathology , Computed Tomography Angiography , Echocardiography , Electrocardiography , Female , Fibrosis , Follow-Up Studies , Heart Atria/surgery , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Patient Acuity , Proportional Hazards Models , Recurrence , Retrospective Studies , Treatment Outcome
13.
Psychol Med ; 51(16): 2875-2885, 2021 12.
Article in English | MEDLINE | ID: mdl-32539883

ABSTRACT

BACKGROUND: Alcohol use disorders can be conceptualised as a learned pattern of maladaptive alcohol-consumption behaviours. The memories encoding these behaviours centrally contribute to long-term excessive alcohol consumption and are therefore an important therapeutic target. The transient period of memory instability sparked during memory reconsolidation offers a therapeutic window to directly rewrite these memories using targeted behavioural interventions. However, clinically-relevant demonstrations of the efficacy of this approach are few. We examined key retrieval parameters for destabilising naturalistic drinking memories and the ability of subsequent counterconditioning to effect long-term reductions in drinking. METHODS: Hazardous/harmful beer-drinking volunteers (N = 120) were factorially randomised to retrieve (RET) or not retrieve (No RET) alcohol reward memories with (PE) or without (No PE) alcohol reward prediction error. All participants subsequently underwent disgust-based counterconditioning of drinking cues. Acute responses to alcohol were assessed pre- and post-manipulation and drinking levels were assessed up to 9 months. RESULTS: Greater long-term reductions in drinking were found when counterconditioning was conducted following retrieval (with and without PE), despite a lack of short-term group differences in motivational responding to acute alcohol. Large variability in acute levels of learning during counterconditioning was noted. 'Responsiveness' to counterconditioning predicted subsequent responses to acute alcohol in RET + PE only, consistent with reconsolidation-update mechanisms. CONCLUSIONS: The longevity of behavioural interventions designed to reduce problematic drinking levels may be enhanced by leveraging reconsolidation-update mechanisms to rewrite maladaptive memory. However, inter-individual variability in levels of corrective learning is likely to determine the efficacy of reconsolidation-updating interventions and should be considered when designing and assessing interventions.


Subject(s)
Alcoholism , Humans , Alcoholism/therapy , Behavior Therapy , Cues , Motivation , Reward
14.
Psychol Med ; 51(1): 158-167, 2021 01.
Article in English | MEDLINE | ID: mdl-31736460

ABSTRACT

BACKGROUND: Maladaptive learning linking environmental food cues to high-palatability food reward plays a central role in overconsumption in obesity and binge eating disorders. The process of memory reconsolidation offers a mechanism to weaken such learning, potentially ameliorating over-eating behaviour. Here we investigated whether putatively interfering with synaptic plasticity using the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, could weaken retrieved chocolate reward memories through blockade of reconsolidation. METHODS: Seventy five healthy volunteers with a tendency to binge eat chocolate were randomised to retrieve chocolate reward memory under 10 mg rapamycin (RET + RAP, active condition), or placebo (RET + PBO), or they received 10 mg rapamycin without subsequent retrieval (NO RET + RAP). Indices of chocolate reward memory strength were assessed one week pre and post manipulation and at one month follow-up. RESULTS: Contrary to hypotheses, the RET + RAP group did not show any greater reduction than control groups on indices of motivational salience of chocolate cues, motivation to consume chocolate or liking of chocolate. Mild evidence of improvement in the RET + RAP group was found, but this was limited to reduced chocolate binge episodes and improved healthy food choices. CONCLUSIONS: We did not find convincing evidence of comprehensive naturalistic chocolate reward memory reconsolidation blockade by rapamycin. The effects on chocolate bingeing and food choices may warrant further investigation. These limited positive findings may be attributable to insufficient interference with mTOR signalling with 10 mg rapamycin, or failure to destabilise chocolate memories during retrieval.


Subject(s)
Bulimia/drug therapy , Bulimia/psychology , Memory Consolidation/drug effects , Sirolimus/pharmacology , Adult , Binge-Eating Disorder/drug therapy , Chocolate , Cues , Double-Blind Method , Female , Humans , Male , Motivation , Placebos , Reward , Surveys and Questionnaires , TOR Serine-Threonine Kinases/pharmacology , Young Adult
15.
Alzheimers Res Ther ; 12(1): 154, 2020 11 18.
Article in English | MEDLINE | ID: mdl-33208190

ABSTRACT

BACKGROUND: Obtaining reliable estimates of the health-related quality of life (HR-QoL) of people with predementia Alzheimer's disease [AD] (preclinical or prodromal AD), mild cognitive impairment (MCI) and dementia is essential for economic evaluations of related health interventions. AIMS: To provide an overview of which quality of life instruments are being used to assess HR-QoL in people with predementia AD, MCI or dementia; and, to summarise their reported HR-QoL levels at each stage of the disease and by type of respondent. METHODS: We systematically searched for and reviewed eligible studies published between January 1990 and the end of April 2017 which reported HR-QoL for people with predementia AD, MCI or dementia. We only included instruments which are preference-based, allowing index scores/utility values to be attached to each health state they describe based on preferences obtained from population surveys. Summary results were presented by respondent type (self or proxy), type of instrument, geographical location and, where possible, stage of disease. Health state utility values derived using the EuroQoL 5-Dimensions (EQ-5D) were meta-analysed by pooling reported results across all studies by disease severity (MCI, mild, mild to moderate, moderate, severe dementia, not specified) and by respondent (person with dementia, carer, general public, not specified), using a fixed-effects approach. RESULTS: We identified 61 studies which reported HR-QoL for people with MCI or dementia using preference-based instruments, of which 48 used the EQ-5D. Thirty-six studies reported HR-QoL for mild and/or moderate disease severities, and 12 studies reported utility values for MCI. We found systematic differences between self-rated and proxy-rated HR-QoL, with proxy-rated utility valued being significantly lower in more severe disease states. CONCLUSIONS: A substantial literature now exists quantifying the impact of dementia on HR-QoL using preference-based measures, giving researchers and modellers a firmer basis on which to select appropriate utility values when estimating the effectiveness and cost-effectiveness of interventions in this area. Further research is required on HR-QoL of people with preclinical and prodromal AD and MCI, possible differences by type of dementia, the effects of comorbidities, study setting and the informal caregiver's own HR-QoL, including any effect of that on their proxy-ratings.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Dementia , Caregivers , Humans , Quality of Life
16.
JACC Clin Electrophysiol ; 6(9): 1089-1102, 2020 09.
Article in English | MEDLINE | ID: mdl-32972543

ABSTRACT

OBJECTIVES: This study aimed to characterize the incidence, clinical characteristics, and electrocardiographic and electrophysiologic features of LVA VA in the absence of CAD and to describe the experience with catheter ablation (CA) in this group. BACKGROUND: The left ventricular apex (LVA) is a well-described source of ventricular arrhythmias (VAs) in patients with coronary artery disease (CAD) and history of apical infarction but is a rare source of VA in the absence of CAD. METHODS: Patients referred for CA of VA at our institution were retrospectively reviewed, and those with LVA VA in the absence of CAD were identified. RESULTS: Of 3,710 consecutive patients undergoing VA ablation, CA of LVA VA was performed in 24 patients (20 with monomorphic ventricular tachycardia, 4 with premature ventricular contractions or nonsustained ventricular tachycardia; 18 men; mean age: 54 ± 15 years). These cases comprised 10 of 35 (29%) hypertrophic cardiomyopathy, 9 of 789 (1.2%) nonischemic cardiomyopathy, and 5 of 1,432 (0.4%) idiopathic VA ablation procedures. VA QRS morphology was predominantly right bundle with slurred upstroke and right superior frontal plane axis with precordial transition ≤V3. Epicardial ablation was performed in 14 of 24 (58%). After a median of 1 procedure (range 1 to 4) at this institution and median follow-up of 47 months (range 0-176), VA recurred in 1 patient (4%). CONCLUSIONS: LVA VA in the absence of CAD is unusual and may occur in patients with hypertrophic cardiomyopathy or nonischemic cardiomyopathy or, rarely, in the absence of structural heart disease. It can be recognized by characteristic ECG features. CA of LVA VA is challenging; multiple procedures, including epicardial approaches, may be required to achieve VA control over long-term follow-up.


Subject(s)
Catheter Ablation , Coronary Artery Disease , Tachycardia, Ventricular , Ventricular Premature Complexes , Heart Ventricles/diagnostic imaging , Heart Ventricles/surgery , Humans , Male , Middle Aged , Retrospective Studies , Tachycardia, Ventricular/epidemiology , Tachycardia, Ventricular/surgery , Ventricular Premature Complexes/surgery
17.
Nat Commun ; 11(1): 3065, 2020 06 11.
Article in English | MEDLINE | ID: mdl-32528103

ABSTRACT

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

19.
Heart Rhythm ; 17(10): 1711-1718, 2020 10.
Article in English | MEDLINE | ID: mdl-32454219

ABSTRACT

BACKGROUND: Twelve-lead electrocardiogram (ECG) criteria have been developed to identify idiopathic ventricular arrhythmias (VAs) from the left ventricular (LV) papillary muscles (PAPs), but accurate localization remains a challenge. OBJECTIVE: The purpose of this study was to develop ECG criteria for accurate localization of LV PAP VAs using lead V1 exclusively. METHODS: Consecutive patients undergoing mapping and ablation of VAs from the LV PAPs guided by intracardiac echocardiography from 2007 to 2018 were reviewed (study group). The QRS morphology in lead V1 was compared to patients with VAs with a "right bundle branch block" morphology from other LV locations (reference group). Patients with structural heart disease were excluded. RESULTS: One hundred eleven patients with LV PAP VAs (mean age 54 ± 16 years; 65% men) were identified, including 64 (55%) from the posteromedial PAP and 47 (42%) from the anterolateral PAP. The reference group included patients with VAs from the following LV locations: fascicles (n = 21), outflow tract (n = 36), ostium (n = 37), inferobasal segment (n = 12), and apex (5). PAP VAs showed 3 distinct QRS morphologies in lead V1 93% of the time: Rr (53%), R with a slurred downslope (29%), and RR (11%). Sensitivity, specificity, positive predictive value, and negative predictive value for the 3 morphologies combined are 93%, 98%, 98%, and 93%, respectively. The intrinsicoid deflection of PAP VAs in lead V1 was shorter than that of the reference group (63 ± 13 ms vs 79 ± 24 ms; P < .001). An intrinsicoid deflection time of <74 ms best differentiated the 2 groups (sensitivity 79%; specificity 87%). CONCLUSION: VAs originating from the LV PAPs manifest unique QRS morphologies in lead V1, which can aid in rapid and accurate localization.


Subject(s)
Arrhythmias, Cardiac/physiopathology , Electrocardiography , Heart Ventricles/physiopathology , Papillary Muscles/physiopathology , Arrhythmias, Cardiac/surgery , Catheter Ablation/methods , Female , Follow-Up Studies , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies
20.
JACC Case Rep ; 2(3): 431-433, 2020 Mar.
Article in English | MEDLINE | ID: mdl-34317256

ABSTRACT

We report the case of a 54-year-old woman who presented for cardiological evaluation having noted a decline in her heart rate on her wearable heart rate monitor. She was found to be in 2:1 atrioventricular block. Subsequent evaluation revealed cardiac and pulmonary sarcoidosis, treated with steroids and implantable cardioverter-defibrillator placement. (Level of Difficulty: Beginner.).

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