International consensus statement on the design, delivery and evaluation of sport-based interventions aimed at promoting social, psychological and physical well-being in prison.

OBJECTIVE: To develop an international consensus statement to advise on designing, delivering and evaluating sport-based interventions (SBIs) aimed at promoting social, psychological and physical well-being in prison. DESIGN: Modified Delphi using two rounds of survey questionnaires and two consensus workshops. PARTICIPANTS: A multidisciplinary panel of more than 40 experts from 15 international jurisdictions was formed, including representation from the following groups and stakeholders: professionals working in the justice system; officials from sport federations and organisations; academics with research experience of prisons, secure forensic mental health settings and SBIs; and policy-makers in criminal justice and sport. RESULTS: A core research team and advisory board developed the initial rationale, statement and survey. This survey produced qualitative data which was analysed thematically. The findings were presented at an in-person workshop. Panellists discussed the findings, and, using a modified nominal group technique, reached a consensus on objectives to be included in a revised statement. The core research team and advisory board revised the statement and recirculated it with a second survey. Findings from the second survey were discussed at a second, virtual, workshop. The core research team and advisory board further revised the consensus statement and recirculated it asking panellists for further comments. This iterative process resulted in seven final statement items; all participants have confirmed that they agreed with the content, objectives and recommendations of the final statement. CONCLUSIONS: The statement can be used to assist those that design, deliver and evaluate SBIs by providing guidance on: (1) minimum levels of competence for those designing and delivering SBIs; (2) the design and delivery of inclusive programmes prioritising disadvantaged groups; and (3) evaluation measures which are carefully calibrated both to capture proposed programme outcomes and to advance an understanding of the systems, processes and experiences of sport engagement in prison.

Effect of esophageal cooling on ablation lesion formation in the left atrium: Insights from Ablation Index data in the IMPACT trial and clinical outcomes.

INTRODUCTION: The IMPACT study established the role of controlled esophageal cooling in preventing esophageal thermal injury during radiofrequency (RF) ablation for atrial fibrillation (AF). The effect of esophageal cooling on ablation lesion delivery and procedural and patient outcomes had not been previously studied. The objective was to determine the effect of esophageal cooling on the formation of RF lesions, the ability to achieve procedural endpoints, and clinical outcomes. METHODS: Participants in the IMPACT trial underwent AF ablation guided by Ablation Index (30 W at 350-400 AI posteriorly, 40 W at ≥450 AI anteriorly). A blinded 1:1 randomization assigned patients to the use of the ensoETM® device to keep esophageal temperature at 4°C during ablation or standard practice using a single-sensor temperature probe. Ablation parameters and clinical outcomes were analyzed. RESULTS: Procedural data from 188 patients were analyzed. Procedure and fluoroscopy times were similar, and all pulmonary veins were isolated. First-pass pulmonary vein isolation and reconnection at the end of the waiting period were similar in both randomized groups (51/64 vs. 51/68; p = 0.54 and 5/64 vs. 7/68; p = 0.76, respectively). Posterior wall isolation was also similar: 24/33 versus 27/38; p = 0.88. Ablation effect on tissue, measured in impedance drop, was no different between the two randomized groups: 8.6Ω (IQR: 6-11.8) versus 8.76Ω (IQR: 6-12.2; p = 0.25). Arrhythmia recurrence was similar after 12 months (21.1% vs. 24.1%; 95% CI: 0.38-1.84; HR: 0.83; p = 0.66). CONCLUSIONS: Esophageal cooling has been shown to be effective in reducing ablation-related thermal injury during RF ablation. This protection does not compromise standard procedural endpoints or clinical success at 12 months.

Anatomical variations in coronary venous drainage: Challenges and solutions in delivering cardiac resynchronization therapy.

AIMS: To investigate the abnormalities of the coronary venous system in candidates for cardiac resynchronization therapy (CRT) and describe methods for circumventing the resulting difficulties. METHODS: From four implanting institutes, data of all CRT implants between October 2008 and October 2020 were screened for abnormal cardiac venous anatomy, defined as an anatomical variation not conforming to the accepted 'normal' anatomy. Patient demographics, procedural detail, and subsequent left ventricle (LV) lead pacing indices were collected. RESULTS: From a total of 3548 CRT implants, 15 (0.42%) patients (80% male) of 72.2 ± 10.6 years in age with an LV ejection fraction of 34 ± 10.3% were identified to have had an abnormal cardiac venous anatomy over the study period. There were 13 cases of persistent left side superior vena cava (pLSVC), five of which had coronary sinus ostium atresia (CSOA) including two with an "unroofed" coronary sinus (CS); one patient had a unique anomalous origin of the CS and one patient had an isolated CSOA. In total 14 patients (60% repeat attempt) had successful percutaneous implant under general anesthesia (46.7%) via the cephalic vein (59.1%), using the femoral approach (53.3%) for levophase venography and/or pull-through, including one case of endocardial LV implant. Pacing follow-up over 37.64 ± 37.6 months demonstrated LV lead threshold between 0.62 and 2.9 volts (pulsewidth 0.4-1.5 ms) in all cases; five patients died within 2.92 ± 1.6 years of a successful implant. CONCLUSION: CRT devices can be implanted percutaneously even in the presence of substantial abnormalities of coronary venous anatomy. Alternative routes of venous access may be required.

Operational and organisational stressors in community correctional work: Insights from probation and parole officers in Ontario, Canada.

In the current article, we investigate the occupational stressors parole and probation officers working in provincial correctional services in Ontario, Canada experience. We examine four specific stressors that emerged thematically from participants' open-ended survey responses, and conceptualize these as operational factors (i.e., the duties of the job) or organisational factors (i.e., structural aspects of the organisation in which parole or probation officers work). Participants identified the operational stressor of exposure to potentially psychologically traumatic events and secondary trauma, as well as three predominant organisational stressors: paperwork and administrative tasks, insufficient human resources, and workplace relationships and tensions. Drawing from literatures on parole and probation, workplace stress, and organisational cultures and behaviours, we analyse how these stressors have detrimental impacts on the mental health and well-being of community correctional workers, which in turn compromises their ability to effectively supervise and support individuals on their caseload. Policy and well-being implications are discussed.

Measurement of snoring and stertor using the Sonomat to assess effectiveness of upper airway surgery in children.

STUDY OBJECTIVES: The success of surgical treatment for pediatric sleep-disordered breathing is typically assessed using the mixed and obstructive apnea-hypopnea index (MOAHI). Although an important metric, previous work has shown that snoring and stertor are also associated with sleep disruption. Our aim was to assess the efficacy of surgery using the Sonomat (Sonomedical Pty Ltd), a noncontact sleep assessment system, that accurately records complete and partial upper airway obstruction. METHODS: Forty children (< 18 years) had a Sonomat study, in their own beds, before and after surgery. As an MOAHI ≥ 1 event/h is considered abnormal, the same threshold was applied to snore/stertor runs. Median (interquartile range) values are reported. RESULTS: Respiratory event-induced movements decreased from 12.0 (8.7-19.0) to 0.5 (0.1-3.2) events/h (P < .01), with no significant change in spontaneous movements: 12.8 (9.8-17.9) to 16.5 (13.7-26.1) events/h (P = .07). The MOAHI decreased from 4.5 (1.9-8.6) to 0.0 (0.0-0.4) events/h (P < .01). Snoring and/or stertor runs decreased from 32.8 (23.4-44.4) to 3.0 (0.2-14.6) events/h (P < .01). Thirty-four children had an MOAHI < 1 event/h following surgery; however, 20 had snore and/or stertor runs ≥ 1 event/h and 11 had snore and/or stertor runs ≥ 5 events/h. Only 14 (35%) children had a postsurgery MOAHI < 1 event/h combined with snoring and/or stertor < 1 runs/h. CONCLUSIONS: Although surgery is effective in improving breathing, success rates are overestimated using the MOAHI. Our results indicate that snoring and/or stertor are still present at levels that may disrupt sleep despite a normalization of the MOAHI and that when obstructed breathing was objectively measured, there was a large variation in its response to surgery. CITATION: Norman MB, Harrison HC, Sullivan CE, Milross MA. Measurement of snoring and stertor using the Sonomat to assess effectiveness of upper airway surgery in children. J Clin Sleep Med. 2022;18(6):1649-1656.

"It's Pure Chaos Every Day": COVID-19 and the work of Canadian federal institutional parole officers.

As the Canadian federal correctional system grappled with the onset of the COVID-19 pandemic, institutional parole officers, who play a central role in prisoners' case management team, remained essential service providers. Working in uncertain circumstances, these correctional workers navigated new and rapidly changing protocols and risks, while attempting to continue to provide support to those on their caseloads. Based on semi-structured interviews with 96 institutional parole officers, conducted after Canada's "first wave" of COVID-19 infections, we analyze three ways in which their work was impacted by the pandemic: shifting workloads, routines, and responsibilities; increased workloads due to decarceration (i.e., efforts to reduce the number of incarcerated individuals); and the navigation of new forms of risk and uncertainty. This study advances the understanding of stress and risk in probation and parole work and presents recommendations to ameliorate the occupational stresses experienced by correctional workers during and beyond COVID-19.

Percutaneous management of lead-related cardiac perforation with limited use of computed tomography and cardiac surgery.

BACKGROUND: Cardiac implantable electronic device (CIED)-related perforation is uncommon but potentially lethal. Management typically includes the use of computed tomography (CT) scanning and often involves cardiac surgery. METHODS: Patients presenting to a single referral centre with CIED-related cardiac perforation between 2013 and 2019 were identified. Demographics, diagnostic modalities, the method of lead revision, and 30-day complications were examined. RESULTS: A total of 46 cases were identified; median time from implantation to diagnosis was 14 days (interquartile range = 4-50). Most were females (29/46, 63%), 9/46 (20%) had cancer, 18 patients (39%) used oral anticoagulants, and no patients had prior cardiac surgery. Active fixation was involved in 98% of cases; 9% involved an implantable cardioverter defibrillator lead. Thirty-seven leads perforated the right ventricle (apex: 24) and 9 punctured the right atrium (lateral wall: 5). Abnormal electrical parameters were noted in 95% of interrogated cases. Perforation was visualized in 41% and 6% of cases with chest X-ray (CXR) and transthoracic echocardiography, respectively. CXR revealed a perforation, gross lead displacement, or left-sided pleural effusion in 74% of cases. Pericardial effusion occurred in 26 patients (57%) of whom 11 (24%) developed tamponade, successfully drained percutaneously. Pre-extraction CT scan was performed in 19 patients but was essential in four cases. Transvenous lead revision (TLR) was successfully performed in all cases with original leads repositioned in six patients, without recourse to surgery. Thirty-day mortality and complications were low (0% and 26%, respectively). CONCLUSION: CT scanning provides incremental diagnostic value in a minority of CIED-related perforations. TLR is a safe and effective strategy.

Contact force sensing in ablation of ventricular arrhythmias using a 56-hole open-irrigation catheter: a propensity-matched analysis.

PURPOSE: The effect of adding contact force (CF) sensing to 56-hole tip irrigation in ventricular arrhythmia (VA) ablation has not been previously studied. We aimed to compare outcomes with and without CF sensing in VA ablation using a 56-hole radiofrequency (RF) catheter. METHODS: A total of 164 patients who underwent first-time VA ablation using Thermocool SmartTouch Surround Flow (TC-STSF) catheter (Biosense-Webster, Diamond Bar, CA, USA) were propensity-matched in a 1:1 fashion to 164 patients who had first-time ablation using Thermocool Surround Flow (TC-SF) catheter. Patients were matched for age, gender, cardiac aetiology, ejection fraction and approach. Acute success, complications and long-term follow-up were compared. RESULTS: There was no difference between procedures utilising either TC-SF or TC-STSF in acute success (TC-SF: 134/164 (82%), TC-STSF: 141/164 (86%), p = 0.3), complications (TC-SF: 11/164 (6.7%), TC-STSF: 11/164 (6.7%), p = 1.0) or VA-free survival (TC-SF: mean arrhythmia-free survival time = 5.9 years, 95% CI = 5.4-6.4, TC-STSF: mean = 3.2 years, 95% CI = 3-3.5, log-rank p = 0.74). Fluoroscopy time was longer in normal hearts with TC-SF (19 min, IQR: 14-30) than TC-STSF (14 min, IQR: 8-25; p = 0.04). CONCLUSION: Both TC-SF and TC-STSF catheters are safe and effective in treating VAs. The use of CF sensing catheters did not improve safety or acute and long-term outcomes, but reduced fluoroscopy time in normal heart VA.

Randomized comparison of oesophageal protection with a temperature control device: results of the IMPACT study.

AIMS: Thermal injury to the oesophagus is an important cause of life-threatening complication after ablation for atrial fibrillation (AF). Thermal protection of the oesophageal lumen by infusing cold liquid reduces thermal injury to a limited extent. We tested the ability of a more powerful method of oesophageal temperature control to reduce the incidence of thermal injury. METHODS AND RESULTS: A single-centre, prospective, double-blinded randomized trial was used to investigate the ability of the ensoETM device to protect the oesophagus from thermal injury. This device was compared in a 1:1 randomization with a control group of standard practice utilizing a single-point temperature probe. In the protected group, the device maintained the luminal temperature at 4°C during radiofrequency (RF) ablation for AF under general anaesthesia. Endoscopic examination was performed at 7 days post-ablation and oesophageal injury was scored. The patient and the endoscopist were blinded to the randomization. We recruited 188 patients, of whom 120 underwent endoscopy. Thermal injury to the mucosa was significantly more common in the control group than in those receiving oesophageal protection (12/60 vs. 2/60; P = 0.008), with a trend toward reduction in gastroparesis (6/60 vs. 2/60, P = 0.27). There was no difference between groups in the duration of RF or in the force applied (P value range= 0.2-0.9). Procedure duration and fluoroscopy duration were similar (P = 0.97, P = 0.91, respectively). CONCLUSION: Thermal protection of the oesophagus significantly reduces ablation-related thermal injury compared with standard care. This method of oesophageal protection is safe and does not compromise the efficacy or efficiency of the ablation procedure.

Multi-catheter cryotherapy compared with radiofrequency ablation in long-standing persistent atrial fibrillation: a randomized clinical trial.

AIMS: Restoring sinus rhythm (SR) by ablation alone is an endpoint used in radiofrequency (RF) ablation for long-standing persistent atrial fibrillation (AF) but not with cryotherapy. The simultaneous use of two cryotherapy catheters can improve ablation efficiency; we compared this with RF ablation in chronic persistent AF aiming for termination to SR by ablation alone. METHODS AND RESULTS: Consecutive patients undergoing their first ablation for persistent AF of >6 months duration were screened. A total of 100 participants were randomized 1:1 to multi-catheter cryotherapy or RF. For cryotherapy, a 28-mm Arctic Front Advance was used in tandem with focal cryoablation catheters. Open-irrigated, non-force sensing catheters were used in the RF group with a 3D mapping system. Pulmonary vein (PV) isolation and non-PV triggers were targeted. Participants were followed up at 6 and 12 months, then yearly. Acute PVI was achieved in all cases. More patients in the multi-catheter cryotherapy group were restored to SR by ablation alone, with a shorter procedure duration. Sinus rhythm continued to the last available follow-up in 16/49 patients (33%) in the multi-catheter at 3.0 ± 1.6 years post-ablation and in 12/50 patients (24%) in the RF group at 4.0 ± 1.2 years post-ablation. The yearly rate of arrhythmia recurrence was similar. CONCLUSION: Multi-catheter cryotherapy can restore SR by ablation alone in more cases and more quickly than RF ablation. Long-term success is difficult to achieve by either methods and is similar with both.

Diverse activation patterns during persistent atrial fibrillation by noncontact charge-density mapping of human atrium.

BACKGROUND: Global simultaneous recording of atrial activation during atrial fibrillation (AF) can elucidate underlying mechanisms contributing to AF maintenance. A better understanding of these mechanisms may allow for an individualized ablation strategy to treat persistent AF. The study aims to characterize left atrial endocardial activation patterns during AF using noncontact charge-density mapping. METHODS: Twenty-five patients with persistent AF were studied. Activation patterns were characterized into three subtypes: (i) focal with centrifugal activation (FCA); (ii) localized rotational activation (LRA); and (iii) localized irregular activation (LIA). Continuous activation patterns were analyzed and distributed in 18 defined regions in the left atrium. RESULTS: A total of 144 AF segments with 1068 activation patterns were analyzed. The most common pattern during AF was LIA (63%) which consists of four disparate features of activation: slow conduction (45%), pivoting (30%), collision (16%), and acceleration (7%). LRA was the second-most common pattern (20%). FCA accounted for 17% of all activations, arising frequently from the pulmonary veins (PVs)/ostia. A majority of patients (24/25; 96%) showed continuous and highly dynamic patterns of activation comprising multiple combinations of FCA, LRA, and LIA, transitioning from one to the other without a discernible order. Preferential conduction areas were typically seen in the mid-anterior (48%) and lower-posterior (40%) walls. CONCLUSION: Atrial fibrillation is characterized by heterogeneous activation patterns identified in PV-ostia and non-PV regions throughout the LA at varying locations between individuals. Clinical implications of individualized ablation strategies guided by charge-density mapping need to be determined.

An Optimization of Liquid-Liquid Extraction of Urinary Volatile and Semi-Volatile Compounds and Its Application for Gas Chromatography-Mass Spectrometry and Proton Nuclear Magnetic Resonance Spectroscopy.

Urinary volatile compounds (VCs) have been recently assessed for disease diagnoses. They belong to very diverse chemical classes, and they are characterized by different volatilities, polarities and concentrations, complicating their analysis via a single analytical procedure. There remains a need for better, lower-cost methods for VC biomarker discovery. Thus, there is a strong need for alternative methods, enabling the detection of a broader range of VCs. Therefore, the main aim of this study was to optimize a simple and reliable liquid-liquid extraction (LLE) procedure for the analysis of VCs in urine using gas chromatography-mass spectrometry (GC-MS), in order to obtain the maximum number of responses. Extraction parameters such as pH, type of solvent and ionic strength were optimized. Moreover, the same extracts were analyzed using Proton Nuclear Magnetic Resonance Spectroscopy (1H-NMR), to evaluate the applicability of a single urine extraction for multiplatform purposes. After the evaluation of experimental conditions, an LLE protocol using 2 mL of urine in the presence of 2 mL of 1 M sulfuric acid and sodium sulphate extracted with dichloromethane was found to be optimal. The optimized method was validated with the external standards and was found to be precise and linear, and allowed for detection of >400 peaks in a single run present in at least 50% of six samples-considerably more than the number of peaks detected by solid-phase microextracton fiber pre-concentration-GC-MS (328 ± 6 vs. 234 ± 4). 1H-NMR spectroscopy of the polar and non-polar extracts extended the range to >40 more (mainly low volatility compounds) metabolites (non-destructively), the majority of which were different from GC-MS. The more peaks detectable, the greater the opportunity of assessing a fingerprint of several compounds to aid biomarker discovery. In summary, we have successfully demonstrated the potential of LLE as a cheap and simple alternative for the analysis of VCs in urine, and for the first time the applicability of a single urine solvent extraction procedure for detecting a wide range of analytes using both GC-MS and 1H-NMR analysis to enhance putative biomarker detection. The proposed method will simplify the transport between laboratories and storage of samples, as compared to intact urine samples.

TcCO2 changes correlate with partial obstruction in children suspected of sleep disordered breathing.

INTRODUCTION: Pediatric sleep disordered breathing (SDB) is characterized by long periods of partial upper airway obstruction (UAO) with low apnea-hypopnea indices (AHI). By measuring snoring and stertor, Sonomat studies allow quantification of these periods of partial UAO. AIM: To determine whether transcutaneous CO2 (TcCO2 ) levels correlate with increasing levels of partial UAO and to examine patterns of ΔTcCo2 in the transitions from (a) wakefulness to sleep and (b) non-rapid eye movement (NREM) to rapid eye movement (REM) sleep. METHODS: This was a retrospective review of sleep studies in seven asymptomatic controls aged 7 to 12 years and 62 symptomatic children with suspected SDB and no comorbidities, aged 2 to 13 years. Both groups underwent overnight polysomnography, including continuous TcCO2 , at one of two pediatric hospitals in Sydney. Changes in carbon dioxide levels between wake to NREM (sleep onset) and NREM to REM sleep were evaluated using an all-night TcCO2 trace time-linked to a hypnogram. Paired Sonomat recordings were used to quantify periods of UAO in the symptomatic group. RESULTS: The ΔTcCO2 at sleep onset was greater in SDB children than controls and ΔTcCO2 with sleep onset correlated with the duration of partial obstruction (r = .60; P < .0001). Children with an increase in TcCO2 from NREM to REM had a higher number of snoring and stertor events compared to those in whom TcCO2 decreased from NREM to REM (91 vs 30 events/h; P = < .0001). CONCLUSIONS: In children without comorbidities, the measurement of TcCO2 during sleep correlates with indicators of partial obstruction.

Validation of Dipole Density Mapping During Atrial Fibrillation and Sinus Rhythm in Human Left Atrium.

OBJECTIVES: This study sought to validate the accuracy of noncontact electrograms against contact electrograms in the left atrium during sinus rhythm (SR) and atrial fibrillation (AF). BACKGROUND: Noncontact mapping offers the opportunity to assess global cardiac activation in the chamber of interest. A novel noncontact mapping system, which records intracardiac voltage to derive cellular charge sources (dipole density), allows real-time mapping of AF to guide ablation. METHODS: Noncontact and contact unipolar electrogram pairs were recorded simultaneously from multiple locations. Morphology correlation and timing difference of reconstructed electrograms obtained from a noncontact catheter were compared with those from contact electrograms obtained from a contact catheter at the same endocardial locations. RESULTS: A total of 796 electrogram pairs in SR and 969 electrogram pairs in AF were compared from 20 patients with persistent AF. The median morphology correlation and timing difference (ms) in SR was 0.85 (interquartile range [IQR]: 0.71 to 0.94) and 6.4 ms (IQR: 2.6 to 17.1 ms); in AF was 0.79 (IQR: 0.69 to 0.88) and 14.4 ms (IQR: 6.7 to 26.2 ms), respectively. The correlation was stronger and the timing difference was less when the radial distance (r) from the noncontact catheter center to the endocardium was ≤ 40 versus > 40 mm; 0.87 (IQR: 0.72 to 0.94) versus 0.73 (IQR: 0.56 to 0.88) and 5.7 ms (IQR: 2.6 to 15.4 ms) versus 15.1 ms (IQR: 4.1 to 27.7 ms); p < 0.01 when in SR; 0.81 (IQR: 0.69 to 0.89) versus 0.67 (IQR: 0.45 to 0.82) and 12.3 ms (IQR: 5.9 to 21.8 ms) versus 28.3 ms (IQR: 16.2 to 36.0 ms); p < 0.01 when in AF. CONCLUSIONS: This novel noncontact dipole density mapping system provides comparable reconstructed atrial electrogram measurements in SR or AF in human left atrium when the anatomical site of interest is ≤40 mm from the mapping catheter.

The Profile of Urinary Headspace Volatile Organic Compounds After 12-Week Intake of Oligofructose-Enriched Inulin by Children and Adolescents with Celiac Disease on a Gluten-Free Diet: Results of a Pilot, Randomized, Placebo-Controlled Clinical Trial.

The concentration of volatile organic compounds (VOCs) can inform about the metabolic condition of the body. In the small intestine of untreated persons with celiac disease (CD), chronic inflammation can occur, leading to nutritional deficiencies, and consequently to functional impairments of the whole body. Metabolomic studies showed differences in the profile of VOCs in biological fluids of patients with CD in comparison to healthy persons; however, there is scarce quantitative and nutritional intervention information. The aim of this study was to evaluate the effect of the supplementation of a gluten-free diet (GFD) with prebiotic oligofructose-enriched inulin (Synergy 1) on the concentration of VOCs in the urine of children and adolescents with CD. Twenty-three participants were randomized to the group receiving Synergy 1 (10 g per day) or placebo for 12 weeks. Urinary VOCs were analyzed using solid-phase microextraction and gas chromatography⁻mass spectrometry. Sixteen compounds were identified and quantified in urine samples. The supplementation of GFD with Synergy 1 resulted in an average concentration drop (36%) of benzaldehyde in urine samples. In summary, Synergy 1, applied as a supplement of GFD for 12 weeks had a moderate impact on the VOC concentrations in the urine of children with CD.

Snoring and stertor are associated with more sleep disturbance than apneas and hypopneas in pediatric SDB.

PURPOSE: Polysomnography is not recommended for children at home and does not adequately capture partial upper airway obstruction (snoring and stertor), the dominant pathology in pediatric sleep-disordered breathing. New methods are required for assessment. Aims were to assess sleep disruption linked to partial upper airway obstruction and to evaluate unattended Sonomat use in a large group of children at home. METHODS: Children with suspected obstructive sleep apnea (OSA) had a single home-based Sonomat recording (n = 231). Quantification of breath sound recordings allowed identification of snoring, stertor, and apneas/hypopneas. Movement signals were used to measure quiescent (sleep) time and sleep disruption. RESULTS: Successful recordings occurred in 213 (92%) and 113 (53%) had no OSA whereas only 11 (5%) had no partial obstruction. Snore/stertor occurred more frequently (15.3 [5.4, 30.1] events/h) and for a longer total duration (69.9 min [15.7, 140.9]) than obstructive/mixed apneas and hypopneas (0.8 [0.0, 4.7] events/h, 1.2 min [0.0, 8.5]); both p < 0.0001. Many non-OSA children had more partial obstruction than those with OSA. Most intervals between snore and stertor runs were < 60 s (79% and 61% respectively), indicating that they occur in clusters. Of 14,145 respiratory-induced movement arousals, 70% were preceded by runs of snore/stertor with the remainder associated with apneas/hypopneas. CONCLUSIONS: Runs of snoring and stertor occur much more frequently than obstructive apneas/hypopneas and are associated with a greater degree of sleep disruption. Children with and without OSA are frequently indistinguishable regarding the amount, frequency, and the degree of sleep disturbance caused by snoring and stertor.

Discovery of ( R)-8-(6-Methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4- b]pyrrol-2-yl)-3-(1-methylcyclopropyl)-2-((1-methylcyclopropyl)amino)quinazolin-4(3 H)-one, a Potent and Selective Pim-1/2 Kinase Inhibitor for Hematological Malignancies.

Pim kinases are a family of constitutively active serine/threonine kinases that are partially redundant and regulate multiple pathways important for cell growth and survival. In human disease, high expression of the three Pim isoforms has been implicated in the progression of hematopoietic and solid tumor cancers, which suggests that Pim kinase inhibitors could provide patients with therapeutic benefit. Herein, we describe the structure-guided optimization of a series of quinazolinone-pyrrolodihydropyrrolone analogs leading to the identification of potent pan-Pim inhibitor 28 with improved potency, solubility, and drug-like properties. Compound 28 demonstrated on-target Pim activity in an in vivo pharmacodynamic assay with significant inhibition of BAD phosphorylation in KMS-12-BM multiple myeloma tumors for 16 h postdose. In a 2-week mouse xenograft model, daily dosing of compound 28 resulted in 33% tumor regression at 100 mg/kg.

Remanufactured circular mapping catheters: safety, effectiveness and cost.

BACKGROUND: The use of remanufactured single-use devices (SUDs), including cardiac electrophysiology catheters, has become established in the USA and other health care systems but without much published scientific evaluation on the relative safety or efficacy of these devices. In the United Kingdom (UK), the use of remanufactured SUDs has not been routine. We performed a structured evaluation of the safety and efficacy of a remanufactured circular mapping catheter (Stryker® remanufactured Lasso NAV 2515) during its introduction in our centre. METHODS: We prospectively evaluated the performance of a remanufactured circular mapping catheter in 100 consecutive patients undergoing an AF ablation. Operator feedback was obtained, assessing the device appearance, ease of use and function. As an indirect measurement of efficacy, acute procedure metrics were compared to those in 100 propensity-matched cases performed by the same operators using a new device. Cost savings were calculated. RESULTS: No complication occurred in association with the remanufactured device. There was one reported failure of device malfunction-the flexion-extension mechanism of a remanufactured catheter and none in the matched-control group. There was satisfactory communication with the electro-anatomic mapping system. Ease of use of the remanufactured catheter was reported to be similar to a newly manufactured device. Procedural duration was similar with remanufactured devices and matched controls. With 100 cases using the remanufactured device, cost savings amounted to £30,444. CONCLUSIONS: The use of remanufactured circular mapping catheters is safe, efficient and reliable. Widespread use of remanufactured SUDs offers the possibility of significant economic benefit.

A novel learning algorithm to predict individual survival after liver transplantation for primary sclerosing cholangitis.

Deciding who should receive a liver transplant (LT) depends on both urgency and utility. Most survival scores are validated through discriminative tests, which compare predicted outcomes between patients. Assessing post-transplant survival utility is not discriminate, but should be "calibrated" to be effective. There are currently no such calibrated models. We developed and validated a novel calibrated model to predict individual survival after LT for Primary Sclerosing Cholangitis (PSC). We applied a software tool, PSSP, to adult patients in the Scientific Registry of Transplant Recipients (n = 2769) who received a LT for PSC between 2002 and 2013; this produced a model for predicting individual survival distributions for novel patients. We also developed an appropriate evaluation measure, D-calibration, to validate this model. The learned PSSP model showed an excellent D-calibration (p = 1.0), and passed the single-time calibration test (Hosmer-Lemeshow p-value of over 0.05) at 0.25, 1, 5 and 10 years. In contrast, the model based on traditional Cox regression showed worse calibration on long-term survival and failed at 10 years (Hosmer-Lemeshow p value = 0.027). The calculator and visualizer are available at: http://pssp.srv.ualberta.ca/calculator/liver_transplant_2002. In conclusion we present a new tool that accurately estimates individual post liver transplantation survival.