Atrial Fibrillation Burden and Atrial Shunt Therapy in Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Atrial fibrillation (AF) is a common comorbidity in patients with heart failure with preserved ejection fraction (HFpEF) and in heart failure with mildly reduced ejection fraction (HFmrEF). OBJECTIVES: This study sought to describe AF burden and its clinical impact among individuals with HFpEF and HFmrEF who participated in a randomized clinical trial of atrial shunt therapy (REDUCE LAP-HF II [A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure]) and to evaluate the effect of atrial shunt therapy on AF burden. METHODS: Study investigators characterized AF burden among patients in the REDUCE LAP-HF II trial by using ambulatory cardiac patch monitoring at baseline (median patch wear time, 6 days) and over a 12-month follow-up (median patch wear time, 125 days). The investigators determined the association of baseline AF burden with long-term clinical events and examined the effect of atrial shunt therapy on AF burden over time. RESULTS: Among 367 patients with cardiac monitoring data at baseline and follow-up, 194 (53%) had a history of AF or atrial flutter (AFL), and median baseline AF burden was 0.012% (IQR: 0%-1.3%). After multivariable adjustment, baseline AF burden ≥0.012% was significantly associated with heart failure (HF) events (HR: 2.00; 95% CI: 1.17-3.44; P = 0.01) both with and without a history of AF or AFL (P for interaction = 0.68). Adjustment for left atrial reservoir strain attenuated the baseline AF burden-HF event association (HR: 1.71; 95% CI: 0.93-3.14; P = 0.08). Of the 367 patients, 141 (38%) had patch-detected AF during follow-up without a history of AF or AFL. Atrial shunt therapy did not change AF incidence or burden during follow-up. CONCLUSIONS: In HFpEF and HFmrEF, nearly 40% of patients have subclinical AF by 1 year. Baseline AF burden, even at low levels, is associated with HF events. Atrial shunt therapy does not affect AF incidence or burden. (A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure [REDUCE LAP-HF II]; NCT03088033).

Hours and costs of formal and informal care following Traumatic Brain Injury and Spinal Cord Injury sustained through Motor Vehicle Accidents: A Cross-sectional Study.

OBJECTIVES: To explore the weekly utilization of formal and informal care, and to calculate and compare the costs associated with these types of care after traumatic brain injury or spinal cord injury sustained through a motor vehicle accident in Australia. DESIGN: Cross-sectional, quantitative design. SUBJECTS: A total of 81 people with traumatic brain injury and 30 people with spinal cord injury from 3 rehabilitation units in New South Wales, Australia. METHODS: Data were collected using questionnaires administered through semi-structured interviews, and analysed using a series of Kruskal-Wallis tests. RESULTS: Spinal cord injury (tetraplegia/ paraplegia) was significantly more expensive for both formal and informal care compared with traumatic brain injury. The costs of formal care were significantly greater for those in the traumatic brain injury group who had a more severe injury (post-traumatic amnesia > 90 days) compared with the other traumatic brain injury groups (post-traumatic amnesia 7-28 days, 29-90 days). The costs of informal care were significantly higher for both traumatic brain injury and spinal cord injury compared with the costs of formal care. CONCLUSION: This study highlights the complementary role of formal and informal care in supporting people with traumatic brain injury or spinal cord injury, particularly highlighting the significant role of informal care, which needs to be more explicitly acknowledged in policy and planning processes.

Evaluation of the LFA-REAL clinician-reported outcome (ClinRO) and patient-reported outcome (PRO): prespecified analysis of the phase III ustekinumab trial in patients with SLE.

OBJECTIVE: The Lupus Foundation of America Rapid Evaluation of Activity in Lupus (LFA-REAL) system is a novel and simple SLE disease activity instrument, consisting of a tandem clinician-reported (ClinRO) and patient-reported (PRO) outcome measure. The aim of this study was to compare the LFA-REAL system with other SLE activity measures in the phase III trial of ustekinumab in patients with active SLE. METHODS: This was a prespecified analysis of data from a randomised, double-blind, placebo-controlled, parallel-group trial conducted at 140 sites in 20 countries. Correlations were evaluated between the LFA-REAL ClinRO and PRO with a panel of clinician-reported and patient-reported disease activity measures commonly used in SLE clinical trials at baseline, week 24 and week 52. All p values are reported as nominal. RESULTS: Trial participants included 516 patients with SLE with a mean (SD) age of 43.5 (8.9), of whom 482 (93.4%) were female. The LFA-REAL ClinRO correlated with Physician Global Assessment (r=0.39, 0.65 and 0.74, p<0.001), British Isles Lupus Assessment Group Index (r=0.43, 0.67 and 0.73, p<0.001) and SLE Disease Activity Index-2000 (r=0.35, 0.60 and 0.62, p<0.001). The LFA-REAL ClinRO arthralgia/arthritis score correlated well with active joint counts (r=0.54, 0.73 and 0.68, p<0.001) and the mucocutaneous global score correlated strongly with Cutaneous Lupus Erythematosus Disease Area and Severity Index total activity (r=0.57, 0.77 and 0.81, p<0.001). The LFA-REAL PRO demonstrated a moderate correlation with Functional Assessment of Chronic Illness Therapy-Fatigue (r=-0.60, -0.55 and -0.58, p<0.001), Lupus QoL physical health (r=-0.42, -0.47 and -0.46, p<0.001), SF-36v2 vitality (r=-0.40, -0.43 and -0.58, p<0.001) and SF-36v2 Physical Component Summary (r=-0.45, -0.53 and -0.53, p<0.001). The LFA-REAL ClinRO and PRO showed a moderate correlation with each other (r=0.32, 0.45 and 0.50, p<0.001). CONCLUSIONS: The LFA-REAL ClinRO and PRO showed varied levels of correlations (weak to strong) with existing physician-based lupus disease activity measures and patient-reported outcome instruments, respectively and were able to more accurately capture organ-specific mucocutaneous and musculoskeletal manifestations. More analyses are needed to determine areas in which patient-reported outcomes are most similar or different to physician-reported end points and the basis for differences.

Direct Integration of Perovskite Solar Cells with Carbon Fiber Substrates.

Integrating photovoltaic devices onto the surface of carbon-fiber-reinforced polymer substrates should create materials with high mechanical strength that are also able to generate electrical power. Such devices are anticipated to find ready applications as structural, energy-harvesting systems in both the automotive and aeronautical sectors. Here, the fabrication of triple-cation perovskite n-i-p solar cells onto the surface of planarized carbon-fiber-reinforced polymer substrates is demonstrated, with devices utilizing a transparent top ITO contact. These devices also contain a "wrinkled" SiO2 interlayer placed between the device and substrate that alleviates thermally induced cracking of the bottom ITO layer. Devices are found to have a maximum stabilized power conversion efficiency of 14.5% and a specific power (power per weight) of 21.4 W g-1 (without encapsulation), making them highly suitable for mobile power applications.

Feasibility, acceptability and practicality of transcranial stimulation in obsessive compulsive symptoms (FEATSOCS): A randomised controlled crossover trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive form of neurostimulation with potential for development as a self-administered intervention. It has shown promise as a safe and effective treatment for obsessive compulsive disorder (OCD) in a small number of studies. The two most favourable stimulation targets appear to be the left orbitofrontal cortex (L-OFC) and the supplementary motor area (SMA). We report the first study to test these targets head-to-head within a randomised sham-controlled trial. Our aim was to inform the design of future clinical research studies, by focussing on the acceptability and safety of the intervention, feasibility of recruitment, adherence to and tolerability of tDCS, and the size of any treatment-effect. METHODS: FEATSOCS was a randomised, double-blind, sham-controlled, cross-over, multicentre study. Twenty adults with DSM-5-defined OCD were randomised to treatment, comprising three courses of clinic-based tDCS (SMA, L-OFC, Sham), randomly allocated and delivered in counterbalanced order. Each course comprised four 20-min 2 mA stimulations, delivered over two consecutive days, separated by a 'washout' period of at least four weeks. Assessments were carried out by raters who were blind to stimulation-type. Clinical outcomes were assessed before, during, and up to four weeks after stimulation. Patient representatives with lived experience of OCD were actively involved at all stages. RESULTS: Clinicians showed willingness to recruit participants and recruitment to target was achieved. Adherence to treatment and study interventions was generally good, with only two dropouts. There were no serious adverse events, and adverse effects which did occur were transient and mostly mild in intensity. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores were numerically improved from baseline to 24 h after the final stimulation across all intervention groups but tended to worsen thereafter. The greatest effect size was seen in the L-OFC arm, (Cohen's d = -0.5 [95% CI -1.2 to 0.2] versus Sham), suggesting this stimulation site should be pursued in further studies. Additional significant sham referenced improvements in secondary outcomes occurred in the L-OFC arm, and to a lesser extent with SMA stimulation. CONCLUSIONS: tDCS was acceptable, practicable to apply, well-tolerated and appears a promising potential treatment for OCD. The L-OFC represents the most promising target based on clinical changes, though the effects on OCD symptoms were not statistically significant compared to sham. SMA stimulation showed lesser signs of promise. Further investigation of tDCS in OCD is warranted, to determine the optimal stimulation protocol (current, frequency, duration), longer-term effectiveness and brain-based mechanisms of effect. If efficacy is substantiated, consideration of home-based approaches represents a rational next step. TRIAL REGISTRATION: ISRCTN17937049. https://doi.org/10.1186/ISRCTN17937049.

From Patient to Provider: How Personal Medical Trauma Can Inform Supervision and Clinical Practice.

Two predoctoral psychology interns share their personal reflections of neurological injuries they experienced during their adolescence and how it has informed and shaped their clinical work. Through their reflections, they provide insights and lessons learned as they have the unique first-hand experience of being a patient and now a rehabilitation psychology trainee and provider. Additionally, they describe how they have applied such knowledge during their clinical work with clients experiencing neurological and chronic health conditions. Issues involving communication with clients, families, and the treatment teams, the benefits and risks of self-disclosure, and the role of hope, meaning in life, and spirituality are discussed. The clinical practice implications of these insights are invaluable for trainees and healthcare specialists at all levels of experience, including the crucial role of supervision during the predoctoral internship year. Recommendations are made for clinical practice including providing developmentally appropriate communication and promoting an environment for growth and recovery. The authors are hopeful that the reflections provided in this article can inspire other trainees to feel comfortable in sharing their personal medical and psychological challenges as appropriate and relevant to help integrate their professional development.

Intraductal fully covered self-expanding metal stents in the management of post-liver transplant anastomotic strictures: a UK wide experience.

Background: Fully covered intraductal self-expanding metal stents (IDSEMS) have been well described in the management of post-liver transplant (LT) anastomotic strictures (ASs). Their antimigration waists and intraductal nature make them suited for deployment across the biliary anastomosis. Objectives: We conducted a multicentre study to analyse their use and efficacy in the management of AS. Design: This was a retrospective, multicentre observational study across nine tertiary centres in the United Kingdom. Methods: Consecutive patients who underwent endoscopic retrograde cholangiopancreatography with IDSEMS insertion were analysed retrospectively. Recorded variables included patient demographics, procedural characteristics, response to therapy and follow-up data. Results: In all, 162 patients (100 males, 62%) underwent 176 episodes of IDSEMS insertion for AS. Aetiology of liver disease in this cohort included hepatocellular carcinoma (n = 35, 22%), followed by alcohol-related liver disease (n = 29, 18%), non-alcoholic steatohepatitis (n = 20, 12%), primary biliary cholangitis (n = 15, 9%), acute liver failure (n = 13, 8%), viral hepatitis (n = 13, 8%) and autoimmune hepatitis (n = 12, 7%). Early AS occurred in 25 (15%) cases, delayed in 32 (20%) cases and late in 95 (59%) cases. Age at transplant was 54 years (range, 12-74), and stent duration was 15 weeks (range, 3 days-78 weeks). In total, 131 (81%) had complete resolution of stricture at endoscopic re-evaluation. Stricture recurrence was observed in 13 (10%) cases, with a median of 19 weeks (range, 4-88 weeks) after stent removal. At removal, there were 21 (12%) adverse events, 5 (3%) episodes of cholangitis and 2 (1%) of pancreatitis. In 11 (6%) cases, the removal wires unravelled, and 3 (2%) stents migrated. All were removed endoscopically. Conclusion: IDSEMS appears to be safe and highly efficacious in the management of post-LT AS, with low rates of AS recurrence.

A case series of desmoplakin cardiomyopathy: a mimic of viral myocarditis.

Background: Clinical features and imaging presentation of myocarditis can overlap with other inflammatory or arrhythmogenic cardiomyopathies. Desmoplakin (DSP) is an important structural cardiac protein. Mutations in the DSP gene are associated with a variant of arrhythmogenic right ventricular cardiomyopathy (ARVC). Interestingly, this distinct genetic cardiomyopathy can also present with a myocardial inflammation and fibrosis pattern that may mimic other forms of myocarditis including viral myocarditis, which can raise a clinical challenge. We report two cases of DSP cardiomyopathy, which were initially thought to represent coronavirus disease of 2019 (COVID-19) myocarditis. Case summary: First patient is a 21-your-old woman with no past medical history but family history of presumed 'viral myocarditis' and ventricular tachycardia in her brother. She presented with acute chest pain and elevated cardiac enzymes. She tested positive for COVID-19 and given the suspicion for possible COVID-19 related acute myocarditis, cardiac magnetic resonance imaging obtained and revealed regional wall motion abnormalities, several areas of subepicardial and pericardial late gadolinium enhancement (LGE). Ambulatory cardiac monitoring showed runs of non-sustained ventricular tachycardia and considering her family history of arrhythmogenic myocarditis, genetic testing was performed that was positive for a likely pathogenic heterozygous mutation of DSP gene. She declined the recommended implantable cardioverter defibrillator (ICD).Second patient is a 34-year-old physician with no significant past medical history who works at a COVID-19 unit and presented with syncope and was found to have ventricular tachycardia. Echocardiogram revealed severely dilated left ventricle and globally depressed systolic function with left ventricular ejection fraction of 20%. Coronary computed tomography angiography showed no evidence of coronary atherosclerosis. Cardiac magnetic resonance imaging revealed several areas of mid myocardial and pericardial LGE. Subcutaneous ICD was implanted and an endomyocardial biopsy had evidence of lymphocytic myocarditis and adipose tissue infiltration of the myocardium. Genetic testing revealed pathogenic heterozygous DSP mutation. He underwent epicardial ablation for the episodes of ventricular tachycardia despite medical therapy. He was able to return to work and has not had any further episodes of arrhythmia. Conclusion: Mutations in the DSP gene are associated with left dominant arrhythmogenic cardiomyopathy, which is a variant of ARVC. Beside left ventricular systolic dysfunction and ventricular tachyarrhythmias, carriers of these mutations may present with episodes of chest pain associated with elevated cardiac enzymes and cardiac imaging findings indistinguishable from other forms of acute myocarditis including viral myocarditis. Currently, there are no guidelines for diagnosis and treatment of this entity.

Continuous Remote Patient Monitoring in Patients With Heart Failure (Cascade Study): Protocol for a Mixed Methods Feasibility Study.

BACKGROUND: Heart failure (HF) is a prevalent chronic disease and is associated with increases in mortality and morbidity. HF is a leading cause of hospitalizations and readmissions in the United States. A potentially promising area for preventing HF readmissions is continuous remote patient monitoring (CRPM). OBJECTIVE: The primary aim of this study is to determine the feasibility and preliminary efficacy of a CRPM solution in patients with HF at NorthShore University HealthSystem. METHODS: This study is a feasibility study and uses a wearable biosensor to continuously remotely monitor patients with HF for 30 days after discharge. Eligible patients admitted with an HF exacerbation at NorthShore University HealthSystem are being recruited, and the wearable biosensor is placed before discharge. The biosensor collects physiological ambulatory data, which are analyzed for signs of patient deterioration. Participants are also completing a daily survey through a dedicated study smartphone. If prespecified criteria from the physiological data and survey results are met, a notification is triggered, and a predetermined electronic health record-based pathway of telephonic management is completed. In phase 1, which has already been completed, 5 patients were enrolled and monitored for 30 days after discharge. The results of phase 1 were analyzed, and modifications to the program were made to optimize it. After analysis of the phase 1 results, 15 patients are being enrolled for phase 2, which is a calibration and testing period to enable further adjustments to be made. After phase 2, we will enroll 45 patients for phase 3. The combined results of phases 1, 2, and 3 will be analyzed to determine the feasibility of a CRPM program in patients with HF. Semistructured interviews are being conducted with key stakeholders, including patients, and these results will be analyzed using the affective adaptation of the technology acceptance model. RESULTS: During phase 1, of the 5 patients, 2 (40%) were readmitted during the study period. The study completion rate for phase 1 was 80% (4/5), and the study attrition rate was 20% (1/5). There were 57 protocol deviations out of 150 patient days in phase 1 of the study. The results of phase 1 were analyzed, and the study protocol was adjusted to optimize it for phases 2 and 3. Phase 2 and phase 3 results will be available by the end of 2022. CONCLUSIONS: A CRPM program may offer a low-risk solution to improve care of patients with HF after hospital discharge and may help to decrease readmission of patients with HF to the hospital. This protocol may also lay the groundwork for the use of CRPM solutions in other groups of patients considered to be at high risk. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/36741.

Phase 3, multicentre, randomised, placebo-controlled study evaluating the efficacy and safety of ustekinumab in patients with systemic lupus erythematosus.

OBJECTIVE: Evaluate the efficacy and safety of ustekinumab, an anti-interleukin-12/23 p40 antibody, in a phase 3, randomised, placebo-controlled study of patients with active systemic lupus erythematosus (SLE) despite receiving standard-of-care. METHODS: Active SLE patients (SLE Disease Activity Index 2000 (SLEDAI-2K) ≥6 during screening and SLEDAI-2K ≥4 for clinical features at week 0) despite receiving oral glucocorticoids, antimalarials, or immunomodulatory drugs were randomised (3:2) to receive ustekinumab (intravenous infusion ~6 mg/kg at week 0, followed by subcutaneous injections of ustekinumab 90 mg at week 8 and every 8 weeks) or placebo through week 48. The primary endpoint was SLE Responder Index (SRI)-4 at week 52, and major secondary endpoints included time to flare through week 52 and SRI-4 at week 24. RESULTS: At baseline, 516 patients were randomised to placebo (n=208) or ustekinumab (n=308). Following the planned interim analysis, the sponsor discontinued the study due to lack of efficacy but no safety concerns. Efficacy analyses included 289 patients (placebo, n=116; ustekinumab, n=173) who completed or would have had a week 52 visit at study discontinuation. At week 52, 44% of ustekinumab patients and 56% of placebo patients had an SRI-4 response; there were no appreciable differences between the treatment groups in the major secondary endpoints. Through week 52, 28% of ustekinumab patients and 32% of placebo patients had a British Isles Lupus Assessment Group flare, with a mean time to first flare of 204.7 and 200.4 days, respectively. Through week 52, 70% of ustekinumab patients and 74% of placebo patients had ≥1 adverse event. CONCLUSIONS: Ustekinumab did not demonstrate superiority over placebo in this population of adults with active SLE; adverse events were consistent with the known safety profile of ustekinumab. TRIAL REGISTRATION NUMBER: NCT03517722.

Opportunities and challenges of applying advanced X-ray spectroscopy to actinide and lanthanide N-donor ligand systems.

N-donor ligands such as n-Pr-BTP [2,6-bis(5,6-dipropyl-1,2,4-triazin-3-yl)pyridine] preferentially bind trivalent actinides (An3+) over trivalent lanthanides (Ln3+) in liquid-liquid separation. However, the chemical and physical processes responsible for this selectivity are not yet well understood. Here, an explorative comparative X-ray spectroscopy and computational (L3-edge) study for the An/Ln L3-edge and the N K-edge of [An/Ln(n-Pr-BTP)3](NO3)3, [Ln(n-Pr-BTP)3](CF3SO3)3 and [Ln(n-Pr-BTP)3](ClO4)3 complexes is presented. High-resolution X-ray absorption near-edge structure (HR-XANES) L3-edge data reveal additional features in the pre- and post-edge range of the spectra that are investigated using the quantum chemical codes FEFF and FDMNES. X-ray Raman spectroscopy studies demonstrate the applicability of this novel technique for investigations of liquid samples of partitioning systems at the N K-edge.

The efficacy of bone marrow mononuclear stem cell transplantation in patients with non-ischemic dilated cardiomyopathy-a meta analysis.

Cardiomyopathy refers to a wide spectrum of heart pathologies that interfere with normal heart function. Management options of patients with cardiomyopathy depended mainly on the severity of the condition. Lifestyle modifications and regular exercise together with a healthy diet is compatible for mild conditions. Severe conditions, however, rely on medications or surgery. Here, we aim to investigate the efficacy of bone marrow mononuclear stem cell transplantation in patients with dilated cardiomyopathy. We searched PubMed, Scopus, and Cochrane CENTRAL for relevant clinical trials and excluded observational studies. We performed the quality assessment of this study following GRADE guidelines. The assessment of the risk of bias was performed by the Cochrane's risk of bias tool. We present an analysis of the following outcomes: left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), and six minutes walking test. Data were pooled as mean differences (MD) and relative confidence intervals (CI). The analysis of 667 patients from 11 studies receiving autologous bone marrow cell therapy for non-ischemic dilated cardiomyopathy is presented. A total of 338 patients were allocated to the treatment group, and 329 participants entered the control group. The mean age of the patients in the treatment group is 52.4 ± 4.3 years, while that of the control is 53.7 ± 3.7 years. Seven studies (14.18-23) reported transplantation through the intracoronary route. Table 1 shows a summary of the baseline characteristics of the included studies and participants, the number of injected cells, and the type of injected cells in each trial. Table 2 summarizes and illustrates the previous treatment history of included patients in each trial, as well as the baseline values of different scores used as outcome measures in this analysis. We found that bone marrow mononuclear stem cell therapy leads to significantly increased LVEF (MD = 4.54%, 95% CI [3.52, 5.56], P < 0.0001). Patients in the transplant group experienced less left ventricular end-diastolic diameter (millimeter) than the control arm (MD = -1.86 mm, 95% CI [-4.01, 0.29], P = 0.09). Additionally, Patients in the transplant group could walk 28.53 m more than the controls (MD = 28.53 m, 95% CI [2.51, 54.55], P = 0.03). Transplantation of bone marrow stem cells yields acceptable results regarding left ventricular ejection fraction and lowers the left ventricular end-diastolic diameter. Additionally, the six minutes walking test is improved in the transplant group. Table 1 Demographic data about the included participants Study Year Sample size Age, years Males, n (%) Diabetics, n (%) Route of administration Number of injected cells Type of injected cells TTT Control TTT Control TTT Control TTT Control Bartolucci 2015 12 11 58 ± 14 57 ± 11 8 (66.7) 9 (81.8) 2 (16.7) 1 (9.1) Intracoronary 1.94 × 10^6 CD34 +  Bocchi 2010 8 15 51 ± 15 NR NR NR NR Intracoronary NR NR Frljak 2018 30 30 56 ± 9 54 ± 11 27 (90) 26 (87) 3 (10) 2 (6) Trans-endocardial NR CD34 +  Hamshere 2015 15 14 57.67 ± 12.32 56.79 ± 9.8 10 12 9(59.9%) 8(57.1%) Intracoronary 4.91 × 10^6 CD34 +  Hu 2011 31 29 56.61 ± 9.72 58.27 ± 8.86 NR NR NR NR NR NR NR Matrino 2015 82 78 51 ± 11.1 49.6 ± 11.1 73.1 68.3 NR NR Intracoronary 10^8 TTT, CD45, CD105, and CD133 Sant'Anna 2014 20 10 48.3 ± 8.71 51.6 ± 7.79 13(65) 5 (50%) NR NR Intra-myocardial 1.06 × 108 CD3, CD4, CD14, CD34, CD38, and CD45 Seth 2010 41 40 45 ± 15 49 ± 9 33 35 NR NR NR 168 × 10^6 Bone marrow mononuclear cells Vrtovec 2011 28 27 52 ± 8 54 ± 7 26 (93) 23 (85) NR NR Intracoronary 123 × 10^6 CD34 +  Vrtovec 2013 55 55 53 ± 8 55 ± 7 45 (82) 44 (80) NR NR Intracoronary NR NR Xiao 2017 16 20 49.5 ± 11.6 54.4 ± 11.6 9 (56.3) 14 (70.0) 6 (37.5) 5 (29.4) Intracoronary infusion (4.9 ± 1.7) × 108 (CD29, CD34, CD44, CD45, and CD166) Data are reported as mean ± SD or n (%) unless proved otherwise TTT treatment group, NR not reported Table 2 Previous history of treatment and drug intake by the patients Study Year Medical therapy, n (%) Baseline scores, mean (SD) Beta blockers ACE inhibitors Digoxin Diuretics LVEF, % LVEDD, mm Six minutes-walk test* TTT Control TTT Control TTT Control TTT Control TTT Control TTT Control TTT Control Bartolucci 2015 10 (83.3) 8 (72.7) NR NR 3 (25) 3 (27.3) 11 (91.6) 10 (90.9) 26.8 ± 4.9 30.3 ± 6.3 NR NR NR NR Bocchi 2010 NR NR NR NR NR NR NR NR 21.8 ± 3.8 30.6 ± 7.3 79 (10) 78 (12) NR NR Frljak 2018 30 (100) 30 (100) 31 (100) 32 (100) 2 (7) 3 (10) 32 (100) 33 (100) 32.2 ± 9.3 31.1 ± 7.8 NR NR NR NR Hamshere 2015 13 14 15 13 6 2 9 8 32.93 ± 16.46 29.75 ± 9.2 NR NR NR NR Hu* 2011 NR NR NR NR NR NR NR NR NR NR NR NR 466 (402, 495) 448 (383, 497) Matrino 2015 9 (11) 8 (10.2) 53 (64.1) 48 (61.1) 63 (77) 62 (79) 74 (89.7) 69 (88.9) 23.8 ± 7.2 24.7 ± 7.0 NR NR 347.3(146.7) 349.8(139.7) Sant'Anna 2014 NR NR NR NR NR NR NR NR NR NR NR NR 358.5 (88.69) 353 (86.67) Seth 2010 29 (70) 29 (72) 41 (100) 40 (100) NR NR NR NR NR NR NR NR NR NR Vrtovec 2011 21 (75) 22 (81) NR NR 5 (18) 6 (22) 26 (93) 24 (88) 25.6 ± 5.1 26.7 ± 3.9 69 ± 10 70 ± 7 NR NR Vrtovec 2013 43 (79) 46 (84) 51 (93) 54 (98) 9 (16) 11 (20) 51 (93) 20 (91) 24.3 ± 6.5 25.7 ± 4.1 69 ± 10 70 ± 7 NR NR Xiao 2017 16 (100) 20 (100) 16 (100) 19 (95) 4 (25.0) 8 (40.0) 5 (31.3) 6 (30.0) 33.1 ± 3.9 33.7 ± 4.0 NR NR 355.0 ± 91.2 323.3 ± 89.4 Data are reported as mean ± SD or n (%) unless proved otherwise TTT treatment group, NR not reported *Data are reported as median (IQR).

Efficacy and Safety of Ustekinumab in Patients With Active Systemic Lupus Erythematosus: Results of a Phase II Open-label Extension Study.

OBJECTIVE: To evaluate the long-term efficacy and safety of ustekinumab through 2 years in patients with active systemic lupus erythematosus (SLE). METHODS: This was a placebo-controlled (week 24), phase II study in 102 patients with seropositive active SLE. Patients were randomized to ustekinumab (approximately 6 mg/kg single intravenous infusion, then subcutaneous [SC] injections of 90 mg every 8 weeks) or placebo, added to background therapy. Placebo patients initiated ustekinumab (90 mg SC every 8 weeks) at week 24. Patients could enter an optional open-label study extension after week 40 (final ustekinumab administration at week 104). Efficacy assessments included Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), SLEDAI-2K Responder Index-4 (SRI-4), physician global assessment (PGA), and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Observed data are reported for the extension period. The final efficacy assessment was at week 112; safety was monitored through week 120. RESULTS: In this subset of patients who entered the study extension, 24 in the ustekinumab group and 14 in the placebo crossover group completed study treatment. At week 112, 79% and 92%, respectively, had an SRI-4 response; 92% in both groups had ≥ 4-point improvement from baseline in SLEDAI-2K score; 79% and 93%, respectively, had ≥ 30% improvement from baseline in PGA; 86% and 91%, respectively, had ≥ 50% improvement in active joint (pain and inflammation) count; and 79% and 100%, respectively, had ≥ 50% improvement in CLASI Activity Score. No deaths, malignancies, opportunistic infections, or tuberculosis cases occurred. Safety events were consistent with the known ustekinumab safety profile. CONCLUSION: Of the 46 patients who entered the voluntary extension of this phase II study, clinical benefit in global and organ-specific SLE activity measures was observed with ustekinumab through 2 years with no new or unexpected safety findings. [ClinicalTrials.gov: NCT02349061].

Continuous Remote Patient Monitoring: Evaluation of the Heart Failure Cascade Soft Launch.

OBJECTIVE: We report on our experience of deploying a continuous remote patient monitoring (CRPM) study soft launch with structured cascading and escalation pathways on heart failure (HF) patients post-discharge. The lessons learned from the soft launch are used to modify and fine-tune the workflow process and study protocol. METHODS: This soft launch was conducted at NorthShore University HealthSystem's Evanston Hospital from December 2020 to March 2021. Patients were provided with non-invasive wearable biosensors that continuously collect ambulatory physiological data, and a study phone that collects patient-reported outcomes. The physiological data are analyzed by machine learning algorithms, potentially identifying physiological perturbation in HF patients. Alerts from this algorithm may be cascaded with other patient status data to inform home health nurses' (HHNs') management via a structured protocol. HHNs review the monitoring platform daily. If the patient's status meets specific criteria, HHNs perform assessments and escalate patient cases to the HF team for further guidance on early intervention. RESULTS: We enrolled five patients into the soft launch. Four participants adhered to study activities. Two out of five patients were readmitted, one due to HF, one due to infection. Observed miscommunication and protocol gaps were noted for protocol amendment. The study team adopted an organizational development method from change management theory to reconfigure the study protocol. CONCLUSION: We sought to automate the monitoring aspects of post-discharge care by aligning a new technology that generates streaming data from a wearable device with a complex, multi-provider workflow into a novel protocol using iterative design, implementation, and evaluation methods to monitor post-discharge HF patients. CRPM with structured escalation and telemonitoring protocol shows potential to maintain patients in their home environment and reduce HF-related readmissions. Our results suggest that further education to engage and empower frontline workers using advanced technology is essential to scale up the approach.

Feasibility and acceptability of transcranial stimulation in obsessive-compulsive symptoms (FEATSOCS): study protocol for a randomised controlled trial of transcranial direct current stimulation (tDCS) in obsessive-compulsive disorder (OCD).

BACKGROUND: Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder which often proves refractory to current treatment approaches. Transcranial direct current stimulation (tDCS), a noninvasive form of neurostimulation, with potential for development as a self-administered intervention, has shown potential as a safe and efficacious treatment for OCD in a small number of trials. The two most promising stimulation sites are located above the orbitofrontal cortex (OFC) and the supplementary motor area (SMA). METHODS: The aim of this feasibility study is to inform the development of a definitive trial, focussing on the acceptability, safety of the intervention, feasibility of recruitment, adherence and tolerability to tDCS and study assessments and the size of the treatment effect. To this end, we will deliver a double-blind, sham-controlled, crossover randomised multicentre study in 25 adults with OCD. Each participant will receive three courses of tDCS (SMA, OFC and sham), randomly allocated and given in counterbalanced order. Each course comprises four 20-min stimulations, delivered over two consecutive days, separated by at least 4 weeks' washout period. We will collect information about recruitment, study conduct and tDCS delivery. Blinded raters will assess clinical outcomes before, during and up to 4 weeks after stimulation using validated scales. We will include relevant objective neurocognitive tasks, testing cognitive flexibility, motor disinhibition, cooperation and habit learning. DISCUSSION: We will analyse the magnitude of the effect of the interventions on OCD symptoms alongside the standard deviation of the outcome measure, to estimate effect size and determine the optimal stimulation target. We will also measure the duration of the effect of stimulation, to provide information on spacing treatments efficiently. We will evaluate the usefulness and limitations of specific neurocognitive tests to determine a definitive test battery. Additionally, qualitative data will be collected from participants to better understand their experience of taking part in a tDCS intervention, as well as the impact on their overall quality of life. These clinical outcomes will enable the project team to further refine the methodology to ensure optimal efficiency in terms of both delivering and assessing the treatment in a full-scale trial. TRIAL REGISTRATION: ISRCTN17937049 . (date applied 08/07/2019). Recruitment (ongoing) began 23rd July 2019 and is anticipated to complete 30th April 2021.

Knowledge by default.

The target article presents strong empirical evidence that knowledge is basic. However, it offers an unsatisfactory account of what makes knowledge basic. Some current ideas in cognitive neuroscience - predictive coding and analysis by synthesis - point to a more plausible account that better explains the evidence.

The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial.

Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor dapagliflozin improves the primary endpoint of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CS), a measure of heart failure-related health status, at 12 weeks after treatment initiation. Secondary endpoints included the 6-minute walk test (6MWT), KCCQ Overall Summary Score (KCCQ-OS), clinically meaningful changes in KCCQ-CS and -OS, and changes in weight, natriuretic peptides, glycated hemoglobin and systolic blood pressure. In total, 324 patients were randomized to dapagliflozin or placebo. Dapagliflozin improved KCCQ-CS (effect size, 5.8 points (95% confidence interval (CI) 2.3-9.2, P = 0.001), meeting the predefined primary endpoint, due to improvements in both KCCQ total symptom score (KCCQ-TS) (5.8 points (95% CI 2.0-9.6, P = 0.003)) and physical limitations scores (5.3 points (95% CI 0.7-10.0, P = 0.026)). Dapagliflozin also improved 6MWT (mean effect size of 20.1 m (95% CI 5.6-34.7, P = 0.007)), KCCQ-OS (4.5 points (95% CI 1.1-7.8, P = 0.009)), proportion of participants with 5-point or greater improvements in KCCQ-OS (odds ratio (OR) = 1.73 (95% CI 1.05-2.85, P = 0.03)) and reduced weight (mean effect size, 0.72 kg (95% CI 0.01-1.42, P = 0.046)). There were no significant differences in other secondary endpoints. Adverse events were similar between dapagliflozin and placebo (44 (27.2%) versus 38 (23.5%) patients, respectively). These results indicate that 12 weeks of dapagliflozin treatment significantly improved patient-reported symptoms, physical limitations and exercise function and was well tolerated in chronic HFpEF.