The implantable cardioverter-defibrillator (ICD) is highly effective in reducing mortality among patients at risk for fatal arrhythmias, but inappropriate ICD activations are frequent, with potential ...adverse effects.
We randomly assigned 1500 patients with a primary-prevention indication to receive an ICD with one of three programming configurations. The primary objective was to determine whether programmed high-rate therapy (with a 2.5-second delay before the initiation of therapy at a heart rate of ≥200 beats per minute) or delayed therapy (with a 60-second delay at 170 to 199 beats per minute, a 12-second delay at 200 to 249 beats per minute, and a 2.5-second delay at ≥250 beats per minute) was associated with a decrease in the number of patients with a first occurrence of inappropriate antitachycardia pacing or shocks, as compared with conventional programming (with a 2.5-second delay at 170 to 199 beats per minute and a 1.0-second delay at ≥200 beats per minute).
During an average follow-up of 1.4 years, high-rate therapy and delayed ICD therapy, as compared with conventional device programming, were associated with reductions in a first occurrence of inappropriate therapy (hazard ratio with high-rate therapy vs. conventional therapy, 0.21; 95% confidence interval CI, 0.13 to 0.34; P<0.001; hazard ratio with delayed therapy vs. conventional therapy, 0.24; 95% CI, 0.15 to 0.40; P<0.001) and reductions in all-cause mortality (hazard ratio with high-rate therapy vs. conventional therapy, 0.45; 95% CI, 0.24 to 0.85; P=0.01; hazard ratio with delayed therapy vs. conventional therapy, 0.56; 95% CI, 0.30 to 1.02; P=0.06). There were no significant differences in procedure-related adverse events among the three treatment groups.
Programming of ICD therapies for tachyarrhythmias of 200 beats per minute or higher or with a prolonged delay in therapy at 170 beats per minute or higher, as compared with conventional programming, was associated with reductions in inappropriate therapy and all-cause mortality during long-term follow-up. (Funded by Boston Scientific; MADIT-RIT ClinicalTrials.gov number, NCT00947310.).
Pancreatic ductal adenocarcinoma (PDAC) is notorious for its associated skeletal muscle wasting (SMW) and mortality. Currently, the relationships between PDAC, SMW, and survival are poorly ...understood. Thus, there is great need for a faithful small animal model with quantitative longitudinal outcome measures that recapitulate clinical PDAC, to define SMW onset and assess progression. Therefore, we aimed to validate dual energy X-ray absorptiometry (DEXA) as a longitudinal measure of lean mass, and demonstrate its utility to quantify SMW in the KCKO murine model of PDAC.
In vivo body composition of: 1) untreated mice at 5, 8, 12, 18, and 22 weeks of age (n = 4) and 2) a cohort of mice with (n = 5) and without PDAC (n = 5), was determined via DEXA and lean mass of the lower hind limbs was predicted via a region of interest analysis by two-independent observers. Total body weight was determined. Tibialis anterior (TA) muscles were weighed and processed for histomorphometry immediately post-mortem. Statistical differences between groups were assessed using ANOVA and Student's t-tests. Linear regression models and correlation analysis were used to measure the association between TA and DEXA mass, and reproducibility of DEXA was quantified via the intraclass correlation coefficient (ICC).
Lean mass in growing untreated mice determined by DEXA correlated with TA mass (r2 = 0.94; p <0.0001) and body weight (r2 = 0.89; p <0.0001). DEXA measurements were highly reproducible between observers (ICC = 0.95; 95% CI: 0.89-0.98). DEXA and TA mass also correlated in the PDAC cohort (r2 = 0.76; p <0.0001). Significant SMW in tumor-bearing mice was detected within 38 days of implantation, by DEXA, TA mass, and histomorphometry.
DEXA is a longitudinal outcome measure of lean mass in mice. The KCKO syngeneic model is a bona fide model of PDAC associated SMW that can be quantified with longitudinal DEXA.
The burden of neurological disorders is increasing, but access to care is limited. Providing specialty care to patients via telemedicine could help alleviate this growing problem.
To evaluate the ...feasibility, effectiveness, and economic benefits of using web-based videoconferencing (telemedicine) to provide specialty care to patients with Parkinson disease in their homes.
A 7-month, 2-center, randomized controlled clinical trial.
Patients' homes and outpatient clinics at 2 academic medical centers.
Twenty patients with Parkinson disease with Internet access at home.
Care from a specialist delivered remotely at home or in person in the clinic.
The primary outcome variable was feasibility, as measured by the percentage of telemedicine visits completed as scheduled. Secondary outcome measures included clinical benefit, as measured by the 39-item Parkinson Disease Questionnaire, and economic value, as measured by time and travel.
Twenty participants enrolled in the study and were randomly assigned to telemedicine (n = 9) or in-person care (n = 11). Of the 27 scheduled telemedicine visits, 25 (93%) were completed, and of the 33 scheduled in-person visits, 30 (91%) were completed (P = .99). In this small study, the change in quality of life did not differ for those randomly assigned to telemedicine compared with those randomly assigned to in-person care (4.0-point improvement vs 6.4-point improvement; P = .61). Compared with in-person visits, each telemedicine visit saved participants, on average, 100 miles of travel and 3 hours of time.
Using web-based videoconferencing to provide specialty care at home is feasible, provides value to patients, and may offer similar clinical benefit to that of in-person care. Larger studies are needed to determine whether the clinical benefits are indeed comparable to those of in-person care and whether the results observed are generalizable.
clinicaltrials.gov Identifier: NCT01476306.
Vessel wall imaging (VWI) using T1 dark blood MRI can depict inflammation of intracranial arteries in patients with cerebral vasculitis. Recently, 3D VWI sequences were introduced at 3 Tesla. We ...aimed to compare 2D and 3D VWI for detection of intracranial vessel wall enhancement (VWE) in patients suspected of cerebral vasculitis.
44 MRI scans of 39 patients were assessed that included bi-planar 2D T1 and whole-brain 3D T1 SPACE dark blood VWI pre and post contrast. Visibility and VWE were analyzed in 31 pre-specified intracranial artery segments. Additionally, leptomeningeal and parenchymal contrast enhancement was assessed.
Overall, more arterial segments were visualized with 3D VWI (p<0.0001). Detection of VWE showed fair agreement between 2D and 3D VWI (κ = 0.583). On segmental level, more VWE was detected in intradural ICA by 2D VWI (p<0.001) and in VA V4 segment by 3D VWI (p<0.05). 3D VWI showed more leptomeningeal (p<0.05) and parenchymal (p<0.01) contrast enhancement. In patients with positive diagnosis of cerebral vasculitis, sensitivity was of 67% (2D and 3D VWI) and specificity was 44% (2D VWI) and 48% (3D VWI); more VWE was seen in arteries distal to VA and ICA compared to non-vasculitic patients.
2D and 3D VWI differed in the ability to detect VWE. Whole brain coverage with better evaluability of VAs and distal intracranial artery segments, and depiction of more parenchymal and leptomeningeal enhancement make 3D VWI more favorable. As VWE in arteries distal to VA and ICA may be used for discrimination of vasculitic and non-vasculitic patients, future increase in spatial resolution of 3D VWI sequences may be beneficial.
Over the past decade, laboratory courses have made a fundamental shift to inquiry-based modules and authentic research experiences. In many cases, these research experiences emphasize addressing ...novel research questions. Insects are ideal for inquiry-based undergraduate laboratory courses because research on insects is not limited by regulatory, economic, and logistical constraints to the same degree as research on vertebrates. While novel research questions could be pursued with model insect species (e.g.,
Drosophila
,
Tribolium
), the opportunities presented by non-model insects are much greater, as less is known about non-model species. We review the literature on the use of non-model insect species in laboratory education to provide a resource for faculty interested in developing new authentic inquiry-based laboratory modules using insects. Broader use of insects in undergraduate laboratory education will support the pedagogical goals of increased inquiry and resesarch experiences while at the same time fostering increased interest and research in entomology.
The incidence of chemotherapy-induced cardiomyopathy is increasing and is associated with poor clinical outcomes.
To assess the association of cardiac resynchronization therapy (CRT) with improvement ...in cardiac function, as well as clinical improvement in patients with chemotherapy-induced cardiomyopathy.
The Multicenter Automatic Defibrillator Implantation Trial-Chemotherapy-Induced Cardiomyopathy was an uncontrolled, prospective, cohort study conducted between November 21, 2014, and June 21, 2018, at 12 tertiary centers with cardio-oncology programs in the United States. Thirty patients were implanted with CRT owing to reduced left ventricular ejection fraction (LVEF≤35%), New York Heart Association class II-IV heart failure symptoms, and wide QRS complex, with established chemotherapy-induced cardiomyopathy and were followed up for 6 months after CRT implantation. The date of final follow-up was February 6, 2019.
CRT implantation according to standard of care.
The primary end point was change in LVEF from baseline to 6 months after initiating CRT. Secondary outcomes included all-cause mortality and change in left ventricular end-systolic volume and end-diastolic volume.
Among 30 patients who were enrolled (mean SD age, 64 11 years; 26 women 87%; 73% had a history of breast cancer; 20% had a history of lymphoma or leukemia), primary end point data were available for 26 patients and secondary end point data were available for 23 patients. Patients had nonischemic cardiomyopathy with left bundle branch block, median LVEF of 29%, and a mean QRS duration of 152 ms. Patients with CRT experienced a statistically significant improvement in mean LVEF at 6 months from 28% to 39% (difference, 10.6% 95% CI, 8.0%-13.3%; P < .001). This was accompanied by a reduction in LV end-systolic volume from 122.7 to 89.0 mL (difference, 37.0 mL 95% CI, 28.2-45.8) and reduction in LV end-diastolic volume from 171.0 to 143.2 mL (difference, 31.9 mL 95% CI, 22.1-41.6) (both P < .001). Adverse events included a procedure-related pneumothorax (1 patient), a device pocket infection (1 patient), and heart failure requiring hospitalization during follow-up (1 patient).
In this preliminary study of patients with chemotherapy-induced cardiomyopathy, CRT was associated with improvement in LVEF after 6 months. The findings are limited by the small sample size, short follow-up, and absence of a control group.
ClinicalTrials.gov Identifier: NCT02164721.
We investigate the use of relaxed decision diagrams (DDs) for computing admissible heuristics for the cost-optimal delete-free planning (DFP) problem. Our main contributions are the introduction of ...two novel DD encodings for a DFP task: a multivalued decision diagram that includes the sequencing aspect of the problem and a binary decision diagram representation of its sequential relaxation. We present construction algorithms for each DD that leverage these different perspectives of the DFP task and provide theoretical and empirical analyses of the associated heuristics. We further show that relaxed DDs can be used beyond heuristic computation to extract delete-free plans, find action landmarks, and identify redundant actions. Our empirical analysis shows that while DD-based heuristics trail the state of the art, even small relaxed DDs are competitive with the linear programming heuristic for the DFP task, thus, revealing novel ways of designing admissible heuristics.
Prognosing life‐threatening orthopedic infections caused by Staphylococcus aureus remains a major clinical challenge. To address this, we developed a multiplex assay to assess the humoral immune ...proteome against S. aureus in patients with musculoskeletal infections. We found initial evidence that antibodies against some antigens (autolysins: Amd, Gmd; secreted immunotoxins: CHIPS, SCIN, Hla) were associated with protection, whereas antibodies against the iron‐regulated surface determinant (Isd) proteins (IsdA, IsdB, IsdH) were aligned with adverse outcomes. To formally test this, we analyzed antibody levels and 1‐year clinical outcomes of 194 patients with confirmed S. aureus bone infections (AO Trauma Clinical Priority Program CPP Bone Infection Registry). A staggering 20.6% of the enrolled patients experienced adverse clinical outcomes (arthrodesis, reinfection, amputation, and septic death) after 1‐year. At enrollment, anti‐S. aureus immunoglobulin G (IgG) levels in patients with adverse outcomes were 1.35‐fold lower than those in patients whose infections were successfully controlled (p < 0.0001). Overall, there was a 51%–69% reduction in adverse outcome risk for every 10‐fold increase in initial IgG concentration against Gmd, Amd, IsdH, CHIPS, SCIN, and Hla (p < 0.05). Notably, anti‐IsdB antibodies remained elevated in patients with adverse outcomes; for every 10‐fold change in the ratio of circulating anti‐Isd to anti‐Atl IgG at enrollment, there was a trending 2.6‐fold increased risk (odds ratio = 2.555) of an adverse event (p = 0.105). Moreover, antibody increases over time correlated with adverse outcomes and decreases with positive outcomes. These studies demonstrate the potential of the humoral immune response against S. aureus as a prognostic indicator for assessing treatment success and identifying patients requiring additional interventions.
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