Clinical impact of remote heart failure management using the multiparameter ICD HeartLogic alert.

INTRODUCTION AND OBJECTIVES: The multiparametric implantable cardioverter-defibrillator HeartLogic index has proven to be a sensitive and timely predictor of impending heart failure (HF) decompensation. We evaluated the impact of a standardized follow-up protocol implemented by nursing staff and based on remote management of alerts. METHODS: The algorithm was activated in HF patients at 19 Spanish centers. Transmitted data were analyzed remotely, and patients were contacted by telephone if alerts were issued. Clinical actions were implemented remotely or through outpatient visits. The primary endpoint consisted of HF hospitalizations or death. Secondary endpoints were HF outpatient visits. We compared the 12-month periods before and after the adoption of the protocol. RESULTS: We analyzed 392 patients (aged 69±10 years, 76% male, 50% ischemic cardiomyopathy) with implantable cardioverter-defibrillators (20%) or cardiac resynchronization therapy defibrillators (80%). The primary endpoint occurred 151 times in 86 (22%) patients during the 12 months before the adoption of the protocol, and 69 times in 45 (11%) patients (P<.001) during the 12 months after its adoption. The mean number of hospitalizations per patient was 0.39±0.89 pre- and 0.18±0.57 postadoption (P<.001). There were 185 outpatient visits for HF in 96 (24%) patients before adoption and 64 in 48 (12%) patients after adoption (P<.001). The mean number of visits per patient was 0.47±1.11 pre- and 0.16±0.51 postadoption (P<.001). CONCLUSIONS: A standardized follow-up protocol based on remote management of HeartLogic alerts enabled effective remote management of HF patients. After its adoption, we observed a significant reduction in HF hospitalizations and outpatient visits.

A summary of the U.S. Marine Recruit Assessment Program (RAP) procedures and survey from 2003 to 2021

The Recruit Assessment Program (RAP) is a cross-sectional, baseline survey of U.S. Marine recruits administered at Marine Corps Recruit Depot, San Diego. This report presents RAP study procedures and survey content that was administered to 229,015 participants between 2003 and 2021. Self-reported data were collected on recruit demographics, physical and mental health, adverse life experiences, lifestyle and risky behaviors, and substance use. In 2013, the survey was updated to remove questions with other linkable and reliable sources and those with low completion rates and low relevance to Marine health research; the removal of these items allowed for the addition of instrument measures for major depression, post-traumatic stress disorder, anger, and resilience with no significant change to overall survey length. Average completion rates are approximately 95%. Multiple studies have shown the utility of RAP data collected thus far as a robust data repository of pre-service health and behavioral measures.

Escalating Oral Treprostinil Dose With Intravenous Treprostinil Bridging Therapy.

Oral treprostinil, approved for the treatment of pulmonary arterial hypertension, remains an attractive option in combination with other medications to delay disease progression and improve exercise capacity. However, patients are often challenged with the ability to overcome adverse effects as outpatients and reach effective doses in a timely manner. We describe a case of a 47-year-old female on oral treprostinil who presented to the clinic with worsening symptoms of disease, necessitating higher dosing. This patient was previously uptitrated outpatient with oral treprostinil, which had allowed her to remain stable for years. Once uptitrated with additional intravenous therapy, the oral treprostinil dose was gradually further increased to the new goal dosage, resulting in improvements in symptoms and right ventricular function. This case highlights the versatility of dose optimization of oral treprostinil with rapid bridging through intravenous therapy.

Designing peptide amphiphiles as novel antibacterials and antibiotic adjuvants against gram-negative bacteria.

Gram-negative strains are intrinsically resistant to most antibiotics due to the robust and impermeable characteristic of their outer membrane. Self-assembling cationic peptide amphiphiles (PAs) have the ability to disrupt bacteria membranes, constituting an excellent antibacterial alternative to small molecule drugs that can be used alone or as antibiotic adjuvants to overcome bacteria resistance. PA1 (C16KHKHK), self-assembled into micelles, which exhibited low antibacterial activity against all strains tested, and showed strong synergistic antibacterial activity in combination with Vancomycin with a Fractional Inhibitory Concentration index (FICi) of 0.15 against E. coli. The molecules, PA2 (C16KRKR) and PA3 (C16AAAKRKR), also self-assembled into micelles, displayed a broad-spectrum antibacterial activity against all strains tested, and low susceptibility to resistance development over 21 days. Finally, PA1, PA 2 and PA3 displayed low cytotoxicity against mammalian cells, and PA2 showed a potent antibacterial activity and low toxicity in preliminary in vivo models using G. mellonella. The results show that PAs are a great platform for the future development of effective antibiotics to slow down the antibiotic resistance and can act as antibiotic adjuvants with synergistic mechanism of action, which can be repurposed for use with existing antibiotics commonly used to treat gram-positive bacteria to treat infections caused by gram-negative bacteria.

24-2 SITA Standard versus 24-2 SITA Faster in Perimetry-Naive Normal Subjects.

PURPOSE: To compare the Swedish Interactive Thresholding Algorithm (SITA) Standard (SS) and SITA Faster (SFR) strategies in normal individuals undergoing standard automated perimetry (SAP) for the first time. DESIGN: Randomized, comparative, observational case series. PARTICIPANTS: Seventy-four perimetry-naive healthy individuals. METHODS: All individuals underwent SAP 24-2 testing with the Humphrey Field Analyzer III (model 850 Zeiss) using the SS and SFR strategies. One eye of each individual was tested. Test order between strategies was randomized, and an interval of 15 minutes was allowed between the tests. MAIN OUTCOME MEASURES: The following variables were compared: test time, foveal threshold, false-positive errors, number of unreliable tests, mean deviation (MD), visual field index (VFI), pattern standard deviation (PSD), glaucoma hemifield test (GHT), and number of depressed points deviating at P < 5%, P < 2%, P < 1%, and P < 0.5% on the total and pattern deviation probability maps. Specificity of the SS and SFR strategies were compared using Anderson's criteria for abnormal visual fields. RESULTS: The SFR tests were 60.4% shorter in time compared with SS (P < 0.001) and were associated with a significantly lower PSD (1.75 ± 0.80 decibel [dB] vs. 2.15 ± 1.25 dB; P = 0.016). There were no significant differences regarding the MD, VFI, foveal threshold, GHT, and number of points depressed at P < 5%, P < 2%, P < 1%, and P < 0.5% on the total deviation and pattern deviation probability maps between SS and SFR. When all exams were analyzed and any of Anderson's criteria was applied, the specificity was 68% with SFR and 61% with SS (P = 0.250). The specificities observed with SFR and SS when only the first or second exams were analyzed were also similar (63% vs. 64% and 72% vs. 58%, respectively, P > 0.05). CONCLUSIONS: The SS and SFR were associated with similar specificities in perimetry-naive individuals. The SFR did not increase the number of depressed points in the total and pattern deviation probability maps. Ophthalmologists should be aware that both strategies are associated with disturbingly high false-positive rates in perimetry-naive individuals. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Remote heart failure management using the HeartLogic algorithm. RE-HEART registry.

INTRODUCTION AND OBJECTIVES: HeartLogic is a multiparametric algorithm incorporated into implantable cardioverter-defibrillators (ICD). The associated alerts predict impending heart failure (HF) decompensations. Our objective was to analyze the association between alerts and clinical events and to describe the implementation of a protocol for remote management in a multicenter registry. METHODS: We evaluated study phase 1 (the investigators were blinded to the alert state) and phases 2 and 3 (after HeartLogic activation, managed as per local practice and with a standardized protocol, respectively). RESULTS: We included 288 patients from 15 centers. In phase 1, the median observation period was 10 months and there were 73 alerts (0.72 alerts/patient-y), with 8 hospitalizations and 2 emergency room admissions for HF (0.10 events/patient-y). There were no HF hospitalizations outside the alert period. In the active phases, the median follow-up was 16 (95%CI, 15-22) months and there were 277 alerts (0.89 alerts/patient-y); 33 were associated with HF hospitalizations or HF death (n=6), 46 with minor decompensations, and 78 with other events. The unexplained alert rate was 0.39 alerts/patient-y. Outside the alert state, there was only 1 HF hospitalization and 1 minor HF decompensation. Most alerts (82% in phase 2 and 81% in phase 3; P=.861) were remotely managed. The median NT-proBNP value was higher within than outside the alert state (7378 vs 1210 pg/mL; P <.001). CONCLUSIONS: The HeartLogic index was frequently associated with HF-related events and other clinically relevant situations, with a low rate of unexplained events. A standardized protocol allowed alerts to be safely and remotely detected and appropriate action to be taken on them.

Engineering threshold-based selection systems.

Using model organisms to identify novel therapeutic targets is frequently constrained by pre-existing genetic toolkits. To expedite positive selection for identification of novel downstream effectors, we engineered conditional expression of activated CED-10/Rac to disrupt Caenorhabditis elegans embryonic morphogenesis, titrated to 100% lethality. The strategy of engineering thresholds for positive selection using experimental animals was validated with pharmacological and genetic suppression and is generalizable to diverse molecular processes and experimental systems.

Immunohistochemical analysis of growth factors in platelet-rich fibrin membranes.

The use of autogenous materials to promote tissue regeneration has guided the direction of modern dentistry, and platelet-rich fibrin (PRF) is a promising biomaterial for tissue engineering. This in vitro immunohistochemical study aimed to analyze the presence of factors of endothelial growth and cell differentiation in PRF membranes by using the CD31 (endothelial cells) and CD163 (monocytes) markers. Five men and 5 women, aged between 25 and 60 years and without systemic health problems, were enrolled in the study. Blood samples were collected, submitted to a centrifugation protocol, and fixed in 4% formaldehyde, and then immunohistochemical analysis was performed. The histologic analysis of the slides showed that the fibrin clot was formed by a dense fiber network and cells trapped in its structure. One sample was excluded from the markers testing due to poor quality. All 9 of the valid samples were positive for the CD31 and CD163 markers, with reactivity ranging from 5% to 30% and 10% to 40% of cells, respectively. The immunohistochemical analysis showed the presence of CD31 and CD163 in the PRF membranes, indicating the potential for vascular neoformation and the significant presence of monocytes, which play an important role in tissue remodeling via their differentiation into macrophages.

Aproximación diagnóstica a la amiloidosis cardiaca por transtiretina en un área no endémica. ¿Qué variables no invasivas orientan a su diagnóstico? / Diagnostic approach to transthyretin amyloidosis in a non-endemic area. Which non-invasive variables could guide the diagnosis?

Al editor: Clásicamente se ha considerado la amiloidosis cardiaca como una afección rara, con un amplio espectro de síntomas que requiere un alto índice de sospecha. Sin embargo, los estudios han demostrado que la amiloidosis cardiaca por transtiretina (TTR) es más común de lo que previamente se creía1,2. Las características clínicas que se han asociado a la amiloidosis cardiaca por TTR son el sexo masculino, la edad avanzada, la hipertrofia concéntrica y la función ventricular izquierda preservada1. Se realizó un análisis descriptivo retrospectivo de las gammagrafías solicitadas en nuestro centro para descartar amiloidosis cardiaca por TTR desde septiembre de 2016 hasta noviembre de 2019. En dicho periodo se realizaron 39 gammagrafías, con una tendencia al alza en los últimos meses. Los objetivos fueron evaluar las gammagrafías solicitadas y conocer el porcentaje de gammagrafías diagnósticas de amiloidosis por TTR, establecer qué características son más frecuentes en los pacientes con amiloidosis por TTR en nuestra población de referencia y analizar las características diferenciales de las distintas posibilidades diagnósticas. Del total de las pruebas, 22 (56.4% de la muestra) mostraron una captación de grado 2-3 de Perugini, diagnóstica de amiloidosis por TTR. De acuerdo con las recomendaciones de diagnóstico no invasivo de amiloidosis cardiaca por TTR3, se descartó la presencia de pico monoclonal. Únicamente se realizó estudio genético a 10 pacientes, en dos de los cuales se detectó una mutación patogénica (Val50Met y variante patogénica c.290C>A en heterocigosis); los ocho restantes no mostraron mutaciones en el estudio molecular del gen TTR.

A Qualitative Examination of Factors That Influence Sleep Among Shipboard Sailors.

INTRODUCTION: Sleep disturbance is prevalent among service members; however, little is known about factors that compromise sleep in unique operational environments, such as naval ships. Given the importance of sleep to health and performance, it is critical to identify both causes and potential solutions to this serious issue. The objective of this qualitative study was to elucidate the barriers to sleep and the strategies service members use to improve their sleep and combat fatigue while living and working aboard ships (i.e., underway). METHODS AND MATERIALS: Interviews were conducted with 22 active duty service members assigned to sea duty. The semi-structured interview guide assessed the experiences of service members sleeping in shipboard environments. Interview transcripts were analyzed using applied thematic content analysis by two independent coders. RESULTS: Participants were largely male (77.8%) and enlisted (88.9%). The most common barrier to obtaining sufficient sleep was stress, followed by rotating schedules, and environmental factors (e.g., noise and light). Additionally, many participants reported prioritizing other activities over sleep when off duty. Many participants did not report using any specific strategies to improve their sleep while underway. Among those who did, most described mitigating environmental barriers (e.g., noise-cancelling headphones or sleep masks). However, some participants also acknowledged these strategies are not always feasible, either attributable to cost or because sailors must be able to respond to alarms or commands. Notably, few sailors reported using stress mitigation or relaxation strategies to help sleep. Ingesting caffeine was the only strategy sailors reported using to alert themselves while fatigued. CONCLUSIONS: Service members reported many unique barriers to sleep in the shipboard environment, yet many did not report the use of strategies to mitigate them. Further, few used alerting techniques when fatigued. This at-risk population could benefit from targeted educational interventions on sleep-promoting behaviors, prioritization of sleep, and fatigue mitigation.

Get up, stand up, stand up for your health! Faculty and student perspectives on addressing prolonged sitting in university settings.

Objective: To assess awareness about prolonged sitting and acceptance of interventions to reduce bouts of prolonged sitting. Participants: Undergraduate, graduate, and professional students and faculty from a large public university. Methods: Eight focus groups were conducted with 4 groups of undergraduate students and 4 groups of graduate/professional students. Eight key informant interviews were conducted with faculty. Content analyses were performed using inductive and deductive techniques to elicit common themes. Results: Many students and faculty were not aware of the detrimental effects associated with prolonged sitting. Barriers to movement in university settings included social acceptability, environmental constraints, and academic requirements. Acceptable interventions included: faculty prompts, changes to pedagogy, educational campaigns, and structural changes to classroom designs. Conclusions: University settings represent an opportunity to address issues related to prolonged sitting that may address immediate health implications, as well as establish behaviors and practices that can be continued in work-based settings.

Studying the Health and Performance of Shipboard Sailors: An Evidence Map.

INTRODUCTION: It is estimated that sailors who are assigned to surface ships and submarines are deployed for more than 1 year across their careers and they spend 15% to 23% of their time away from home. Research suggests that shipboard sailors experience rates of behavioral health issues similar to those with ground combat experiences. Despite the rigorous operational tempo and the unique shipboard environment experienced by these service members, little military health research has examined the health outcomes of sailors serving aboard ships. The objectives of this study were to develop an evidence map of the peer-reviewed literature to (1) identify potential threats to the health and readiness of shipboard sailors, (2) identify health and performance issues experienced by this population, and (3) identify gaps in the current peer-reviewed published literature on shipboard health and performance. MATERIALS AND METHODS: A systematic review of the existing peer-reviewed literature pertaining to the health, experiences, and performance of shipboard service members was conducted. Comprehensive search terms were used to identify articles published between January 2000 and April 2018. Identified articles were subject to a two-level review process. Study characteristics for all articles selected for final review were extracted, and articles were categorized into 13 content areas that were selected a priori. Findings are presented in an evidence map. RESULTS: The initial literature search yielded 8,858 unique articles, 90 of which were eligible for full review. Most articles primarily examined active duty sailors from the U.S. or other foreign militaries (88.9%). A total of 60 articles (67.8%) included information about the type of ship studied; the most frequently examined were submarines (29.5%) and aircraft carriers (27.9%). Most of the included studies used cross-sectional (63.3%) or longitudinal (24.4%) designs. Only 7.8% (n = 7) of articles described interventions. The most commonly examined focal areas included physical health issues, such as viral infections and injuries (56.7%), and health behaviors, such as substance use/misuse (40.0%). Other frequently addressed content areas were occupational stress (38.9%), interpersonal issues (32.2%), ship conditions (30.0%), and mental health (28.9%). Most articles (73.3%) addressed more than one content area. There was a high degree of variation in the measurement tools used; self-report surveys were the most common (48.9%), followed by objective physical, biological, or cognitive measures (32.2%) and medical and personnel record reviews (31.1%). CONCLUSIONS: The evidence map identified various gaps in the research pertaining to the health and performance of shipboard sailors. These gaps included a lack of research on the risk factors for common health and performance issues experienced by sailors and on the relationship between stressors of shipboard life and sailors' health, performance, and readiness. The results of this evidence map should be used to inform the development, implementation, and evaluation of interventions to improve the shipboard environment and/or the preventive health behaviors used by sailors while underway or deployed.

Parental Knowledge of Appropriate Placement of Child Restraint Systems Before and After Educational Intervention in a Pediatric Emergency Department.

OBJECTIVE: This study aimed to determine caregiver's knowledge of appropriate car restraint systems (CRSs) use and compare this with the actual use among children presenting to the pediatric emergency department (PED), and to determine the efficacy of PED-based intervention on improving knowledge. METHODS: We conducted a prospective, intervention study of children (<8 years old) during a 12-month period in the PED. Based on their height and weight, children were assigned to group 1 (rear facing), group 2 (forward facing), or group 3 (booster). Caregivers were surveyed in their baseline CRS knowledge. Certified child passenger safety technicians evaluated each CRS and gave caregivers one-on-one education. Participants were called back to answer a posttest to determine if the information given was retained. RESULTS: Of the 170 children enrolled, 64 (37.6%) were assigned to group 1, 68 (40%) to group 2, and 38 (22.3%) to group 3. Of these, 63% were not aware of the state law regarding CRS use. Among those without a CRS, 18% belonged to group 1, 36% to group 2, and 46% to group 3. Even among those who reportedly had CRS, 13% of children did not have one-on-on inspection. After inspection, 84% of group 1, 71% of group 2, and 70% of group 3 were in the appropriate one. Nearly 45% were not compliant with American Academy of Pediatrics guidelines of children riding in rear-facing CRS until 2 years of age. CONCLUSIONS: A significant proportion of children visiting the PED are not in appropriate CRS, and caretaker knowledge about correct CRS types and installation is poor. Future educational efforts should focus on rear-facing and booster seat age-group children.

The Great Imitator Strikes Again: A Case of a Lupus Flare-up Presenting Like an Acute Abdomen.

Description Systemic lupus erythematosus (SLE) is an autoimmune disease affecting all age groups and can manifest in various forms, often making the initial or successive presentations difficult to diagnose. Peritonitis secondary to lupus is a rare manifestation of this disease and the prevalence is said to be much lower in children. We present a case report of an adolescent male with a known history of lupus who presented to the emergency department with a clinical picture consistent with an acute surgical abdomen and underwent an appendectomy. Subsequent workup identified the culprit as a lupus-related peritonitis requiring corticosteroids for resolution.

Furosemida subcutánea como tratamiento para pacientes con insuficiencia cardiaca refractaria / Subcutaneous furosemide in patients with refractory heart failure

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Indinavir Increases Midazolam N-Glucuronidation in Humans: Identification of an Alternate CYP3A Inhibitor Using an In Vitro to In Vivo Approach.

Midazolam is a widely used index substrate for assessing effects of xenobiotics on CYP3A activity. A previous study involving human hepatocytes showed the primary route of midazolam metabolism, 1'-hydroxylation, shifted to N-glucuronidation in the presence of the CYP3A inhibitor ketoconazole, which may lead to an overprediction of the magnitude of a xenobiotic-midazolam interaction. Because ketoconazole is no longer recommended as a clinical CYP3A inhibitor, indinavir was selected as an alternate CYP3A inhibitor to evaluate the contribution of the N-glucuronidation pathway to midazolam metabolism. The effects of indinavir on midazolam 1'-hydroxylation and N-glucuronidation were first characterized in human-derived in vitro systems. Compared with vehicle, indinavir (10 µM) inhibited midazolam 1'-hydroxylation by recombinant CYP3A4, human liver microsomes, and high-CYP3A activity cryopreserved human hepatocytes by ≥70%; the IC50 obtained with hepatocytes (2.7 µM) was within reported human unbound indinavir Cmax (≤5 µM). Midazolam N-glucuronidation in hepatocytes increased in the presence of indinavir in both a concentration-dependent (1-33 µM) and time-dependent (0-4 hours) manner (by up to 2.5-fold), prompting assessment in human volunteers (n = 8). As predicted by these in vitro data, indinavir was a strong inhibitor of the 1'-hydroxylation pathway, decreasing the 1'-hydroxymidazolam/midazolam area under the plasma concentration versus time curve (AUC)0-12h ratio by 80%. Although not statistically significant, the midazolam N-glucuronide/midazolam AUC0-12h ratio increased by 40%, suggesting a shift to the N-glucuronidation pathway. The amount of midazolam N-glucuronide recovered in urine increased 4-fold but remained <10% of the oral midazolam dose (2.5 mg). A powered clinical study would clarify whether N-glucuronidation should be considered when assessing the magnitude of a xenobiotic-midazolam interaction.

The importance of drug safety and tolerability in the development of new immunosuppressive therapy for transplant recipients: The Transplant Therapeutics Consortium's position statement.

The Transplant Therapeutics Consortium (TTC) is a public-private partnership between the US Food and Drug Administration and the transplantation community including the transplantation societies and members of the biopharmaceutical industry. The TTC was formed to accelerate the process of developing new medical products for transplant patients. The initial goals of this collaboration are the following: (a) To define which aspects of the kidney transplant drug-development process have clear needs for improvement from an industry and regulatory perspective; (b) to define which of the unmet needs in the process could be positively impacted through the development of specific drug-development tools based on available data; and (c) to determine the most appropriate pathway to achieve regulatory acceptance of the proposed process-accelerating tools. The TTC has identified 2 major areas of emphasis: new biomarkers or endpoints for determining the efficacy of new therapies and new tools to assess the safety or tolerability of new therapies. This article presents the rationale and planned approach to develop new tools to assess safety and tolerability of therapies for transplant patients. We also discuss how similar efforts might support the continued development of patient-reported outcome measures in the future.

The UCP2 -866G/A, Ala55Val and UCP3 -55C/T polymorphisms are associated with premature coronary artery disease and cardiovascular risk factors in Mexican population.

We examined the role of UCP gene polymorphisms as susceptibility markers for premature coronary artery disease (pCAD). The UCP2 Ala55Val (C/T rs660339), UCP2 -866G/A (rs659366), and UCP3 -55C/T (rs1800849) polymorphisms were genotyped in 948 patients with pCAD, and 763 controls. The distribution of the UCP2 A55V (C/T rs660339) and UCP3 -55 (rs1800849) was similar in patients and controls. However, under a recessive model, the UCP2 -866 (rs659366) A allele was associated with increased risk of developing pCAD (OR = 1.43, Pc = 0.003). On the other hand, patients with pCAD and UCP2 A55V (rs660339) TT showed high levels of visceral abdominal fat (VAF) (Pc = 0.002), low levels of subcutaneous abdominal fat (SAF) (Pc = 0.001) and high VAT/SAT ratio (Pc < 0.001). Also, patients with UCP2 -866 (rs659366) AA showed increased levels of VAF (Pc = 0.003), low levels of SAF (Pc = 0.001) and a high VAT/SAT ratio (Pc = 0.002), whereas patients with the UCP3 -55 (rs1800849) TT presented high levels of VAF (Pc = 0.002). The results suggest the association of the UCP2 -866 (rs659366) polymorphism with risk of developing pCAD. Some polymorphisms were associated with abdominal fat levels and cardiovascular risk factors.